Global Biotechnology and Pharmaceuticals 24th September 2013 Multiple Sclerosis – ECTRIMS 2013 Prep-Pack It’s A Revolution! But Just How Big?
Research Analysts Ravi Mehrotra, Ph.D.
212-325-3487
EU Pharma Team Koon Ching, Ph.D. Vamil Divan Lee Kalowski 44 20 7888 0304 212 325 6286 212 538 5394 212-325-3777 [email protected] [email protected] [email protected] [email protected]
Ari Jahja Ronak Shah, Pharm.D., CFA Anuj Shah Jason Kantor 212 325 0767 212 325 9799 212 325 6931 415 249 7942 [email protected] [email protected] [email protected] [email protected]
DISCLOSURE APPENDIX CONTAINS IMPORTANT DISCLOSURES, ANALYST CERTIFICATIONS, INFORMATION ON TRADE ALERTS, ANALYST MODEL PORTFOLIOS AND THE STATUS OF NON-U.S ANALYSTS. U.S. Disclosure: Credit Suisse does and seeks to do business with companies covered in its research reports. As a result, investors should be aware that the Firm may have a conflict of interest that could affect the objectivity of this report. Investors should consider this report as only a single factor in making their investment decision. Evolution AND Revolution! As a humorous point/observation, we find the titles of the two Biogen sponsored symposium to be held at ECTRIMS very interesting: 10/2 17.15 “Biogen Idec: Reinventing MS care – Evolution” and 10/3 07.45 “Biogen Idec: Reinventing MS care – Revolution”. Umm, we wonder where they got that inspiration from…
Slide 2 September 2013
Table of Contents: It’s A Revolution! At ECTRIMS 2013, we are focused on these particular areas: 1) Dynamics of Tecfidera’s launch - Warehoused vs. +/ - Three bucket hypothesis 2) Other new entrant dynamics – Aubagio, Laquinimod 3) Earlier and treat-to-goal treatment management 4) Increasing focus on MRI in diagnosis and treatment ECTRIMS 2013 – Introduction/Key summary slides …………………………...... 4 ECTRIMS 2013 – Key Must-Attend Sessions…………………………………...... 22 ECTRIMS 2013 – Sessions by Day…………………………………………………………………………….... 35 ECTRIMS 2013 – Sessions by Product.……………………………………………………………………….... 56 3 Buckets Thesis……………………………………………………………………...... 72 New MS Drugs – Drug Profiles…………………………………………………………………………………... 82 Biogen Idec: BG-12………………………………...... 89 Sanofi: Aubagio (Teriflunomide)…………………………………………………………………………………128 Sanofi / Bayer: Lemtrada…………………………………………………………………………………………138 Biogen Idec / AbbVie: Daclizumab…………………………………………………………………………...... 146 Roche / Biogen Idec: Ocrelizumab…………………………………………………………………………….. 151 Teva / Active Biotech: Laquinimod……………………………………………………………………………… 158 Novartis: Gilenya…………………………………………………………………………………………………. 164 Biogen Idec/Elan: Tysabri……………………………………………………………………………………….. 169 Appendix - Additional Background Slides……………………………………………………………………… 175
Slide 3 September 2013 ECTRIMS 2013: It’s a Revolution! – But Just How Big?
. In our view, it’s not a question of whether it is a revolution or evolution anymore; the MS market IS undergoing a revolution! . The question is now just how big a revolution (and for investors what is not priced into the stocks!) . This revolution in the clinical management of MS is being driven not only by the launch of next-gen agents but also by changing treatment and diagnosis paradigms. . The consequence of this revolution is that MS is rapidly changing from a “diagnose, treat, and see” to a “treat aggressively to the goal” therapeutic area. . The upcoming ECTRIMS meeting (Copenhagen Oct 2-5), will deliver incremental clinical data (rather than key pivotal data) for next-gen MS agents. . More importantly, the meeting will act as an important “front-line forum” to gauge the massively changing dynamics within the MS therapeutic area. . Within this pre-pack, we provide (1) An itinerary planner for the meeting arranged by “must attend”, “day-by-day” and “MS Therapy” (2) A MS market overview and (3) Next-Gen agent profiles Sources: Company data, Credit Suisse analysis Slide 4 September 2013 Our top-10 sound bites/observation/questions/focal points for the conference(cont.) . (1) “Warehoused” untreated MS population remains an important sensitivity. . (2) Earlier and “treat-to-goal” like management to drive a dynamic market. . (3) Increasing focus on MRI clinical measures in diagnosis and treatment . (4) Is our “three buckets hypothesis” still valid? . (5) Is price of drugs influencing treatment choices? . (6) What is interesting in the earlier stage development pipeline? . (7) How do physicians view the relative clinical efficacy of MS therapeutics? . (8) How will the treatment sequencing change? . (9) What is the emerging side effect profile of Tecfidera? (especially (a) Is PML a real gating point concern?; (b) What is the real world flush/GI impact?) . (10) How do physicians view Tecfidera leukocyte and lymphocyte monitoring?
Sources: Company data, Credit Suisse analysis Slide 5 September 2013 ECTRIMS 2013: Incremental data on next-gen agents
. Tecfidera (BIIB): 3-year, follow-up integrated (efficacy inc MRI) data from DEFINE, CONFIRM, and ENDORSE. A long-term, interim update on safety from the ENDORSE study (10/3 at 15:45-17:00: P537, P563; 10/4 at 15:30-17:00: P990, P1013, P1018) . Plegridy (BIIB): Further efficacy and safety analyses of ADVANCE data will be presented. (10/3 at 15:45-17:00: P539, P540; 10/4 at 15:30-17:00: P989, P1061) . Aubagio/ Lemtrada (Sanofi): Pooled efficacy and safety PIII data/3-year disability, safety data + lymphocyte dynamics in CARE-MS II data. (10/3 at 15:45-17:00: P544, P618, P633; 10/4 at 15:30- 17:00: P1093, P1095) . Laquinimod (TEVA/Active Biotech): PIII CONCERTO trial design for 0.6mg and 1.0mg doses. (10/4 at 15:30-17:00: P1054) . Gilenya (Novartis/Mitsubishi): Long-term efficacy FREEDOMS II data. (10/4 at 15:30-17:00:P1092) . RPC1063 (RCPT): Focus will be on PI and QT/QTc data. (10/3 at 15:45-17:00: P375; 10/4 at 15:30- 17:00: P983) . Ponesimod (ATLN), ONO-4641 (Ono/ Merck KgaA): Additional PII data will be presented. (10/4 at 15:30-17:00: P995) . Siponimod (Novartis): PI QT/QTc data on "placebo-like" AV effects will be of interest. (10/3 at 15:45- 17:00: P626) . Ocrelizumab (BIIB/Roche)/Daclizumab (BIIB/ABBV). No major new data, but Roche is hosting a whole symposium devoted to B-cell therapy.
Sources: Company data, Credit Suisse analysis Slide 6 September 2013 3 Buckets Thesis: Our View on the Potential Evolution of the MS Market
Current Treatment Options - $14B (2012) Potential Future Treatment Options - $19B (2018) ABCRs High-Efficacy/ ABCRs Orals High-Efficacy/ Second-Line Second-Line Avonex – BIIB Tysabri – BIIB/ELN The 2012-2018 Avonex – BIIB Tecfidera – BIIB Tysabri – BIIB/ELN Betaseron – BAY Gilenya – NVS MS Revolution Betaseron – BAY Aubagio – SNY Lemtrada – SNY Copaxone – TEVA Copaxone – TEVA Gilenya – NVS Ocrelizumab – ROG/BIIB Rebif – PFE/eMRK Rebif – PFE/eMRK Laquinimod – ACTI/TEVA Approved Drugs Plegridy – BIIB Daclizumab – BIIB/ABBV ca80% market share ca20% market share Pipeline Drugs RPC1063* – RCPT Efficacy: RR 20-30% Efficacy: RR >50% Efficacy: EDSS <25% EDSS >30% > or = to ABCRs
Key Points to Our 3 Bucket Thesis: (1) We view MS therapeutics in 3 broad buckets: Two established buckets (i) ABCR and (ii) High-Efficacy/Second-Line agents and an emerging new class of products that we call (iii) Oral agents (2) The overall MS market is still dominated (~80% market share by value) by ABCRs (despite their relative modest efficacy and less than ideal side effect profile) as they are the only alternatives to High-Efficacy/Second-Line agents (~20% market share by value) and their associated serious infections concerns (3) Tecfidera is the leading Oral, showing efficacy above ABCRs/near High-Efficacy/Second-Line AND possessing a better safety profile than High-Efficacy/Second-Line (and ABCRs). In our view this will allow significant market share in new patients, but also propagate significant switching from ABCRs (4) RPC1063 is an S1P1 modulator, within the same class as Gilenya. In our view, the totality of RCP1063’s clinical profile, notably improved half-life/fast recovery of lymphocytes and improved cardiotoxicity/hepatoxicity over Gilenya could effectively position RCP1063 in a different bucket relative to Gilenya
Sources: Company data, Credit Suisse research MS Drug Launch Timeline 1997 2009 2011 2013 2015 2017 1993 1996 2002 2004 2006 2010 2012 2014 2016 2018
Betaseron Extavia Daclizumab Avonex Rebif Gilenya Plegridy RPC1063 Copaxone Tysabri Aubagio Ocrelizumab U.S. Tecfidera Laquinimod Lemtrada
Betaseron Tysabri Gilenya Daclizumab
Avonex Extavia Aubagio RPC1063 Copaxone Lemtrada Rebif Tecfidera Ex-U.S. Plegridy ABCRs Laquinimod Orals High-Efficacy / 2nd-Line Ocrelizumab
Sources: Company data, Credit Suisse research Multiple Sclerosis clinical development pipeline
Phase I Phase II Phase III
SP F F ABT-413 ARX424 Masitinib RPC1063 Lemtrada Plegridy AbbVie AbbVie AB Science Receptos Sanofi Biogen Idec
F SP ATX-MS-1467 AZ01 BHT-3009 Ponesimod Generic Copaxone Siponimod Merck KGaA Allozyne Bayhill Actelion Momenta / Novartis Novartis
SP CS-0777 ER IFNβ1a Tcelna Secukinumab Daclizumab Laquinimod Daiichi Flamel Opexa Novartis Biogen Idec / AbbVie Teva / Active Biotech
Fc-Interferon LAS186323 Anti-LINGO-1 Ofatumumab NU100 Ocrelizumab Merck KGaA Almirall Biogen Idec GSK Nuron Biotech Roche / Biogen Idec
SP MOR103 NRT-36 ATL1102 CNDO-201 Tysabri GSK Nectid Antisense Coronado Biogen Idec
PI-2301 rHIgM22 Cyrevia Firategrast Merck KGaA Acorda Accentia GSK
RTL1000 VX15 GSK 239512 MIS416 Artielle Vaccinex GSK Innate
XP23829 ONO-4641 PDA-001 Xenoport Ono Celgene
RHB-104 Tabalumab Redhill Eli Lilly
Catena MEDI-551 Santhera AstraZeneca
F Filed Olesoxime Trophos SP Secondary Progressive Multiple Sclerosis
Sources: BioMedTracker, Credit Suisse research Apples-to-Oranges Comparison of Reduction in Relapse Rates and EDSS Progression (vs. Placebo) for Major MS agents
80%
70%
60%
50%
40% RelapseRates
Relative reduction in reduction Relative 30%
20%
10%
0% Laquinimod Laquinimod Avonex Copaxone Rebif Betaseron Plegridy Plegridy Aubagio Copaxone Tecfidera Tecfidera Gilenya Tysabri BRAVO ALLEGRO Q4W Q2W CONFIRM CONFIRM DEFINE
Gilenya 40% Gilenya 58% Tysabri 41% Tysabri 67% 45%
40%
35%
30%
25%
20%
EDSS Progression EDSS Relative Reduction in in Reduction Relative 15%
10%
5%
0% Laquinimod Laquinimod Avonex Copaxone Rebif Betaseron Plegridy Plegridy Aubagio Copaxone Tecfidera Tecfidera Gilenya Tysabri BRAVO ALLEGRO Q4W Q2W CONFIRM CONFIRM DEFINE
Sources: Company data, Credit Suisse research and analysis Slide 10 September 2013 What is the appropriate clinical endpoint?
Endpoint Description Advantages Disadvantages Relapse Rate . Calculates number of attacks over a . Offers reasonable statistical powering . Uncertain relationship between specific period of time . Confirmable with MRI measures exacerbation rate and long-term . Classified as a “true” attack if it lasts . Provides estimate of biologic activity disability ≥24 hours and is separated from of disease when combined with MRI previous one by ≥30 days measures EDSS . Measures disability/impairment on a . Evaluates impact of MS on function . Complicated to score Progression 20-point scale from 0 (normal over a period of time . Highly subjective neurologic function) to 10 (death due . Widely known by neurologists . Non-linear relationship between actual to MS) level of function and EDSS scale . Considered “gold standard” by FDA MRI Clinical . Evaluates disease activity and severity . Provides objective measure of some . Sensitive to MRI techniques Measures . Examines T1, T2, and Gd+ lesions as aspects of disease pathology . Encounters same errors inherent in well as brain atrophy clinical assessment
Multiple . Measures impairment based on a . Examines physical and mental function . Remains correlated with EDSS Sclerosis number of scores including a 25-foot . Can be performed by technician . Does not account for visual Functional timed walk, paced auditory serial . Fairly reproducible impairment Composite addition test (PASAT), and 9-hole peg (MSFC) test (9HPT) Scripps . Assesses impairment, placing more . Can be scored based on a routine . Remains fairly cross-correlated with Neurological weight on physical rather than mental standardized neurological examination EDSS Rating Scale function . Appears to be more sensitive to (SNRS) change than EDSS
Sources: R. Herndon Handbook of Neurologic Rating Scales, National Multiple Sclerosis Society, Credit Suisse research Previously published CS MS Notes – Directly Tecfidera Related
NOTE: Please right click “Full Note” and click “Open Hyperlink” to access the Full Note.
Multiple Sclerosis - Addressing PML head on – July 31 2013 Bottom Line: PML is clearly a primary concern in the MS community. The note addressed two events related to PML have occurred over the last two weeks – 3rd PML case in Gilenya taking patient and BIIB prepping street for PML concerns for patients on Tecfidera . We retain our view (and much more importantly gauge that the majority of physicians views are) that neither Gilenya / (or any S1P1s) nor Tecfidera mechanistically contribute to PML occurrence. [Full Note]
BIIB: There is no easy answer - 160 and counting – Jun 12 2013 Bottom Line: We go over the real issues on Tecfidera receiving regulatory data protection (RDP) in the EU. Key points: - Exclusivity can be garnered via the “New Active Substance” or “Independent Development principle” pathway. BIIB is attempting to go via the “Independent Development principle” pathway. - Regulatory protection is separate and independent from patent protection. The lack of regulatory protection should not have any impact on the patents. - We strongly reiterate that the ‘065 patent is key and that it DOES provide protection until October 2019. - We made no changes to our modeling assumptions (which never included RDP) - Focus on the TRx market share - The level/impact of pent-up demand from “warehoused” patients is a much more important consideration than raw NRx numbers of different sample packs! [Full Note]
Not Necessarily a Storm in a Tea Cup – May 30 2013 Bottom Line: When the dust settles on BIIB’s decision to delay EMA approval of Tecfidera to secure regulatory data protection (RDP), there are two main scenarios, and we still see more overall upside risk than downside risk. [Full Note]
Slide 12 September 2013 Previously published CS MS Notes – Directly Tecfidera Related (cont.)
“NEJM Articles on PML in Patients Treated with Fum aric Acid – 2nd Opinion” – Apr 25 2013 Bottom Line: Feedback on NEJM articles in which we highlighted that we were still Tecfidera bulls (with risk on the upside for estimates) but also flagging that to completely ignore the NEJM articles would be overly dismissive. [Full Note]
“NEJM Articles on PML in Patients Treated with Fum aric Acid – Opinion” – Apr 24 2013 Bottom Line: Key take-homes from the NEJM articles and BIIB’s response, in our first-glance view, are: (a) 2 of the 4 patients had severe lymphopenia for 2-5 years before diagnosis of PML, the other two patients has significant compounding factors (treatment with methotrexate and efalizumab); (b) Much of the focus of the articles is on the lymphopenia issues. [Full Note]
The price of today's sushi is reasonable – Apr 1 2013 Bottom Line: U.S. Tecfidera pricing is in-line with expectations: The U.S. pricing of Tecfidera became available on Friday (post the FDA approval on 03/27/13); Tecfidera’s wholesale acquisition cost (WAC) is $54.9K per year, a slight premium to average ABCR pricing ($52.5K per year), but at a notable discount to Gilenya’s pricing ($60.4k per year). We strongly reiterate our view that the launch trajectory of Tecfidera is not only important for BIIB stock (obviously!) but also for the large-cap biotech sector in general. [Full Note]
So let's find out if this is actually a revolution or evolution: "warehousing" could drive near term upside – Mar 27 2013 Bottom Line: FDA announced that it had approved Tecfidera for the treatment of relapsing remitting multiple sclerosis (RRMS) and Tecfidera’s label was made available. The focus now shifts to the Tecfidera ramp. Pricing (and post marketing requirements) are expected to be disclosed within the next day or so. We re-highlight that warehousing ahead of Tecfidera’s launch could provide upside to near-term estimates. [Full Note]
Positive CHMP opinion for Tecfidera and Aubagio – Mar 22 2013 Bottom Line: BIIB’s Tecfidera (BG-12) and Sanofi’s Aubagio (Teriflunomide) received a positive CHMP opinion today. We reiterate our view that Tecfidera’s higher efficacy and overall better profile positions this drug as the key NIMO agent. [Full Note]
Slide 13 September 2013 Previously published CS MS Notes – Directly Tecfidera Related (cont.)
Synaplin (BG12) remains a NIMO based on putative labeling information – Jan 17 2013 Bottom Line: Putative Synaplin label raises no major surprises. Examination of temporarily publically-available beta websites for Synaplin (BG- 12), and concomitant comparison of the indication and safety information to currently marketed MS agents raise no major surprises and in essence places Synaplin’s label on an even playing field. MS therapeutic success has historically not been about the label per se; the commercial battle remains focused on marketing, messaging, and positioning. [Full Note]
Synaplin (BG-12) Citizen Petition Filed – Jan 10 2013 Bottom Line: TEVA’s CP is unlikely to delay FDA’s approval of BG-12, which we still assume takes place in late September 2013. Of the three statements in the CP, the second one regarding safety issues identified in MS therapies after FDA approval (Tysabri, Gilenya) is the most important. [Full Note]
BG-12's 3-month delay; it's not that unusual – Oct 18 2012 Bottom Line: We strongly believe that there is no significant clinical reason. We base this conclusion on the fact that: (1) we have already seen the granularity of DEFINE and CONFIRM (NEJM, AAN, ECTRIMS). (2) Physician excitement for BG-12 remains high, following our channel checks at the latest ECTRIMS. [Full Note]
BG12 Patent Update - NIMO Is Refusing To Sit On The Couch – May 22 2012 Bottom Line: An update of our original deep-dive BG12 patent analysis first published in June 2011. Over the last 12 months, the clinical profile of BG12 has become much clearer with DEFINE and CONFIRM datasets. We think the debate on BG12’s IP will intensify over the next 12 months and note that the ultimate IP protection of BG12 will have significant impact on all players within the MS space [Full Note]
Slide 14 September 2013
Previously published CS MS Notes – Evolution/Revolution
NOTE: Please right click “Full Note” and click “Open Hyperlink” to access the Full Note.
It's a Revolution! – Just How Big? – Adapting our CS NIMO/3-bucket thesis – Sept 13 2013 Bottom Line: In this note, we discuss and adapt our NIMO/3-bucket thesis on the basis of Tecfidera and Aubagio's PIII data and launches as well as significant physician and company feedback. The key subtle changes in our new adaptation are: (1) "NIMO" bucket = "Oral" bucket. (2) “Immuno-suppressives” = “High-Efficacy/2nd-Line”. [Full Note]
It's a Revolution! – Just How Big? – Driving Market Growth: Past, Present & Future – Sept 11 2013 Bottom Line: The MS market has grown massively over the last 10 years – patient numbers doubled, but value quadrupled. [Full Note]
Evolution or Revolution - Tecfidera Rx numbers - What it all means – May 23 2013 Bottom Line: Lots of “noise” in NRx data, nevertheless TRx data suggests significant upside to 2013 and 2014 Tecfidera numbers. The extrapolation of Rx numbers just 6 weeks into launch to Q2’13 or FY’13 numbers could be highly inaccurate in our view. [Full Note]
Evolution or Revolution – “The first harvest for Tecfidera - How big is the warehouse?’” – Apr 11 2013 Bottom Line: Within this note we further expand our thesis that there is pent-up, near-term demand for Tecfidera from “warehoused patients”. Specifically, we describe 3 distinct populations of warehoused patients: ‘Anticipatory”, “Switch”, and “Historical”. [Full Note]
Evolution or Revolution – AAN Meeting - The winners and losers in the revolution – Mar 18 2013 Bottom Line: We project that the global MS market could grow from $14.1B in 2012 to $19.2B in 2019, driven by the launch of next-gen agents and changing diagnosis and treatment paradigms. We reiterate our view that this AAN Meeting is about “market dynamics over data.” The consequence is that MS is rapidly changing from a “diagnose, treat, and see” to a “treat aggressively to the goal” therapeutic area. [Full Note]
Slide 15 September 2013 Previously published CS MS Notes – Evolution/Revolution (Cont.)
Evolution or Revolution: Observations about Tecfidera's possible efficacy label claims – Mar 15 2013 Bottom Line: Tecfidera is set to be the biggest drug in the MS market. Tecfidera’s CONFIRM was the first to use Copaxone as the active comparator. In our eyes Tecfidera’s efficacy sits in between ABCR’s and Immunosuppressive’s from our recent channel checks is that many physicians consider Tecfidera to have efficacy that is comparable to Gilenya’s. [Full Note]
Evolution or Revolution – NIMO's don't like to be labeled – Mar 1 2013 Bottom Line: Within this note, we summarize the Warnings & Precautions (W&P) language for all MS drugs. “Innocuous" leukocyte/lymphocyte monitoring recommendations is common on MS drug labels. Tecfidera’s effect on leukocyte/lymphocyte counts are well- defined from PIII studies and warrants similar "innocuous" label wording. [Full Note]
Evolution or Revolution – Tecfidera launch ramp detailed analysis – Feb 6 2013 Bottom Line: In our view, Tecfidera’s ramp should significantly beat Gilenya’s based on our NIMO/3 buckets hypothesis. BIIB remains our key pick in the large cap space based on our four-point perfect storm thesis. We focus on: (1) First-principles, patient-number/ share modeling; (2) Phased EU launch based on recent BIIB guidance and EU drug launches; (3) Comparison of Tecfidera’s launch to Gilenya’s. [Full Note]
Evolution or Revolution – MS 2.0 - Next-gens driving revolution or evolution? – Oct 8 2012 Bottom Line: The MS market is set to undergo significant changes over the coming years due to the introduction of a plethora of “next-gen” or “2.0” new MS therapies. Five key observations: (1) Global MS Market – a highly penetrated market but still significant potential for next-gen agents (2) US vs. ROW – Differential pricing dynamics a key sensitivity (3) “Warehoused” untreated MS population = a very significant opportunity for next-gen agents (4) Switching dynamics are important especially from ABCRs. (5) The NIMO effect: BG12 2018 sales estimated upgraded [Full Note]
Slide 16 September 2013 Previously published CS MS Notes – AAN/ECTRIMS/CS Therapeutics Day Related
NOTE: Please right click “Full Note” and click “Open Hyperlink” to access the Full Note.
Revolution over Evolution: ECTRIMS 2013 – It's a Revolution! – But Just How Big? – Sep 09 2013 Bottom Line: The upcoming ECTRIMS meeting (Copenhagen Oct 2-5) will deliver incremental clinical data (rather than key pivotal data) for next- gen MS agents. Within this note, we include a detailed ECTRIMS planner. [Full Note]
Credit Suisse 5th Annual Therapeutics Day - Key Takeaways – May 13 2013 Bottom Line: We held our 5th Annual Therapeutics Day with expert physician panels covering 5 therapeutic areas. Will the MS marketplace go through an evolution or revolution? Our panelists said Revolution! Is Tecfidera really the winner in the revolution? Our experts said yes, but there are others as well, esp. Gilenya and Tysabri. Are there any other rebels out there? Our panelists were notably positive on Lemtrada and 2nd generation S1P1’s. [Full Note]
Credit Suisse 5th Annual Therapeutics Day: MS Panel “Evolution or Revolution”– May 9 2013 [Full Note]
AAN 2013 - Plegridy: PIII ADVANCE granularity released – Mar 21 2013 Bottom Line: BIIB provided additional PIII ADVANCE data for twice-monthly (Q2W) and once-monthly (Q4W) Plegridy (Pegylated Avonex). Plegridy Q4W though still looks better than “standard” Avonex. While physicians would have preferred once-monthly dosing, Plegridy Q2W still provides the best dosing convenience of all interferons. Elevated transaminases for Plegridy Q2W and Q4W were not overly concerning. Plegridy could grow BIIB’s overall share of the ABCR market. [Full Note]
AAN 2013 - Tecfidera: Warehousing on the upside – Mar 20 2013 Bottom Line: One of the most consistent themes coming out of our channel checks with physicians at the AAN Meeting is the concept of warehousing patients in anticipation of Tecfidera’s launch. Warehousing has been occurring in MS for some time now. This population includes patients who were (1) previously treated, but currently untreated, and (2) diagnosed and currently untreated. [Full Note]
Slide 17 September 2013 Previously published CS MS Notes – AAN/ECTRIMS/CS Therapeutics Day Related (Cont.)
AAN 2013 - Summary of Poster Information – Mar 19 2013 Bottom Line: Posters for the AAN 2013 Meeting were made available yesterday, post market close. In our preview, we had flagged 200+ presentations and posters focused on MS therapies. In this note, we provide some of the takeaways from the key posters [Full Note]
AAN 2013 - RCC - Really! Clarifying chatter on ENDORSE malignancies - nothing new – Mar 18 2013 Bottom Line: We reiterate our conclusions that malignancies in this study (including RCC) were not an issue and that investigators had noted that there was no evidence of increased risk of malignancies in patients treated with Tecfidera. There were “no specific patterns of malignancies or type”, and there was no evidence of increased risk of renal adverse events associated with Tecfidera. [Full Note]
AAN 2013 planner - Market dynamics over data – Mar 1 2013 Bottom Line: The 65th AAN Meeting will deliver incremental clinical data (rather than key pivotal data) for next-gen MS agents. The consequence of this revolution is that MS is rapidly changing from a “diagnose, treat, and see” to a “treat aggressively to the goal” therapeutic area. [Full Note]
Tysabri restructuring: 3 bucket hypothesis = upside to operational leverage AND revenues – Feb 8 2013 Bottom Line: We view the restructuring of BIIB's collaboration on Tysabri with ELN as a significant positive. We see potential not just from an operational gearing perspective, but also a revenues point of view for every drug within BIIB’s MS franchise. The key aspects of our “3 buckets” thesis are potential for long-term SG&A operational gearing and revenue increases of all MS drugs. In our view, over time, we could see consolidation towards one sales-force with a message that effectively states “We are THE MS company. We have the best drug in each segment”. [Full Note]
ECTRIMS 2012 - Spotlight on next-gen S1P1 m odulators – Oct 15 2012 Bottom Line: The most interesting aspect was the incremental data on the next-gen S1P modulators from Actelion, Ono / Merck Serono, Novartis, and Receptos. To differentiate relative to Gilenya, we believe next-gen S1P1s will likely need to improve upon two major deficiencies: (1) CV side effects (2) Reducing time needed to return to normal lymphocyte counts by reducing half-life. Our key take-aways on the S1P1 modulators are included within. [Full Note]
Slide 18 September 2013 Previously published CS MS Notes – AAN/ECTRIMS/CS Therapeutics Day Related (Cont.)
ECTRIMS 2012 - Day Du - BG-12: Additional data supports clinical profile – Oct 12 2012 Bottom Line: Our key take-homes on BG-12 are: (1) Integrated analysis confirms BG-12’s efficacy. (2) Details of integrated analysis affirms BG-12’s safety. (3) Malignancies are NOT an issue. (4) Further evidence of BG-12’s neuro-protective properties. [Full Note]
ECTRIMS 2012 - Day Un: Granularity and support for our warehoused patient hypothesis – Oct 11 2012 Bottom Line: We got some very interesting granularity on this topic at ECTRIMS, supporting our hypothesis that this population could be a significant one for next-gen agents: (i) There is a debate about treating at very first symptoms because of life-long commitment to therapy, in which (especially for ABCRs)…(ii)…adherence is a big challenge with real-world 4-year discontinuation rates of 27-30%; most drop outs occur in the first year, with most NOT going back on therapy. (iii) Even in patients that persist with treatment, physicians estimate that <45% take the proper prescribed dose. [Full Note]
ECTRIMS 2012 Prep Pack – Oct 8 2012 Bottom Line: ECTRIMS meeting will be an important forum providing: 1) incremental clinical data for all agents as described below, 2) premarket messaging, in particular for Sanofi’s (OK technically Genzyme’s) Aubagio (approved 9/12/2012) and Alemtuzumab (PDUFA, Q2’13), and BIIB’s BG-12 (PDUFA, 12/28/2012), and 3) we also flag S1P1 modulators as potential game changers [Full Note]
ECTRIMS 2012: Appetizers are available now – Sept 25 2012 Bottom Line: Within this note, we include a detailed ECTRIMS planner. Full abstracts became available at 6pm EDT. [Full Note]
Global Biotechnology and Pharmaceuticals - ECTRIMS 2012: NIMO et Amis Go Gastronomic – Aug 17 2012 Bottom Line: Titles of the presentations and abstracts became available this week and are detailed in this note. [Full Note]
Slide 19 September 2013 Previously published CS MS Notes – Receptos (RCPT)
NOTE: Please right click “Full Note” and click “Open Hyperlink” to access the Full Note.
Receptos – A Potential Revolutionary Candidate – Development timelines for pipeline are intact – Aug 08 2013 Bottom Line: Focus remains on RPC1063 in Relapsing Multiple Sclerosis (RMS). RCPT is not an earnings-driven story. RCPT reaffirmed timelines for RPC1063's PII/III RADIANCE study. RCPT continues to enroll the TOUCHSTONE PII trial in Ulcerative Colitis (UC). [Full Note]
Receptos – Another Potential Winner in the Revolution – June 03 2013 Bottom Line: We Are Initiating Coverage of Receptos (RCPT) with Outperform and $21 Target Price (~30% Upside Potential). RCPT is focused on the research and development of drugs for the treatment of immunological and metabolic disorders. RCPT’s key asset is RPC1063, which is a “2nd-generation” S1P1 modulator, currently enrolling into a PII/III trial for relapsing multiple sclerosis (RMS) and a PII for ulcerative colitis. We believe that RPC1063 could be a significant winner in the MS revolution. [Full Note]
Slide 20 September 2013 Coverage Universe
Market Cap CS Market Cap CS Company Name Ticker ($M) CS Rating Target Price Last Price Coverage Company Name Ticker ($M) CS Rating Target Price Last Price Coverage Large Cap Hospital Antibiotics Amgen Inc. AMGN $86,674 NEUTRAL $120.00 $115.31 RM/LK Cubist Pharmaceuticals, Inc. CBST $4,169 OUTPERFORM $69.00 $64.50 JK/JS Biogen Idec Inc. BIIB $57,677 OUTPERFORM $255.00 $243.41 RM/LK Durata Therapeutics, Inc. DRTX $239 OUTPERFORM $15.00 $8.96 JK/JS Celgene Corporation CELG $60,367 NEUTRAL $135.00 $147.36 RM/LK The Medicines Company MDCO $1,835 OUTPERFORM $15.00 $14.93 JK/JS Gilead Sciences, Inc. GILD $95,787 OUTPERFORM $67.00 $63.00 RM/LK Obesity SMID Cap Arena Pharmaceuticals, Inc. ARNA $1,267 UNDERPERFORM $5.00 $5.86 LK/RM Antibody Orexigen Therapeutics, Inc. OREX $654 OUTPERFORM $11.00 $6.53 LK/RM ImmunoGen, Inc. IMGN $1,438 NEUTRAL $16.00 $16.77 JK/JS VIVUS, Inc. VVUS $1,003 NEUTRAL $14.00 $9.77 LK/RM PDL BioPharma, Inc. PDLI $1,119 UNDERPERFORM $6.00 $8.03 JK/JS Oncology SMID Regeneron Pharmaceuticals, Inc. REGN $29,206 OUTPERFORM $275.00 $298.51 JK/JS Ariad Pharmaceuticals Inc. ARIA $3,704 NEUTRAL $22.00 $20.09 JK/JS Seattle Genetics, Inc. SGEN $5,384 OUTPERFORM $46.00 $43.90 JK/JS Clovis Oncology, Inc. CLVS $2,201 OUTPERFORM $78.00 $73.47 RM/LK XOMA Corporation XOMA $412 OUTPERFORM $5.00 $4.47 JK/JS Endocyte ECYT $483 OUTPERFORM $24.00 $14.01 JK/JS Commercial-Stage SMID Infinity Pharmaceuticals INFI $921 OUTPERFORM $32.00 $18.53 JK/JS Actelion Ltd. ATLN-CH $8,416 OUTPERFORM CHF 66.00 CHF 63.55 RM/LK Pharmacyclics PCYC $8,720 OUTPERFORM $121.00 $119.21 JK/JS Corcept Therapeutics Incorporated.CORT $169 NEUTRAL $2.00 $1.69 RM/KC Sunesis Pharmaceuticals SNSS $240 NEUTRAL $6.00 $4.65 JK/JS InterMune, Inc. ITMN $1,223 OUTPERFORM $15.00 $14.93 RM/KC Spectrum Pharmaceuticals SPPI $525 UNDERPERFORM $7.00 $8.29 JK/JS United Therapeutics Corporation UTHR $3,864 NEUTRAL $40.00 $77.55 RM/KC Orphan Drugs XenoPort, Inc. XNPT $269 OUTPERFORM $7.00 $5.59 RM/KC Alexion Pharmaceuticals Inc. ALXN $22,000 NEUTRAL $114.00 $114.30 LK/RM Constipation / IBS-C BioMarin Pharmaceutical Inc. BMRN $10,326 NEUTRAL $68.00 $73.96 LK/RM Ironwood Pharmaceuticals, Inc. ClassIRWD A $1,452 OUTPERFORM $16.00 $11.91 RM/JC PTC Therapeutics Inc. PTCT $560 OUTPERFORM $24.00 $21.07 JK/JS Sucampo Pharmaceuticals, Inc. ClassSCMP A $261 NEUTRAL $8.00 $6.14 RM/JC Prostate Cancer Synergy Pharmaceuticals, Inc. SGYP $434 OUTPERFORM $9.30 $4.81 RM/JC Algeta ASA ALGETA-OSL $1,780 NEUTRAL NOK 215.00 NOK 241.00 LK/RM Development-Stage SMID Dendreon Corporation DNDN $479 NEUTRAL $3.00 $2.99 LK/RM Esperion Therapeutics, Inc. ESPR $271 OUTPERFORM $26.00 $17.65 JK/JS Exelixis, Inc. EXEL $1,044 NEUTRAL $5.00 $5.70 LK/RM Portola Pharmaceuticals, Inc. PTLA $894 OUTPERFORM $32.00 $25.42 JK/JS Medivation, Inc. MDVN $4,313 OUTPERFORM $77.00 $57.84 LK/RM Receptos, Inc. RCPT $413 OUTPERFORM $21.00 $22.53 RM/KC * Last Price as of Sept 24, 2013 Vical Incorporated VICL $108 NEUTRAL $2.00 $1.25 LK/RM HCV Achillion Pharmaceuticals, Inc. ACHN $716 OUTPERFORM $11.00 $7.25 RM/KC Enanta Pharmaceuticals, Inc. ENTA $423 OUTPERFORM $29.00 $23.30 RM/KC Idenix Pharmaceuticals, Inc. IDIX $742 UNDERPERFORM $4.00 $5.54 RM/KC Medivir AB Class B MVIR.B-OME $451 OUTPERFORM SEK 115.00 SEK 96.25 RM/KC Vertex Pharmaceuticals IncorporatedVRTX $17,598 NEUTRAL $80.00 $74.26 RM/KC
Slide 21 September 2013 ECTRIMS 2013 Key “Must-Attend” Sessions Key Sessions at ECTRIMS 2013
Wednesday, October 2, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 08:30 - 09:00 Teaching Course Hall A S. Fredrikson "How do I choose the correct disease-modifying 6 Company Events ONO-4641 treatment for my MS patient?" - To treat or not to Aubagio Ponesimod treat CIS and RRMS Alemtuzumab RPC1063 09:00 - 09:30 Teaching Course Hall A R. Fox "How do I choose the correct disease-modifying 7 Tecfidera Copaxone treatment for my MS patient?" - Choosing the Daclizumab BIIB033 right treatment for the individual patient Laquinimod Other Compounds 09:30 - 10:00 Teaching Course Hall A B. Kieseier "How do I choose the correct disease-modifying 8 Ocrelizumab Plegridy treatment for my MS patient?" - When and how Tysabri Secukinumab should treatment be switched or escalated? Gilenya 10:30 - 11:00 Teaching Course Hall C A. Rovira "MRI issues in clinical practice" - Use of brain and 33 spinal cord MRI for differential diagnosis 10:30 - 11:00 Teaching Course Hall F N. de Stefano "MRI relevance in neurodegeneration" - Brain 36 MRI: biomarkers of neurodegeneration 10:30 - 11:00 Teaching Course Hall A P. Vermersch "Differential diagnoses and diagnostic dilemmas 21 in MS" - Diagnostic approach to multiple sclerosis 11:00 - 11:30 Teaching Course Hall C M. Wattjes "MRI issues in clinical practice" - How and when 34 should brain and spinal cord MRI be performed in the diagnostic process? 11:30 - 12:00 Teaching Course Hall C X. Montalban "MRI issues in clinical practice" - MRI in predicting 35 treatment response: ready to be used in individual patients?
Source: ECTRIMS 2013 Slide 23 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Wednesday, October 2, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 17:15 - 17:35 Satellite Symposium Hall A H.-P. Hartung "Biogen Idec: Reinventing MS care – evolution" - 65 Company Events ONO-4641 Tailoring choice: a drug for each patient at the Aubagio Ponesimod right time Alemtuzumab RPC1063 17:35 - 17:55 Satellite Symposium Hall A G. Giovannoni "Biogen Idec: Reinventing MS care – evolution" - 66 Tecfidera Copaxone Silencing the disease from the start Daclizumab BIIB033 17:55 - 18:15 Satellite Symposium Hall A P. Calabresi "Biogen Idec: Reinventing MS care – evolution" - 67 Laquinimod Other Compounds Advancing interferons for people with MS Ocrelizumab Plegridy 18:30 - 18:35 Satellite Symposium Hall A D. Bates "Merck Serono: Supporting patient engagement 68 Tysabri Secukinumab for optimized treatment management in MS" - Gilenya Introduction 18:35 - 18:50 Satellite Symposium Hall A M.S. Freedman "Merck Serono: Supporting patient engagement 69 for optimized treatment management in MS" - Defining goals at the start of treatment 18:50 - 19:05 Satellite Symposium Hall A A. Feinstein "Merck Serono: Supporting patient engagement 70 for optimized treatment management in MS" - Understanding our patients: the importance of effective communication 19:05 - 19:20 Satellite Symposium Hall A A. Lugaresi "Merck Serono: Supporting patient engagement 71 for optimized treatment management in MS" - Engaging with patients to achieve treatment goals
19:20 - 19:30 Satellite Symposium Hall A D. Bates, D. Lowden "Merck Serono: Supporting patient engagement 72 for optimized treatment management in MS" - Discussion: patient engagement with MS treatments 18:30 - 19:30 Satellite Symposium Hall A D. Bates "Merck Serono: Supporting patient engagement 73 for optimized treatment management in MS" - Close
Source: ECTRIMS 2013 Slide 24 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Thursday, October 3, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 07:45 - 08:05 Satellite Symposium Hall A X. Montalban "Biogen Idec: Reinventing MS care – revolution" - 74 Company Events ONO-4641 Defending the brain Aubagio Ponesimod 08:05 - 08:25 Satellite Symposium Hall A T. Berger "Biogen Idec: Reinventing MS care – revolution" - 75 Alemtuzumab RPC1063 Returning mobility and QoL to people with MS Tecfidera Copaxone 08:25 - 08:45 Satellite Symposium Hall A A. Sandrock Biogen Idec: Reinventing MS care – revolution - 76 Daclizumab BIIB033 The future is repair Laquinimod Other Compounds 09:30 - 10:15 Plenary Session 1 Hall A G. Comi "Welcome Address and ECTRIMS Lecture" - 81 Ocrelizumab Plegridy Early treatment of multiple sclerosis Tysabri Secukinumab 11:05 - 11:25 Window of Hall A J. Cohen Long-term benefits of MS treatment 95 Gilenya opportunity in MS 13:00 - 13:15 Satellitetreatment Symposium Hall A P.S. Sorensen "Teva Neuroscience: Re-evaluating the treatment 105 algorithm in multiple sclerosis: emerging insights" - Welcome and introduction 13:15 - 13:30 Satellite Symposium Hall A F. Zipp "Teva Neuroscience: Re-evaluating the treatment 106 algorithm in multiple sclerosis: emerging insights" - Multiple sclerosis: changing concepts, new targets
13:30 - 13:45 Satellite Symposium Hall A P. Vermersch "Teva Neuroscience: Re-evaluating the treatment 107 algorithm in multiple sclerosis: emerging insights" - Treatment sequencing or treatment selection: time to re-evaluate our approach? 13:45 14:00 Satellite Symposium Hall A F. Lublin "Teva Neuroscience: Re-evaluating the treatment 108 algorithm in multiple sclerosis: emerging insights" - Older, but wiser? Re-evaluating the role of established multiple sclerosis therapies 15:45 - 17:00 Experimental models - - - - - R. Peach, J. Brooks, H. Dedman, R. Powell, F. RPC1063, a potent and selective sphingosine 1- P 375 Scott, G. Timony phosphate 1 receptor modulator, has a favourable preclinical safety profile 15:45 - 17:00 Immunomodulation/ - - - - - P. Calabresi, B. Kieseier, D. Arnold, L. Balcer, Peginterferon beta-1a provides improvements in P 514 Immunosuppression A. Boyko, J. Pelletier, S. Liu, Y. Zhu, X. You, A. clinical and radiological disease activity in Seddighzadeh, B. Sperling, S. Hung, A. Deykin relapsing-remitting multiple sclerosis: year 1 findings from the phase 3 ADVANCE study
Source: ECTRIMS 2013 Slide 25 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Thursday, October 3, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:45 - 17:00 Immunomodulation/ - - - - - L.H. Kasper, D.L. Arnold, J.A. Cohen, A.J. Lymphocyte subset dynamics following P 531 Company Events ONO-4641 Immunosuppression Coles, E.J. Fox, H.-P. Hartung, E. Havrdova, alemtuzumab treatment in the CARE-MS II study Aubagio Ponesimod K.W. Selmaj, H.L. Weiner, J. Palmer, D.H. Alemtuzumab RPC1063 Margolin, M.A. Panzara, D.A.S. Compston Tecfidera Copaxone Daclizumab BIIB033 15:45 - 17:00 Immunomodulation/ - - - - - K. Selmaj, F. Zipp, T. Vollmer, A. Bar-Or, B. Effect of ONO-4641, a potent, oral, selective P 536 Laquinimod Other Compounds Immunosuppression Due, T.Z. Fischer, K. Thangavelu on behalf of sphingosine-1-phosphate receptor-1 and -5 Ocrelizumab Plegridy the DreaMS study investigators agonist, on MRI outcomes in patients with Tysabri Secukinumab relapsing remitting multiple sclerosis: subgroup Gilenya analyses from the phase 2 DreaMS study
15:45 - 17:00 Immunomodulation/ - - - - - K. Selmaj, R. Gold, R. J. Fox, E. Havrdova, G. Flushing and gastrointestinal tolerability events in P 537 Immunosuppression Giovannoni, A. Pace, M. Novas, L. Meltzer, C. relapsing remitting multiple sclerosis (RRMS) Hotermans, V. Viglietta, J. T. Phillips patients treated with oral BG-12 dimethyl fumarate) in the phase 3 DEFINE and CONFIRM trials 15:45 - 17:00 Immunomodulation/ - - - - - R. Gold, J. T. Phillips, A. Bar-Or, M. Three-year follow-up of oral BG-12 (dimethyl P 538 Immunosuppression Hutchinson, L. Kappos, R. Zhang, M. Yang, V. fumarate) treatment in relapsing remitting multiple Viglietta, S. I. Sheikh, R. J. Fox sclerosis (RRMS): integrated clinical efficacy data from the DEFINE, CONFIRM, and ENDORSE studies 15:45 - 17:00 Immunomodulation/ - - - - - B. Kieseier, P. Calabresi, D. Arnold, Y. Zhu, S. Subgroup and sensitivity analyses of the primary P 539 Immunosuppression Liu, S. Hung, A. Deykin, S. Sheikh endpoint from the peginterferon beta-1a ADVANCE study: a pivotal phase 3 study in patients with relapsing-remitting multiple sclerosis
15:45 - 17:00 Immunomodulation/ - - - - - B. Kieseier, P. Calabresi, S. Liu, Y. Zhu, X. Effect of peginterferon beta-1a on disability P 540 Immunosuppression You, B. Sperling, S. Sheikh, S. Hung, A. Deykin progression in patients with relapsing remitting multiple sclerosis: year 1 data from the pivotal phase 3 ADVANCE study 15:45 - 17:00 Immunomodulation/ - - - - - M. Freedman, J. Wolinsky, G. Comi, L. Long-term safety and efficacy of teriflunomide in P 544 Immunosuppression Kappos, T. Olsson, A. Miller, M. Benamor, D. patients with relapsing forms of multiple sclerosis Dukovic, J. Liang, P. Truffinet, P. O'Connor in the TEMSO extension trial
Source: ECTRIMS 2013 Slide 26 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Thursday, October 3, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:45 - 17:00 Immunomodulation/ - - - - - D. Cadavid, I. Melamed, H. Gevorkyan, N. The use of magnetic resonance imaging to P 545 Company Events ONO-4641 Immunosuppression Richert monitor the safety of anti-LINGO-1: findings from Aubagio Ponesimod phase 1 studies in healthy volunteers and Alemtuzumab RPC1063 subjects with multiple sclerosis Tecfidera Copaxone 15:45 - 17:00 Immunomodulation/ - - - - - T. Vollmer, F. Zipp, A. Bar-Or, B. Due, K. Magnetic resonance imaging measures of P 547 Daclizumab BIIB033 Immunosuppression Thangavelu, T.Z. Fischer, K. Selmaj on behalf efficacy in patients with multiple sclerosis Laquinimod Other Compounds of the DreaMS study investigators receiving ONO-4641, a sphingosine-1-phosphate Ocrelizumab Plegridy receptor-1 and -5 agonist: interim results from an Tysabri Secukinumab extension of the DreaMS study Gilenya 15:45 - 17:00 Immunomodulation/ - - - - - S.Y. Hong, J. Park, W. Park, H. Park, D. Park, Efficacy and safety of LC510201, an orally active, P 552 Immunosuppression J. Choi, S. Baek, J. Park, H. Park selective sphingosine-1-phosphate receptor 1 (S1P1) and -5 (S1P5) agonist, in preclinical models of multiple sclerosis 15:45 - 17:00 Immunomodulation/ - - - - - M. Hutchinson, R. Gold, R. J. Fox, E. Clinical efficacy of BG-12 (dimethyl fumarate) for P 563 Immunosuppression Havrdova, G. Giovannoni, A. Zhang, C. relapsing remitting multiple sclerosis according to Hotermans, M. Stephan, A. Bar-Or prior therapy: an integrated analysis of the phase 3 DEFINE and CONFIRM studies
15:45 - 17:00 Immunomodulation/ - - - - - A. Savinainen, S. El Bawab, T. Crandall, R. ONO-4641, a potent and selective sphingosine-1- Immunosuppression Chang, U. Boschert, T. Dellovade phosphate receptor-1 and -5 agonist, results in less lymphopenia than fingolimod at effective doses in a preclinical model of multiple sclerosis
15:45 - 17:00 Long-term treatment - - - - - H.-P. Hartung, D.L. Arnold, J.A. Cohen, A.J. Reduction of disability with alemtuzumab in P 592 monitoring Coles, E.J. Fox, E. Havrdova, K.W. Selmaj, relapsing remitting multiple sclerosis patients who H.L. Weiner, J. Palmer, D.H. Margolin, M.A. participated in CARE-MS II: three year follow-up Panzara, D.A.S. Compston 15:45 - 17:00 Risk management - - - - - V. Limmroth, S. Hoyer, K. Schuh, M. Lang, O. Good cardiac safety profile after fingolimod P 602 for disease modifying Hoffmann, T. Ziemssen (Gilenya®) treatment initiation in patients with treatments relapsing remitting multiple sclerosis: first interim analysis of the START study 15:45 - 17:00 Risk management - - - - - E. Havrdova, D.L. Arnold, J.A. Cohen, A.J. Infection risk with alemtuzumab in patients with P 603 for disease modifying Coles, E.J. Fox, H.-P. Hartung, K. Selmaj, H.L. relapsing remitting multiple sclerosis: pooled treatments Weiner, J. Palmer, D.H. Margolin, P. Oyuela, results from the CARE-MS I and CARE-MS II M.A. Panzara, D.A.S. Compston trials 15:45 - 17:00 Others - - - - - L. Kappos, G. Comi, M.S. Freedman, A.E. Pooled efficacy data from two phase 3 placebo- P 618 Miller, T.P. Olsson, J.S. Wolinsky, P. Truffinet, controlled trials of oral, once-daily teriflunomide S. Cavalier, J.-L. Delhay, D. Dukovic, P. O’Connor
Source: ECTRIMS 2013 Slide 27 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Thursday, October 3, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:45 - 17:00 Others - - - - - J. Cohen, J. Pelletier, P. Chin, N. Sfikas, G. Efficacy of fingolimod in relapsing remitting P 620 Company Events ONO-4641 Karlsson, P. von Rosenstiel, L. Kappos multiple sclerosis (RRMS) as measured by Aubagio Ponesimod multiple sclerosis functional composite: results Alemtuzumab RPC1063 from the TRANSFORMS, FREEDOMS, and Tecfidera Copaxone FREEDOMS II phase 3 studies Daclizumab BIIB033 Laquinimod Other Compounds 15:45 - 17:00 Others - - - - - K. Shakeri-Nejad, B. Brendani, N. Pezous, L. Placebo-like occurrence of atrioventricular blocks P 626 Ocrelizumab Plegridy Mooney, A. Juan, M. Allison, R.G. Perry, E. and sinus pauses: results from a siponimod Tysabri Secukinumab Legangneux QT/QTc study Gilenya 15:45 - 17:00 Others - - - - - T. Leist, M. Freedman, L. Kappos, T. Olsson, Pooled safety data from three placebo-controlled P 633 A. Miller, J. Wolinsky, P. O'Connor, M. teriflunomide studies Benamor, J. Delhay, P. Truffinet, D. Dukovic, J. Li, G. Comi 18:05 - 18:20 Satellite Symposium Hall A H. Wiendl "Medscape Education: Evolving the management 142 of MS: new insights and new directions" - The changing landscape for clinical decisions in managing RRMS with oral therapies 18:20 - 18:35 Satellite Symposium Hall B J. Sastre-Garriga "Medscape Education: Evolving the management 143 of MS: new insights and new directions" - Beyond reducing-relapses in RRMS: the importance of neuroprotection - 18:35 - 18:50 Satellite Symposium Hall B H. Butzkueven "Medscape Education: Evolving the management 144 of MS: new insights and new directions" - Balancing efficacy and safety in the real world 18:50 - 19:00 Satellite Symposium Hall B H. Wiendl "Medscape Education: Evolving the management 145 of MS: new insights and new directions" - Panel discussion and Q&A 19:15 - 19:30 Satellite Symposium Hall B F. Lublin "Bayer HealthCare: 25 years of partnership: 146 working towards a better future for patients with MS" - 25 Years of partnership: working towards a better future for patients with MS 19:30 - 19:50 Satellite Symposium Hall B M. Cascione "Bayer HealthCare: 25 years of partnership: 148 working towards a better future for patients with MS" - 25 Years of partnership: current focus 19:50 - 20:10 Satellite Symposium Hall B A. Chan "Bayer HealthCare: 25 years of partnership: 149 working towards a better future for patients with MS" - 25 Years of partnership: continuous efforts to improve MS patient support
Source: ECTRIMS 2013 Slide 28 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Friday, October 4, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 08:00 - 08:05 Satellite Symposium Hall B H.-P. Hartung F. Hoffmann- La Roche Ltd: Selective targeting of 150 Company Events ONO-4641 B Cells: establishing a new horizon for multiple Aubagio Ponesimod sclerosis treatment - Welcome and introduction Alemtuzumab RPC1063 Tecfidera Copaxone 08:05 - 08:20 Satellite Symposium Hall B A. Bar-Or F. Hoffmann- La Roche Ltd: Selective targeting of 151 Daclizumab BIIB033 B Cells: establishing a new horizon for multiple Laquinimod Other Compounds sclerosis treatment - B cells as key players in the Ocrelizumab Plegridy pathobiology of multiple sclerosis Tysabri Secukinumab Gilenya 08:20 - 08:35 Satellite Symposium Hall B A. Chan F. Hoffmann- La Roche Ltd: Selective targeting of 152 B Cells: establishing a new horizon for multiple sclerosis treatment - Mechanisms of anti-CD20 antibodies in autoimmune diseases 08:35 - 08:50 Satellite Symposium Hall B S. Hauser F. Hoffmann- La Roche Ltd: Selective targeting of 153 B Cells: establishing a new horizon for multiple sclerosis treatment - Selective targeting of B cells with ACD20: a promising future for multiple sclerosis therapies? 08:50 - 09:00 Satellite Symposium Hall B H.-P. Hartung F. Hoffmann- La Roche Ltd: Selective targeting of 154 B Cells: establishing a new horizon for multiple sclerosis treatment - Question and answer session 10:45 - 11:05 Management of risk Hall A P.S. Sørensen Is risk stratification possible with the new 176 in MS therapy treatments? 11:05 - 11:25 Management of risk Hall A R. Gold, B. Kieseier Occurrence and management of PML and IRIS 177 in MS therapy 14:00 - 14:20 Progressive MS Hall A R. Fox From relapsing-remitting to secondary 195 progressive MS
Source: ECTRIMS 2013 Slide 29 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Friday, October 4, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 14:20 - 14:40 Progressive MS Hall A F. Sellebjerg Therapeutic opportunities for progressive MS 196 Company Events ONO-4641 14:20 - 14:40 Looking into the Hall D L. Kappos What is in the pipeline? 208 Aubagio Ponesimod future: experimental Alemtuzumab RPC1063 studies of new Tecfidera Copaxone therapies Daclizumab BIIB033 Laquinimod Other Compounds 15:30 - 17:00 Immunology - - - - - G. Giovannoni, A. Mikulskis, M. McNeil, K. Evaluation of immunogenicity in multiple sclerosis P 864 Ocrelizumab Plegridy Riester, M. Sweetser, J. Elkins, L. Amaravadi patients continuously treated with daclizumab- Tysabri Secukinumab HYP during the SELECT and SELECTION clinical Gilenya trials 15:30 - 17:00 Immunomodulation/ - - - - - T. Ziemssen, O. Bajenaru, A. Carrá, N. de COPTIMIZE: a two-year observational survey of P 973 Immunosuppression Klippel, J. de Sá, A. Edland, J. Frederiksen, O. patients with relapsing remitting multiple sclerosis Heinzlef, K. Karageorgiou, A.M. Landtblom, M. switching to glatiramer acetate 20 mg daily Macías Islas, N. Tubridy, Y. Gilgun-Sherki
15:30 - 17:00 Immunomodulation/ - - - - - E.W. Radue, D. Stefoski, R. Gold, M. McNeill, Reduction in brain atrophy with extended P 977 Immunosuppression K. Riester, J. Elkins daclizumab HYP treatment: results of SELECT and the SELECT extension study 15:30 - 17:00 Immunomodulation/ - - - - - J. Hartung, A. Olson, R. Peach, M. Boehm, B. Results of a thorough QT/QTc (TQT) study of P 983 Immunosuppression Mendzelevski, D. Chanter, H. Smith, C. Pan, G. orally administered RPC1063, a novel, selective Timony, S. Gujrathi S1P1 receptor agonist, in healthy adult volunteers
15:30 - 17:00 Immunomodulation/ - - - - - D. Arnold, P. Calabresi, B. Kieseier, Y. Zhu, S. Magnetic resonance imaging results from the first P 989 Immunosuppression Liu, S. Hung, A. Deykin, S. Sheikh year of the ADVANCE study, a pivotal phase 3 trial of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis
15:30 - 17:00 Immunomodulation/ - - - - - R. Gold, G. Giovannoni, J. T. Phillips, R. J. Fox, Effect of BG-12 (dimethyl fumarate) in newly P 990 Immunosuppression A. Zhang, L. Meltzer, N. C. Kurukulasuriya diagnosed relapsing remitting multiple sclerosis (RRMS) patients from the DEFINE and CONFIRM studies 15:30 - 17:00 Immunomodulation/ - - - - - R. Gold, J. T. Phillips, E. Havrdova, A. Bar-Or, Oral BG-12 (dimethyl fumarate) and pregnancy: P 991 Immunosuppression L. Kappos, J. Clarke, H. Yuan, M. Novas, M. T. preclinical studies and pregnancy outcomes Sweetser, N. C. Kurukulasuriya, V. Viglietta, R. reported during the clinical development J. Fox programme
Source: ECTRIMS 2013 Slide 30 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Friday, October 4, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:30 - 17:00 Immunomodulation/ - - - - - F. Zipp, T. Vollmer, A. Bar-Or, B. Due, K. Relapse rates in patients with multiple sclerosis P 992 Company Events ONO-4641 Immunosuppression Thangavelu, T.Z. Fischer, K. Selmaj on behalf receiving ONO-4641, a sphingosine-1-phosphate Aubagio Ponesimod of the DreaMS study investigators receptor-1 and -5 agonist: interim results from an Alemtuzumab RPC1063 extension of the DreaMS study Tecfidera Copaxone 15:30 - 17:00 Immunomodulation/ - - - - - C. Pozzilli, Ó. Fernández, T. Olsson, M.S. Maintenance of efficacy, safety and tolerability of P 995 Daclizumab BIIB033 Immunosuppression Freedman, M. Melanson, A. Boster, E.-W. ponesimod in patients with relapsing remitting Laquinimod Other Compounds Radue, B. Hennessy, A. Rames, D. D'Ambrosio multiple sclerosis: phase II extension study Ocrelizumab Plegridy Tysabri Secukinumab 15:30 - 17:00 Immunomodulation/ - - - - - J.T. Phillips, R.J. Fox, K. Selmaj, M. Yang, R. Safety profile of BG-12 (dimethyl fumarate) in P 996 Gilenya Immunosuppression Zhang, M. Novas, M.T. Sweetser, V. Viglietta, relapsing remitting multiple sclerosis: long-term R. Gold interim results from the ENDORSE extension study 15:30 - 17:00 Immunomodulation/ - - - - - A. Bar-Or, F. Zipp, T. Vollmer, B. Due, K. Safety of ONO-4641 in patients with relapsing P 997 Immunosuppression Thangavelu, J. Johnson, K. Selmaj on behalf of remitting multiple sclerosis: results from a six- the DreaMS study investigators month interim analysis of the DreaMS extension study 15:30 - 17:00 Immunomodulation/ - - - - - D. H. Miller, R. J. Fox, R. Gold, E. Havrdova, L. Three-year follow-up of oral BG-12 (dimethyl P 1004 Immunosuppression Kappos, D. MacManus, T. Yousry, R. Zhang, fumarate) treatment in relapsing remitting multiple M. Yang, V. Viglietta, S. I. Sheikh, K. T. sclerosis (RRMS): integrated magnetic resonance Dawson, D. L. Arnold imaging (MRI) outcomes from DEFINE, CONFIRM, and ENDORSE 15:30 - 17:00 Immunomodulation/ - - - - - F. Bernard, D. Yu, A. Gray, U. Boschert, T. Efficacy of ONO-4641, a potent and selective P 1007 Immunosuppression Dellovade, D. Graham sphingosine-1-phosphate receptor-1 and -5 agonist, in a preclinical model of multiple sclerosis
15:30 - 17:00 Immunomodulation/ - - - - - M. Hutchinson, R.J. Fox, A. Bar-Or, E. Efficacy of BG-12 (dimethyl fumarate) in relapsing P 1013 Immunosuppression Havrdova, M. Yang, R. Zhang, V. Viglietta, S.I. remitting multiple sclerosis in patients from Sheikh, R. Gold Europe: an integrated analysis of the phase 3 DEFINE and CONFIRM studies 15:30 - 17:00 Immunomodulation/ - - - - - R. J. Fox, R. Gold, J. T. Phillips, K. Selmaj, K. Lymphocyte count reductions in relapsing P 1018 Immunosuppression Raghupathi, H. Yuan, J. O'Gorman, M. Novas, remitting multiple sclerosis (RRMS) patients V. Viglietta, N. C. Kurukulasuriya treated with oral BG-12 (dimethyl fumarate): integrated analysis of the placebo-controlled studies
Source: ECTRIMS 2013 Slide 31 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Friday, October 4, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:30 - 17:00 Long-term treatment - - - - - L. Kappos, J. A Cohen, F. Barkhof, L. Relapse rates and disability remain consistently P 1052 Company Events ONO-4641 monitoring Cappiello, Y. Zhang, P. Von Rosenstiel low with long-term fingolimod therapy: five-year Aubagio Ponesimod interim results of the LONGTERMS extension Alemtuzumab RPC1063 study Tecfidera Copaxone 15:30 - 17:00 Long-term treatment - - - - - J. Lycke, D.L. Arnold, J.A. Cohen, A.J. Coles, Adverse event profile of alemtuzumab in active P 1053 Daclizumab BIIB033 monitoring E.J. Fox, H.-P. Hartung, E. Havrdova, K.W. relapsing remitting multiple sclerosis patients who Laquinimod Other Compounds Selmaj, H.L. Weiner, J. Palmer, D.H. Margolin, participated in the CARE-MS studies: three-year Ocrelizumab Plegridy P. Oyuela, M.A. Panzara, D.A.S. Compston follow-up Tysabri Secukinumab Gilenya 15:30 - 17:00 Long-term treatment - - - - - T. Vollmer, X. Montalban, G. Comi, T. Multicentre, randomized, placebo controlled study P 1054 monitoring Ziemssen, A. Boyko, P. Vermersch, N. Sasson, to evaluate the efficacy, safety and tolerability of T. Gorfine, V. Knappertz, M. Filippi two doses of oral laquinimod (0.6mg/day and 1.2mg/day) for the treatment of patients with relapsing remitting multiple sclerosis
15:30 - 17:00 Long-term treatment - - - - - T. Vollmer, P.S. Sorensen, K. Selmaj, F. Zipp, Results of switching to laquinimod in the open- P 1055 monitoring E. Havrdova, J. Cohen, Y. Sidi, T. Gorfine, D. label extension phase of the BRAVO study Arnold for the BRAVO Study Group
15:30 - 17:00 Long-term treatment - - - - - P.S. Sorensen, G. Cutter, T. Vollmer, G. Comi, The risk of disability progression is associated P 1057 monitoring D. Ladkani, N. Sasson, V. Knappertz with multiple sclerosis functional composite (MSFC) scores in the laquinimod phase 3 trials
15:30 - 17:00 Risk management - - - - - B. Kieseier, P. Calabresi, T. Song, Y. Zhu, S. Safety and tolerability of peginterferon beta-1a in P 1061 for disease modifying Hung, A. Deykin, A. Seddighzadeh patients with relapsing-remitting multiple treatments sclerosis: data from the pivotal phase 3 ADVANCE study 15:30 - 17:00 Treatment of - - - - - D. Mikol, M. S. Freedman, M. D. Goldman, H-P ASCEND study of natalizumab efficacy on P 1087 progressive MS Hartung, E. Havrdova, D. Jeffery, R. Kapoor, A. reducing disability in patients with secondary Miller, F. Sellebjerg, S. Lee, Y. Chen, D. progressive multiple sclerosis: baseline Cadavid, B. Ticho demographics and disease characteristics 15:30 - 17:00 Treatment of - - - - - D. Cadavid, B. Brochet, G.L. Mancardi, U. The MS-COG, a novel endpoint for measurement P 1088 progressive MS Nocentini, T. Kaushik, L. Xu, Y. Chen, D. Mikol, of cognitive function in multiple sclerosis clinical B. Ticho trials: baseline characteristics of the cognitive substudy of the ASCEND natalizumab secondary progressive multiple sclerosis study
15:30 - 17:00 Others - - - - - A. T. Reder, D. Jeffery, D. Goodin, L. Kappos, Long-term efficacy of fingolimod in patients with P 1092 F. D. Lublin, E. W. Radue, K. Rammohan, T. relapsing remitting multiple sclerosis: results from Vollmer, M. A. Agius, T. Stites, B. Li, L. the phase 3 FREEDOMS II extension study Cappiello, P. von Rosenstiel, P. A. Calabresi
15:30 - 17:00 Others - - - - - M. Mäurer, F. Lublin, G. Comi, M. Freedman, L. Impact of severe relapses on disability, fatigue P 1093 Kappos, A. Miller, T. Olsson, J. Wolinsky, C. and health-related quality of life outcomes: a Dive-Pouletty, S. Bozzi, P. O'Connor pooled dataset of the phase 3 TEMSO and TOWER studies
Source: ECTRIMS 2013 Slide 32 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Friday, October 4, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:30 - 17:00 Others - - - - - R. Macdonell, F. Lublin, G. Comi, M.S. Teriflunomide reduces relapse-related sequelae, P 1095 Company Events ONO-4641 Freedman, L. Kappos, M. Mäurer, A. Miller, severe relapses, hospitalisations and Aubagio Ponesimod T.P. Olsson, J.S. Wolinsky, S. Bozzi, C. Dive- corticosteroid use: pooled data from the phase 3 Alemtuzumab RPC1063 Pouletty, P. O'Connor TEMSO and TOWER studies Tecfidera Copaxone 15:30 - 17:00 Others - - - - - W. Camu, E. Thouvenot, M. Meinel, N. Sfikas, Influence of baseline clinical and demographic P 1101 Daclizumab BIIB033 P. Chin, D. Piani-Meier, D. Tomic, E. Verdun characteristics on disease evolution in the phase Laquinimod Other Compounds 3 FREEDOMS study in patients with relapsing Ocrelizumab Plegridy remitting multiple sclerosis Tysabri Secukinumab 15:30 - 17:00 Others - - - - - R. Rudick, H. Wiendl, L. Steinman, A. Bar-Or, Efficacy and safety of AIN457 (secukinumab) in P 1103 Gilenya R. Bhore, D. Bennett, M. Bieniek, A. de Vera, patients with relapsing multiple sclerosis: design X. Montalban of an adaptive dose-ranging phase 2 study
15:30 - 17:00 Quality of life - - - - - M. Kita, R.J. Fox, R. Gold, G. Giovannoni, J.T. Interim analysis of quality of life in patients with P 1127 Phillips, S.P. Sarda, J. Kong, R. Zhang, V. relapsing remitting multiple sclerosis treated with Viglietta, S.I. Sheikh, L. Kappos BG-12 (dimethyl fumarate) in the ENDORSE study 18:00 - 18:05 Satellite Symposium Hall A P.S. Sorensen "Genzyme, a Sanofi Company: The challenges of 222 disease management in MS: navigating the changing landscape" - Welcome and introduction 18:05 - 18:30 Satellite Symposium - - - - - G. Giovannoni "Genzyme, a Sanofi Company: The challenges of 223 disease management in MS: navigating the changing landscape" - Evolving considerations for patient management & treatment selection 18: 30 - 18:55 Satellite Symposium - - - - - P. Coyle, T. Ziemssen "Genzyme, a Sanofi Company: The challenges of 224 disease management in MS: navigating the changing landscape" - Highlights from the changing landscape in MS 19:15 - 19:30 Satellite Symposium Hall A H. Lassmann "Teva Neuroscience: Multiple sclerosis 225 management: Have we got the focus right?" - Pathogenesis of multiple sclerosis: looking back to the future 19:30 - 19:45 Satellite Symposium G. Cutter "Teva Neuroscience: Multiple sclerosis 226 management: Have we got the focus right?" - Treatment goals in multiple sclerosis: a moving target? 19:45 - 20:00 Satellite Symposium A. Thompson "Teva Neuroscience: Multiple sclerosis 227 management: Have we got the focus right?" - Putting the patient first: outcomes that matter
Source: ECTRIMS 2013 Slide 33 September 2013 Key Sessions at ECTRIMS 2013 (cont.)
Saturday, October 5, 2013 Legend: Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 07:15 - 07:20 Satellite Symposium Hall B M. Trojano "Merck Serono: Grant for Multiple Sclerosis 228 Company Events ONO-4641 Innovation Awards" - Introduction Aubagio Ponesimod 07:20 - 07:35 Satellite Symposium Hall B P. Rieckmann "Merck Serono: Grant for Multiple Sclerosis 229 Alemtuzumab RPC1063 Innovation Awards" - MS treatment in the 21st Tecfidera Copaxone century Daclizumab BIIB033 07:35 - 07:55 Satellite Symposium Hall B - - - - - "Merck Serono: Grant for Multiple Sclerosis 230 Laquinimod Other Compounds Innovation Awards" - Vignette talks from Ocrelizumab Plegridy recipients of the 2013 award Tysabri Secukinumab 10:30 - 10:50 Closing Session Hall B S. Hauser Charcot Lecture - Beating MS: A story of B cells, 239 Gilenya with twists and turns 10:50 - 11:10 Closing Session Hall B B. Kieseier ECTRIMS Highlights: trials 240
11:10 - 11:30 Closing Session Hall B A. Prat ECTRIMS Scientific Highlights 241
Source: ECTRIMS 2013 Slide 34 September 2013 ECTRIMS 2013 Sessions by Day Wednesday, October 2, 2013
Wednesday, October 2, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 08:30 - 09:00 Teaching Course Hall A S. Fredrikson "How do I choose the correct disease-modifying 6 Company Events ONO-4641 treatment for my MS patient?" - To treat or not to Aubagio Ponesimod treat CIS and RRMS Alemtuzumab RPC1063 08:30 - 09:00 Teaching Course Hall D D. Pelletier "Clinically isolated syndromes (CIS)" - Definition 9 Tecfidera Copaxone of CIS: adults versus children Daclizumab BIIB033 08:30 - 09:00 Teaching Course Hall G G.E. Holder "Electrodiagnostic examinations in MS" - Visual 18 Laquinimod Other Compounds electrophysiology (VEP, ERG) Ocrelizumab Plegridy ● 09:00 - 09:30 Teaching Course Hall A R. Fox "How do I choose the correct disease-modifying 7 Tysabri Secukinumab treatment for my MS patient?" - Choosing the right treatment for the individual patient Gilenya 09:00 - 09:30 Teaching Course Hall D O. Ciccarelli "Clinically isolated syndromes (CIS)" - What are 10 the clinical, CSF, and MRI predictors of conversion to MS? ● 09:30 - 10:00 Teaching Course Hall A B. Kieseier "How do I choose the correct disease-modifying 8 treatment for my MS patient?" - When and how should treatment be switched or escalated? 09:30 - 10:00 Teaching Course Hall D M. Tintoré "Clinically isolated syndromes (CIS)" - Definition 11 of CIS: adults versus children - How can we treat and manage CIS patients? 09:30 - 10:00 Teaching Course Hall F M. Houtchens "Management of the pregnant MS patient" - 17 Therapeutic consideration during pregnancy 09:30 - 10:00 Teaching Course Hall G E.S. Papathanasiou "Electrodiagnostic examinations in MS" - Evoked 20 potentials ● 10:30 - 11:00 Teaching Course Hall C A. Rovira "MRI issues in clinical practice" - Use of brain and 33 spinal cord MRI for differential diagnosis ● 10:30 - 11:00 Teaching Course Hall F N. de Stefano "MRI relevance in neurodegeneration" - Brain 36 MRI: biomarkers of neurodegeneration 10:30 - 11:00 Teaching Course Hall G V. Entwistle "Shared decision making to improve treatment 39 decisions" - What is SDM? ● 10:30 - 11:00 Teaching Course Hall A P. Vermersch "Differential diagnoses and diagnostic dilemmas 21 in MS" - Diagnostic approach to multiple sclerosis ● 11:00 - 11:30 Teaching Course Hall C M. Wattjes "MRI issues in clinical practice" - How and when 34 should brain and spinal cord MRI be performed in the diagnostic process? 11:00 - 11:30 Teaching Course Hall F M. Rocca "MRI relevance in neurodegeneration" - Spinal 37 cord MRI: biomarkers of neurodegeneration 11:00 - 11:30 Teaching Course Hall G C. Heesen "Shared decision making to improve treatment 40 decisions" - How can SDM be enhanced in MS? Patient-mediated interventions ● 11:30 - 12:00 Teaching Course Hall C X. Montalban "MRI issues in clinical practice" - MRI in predicting 35 treatment response: ready to be used in individual patients?
Source: ECTRIMS 2013 Slide 36 September 2013 Wednesday, October 2, 2013
Wednesday, October 2, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 11:30 - 12:00 Teaching Course Hall F C. Enzinger "MRI relevance in neurodegeneration" - Imaging 38 Company Events ONO-4641 of iron accumulation Aubagio Ponesimod 11:30 - 12:00 Teaching Course Hall G A. Solari "Shared decision making to improve treatment 41 Alemtuzumab RPC1063 decisions" - How can SDM be enhanced in MS? Tecfidera Copaxone Clinician-mediated interventions Daclizumab BIIB033 12:30 - 13:00 European Charcot Hall A G. Ebers, A. Ascherio "The controversial role of vitamin D in multiple 42 Laquinimod Other Compounds Foundation sclerosis" - Is the evidence sufficient to give Ocrelizumab Plegridy vitamin D to everybody in the general population to prevent multiple sclerosis? Tysabri Secukinumab Gilenya 13:00 - 13:30 European Charcot Hall A G. Edan, X. Montalban "The controversial role of vitamin D in multiple 44 Foundation sclerosis" - Clinical trials are necessary and feasible 16:12 - 16:24 Young Scientific Hall B L. Galleguillos Goiry, D. Henault, T.A. Johnson, Relation between total peripheral blood 58 Investigators' A. Bar-Or, J.P. Antel lymphocyte counts and T cell subset profiles in Session 2 FTY720-treated multiple sclerosis patients ● 17:15 - 17:35 Satellite Symposium Hall A H.-P. Hartung "Biogen Idec: Reinventing MS care – evolution" - 65 Tailoring choice: a drug for each patient at the right time ● 17:35 - 17:55 Satellite Symposium Hall A G. Giovannoni "Biogen Idec: Reinventing MS care – evolution" - 66 Silencing the disease from the start ● 17:55 - 18:15 Satellite Symposium Hall A P. Calabresi "Biogen Idec: Reinventing MS care – evolution" - 67 Advancing interferons for people with MS ● 18:30 - 18:35 Satellite Symposium Hall A D. Bates "Merck Serono: Supporting patient engagement 68 for optimized treatment management in MS" - Introduction ● 18:35 - 18:50 Satellite Symposium Hall A M.S. Freedman "Merck Serono: Supporting patient engagement 69 for optimized treatment management in MS" - Defining goals at the start of treatment ● 18:50 - 19:05 Satellite Symposium Hall A A. Feinstein "Merck Serono: Supporting patient engagement 70 for optimized treatment management in MS" - Understanding our patients: the importance of effective communication ● 19:05 - 19:20 Satellite Symposium Hall A A. Lugaresi "Merck Serono: Supporting patient engagement 71 for optimized treatment management in MS" - Engaging with patients to achieve treatment goals
● 19:20 - 19:30 Satellite Symposium Hall A D. Bates, D. Lowden "Merck Serono: Supporting patient engagement 72 for optimized treatment management in MS" - Discussion: patient engagement with MS treatments ● 18:30 - 19:30 Satellite Symposium Hall A D. Bates "Merck Serono: Supporting patient engagement 73 for optimized treatment management in MS" - Close
Source: ECTRIMS 2013 Slide 37 September 2013 Thursday, October 3, 2013
Thursday, October 3, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 07:45 - 08:05 Satellite Symposium Hall A X. Montalban "Biogen Idec: Reinventing MS care – revolution" - 74 Company Events ONO-4641 Defending the brain Aubagio Ponesimod ● 08:05 - 08:25 Satellite Symposium Hall A T. Berger "Biogen Idec: Reinventing MS care – revolution" - 75 Alemtuzumab RPC1063 Returning mobility and QoL to people with MS Tecfidera Copaxone ● 08:25 - 08:45 Satellite Symposium Hall A A. Sandrock Biogen Idec: Reinventing MS care – revolution - 76 Daclizumab BIIB033 The future is repair Laquinimod Other Compounds ● 09:30 - 10:15 Plenary Session 1 Hall A G. Comi "Welcome Address and ECTRIMS Lecture" - 81 Ocrelizumab Plegridy Early treatment of multiple sclerosis Tysabri Secukinumab ● 11:05 - 11:25 Window of Hall A J. Cohen Long-term benefits of MS treatment 95 opportunity in MS Gilenya 11:49 - 12:01 Windowtreatment of Hall A M. Romeo, V. Martinelli, M. Rodegher, L. Early predictors of long-term disability progression 98 opportunity in MS Moiola, B. Colombo, M.J. Messina, M. Radaelli, in relapsing remitting multiple sclerosis patients treatment G. Comi treated with disease-modifying treatments
12:01 - 12:13 Window of Hall A A. Miller, J. Wolinsky, L. Kappos, G. Comi, TOPIC main outcomes: efficacy and safety of 99 opportunity in MS M.S. Freedman, T. Olsson, A. Rugina, D. once-daily oral teriflunomide in patients with treatment Bauer, J. Delhay, B. Wamil, P. Truffinet, P. clinically isolated syndrome ● 13:00 - 13:15 Satellite Symposium Hall A P.S.O’Connor Sorensen "Teva Neuroscience: Re-evaluating the treatment 105 algorithm in multiple sclerosis: emerging insights" - Welcome and introduction ● 13:15 - 13:30 Satellite Symposium Hall A F. Zipp "Teva Neuroscience: Re-evaluating the treatment 106 algorithm in multiple sclerosis: emerging insights" - Multiple sclerosis: changing concepts, new targets
● 13:30 - 13:45 Satellite Symposium Hall A P. Vermersch "Teva Neuroscience: Re-evaluating the treatment 107 algorithm in multiple sclerosis: emerging insights" - Treatment sequencing or treatment selection: time to re-evaluate our approach? ● 13:45 14:00 Satellite Symposium Hall A F. Lublin "Teva Neuroscience: Re-evaluating the treatment 108 algorithm in multiple sclerosis: emerging insights" - Older, but wiser? Re-evaluating the role of established multiple sclerosis therapies 14:15 - 14:35 Clinical and Hall A A. Rovira Magnetic resonance monitoring of lesion evolution 121 paraclinical in multiple sclerosis monitoring of MS evolution
Source: ECTRIMS 2013 Slide 38 September 2013 Thursday, October 3, 2013
Thursday, October 3, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 14:55 - 15:07 MS and gender Hall D T. Kalincik, V. Vivek, V. Jokubaitis, J. Lechner- Relapse incidence in women and men throughout 111 Company Events ONO-4641 Scott, M. Trojano, G. Izquierdo, A. Lugaresi, F. the course of multiple sclerosis: an MSBase Aubagio Ponesimod Grand'Maison, R. Hupperts, C. Oreja-Guevara, cohort study Alemtuzumab RPC1063 R. Bergamaschi, G. Iuliano, R. Alroughani, V. Tecfidera Copaxone Van Pesch, M.P. Amato, M. Slee, F. Verheul, R. Fernandez-Bolanos, M. Fiol, D. La Spitaleri, Daclizumab BIIB033 E. Cristiano, O. Gray, J. Cabrera-Gomez, V. Laquinimod Other Compounds Shaygannejad, J. Herbert, S. Vucic, M. Ocrelizumab Plegridy Needham, T. Petkovska-Boskova, C. Sirbu, P. Tysabri Secukinumab Duquette, M. Girard, P. Grammond, C. Boz, G. Gilenya Giuliani, M. Rio, M. Barnett, S. Flechter, F. Moore, B. Singhal, E. Bacie Bacile, M. Saladino, C. Shaw, E. Skromne, N. Vella, T. Spelman, D. Liew, T. Kilpatrick, H. Butzkueven on behalf of the MSBase Study Group
15:31 - 15:43 MS and gender Hall D K. Hellwig, G. Koren, H. Butzkueven, H. Tilson, Cumulative data on pregnancy outcomes after 114 S. Hernández-Diaz, T. Macdonald, E. exposure to fingolimod Kornyeyeva, E. Plana, Y. Lu, M. Cremer, R.K Amar, R. Schlosshauer, W. Collins, Y. Geissbühler, G. Karlsson 15:45 - 17:00 Economic burden - - - - - C Carroll, K. Fairman, M. Lage Medical and pharmacy costs for US patients with P 352 multiple sclerosis in 2011 ● 15:45 - 17:00 Experimental models - - - - - R. Peach, J. Brooks, H. Dedman, R. Powell, F. RPC1063, a potent and selective sphingosine 1- P 375 Scott, G. Timony phosphate 1 receptor modulator, has a favourable preclinical safety profile 15:45 - 17:00 Experimental models - - - - - B. Hu, K-F. So, B. Pepinsky, S. Mi Blocking LINGO1 promotes axonal regeneration P 378 in the rat optic nerve crush model 15:45 - 17:00 Immunomodulation/ - - - - - R. Bermel, R. Hashmonay, X. Meng, S. Fingolimod first-dose effects in patients with P 511 Immunosuppression Randhawa, P. Von Rosenstiel, N. Sfikas, D. relapsing multiple sclerosis concomitantly treated Kantor with serotonin-specific reuptake inhibitors 15:45 - 17:00 Immunomodulation/ - - - - - G. Comi, R. Gold, L. Kappos, P. Von Relapse and safety outcomes in patients who P 513 Immunosuppression Rosenstiel, A. Sinha, D. Tomic transitioned from glatiramer acetate or interferon beta to fingolimod in the open-label FIRST study ● 15:45 - 17:00 Immunomodulation/ - - - - - P. Calabresi, B. Kieseier, D. Arnold, L. Balcer, Peginterferon beta-1a provides improvements in P 514 Immunosuppression A. Boyko, J. Pelletier, S. Liu, Y. Zhu, X. You, A. clinical and radiological disease activity in Seddighzadeh, B. Sperling, S. Hung, A. Deykin relapsing-remitting multiple sclerosis: year 1 findings from the phase 3 ADVANCE study
Source: ECTRIMS 2013 Slide 39 September 2013 Thursday, October 3, 2013
Thursday, October 3, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:45 - 17:00 Immunomodulation/ - - - - - P.S. Sorensen, D.L. Arnold, J.A. Cohen, E.J. Lymphocyte counts and efficacy outcomes after P 515 Company Events ONO-4641 Immunosuppression Fox, H.-P. Hartung, E. Havrdova, K. Selmaj, H. alemtuzumab in relapsing remitting multiple Aubagio Ponesimod Weiner, J. Palmer, D.H. Margolin, M.A. sclerosis patients: the CARE-MS studies Alemtuzumab RPC1063 Panzara, D.A.S. Compston, A.J. Coles Tecfidera Copaxone Daclizumab BIIB033 15:45 - 17:00 Immunomodulation/ - - - - - F. Barkhof, J.A. Cohen, E. Radue, L. Kappos, Brain volume changes, on-study correlations and P 518 Laquinimod Other Compounds Immunosuppression P. Calabresi, D. Häring, N. Sfikas, P. Von the link to disability in three fingolimod phase 3 Ocrelizumab Plegridy Rosenstiel, G. Francis studies Tysabri Secukinumab 15:45 - 17:00 Immunomodulation/ - - - - - E. Havrdova, D. Bates, S. Galetta, G. Effects of natalizumab treatment on freedom from P 519 Immunosuppression Giovannoni, M. Hutchinson, F. Lublin, P. disease activity by baseline characteristics in Gilenya O’Connor, F. Pellegrini, J. Phillips, C. Polman, AFFIRM H. Wiendl, S. Belachew, R. Patel, A. Pace
15:45 - 17:00 Immunomodulation/ - - - - - E. Havrdova, A. Belova, A. Goloborodko, A. Sensitivity analysis of a phase IIa study of P 520 Immunosuppression Tisserant, A. Wright, H. Garren, E. Wallstroem, secukinumab in relapsing remitting multiple A. de Vera, D.R. Johns sclerosis 15:45 - 17:00 Immunomodulation/ - - - - - E. Havrdova, R. Gold, R.J. Fox, L. Kappos, J.T. Effect of BG-12 (dimethyl fumarate) on freedom P 521 Immunosuppression Phillips, A. Zhang, N.C. Kurukulasuriya, S.I. from measured clinical and neuroradiological Sheikh, V. Viglietta, G. Giovannoni disease activity over time in patients with relapsing remitting multiple sclerosis: results from the phase 3 studies 15:45 - 17:00 Immunomodulation/ - - - - - O. Khan, B.A.C. Cree, P. Cabre, M. Inglese, J. The efficacy and safety of fingolimod in an African- P 522 Immunosuppression Perumal, X. Meng, R. Hashmonay, L. Barbato, American patient subgroup from FREEDOMS II P.K. Coyle 15:45 - 17:00 Immunomodulation/ - - - - - T. Ziemssen, D.L. Arnold, J.A. Cohen, A.J. Immunogenicity of alemtuzumab does not impact P 523 Immunosuppression Coles, E.J. Fox, H.-P. Hartung, E. Havrdova, safety and efficacy in relapsing remitting multiple K.W. Selmaj, H.L. Weiner, J. Palmer, D.H. sclerosis patients in the CARE-MS I study Margolin, S. Richards, C. Sung, M.A. Panzara, D.A.S. Compston 15:45 - 17:00 Immunomodulation/ - - - - - F. Lublin, G. Cutter, G. Giovannoni, C. Polman, Natalizumab reduces the disabling amplitude of P 524 Immunosuppression D. Paes, R. Patel, J. Sun, S. Belachew multiple sclerosis relapses and improves post- relapse residual disability 15:45 - 17:00 Immunomodulation/ - - - - - E. Radue, E. Havrodova, M. McNeill, K. Decrease in T1 black hole volume over 2 years of P 525 Immunosuppression Riester, J. Elkins daclizumab high-yield process treatment
15:45 - 17:00 Immunomodulation/ - - - - - E. Radue, J.A. Cohen, F. Barkhof, L. Kappos, Baseline predictors of brain atrophy in phase 3 P 526 Immunosuppression P. Calabresi, D. Häring, N. Sfikas, P. Von studies of fingolimod Rosenstiel, G. Francis
Source: ECTRIMS 2013 Slide 40 September 2013 Thursday, October 3, 2013
Thursday, October 3, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:45 - 17:00 Immunomodulation/ - - - - - J. Woodworth, P. Duda, E. Fox, N. Lucas, T. Comparative pharmacokinetics and P 529 Company Events ONO-4641 Immunosuppression Plavina pharmacodynamics of subcutaneous and Aubagio Ponesimod intravenous administration of natalizumab Alemtuzumab RPC1063 ● 15:45 - 17:00 Immunomodulation/ - - - - - L.H. Kasper, D.L. Arnold, J.A. Cohen, A.J. Lymphocyte subset dynamics following P 531 Tecfidera Copaxone Immunosuppression Coles, E.J. Fox, H.-P. Hartung, E. Havrdova, alemtuzumab treatment in the CARE-MS II study Daclizumab BIIB033 K.W. Selmaj, H.L. Weiner, J. Palmer, D.H. Laquinimod Other Compounds Margolin, M.A. Panzara, D.A.S. Compston Ocrelizumab Plegridy ● 15:45 - 17:00 Immunomodulation/ - - - - - K. Selmaj, F. Zipp, T. Vollmer, A. Bar-Or, B. Effect of ONO-4641, a potent, oral, selective P 536 Tysabri Secukinumab Immunosuppression Due, T.Z. Fischer, K. Thangavelu on behalf of sphingosine-1-phosphate receptor-1 and -5 the DreaMS study investigators agonist, on MRI outcomes in patients with Gilenya relapsing remitting multiple sclerosis: subgroup analyses from the phase 2 DreaMS study
● 15:45 - 17:00 Immunomodulation/ - - - - - K. Selmaj, R. Gold, R. J. Fox, E. Havrdova, G. Flushing and gastrointestinal tolerability events in P 537 Immunosuppression Giovannoni, A. Pace, M. Novas, L. Meltzer, C. relapsing remitting multiple sclerosis (RRMS) Hotermans, V. Viglietta, J. T. Phillips patients treated with oral BG-12 dimethyl fumarate) in the phase 3 DEFINE and CONFIRM trials ● 15:45 - 17:00 Immunomodulation/ - - - - - R. Gold, J. T. Phillips, A. Bar-Or, M. Three-year follow-up of oral BG-12 (dimethyl P 538 Immunosuppression Hutchinson, L. Kappos, R. Zhang, M. Yang, V. fumarate) treatment in relapsing remitting multiple Viglietta, S. I. Sheikh, R. J. Fox sclerosis (RRMS): integrated clinical efficacy data from the DEFINE, CONFIRM, and ENDORSE studies ● 15:45 - 17:00 Immunomodulation/ - - - - - B. Kieseier, P. Calabresi, D. Arnold, Y. Zhu, S. Subgroup and sensitivity analyses of the primary P 539 Immunosuppression Liu, S. Hung, A. Deykin, S. Sheikh endpoint from the peginterferon beta-1a ADVANCE study: a pivotal phase 3 study in patients with relapsing-remitting multiple sclerosis
● 15:45 - 17:00 Immunomodulation/ - - - - - B. Kieseier, P. Calabresi, S. Liu, Y. Zhu, X. Effect of peginterferon beta-1a on disability P 540 Immunosuppression You, B. Sperling, S. Sheikh, S. Hung, A. Deykin progression in patients with relapsing remitting multiple sclerosis: year 1 data from the pivotal phase 3 ADVANCE study 15:45 - 17:00 Immunomodulation/ - - - - - B. Kieseier, O. Stüve, M. Benamor, J. Delhay, Updated pregnancy outcomes from the P 541 Immunosuppression P. Truffinet teriflunomide clinical development programme: retrospective analysis of the teriflunomide clinical trial database
Source: ECTRIMS 2013 Slide 41 September 2013 Thursday, October 3, 2013
Thursday, October 3, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 15:45 - 17:00 Immunomodulation/ - - - - - M. Freedman, J. Wolinsky, G. Comi, L. Long-term safety and efficacy of teriflunomide in P 544 Company Events ONO-4641 Immunosuppression Kappos, T. Olsson, A. Miller, M. Benamor, D. patients with relapsing forms of multiple sclerosis Aubagio Ponesimod Dukovic, J. Liang, P. Truffinet, P. O'Connor in the TEMSO extension trial Alemtuzumab RPC1063 Tecfidera Copaxone ● 15:45 - 17:00 Immunomodulation/ - - - - - D. Cadavid, I. Melamed, H. Gevorkyan, N. The use of magnetic resonance imaging to P 545 Daclizumab BIIB033 Immunosuppression Richert monitor the safety of anti-LINGO-1: findings from Laquinimod Other Compounds phase 1 studies in healthy volunteers and subjects with multiple sclerosis Ocrelizumab Plegridy Tysabri Secukinumab ● 15:45 - 17:00 Immunomodulation/ - - - - - T. Vollmer, F. Zipp, A. Bar-Or, B. Due, K. Magnetic resonance imaging measures of P 547 Immunosuppression Thangavelu, T.Z. Fischer, K. Selmaj on behalf efficacy in patients with multiple sclerosis Gilenya of the DreaMS study investigators receiving ONO-4641, a sphingosine-1-phosphate receptor-1 and -5 agonist: interim results from an extension of the DreaMS study 15:45 - 17:00 Immunomodulation/ - - - - - J. T. Phillips, M. Hutchinson, R. Fox, R. Gold, Management strategies for fushing and P 549 Immunosuppression E. Havrdova gastrointestinal events associated with BG-12 (dimethyl fumarate): expert panel recommendations ● 15:45 - 17:00 Immunomodulation/ - - - - - S.Y. Hong, J. Park, W. Park, H. Park, D. Park, Efficacy and safety of LC510201, an orally active, P 552 Immunosuppression J. Choi, S. Baek, J. Park, H. Park selective sphingosine-1-phosphate receptor 1 (S1P1) and -5 (S1P5) agonist, in preclinical models of multiple sclerosis 15:45 - 17:00 Immunomodulation/ - - - - - K. R. Edwards, H. Crayton, J. Calkwood, N. Patient- and physician-reported outcomes after P 555 Immunosuppression Agashivala, S. Li, P. Chin, S. Randhawa therapy switch from interferon beta to fingolimod versus staying on interferon beta therapy
● 15:45 - 17:00 Immunomodulation/ - - - - - M. Hutchinson, R. Gold, R. J. Fox, E. Clinical efficacy of BG-12 (dimethyl fumarate) for P 563 Immunosuppression Havrdova, G. Giovannoni, A. Zhang, C. relapsing remitting multiple sclerosis according to Hotermans, M. Stephan, A. Bar-Or prior therapy: an integrated analysis of the phase 3 DEFINE and CONFIRM studies
● 15:45 - 17:00 Immunomodulation/ - - - - - A. Savinainen, S. El Bawab, T. Crandall, R. ONO-4641, a potent and selective sphingosine-1- Immunosuppression Chang, U. Boschert, T. Dellovade phosphate receptor-1 and -5 agonist, results in less lymphopenia than fingolimod at effective doses in a preclinical model of multiple sclerosis
15:45 - 17:00 Immunomodulation/ - - - - - U. Schulze-Topphoff, M. Varrin-Doyer, K. Dimethyl fumarate utilizes Nrf2-independent and Immunosuppression Pekarek, R. H. Scannevin, S. S. Zamvil Nrf2-dependent pathways for immune modulation
Source: ECTRIMS 2013 Slide 42 September 2013 Thursday, October 3, 2013
Thursday, October 3, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:45 - 17:00 Neuroprotection - - - - - B. Parodi, C. Cordano, D. Giunti, C. Usai, N. Monomethylfumarate induces a switch of Company Events ONO-4641 Kerlero de Rosbo, R. Scannevin, A. Uccelli activated microglia from a pro-inflammatory to a Aubagio Ponesimod neuroprotective phenotype Alemtuzumab RPC1063 15:45 - 17:00 Long-term treatment - - - - - C. Ford, D. Ladkani on behalf of the US Open- Twenty years of continuous treatment of multiple P 577 Tecfidera Copaxone monitoring Label Glatiramer Acetate Study Group sclerosis with glatiramer acetate 20mg daily: long- Daclizumab BIIB033 term clinical results of the US open-label Laquinimod Other Compounds extension study Ocrelizumab Plegridy ● 15:45 - 17:00 Long-term treatment - - - - - H.-P. Hartung, D.L. Arnold, J.A. Cohen, A.J. Reduction of disability with alemtuzumab in P 592 Tysabri Secukinumab monitoring Coles, E.J. Fox, E. Havrdova, K.W. Selmaj, relapsing remitting multiple sclerosis patients who H.L. Weiner, J. Palmer, D.H. Margolin, M.A. participated in CARE-MS II: three year follow-up Gilenya Panzara, D.A.S. Compston 15:45 - 17:00 Long-term treatment - - - - - R. Rudick, A. Goodman, L. Kappos, F. Lublin, Six-year natalizumab safety and efficacy data P 593 monitoring P. O’Connor, C. Polman, F. Forrestal, M. from the STRATA study Chirieac, P. Duda 15:45 - 17:00 Risk management - - - - - J. White, P. Calabresi, Y. Zhu, T. Song, A. Immunogenicity with peginterferon beta-1a in P 600 for disease modifying Seddighzadeh, S. Hung , A. Deykin, M. patients with relapsing-remitting multiple treatments Subramanyam sclerosis: data from the pivotal phase 3 ADVANCE study ● 15:45 - 17:00 Risk management - - - - - V. Limmroth, S. Hoyer, K. Schuh, M. Lang, O. Good cardiac safety profile after fingolimod P 602 for disease modifying Hoffmann, T. Ziemssen (Gilenya®) treatment initiation in patients with treatments relapsing remitting multiple sclerosis: first interim analysis of the START study ● 15:45 - 17:00 Risk management - - - - - E. Havrdova, D.L. Arnold, J.A. Cohen, A.J. Infection risk with alemtuzumab in patients with P 603 for disease modifying Coles, E.J. Fox, H.-P. Hartung, K. Selmaj, H.L. relapsing remitting multiple sclerosis: pooled treatments Weiner, J. Palmer, D.H. Margolin, P. Oyuela, results from the CARE-MS I and CARE-MS II M.A. Panzara, D.A.S. Compston trials 15:45 - 17:00 Tools for detecting - - - - - M.P. Sormani, E.W, Radue, N De Stefano, T. Does the effect of fingolimod on brain atrophy P 611 therapeutic response Sprenger, P. Chin, G. Francis, L. Kappos independently contribute to effects on disability? A patient-level analysis of the FREEDOMS study
15:45 - 17:00 Treatment of - - - - - S.F. Hunter, H.M. Hunter, D. Kantor Phase 1 trial monitoring response to P 616 progressive MS alemtuzumab (ALE) in naive and ALE- experienced subjects with refractory multiple sclerosis (MS)
Source: ECTRIMS 2013 Slide 43 September 2013 Thursday, October 3, 2013
Thursday, October 3, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 15:45 - 17:00 Others - - - - - L. Kappos, G. Comi, M.S. Freedman, A.E. Pooled efficacy data from two phase 3 placebo- P 618 Company Events ONO-4641 Miller, T.P. Olsson, J.S. Wolinsky, P. Truffinet, controlled trials of oral, once-daily teriflunomide Aubagio Ponesimod S. Cavalier, J.-L. Delhay, D. Dukovic, P. Alemtuzumab RPC1063 O’Connor Tecfidera Copaxone 15:45 - 17:00 Others - - - - - L. Kappos, E. W. Radue, P. Connor, M.P. Switching therapy to fingolimod improves clinical P 619 Daclizumab BIIB033 Amato, L. Zhang-Auberson, D. A. Häring, G. and MRI outcomes: subgroup analysis from the Laquinimod Other Compounds Francis fingolimod phase III FREEDOMS extension (up to four years) study Ocrelizumab Plegridy Tysabri Secukinumab ● 15:45 - 17:00 Others - - - - - J. Cohen, J. Pelletier, P. Chin, N. Sfikas, G. Efficacy of fingolimod in relapsing remitting P 620 Karlsson, P. von Rosenstiel, L. Kappos multiple sclerosis (RRMS) as measured by Gilenya multiple sclerosis functional composite: results from the TRANSFORMS, FREEDOMS, and FREEDOMS II phase 3 studies
● 15:45 - 17:00 Others - - - - - K. Shakeri-Nejad, B. Brendani, N. Pezous, L. Placebo-like occurrence of atrioventricular blocks P 626 Mooney, A. Juan, M. Allison, R.G. Perry, E. and sinus pauses: results from a siponimod Legangneux QT/QTc study 15:45 - 17:00 Others - - - - - S. Biswal, U.K. Veldandi, C. Derne, G. Golla, N. Effect of oral siponimod (BAF312) on the P 627 Muhsen, K. Shakeri-Nejad, E. Legangneux pharmacokinetics and pharmacodynamics of a monophasic oral contraceptive in healthy female subjects 15:45 - 17:00 Others - - - - - H. Zwibel, P. Coyle, B. Cohen, C. Markowitz, Multiple sclerosis therapy adherence and relapse P 631 M. Tullman, T. Leist, M. Oleen-Burkey, M. risk among those switching versus maintaining Schwartz therapies in the TOP MS study ● 15:45 - 17:00 Others - - - - - T. Leist, M. Freedman, L. Kappos, T. Olsson, Pooled safety data from three placebo-controlled P 633 A. Miller, J. Wolinsky, P. O'Connor, M. teriflunomide studies Benamor, J. Delhay, P. Truffinet, D. Dukovic, J. Li, G. Comi 15:45 - 17:00 Others - - - - - N. Bergvall, R. Lahoz, N. Agashivala, A. Relapse rates among patients with multiple P 635 Pradhan, G. Capkun-Niggli, J. R. Korn, A. A. sclerosis who switch from interferon therapy to Petrilla, S. U. Karkare, C. Balderston fingolimod or glatiramer acetate: a retrospective McGuiness, C. Makin US claims database analysis 15:45 - 17:00 Others - - - - - N. Bergvall, M. Costa-Scharplatz, R. Hettle, M. Cost-effectiveness of fingolimod compared to P 636 Tambour, F. Henriksson, S. Fredrikson interferon beta 1a based on patient transitions in TRANSFORMS
Source: ECTRIMS 2013 Slide 44 September 2013 Thursday, October 3, 2013
Thursday, October 3, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:45 - 17:00 Others - - - - - N. Bergvall, R. Lahoz, N. Agashivala, A. Relapse rates among patients with a history of P 637 Company Events ONO-4641 Pradhan, G. Capkun-Niggli, J. R. Korn, A. A. relapses treated with fingolimod compared with Aubagio Ponesimod Petrilla, S. U. Karkare, C. Balderston interferons or glatiramer acetate for the treatment Alemtuzumab RPC1063 McGuiness, C. Makin of multiple sclerosis: a retrospective US claims Tecfidera Copaxone database analysis Daclizumab BIIB033 15:45 - 17:00 Treatment of specific - - - - - V. Brinar, D.L. Arnold, J. Cohen, A.J. Coles, Alemtuzumab improves expanded disability status P 649 Laquinimod Other Compounds symptoms E.J. Fox, H.-P. Hartung, E. Havrdova, K. scale (EDSS) via effects on functional systems: Ocrelizumab Plegridy Selmaj, H. Weiner, J. Palmer, D.H. Margolin, CARE-MS II M.A. Panzara, D.A.S. Compston Tysabri Secukinumab Gilenya 15:45 - 17:00 Treatment of specific - - - - - J. O'Gorman, H. Russell, J. Li, G. Phillips, C. Effect of Aspirin pretreatment or slow dose P 651 symptoms Hotermans, N. C. Kurukulasuriya, V. Viglietta titration on the incidence and severity of flushing and gastrointestinal events associated with BG-12 (dimethyl fumarate) 15:45 - 17:00 Quality of life - - - - - S. Sarda, G. Phillips, J. A. Gaebler, N. C. Health-related quality of life in relapsing remitting P 662 Kurukulasuriya multiple sclerosis (RRMS) patients treated with placebo or BG-12 (dimethyl fumarate): comparison with other medical conditions
15:45 - 17:00 Quality of life - - - - - R. Macdonell, P.S. Sorensen, C. Pozzilli, G. Long-term prolonged-release fampridine P 665 Nagels, D. Laplaud, B. de Jong, A. Martins treatment and health-related quality of life Silva, R. Nicholas, J.A. Gaebler, S. Agarwal, J. outcomes: nine-month interim analysis of the Sun ENABLE study 15:45 - 17:00 Quality of life - - - - - C. Pozzilli, R. Macdonell, P.S. Sorensen, G. Health-related quality of life outcomes following P 658 Nagels, D. Laplaud, B. de Jong, A. Martins long-term treatment with prolonged-release Silva, R. Nicholas, J. Gaebler, J. Sun fampridine: impact on psychological outcomes in the ENABLE study
Source: ECTRIMS 2013 Slide 45 September 2013 Thursday, October 3, 2013
Thursday, October 3, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:45 - 17:00 Hot Topic Hall A M.P. Sormani "Can immunomodulatory treatment change the 135 Company Events ONO-4641 natural history of MS?" - Can we measure long- Aubagio Ponesimod term treatment effects in MS? Alemtuzumab RPC1063 15:45 - 17:00 Hot Topic Hall A N. Koch-Henriksen "Can immunomodulatory treatment change the 136 Tecfidera Copaxone natural history of MS?" - Use of historical controls Daclizumab BIIB033 to compare treatment effects in MS Laquinimod Other Compounds ● 18:05 - 18:20 Satellite Symposium Hall A H. Wiendl "Medscape Education: Evolving the management 142 Ocrelizumab Plegridy of MS: new insights and new directions" - The changing landscape for clinical decisions in Tysabri Secukinumab managing RRMS with oral therapies Gilenya ● 18:20 - 18:35 Satellite Symposium Hall B J. Sastre-Garriga "Medscape Education: Evolving the management 143 of MS: new insights and new directions" - Beyond reducing-relapses in RRMS: the importance of neuroprotection - ● 18:35 - 18:50 Satellite Symposium Hall B H. Butzkueven "Medscape Education: Evolving the management 144 of MS: new insights and new directions" - Balancing efficacy and safety in the real world ● 18:50 - 19:00 Satellite Symposium Hall B H. Wiendl "Medscape Education: Evolving the management 145 of MS: new insights and new directions" - Panel discussion and Q&A ● 19:15 - 19:30 Satellite Symposium Hall B F. Lublin "Bayer HealthCare: 25 years of partnership: 146 working towards a better future for patients with MS" - 25 Years of partnership: working towards a better future for patients with MS ● 19:30 - 19:50 Satellite Symposium Hall B M. Cascione "Bayer HealthCare: 25 years of partnership: 148 working towards a better future for patients with MS" - 25 Years of partnership: current focus ● 19:50 - 20:10 Satellite Symposium Hall B A. Chan "Bayer HealthCare: 25 years of partnership: 149 working towards a better future for patients with MS" - 25 Years of partnership: continuous efforts to improve MS patient support
Source: ECTRIMS 2013 Slide 46 September 2013 Friday, October 4, 2013
Friday, October 4, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 08:00 - 08:05 Satellite Symposium Hall B H.-P. Hartung F. Hoffmann- La Roche Ltd: Selective targeting of 150 Company Events ONO-4641 B Cells: establishing a new horizon for multiple Aubagio Ponesimod sclerosis treatment - Welcome and introduction Alemtuzumab RPC1063 Tecfidera Copaxone ● 08:05 - 08:20 Satellite Symposium Hall B A. Bar-Or F. Hoffmann- La Roche Ltd: Selective targeting of 151 Daclizumab BIIB033 B Cells: establishing a new horizon for multiple Laquinimod Other Compounds sclerosis treatment - B cells as key players in the pathobiology of multiple sclerosis Ocrelizumab Plegridy Tysabri Secukinumab Gilenya ● 08:20 - 08:35 Satellite Symposium Hall B A. Chan F. Hoffmann- La Roche Ltd: Selective targeting of 152 B Cells: establishing a new horizon for multiple sclerosis treatment - Mechanisms of anti-CD20 antibodies in autoimmune diseases ● 08:35 - 08:50 Satellite Symposium Hall B S. Hauser F. Hoffmann- La Roche Ltd: Selective targeting of 153 B Cells: establishing a new horizon for multiple sclerosis treatment - Selective targeting of B cells with ACD20: a promising future for multiple sclerosis therapies? ● 08:50 - 09:00 Satellite Symposium Hall B H.-P. Hartung F. Hoffmann- La Roche Ltd: Selective targeting of 154 B Cells: establishing a new horizon for multiple sclerosis treatment - Question and answer session 09:39 - 09:51 Free Hall D L. Kappos, E. W. Radue, G. Comi, X. Disease control and safety in relapsing-remitting 167 Communications 3 Montalban, H. Butzkueven, H. Wiendl, G. multiple sclerosis (RRMS) patients switching from Giovannoni, Y. Naegelin, T. Sprenger, N. natalizumab to fingolimod: a 32-week, rater- and Mueller-Lenke, F. Dahlke, R. Gottschalk, P. patient-blind, randomized, parallel-group study von Rosenstiel, Y. Zhang, D. Tomic (TOFINGO) ● 10:45 - 11:05 Management of risk Hall A P.S. Sørensen Is risk stratification possible with the new 176 in MS therapy treatments? ● 11:05 - 11:25 Management of risk Hall A R. Gold, B. Kieseier Occurrence and management of PML and IRIS 177 in MS therapy 11:25 - 11:37 Management of risk Hall A A. Voldsgaard, N. Koch-Henriksen, M. Magyari, Cardiac and pulmonary effects related to initiation 178 in MS therapy P.S. Sørensen, A. Oturai of fingolimod treatment ● 14:00 - 14:20 Progressive MS Hall A R. Fox From relapsing-remitting to secondary 195 progressive MS
Source: ECTRIMS 2013 Slide 47 September 2013 Friday, October 4, 2013
Friday, October 4, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 14:20 - 14:40 Progressive MS Hall A F. Sellebjerg Therapeutic opportunities for progressive MS 196 Company Events ONO-4641 ● 14:20 - 14:40 Looking into the Hall D L. Kappos What is in the pipeline? 208 Aubagio Ponesimod future: experimental Alemtuzumab RPC1063 studies of new Tecfidera Copaxone therapies Daclizumab BIIB033 Laquinimod Other Compounds 14:40 - 14:52 Looking into the Hall D S.H. Nye, S. Medicetty, B.D. Trapp, J.G. Yarger NDC-1308 induces remyelination in experimental 209 Ocrelizumab Plegridy future: experimental models of multiple sclerosis studies of new Tysabri Secukinumab therapies Gilenya
15:30 - 17:00 Diagnosis and - - - - - A. Tourbah, N. Caucheteux, M. Genevray, E. Multiple sclerosis diagnosis at the first MRI: is P 723 differential diagnosis Leray, L. Daelman, R. Deschamps, J. Ferré, O. there still space for temporal dissemination? Gout, A. Maarouf, J. Pelletier, G. Edan
15:30 - 17:00 Epidemiology - - - - - N. Makhani, S. Morrow, J. Fisk, C. Evans, S.G. Trends in multiple sclerosis incidence and P 770 Beland, S. Kulaga, E. Kingwell, J. Marriott, J. prevalence in Africa, Asia, Australia and New Dykeman, N. Jetté, T. Pringsheim, C. Wolfson, Zealand: a systematic review R.A. Marrie, M. Koch
15:30 - 17:00 Economic burden - - - - - S. Moser, S. Ortler, T. van Lokven, W. Pharmacoeconomic and clinical characteristics in P 807 Hoffmann, T. Ziemssen patients with multiple sclerosis treated with disease modifying therapies (PEARL): 12 month interim results ● 15:30 - 17:00 Immunology - - - - - G. Giovannoni, A. Mikulskis, M. McNeil, K. Evaluation of immunogenicity in multiple sclerosis P 864 Riester, M. Sweetser, J. Elkins, L. Amaravadi patients continuously treated with daclizumab- HYP during the SELECT and SELECTION clinical trials ● 15:30 - 17:00 Immunomodulation/ - - - - - T. Ziemssen, O. Bajenaru, A. Carrá, N. de COPTIMIZE: a two-year observational survey of P 973 Immunosuppression Klippel, J. de Sá, A. Edland, J. Frederiksen, O. patients with relapsing remitting multiple sclerosis Heinzlef, K. Karageorgiou, A.M. Landtblom, M. switching to glatiramer acetate 20 mg daily Macías Islas, N. Tubridy, Y. Gilgun-Sherki
● 15:30 - 17:00 Immunomodulation/ - - - - - E.W. Radue, D. Stefoski, R. Gold, M. McNeill, Reduction in brain atrophy with extended P 977 Immunosuppression K. Riester, J. Elkins daclizumab HYP treatment: results of SELECT and the SELECT extension study
Source: ECTRIMS 2013 Slide 48 September 2013 Friday, October 4, 2013
Friday, October 4, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 15:30 - 17:00 Immunomodulation/ - - - - - J. Hartung, A. Olson, R. Peach, M. Boehm, B. Results of a thorough QT/QTc (TQT) study of P 983 Company Events ONO-4641 Immunosuppression Mendzelevski, D. Chanter, H. Smith, C. Pan, G. orally administered RPC1063, a novel, selective Aubagio Ponesimod Timony, S. Gujrathi S1P1 receptor agonist, in healthy adult volunteers Alemtuzumab RPC1063 Tecfidera Copaxone ● 15:30 - 17:00 Immunomodulation/ - - - - - D. Arnold, P. Calabresi, B. Kieseier, Y. Zhu, S. Magnetic resonance imaging results from the first P 989 Daclizumab BIIB033 Immunosuppression Liu, S. Hung, A. Deykin, S. Sheikh year of the ADVANCE study, a pivotal phase 3 Laquinimod Other Compounds trial of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis Ocrelizumab Plegridy Tysabri Secukinumab Gilenya ● 15:30 - 17:00 Immunomodulation/ - - - - - R. Gold, G. Giovannoni, J. T. Phillips, R. J. Fox, Effect of BG-12 (dimethyl fumarate) in newly P 990 Immunosuppression A. Zhang, L. Meltzer, N. C. Kurukulasuriya diagnosed relapsing remitting multiple sclerosis (RRMS) patients from the DEFINE and CONFIRM studies ● 15:30 - 17:00 Immunomodulation/ - - - - - R. Gold, J. T. Phillips, E. Havrdova, A. Bar-Or, Oral BG-12 (dimethyl fumarate) and pregnancy: P 991 Immunosuppression L. Kappos, J. Clarke, H. Yuan, M. Novas, M. T. preclinical studies and pregnancy outcomes Sweetser, N. C. Kurukulasuriya, V. Viglietta, R. reported during the clinical development J. Fox programme ● 15:30 - 17:00 Immunomodulation/ - - - - - F. Zipp, T. Vollmer, A. Bar-Or, B. Due, K. Relapse rates in patients with multiple sclerosis P 992 Immunosuppression Thangavelu, T.Z. Fischer, K. Selmaj on behalf receiving ONO-4641, a sphingosine-1-phosphate of the DreaMS study investigators receptor-1 and -5 agonist: interim results from an extension of the DreaMS study ● 15:30 - 17:00 Immunomodulation/ - - - - - C. Pozzilli, Ó. Fernández, T. Olsson, M.S. Maintenance of efficacy, safety and tolerability of P 995 Immunosuppression Freedman, M. Melanson, A. Boster, E.-W. ponesimod in patients with relapsing remitting Radue, B. Hennessy, A. Rames, D. D'Ambrosio multiple sclerosis: phase II extension study
● 15:30 - 17:00 Immunomodulation/ - - - - - J.T. Phillips, R.J. Fox, K. Selmaj, M. Yang, R. Safety profile of BG-12 (dimethyl fumarate) in P 996 Immunosuppression Zhang, M. Novas, M.T. Sweetser, V. Viglietta, relapsing remitting multiple sclerosis: long-term R. Gold interim results from the ENDORSE extension study ● 15:30 - 17:00 Immunomodulation/ - - - - - A. Bar-Or, F. Zipp, T. Vollmer, B. Due, K. Safety of ONO-4641 in patients with relapsing P 997 Immunosuppression Thangavelu, J. Johnson, K. Selmaj on behalf of remitting multiple sclerosis: results from a six- the DreaMS study investigators month interim analysis of the DreaMS extension study
Source: ECTRIMS 2013 Slide 49 September 2013 Friday, October 4, 2013
Friday, October 4, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:30 - 17:00 Immunomodulation/ - - - - - K. Jeanneau, G. Elain, A.K. Mir, K.K. Dev The Anti-IL17A monoclonal antibody P 998 Company Events ONO-4641 Immunosuppression secukinumab (AIN457) attenuates IL17 and TNF- Aubagio Ponesimod induced production of IL6 in human astrocytes Alemtuzumab RPC1063 Tecfidera Copaxone 15:30 - 17:00 Immunomodulation/ - - - - - T. Dehmel, K. Wolffram, C. Warnke, D. The effects of fingolimod on peripheral blood P 999 Daclizumab BIIB033 Immunosuppression Hermsen, F. Boege, T. Bergstroem, M. Pawlita, mononuclear cell phenotypes and Laquinimod Other Compounds H.-P. Hartung, M. Diaz-Lorente, B. C. Kieseier immunoglobulins: results from the BIOBANK study Ocrelizumab Plegridy Tysabri Secukinumab 15:30 - 17:00 Immunomodulation/ - - - - - Y. Naegelin*, M. Rasenack*, N. Sanderson, M. An observational study evaluating disease control, P 1002 Immunosuppression Mehling, C. Sievers, B. Fischer-Barnicol, M. safety, and immunological changes in patients Gilenya Andelova, C. Stippich, E-W. Radue, R.L.P. with relapsing remitting multiple sclerosis Lindberg, L. Kappos, T. Sprenger, T. Derfuss switching from previous treatment with natalizumab to fingolimod (SWITCH-UHBS)
● 15:30 - 17:00 Immunomodulation/ - - - - - D. H. Miller, R. J. Fox, R. Gold, E. Havrdova, L. Three-year follow-up of oral BG-12 (dimethyl P 1004 Immunosuppression Kappos, D. MacManus, T. Yousry, R. Zhang, fumarate) treatment in relapsing remitting multiple M. Yang, V. Viglietta, S. I. Sheikh, K. T. sclerosis (RRMS): integrated magnetic resonance Dawson, D. L. Arnold imaging (MRI) outcomes from DEFINE, CONFIRM, and ENDORSE ● 15:30 - 17:00 Immunomodulation/ - - - - - F. Bernard, D. Yu, A. Gray, U. Boschert, T. Efficacy of ONO-4641, a potent and selective P 1007 Immunosuppression Dellovade, D. Graham sphingosine-1-phosphate receptor-1 and -5 agonist, in a preclinical model of multiple sclerosis
● 15:30 - 17:00 Immunomodulation/ - - - - - M. Hutchinson, R.J. Fox, A. Bar-Or, E. Efficacy of BG-12 (dimethyl fumarate) in relapsing P 1013 Immunosuppression Havrdova, M. Yang, R. Zhang, V. Viglietta, S.I. remitting multiple sclerosis in patients from Sheikh, R. Gold Europe: an integrated analysis of the phase 3 DEFINE and CONFIRM studies ● 15:30 - 17:00 Immunomodulation/ - - - - - R. J. Fox, R. Gold, J. T. Phillips, K. Selmaj, K. Lymphocyte count reductions in relapsing P 1018 Immunosuppression Raghupathi, H. Yuan, J. O'Gorman, M. Novas, remitting multiple sclerosis (RRMS) patients V. Viglietta, N. C. Kurukulasuriya treated with oral BG-12 (dimethyl fumarate): integrated analysis of the placebo-controlled studies 15:30 - 17:00 Long-term treatment - - - - - H. Wiendl, H. Butzkueven, L. Kappos, F. Disease activity and disability progression P 1050 monitoring Pellegrini, M. Trojano, D. Paes, A. Zhang, S. decrease beyond two years on natalizumab in Belachew relapsing multiple sclerosis patients in the TYSABRI® (natalizumab) Observational Programme
Source: ECTRIMS 2013 Slide 50 September 2013 Friday, October 4, 2013
Friday, October 4, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 15:30 - 17:00 Long-term treatment - - - - - L. Kappos, J. A Cohen, F. Barkhof, L. Relapse rates and disability remain consistently P 1052 Company Events ONO-4641 monitoring Cappiello, Y. Zhang, P. Von Rosenstiel low with long-term fingolimod therapy: five-year Aubagio Ponesimod interim results of the LONGTERMS extension Alemtuzumab RPC1063 study Tecfidera Copaxone ● 15:30 - 17:00 Long-term treatment - - - - - J. Lycke, D.L. Arnold, J.A. Cohen, A.J. Coles, Adverse event profile of alemtuzumab in active P 1053 Daclizumab BIIB033 monitoring E.J. Fox, H.-P. Hartung, E. Havrdova, K.W. relapsing remitting multiple sclerosis patients who Laquinimod Other Compounds Selmaj, H.L. Weiner, J. Palmer, D.H. Margolin, participated in the CARE-MS studies: three-year P. Oyuela, M.A. Panzara, D.A.S. Compston follow-up Ocrelizumab Plegridy Tysabri Secukinumab Gilenya ● 15:30 - 17:00 Long-term treatment - - - - - T. Vollmer, X. Montalban, G. Comi, T. Multicentre, randomized, placebo controlled study P 1054 monitoring Ziemssen, A. Boyko, P. Vermersch, N. Sasson, to evaluate the efficacy, safety and tolerability of T. Gorfine, V. Knappertz, M. Filippi two doses of oral laquinimod (0.6mg/day and 1.2mg/day) for the treatment of patients with relapsing remitting multiple sclerosis
● 15:30 - 17:00 Long-term treatment - - - - - T. Vollmer, P.S. Sorensen, K. Selmaj, F. Zipp, Results of switching to laquinimod in the open- P 1055 monitoring E. Havrdova, J. Cohen, Y. Sidi, T. Gorfine, D. label extension phase of the BRAVO study Arnold for the BRAVO Study Group
● 15:30 - 17:00 Long-term treatment - - - - - P.S. Sorensen, G. Cutter, T. Vollmer, G. Comi, The risk of disability progression is associated P 1057 monitoring D. Ladkani, N. Sasson, V. Knappertz with multiple sclerosis functional composite (MSFC) scores in the laquinimod phase 3 trials
● 15:30 - 17:00 Risk management - - - - - B. Kieseier, P. Calabresi, T. Song, Y. Zhu, S. Safety and tolerability of peginterferon beta-1a in P 1061 for disease modifying Hung, A. Deykin, A. Seddighzadeh patients with relapsing-remitting multiple treatments sclerosis: data from the pivotal phase 3 ADVANCE study 15:30 - 17:00 Tools for detecting - - - - - M.P. Sormani, G. Cutter, G. Comi, T. Vollmer, Evaluating the relationship between laquinimod's P 1080 therapeutic response P.S. Sorensen, D. Ladkani, N. Sasson, V. effects on relapse and disability progression Knappertz ● 15:30 - 17:00 Treatment of - - - - - D. Mikol, M. S. Freedman, M. D. Goldman, H-P ASCEND study of natalizumab efficacy on P 1087 progressive MS Hartung, E. Havrdova, D. Jeffery, R. Kapoor, A. reducing disability in patients with secondary Miller, F. Sellebjerg, S. Lee, Y. Chen, D. progressive multiple sclerosis: baseline Cadavid, B. Ticho demographics and disease characteristics
Source: ECTRIMS 2013 Slide 51 September 2013 Friday, October 4, 2013
Friday, October 4, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 15:30 - 17:00 Treatment of - - - - - D. Cadavid, B. Brochet, G.L. Mancardi, U. The MS-COG, a novel endpoint for measurement P 1088 Company Events ONO-4641 progressive MS Nocentini, T. Kaushik, L. Xu, Y. Chen, D. Mikol, of cognitive function in multiple sclerosis clinical Aubagio Ponesimod B. Ticho trials: baseline characteristics of the cognitive Alemtuzumab RPC1063 substudy of the ASCEND natalizumab secondary Tecfidera Copaxone progressive multiple sclerosis study Daclizumab BIIB033 Laquinimod Other Compounds 15:30 - 17:00 Others - - - - - A. Laroni, D. Brogi, V. Brescia Morra, L. Guidi, Safety of the first dose of fingolimod for multiple P 1091 Ocrelizumab Plegridy C. Pozzilli, G. Comi, A. Lugaresi, R. Turrini, D. sclerosis: results of an open-label clinical trial Raimondi, A. Uccelli, G. Mancardi for the EAP Tysabri Secukinumab Investigators Gilenya ● 15:30 - 17:00 Others - - - - - A. T. Reder, D. Jeffery, D. Goodin, L. Kappos, Long-term efficacy of fingolimod in patients with P 1092 F. D. Lublin, E. W. Radue, K. Rammohan, T. relapsing remitting multiple sclerosis: results from Vollmer, M. A. Agius, T. Stites, B. Li, L. the phase 3 FREEDOMS II extension study Cappiello, P. von Rosenstiel, P. A. Calabresi
● 15:30 - 17:00 Others - - - - - M. Mäurer, F. Lublin, G. Comi, M. Freedman, L. Impact of severe relapses on disability, fatigue P 1093 Kappos, A. Miller, T. Olsson, J. Wolinsky, C. and health-related quality of life outcomes: a Dive-Pouletty, S. Bozzi, P. O'Connor pooled dataset of the phase 3 TEMSO and TOWER studies ● 15:30 - 17:00 Others - - - - - R. Macdonell, F. Lublin, G. Comi, M.S. Teriflunomide reduces relapse-related sequelae, P 1095 Freedman, L. Kappos, M. Mäurer, A. Miller, severe relapses, hospitalisations and T.P. Olsson, J.S. Wolinsky, S. Bozzi, C. Dive- corticosteroid use: pooled data from the phase 3 Pouletty, P. O'Connor TEMSO and TOWER studies ● 15:30 - 17:00 Others - - - - - W. Camu, E. Thouvenot, M. Meinel, N. Sfikas, Influence of baseline clinical and demographic P 1101 P. Chin, D. Piani-Meier, D. Tomic, E. Verdun characteristics on disease evolution in the phase 3 FREEDOMS study in patients with relapsing remitting multiple sclerosis ● 15:30 - 17:00 Others - - - - - R. Rudick, H. Wiendl, L. Steinman, A. Bar-Or, Efficacy and safety of AIN457 (secukinumab) in P 1103 R. Bhore, D. Bennett, M. Bieniek, A. de Vera, patients with relapsing multiple sclerosis: design X. Montalban of an adaptive dose-ranging phase 2 study
15:30 - 17:00 Others - - - - - N. Bergvall, R. Nixon, D. Tomic, N. Sfikas, G. Efficacy of oral fingolimod versus dimethyl P 1105 Cutter, G. Giovannoni fumarate on measures of freedom from disease activity in patients with multiple sclerosis, based on indirect comparisons of phase 3 trials
Source: ECTRIMS 2013 Slide 52 September 2013 Friday, October 4, 2013
Friday, October 4, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 15:30 - 17:00 Others - - - - - N. Bergvall, R. Lahoz, N. Agashivala, A. Persistence and adherence of fingolimod P 1107 Company Events ONO-4641 Pradhan, G. Capkun-Niggli, J. R. Korn, A. A. compared with other disease modifying therapies Aubagio Ponesimod Petrilla, S. U. Karkare, C. Balderston for the treatment of multiple sclerosis: a Alemtuzumab RPC1063 McGuiness, C. Makin retrospective US claims database analysis Tecfidera Copaxone Daclizumab BIIB033 15:30 - 17:00 Treatment of specific - - - - - S. Belachew, C. Hotermans, D. Paes, X. You Effects of natalizumab on measures of P 1120 Laquinimod Other Compounds symptoms ambulation in relapsing remitting multiple Ocrelizumab Plegridy sclerosis patients in the prospective, open-label TIMER study Tysabri Secukinumab Gilenya ● 15:30 - 17:00 Quality of life - - - - - M. Kita, R.J. Fox, R. Gold, G. Giovannoni, J.T. Interim analysis of quality of life in patients with P 1127 Phillips, S.P. Sarda, J. Kong, R. Zhang, V. relapsing remitting multiple sclerosis treated with Viglietta, S.I. Sheikh, L. Kappos BG-12 (dimethyl fumarate) in the ENDORSE study 15:30 - 17:00 Quality of life - - - - - P.S. Sorensen, R. Macdonell, C. Pozzilli, G. Changes in physical functioning and activity P 1128 Nagels, D. Laplaud, B. de Jong, A. Martins following long-term treatment with prolonged- Silva, R. Nicholas, J. Gaebler, S. Agarwal, J. release fampridine in the ENABLE study Sun 15:30 - 17:00 Late Breaking News - - - - - I.B. Bruinsma, S. van Vugt, H. ter Burg, T. van miR-219: clinical implications for MS? P 1191 de Lisdonk, E.J. Kooi, S.E. Baranzini, X. Ji, R.A. Sobel, J.J.G. Geurts, L. Steinman, B.A. de Jong 15:30 - 17:00 Late Breaking News - - - - - J.O. Watzlawik, A.E. Warrington, M. Rodriguez rHIgM22 stimulates remyelination in chronically P 1194 demyelinated spinal cord lesions through a single minimal dose 15:30 - 17:00 Late Breaking News - - - - - J.O. Watzlawik, A.E. Warrington, M. Rodriguez Growth factors PDGF and FGF-2 are required for P 1195 human recombinant rHIgM22-mediated stimulation of oligodendrocyte proliferation and survival ● 18:00 - 18:05 Satellite Symposium Hall A P.S. Sorensen "Genzyme, a Sanofi Company: The challenges of 222 disease management in MS: navigating the changing landscape" - Welcome and introduction ● 18:05 - 18:30 Satellite Symposium - - - - - G. Giovannoni "Genzyme, a Sanofi Company: The challenges of 223 disease management in MS: navigating the changing landscape" - Evolving considerations for patient management & treatment selection ● 18: 30 - 18:55 Satellite Symposium - - - - - P. Coyle, T. Ziemssen "Genzyme, a Sanofi Company: The challenges of 224 disease management in MS: navigating the changing landscape" - Highlights from the changing landscape in MS
Source: ECTRIMS 2013 Slide 53 September 2013 Friday, October 4, 2013
Friday, October 4, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 19:15 - 19:30 Satellite Symposium Hall A H. Lassmann "Teva Neuroscience: Multiple sclerosis 225 Company Events ONO-4641 management: Have we got the focus right?" - Aubagio Ponesimod Pathogenesis of multiple sclerosis: looking back Alemtuzumab RPC1063 to the future Tecfidera Copaxone ● 19:30 - 19:45 Satellite Symposium G. Cutter "Teva Neuroscience: Multiple sclerosis 226 Daclizumab BIIB033 management: Have we got the focus right?" - Laquinimod Other Compounds Treatment goals in multiple sclerosis: a moving target? Ocrelizumab Plegridy Tysabri Secukinumab ● 19:45 - 20:00 Satellite Symposium A. Thompson "Teva Neuroscience: Multiple sclerosis 227 management: Have we got the focus right?" - Gilenya Putting the patient first: outcomes that matter
Source: ECTRIMS 2013 Slide 54 September 2013 Saturday, October 5, 2013
Saturday, October 5, 2013 Legend: Key? Time Event/Topic Location Authors Title ID Sessions To Consider BAF312 ● 07:15 - 07:20 Satellite Symposium Hall B M. Trojano "Merck Serono: Grant for Multiple Sclerosis 228 Company Events ONO-4641 Innovation Awards" - Introduction Aubagio Ponesimod ● 07:20 - 07:35 Satellite Symposium Hall B P. Rieckmann "Merck Serono: Grant for Multiple Sclerosis 229 Alemtuzumab RPC1063 Innovation Awards" - MS treatment in the 21st Tecfidera Copaxone century Daclizumab BIIB033 ● 07:35 - 07:55 Satellite Symposium Hall B - - - - - "Merck Serono: Grant for Multiple Sclerosis 230 Laquinimod Other Compounds Innovation Awards" - Vignette talks from Ocrelizumab Plegridy recipients of the 2013 award Tysabri Secukinumab ● 10:30 - 10:50 Closing Session Hall B S. Hauser Charcot Lecture - Beating MS: A story of B cells, 239 with twists and turns Gilenya ● 10:50 - 11:10 Closing Session Hall B B. Kieseier ECTRIMS Highlights: trials 240
● 11:10 - 11:30 Closing Session Hall B A. Prat ECTRIMS Scientific Highlights 241
Source: ECTRIMS 2013 Slide 55 September 2013 ECTRIMS 2013 Sessions by MS Therapy Aubagio (SASY)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Immunomodulation/ - - - - - M. Freedman, J. Wolinsky, G. Comi, L. Long-term safety and efficacy of teriflunomide in patients with P 544 Immunosuppression Kappos, T. Olsson, A. Miller, M. relapsing forms of multiple sclerosis in the TEMSO extension Benamor, D. Dukovic, J. Liang, P. trial Truffinet, P. O'Connor ● 15:45 - 17:00 Others - - - - - L. Kappos, G. Comi, M.S. Freedman, Pooled efficacy data from two phase 3 placebo-controlled trials P 618 A.E. Miller, T.P. Olsson, J.S. Wolinsky, of oral, once-daily teriflunomide P. Truffinet, S. Cavalier, J.-L. Delhay, D. Dukovic, P. O’Connor
● 15:45 - 17:00 Others - - - - - T. Leist, M. Freedman, L. Kappos, T. Pooled safety data from three placebo-controlled teriflunomide P 633 Olsson, A. Miller, J. Wolinsky, P. studies O'Connor, M. Benamor, J. Delhay, P. Truffinet, D. Dukovic, J. Li, G. Comi
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Others - - - - - M. Mäurer, F. Lublin, G. Comi, M. Impact of severe relapses on disability, fatigue and health- P 1093 Freedman, L. Kappos, A. Miller, T. related quality of life outcomes: a pooled dataset of the phase 3 Olsson, J. Wolinsky, C. Dive-Pouletty, TEMSO and TOWER studies S. Bozzi, P. O'Connor ● 15:30 - 17:00 Others - - - - - R. Macdonell, F. Lublin, G. Comi, M.S. Teriflunomide reduces relapse-related sequelae, severe P 1095 Freedman, L. Kappos, M. Mäurer, A. relapses, hospitalisations and corticosteroid use: pooled data Miller, T.P. Olsson, J.S. Wolinsky, S. from the phase 3 TEMSO and TOWER studies Bozzi, C. Dive-Pouletty, P. O'Connor
Source: ECTRIMS 2013 Slide 57 September 2013 BIIB033 (Anti-LINGO) (BIIB)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Immunomodulation/ - - - - - D. Cadavid, I. Melamed, H. Gevorkyan, The use of magnetic resonance imaging to monitor the safety of P 545 Immunosuppression N. Richert anti-LINGO-1: findings from phase 1 studies in healthy volunteers and subjects with multiple sclerosis
Source: ECTRIMS 2013 Slide 58 September 2013 Copaxone (TEVA)
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Immunomodulation/ - - - - - T. Ziemssen, O. Bajenaru, A. Carrá, N. COPTIMIZE: a two-year observational survey of patients with P 973 Immunosuppression de Klippel, J. de Sá, A. Edland, J. relapsing remitting multiple sclerosis switching to glatiramer Frederiksen, O. Heinzlef, K. acetate 20 mg daily Karageorgiou, A.M. Landtblom, M. Macías Islas, N. Tubridy, Y. Gilgun- Sherki
Source: ECTRIMS 2013 Slide 59 September 2013 Daclizumab (ABBV/BIIB)
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Immunology - - - - - G. Giovannoni, A. Mikulskis, M. McNeil, Evaluation of immunogenicity in multiple sclerosis patients P 864 K. Riester, M. Sweetser, J. Elkins, L. continuously treated with daclizumab-HYP during the SELECT Amaravadi and SELECTION clinical trials ● 15:30 - 17:00 Immunomodulation/ - - - - - E.W. Radue, D. Stefoski, R. Gold, M. Reduction in brain atrophy with extended daclizumab HYP P 977 Immunosuppression McNeill, K. Riester, J. Elkins treatment: results of SELECT and the SELECT extension study
Source: ECTRIMS 2013 Slide 60 September 2013 Gilenya (NOVN)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Risk management for disease - - - - - V. Limmroth, S. Hoyer, K. Schuh, M. Good cardiac safety profile after fingolimod (Gilenya®) P 602 modifying treatments Lang, O. Hoffmann, T. Ziemssen treatment initiation in patients with relapsing remitting multiple sclerosis: first interim analysis of the START study ● 15:45 - 17:00 Others - - - - - J. Cohen, J. Pelletier, P. Chin, N. Efficacy of fingolimod in relapsing remitting multiple sclerosis P 620 Sfikas, G. Karlsson, P. von Rosenstiel, (RRMS) as measured by multiple sclerosis functional L. Kappos composite: results from the TRANSFORMS, FREEDOMS, and FREEDOMS II phase 3 studies
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Long-term treatment - - - - - L. Kappos, J. A Cohen, F. Barkhof, L. Relapse rates and disability remain consistently low with long- P 1052 monitoring Cappiello, Y. Zhang, P. Von Rosenstiel term fingolimod therapy: five-year interim results of the LONGTERMS extension study ● 15:30 - 17:00 Others - - - - - A. T. Reder, D. Jeffery, D. Goodin, L. Long-term efficacy of fingolimod in patients with relapsing P 1092 Kappos, F. D. Lublin, E. W. Radue, K. remitting multiple sclerosis: results from the phase 3 Rammohan, T. Vollmer, M. A. Agius, T. FREEDOMS II extension study Stites, B. Li, L. Cappiello, P. von Rosenstiel, P. A. Calabresi ● 15:30 - 17:00 Others - - - - - W. Camu, E. Thouvenot, M. Meinel, N. Influence of baseline clinical and demographic characteristics P 1101 Sfikas, P. Chin, D. Piani-Meier, D. on disease evolution in the phase 3 FREEDOMS study in Tomic, E. Verdun patients with relapsing remitting multiple sclerosis
Source: ECTRIMS 2013 Slide 61 September 2013 Laquinimod (TEVA/ACTI)
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Long-term treatment - - - - - T. Vollmer, X. Montalban, G. Comi, T. Multicentre, randomized, placebo controlled study to evaluate P 1054 monitoring Ziemssen, A. Boyko, P. Vermersch, N. the efficacy, safety and tolerability of two doses of oral Sasson, T. Gorfine, V. Knappertz, M. laquinimod (0.6mg/day and 1.2mg/day) for the treatment of Filippi patients with relapsing remitting multiple sclerosis
● 15:30 - 17:00 Long-term treatment - - - - - T. Vollmer, P.S. Sorensen, K. Selmaj, Results of switching to laquinimod in the open-label extension P 1055 monitoring F. Zipp, E. Havrdova, J. Cohen, Y. Sidi, phase of the BRAVO study T. Gorfine, D. Arnold for the BRAVO Study Group ● 15:30 - 17:00 Long-term treatment - - - - - P.S. Sorensen, G. Cutter, T. Vollmer, The risk of disability progression is associated with multiple P 1057 monitoring G. Comi, D. Ladkani, N. Sasson, V. sclerosis functional composite (MSFC) scores in the laquinimod Knappertz phase 3 trials
Source: ECTRIMS 2013 Slide 62 September 2013 Lemtrada (SASY)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Immunomodulation/ - - - - - L.H. Kasper, D.L. Arnold, J.A. Cohen, Lymphocyte subset dynamics following alemtuzumab treatment P 531 Immunosuppression A.J. Coles, E.J. Fox, H.-P. Hartung, E. in the CARE-MS II study Havrdova, K.W. Selmaj, H.L. Weiner, J. Palmer, D.H. Margolin, M.A. Panzara, D.A.S. Compston
● 15:45 - 17:00 Long-term treatment - - - - - H.-P. Hartung, D.L. Arnold, J.A. Cohen, Reduction of disability with alemtuzumab in relapsing remitting P 592 monitoring A.J. Coles, E.J. Fox, E. Havrdova, K.W. multiple sclerosis patients who participated in CARE-MS II: Selmaj, H.L. Weiner, J. Palmer, D.H. three year follow-up Margolin, M.A. Panzara, D.A.S. Compston ● 15:45 - 17:00 Risk management for disease - - - - - E. Havrdova, D.L. Arnold, J.A. Cohen, Infection risk with alemtuzumab in patients with relapsing P 603 modifying treatments A.J. Coles, E.J. Fox, H.-P. Hartung, K. remitting multiple sclerosis: pooled results from the CARE-MS I Selmaj, H.L. Weiner, J. Palmer, D.H. and CARE-MS II trials Margolin, P. Oyuela, M.A. Panzara, D.A.S. Compston
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Long-term treatment - - - - - J. Lycke, D.L. Arnold, J.A. Cohen, A.J. Adverse event profile of alemtuzumab in active relapsing P 1053 monitoring Coles, E.J. Fox, H.-P. Hartung, E. remitting multiple sclerosis patients who participated in the Havrdova, K.W. Selmaj, H.L. Weiner, J. CARE-MS studies: three-year follow-up Palmer, D.H. Margolin, P. Oyuela, M.A. Panzara, D.A.S. Compston
Source: ECTRIMS 2013 Slide 63 September 2013 ONO-4641 (MRCG/ Mitsubishi)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Immunomodulation/ - - - - - K. Selmaj, F. Zipp, T. Vollmer, A. Bar- Effect of ONO-4641, a potent, oral, selective sphingosine-1- P 536 Immunosuppression Or, B. Due, T.Z. Fischer, K. phosphate receptor-1 and -5 agonist, on MRI outcomes in Thangavelu on behalf of the DreaMS patients with relapsing remitting multiple sclerosis: subgroup study investigators analyses from the phase 2 DreaMS study ● 15:45 - 17:00 Immunomodulation/ - - - - - T. Vollmer, F. Zipp, A. Bar-Or, B. Due, Magnetic resonance imaging measures of efficacy in patients P 547 Immunosuppression K. Thangavelu, T.Z. Fischer, K. Selmaj with multiple sclerosis receiving ONO-4641, a sphingosine-1- on behalf of the DreaMS study phosphate receptor-1 and -5 agonist: interim results from an investigators extension of the DreaMS study ● 15:45 - 17:00 Immunomodulation/ - - - - - A. Savinainen, S. El Bawab, T. ONO-4641, a potent and selective sphingosine-1-phosphate Immunosuppression Crandall, R. Chang, U. Boschert, T. receptor-1 and -5 agonist, results in less lymphopenia than Dellovade fingolimod at effective doses in a preclinical model of multiple sclerosis
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Immunomodulation/ - - - - - F. Zipp, T. Vollmer, A. Bar-Or, B. Due, Relapse rates in patients with multiple sclerosis receiving ONO- P 992 Immunosuppression K. Thangavelu, T.Z. Fischer, K. Selmaj 4641, a sphingosine-1-phosphate receptor-1 and -5 agonist: on behalf of the DreaMS study interim results from an extension of the DreaMS study investigators ● 15:30 - 17:00 Immunomodulation/ - - - - - A. Bar-Or, F. Zipp, T. Vollmer, B. Due, Safety of ONO-4641 in patients with relapsing remitting multiple P 997 Immunosuppression K. Thangavelu, J. Johnson, K. Selmaj sclerosis: results from a six-month interim analysis of the on behalf of the DreaMS study DreaMS extension study investigators ● 15:30 - 17:00 Immunomodulation/ - - - - - F. Bernard, D. Yu, A. Gray, U. Efficacy of ONO-4641, a potent and selective sphingosine-1- P 1007 Immunosuppression Boschert, T. Dellovade, D. Graham phosphate receptor-1 and -5 agonist, in a preclinical model of multiple sclerosis
Source: ECTRIMS 2013 Slide 64 September 2013 Plegridy (BIIB)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Immunomodulation/ - - - - - P. Calabresi, B. Kieseier, D. Arnold, L. Peginterferon beta-1a provides improvements in clinical and P 514 Immunosuppression Balcer, A. Boyko, J. Pelletier, S. Liu, Y. radiological disease activity in relapsing-remitting multiple Zhu, X. You, A. Seddighzadeh, B. sclerosis: year 1 findings from the phase 3 ADVANCE study Sperling, S. Hung, A. Deykin
● 15:45 - 17:00 Immunomodulation/ - - - - - B. Kieseier, P. Calabresi, D. Arnold, Y. Subgroup and sensitivity analyses of the primary endpoint from P 539 Immunosuppression Zhu, S. Liu, S. Hung, A. Deykin, S. the peginterferon beta-1a ADVANCE study: a pivotal phase 3 Sheikh study in patients with relapsing-remitting multiple sclerosis
● 15:45 - 17:00 Immunomodulation/ - - - - - B. Kieseier, P. Calabresi, S. Liu, Y. Effect of peginterferon beta-1a on disability progression in P 540 Immunosuppression Zhu, X. You, B. Sperling, S. Sheikh, S. patients with relapsing remitting multiple sclerosis: year 1 data Hung, A. Deykin from the pivotal phase 3 ADVANCE study
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Immunomodulation/ - - - - - D. Arnold, P. Calabresi, B. Kieseier, Y. Magnetic resonance imaging results from the first year of the P 989 Immunosuppression Zhu, S. Liu, S. Hung, A. Deykin, S. ADVANCE study, a pivotal phase 3 trial of peginterferon beta- Sheikh 1a in patients with relapsing-remitting multiple sclerosis
● 15:30 - 17:00 Risk management for disease - - - - - B. Kieseier, P. Calabresi, T. Song, Y. Safety and tolerability of peginterferon beta-1a in patients with P 1061 modifying treatments Zhu, S. Hung, A. Deykin, A. relapsing-remitting multiple sclerosis: data from the pivotal Seddighzadeh phase 3 ADVANCE study
Source: ECTRIMS 2013 Slide 65 September 2013 RPC1063 (RCPT)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Experimental models - - - - - R. Peach, J. Brooks, H. Dedman, R. RPC1063, a potent and selective sphingosine 1-phosphate 1 P 375 Powell, F. Scott, G. Timony receptor modulator, has a favourable preclinical safety profile
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Immunomodulation/ - - - - - J. Hartung, A. Olson, R. Peach, M. Results of a thorough QT/QTc (TQT) study of orally P 983 Immunosuppression Boehm, B. Mendzelevski, D. Chanter, administered RPC1063, a novel, selective S1P1 receptor H. Smith, C. Pan, G. Timony, S. agonist, in healthy adult volunteers Gujrathi
Source: ECTRIMS 2013 Slide 66 September 2013 Secukinumab (NOVN)
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Others - - - - - R. Rudick, H. Wiendl, L. Steinman, A. Efficacy and safety of AIN457 (secukinumab) in patients with P 1103 Bar-Or, R. Bhore, D. Bennett, M. relapsing multiple sclerosis: design of an adaptive dose-ranging Bieniek, A. de Vera, X. Montalban phase 2 study
Source: ECTRIMS 2013 Slide 67 September 2013 Siponimod (NOVN)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Others - - - - - K. Shakeri-Nejad, B. Brendani, N. Placebo-like occurrence of atrioventricular blocks and sinus P 626 Pezous, L. Mooney, A. Juan, M. Allison, pauses: results from a siponimod QT/QTc study R.G. Perry, E. Legangneux
Source: ECTRIMS 2013 Slide 68 September 2013 Tecfidera (BIIB)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Immunomodulation/ - - - - - K. Selmaj, R. Gold, R. J. Fox, E. Flushing and gastrointestinal tolerability events in relapsing P 537 Immunosuppression Havrdova, G. Giovannoni, A. Pace, M. remitting multiple sclerosis (RRMS) patients treated with oral Novas, L. Meltzer, C. Hotermans, V. BG-12 dimethyl fumarate) in the phase 3 DEFINE and Viglietta, J. T. Phillips CONFIRM trials ● 15:45 - 17:00 Immunomodulation/ - - - - - R. Gold, J. T. Phillips, A. Bar-Or, M. Three-year follow-up of oral BG-12 (dimethyl fumarate) P 538 Immunosuppression Hutchinson, L. Kappos, R. Zhang, M. treatment in relapsing remitting multiple sclerosis (RRMS): Yang, V. Viglietta, S. I. Sheikh, R. J. integrated clinical efficacy data from the DEFINE, CONFIRM, Fox and ENDORSE studies ● 15:45 - 17:00 Immunomodulation/ - - - - - M. Hutchinson, R. Gold, R. J. Fox, E. Clinical efficacy of BG-12 (dimethyl fumarate) for relapsing P 563 Immunosuppression Havrdova, G. Giovannoni, A. Zhang, C. remitting multiple sclerosis according to prior therapy: an Hotermans, M. Stephan, A. Bar-Or integrated analysis of the phase 3 DEFINE and CONFIRM studies
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Immunomodulation/ - - - - - R. Gold, G. Giovannoni, J. T. Phillips, Effect of BG-12 (dimethyl fumarate) in newly diagnosed P 990 Immunosuppression R. J. Fox, A. Zhang, L. Meltzer, N. C. relapsing remitting multiple sclerosis (RRMS) patients from the Kurukulasuriya DEFINE and CONFIRM studies ● 15:30 - 17:00 Immunomodulation/ - - - - - R. Gold, J. T. Phillips, E. Havrdova, A. Oral BG-12 (dimethyl fumarate) and pregnancy: preclinical P 991 Immunosuppression Bar-Or, L. Kappos, J. Clarke, H. Yuan, studies and pregnancy outcomes reported during the clinical M. Novas, M. T. Sweetser, N. C. development programme Kurukulasuriya, V. Viglietta, R. J. Fox
● 15:30 - 17:00 Immunomodulation/ - - - - - J.T. Phillips, R.J. Fox, K. Selmaj, M. Safety profile of BG-12 (dimethyl fumarate) in relapsing P 996 Immunosuppression Yang, R. Zhang, M. Novas, M.T. remitting multiple sclerosis: long-term interim results from the Sweetser, V. Viglietta, R. Gold ENDORSE extension study ● 15:30 - 17:00 Immunomodulation/ - - - - - D. H. Miller, R. J. Fox, R. Gold, E. Three-year follow-up of oral BG-12 (dimethyl fumarate) P 1004 Immunosuppression Havrdova, L. Kappos, D. MacManus, T. treatment in relapsing remitting multiple sclerosis (RRMS): Yousry, R. Zhang, M. Yang, V. Viglietta, integrated magnetic resonance imaging (MRI) outcomes from S. I. Sheikh, K. T. Dawson, D. L. Arnold DEFINE, CONFIRM, and ENDORSE
● 15:30 - 17:00 Immunomodulation/ - - - - - M. Hutchinson, R.J. Fox, A. Bar-Or, E. Efficacy of BG-12 (dimethyl fumarate) in relapsing remitting P 1013 Immunosuppression Havrdova, M. Yang, R. Zhang, V. multiple sclerosis in patients from Europe: an integrated Viglietta, S.I. Sheikh, R. Gold analysis of the phase 3 DEFINE and CONFIRM studies ● 15:30 - 17:00 Immunomodulation/ - - - - - R. J. Fox, R. Gold, J. T. Phillips, K. Lymphocyte count reductions in relapsing remitting multiple P 1018 Immunosuppression Selmaj, K. Raghupathi, H. Yuan, J. sclerosis (RRMS) patients treated with oral BG-12 (dimethyl O'Gorman, M. Novas, V. Viglietta, N. C. fumarate): integrated analysis of the placebo-controlled studies Kurukulasuriya ● 15:30 - 17:00 Quality of life - - - - - M. Kita, R.J. Fox, R. Gold, G. Interim analysis of quality of life in patients with relapsing P 1127 Giovannoni, J.T. Phillips, S.P. Sarda, J. remitting multiple sclerosis treated with BG-12 (dimethyl Kong, R. Zhang, V. Viglietta, S.I. fumarate) in the ENDORSE study Sheikh, L. Kappos
Source: ECTRIMS 2013 Slide 69 September 2013 Tysabri (BIIB)
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Treatment of progressive MS - - - - - D. Mikol, M. S. Freedman, M. D. ASCEND study of natalizumab efficacy on reducing disability in P 1087 Goldman, H-P Hartung, E. Havrdova, patients with secondary progressive multiple sclerosis: baseline D. Jeffery, R. Kapoor, A. Miller, F. demographics and disease characteristics Sellebjerg, S. Lee, Y. Chen, D. Cadavid, B. Ticho ● 15:30 - 17:00 Treatment of progressive MS - - - - - D. Cadavid, B. Brochet, G.L. Mancardi, The MS-COG, a novel endpoint for measurement of cognitive P 1088 U. Nocentini, T. Kaushik, L. Xu, Y. function in multiple sclerosis clinical trials: baseline Chen, D. Mikol, B. Ticho characteristics of the cognitive substudy of the ASCEND natalizumab secondary progressive multiple sclerosis study
Source: ECTRIMS 2013 Slide 70 September 2013 Other Compounds (LG/ATLN)
Thursday, October 3, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:45 - 17:00 Immunomodulation/ - - - - - S.Y. Hong, J. Park, W. Park, H. Park, Efficacy and safety of LC510201, an orally active, selective P 552 Immunosuppression D. Park, J. Choi, S. Baek, J. Park, H. sphingosine-1-phosphate receptor 1 (S1P1) and -5 (S1P5) Park agonist, in preclinical models of multiple sclerosis
Friday, October 4, 2013 Key? Time Event/Topic Location Authors Title ID ● 15:30 - 17:00 Immunomodulation/ - - - - - C. Pozzilli, Ó. Fernández, T. Olsson, Maintenance of efficacy, safety and tolerability of ponesimod in P 995 Immunosuppression M.S. Freedman, M. Melanson, A. patients with relapsing remitting multiple sclerosis: phase II Boster, E.-W. Radue, B. Hennessy, A. extension study Rames, D. D'Ambrosio
Source: ECTRIMS 2013 Slide 71 September 2013 Multiple Sclerosis Market Overview 3 Buckets Thesis 3 Buckets Thesis: Our View on the Potential Evolution of the MS Market
Current Treatment Options - $14B (2012) Potential Future Treatment Options - $19B (2018) ABCRs High-Efficacy/ ABCRs Orals High-Efficacy/ Second-Line Second-Line Avonex – BIIB Tysabri – BIIB/ELN The 2012-2018 Avonex – BIIB Tecfidera – BIIB Tysabri – BIIB/ELN Betaseron – BAY Gilenya – NVS MS Revolution Betaseron – BAY Aubagio – SNY Lemtrada – SNY Copaxone – TEVA Copaxone – TEVA Gilenya – NVS Ocrelizumab – ROG/BIIB Rebif – PFE/eMRK Rebif – PFE/eMRK Laquinimod – ACTI/TEVA Approved Drugs Plegridy – BIIB Daclizumab – BIIB/ABBV ca80% market share ca20% market share Pipeline Drugs RPC1063* – RCPT Efficacy: RR 20-30% Efficacy: RR >50% Efficacy: EDSS <25% EDSS >30% > or = to ABCRs
Key Points to Our 3 Bucket Thesis: (1) We view MS therapeutics in 3 broad buckets: Two established buckets (i) ABCR and (ii) High-Efficacy/Second-Line agents and an emerging new class of products that we call (iii) Oral agents (2) The overall MS market is still dominated (~80% market share by value) by ABCRs (despite their relative modest efficacy and less than ideal side effect profile) as they are the only alternatives to High-Efficacy/Second-Line agents (~20% market share by value) and their associated serious infections concerns (3) Tecfidera is the leading Oral, showing efficacy above ABCRs/near High-Efficacy/Second-Line AND possessing a better safety profile than High-Efficacy/Second-Line (and ABCRs). In our view this will allow significant market share in new patients, but also propagate significant switching from ABCRs (4) RPC1063 is an S1P1 modulator, within the same class as Gilenya. In our view, the totality of RCP1063’s clinical profile, notably improved half-life/fast recovery of lymphocytes and improved cardiotoxicity/hepatoxicity over Gilenya could effectively position RCP1063 in a different bucket relative to Gilenya
Sources: Company data, Credit Suisse research “Old-Gen” MS Drug Performance (vs. Placebo)
Betaseron Avonex Copaxone Rebif Tysabri Avonex Copaxone Trial Source n=372 ('95) MSCRG ('96) Phase III PRISMS AFFIRM BRAVO CONFIRM Patient Number 1721 301 251 560 942 1331 1417 FDA Approval Year 1993 1996 1996 2002 2004 1996 1996 Pbo Relapse Rate 1.31 0.82 1.68 2.56 0.73 0.34 0.40 Absolute Decrease in 0.41 0.15 0.49 0.83 0.50 0.08 0.12 Relapse Rate Relative Decrease in 31% 18% 29% 32% 68% 24% 29% Relapse Rate Starting EDSS (Pbo) 1.50 2.40 2.40 2.40 2.3 - - - 2.60 Starting EDSS (Tx) 1.60 2.40 2.80 2.50 2.3 - - - 2.60 Starting EDSS Range 0.0-5.5 1.0-3.5 0.0-6.5 0.0-5.0 0.0-6.0 0.0-5.5 0.0-5.0 RR in 3-Month EDSS 16% 37% 4% 26% 42% - - - 7% Progression % with 6-Month EDSS ------Progression (Pbo) % with 6-Month EDSS ------Progression (Tx) RR in 6-Month EDSS ------Progression >1.0 or >0.5 if BL ≥ 6 over 6 >1.0 over 6 months >1.0 over 3 months >1.0 over 3 months >1.0 (BL≥1) or >1.5 (BL=0) for N/A ≥1.0 (BL≥1.0) or ≥1.5 (BL=0) EDSS Progression months 12 weeks over 24 months for ≥12 weeks over 2 years Definition Change in lesion number was Volume changed 147.4 mm³ vs Lesion number was 4.48 vs - - - Lesion number was 0.6 vs 2.3 - - - 41% drop in new lesion 0.2 vs 0.3 for pbo at 24mo 502.8 mm³ for pbo at 24mo 5.03 for pbo at 24mo (p=NS). for pbo at 1yr (p<0.001). number vs pbo at 2yr T1 Hypointense (p<0.001). (p=0.065). (p=0.0021). Lesions Endpoint
Volume changed -1% vs +21% Volume changed -13% vs - Unique active lesion was 178 Active lesion number was 0.75 New/enlarging lesion number 52% reduction in 54% reduction in for pbo (p=0.0001). 6.5% for pbo at 24mo (p=0.36). vs 213 for pbo (p=0.022). for 22μg (p<0.0001), 0.50 for was 1.9 vs 11.0 for pbo at new/enlarging lesion number new/enlarging lesion number 44μg (p<0.0001) vs 2.25 for 24mo (p<0.001). vs pbo at 2yr. vs pbo at 2yr T2 not specified - plaque pbo. (7.03 vs 14.74) (p<0.0001). T2 Hyperintense burden (p<0.0001) Lesions Endpoint
Lesion number was 2.2 vs 4.6 Lesion number was 0.8 vs 1.6 Lesion number was 0.91 vs - - - New/enlarging lesion number 60% reduction in new lesion 61% drop in odds of more Gd+ for pbo at 24mo (p<0.0001). for pbo at 24mo (p=0.05). 1.41 for at 24mo (p=NS). was 0.1 vs 1.2 for pbo at 24mo number vs pbo at 2yr. lesions vs pbo at 2yr (p<0.001). (0.45 vs. 1.14) (p=0.0003). Gd+ Lesion (p<0.0001) Endpoints
------9% increase in brain atrophy - - - based on BVR vs pbo (p=0.14). Brain Atrophy
Sources: Company data, Credit Suisse research and analysis Slide 74 September 2013 “Next-Gen” MS Drug Performance (vs. Placebo)
Gilenya Aubagio Plegridy Laquinimod Copaxone Tecfidera BID Tecfidera BID Trial Source FREEDOMS TEMSO ADVANCE BRAVO CONFIRM CONFIRM DEFINE Patient Number 1272 1086 1516 1331 1417 1417 1234 FDA Approval Year 2010 2012 2014? 2017? 1996 2013 2013 Pbo Relapse Rate 0.40 0.54 0.40 0.34 0.40 0.40 0.36 Absolute Decrease in 0.24 (1.25mg) 0.17 (7mg) 0.14 (Q2W) 0.06 0.12 0.18 0.19 Relapse Rate 0.22 (0.5mg) 0.17 (14mg) 0.11 (Q4W) Relative Decrease in 60% (1.25mg) 31% (7mg) 36% (Q2W) 18% 29% 44% 53% Relapse Rate 55% (0.5mg) 31% (14mg) 28% (Q4W) Starting EDSS (Pbo) 2.5 2.68 2.44 - - - 2.60 2.60 2.48 2.4 (1.25mg) 2.68 (7mg) 2.47 (Q2W) - - - 2.60 2.60 2.40 Starting EDSS (Tx) 2.3 (0.5mg) 2.67 (14mg) 2.48 (Q4W) Starting EDSS Range 0.0-5.5 0.0-5.5 0.0-5.0 0.0-5.5 0.0-5.0 0.0-5.0 0.0-5.0 RR in 3-Month EDSS 32% (1.25mg) 24% (7mg) 38% (Q2W) 34% 7% 21% 38% Progression 30% (0.5mg) 30% (14mg) 38% (Q4W) % with 6-Month EDSS 19.0% ------Progression (Pbo) % with 6-Month EDSS 11.5% (1.25mg) ------Progression (Tx) 12.5% (0.5mg) RR in 6-Month EDSS 40% (1.25mg) ------Progression 37% (0.5mg) >1.0 (BL<5.5) or >0.5 (BL=5.5) >1.0 (BL<5.5) or >0.5 (BL≥5.5) ≥1.0 (BL≥1.0) or ≥1.5 (BL=0) N/A ≥1.0 (BL≥1.0) or ≥1.5 (BL=0) ≥1.0 (BL≥1.0) or ≥1.5 (BL=0) ≥1.0 (BL≥1.0) or ≥1.5 (BL=0) EDSS Progression for 3/6 months over 24 months for 12 weeks over 108 weeks for ≥12 weeks over 2 years for ≥12 weeks over 2 years for ≥12 weeks over 2 years Definition ≥ Volume changed 12% for Volume changed 0.50 for 7mg ------41% drop in new lesion 57% drop in new lesion 72% drop in new lesion 1.25mg (p=0.02), 9% for (p=0.19), 0.33 for 14mg number vs pbo at 2yr number vs pbo at 2yr number vs pbo at 2yr. T1 Hypointense 0.5mg (p=0.01) vs 51% for pbo (p=0.02) vs 0.53 for pbo at (p=0.0021). (p<0.0001). (1.5 vs 5.6) Lesions Endpoint at 24mo. 24mo. (p<0.0001)
New/enlarging lesion number Unique active lesion number 67% reduction in 19% reduction in 54% reduction in 71% reduction in 85% reduction in was 2.5 for 0.5mg/1.25mg vs was 1.288 for 7mg (p<0.0001), new/enlarging lesion number new/enlarging lesion number new/enlarging lesion number new/enlarging lesion number new/enlarging lesion number 9.8 for pbo at 24mo (p<0.001). 0.754 for 14mg (p<0.0001) vs for Q2W vs pbo at 1yr vs pbo at 2yr. vs pbo at 2yr vs pbo at 2yr vs pbo at 2yr. 2.463 for pbo at 24mo. (p<0.001). (11.98 vs 14.74) (p<0.0001). (p<0.0001). (2.6 vs 17.0) (p<0.0001) T2 Hyperintense (p=0.037) Lesions Endpoint Volume changed 0.81 for 7mg 28% reduction in (p=0.04), 0.39 for 14mg new/enlarging lesion number (p<0.001) vs 1.67 for pbo at for Q4W vs pbo at 2yr 24mo. (p<0.001).
Lesion number was 0.2 for Active lesion number was 86% drop in Gd+ lesion 22% reduction in new lesion 61% drop in odds of more Gd+ 74% drop in odds of more Gd+ 90% reduction in new lesion 0.5mg/1.25mg vs 9.8 for pbo at 0.570 for 7mg (p<0.001), 0.261 number vs pbo at 1yr for Q2W number vs pbo at 2yr. lesions vs pbo at 2yr lesions vs pbo at 2yr number vs pbo at 2yr. 24mo (p<0.001). for 14mg (p<0.001) vs 1.331 (p<0.0001). (0.89 vs. 1.14) (p=0.0003). (p<0.0001). (0.1 vs 1.8) Gd+ Lesion for pbo at 24mo. (p=0.062) (p<0.001) Endpoints 36% drop in Gd+ lesion number vs pbo at 1yr for Q4W (p=0.0738). -0.89 for 1.25mg, -0.84 for BPF dropped by 0.003 for 7mg - - - 28% reduction brain atrophy ------30% reduction in brain atrophy 0.5mg vs -1.31 for pbo at (p=0.19), 0.003 for 14mg based on brain reduction (based on WBV change) vs 24mo (p<0.001). (p=0.35) vs 0.004 for pbo at volume vs pbo (p=0.0001). pbo at 2yr. Brain Atrophy 24mo. -0.46% vs -0.66% (p=0.0214)
Sources: Company data, Credit Suisse research and analysis Slide 75 September 2013 MS Drug Performance (vs. ABCRs)
Drug Tysabri Lemtrada Teriflunomide Gilenya Laquinimod BG-12 Dose 3-6mg/kg QM 12mg QD 7mg or 14mg QD 1.25mg/0.5mg QD 0.6mg QD 240mg BID or TID Administration Intravenous Intravenous Oral Oral Oral Oral Comparator Arm Avonex Rebif Rebif Avonex Avonex Copaxone Study/Datasource SENTINEL CARE-MS I TENERE TRANSFORMS BRAVO CONFIRM Number of Patients 1171 581 324 1292 1331 1430 MS Sub-Type(s) Relapsing-Remitting Relapsing-Remitting Relapsing Forms Relapsing-Remitting Relapsing-Remitting Relapsing-Remitting Starting ARR (Control) 1.49 1.8 ? 1.5 ? 1.40 Starting ARR (Experimental) 1.44 1.8 ? 1.5 ? 1.40 55% reduction over 2 years for 55% reduction over 2 years for RR: 0.259 for 14mg vs. 0.410 for 0.33 (Avonex) vs. 0.20, 39% RR 21% reduction over 2 years for 44% reduction over 2 years for Tysabri vs. Avonex (p<0.001) Lemtrada vs. Rebif (p<0.0001) 7mg vs. 0.216 for Rebif (1.25mg); vs. 0.16, 52% RR (0.5 Laquinimod vs. pbo (0.29 vs. BG-12 BID vs. pbo (p<0.0001) RR: 0.34 for Tysabri/Avonex vs. RR at 2yrs: 0.18 Lemtrada vs. mg) at 1 year p<0.001 0.37, p=0.03) 51% reduction over 2 years for 0.75 for Avonex 0.39 Rebif 29% reduction over 2 years for BG-12 TID vs. pbo (p<0.0001) Avonex vs. pbo (0.27 vs. 0.37, 29% reduction over 2 years for Reduction in Relapse Rates p=0.002) Copaxone vs. pbo (p<0.02) 24% reduction over 2 years for BG-12 BID vs. Copaxone (p=0.010) 31% reduction over 2 years for BG-12 TID vs. Copaxone N/A N/A N/A +0.11 for Avonex vs. -0.08 for N/A N/A(p=0.02) EDSS Reduction 0.5 mg (p=0.06) vs. -0.23 for 1.25 mg at 1 year (p=0.02) 23% for Tysabri/Avonex vs. 29% 8% Lemtrada vs. 11% Rebif at 2 N/A N/A 34% reduction over 2 years for 21% reduction over 2 years for for Avonex at 2 years (p=0.02) years (p=0.22) Laquinimod vs. pbo (p=0.04) BG-12 BID vs. pbo (p=NS) Percent with Sustained 29% reduction over 2 years for 24% reduction over 2 years for Increase in Disability Avonex vs. pbo (p=0.09) BG-12 TID vs. pbo (p=NS) 7% reduction over 2 years for Copaxone vs. pbo (p=NS) Headache, Fatigue, Arthralgias, Infusion-Associated Reactions, Diarrhea, Hair Thinning, Elevated Skin Cancer, Bradycardia, AV Nausea, Iritis Flushing, GI Disorders, Nausea Hypersensitivity-Like Reactions, Infections involving Upper ALTs, High Blood Pressure block, Macular Edema, Herpevirus Common Side Effects PML Respiratory Tract, Urinary Tract, Infection Oral Herpes
Sources: Company data, Credit Suisse research and analysis Slide 76 September 2013 MS Pipeline Summary
3 Bucket Thesis/ Product Company Stage Next Milestone Comments Recent Efficacy Results Recent Safety Results ECTRIMS 2013 Mechanism of Action Tecfidera Oral Biogen Idec On EMA RDP Decision Tecfidera's launch is off to a great start in CONFIRM PIII (BID, TID, C* vs. Pbo): CONFIRM PIII (BID, TID, C, Pbo): Integrated analysis of CONFIRM and Via Nrf 2, T1/T2 Shift Market (Q3'13/H1'14) the US, capturing ~10% share of all MS RR: 44%, 51%, 29% Flushing: 31%, 24%, 2%, 4% DEFINE efficacy and safety data on 10/3 (US) TRx's (adjusted for Tysabri) as of Sep EDSS: 21%, 24%, 7% Discontinuations: 12%, 12%, 10%, 10% at 15:45-17:00 (P537, P563) and 10/4 at 13, 2013. In addition to the US launch, Infections: 56%, 56%, 50%, 50% 15:30-17:00 (P990, P1013, P1018). Filing the near-term focus for Tecfidera is on DEFINE PIII (BID, TID vs. Pbo): (EU) potential "headline" PML risk and EMA's RR: 53%, 48% DEFINE PIII (BID, TID, Pbo): Long-term safety data from ENDORSE decision on RDP status. EDSS: 38%, 34% Flushing: 38%, 32%, 5% on 10/4 at 15:30-17:00 (P996, P 1127). Discontinuations: 16%, 16%, 13% *C = Copaxone Infections: 64%, 68%, 65% Aubagio Oral Sanofi On Q3'13 Sales Like Tecfidera, Aubagio has a broad TENERE PIII showed Aubagio is TENERE showed Aubagio could be safer Pooled efficacy efficacy and safety data Via DHDH Inhibition Market label; Aubagio is currently indicated for comparable to Rebif from a statistical than Rebif. Incidence of TEAEs were on 10/3 at 15:45-17:00 (P544, P618, (US) treatment of RMS. Aubagio was priced at point of view. However, both doses failed lower in Aubagio than Rebif (8.2% for P633) and 10/4 at 15:30-17:00 (P1093, a slight discount to ABCRs in the US. to show lower RR (vs. Rebif). 7mg vs. 10.9% for 14mg vs. 21.8% for P1095). On Rebif). Market TOWER PIII (vs. Pbo) (EU) RR: 22.3% (7mg), 36.3% (14mg) EDSS: NM (7mg), 31.5% (14mg)
TEMSO III (vs. Pbo) RR: 31% (7mg), 32% (14mg) EDSS: 24% (7mg), 30% (14mg) Lemtrada High-Efficacy/ Sanofi/ Filing sBLA PDUFA Lemtrada has unique dosing (once-per- CARE-MS II PIII (vs. Rebif) Lemtrada increased the incidence of Additional analyses of CARE-MS I and 2nd-Line Bayer (US) (Q4'13) year). CARE-MS I (treatment naive) RR: 49%, p<0.0001 autoimmune thyroid-related conditions, CARE-MS II data on 10/3 at 15:45-17:00 Anti-CD52 mAb showed strong efficacy (vs. Rebif) on EDSS: 42%, p=0.0084 ITP, and infections. (P531, P591, P592, P603) and 10/4 at On Q4'13 Sales RR, but no benefit on EDSS progression 15:30-17:00 (P1053). Market (with early disease/low progression being CARE-MS I PIII (vs. Rebif) (EU) cited by Sanofi). CARE-MS II (treatment RR: 55%, p<0.0001 experienced) showed superior efficacy EDSS: Not Meaningful (p=NS) (vs. Rebif) on RR and EDSS progression. Plegridy ABCR Biogen Idec Filing BLA PDUFA Plegridy offers more convenient dosing ADVANCE PIII (Q2W, Q4W vs. Pbo) The incidence of AEs and SAEs were ADVANCE data on 10/3 at 15:45-17:00 (May 21, 2014) (Q2W, Q4W) relative to the ABCRs. Of RR: 36%, 28% comparable between Plegridy and Pbo. (P514, P539, P540) and 10/4 at 15:30- the two dosing regimens, Q2W appears EDSS: 38%, 38% The most common AEs associated with 17:00 (P989, P1061). CHMP Opinion to be more efficacious. Plegridy were injection-site redness and (2014) flu-like symptoms. M356 ABCR Momenta Filing - - - - - M356 is a generic version of Copaxone. ------CAFC recently issued a favorable opinion, potentially paving the way for a launch in May 2014. Daclizumab High-Efficacy/ Biogen Idec/ PIII DECIDE PIII Data We saw granularity of SELECT at SELECT PIIb (150mg, 300mg vs. Pbo): SELECT PIIb (150mg, 300mg, Pbo) SELECT data on 10/4 at 15:30-17:00 2nd-Line Abbott (H1'14) ECTRIMS 2011. Daclizumab is given via RR: 54%, 50% Serious Infections: 3%, 1%, 0% (P864, P977). Anti-CD25/IL2R-alpha a subcutaneous injection every 4 weeks. Gd+: 79%, 86% LFT 5x ULN: 4%, 4%, <1% (T-Cell Targeted) Daclizumab has a novel mechanism of T2: 70%, 79% action. SELECT showed decent efficacy, but raised some safety concerns with respect to infection risk.
Sources: Company data, Credit Suisse research and analysis Slide 77 September 2013 MS Pipeline Summary (cont.)
3 Bucket Thesis/ Product Company Stage Next Milestone Comments Recent Efficacy Results Recent Safety Results ECTRIMS 2013 Mechanism of Action Laquinimod Oral Teva/ PIII CHMP Opinion Laquinimod is being studied in a third PIII BRAVO PIII (Laq, A vs. Pbo): Laquinimod showed a clean side effect CONCERTO PIII trial setup on 10/4 at Via T1/T2 Shift Active (H2'13) trial (CONCERTO) with a primary Failed to show statistical significance profile. Importantly, there was no 15:30-17:00 (P1054). Biotech endpoint of time-to-progression. relative to pbo. cardiopulmonary signal, which originally CONCERTO PIII Data CONCERTO will examine two doses: ARR: 19% Laq vs. 26% A had been seen with Linomide. (2016) 0.6mg (used in BRAVO/ALLEGRO) and EDSS: 34% Laq vs. 29% A 1.2mg. ALLEGRO PIII (vs. Pbo): A PII trial evaluating the combination of RR: 23% Laquinimod and Copaxone in multiple EDSS: 36% sclerosis is expected to start in H2'13. Ocrelizumab High-Efficacy/ Roche/ PIII OPERA I/II PIII Data A large PIII program was initiated in The PII trial demonstrated strong efficacy Trials in RA and lupus was terminated in There is no major data, but Roche is 2nd-Line Biogen Idec (2015/2016) Q3'11: (1) OPERA I/II in RRMS vs. Rebif data. Ocrelizumab had ARR at 24 wks 2010 due to serious infections. Roche hosting a whole symposium devoted to B- Anti-CD20 mAb for 800 RRMS patients for each, with a (vs. pbo) of 73% (600mg) and 80% considers that a lower dose, younger cell therapy. primary endpoint of ARR at 96 weeks (2) (2000mg). patient population, and the absence of ORATORIO in PPMS for 630 patients, concomitant immunosuppressants may with a primary endpoint of time to result in better safety profile. sustained disability. Siponimod S1P1 Modulator Novartis PIII EXPAND PIII Data Siponimod is being studied in a PIII trial Siponimod had ARR at 6 mo (vs. pbo) of Siponimod appears to have a slightly PI QT/QTc data on 10/3 at 15:45-17:00 (2016) in SPMS. Novartis will be examining 65.5% (2mg) and 49.1% (10mg). The worse safety profile than Gilenya. (P626). several doses in this pivotal study. 0.5mg dose have not benefit in ARR at 6 mo. BAF312 had an ARR at 3 mo (vs. pbo) of 5.2% (0.25mg) and 60.3% (1.25mg). Tysabri High-Efficacy/ Biogen Idec PIII ASCEND PIII Data Tysabri is being examined in a PIII trial in ------ASCEND PIII trial setup on 10/4 at 15:30- 2nd-Line (2014/2015) SPMS. The primary endpoint is 17:00 (P1087, P1088). Anti-α4 mAb percentage experiencing confirmed progression of disability in one or more of EDSS, T25FW, or 9HPT. Enrollment had been completed as of Jul 12, 2013 according to www.clinicaltrials.gov. AZ01 ABCR Allozyne PIII PIII Trial Start AZ01 is a long-acting interferon beta-1a. ------In PI trials, AZ01 had a half-life that was two to three times longer than other pegylated interferon beta-1a's.
Masitinib c-Kit-R Inhibitor AB Science PIIb/III PIIb/III Data Masitinib is being evaluated in a PIIb/III Masitinib had a MSFC clinical response The most common AEs associated with - - - - - (2014/2015) trial in PPMS and relapse-free SPMS. rate of 30% (vs. 0% for pbo). A response Masitinib were asthenia (41%), nausea The primary endpoint is MSFC clinical was defined as at each timepoint as over (26%), diarrhea (11%), rash (11%), response rate. 100% increase from baseline in MSFC urinary infection (11%), and weight loss score. (11%). RPC1063 Oral Receptos PII/III RADIANCE PII Data The PII portion of RADIANCE examines - - - - - RPC1063 appears to have a better PI QT/QTc data on 10/3 at 15:45-17:00 (S1P1 Modulator) (2014) 1.0mg RPC1063 (vs. pbo) in RMS. The safety profile than Gilenya in PI trials. (P375) and 10/4 15:30-17:00 (P983). primary endpoint is reduction in cumulative number of GdE lesions from Week 12 to Week 24. The interim analysis will enable RCPT to begin enrolling the PIII portion of the trial.
Sources: Company data, Credit Suisse research and analysis Slide 78 September 2013 MS Pipeline Summary (cont.)
3 Bucket Thesis/ Product Company Stage Next Milestone Comments Recent Efficacy Results Recent Safety Results ECTRIMS 2013 Mechanism of Action ONO-4641 Oral Merck KGaA/ PII/III - - - - - Merck KGaA and Ono Pharma are ONO-4641 showed ARR at 26 wk (vs. Most common AEs were transient DreaMS PII data on 10/3 at 15:45-17:00 (S1P1 Modulator) Ono Pharma currently evaluating whether to proceed pbo) of 25% (0.05mg), 69.6% (0.10mg), asymptomatic AV block and bradycardia (P536, P547) and 10/4 at 15:30-17:00 into a PIII program in RMS. and 39.2% (0.15mg). as well as lymphopenia. (P992, P997). Ponesimod Oral Actelion PII/III - - - - - Actelion has effectively placed the clinical Ponesimod had the best efficacy at the Ponesimod causes cardivascular and Extension PII data on 10/4 at 15:30- (S1P1 Modulator) development of Ponesimod on hold. 40mg dose, showing ARR at 24 wks (vs. lymphocyte reduction AEs. 17:00 (P995). Actelion is currently evaluating an earlier pbo) of 52%. stage S1P1 modulator, which has the potential for an improved safety profile.
Tcelna MRTC Immunotherapy Opexa/ PIIb PIIb Data Tcelna is being examined in a PIIb trial in In TERMS, patients with RRMS that TERMS showed that Tclena appeared to - - - - - Merck KGaA (2016) SPMS. The primary endpoint is closely mirrors SPMS showed a be generally safe. There were no percentage of brain atrophy. significant improvement in disability, 56% reported SAEs. The most common AE reduction in ARR, and 88% reduction in was mild to moderate injection site brain atrophy. reactions. MN-166 PDE Inhibitor MediciNova PIIb PIIb Trial Start SPRINT-MS examines MN-166 in PPMS ------and SPMS. The primary endpoint is quantitative analysis of whole brain atrophy as well as safety/tolerability. Arzerra Human Anti-CD20 mAb GSK/ PII PII Data Arzerra is being evaluated in a PII trial in ------Genmab (H2'13) RRMS. The primary endpoint is cumulative number of new T1GdE lesions at 12 weeks. BIIB033 Anti-LINGO-1 mAb Biogen Idec PII 214ON201 PII Data BIIB033 is being examined in two PII - - - - - BIIB033 appears to be generally safe PI data on 10/3 at 15:45-17:00 (P545). (H2'14) trials. 214ON201 examines 100mg/kg IV and well-tolerated. Q4W BIIB033 in acute optic neuritis. The primary endpoint is change in optic nerve conduction velocity at 24 weeks for the affected eye from the baseline of unaffected fellow eye as determined by FF-VEP. SYNERGY examines 3mg/kg, 10mg/kg, 30mg/kg, and 100mg/kg IV Q4W BIIB033 with Avonex in patients with RMS. The primary endpoint is percentage of patients experiencing confirmed improvement of neuro- physical and/or cognitive function and/or disability. GSK 239512 HRH3 Antagonist GSK PII PII Data GSK is conducting a proof-of-concept PII ------(2014) trial intended to show that GSK 239512 can remyelinate lesions in RRMS. The primary endpoint in this PII trial is mean change in GdE lesion MTR differences from before enhancement to stable recovery and mean change in Delta MTR lesion differences from before lesion appearance to stable recovery.
Sources: Company data, Credit Suisse research and analysis Slide 79 September 2013 MS Pipeline Summary (cont.)
3 Bucket Thesis/ Product Company Stage Next Milestone Comments Recent Efficacy Results Recent Safety Results ECTRIMS 2013 Mechanism of Action Secukinumab Anti-IL17A mAb Novartis PII PII Data Novartis is examining Secukinumab in a Secukinumab had an ARR at 24 wks (vs. Secukinumab appeared to be generally PII trial design on 10/4 at 15:30-17:00 (2015) PII trial in RRMS. The primary endpoint pbo) of 42.9%. safe. All AEs were considered mild to (P1103). Tabalumab Anti-BAFF Ab Eli Lilly PII ------
MIS416 Immunotherapy Innate PII - - - - - MIS416 is a bacterially-derived therapy ------intended to activate the innate immune system. RHB-104 - - - - - RedHill PIIa PIIa Data CEASE-MS examines RHB-104 as an ------(2014) add-on therapy to IFN Beta-1a in RRMS. The primary endpoint is combined unique active lesions. Catena CoQ10 Analog Santhera PI/II PI/II Data Catena is being evaluated in a PI/II trial ------(2016) in PPMS. The primary endpoint is inhibition of development of brain CNDO-201 - - - - - Coronado PI/II PI/II Data CNDO-201 is a therapy that consists of ------(HI Immunomodulator) (2013/2014) T. suis ova. T. suis has been shown to blunt Th1 responses and promote Th2 responses via increased production of IL- 3 and IL-4. MEDI-551 Anti-CD19 Ab AstraZeneca PI/II PI/II Data MEDI-551 is an anti-CD19 Ab that ------(2014) depletes B-cells. Olesoxime MPTP Modulator Trophos PI/II PI/II Data Olesoxime has shown strong ------(2014) neuroprotective properties. This compound had been previously studied in a PIII trial in ALS; however, this compound did not show a survival benefit. ATX-MS-1467 Vaccine Merck KGaA/ PI PII Trial Start ATX-MS-1467 consists of four peptides ATX-MS-1467 showed a significant ------Apitope derived from human myelin basic protein. decrease in number of CEL in patients This investigational agent targets MHC II with RRMS. protein. XP23829 NF-Kappa B Xenoport PI PII Trial Start Xenoport plans to engage the FDA by 400mg BID of Formulation #1 had a Xenoport has suggested that XP238829 - - - - - the end of this year to discuss clinical MMF PK profile that was similar to has the potential to have lower development options for XP23829. The 240mg BID Tecfidera. 800mg QD incidences of flushing and GI side effects focus is clearly on the possibility of using Formulation #2 had a favorable PK than Tecfidera. the 505(b)(2) pathway. profile, potentially enabling once-daily PI-2301 - - - - - Merck KGaA PI PII Trial Start PI-2301 is a second-generation peptide - - - - - PI-2301 appears to be generally safe and - - - - - copolymer (in the same class as well-tolerated. Copaxone). MOR103 Anti-GM-CSF Ab GSK/ PIb PIb Data ------MorphoSys (H1'14) rHIgM22 HuIgM Acorda PI PI Data rHIgM22 has the potential to promote ------(2014) remyelination. VX15 Anti-SEMA4D Vaccinex PI PI Data ------(2015)
Sources: Company data, Credit Suisse research and analysis Slide 80 September 2013 MS Pipeline Summary (cont.)
3 Bucket Thesis/ Product Company Stage Next Milestone Comments Recent Efficacy Results Recent Safety Results ECTRIMS 2013 Mechanism of Action ABT-413 S1P1 Modulator AbbVie PI ------
ARX424 Interferon Merck KGaA PI - - - - - ARX424 is a long-acting interferon. ------
CS-0777 S1P1 Modulator Daiichi PI ------Sankyo ER Interferon - - - - - Flamel PI - - - - - ER Interferon is an extended release ------interferon. Fc-Interferon - - - - - Merck KGaA PI - - - - - Fc Interferon is a long-acting interferon. ------
LAS186323 DHODH Inhibitor Almirall PI ------
NRT-36 MT1/MT2 Agonist Nectid PI - - - - - NRT-36 appears to be a "repurposed" ------version of agomelatine, a drug approved for treatment of major depressive disorder in Ex-US. ATLN-S1P1 S1P1 Modulator Actelion PI - - - - - This S1P1 modulator has the potential ------for an improved safety profile. CAT-4001 NF-Kappa B Catabasis PC ------
LAS189913 S1P1 Modulator Almirall PC ------
MMF Prodrug NF-Kappa B Alkermes PC ------
FP187 NF-Kappa B Forward PC ------
Sources: Company data, Credit Suisse research and analysis Slide 81 September 2013 New MS Drugs Drug Profiles BIIB: Tecfidera Overview
General . Orally-administered dimethyl fumarate, a prodrug of monomethyl fumarate Overview . Immunomodulator with neuroprotective properties . Obtained through acquisition of Fumapharm AG in 2006 . Tecfidera’s launch in the U.S. is off to a good start, capturing ~10% TRx share . CS assumes protection in the U.S. until 2023 and in the EU until 2019 . Phase III program (DEFINE and CONFIRM) evaluated BG-12 in RRMS Drug . Tecfidera appears to be superior to ABCRs from efficacy and safety standpoints Profile . Tecfidera had impressive efficacy and excellent safety/tolerability in DEFINE – Reduced relapse rates (vs pbo) by 53% for BID (p<0.0001) and 48% for TID (p<0.0001) – Reduced EDSS progression (vs pbo) by 38% for BID (p=0.0050) and 34% for TID (p=0.128) . CONFIRM generally “confirmed” Tecfidera’s profile established in DEFINE – Reduced relapse rates (vs pbo) 44% for BID and 51% for TID – Reduced EDSS progression (vs pbo) by 21% for BID (p=NS) and 24% for TID (p=NS) – BG-12 showed numerical superiority in reducing relapse rates and EDSS disease progression . Most common AEs in DEFINE and CONFIRM were transient flushing and GI disorders . Reduction in EDSS progression supported by integrated analysis of DEFINE and CONFIRM (32%, BID, p=0.0034 and 30%, TID, p=0.0059) Next . Q3’13 sales Catalysts . EMA decision on RDP status in late 2013 / early 2014
Sources: Biogen Idec, Credit Suisse research and analysis Slide 83 September 2013 Sanofi: Aubagio (Teriflunomide) Overview
General . Orally administered active metabolite of leflunomide Overview . Immunomodulator that reduces B- and T-cell counts by stopping cell division . Reported Q2’12 sales of €33M (launched in early Oct 2012) . Phase III program evaluated Aubagio in RRMS (TEMSO, TOWER, TENERE) and first clinical episodes suggestive of MS (TOPIC) . Being positioned for patients with early MS or moderate RRMS . CS views as potential wildcard competitor to BG-12 Drug . Efficacy appears to be comparable to ABCRs, but inferior to Immunosuppressives Profile . Safety appears to be slightly better than both ABCRs and Immunosuppressives . In TEMSO, Aubagio demonstrated modest efficacy and good safety/tolerability – Reduced relapse rates at 2 years (vs pbo) by 31% for 7 mg (p<0.001) and 32% for 14 mg (p<0.001) – Reduced EDSS (vs pbo) by 24% for 7 mg (p=0.08) and 30% for 14 mg (p=0.03) – Most common AEs due to Aubagio were diarrhea, hair thinning, elevated ALTs, and high blood pressure . TOWER confirmed the efficacy of 14mg dose . In TENERE, Aubagio showed comparable efficacy to Rebif (and rest of ABCRs) – Risk of treatment failure was comparable in all arms (49% for 7 mg, 38% for 14 mg, 42% for Rebif) – Both doses had higher annual relapse rates (0.410 for 7 mg, 0.259 for 14 mg) than Rebif (0.216) – Aubagio appears to have safety/tolerability profile comparable to that observed in TEMSO Next . Q3’13 sales Catalysts
Sources: Sanofi, Credit Suisse research and analysis Slide 84 September 2013 Sanofi: Lemtrada (Alemtuzumab) Overview
General . Yearly IV-administered humanized anti-CD52 mAb targeting B- and T-cells Overview . Immunosuppressive mechanism of action . Currently approved for treatment of B-cell chronic lymphocytic leukemia (B-CLL) . Obtained through acquisition of Genzyme . Being positioned for treatment of severe RMS . Approved by EMA on Sep 17, 2013 . Likely competitor of other Immunosuppressives (e.g. Gilenya, Tysabri) Drug . Efficacy is generally superior to ABCRs, and comparable to Immunosuppressives Profile . Both Phase III trials showed high efficacy in reducing relapse rates relative to Rebif – Reduced relapse rates (vs Rebif) by 55% in CARE-MS I (p<0.0001) and 49% in CARE-MS II (p<0.0001) . However, only CARE-MS II showed a statistically significant reduction in disease progression – In CARE-MS I, there was no statistical significant reduction in EDSS progression (vs Rebif) – In CARE-MS II, there was a 42% reduction in EDSS progression (vs Rebif) . Safety remains a concern due to increased risk of immune-related conditions including autoimmune thyroid disorders, immune thrombocytopenia, and infections . AEs leading to withdrawal and discontinuation were lower for Lemtrada relative to Rebif Next . sBLA PDUFA in Q4’13 Catalysts
Sources: Sanofi, Credit Suisse research and analysis Slide 85 September 2013 Teva/Active Biotech: Laquinimod Overview
General . Orally administered linomide successor Overview . Immunomodulator with potential neuroprotective properties . Expecting CHMP opinion in Q3’13 . Being developed by Teva (Obtained via partnership agreement with Active Biotech) . Originally evaluated in 2 Phase III trials, ALLEGRO and BRAVO . Teva recently initiated a third Phase III trial (CONCERTO) in RRMS evaluating two doses (0.6mg and 1.2mg) Drug . BRAVO failed to hit the primary endpoint Profile – Failed to show statistically significant reduction in relapse rates (vs pbo) – Failed to show numerical superiority in reducing relapse rates relative to active comparator Avonex – Demonstrated reduction in EDSS progression of 33.5% (p=0.044) .However, ALLEGRO did hit the primary endpoint – Showed ARR of 26% (p=0.002) and reduction in EDSS progression of 36% (p=0.0122) . Both trials though showed some very good MRI outcomes, suggesting that Laquinimode could be neuroprotective
Next . CONCERTO PIII data in 2014/2015 Catalysts
Sources: Teva, Active Biotech, Credit Suisse research and analysis Slide 86 September 2013 Roche/BIIB: Ocrelizumab Overview
General . Twice-a-year IV-administered, humanized anti-CD20 mAb targeting CD20+ B-cells Overview . Considered next-generation Rituxan . Roche/Genentech are lead developers, while Biogen Idec retains an economic interest . Phase III program is examining Ocrelizumab in RRMS (OPERA I/II) and PPMS (ORATORIO) . Initiated ORATORIO in Q1’11 and OPERA I/II in Q3’11 Drug . Ocrelizumab demonstrated high efficacy and good safety in a Phase II trial Profile – Reduced relapse rates at 24 weeks (vs pbo) by 80% for 600 mg arm (p=0.0005) and 73% for 2000 mg arm (p=0.0014) – Both doses showed numerical superiority in reducing relapse rates (vs pbo) over Avonex (43% vs pbo) – Incidence of SAEs were comparable across arms: 2% (600 mg), 5% (2000 mg), 4% (Avonex), 4% (pbo) – There was one death due to brain swelling in 2000 mg arm . However, safety remains a concern, as separate trials in rheumatoid arthritis and lupus erthymatosus (for 1000 mg dose) were terminated in 2010 due to side effects – DSMB review of the STAGE trial showed that numerous patients developed serious infections, of which some were fatal – Roche believes the lower dose, younger patient population, and absence of concomitant immunosuppressant use could result in a better safety/tolerability profile in patients with MS Next . Readout from OPERA I/II in 2015/2016 Catalysts . Readout from ORATORIO in 2017
Sources: Biogen Idec, Roche, Credit Suisse research and analysis Slide 87 September 2013 Daclizumab Overview
General . Humanized anti-CD25 (IL2R-alpha) mAb – T Cell targeting Overview . Subcutaneous injection, once every 4 weeks . Approved (but not marketed for commercial reasons) for transplant rejection as Zenapax . Developed in 50/50 collaboration with AbbVie (via Facet Biotech) . Currently being studied in DECIDE Phase III trial for RRMS (Enrollment started in May 2010). Drug .Positive results from adding daclizumab to interferon beta as shown in Phase II CHOICE study Profile . Reported positive topline efficacy data from SELECT Phase II/III trial (vs. placebo, 1 year study) – 54% (150mg) and 50%(300mg) relative decrease in relapse rates – Showed reduced number of new or newly enlarging T2 hyperintense lesions at 1 year (70% for 150mg, 79% for 300mg) – Demonstrated statistically significant reduction in cumulative number of new lesions between 8-24 weeks (69% for 150mg, 78% for 300mg) – Some infectious disease concerns (serious 2% vs. 0%, plac/dac) and LFT 5x UNL 4% vs. 1% Next . DECIDE PIII data in 2014 Steps
Sources: Biogen Idec, AbbVie, Credit Suisse research and analysis Slide 88 September 2013 Biogen Idec Tecfidera (BG-12) Tecfidera Overview
. Orally administered dimethyl fumarate . Immunomodulator with neuroprotective properties . Obtained through acquisition of Fumapharm AG (2006) . Tecfidera has captured ~10% TRx share in the U.S. so far . CS assumes protection in the U.S. until 2023 and in the EU until 2019 . PIII program consisted of two trials, DEFINE and CONFIRM, in RRMS . Approved by the FDA on Mar 27, 2013 . Expecting EMA decision on RDP status in late 2013 / early 2014 . Superior to ABCRs in efficacy and safety based on DEFINE and CONFIRM
DEFINE CONFIRM Reduction in Relapse Rate 53% BID / 48% TID 44% BID / 51% TID / 29% Copaxone Reduction in EDSS Progression 38% BID / 34% TID 21% BID / 24% TID / 7% Copaxone Reduction in New/Enlarging T2 Lesions 85% BID / 74% TID 71% BID / 73% TID Reduction in T1 Lesions 72% BID / 63% TID 57% BID / 65% TID Reduction in Gd+ Lesions 90% BID / 73% TID N/A Safety/Tolerability Transient flushing and GI disorders Transient flushing and GI disorders
Sources: Biogen Idec, Credit Suisse research and analysis Slide 90 September 2013 What have we learned from DEFINE and CONFIRM?
. BG-12 has superior efficacy and safety relative to ABCRs – In DEFINE, ARR and reduction in EDSS progression were more substantial relative to historical data for ABCRs
. ARR reduction: 53% BID, 48% TID / EDSS reduction: 38% BID, 34% TID – In CONFIRM, BG-12 arms were superior to the Copaxone comparator arm in reducing ARR and EDSS progression
. ARR reduction: 44% BID, 51% TID, 29% Copaxone / EDSS reduction: 21% BID, 24% TID, 7% Copaxone – Most common adverse events observed in DEFINE and CONFIRM were flushing and GI disorders, both of which were transient in nature . Most common AEs (e.g. flushing and GI disorders) due to BG-12 are transient and generally easily managed, as observed in DEFINE and CONFIRM – Incidence of flushing drops off significantly after the first month (~30% ~5%) – Incidence of GI disorders follows a similar pattern seen in flushing (~25% ~5%) – Flushing accounted for 2% and 1% of discontinuations in BID and TID arms respectively – Aspirin can be used to reduce incidence and severity of flushing, as BIIB showed in a small trial in healthy volunteers
Sources: Biogen Idec, Credit Suisse research and analysis Slide 91 September 2013 What have we learned from DEFINE and CONFIRM? (cont.)
. MRI data appears to provide additional support for BG-12’s possible neuroprotective mechanism of action based on DEFINE and CONFIRM data sets
Data at Year 2 DEFINE CONFIRM BG-12 BID BG-12 TID BG-12 BID BG-12 TID Number of Gd+ Lesions 90% 73% N/A N/A Number of T1 Lesions 72% 63% 65% 41% Number of New/Enlarging T2 Lesions 85% 74% 71% 73%
. BG-12 appears to be more modulatory than suppressive on the immune system as shown in DEFINE and CONFIRM – Incidence of infections did not increase due to BG-12 in either trial – DEFINE: 65% pbo, 64% BID, 68% TID; CONFIRM: 50% pbo, 56% BID, 56% TID – Both white blood cell and lymphocyte counts decreased, but remained within normal limits . Integrated analysis of DEFINE and CONFIRM supports claims that BG-12 reduces disability – Reduction in EDSS progression was 32% for BID (p=0.0034) and 30% (TID, p=0.0059) in the integrated analysis – Recall, DEFINE (but not CONFIRM) showed a statistically significant reduction in EDSS progression
Sources: Biogen Idec, Credit Suisse research and analysis Slide 92 September 2013 DEFINE vs. CONFIRM: Key Data Comparisons
DEFINE CONFIRM Number of Patients 1234 1011 Study Duration 2 years 2 years Patient Characteristics RRMS RRMS Comparator Placebo Placebo, Copaxone Reduction in Relapse Rate 53% BID (p<0.0001) / 48% TID (p<0.0001) 44% BID (p<0.0001) / 51% TID (p<0.0001) at 2 Years 29% Copaxone (p<0.02) Reduction in EDSS 38% BID (p=0.0050) / 34% TID (p=0.0128) 21% BID (p=NS) / 24% TID (p=NS) Progression at 2 Years 7% Copaxone (p=NS) Reduction in New/Enlarging 85% BID (p<0.0001) / 74% TID (p<0.0001) 71% BID (p<0.0001) / 73% TID (p<0.0001) T2 Lesions 54% Copaxone (p<0.0001) Reduction in T1 Lesions 72% BID (p<0.0001) / 63% TID (p<0.0001) 57% BID (p<0.0001) / 65% TID (p<0.0001) 41% Copaxone (p<0.0001) Reduction in Gd+ Lesions 90% (p<0.0001) BID / 73% TID (p<0.0001) N/A Reduction in Proportion N/A 34% BID (p<0.0001) / 45% TID (p<0.0001) Relapsed 29% Copaxone (p<0.01) Safety/Tolerability . Flushing (38% BID, 32% TID)* . Flushing (31% BID, 23% TID)* . GI Disorders (~25% BID, ~25% TID)* . GI Disorders (~25% BID, ~25% TID)* * Transient (significant reduction in incidence after 1 month of treatment with BG-12
Sources: Biogen Idec, Credit Suisse research and analysis Slide 93 September 2013 CONFIRM vs. DEFINE: Trial Design
Year 1 Year 2 Year 1 Year 2
BG00012 PO 240mg TID BG12 PO 240mg TID (720mg/ day – 120mg tablets) (720mg/ day – 120mg tablets)
BG00012 PO 240mg BID BG12 PO 240mg BID Randomization (480mg/ day – 120mg tablets) Randomization (480mg/ day – 120mg tablets) 1:1:1:1 1:1:1 1,232 patients 1,011 patients Placebo Placebo
Copaxone SC 20mg/ day
Optional Optional Rescue Tx Rescue Tx
EDSS EDSS
MSFC/ VFT MSFC/ VFT
MRI MRI
0 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 96
Study Week Study Week
Unlike DEFINE, CONFIRM includes a Copaxone comparator arm
Sources: Adapted from Fox , Biogen Idec 2010 CSN Roundtable Presentation Touch Briefing 2008, Credit Suisse research and analysis Slide 94 September 2013 CONFIRM vs. DEFINE: Trial Overview
Patient . RRMS . RRMS Population . Excludes patients who were on GA at anytime . Excludes patients who were on SC/Oral GA within 3 months of randomization Duration . 100 weeks . 100 weeks Dosing . Oral 240mg TID or 240 BID . Oral 240mg TID or 240 BID Placebo . Yes . Yes Comparator . Copaxone (GA) Arm 20mg QD . None Data . MTR and brain atrophy at 24, 48, and 96 weeks . MTR and brain atrophy at 24, 48, and 96 weeks Collection . EDSS at every 12 weeks . EDSS at every 12 weeks . MSFC/VFT at every 12 weeks . MSFC/VFT at every 12 weeks Primary . Rate of clinical relapse at 2yrs . Proportion of patients relapsing at 2yrs Endpoint(s) Secondary . # of new or enlarging T2-hyperintense lesions over 2yrs . # of new or enlarging T2-hyperintense lesions over 2yrs Endpoint(s) . # of new T1-hyperintense lesions at 2yrs . # of Gd+ lesions at 2yrs . Proportion of patients relapsing at 2 yrs . Rate of clinical relapse at 1yr . (BG12 vs. Placebo) relative to (GA vs. Placebo) . Rate of disability progression at 2yrs . Rate of disability progression at 2yrs Other . Option to switch to open-label rescue MS therapy if patient . Option to switch to open-label rescue MS therapy if patient experiences: experiences: – 2 confirmed relapses at any time and have completed – 1 confirmed response >24 weeks and have completed ≥48 weeks of blinded therapy, OR ≥48 weeks of blinded therapy, OR – Significant protocol-defined disability progression – Significant protocol-defined disability progression
Sources: Biogen Idec, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 95 September 2013 CONFIRM vs. DEFINE: Key Differences
Comments
Patient . Excludes patients who were on GA at . Excludes patients who were on . CONFIRM and DEFINE have different patient Population anytime SC/Oral GA within 3 months of populations associated with prior Copaxone usage randomization Comparator . Copaxone (GA) Arm 20mg QD . None . CONFIRM has a Copaxone comparator arm with no Arm inferiority/superiority endpoints . CONFIRM will compare benefit of BG12 vs. Placebo relative to Copaxone vs. Placebo Primary . Rate of clinical relapse at 2yrs . Proportion of patients relapsing at 2yrs . Relative to DEFINE, CONFIRM uses a “typical” primary Endpoints endpoint that is assessed in other clinical trials for MS . Historically, the endpoint for DEFINE is harder to achieve relative to the endpoint for CONFIRM Secondary . # of new or enlarging T2-hyperintense . # of new or enlarging T2-hyperintense . Both clinical trials measure similar secondary endpoints Endpoints lesions over 2yrs lesions over 2yrs (T2-hyperintense lesions, rate of disability progression) . # of new T1-hyperintense lesions at . # of Gd+ lesions at 2yrs . CONFIRM evaluates neuroprotective capabilities of 2yrs . Rate of clinical relapse at 1yr BG12 by measuring T1-hyperintense lesions . Proportion of patients relapsing at 2yrs . Rate of disability progression at 2yrs . DEFINE assessed anti-inflammatory effects of BG12 via . Rate of disability progression at 2yrs Gd+ lesion measurement . CONFIRM assesses the primary endpoint of DEFINE as a secondary endpoint, and vice versa Other . Switch to rescue MS therapy: . Switch to rescue MS therapy: . CONFIRM and DEFINE have slightly different criteria – 2 confirmed relapses at any time – 1 confirmed response >24 weeks for switching patients to rescue MS therapy, with and have completed ≥48 weeks of and have completed ≥48 weeks of CONFIRM appearing to be more strict than DEFINE blinded therapy, OR blinded therapy, OR – Significant protocol-defined – Significant protocol-defined disability progression disability progression
Sources: Biogen Idec, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 96 September 2013 DEFINE Phase III Trial Data
DEFINE Phase III Trial Data Clinical Outcomes at 2 Years BG-12 BID BG-12 TID Reduction in Relapse Rates 53% (p<0.0001) 48% (p<0.0001) Reduction in EDSS Disease Progression 36% (p=0.0050) 34% (p=0.0128) MRI Outcomes Year 0-1 Year 1-2 Year 0-2 Reduction in Gd+ Lesions 92% BID* / 87% TID* N/A 90% BID* / 73% TID* Reduction in New/Enlarging T2 Lesions 84% BID* / 75% TID* 87% BID* / 76% TID* 85% BID* / 74% TID* Reduction in T1 Lesions 69% BID* / 61% TID* 79% BID* / 69% TID* 72% BID* / 63% TID* Safety and Tolerability BG-12 BID BG-12 TID Placebo Serious Adverse Event Incidence 18% 16% 21% Severe Adverse Event Incidence 16% 17% 17% Discontinuations from Adverse Events 16% 16% 13% Infection Incidence 64% 68% 65% Serious Infection Incidence 2% 2% 2% Malignancy Incidence <1% <1% <1% Most Common Adverse Events . Flushing (38% BID, 32% TID), GI Disorders (~25% BID, ~25% TID) . Both flushing and GI disorders were transient, as significant drops in incidence were observed after 1 month of treatment with BG-12 . The counts of white blood cell and lymphocyte counts decreased, but remained within normal limits * p<0.0001 vs pbo
Sources: Biogen Idec, Credit Suisse research and analysis Slide 97 September 2013 DEFINE: Baseline Characteristics
Characteristic Placebo (n=408) BG12 240mg BID (n=410) BG12 240mg TID (n=416 Age, years Mean (SD) 38.5 (9.14) 38.1 (9.11) 38.8 (8.85) Range 18–56 18–55 18–56 Female, n (%) 306 (75) 296 (72) 306 (74) Weight, kg, mean (SD) 71.1 (17.01) 70.7 (18.54) 71.3 (16.92) Race, n (%) White 318 (78) 321 (78) 330 (79) Asiana 42 (10) 38 (9) 36 (9) Black/African American 8 (2) 8 (2) 10 (2) Other/unknown 40 (10) 43 (10) 40 (10) Prior approved treatments for RRMS, %b 42 40 40 Time since first MS symptoms, years, mean (SD) 8.6 (6.58) 8.7 (7.08) 8.0 (5.95) Time since diagnosis, years Mean (SD) 5.8 (5.78) 5.6 (5.39) 5.1 (5.29) Range 0–31 0–32 0–23 Relapses in previous 12 months, mean (SD) 1.3 (0.67) 1.3 (0.67) 1.3 (0.60) Relapses in previous 36 months, mean (SD) 2.5 (1.56) 2.5 (1.44) 2.4 (1.27) Time since recent prestudy relapse, months, mean (SD) 6.6 (7.27) 6.6 (7.01) 6.6 (7.35) EDSS score at baseline, mean (SD) 2.48 (1.24) 2.40 (1.29) 2.36 (1.19) MRI characteristics Gd+ lesion number, mean (SD) 1.6 (3.5) 1.2 (3.3) 1.2 (4.1) T1 hypointense lesion number, mean (SD) 27.3 (28.5) 27.8 (29.7) 33.6 (34.7) T2 lesion number, mean (SD) 49.2 (38.6) 47.6 (34.7) 55.8 (44.3) T2 lesion volume, mm3, mean 6524.9 8463.8 9014.5 Normalized whole brain volume, cm3, mean (SD) 1586.7 (81.68) 1573.5 (85.82) 1565.5 (93.13)
Sources: K Selmaj et al “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis; DL Arnold et al. “Efficacy on MRI Endpoints of BG-12, an Oral Therapy, in Relapsing-Remitting Multiple Slide 98 Sclerosis: Data from the Phase 3 DEFINE Trial”; L Kappos et al. “BG-12 Effects on Patient-Reported Outcomes in Relapsing- September 2013 Remitting Multiple Sclerosis: Results from the DEFINE Study”; R Gold et al BG-12 Oral Presentation DEFINE: Cumulative Probability of Relapse
Source: R Gold et al NEJM 2012, 367; 1098-1107 Slide 99 September 2013 DEFINE: Annualized Relapse Rate at 2 Years
Source: R Gold et al BG12 Oral Presentation (ECTRIMS 2011) Slide 100 September 2013 DEFINE: Time to 12-Week Confirmed Disability Progression
Source: R Gold et al BG12 Oral Presentation (ECTRIMS 2011) Slide 101 September 2013 DEFINE: New or Newly Enlarging T2 Lesions
Source: DL Arnold et al. “Efficacy on MRI Endpoints of BG-12, an Oral Therapy, in Relapsing-Remitting Multiple Sclerosis: Data from the Phase 3 DEFINE Trial” (ECTRIMS 2011) Slide 102 September 2013 DEFINE: Gd+ Lesions
Source: DL Arnold et al. “Efficacy on MRI Endpoints of BG-12, an Oral Therapy, in Relapsing-Remitting Multiple Sclerosis: Data from the Phase 3 DEFINE Trial” (ECTRIMS 2011) Slide 103 September 2013 DEFINE: T1 Hypointense Lesions
Source: DL Arnold et al. “Efficacy on MRI Endpoints of BG-12, an Oral Therapy, in Relapsing-Remitting Multiple Sclerosis: Data from the Phase 3 DEFINE Trial” (ECTRIMS 2011) Slide 104 September 2013 DEFINE: Summary of Adverse Events
Placebo BG12 240mg BG12 240mg Total BG12 (n=408) BID TID (n=826) (n=410) (n=416) All AEs 387 (95) 395 (96) 396 (95) 791 (96) Serious AEs 86 (21) 74 (18) 65 (16) 139 (17) Severe AEs 71 (17) 67 (16) 71 (17) 138 (17) All infections 264 (65) 263 (64) 281 (68) 544 (66) Serious infections 7 (2) 10 (2) 8 (2) 18 (2) Discontinued treatment due to an event 55 (13) 65 (16) 68 (16) 133 (16) Died 0 1 (<1)a 1 (<1)b 2 (<1) aSubject died 3 weeks after withdrawing from the study due to traumatic brain injury from a cycling accident bSubject died in a road traffic accident during the study.
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 105 September 2013 DEFINE: Breakdown of Withdrawals - BG-12 BID vs. Placebo
Source: R Gold et al BG12 Oral Presentation (ECTRIMS 2011) Slide 106 September 2013 DEFINE: Breakdown of Withdrawals - BG-12 BID vs. BG-12 TID
Source: R Gold et al BG12 Oral Presentation (ECTRIMS 2011) Slide 107 September 2013 DEFINE: Summary of Adverse Events
Source: R Gold et al BG12 Oral Presentation (ECTRIMS 2011) Slide 108 September 2013 DEFINE: Common Adverse Events
AE, n (%) Placebo (n=408) BG12 240mg BG12 240mg TID Total BG12 BID (n=410) (n=416) (n=826) Any event 387 (95) 395 (96) 396 (95) 791 (96) Flushing 20 (5) 154 (38) 132 (32) 286 (35) MS relapse 189 (46) 111 (27) 114 (27) 225 (27) Nasopharyngitis 101 (25) 108 (26) 109 (26) 217 (26) Headache 80 (20) 81 (20) 80 (19) 161 (19) Diarrhea 55 (13) 62 (15) 78 (19) 140 (17) Fatigue 54 (13) 57 (14) 63 (15) 120 (15) Upper respiratory tract infection 53 (13) 63 (15) 51 (12) 114 (14) Urinary tract infection 53 (13) 55 (13) 54 (13) 109 (13) Nausea 38 (9) 53 (13) 54 (13) 107 (13) Back pain 57 (14) 59 (14) 46 (11) 105 (13) Upper abdominal pain 28 (7) 40 (10) 52 (13) 92 (11) Proteinuria 34 (8) 38 (9) 50 (12) 88 (11) Abdominal pain 22 (5) 46 (11) 37 (9) 83 (10) Arthralgia 39 (10) 46 (11) 37 (9) 83 (10) Influenza 39 (10) 34 (8) 48 (12) 82 (10) Pruritus 19 (5) 42 (10) 34 (8) 76 (9) Vomiting 24 (6) 40 (10) 30 (7) 70 (8)
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 109 September 2013 DEFINE: Adverse Events Leading to Drug Discontinuation
Placebo BG12 240mg BID BG12 240mg TID Total BG12 (n=408) (n=410) (n=416) (n=826) Discontinued Study Drug, n (%) 55 (13) 65 (16) 68 (16) 133 (16) Flushing 1 (<1) 10 (2) 6 (1) 16 (2) MS relapse 31 (8) 5 (1) 10 (2) 15 (2) Diarrhea 1 (<1) 5 (1) 8 (2) 13 (2) Abdominal Pain, Upper 1 (<1) 5 (1) 6 (1) 11 (1) Nausea 0 5 (1) 6 (1) 11 (1) Vomiting 0 5 (1) 6 (1) 11 (1) Abdominal Pain 0 3 (<1) 7 (2) 10 (1)
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 110 September 2013 DEFINE: Flushing Events by Study Month
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 111 September 2013 DEFINE: GI Events by Study Month
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 112 September 2013 DEFINE: Serious Adverse Events
Placebo BG-12 240 mg BID BG-12 240 mg TID Total BG-12 SAE, n (%) (n=408) (n=410) (n=416) (n=826) Any event 86 (21) 74 (18) 65 (16) 139 (17) MS relapse 60 (15) 39 (10) 32 (8) 71 (9) Gastroenteritis 0 4 (<1) 1 (<1) 5 (<1) Gastritis 0 0 3 (<1) 3 (<1) Ovarian cyst 1 (<1) 1 (<1) 2 (<1) 3 (<1) Headache 0 0 2 (<1) 2 (<1) Pneumonia 1 (<1) 2 (<1) 0 2 (<1)
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 113 September 2013 DEFINE: Infections Reported as Serious Adverse Events
AE, n (%) Placebo (n=408) BG12 240mg BID (n=410) BG12 240mg TID (n=416) Patients with any event 7 (2) 10 (2) 8 (2) Gastroenteritis 0 4 (<1) 1 (<1) Pneumonia 1 (<1) 2 (<1) 0 Sinusitis 0 1 (<1) 1 (<1) Viral infection 0 1 (<1) 1 (<1) Appendicitis 0 1 (<1) 0 Cellulitis 0 0 1 (<1) H1N1 influenza 1 (<1) 0 1 (<1) Influenza 0 0 1 (<1) Peritonsillar abscess 0 0 1 (<1) Postviral fatigue 0 1 (<1) 0 Urinary tract infection 0 0 1 (<1) Vulval abscess 0 0 1 (<1)
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 114 September 2013 DEFINE: Reported Malignancies
AE, n (%) Placebo (n=408) BG12 240mg BID BG12 240mg TID (n=410) (n=416) Malignancies 2 (<1) 2 (<1) 2 (<1) Basal cell carcinoma 1 (<1) 1 (<1) 0 Breast cancer 1 (<1) 0 1 (<1) Cervix carcinoma 0 0 1 (<1) Transitional cell carcinoma 0 1 (<1) 0
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 115 September 2013 DEFINE: Hematology Data
. “Decreases in white blood cell (WBC) and lymphocyte counts were observed in both BG-12 groups compared with the placebo group.” – “Overall mean and median WBC and lymphocyte counts decreased over the first year and then plateaued. Mean and median counts remained within normal limits.” – “Low WBC counts (<3.0×109/L) and lymphocyte counts (<0.5×109/L) were observed in 1% and <1%, respectively, of patients receiving placebo, and in 4% and 4%, respectively, of patients receiving BG-12.”
Sources: K Selmaj et al “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis; DL Arnold et al. “Efficacy on MRI Endpoints of BG-12, an Oral Therapy, in Relapsing-Remitting Multiple Slide 116 Sclerosis: Data from the Phase 3 DEFINE Trial”; L Kappos et al. “BG-12 Effects on Patient-Reported Outcomes in Relapsing- September 2013 Remitting Multiple Sclerosis: Results from the DEFINE Study”; R Gold et al BG-12 Oral Presentation DEFINE: Hepatic Blood Chemistry
Placebo (n=408) BG12 240mg BID BG12 240mg TID Total BG12 (n=410) (n=416) (n=826) Total 404 (100) 401 (100) 405 (100) 806 (100) ALT ≥3×ULN 14 (3) 26 (6) 24 (6) 50 (6) >5×ULN 7 (2) 6 (1) 10 (2) 16 (2) AST ≥3×ULN 7 (2) 8 (2) 8 (2) 16 (2) >5×ULN 4 (<1) 1 (<1) 2 (<1) 3 (<1) ALT/AST ≥3×ULN 0 0 0 0 with concurrently elevated bilirubin, defined as >2×ULN
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 117 September 2013 DEFINE: SF-36 Mean Change from Baseline in PCS over 2 Years
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 118 September 2013 DEFINE: SF-36 Mean Change from Baseline in MCS over 2 Years
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 119 September 2013 DEFINE: SF-36 Subscale Scores
Source: K Selmaj et al. “Safety and Tolerability of BG-12 in the Phase 3 DEFINE Trial in Patients with Relapsing-Remitting Multiple Sclerosis” (ECTRIMS 2011) Slide 120 September 2013 CONFIRM: Baseline Characteristics
Source: R. Fox et al. NEJM 2012 Slide 121 September 2013 CONFIRM: Annualized Relapse Rates
Source: R. Fox et al. NEJM 2012 Slide 122 September 2013 CONFIRM: 12-Week EDSS Progression
Source: R. Fox et al. NEJM 2012 Slide 123 September 2013 CONFIRM: Clinical Efficacy Overview
Source: R. Fox et al. NEJM 2012 Slide 124 September 2013 CONFIRM: Safety Data Overview
Source: R. Fox et al. NEJM 2012 Slide 125 September 2013 Tecfidera Efficacy from Integrated Analysis of CONFIRM/DEFINE
Annualized Relapse Rate (ARR) Disability Progression
. Tecfidera (BG-12) reduced ARR relative to . Tecfidera (BG-12) reduced disability placebo by 49% (BID) and 49% (TID) progression relative to placebo by 32% (BID) and 30% (TID)
Sources: K. Fox et al. Integrated Analysis of CONFIRM and DEFINE Poster at AAN 2013 Slide 6 Tecfidera Safety from Integrated Analysis of CONFIRM/DEFINE Common Adverse Events Flushing Incidence by Month
GI Side Effect Incidence by Month
. Tecfidera has a very favorable safety profile . Most common adverse events are transient flushing and gastrointestinal side effects
Sources: K. Selmaj et al. Integrated Analysis of CONFIRM and DEFINE Poster at ECTRIMS 2012 Slide 7 Sanofi Aubagio (Teriflunomide) Aubagio (Teriflunomide) Overview
. Orally administered active metabolite of leflunomide . Immunomodulator that reduces B- and T-cell counts by stopping cell division . Approved by FDA on Sep 12, 2012 and EMA on Aug 30, 2013 . Received RDP status in the EU as a new active substance . Phase III program evaluated Aubagio in RMS (TEMSO, TOWER, TENERE) and first clinical episodes suggestive of MS (TOPIC) as well as Aubagio + IFN Beta I in RMS (TERACLES) . Being positioned for patients with early MS or moderate RRMS . In TEMSO, Aubagio has demonstrated modest efficacy, but good safety/tolerability: – Reduced ARR (vs pbo) by 31% for 7 mg and 32% for 14 mg – Reduced EDSS progression (vs pbo) by 24% for 7 mg and 30% for 14 mg – Most common adverse events were diarrhea, hair thinning, elevated ALTs, and high blood pressure . TOWER confirmed efficacy of 14mg dose . In TENERE, Aubagio showed that it is comparable to Rebif from statistical point of view – Risk of treatment failure was comparable in all arms (49% for 7 mg, 38% for 14 mg, 42% for Rebif) – Both doses had higher ARR (0.410 for 7 mg, 0.259 for 14 mg) than Rebif (0.216) – Side effects were similar to those observed in TEMSO
Sources: Sanofi, Credit Suisse research and analysis Slide 129 September 2013 What we learned from TEMSO, TOWER, and TENERE?
. TEMSO showed that the 14 mg Aubagio is effective in both reducing relapse rates and slowing disease progression (vs placebo) – 14 mg dose demonstrated statistical significance in reducing relapse rates (31.5%, p=0.0005) and slowing EDSS progression (29.8%, p=0.0279) – 7 mg dose showed statistical significant in reducing relapse rates (31.2%, p=0.0002), but failed to demonstrate statistical significance in slowing EDSS progression (23.7%, p=0.08) . TENERE suggests that Aubagio is comparable in efficacy to Rebif from a statistical view – Both doses did not show statistical significance in risk of treatment failure and reduction in annual relapse rates relative to Rebif – Percentage of patients reaching primary endpoint of risk of treatment failure was 48.6% for 7 mg, 37.8% for 14 mg, and 42.3% for Rebif – ARR was 0.410 for 7 mg and 0.259 for 14 mg as compared to 0.216 for Rebif . TOWER confirmed efficacy of 14mg dose in reducing relapse rates (36.3%) and 12-week EDSS progression (31.5%). . The slightly higher number of relapses in Aubagio arms (vs Rebif) in TENERE could be a slight negative for Aubagio from a commercial view – Both doses had higher relapse rates (0.410 for 7 mg, 0.259 for 14 mg) relative to Rebif (0.216)
Sources: Sanofi, Credit Suisse research and analysis Slide 130 September 2013 What we learned from TEMSO, TOWER, and TENERE? (cont.)
. MRI data from TEMSO is generally positive for Aubagio
7 mg Aubagio 14 mg Aubagio Placebo Reduction in Total Lesion Volume (vs Pbo) 39.4% (p=0.03) 67.4% (p<0.001) - - - - - Reduction in T1 Hypointense Lesion Volume (vs Pbo) 16.7% (p=0.19) 31.3% (p=0.02) - - - - - Absence of Gd+ Lesions (% of Patients) 51.4% 64.1% 39.0% Reduction in T2 Hyperintense Lesion Volume 44.0% (p=0.04) 76.7% (p<0.001) - - - - - Number of Gd+ Lesions 0.57 (p<0.001) 0.26 (p<0.001) 1.33 Number of Unique Active Lesions 1.29 (p<0.001) 0.75 (p<0.001) 2.46 Brain Parenchymal Fraction -0.003 (p=0.19) -0.003 (p=0.35) -0.004 . Both trials have shown that Aubagio has a favorable safety/tolerability profile – Most common side effects in TEMSO were diarrhea, hair thinning, elevated ALTs, and high blood pressure – Safety profile in TENERE was similar to that observed in TEMSO . TENERE does show that Aubagio has a better safety/tolerability profile than Rebif – Incidence of TEAEs were lower in Aubagio (8.2% for 7 mg, 10.9% for 14 mg) than Rebif (21.8%) . TEMSO suggests Aubagio could be more immunomodulatory than immunosuppressive – Mean reductions in neutrophil and lymphocyte counts were low in magnitude, but3 patients did develop moderate neutropenia
Sources: Sanofi, Credit Suisse research and analysis Slide 131 September 2013 TEMSO Phase III Trial Design
ARM Week (N) 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108
1 7 mg Teriflunomide QD (365)
RMS 2 Patients 14 mg Teriflunomide QD (358) (N=1088)
3 Placebo (363)
MRI X X X X X
Duration . 108 weeks Patient . RMS (RRMS, SPMS, PRMS) Population . Experienced ≥1 relapse over 1 year or ≥2 relapse over 2 years prior to start of trial Primary . Annualized relapse rate (Number of confirmed relapses per patient-year) Endpoint(s) Secondary . Time to disability progression by EDSS Endpoint(s) . Proportion of patients who are free of disability progression (at 0.5, 1, and 2 years) . Burden of disease based on change in baseline in volume of abnormal brain tissue by MRI Readout . Full data published in NEJM on Oct 6, 2011
Sources: Sanofi, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 132 September 2013 TENERE Phase III Trial Design
ARM Week (N) Initial Treatment Period (>48 weeks) Extension Period (=48 weeks)
1 7 mg Teriflunomide QD Extension: 14 mg Teriflunomide QD (109) RMS 2 Patients 14 mg Teriflunomide QD Extension: 14 mg Teriflunomide QD (111) (N=324) 3 44 μg Rebif IM 3 x QW Extension: 14 mg Teriflunomide QD (104)
Duration . 96+ weeks Patient . RMS Population Primary . Time to failure (first occurrence of relapse or permanent discontinuation) Endpoint(s) Secondary . Annualized relapse rate (Number of relapses per patient-year) Endpoint(s) . Reported fatigue as assessed by FIS . Satisfaction based on TSQM Readout . Headline data was released in Q4’11
Sources: Sanofi, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 133 September 2013 TOWER Phase III Trial Design
ARM Week Extension (N) Initial Treatment Period (>48 weeks) Extension Period (=48 weeks)
1 7 mg Teriflunomide QD Extension: 14 mg Teriflunomide QD
RMS 2 Patients 14 mg Teriflunomide QD Extension: 14 mg Teriflunomide QD (N=1169) 3 Placebo Extension: 14 mg Teriflunomide QD
Duration . 96+ weeks Patient . RMS Population . Experienced ≥1 relapse over 1 year or ≥2 relapse over 2 years prior to start of trial Primary . Annualized relapse rate (Number of relapses per patient-year) Endpoint(s) Secondary . Time to disability progression by EDSS Endpoint(s) . Change from baseline in reported fatigue based on FIS . Change from baseline in short form generic health survey Readout . Headline data was released in Q3’12
Sources: Sanofi, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 134 September 2013 TOPIC Phase III Trial Design
ARM Week (N) 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108
1 7 mg Teriflunomide QD (206) CIS 2 Patients 14 mg Teriflunomide QD (206) (N=618) 3 Placebo (206)
MRI X X X X X X
Duration . 108 weeks Patient . Patients with first clinical episode consistent with MS Population . Onset of MS symptoms within 90 days of randomization . Screening MRI scan with 2+ T2 lesions at least 3mm in diameter characteristics of MS Primary . Conversion to clinically definite MS defined by the occurrence of a relapse Endpoint(s) Secondary . Conversion to definite MS as demonstrated by dissemination of cerebral MRI lesions in time Endpoint(s) . Annualized relapse rate . Burden of disease measured by change from baseline in volume of abnormal brain tissue via MRI Readout . Potential data readout in 2013
Sources: Sanofi, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 135 September 2013 TERACLES Phase III Trial Design
ARM Treatment Duration (N) Initial Treatment Period (>48 weeks) Extension Period (~48 weeks)
1 7 mg Teriflunomide QD + IFN Beta Extension (485) RMS 2 Patients 14 mg Teriflunomide QD + IFN Beta Extension (485) (N=1455) 3 IFN Beta Extension (485)
Duration . 96+ weeks Patient . RMS Population . Stable dose of IFN Beta ≥6 months prior to randomization . Disease activity in 12 months prior to randomization and after first 3 months of IFN Beta Primary . Annualized relapse rate (Number of confirmed relapses per patient-year) Endpoint(s) Secondary . Number of Gd+ lesions Endpoint(s) . Time to disability progression measured by EDSS . Burden of disease measured by change from baseline in volume of abnormal brain tissue via MRI . Time to first confirmed relapse . Proportion relapse-free . Fatigue measured by FIS score . General health measured by SF-36 score Readout . Potential data readout in 2014
Sources: Sanofi, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 136 September 2013 TEMSO Phase III Data
7 mg Aubagio 14 mg Aubagio Placebo Clinical Outcomes Reduction in ARR at 2 Years (vs Pbo) 31.2% (p=0.0002) 31.5% (p=0.0005) - - - - - Proportion Relapse-Free at 2 Years 53.7% (p=0.01) 56.5% (p=0.003) 45.6% Reduction in EDSS HR at 2 Years (vs Pbo) 23.7% (p=0.08) 29.8% (p=0.03) - - - - - Change in FIS Score from Baseline 2.3 (p=0.39) 3.8 (p=0.83) 4.3 MRI Outcomes Reduction in Total Lesion Volume (vs Pbo) 39.4% (p=0.03) 67.4% (p<0.001) - - - - - Reduction in T1 Hypointense Lesion Volume (vs Pbo) 16.7% (p=0.19) 31.3% (p=0.02) - - - - - Absence of Gd+ Lesions (% of Patients) 51.4% 64.1% 39.0% Reduction in T2 Hyperintense Lesion Volume 44.0% (p=0.04) 76.7% (p<0.001) - - - - - Number of Gd+ Lesions 0.57 (p<0.001) 0.26 (p<0.001) 1.33 Number of Unique Active Lesions 1.29 (p<0.001) 0.75 (p<0.001) 2.46 Brain Parenchymal Fraction -0.003 (p=0.19) -0.003 (p=0.35) -0.004 Safety/Tolerability Adverse Events 89.1% 90.8% 87.5% Adverse Events Leading to Discontinuations 9.8% 10.9% 8.1% Serious Adverse Events 14.1% 15.9% 12.8% Common Adverse Events . Diarrhea (14.7%, 17.9%, 8.9%); Hair Thinning (10.3%, 13.1%, 3.3%); Elevated (7 mg Aubagio, 14 mg Aubagio, Placebo) ALTs (12.0%, 14.2%, 6.7%), High Blood Pressure (5.4%, 5.0%, 3.1%) . Mean reductions in neutrophil and lymphocyte counts were low in magnitude, but 3 patients did develop moderate neutropenia
Sources: O’Connor et al. NEJM 2011, Credit Suisse research and analysis Slide 137 September 2013 Sanofi / Bayer Lemtrada (Alemtuzumab) Lemtrada (Alemtuzumab) Overview
. IV-administered humanized anti-CD52 mAb targeting B- and T-cells . Immunosuppressive mechanism of action . Currently approved for treatment of B-cell chronic lymphocytic leukemia (B-CLL) . Expecting sBLA PDUFA in Q4’13; Received EMA approval on Sep 17, 2013 . Being positioned for treatment of severe RMS . Once-yearly dosing schedule is convenient, but IV administration is not ideal . Efficacy is generally superior to ABCRs, and comparable to High-Efficacy/2nd-Line, but safety though seems to be worse than ABCRs . Both Phase III trials showed high efficacy in reducing relapse rates relative to Rebif – Reduced ARR (vs Rebif) by 55% in CARE-MS I (p<0.0001) and 49% in CARE-MS II (p<0.0001) . However, only CARE-MS II showed a statistically significant reduction in disease progression – In CARE-MS I, there was no statistical significant reduction in EDSS progression (vs Rebif) – In CARE-MS II, there was a 42% reduction in EDSS progression (vs Rebif) . Safety remains a concern due to increased risk of immune-related conditions including autoimmune thyroid disorders, immune thrombocytopenia, and infections
Sources: Sanofi, Credit Suisse research and analysis Slide 139 September 2013 What have we learned from CARE-MS I and CARE-MS II?
. Lemtrada is generally superior to Rebif (and other ABCRs) – Reductions in relapse rates at 2 years (vs Rebif) were 55% in CARE-MS I (p<0.0001) and 49% for in CARE-MS II (p<0.0001) – Reductions in EDSS progression (vs Rebif) were 42% in CARE-MS II (p=0.0084) and not meaningful in CARE-MS I (p=NS) . Lemtrada appears to be more effective in treating moderate-to-severe RRMS relative to Rebif – CARE-MS I failed to showed a statistically significant reduction in EDSS progression in naïve RRMS – CARE-MS II showed Lemtrada could be beneficial in experienced (relapsed on prior treatment) RRMS . Safety is a major concern, which could further make Lemtrada a treatment option primarily for moderate-to-severe RRMS – Most common adverse events caused by Lemtrada include autoimmune thyroid disorders, immune thrombocytopenia, and infections in CARE-MS I and CARE-MS II – The risk-benefit ratio is particularly skewed towards the downside in naïve RRMS, given safety/tolerability issues and lack of meaningful reduction in EDSS progression – However, the AEs leading to withdrawal or discontinuation were lower for Lemtrada than Rebif
Sources: Sanofi, Credit Suisse research and analysis Slide 140 September 2013 What have we learned from CARE-MS I and CARE-MS II? (cont.)
. MRI data is generally positive for Lemtrada
12 mg Lemtrada MRI Outcomes* Year 0-1 Year 1-2 Year 0-2 Proportion with Gd+ Lesions 11.9 vs. 12.5 (p=0.78) 7.1 vs. 19.1 (p<0.0001) 15.4 vs. 27.0 (p=0.0008) Proportion with New/Enlarging Gd+ Lesions 40.0 vs. 47.7 (p=0.065) 23.1 vs. 40.6 (p<0.0001) 48.5 vs. 57.6 (p=0.035) Proportion with New/Enlarging T2 Lesions 40.0 vs. 47.7 (p=0.065) 23.1 vs. 40.6 (p<0.0001) 48.5 vs. 57.6 (p=0.035) Median % Change in T2 Lesion Volume -7.1 vs. -8.4 (p=0.035) -1.8 vs. 0.0 (p=0.036) -9.3 vs. -6.5 (p=0.31) Proportion with New T1 Lesions 19.5 vs. 25.3 (p=0.10) 6.8 vs. 18.2 (p=0.0001) 24.0 vs. 31.4 (p=0.054) Median % Change in Lesion Volume -15.0 vs. -9.5 (p=0.046) 0.0 vs. 4.1 (p=0.039) -21.6 vs. -0.1 (p=0.0018) Median Change in Brain Parenchymal Function -0.59 vs. -0.94 (p<0.0001) -0.25 vs. -0.50 (p=0.0052) -0.87 vs. -1.49 (p<0.0001)
. Lack of statistical significance in reducing EDSS in CARE-MS I could make claims on slowing disease progression for Lemtrada less clear-cut – Sanofi believes this miss occurred because patients in this trial had early stage MS, leading to stable disease throughout the trial
Sources: Sanofi, Credit Suisse research and analysis Slide 141 September 2013 CARE-MS I vs. CARE-MS II: Key Data Comparison
CARE-MS I CARE-MS II Number of Patients 581 840 Study Duration 2 years 2 years Patient Characteristics Treatment-Naïve Treatment-Experienced (Relapsed) Comparator Rebif Rebif Reduction in Relapse Rate at 2 Years* 55% (p<0.0001) 49% (p<0.0001) Reduction in EDSS Progression* 30% (p=0.22) 42% (p=0.0084) Safety/Tolerability . Autoimmune Thyroid-Related (18.1%) . Autoimmune Thyroid-Related (16%) . Immune Thrombocytopenia (0.8%) . Immune Thrombocytopenia (1%) . Infections (67%) . Mild to Moderate Infections
* Co-primary endpoints in CARE-MS I and CARE-MS II . Lemtrada hits only 1 of 2 co-primary endpoints in CARE-MS I, but achieves both co-primary endpoints in CARE-MS II – Lemtrada fails to show a reduction in EDSS disease progression in CARE-MS I . The safety/tolerability profiles for Lemtrada observed in CARE-MS I and CARE-MS II were generally comparable – The major adverse events include autoimmune-thyroid-related disorders, immune thrombocytopenia, and infections
Sources: Sanofi, Credit Suisse research and analysis Slide 142 September 2013 CARE-MS I Phase III Data
12 mg Lemtrada Clinical Outcomes* Description Reduction in Relapse Rates 55% at 2 years (p<0.0001) Relapse-Free Proportion 78%in Lemtrada vs. 11% in Rebif Reduction in EDSS Disease Progression 30% (p=0.22); EDSS: 8% in Lemtrada vs. 11% in Rebif MRI Outcomes* Year 0-1 Year 1-2 Year 0-2 Proportion with Gd+ Lesions 11.9 vs. 12.5 (p=0.78) 7.1 vs. 19.1 (p<0.0001) 15.4 vs. 27.0 (p=0.0008) Proportion with New/Enlarging Gd+ Lesions 40.0 vs. 47.7 (p=0.065) 23.1 vs. 40.6 (p<0.0001) 48.5 vs. 57.6 (p=0.035) Proportion with New/Enlarging T2 Lesions 40.0 vs. 47.7 (p=0.065) 23.1 vs. 40.6 (p<0.0001) 48.5 vs. 57.6 (p=0.035) Median % Change in T2 Lesion Volume -7.1 vs. -8.4 (p=0.035) -1.8 vs. 0.0 (p=0.036) -9.3 vs. -6.5 (p=0.31) Proportion with New T1 Lesions 19.5 vs. 25.3 (p=0.10) 6.8 vs. 18.2 (p=0.0001) 24.0 vs. 31.4 (p=0.054) Median % Change in Lesion Volume -15.0 vs. -9.5 (p=0.046) 0.0 vs. 4.1 (p=0.039) -21.6 vs. -0.1 (p=0.0018) Median Change in Brain Parenchymal Function -0.59 vs. -0.94 (p<0.0001) -0.25 vs. -0.50 (p=0.0052) -0.87 vs. -1.49 (p<0.0001) Secondary Endpoints – Other* . MSFC: 0.12 vs. 0.05 (p=0.012); MSFC + Sloan 1.25%: 0.09 vs. -0.02 Safety and Tolerability* . Adverse Events: 96% vs. 92% / Serious Adverse Events: 18% vs. 14% . Adverse Events Leading to Treatment Withdrawal: 1.3% vs. 5.9% / Adverse Events Leading to Study Discontinuation: 0% vs. 2.7% . AE: Infections (67% vs. 46%), Autoimmune Thyroid Disease (18.1% vs. 6.4%) . SAE: Infections (1.9% vs. 1.1%), Autoimmune Thyroid Disease (1.1%), Immune Thrombocytopenic Purpura (0.8% vs. 1.6%)
* Data is organized as Lemtrada vs. Rebif
Sources: Coles et al. CARE-MS I ECTRIMS Presentation 2011 Sanofi, Credit Suisse research and analysis Slide 143 September 2013 CARE-MS I vs. CARE-MS II: Trial Overviews
CARE-MS I CARE-MS II Stage . Phase III . Phase III # of Patients . 581 . 840 Patient . Treatment naïve RRMS . Treatment experienced RRMS Characteristics . EDSS score 0.0 – 3.0 . EDSS score 0.0 – 5.0 . ≥2 relapses in 24 months, with ≥1 relapse in 12 months . ≥2 relapses in 24 months, with ≥1 relapse in 12 months . Onset of symptoms within 5 years . Onset of symptoms within 10 years . ≥1 relapse on treatment with IFN B or GA for >6 months Experimental . 12 mg Lemtrada IV, QY . 12 mg Lemtrada IV, QY Arm(s)* – QD x 5 days at month 0 – QD x 5 days at month 0 – QD x 3 days at month 12 – QD x 3 days at month 12 Comparator . 44 mcg Rebif SC, TIW . 44 mcg Rebif SC, TIW Arm(s)* Primary . 6-month EDSS . 6-month EDSS Endpoint(s) . Relapse rate at 2 years . Relapse rate at 2 years
Secondary . Proportion of patients who are relapse free at year 2 . Proportion of patients who are relapse free at year 2 Endpoint(s) . Change from baseline in EDSS . Change from baseline in EDSS . Acquisition of disability as measured by change from . Acquisition of disability as measured by change from baseline in MSFC score baseline in MSFC score . Percent change from baseline in MRI T2 hyperintense . Percent change from baseline in MRI T2 hyperintense lesion volume at year 2 lesion volume at year 2
* 1000 mg methylprednisolone IV, QD x 3 days at months 0 and 12
Sources: Sanofi, www.clincaltrials.gov, Credit Suisse research and analysis Slide 144 September 2013 CARE-MS I vs. CARE-MS II: Trial Design Comparison
CARE-MS I ARM Month (N) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
1 12 mg IV Lemtrada (5 x QD in Month 0, 3 x QD in Month 12) + 1 g IV Methylprednisone (3 x QD, QY) RRMS (386) Patients (581) 2 44 μg Rebif (3 x QW) + 1 g IV Methylprednisone (3 x QD, QY) (195)
EDSS X X X X X X X X X MRI X X X
CARE-MS II ARM Month (N) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
1 12 mg IV Lemtrada (5 x QD in Month 0, 3 x QD in Month 12) + 1 g IV Methylprednisone (3 x QD, QY) RRMS (436) Patients (667) 2 44 μg Rebif (3 x QW) + 1 g IV Methylprednisone (3 x QD, QY) (231)
EDSS X X X X X X X X X MRI X X X CARE-MS II originally included a 24 mg Lemtrada arm. Sanofi decided to stop enrollment into this arm at the start of the trial.
Sources: Sanofi, www.clincaltrials.gov, Credit Suisse research and analysis Slide 145 September 2013 AbbVie / Biogen Idec Daclizumab Daclizumab Overview
. Approved (but not marketed for commercial reasons) for transplant rejection as Zenapax Developing 50/50 collaboration with AbbVie (via Facet Biotech) . Humanized anti-CD25 (IL2R-alpha) mAb – T Cell targeting – Subcutaneous injection, once every 4 weeks . Produced positive results from adding daclizumab to interferon beta as shown in the Phase II CHOICE study . Developing in collaboration with AbbVie. Reported positive topline efficacy data from SELECT Phase II/III trial (vs. placebo, 1 year study) – 54% (150mg) and 50%(300mg) relative decrease in relapse rates – Reduction in number of new or newly enlarging T2 hyperintense lesions at 1 year (70% for 150mg, 79% for 300mg) – Statistically significant reduction in cumulative number of new lesions between 8-24 weeks (69% for 150mg, 78% for 300mg) – Some infectious disease concerns (serious 2% vs. 0%, plac/dac) and LFT 5x UNL 4% vs. 1% . Currently being studied in DECIDE Phase III trial for RRMS (enrollment started May 2010, with final readout expected in 2014. Requested SPA from FDA)
Sources: Biogen Idec, AbbVie, Credit Suisse research and analysis Slide 147 September 2013 SELECT Phase II Trial Data
150 mg Daclizumab 300 mg Daclizumab Placebo Number of Patients 201 203 196 Clinical Outcomes Reduction in ARR vs Pbo 54% (p<0.0001) 50% (p=0.0002) - - - - - Proporiton Relapse-Free 81% 80% 64% Decrease in Proportion Relapse-Free 55% (p<0.0001) 51% (p=0.0003) - - - - - Improvement in MSIS-29 Score 4.1 points (p=0.0007) 1.6 point (p=0.12) - - - - - Reduction in EDSS Progression 57% (p=0.021) 43% (p=0.091) - - - - - MRI Outcomes Reduction in Gd+ Lesions 79% (p<0.0001) 86% (p<0.0001) - - - - - Reduction in T2 Lesions 70% (p<0.0001) 79% (p<0.0001) - - - - - Safety Data Adverse Events 72% 76% 78% Serious Adverse Events 16% 18% 27% Infections 49% 53% 43% Serious Infections 3% 1% 0% Other . Most common adverse event was transminitis, with liver enzyme levels greater than 5 times the upper limit of normal in 4% of patients treated with daclizumab . No opportunistic infections were reported . 1 patient died due to complications with psoas abscess
Sources: Biogen Idec, AbbVie, Credit Suisse research and analysis Slide 148 September 2013 SELECT Phase II Trial Design
ARM Week (N) 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72
1 150 mg Daclizumab SC Q4W Washout or Extension (196)
RMS 2 Patients 300 mg Daclizumab SC Q4W Washout or Extension (201) (N=600)
3 Placebo Washout or Extension (203)
MRI X X X X X X X X X
Duration . 48 weeks Indication . RRMS . Experienced ≥1 relapse in 12 months prior to randomization with brain MRI consistent with MS or Gd+ lesion activity on brain MRI within 6 weeks prior to randomization Primary . Annualized relapse rate Endpoint(s) Secondary . New Gd+ lesions from weeks 8 to 24 Endpoint(s) . New T2 lesions at week 52 . Proportion of relapsing patients . Improvement in quality of life (Change in MSIS-29 physical score) . EDSS progression at week 52 Readout . Full data set was presented at ECTRIMS 2011
Sources: Biogen Idec, AbbVie, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 149 September 2013 DECIDE Phase III Trial Design
ARM Week (N) 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 - 104
1 150 Daclizumab SC Q4W RRMS (900) Patients (1800) 2 30 mg Avonex IM (900)
Purpose . Evaluate efficacy and safety of daclizumab in RRMS . Determine superiority of daclizumab compared to interferon beta-1a Duration . 144 weeks Indication . RRMS Primary . Superiority of daclizumab compared to interferon beta-1a in preventing MS relapse Endpoint(s) Secondary . Superiority of daclizumab compared to interferon beta-1a in slowing functional decline and disability progression as well Endpoint(s) as maintaining quality of life Data . Potential data readout in 2014 Readout
Sources: Biogen Idec, AbbVie, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 150 September 2013 Roche / Biogen Idec Ocrelizumab Ocrelizumab Overview
. IV-administered, humanized anti-CD20 mAb targeting CD20+ B-cells . Roche/Genentech are lead developers, while Biogen Idec retains an economic interest . Phase III program is evaluating in RRMS (OPERA I and II) and PPMS (ORATORIO) . Initiated ORATORIO in Q1’11 and OPERA I/II in Q3’11 . Readouts from OPERA I/II will likely occur in 2015/2016 . Ocrelizumab demonstrated high efficacy and good safety in a Phase II trial – Reduced relapse rates at 24 weeks (vs pbo) by 80% for 600 mg arm (p=0.0005) and 73% for 2000 mg arm (p=0.0014) – Both doses showed superiority in reducing relapse rates (vs pbo) over Avonex (43% vs pbo) – Incidence of SAEs were similar across arms: 2% (600 mg), 5% (2000 mg), 4% (Avonex), 4% (pbo) – There was one death due to brain swelling in 2000 mg arm . However, safety remains a concern, as separate trials in rheumatoid arthritis and lupus erthymatosus (for 1000 mg dose) were terminated in 2010 due to side effects – DSMB review of the STAGE trial showed that numerous patients developed serious infections, of which some were fatal – Roche believes the lower dose, younger patient population, and absence of concomitant immunosuppressant use could result in a better safety/tolerability profile in patients with MS
Sources: Biogen Idec, Roche, Credit Suisse research and analysis Slide 152 September 2013 Ocrelizumab: Phase II Trial Design
ARM Week (N) 0 2 4 6 8 10 12 14 16 18 20 22 24 36 48 60 72 84 96
1 600 mg IV Ocrelizumab (300 mg Q3W per 24 Weeks) + MP Extension (55)
2 2000 mg IV Ocrelizumab (1000 mg Q3W per 24 Weeks) + MP Extension RRMS (55) Patients (N=218) 3 30 μg IM Avonex QW + MP Extension (54)
4 Placebo + MP Extension (54)
MRI X X X X X X X
MP: Methylprednisone
Duration . 96 weeks Patient . RRMS Population Primary . Total number of Gd+ T1 lesions (at weeks 12, 16, 20, 24) Endpoint(s) Secondary . Annualized relapse rate (at week 24) Endpoint(s) . Proportion of patients who remain relapse free (at week 24) . Change in total volume of T2 lesions from baseline (at week 24) Data . Data published in Lancet in November 2011 Readout
Sources: Biogen Idec, Roche, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 153 September 2013 Ocrelizumab: Phase II Trial Treatment Cycles
ARM Week (N) 0 2 4 6 8 10 12 14 16 18 20 22 24 36 48 60 72 84 96
1 600 mg IV Ocrelizumab (300 mg Q3W per 24 Weeks) + MP Extension (55)
2 2000 mg IV Ocrelizumab (1000 mg Q3W per 24 Weeks) + MP Extension RRMS (55) Patients (N=218) 3 30 μg IM Avonex QW + MP Extension (54)
4 Placebo + MP Extension (54)
MRI X X X X X X X
MP: Methylprednisone
First Cycle Second Cycle Third Cycle Fourth Cycle Arm 1 300 mg Ocrelizumab IV 600 mg Ocrelizumab IV 600 mg Ocrelizumab IV 600 mg Ocrelizumab IV at weeks 0 and 2 each at week 24 at week 48 at week 72 Arm 2 1000 mg Ocrelizumab IV 1000 mg Ocrelizumab IV 1000 mg Ocrelizumab IV 600 mg Ocrelizumab IV at weeks 0 and 2 each at week 24 at week 48 at week 72 Arm 3 300 μg Avonex 300 mg Ocrelizumab IV 300 mg Ocrelizumab IV 600 mg Ocrelizumab IV QW at weeks 24 and 26 each at weeks 48 and 50 each at week 72 Arm 4 Placebo IV 300 mg Ocrelizumab IV 300 mg Ocrelizumab IV 600 mg Ocrelizumab IV at weeks 0 and 2 each at weeks 24 and 26 each at weeks 48 and 50 each at week 72
Sources: Biogen Idec, Roche, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 154 September 2013 Ocrelizumab: Key Phase II Data
600 mg 2000 mg Avonex* Placebo* Ocrelizumab* Ocrelizumab* Number of Patients 55 55 54 54 Efficacy Data (Week 24) Reduction in Gd+ T1 Lesions vs Pbo 89% (p<0.0001) 89% (p<0.0001) N/A* (p=0.9) - - - - - Reduction in ARR vs Pbo 80% (p=0.0005) 73% (p=0.0014) 44% (p=0.07) - - - - - Proportion Relapse-Free 87% 82% 78% 76% Change in T2 Lesion Volume -841.4 mm3 (p=0.2) -578.1 mm3 (p=0.2) +996.7 mm3 (p=0.5) -114.0 mm3 Safety Data through Week 24 Adverse Events 62% 66% 56% 70% Serious Adverse Events 2% 6% 4% 4% Adverse Events Causing Withdrawals 4% 2% 2% 0% Infections 42% 33% 20% 41% Serious Infections 0% 0% 0% 2% Other . Most common adverse events were infusion-related . No opportunistic infections were reported . 1 patient died due to systemic inflammatory response syndrome in the 2000 mg dose cohort
Both doses showed activity in treating RRMS (vs placebo) with no major side effects
Sources: Biogen Idec, Roche, Kappos et al. Lancet 2011 www.clinicaltrials.gov, Credit Suisse research and analysis Slide 155 September 2013 Ocrelizumab: “ORCHESTRA” Phase III Program
OPERA I OPERA II ORATORIO Stage . Phase III . Phase III . Phase III Patients (N) . 800 . 800 . 630 Indication . RRMS . RRMS . PPMS Duration . 96 weeks . 96 weeks . 120 weeks Trial Arms . Ocrelizumab IV: 2 x 300 mg on day 1 . Ocrelizumab IV: 2 x 300 mg on day 1 . Ocrelizumab IV: 2 x 300 mg on day 1 and 15 of cycle 1 followed by 600 mg and 15 of cycle 1 followed by 600 mg and 15 of each cycle* on day 1 of each following cycle on day 1 of each following cycle . Placebo* . Rebif IM: Standard dosing . Rebif IM: Standard dosing Primary . ARR at 96 weeks . ARR at 96 wks . Time to sustained disability Endpoint(s) progression for ≥12 weeks Secondary . Time to sustained disability . Time to sustained disability . Time to sustained disability Endpoint(s) progression for ≥12 and ≥ 24 weeks progression for ≥12 and ≥ 24 weeks progression for ≥24 weeks . Proportion of relapse-free patients . Proportion of relapse-free patients . Change in timed 25-foot walk . Change in total T2 lesion volume . Change in total T2 lesion volume . Change in T2 lesion volume . Total number of new and/or enlarging . Total number of new and/or enlarging . Safety/Tolerability T2 hyperintense lesions T2 hyperintense lesions . Change in MSFCS score . Change in MSFCS score . Change in brain volume . Change in brain volume . AEs, PK, Immunogenicity . AEs, PK, Immunogenicity Upcoming . Data expected in 2014/2015 . Data expected in 2014/2015 . Data expected in 2017 Milestones * Background Methylprednisone
Sources: Biogen Idec, Roche, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 156 September 2013 “ORCHESTRA” Phase III Trial Design
OPERA I/ II ARM Week (N) 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96
1 600 mg IV Ocrelizumab RRMS (400) Patients (800) 2 Standard Dose IM Rebif (400)
Dosing: 2 x 300 mg IV Ocrelizumab on day 1 and 15 of cycle 1, followed by 600 mg on day of each cycle afterwards
ORATORIO ARM Week (N) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 100 104 108
1 600 mg IV Ocrelizumab + Methylprednisone PPMS (315) Patients (630) 2 Placebo + Methylprednisone (315)
Dosing: 2 x 300 mg IV Ocrelizumab on day 1 and 15 of each cycle
Sources: Biogen Idec, Roche, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 157 September 2013 Teva / Active Biotech Laquinimod Laquinimod Overview
. Orally administered linomide successor . Immunomodulator with potential neuroprotective properties . Being developed by Teva in collaboration with Active Biotech . CHMP opinion expected in Q3’13 . Being studied in a third Phase III trial (CONCERTO) in RRMS at two doses . Remains in “limbo” after failed BRAVO Phase III trial – Failed to show statistically significant reduction in relapse rates (vs pbo) – Failed to show numerical superiority in reducing relapse rates relative to active comparator Avonex . Originally evaluated in two Phase III trials, ALLEGRO and BRAVO
ALLEGRO BRAVO Reduction in Relapse Rate 23% (p=0.002) Laquinimod: 18.5% (p=0.075)*, 21.3% (p=0.026)** Avonex: 21.3% (p=0.026)*, 29% (p=SS)** Reduction in EDSS 36% (p=0.0122) 33.5% (p=0.044) Progression 28.7% (p=0.09) Avonex Reduction in T1 Lesions 27% (p=0.0039) N/A New/Enlarging T2 Lesions 5.03 laquinimod vs 7.14 pbo N/A Gd+ Lesions 1.33 laquinimod vs 2.12 pbo N/A Safety/Tolerability Elevated ALTs (5% laquinimod vs 2% pbo) N/A * Without corrections for baseline MRI characteristics; ** With corrections for baseline MRI characteristics
Sources: Active Biotech, Teva, www.clinicaltrials.gov, Credit Suisse research Slide 159 September 2013 Laquinimod: Comparison of Phase III Trial Designs
ALLEGRO BRAVO CONCERTO Patient . RRMS . RRMS . RRMS Population Duration . 24 months . 24 months . Up to 24 months
Dosing . 0.6 mg . 0.6 mg . 0.6mg, 1.2mg
Placebo . Yes . No . Yes
Comparator . None . Avonex . None
Primary . Number of relapses during treatment . Number of relapses during treatment . Time to confirmed EDSS progression Endpoint(s) phase phase Secondary . Time to confirmed EDSS progression . Time to confirmed EDSS progression . Annualized relapse rate Endpoint(s) . MRI outcomes at 12 and 24 weeks . MRI endpoints . Annualized relapse rate . Safety/tolerability . # of Gd+ lesions . # of new or enlarged T2 lesions at 12 and 24 months . Change in brain volume from baseline to 24 months . MSFC score
Sources: Active Biotech, Teva, www.clinicaltrials.gov, Credit Suisse research Slide 160 September 2013 Laquinimod: CONCERTO Phase III Trial Design
ARM Week (N) 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96
1 0.6mg Laquinimod QD (600)
RMS 2 Patients 2 x 0.6mg Laquinimod QD (600) (N=1800)
3 Placebo (600)
Duration . 96 weeks Patient . RRMS Population Primary . Time to EDSS progression Endpoint(s) Secondary . Percent change in brain volume Endpoint(s) . Annualized relapse rate . Safety/tolerability Data . Potential data readout in 2014/2015 Readout
Sources: Active Biotech, Teva, www.clinicaltrials.gov, Credit Suisse research Slide 161 September 2013 Laquinimod: BRAVO is more important due to the Avonex arm
Sources: Active Biotech, Teva, www.clinicaltrials.gov, Credit Suisse research Slide 162 September 2013 Laquinimod: Combo studies to start in 2013
. Teva plans to study Laquinimod + Copaxone and Laquinimod + Other Oral Drugs in 2013 . Combining Laquinimod’s neuroprotective properties with other oral drug’s anti-inflammatory properties could drive further use of Laquinimod . Few details have been disclosed to date
Sources: Active Biotech, Teva, www.clinicaltrials.gov, Credit Suisse research Slide 163 September 2013 Novartis Gilenya (Fingolimod) Gilenya Overview
. Examined in 2 Phase III trials: 0.6 P<0.001 0.5 P<0.001 P=0.16 – TRANSFORMS 0.4 0.33 . Over 1150 Patients randomized to receive either 0.3 0.20
low or high dose Gilenya, or Avonex 0.2 0.16 RelapseRate . Gilenya patients in both arms demonstrated 0.1 significantly lower relapse rates than Avonex Annualized Adjusted 0.0 – FREEDOMS Interferon Fingolimod, 0.5 mg Fingolimod, 1.25 (N = 431) (N = 429) mg (N = 420) . Over 1270 pts randomized to receive either low or high dose Gilenya or placebo 100 . Patients in both treatment arms had significantly 80 lower relapse rates than placebo 60
40 20
Patients FreePatientsfrom 0 Confirmed Relapse (%) Relapse (%)Confirmed 0 120 240 360 480 600 720 Fingolimod, 1.25Time mg to FirstFingolimod, Relapse (Days) 0.5 mg Placebo
No. at Risk
Fingolimod, 1.25 mg 429 383 356 333 313 299 239
Fingolimod, 0.5 mg 425 374 349 324 309 295 219
Placebo 418 346 293 242 223 198 145
Sources: Novartis, Credit Suisse research and analysis Slide 165 September 2013 Gilenya Safety Recommendations
. Monitoring for bradycardia 6 hrs after 1st dose . Eye exam less than 6 months before and 3-4 months after 1st treatment . Complete blood count less than 6 months before treatment . Liver function tests less than 6 months prior to treatment
Sources: Novartis, Credit Suisse research and analysis Slide 166 September 2013 Gilenya Launch Sensitivities
. Novartis sales force leverage: – Launched Extavia (generic form of Betaseron) in 2009 – <5% market share currently – Used to establish neurologist relationships which Novartis will then exploit for Gilenya launch . Aggressive Launch Strategy: – $48K annual wholesale price – Has agreed to pay as much as $800 in co-pay for treatment – Will also pay as much as $600/pt for monitoring costs
Sources: Novartis, Credit Suisse research and analysis Slide 167 September 2013 Gilenya Launch
Gilenya’s launch has been impressive so far, gaining 6.8% share of the U.S. market, and generating worldwide sales of nearly ~$500M in 2011
Sources: Novartis, Credit Suisse research and analysis Slide 168 September 2013 Biogen Idec / Elan Tysabri Tysabri Breakdown
. Co-marketed with Elan in US . Monoclonal antibody against the α4 subunit of the integrin receptor which facilitates migration and adhesion of inflammatory cells. . Originally launched in 2004, but then pulled from market in 2005 because of reported cases of progressive multifocal leukoencephalopathy (PML). . Re-launched in 2006 for patients who failed or are not tolerant of ABCR therapy . IV infusion every 4 weeks . To address safety, Biogen/Elan is developing a test to determine PML risk in Tysabri patients
Sources: Biogen Idec, Elan, Credit Suisse research and analysis What is PML?
. Progressive Multifocal Leukencephalopathy . Demyelinating disease caused by reactivation of JC virus . 50-92% of Americans have been infected with JC virus according to various clinical studies . Vast majority of infected patients are healthy since immune response keeps virus at bay and prevents reactivation (PML) . Disease usually seen in immunosuppressed individuals (i.e HIV, transplant recipients)
Sources: Biogen Idec, Elan, Credit Suisse research and analysis Slide 171 September 2013 JC Virus Assay
. Detects exposure to JC virus – Measures presence of anti-JCV antibodies in serum – Detecting viral DNA preferable method but not dependable because it is hard to isolate from serum – Viral DNA is easier to find in urine, but only 25% of PML patients shed virus this way . Three important read-throughs – Can the JCV test accurately detect JCV antibodies? (STRATIFY-1 full data) – What percentage of Tysabri patients are JCV antibody negative? (STRATIFY-1) – What’s the risk of PML in patients who are positive and negative for JCV antibody? (STRATIFY-2)
Sources: Biogen Idec, Elan, Credit Suisse research and analysis What do we know about the test?
. JCV-like particles called MAD-1 Protein are placed into a plate . Human serum that may or may-not contain JCV antibodies are added . An anti-human IgG antibody linked to a colored substrate is then added to the mixture . A is tested for absorbance at 450nm – data read as normalized optical density units (nOD) – nOD>0.25 – seropositive – nOD<0.10 – seronegative – 0.10
Sources: Biogen Idec, Elan, Credit Suisse research and analysis JCV Assay Cont’d
. Assay tested earlier in STRATA trial . 831pts . All patients gave serum AND urine samples . 2.5% of patients shedding virus in urine (N=204) had negative test . 54% seropositive rate – Prevalence plateaus in early-mid 20’s, then increases with age – Seropositive rate ranges from 33-91% in earlier and smaller trials . 2% seroconversion rate (becoming seropositive after originally testing seronegative)
Sources: Biogen Idec, Elan, Credit Suisse research and analysis Appendix Additional Background Slides How does BG-12 work?
. But also an activator of NrF2 Pathway . Believed to work via Th1-Th2 shift which is: . Th1: Thought to regulate cell-mediated – Cellular cytoprotective/Neuroprotective immunity – Anti-inflammatory . Th2: Stimulates cytokines that could promote Anti-oxidant MS recovery –
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 177 September 2013 What is BG-12?
. 2nd Generation fumarate . Contains: – 120 mg dimethylfumarate – 87 mg Ethylhydrogenfumarate Ca salt – 5 mg Ethylhydrogenfumarate Mg salt – 3 mg Ethylhydrogenfumarate Zn salt
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 178 September 2013 Treatments for RRMS
. First Line (ABCR) – Interferon β . Introduced in 1993 . Proven to decrease relapse rate and slow down progression of disease, but not sure how it works . All injected (subcutaneous or intramuscular) . Commonly causes injection site reactions, flu-like symptoms, and elevated liver enzymes . Three on Market Avonex – Manufactured by Biogen. Introduced in 1996. Given once/wk (IM). Betaseron – Manufactured by Bayer. First on market in 1993. Given once every 2 days (SQ). Rebif – Co-marketed by Pfizer and Merck Serono. Brought to U.S. in 2002. Given 3x/wk (SQ). – Copaxone . Random set of polymers that resemble myelin basic protein . May work by directing immune response away from brain and spinal cord . Marketed by Teva and Sanofi-Aventis . Approved in 1996 . Tysabri (Biogen/Elan) – Monoclonal antibody to alpha-subunit of integrin receptor – introduced in 2004 – Effective in MS, but only indicated for pts that have failed or are intolerant to ABCR therapy – IV, once a month – Use hindered by PML concerns
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Multiple Sclerosis
. Facts – Neurological disease in which the immune system attacks the protective coating of the brain and spinal cord – 350-400K pts treated for disease in U.S. – Most pts are women, diagnosed between 20-40 years of age – No known cure . Four subtypes – Relapsing-Remitting – Pts suffer clearly defined attacks followed by periods of partial or complete recovery. 85% of patients have this type upon diagnosis. Most treatable type. – Primary Progressive – No distinct relapses or remissions, but gradually worsening symptoms from beginning – Secondary Progressive – Patient originally has RRMS, but it then follows a more progressive course – Progressive RR – Clearly defined attacks and recovery on top of gradually worsening symptoms at baseline
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 180 September 2013 History of Fumarate in MS
. First evaluated in MS in 2005 study by Schrimrigk et. al
. 10 patients
. 18-55 years of age
. ≥1 relapse prior to enrollment
. EDSS Score of 2.0-6.0 . Treatment phases (70 weeks total)
. Weeks 0-18: Pts started at 30mg QD and titrated to a max of 240mg TID
. Weeks 19-22: Washout phase
. Weeks 23-70: Pts started at 30mg QD and titrated to a max of 120mg TID . Had significant reductions from baseline in the number (p<0.05) and size of Gd+ lesions (p<0.001)
. 5 patients (50%) experienced flushing . 1 discontinuation because of GI adverse event
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 181 September 2013 BG12 Phase II Results
. Prior phase IIb met efficacy endpoint which was number of MRI (GDE) lesions at weeks 12,16,18, and 24.
. Was not powered to detect differences in annualized relapse rate
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 182 September 2013 Flushing and Abdominal Pain most common AEs
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 183 September 2013 How do MRI Findings correlate with Clinical Status?
. T1-Weighted Lesion – Picked up on a basic MRI scan that differentiates fat from water. Fat appears brighter than water in these scans. – Used to pick up “black holes” – areas of permanent axonal damage. Likely due to the loss of fatty myelin surrounding the axons – Thought to be correlated with disability . T2-Weighted Lesion – Used to detect MRI lesions which are bright – “hyperintense” – Monitors “disease load” – May be correlated with inflammation/relapses . Gadolinium -Enhancing Lesion – Used to detect the breakdown in the blood-brain barrier – Good for spotting areas of acute inflammation – May be correlated with relapses
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 184 September 2013 What do relative relapse rates really tell us?
Placebo relapse rates have trended downward since 1996....
....As a result, neurologists focus less on relative RR reduction... But one also could argue that each % point RR decrease is harder to obtain on lower placebo annual relapse rate baselines
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 185 September 2013 EDSS progression – A better but still imperfect measure of efficacyMS drug monotherapy pivotal studies show that starting EDSS scores over time have remained stable around 2.4...... hence, there is an argument that EDSS data from ALLEGRO is more meaningful than relapse rates
Interesting thought: RR rates (and betterment over time) are not correlated with improving EDSS – subjective evidence that RR and EDSS have poor correlation?
.... However, we also note that measurement of EDSS disability progression between trials is modestly different (between a 0.5 an 1.0 point increase sustained for 3-6 months).
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 186 September 2013 BIIB017 Background
. Long-acting version of Avonex - PEGylated at N-terminus . Potential to be given SC every 2-4 weeks vs. a weekly IM injection (Avonex)
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 187 September 2013 BIIB017 Phase I
. Phase I trial demonstrated antiviral activity for longer period of time vs. Avonex . PEG arms also had higher neopterin (known marker of interferon activity) concentration for longer period of time . 125mcg dose had similar incidence of flu- like symptoms to Avonex . Started Phase III in May 2009 . Given fast-track status by FDA in July 2009
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 188 September 2013 ADVANCE Trial
. Global 2 year double blind, placebo controlled . 1,260 patients with RRMS . Primary endpoint – annualized relapse rate at 1 year . Enrolment goal is YE2010 – likely results in 2013 . Received special protocol assessment from FDA in Q2
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 189 September 2013 Our take on BIIB017
. Hurdle lower than other drugs since interferons have rich history . However, only Phase I data is available, so it’s hard to access efficacy and safety risk . If approved, we expect it to cannabalize Avonex sales and its added convenience should offset pressure from orals . However, by the time PEG-Avonex is approved, we expect a paradigm shift to orals so that it won’t completely offset lost Avonex revenues
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Kurtzke Expanded Disability Score (EDSS) – Do absolute changes actually mean anything? Score Description 0.0 Normal neurological examination 1.0 No disability, minimal signs in one functional system (FS) 1.5 No disability, minimal signs in more than one FS 2.0 Minimal disability in one FS 2.5 Mild disability in one FS or minimal disability in two FS 3.0 Moderate disability in one FS, or mild disability in three or four FS. Fully ambulatory . Average starting EDSS 3.5 Fully ambulatory but with moderate disability in one FS and more than minimal disability in several others in all pivotal MS studies 4.0 Fully ambulatory without aid, self-sufficient, up and about some 12 hours a day despite relatively severe disability; able was 2.48 (2.30-2.68). to walk without aid or rest some 500 meters 4.5 Fully ambulatory without aid, up and about much of the day, able to work a full day, may otherwise have some . The average placebo limitation of full activity or require minimal assistance; characterized by relatively severe disability; able to walk without increase (over 2 years) aid or rest some 300 meters. was 0.26 (0.13-0.48) 5.0 Ambulatory without aid or rest for about 200 meters; disability severe enough to impair full daily activities (work a full day without special provisions) . The average active drug 5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to preclude full daily activities increase was 0.17 with 6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without Copaxone and Gilenya resting being the only MS 6.5 Constant bilateral assistance (canes, crutches, braces) required to walk about 20 meters without resting treatments to improved 7.0 Unable to walk beyond approximately five meters even with aid, essentially restricted to wheelchair; wheels self in EDSS standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day . CS Observation: Do 7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry absolute changes in on in standard wheelchair a full day; May require motorized wheelchair 8.0 Essentially restricted to bed or chair or perambulated in wheelchair, but may be out of bed itself much of the day; EDSS over a 2 year retains many self-care functions; generally has effective use of arms period actually mean 8.5 Essentially restricted to bed much of day; has some effective use of arms retains some self care functions anything in he real 9.0 Confined to bed; can still communicate and eat. world clinical setting in 9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow the setting of low 10.0 Death due to MS starting EDSS scores? Functional status assessed across seven categories including: pyramidal functions, cerebellar functions, brainstem functions, sensory functions, bowel and bladder functions, visual/optic functions and cerebral/mental functions with up to 6 degrees of severity in each
Sources: Company reports, www.clinicaltrials.gov, Credit Suisse research and analysis Slide 191 September 2013 Disclosures
Companies Mentioned (Price as of 24-Sep-2013) Volatility Indicator [V] : A stock is defined as volatile if the stock price has moved up or down by 20% or more in a month in at least 8 of the past 24 AbbVie Inc. (ABBV.N, $45.98) months or the analyst expects significant volatility going forward. Achillion Pharmaceuticals Inc. (ACHN.OQ, $7.24) Actelion (ATLN.VX, SFr63.55) Active Biotech (ACTI.ST, Skr63.25) Analysts’ sector weightings are distinct from analysts’ stock ratings and are based on the analyst’s expectations for the fundamentals and/or valuation of Alexion Pharmaceuticals Inc. (ALXN.OQ, $113.59) the sector* relative to the group’s historic fundamentals and/or valuation: Algeta (ALGETA.OL, Nkr241.0) Amgen Inc. (AMGN.OQ, $114.78) Overweight : The analyst’s expectation for the sector’s fundamentals and/or valuation is favorable over the next 12 months. Arena Pharmaceuticals Inc (ARNA.OQ, $5.79) Ariad Pharmaceuticals, Inc. (ARIA.OQ, $19.81) Market Weight : The analyst’s expectation for the sector’s fundamentals and/or valuation is neutral over the next 12 months. Bayer (BAYGn.DE, €86.47) BioMarin Pharmaceutical, Inc. (BMRN.OQ, $73.63) Underweight : The analyst’s expectation for the sector’s fundamentals and/or valuation is cautious over the next 12 months. Biogen Idec (BIIB.OQ, $243.54) Celgene Corp. (CELG.OQ, $146.44) *An analyst’s coverage sector consists of all companies covered by the analyst within the relevant sector. An analyst may cover multiple sectors. Clovis Oncology, Inc. (CLVS.OQ, $73.52) Corcept Therapeutics (CORT.OQ, $1.68) Credit Suisse's distribution of stock ratings (and banking clients) is: Cubist Pharmaceuticals (CBST.OQ, $64.34) Dendreon Corp. (DNDN.OQ, $2.98) Durata Therapeutics (DRTX.OQ, $9.02) Global Ratings Distribution Elan Corp (ELN.I, €11.52) Enanta Pharmaceuticals (ENTA.OQ, $22.95) Rating Versus universe (%) Of which banking clients (%) Endocyte, Inc. (ECYT.OQ, $14.02) Esperion Therapeutics (ESPR.OQ, $18.16) Outperform/Buy* 42% (55% banking clients) Exelixis (EXEL.OQ, $5.6) Neutral/Hold* 40% (49% banking clients) Gilead Sciences Inc. (GILD.OQ, $62.74) Underperform/Sell* 15% (40% banking clients) Idenix Pharmaceuticals Inc. (IDIX.OQ, $5.53) ImmunoGen, Inc. (IMGN.OQ, $16.68) Restricted 3% Infinity Pharmaceuticals, Inc. (INFI.OQ, $18.35) *For purposes of the NYSE and NASD ratings distribution disclosure requirements, our stock ratings of Outperform, Neutral, and Underperform most closely correspond InterMune, Inc. (ITMN.OQ, $14.8) to Buy, Hold, and Sell, respectively; however, the meanings are not the same, as our stock ratings are determined on a relative basis. (Please refer to definitions above.) Ironwood Pharmaceuticals, Inc. (IRWD.OQ, $11.88) An investor's decision to buy or sell a security should be based on investment objectives, current holdings, and other individual factors. Medivation (MDVN.OQ, $57.47) Medivir SE (MVIRb.ST, Skr96.25) Merck & Co., Inc. (MRK.N, $47.53) Credit Suisse’s policy is to update research reports as it deems appropriate, based on developments with the subject company, the sector or the market Novartis (NOVN.VX, SFr69.7) that may have a material impact on the research views or opinions stated herein. Orexigen Therapeutics Inc. (OREX.OQ, $6.51) PDL Biopharma (PDLI.OQ, $8.02) Credit Suisse's policy is only to publish investment research that is impartial, independent, clear, fair and not misleading. For more detail please refer to PTC Therapeutics, Inc (PTCT.OQ, $21.39) Credit Suisse's Policies for Managing Conflicts of Interest in connection with Investment Research: http://www.csfb.com/research and Pfizer (PFE.N, $28.71) Pharmacyclics, Inc. (PCYC.OQ, $120.88) analytics/disclaimer/managing_conflicts_disclaimer.html Portola Pharmaceuticals, Inc. (PTLA.OQ, $24.27) Receptos (RCPT.OQ, $22.61) Credit Suisse does not provide any tax advice. Any statement herein regarding any US federal tax is not intended or written to be used, and cannot be Regeneron Pharmaceutical (REGN.OQ, $295.11) used, by any taxpayer for the purposes of avoiding any penalties. Roche (ROG.VX, SFr239.6) Sanofi (SASY.PA, €74.87) Please refer to the firm's disclosure website at https://rave.credit-suisse.com/disclosures for the definitions of abbreviations typically used in the target Seattle Genetics (SGEN.OQ, $43.52) Spectrum Pharmaceuticals (SPPI.OQ, $8.22) price method and risk sections. Sucampo Pharmaceuticals (SCMP.OQ, $6.19) Sunesis Pharmaceuticals (SNSS.OQ, $4.61) See the Companies Mentioned section for full company names Synergy Pharmaceuticals (SGYP.OQ, $4.8) Teva Pharmaceutical Ind. (TEVA.N, $38.72) The subject company (ACHN.OQ, AMGN.OQ, BIIB.OQ, CELG.OQ, CLVS.OQ, CORT.OQ, ITMN.OQ, MDVN.OQ, DNDN.OQ, DRTX.OQ, EXEL.OQ, The Medicines Company (MDCO.OQ, $32.02) IMGN.OQ, OREX.OQ, REGN.OQ, SGEN.OQ, VICL.OQ, VVUS.OQ, XNPT.OQ, XOMA.OQ, PTCT.OQ, BMRN.OQ, ENTA.OQ, RCPT.OQ, PTLA.OQ, United Therapeutics Corp (UTHR.OQ, $77.16) VIVUS, Inc. (VVUS.OQ, $9.55) SGYP.OQ, ESPR.OQ, BAYGn.DE, ELN.I, MRK.N, PFE.N, NOVN.VX, ROG.VX) currently is, or was during the 12-month period preceding the date of Vertex Pharmaceuticals Inc. (VRTX.OQ, $74.53) distribution of this report, a client of Credit Suisse. Vical Inc. (VICL.OQ, $1.27) XOMA Corporation (XOMA.OQ, $4.5) Credit Suisse provided investment banking services to the subject company (AMGN.OQ, BIIB.OQ, CELG.OQ, CLVS.OQ, CORT.OQ, DRTX.OQ, XenoPort (XNPT.OQ, $5.63) EXEL.OQ, OREX.OQ, XNPT.OQ, XOMA.OQ, PTCT.OQ, ENTA.OQ, RCPT.OQ, PTLA.OQ, SGYP.OQ, ESPR.OQ, MRK.N, PFE.N, NOVN.VX) within
the past 12 months. Disclosure Appendix Credit Suisse provided non-investment banking services to the subject company (ROG.VX) within the past 12 months Credit Suisse has managed or co-managed a public offering of securities for the subject company (CLVS.OQ, DRTX.OQ, OREX.OQ, XOMA.OQ, Important Global Disclosures PTCT.OQ, ENTA.OQ, RCPT.OQ, PTLA.OQ, SGYP.OQ, ESPR.OQ, MRK.N, PFE.N) within the past 12 months. Ravi Mehrotra PhD, Jason Kantor, PhD and Lee Kalowski each certify, with respect to the companies or securities that the individual analyzes, that (1) Credit Suisse has received investment banking related compensation from the subject company (AMGN.OQ, BIIB.OQ, CELG.OQ, CLVS.OQ, the views expressed in this report accurately reflect his or her personal views about all of the subject companies and securities and (2) no part of his or CORT.OQ, DRTX.OQ, EXEL.OQ, OREX.OQ, XNPT.OQ, XOMA.OQ, PTCT.OQ, ENTA.OQ, RCPT.OQ, PTLA.OQ, SGYP.OQ, ESPR.OQ, MRK.N, her compensation was, is or will be directly or indirectly related to the specific recommendations or views expressed in this report. PFE.N, NOVN.VX) within the past 12 months The analyst(s) responsible for preparing this research report received Compensation that is based upon various factors including Credit Suisse's total Credit Suisse expects to receive or intends to seek investment banking related compensation from the subject company (ACHN.OQ, AMGN.OQ, revenues, a portion of which are generated by Credit Suisse's investment banking activities BIIB.OQ, CELG.OQ, CLVS.OQ, CORT.OQ, GILD.OQ, IDIX.OQ, ITMN.OQ, MDVN.OQ, DNDN.OQ, DRTX.OQ, EXEL.OQ, IMGN.OQ, OREX.OQ, As of December 10, 2012 Analysts’ stock rating are defined as follows: PDLI.OQ, REGN.OQ, SGEN.OQ, VICL.OQ, VVUS.OQ, XNPT.OQ, XOMA.OQ, PTCT.OQ, BMRN.OQ, ALXN.OQ, ARIA.OQ, MDCO.OQ, CBST.OQ, ENTA.OQ, RCPT.OQ, PTLA.OQ, SGYP.OQ, IRWD.OQ, ESPR.OQ, BAYGn.DE, ELN.I, MRK.N, PFE.N, NOVN.VX, ABBV.N) within the next 3 months. Outperform (O) : The stock’s total return is expected to outperform the relevant benchmark*over the next 12 months. Credit Suisse has received compensation for products and services other than investment banking services from the subject company (ROG.VX) within Neutral (N) : The stock’s total return is expected to be in line with the relevant benchmark* over the next 12 months. the past 12 months Underperform (U) : The stock’s total return is expected to underperform the relevant benchmark* over the next 12 months. As of the date of this report, Credit Suisse makes a market in the following subject companies (ACHN.OQ, AMGN.OQ, ARNA.OQ, BIIB.OQ, CELG.OQ, *Relevant benchmark by region: As of 10th December 2012, Japanese ratings are based on a stock’s total return relative to the analyst's coverage universe which CLVS.OQ, CORT.OQ, GILD.OQ, IDIX.OQ, ITMN.OQ, MDVN.OQ, UTHR.OQ, VRTX.OQ, DNDN.OQ, DRTX.OQ, EXEL.OQ, IMGN.OQ, OREX.OQ, consists of all companies covered by the analyst within the relevant sector, with Outperforms representing the most attractive, Neutrals the less attractive, and PDLI.OQ, REGN.OQ, SGEN.OQ, VICL.OQ, VVUS.OQ, XNPT.OQ, XOMA.OQ, BMRN.OQ, ALXN.OQ, ARIA.OQ, MDCO.OQ, CBST.OQ, ENTA.OQ, Underperforms the least attractive investment opportunities. As of 2nd October 2012, U.S. and Canadian as well as European ra tings are based on a stock’s total return relative to the analyst's coverage universe which consists of all companies covered by the analyst within the relevant sector, with Outperforms representing the most RCPT.OQ, PTLA.OQ, SGYP.OQ, SCMP.OQ, IRWD.OQ, ESPR.OQ, MRK.N, PFE.N, ABBV.N). attractive, Neutrals the less attractive, and Underperforms the least attractive investment opportunities. For Latin American and non-Japan Asia stocks, ratings are As of the end of the preceding month, Credit Suisse beneficially own 1% or more of a class of common equity securities of (ATLN.VX, PTCT.OQ, based on a stock’s total return relative to the average total return of the relevant country or regional benchmark; Australia, New Zealand are, and prior to 2nd October NOVN.VX). 2012 U.S. and Canadian ratings were based on (1) a stock’s absolute total return potential to its current share price and (2) the relative attractiveness of a stock’s total return potential within an analyst’s coverage universe. For Australian and New Zealand stocks, 12-month rolling yield is incorporated in the absolute total return Credit Suisse has a material conflict of interest with the subject company (ACHN.OQ) . A Credit Suisse analyst involved in the preparation of this report calculation and a 15% and a 7.5% threshold replace the 10-15% level in the Outperform and Underperform stock rating definitions, respectively. The 15% and 7.5% has a long position in the common stock of ACHN thresholds replace the +10-15% and -10-15% levels in the Neutral stock rating definition, respectively. Prior to 10th December 2012, Japanese ratings were based on a stock’s total return relative to the average total return of the relevant country or regional benchmark. Credit Suisse has a material conflict of interest with the subject company (CLVS.OQ) . Clovis Oncology is a development-stage biotechnology company Restricted (R) : In certain circumstances, Credit Suisse policy and/or applicable law and regulations preclude certain types of focused on developing drugs and associated diagnostics for treatment of various cancers. communications, including an investment recommendation, during the course of Credit Suisse's engagement in an investment Credit Suisse has a material conflict of interest with the subject company (GILD.OQ) . A Credit Suisse analyst involved in the banking transaction and in certain other circumstances. preparation of this report has a long position in the common stock of GILD.
Slide 192 September 2013 Disclosures (continued)
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