Cowen & Co. Annual Health Care Conference 2017
Camurus Advancing late stage pipeline with high market potential
Company Presentation, 7 March 2017 Forward-looking statements
This presentation contains forward-looking statements that provide our expectations or forecasts of future events such as new product developments and regulatory approvals and financial performance. Camurus is providing the following cautionary statement. Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions. This may cause actual results to differ materially from expectations and it may cause any or all of our forward-looking statements here or in other publications to be wrong. Factors that may affect future results include currency exchange rate fluctuations, delay or failure of development projects, loss or expiry of patents, production problems, unexpected contract, patent, breaches or terminations, government-mandated or market-driven price decreases, introduction of competing products, Camurus‘ ability to successfully market products, exposure to product liability claims and other lawsuits, changes in reimbursement rules and governmental laws and interpretation thereof, and unexpected cost increases. Camurus undertakes no obligation to update forward-looking statements
2 Camurus overview LISTED ON NASDAQ STOCKHOLM • Innovation that delivers 3rd DEC, 2015 − Proprietary FluidCrystal® technology used in 10 clinical programs
− Preclinical to NDA/MAA enabling MARKET CAP pipeline programs − Expansive and rewarding pharma partnerships ~450 million USD − Emerging European commercial organization
• Superior products for unmet markets
− Long-acting medications for better treatment CASH POSITION outcomes and quality of life for patients − Initial focus on opioid dependence and chronic 55 million USD pain END 2016 • Lean and experienced team − 64 employees with 45 in R&D − Headquarter in Lund, Sweden
3 Late-stage, diversified pipeline
PARTNERS PRODUCT PRECLINICAL PHASE 1/2 PHASE 3 REGISTRATION
CAM2038 Weekly Opioid dependence
CAM2038 Monthly Opioid dependence
CAM2038 Weekly Chronic pain
CAM2038 Monthly Chronic pain
CAM2029 Neuroendocrine tumours
CAM2029 Acromegaly
CAM2032 Prostate cancer
CAM4071 Not disclosed
CAM2047 CINV*
CAM2048 Pain
CAM2058 Pain, nausea and vomiting
*CINV Chemotherapy nausea and vomiting
4 Strong collaborations with strategic partners
CAM2038, CAM2048, CAM2058 CAM2029, CAM4071 + other products CAM4072
Acromegaly, neuroendocrine Opioid dependence and pain Genetic obesity
Field tumours and other indications
• Exclusive license agreement for • Exclusive, worldwide, collaboration • Exclusive license to FluidCrystal® North America, with option to China, and license agreement Injection depot for setmelanotide Scope Japan, Korea, and Taiwan • USD 20 million in upfront license fee • USD 50 million received in upfront, • USD 65 million in potential received option exercise and development development • + USD 130 million in total potential milestones and sales milestones development and sales milestones • USD 700 million in total potential • Mid to mid-high single digit % • Mid double digit % royalties on sales development and sales milestones royalties on sales
Financials • Mid to high single digit % royalties on “New Hope in The Search for Treatment for sales Obesity”, WSJ, August 26, 2016”
5 R&D highlights from 2016
PRODUCT EVENT TIME
CAM2038 Opioid dependence • Positive results from pivotal Phase 3 efficacy trial November
• Positive results from Phase 2 opioid challenge trial May
• Completed enrollment in Phase 3 long-term safety trial April
CAM2038 Chronic pain • First patient enrolled in Phase 3 efficacy trial September
• Completed enrollment in pivotal Phase 2 chronic pain trial April
CAM2029 Acromegaly & NET* • Positive results from Phase 2 trial in acromegaly and NET July
CAM2032 Prostate cancer • Positive results from Phase 2 trial in prostate cancer June
CAM4071 Not disclosed indication • Phase 1 clinical trial completed June
CAM2047 CINV** • Phase 1 trial started October CAM2048 Pain CAM2058 Pain & nausea and vomiting
*NET: Neuroendocrine tumours **CINV: Chemotherapy induced nausea and vomiting
6 FluidCrystal® technology Leader in lipid science and formulation technologies FluidCrystal® injection depot
The FluidCrystal® technology is based on +400 functional liquid crystal nanostructures PATENTS & APPLICATIONS
lipid 1 17 L2 CLINICAL FluidCrystal® topical bioadhesive TRIALS WITH FC TECHNOLOGY I2
H 1 2 COMMERCIAL PRODUCT
La water lipid 2 FluidCrystal® nanoparticles
8 FluidCrystal® injection depot for easy and convenient dosing
~1500 SUBJECTS HAVE RECEIVED >10,000 INJECTIONS IN CLINICAL TRIALS Easy and convenient administration of long-acting injectables
Good safety and local tolerability
Applicable across drug substance classes
Manufacturing by standard processes
9 Clinical performance of FluidCrystal® injection depot
Weekly or monthly FluidCrystal® depot provides buprenorphine exposure within the range of current sublingual products for daily dosing – single dose and steady-state
100
10
1 Plasma concentration BPN (ng/mL)
0 0 7 14 21 28 Time (days)
FluidCrystal® weekly depot (exemplified with buprenorphine clinical data) FluidCrystal® monthly depot (single dose, exemplified with buprenorphine clinical data) FluidCrystal® monthly depot (at steady state, simulated data) Comparator once daily product (exemplified with daily sublingual buprenorphine)
10 CAM2038: Weekly and Monthly Buprenorphine Injection Depots for Opioid Use Disorder Treatment Opioid dependence is a growing global health problem EACH DAY
30,1 28,6 4 91 1 US overdose epidemic • Estimated 32 million opioid users globally 24,5 Thousands AMERICAN’S DIE 21,3 21,9 1 19,7 FROM OPIOID ‒ Largest society burden of all drugs 18,9 17,8 16,8 OVERDOSES ‒ About 4 million diagnosed patients in Europe and 15,8 12,9 11,7 the US 10,6 9,5 2,3 7,3 ‒ Less than half in treatment (Europe and US ) 6,0 6,2
• Escalating opioid crisis
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 ‒ 207,400 drug related deaths worldwide 1999 • 30,000 US opioid overdose deaths in 2015 5 1000 • Growing concerns in Europe Opioid deaths in Sweden 900 Annual deaths with illicit drugs or opioid pharmaceutics 800 present during forensic examination 700 • A chronic relapsing disease 600 500 400 ‒ Opioid-use trajectories show that the disease is chronic 300 with less than 30% abstinence achieved over time 200 100 ‒ Opioid dependence mortality continues to increase 0 over time6 Heroin Non-heroin opioids Other drugs
Source: 1. UNODC, World Drug Report 2015; 2. SAHMSA, National Survey on Drug Use and Health (NSDUH) – 2014; 3. EMCDD, European Drug Report Trends and Developments 2015; 4. Center for Disease Control & Prevention 2016; 5. Toxreg 2016; 6. Hser et al. Harvard Review Psychiatry 2015; 23: 76-89
12 Medication assisted treatment considered best practice treatment for opioid use disorder
Large evidence-base for efficacy Important unmet medical needs
• Standard of care with daily buprenorphine or • Limited adherence to treatment methadone medications ‒ Poor treatment retention with continued illicit opioid use / “use on top” • Demonstrated effective in treating opioid ‒ Extensive misuse and diversion dependence • Safety issues ‒ Suppresses withdrawal and reduces cravings ‒ Overdoses ‒ Decreases illicit drug use ‒ Cardiac events (methadone) ‒ Reduces risky behavior, spreading of blood-borne disease and mortality • Need for daily, frequently supervised, dosing • On the World Health Organization’s Essential ‒ Inconvenient, stigma, and reduced quality of life Medicines List ‒ Burdens to the healthcare and criminal justice systems
No significant innovation in opioid use disorder treatment for the past 20 years
13 CAM2038 – a paradigm shift in opioid dependence treatment
Buprenorphine FluidCrystal® injection depot CAM2038 key attributes
• Small volume, subcutaneous, liquid injection • Encapsulating gel phase formed immediately Long-acting release and continuous after injection treatment effect
Long-acting buprenorphine Rapid and sustained suppression of • Multiple doses of both weekly and monthly formulations withdrawal and blockade of opioid effects allow flexible, individualized treatment Safeguards against diversion, misuse and • Provided ready for use in a prefilled syringe accidental pediatric exposure • Room temperature storage
Reduced number of doses/decisions Extensive clinical documentation from 365 to 12 times per year • From 7 clinical trials (phase 1, phase 2, phase 3) • Pharmacokinetics, pharmacodynamics, efficacy, and No daily supervised dosing and related safety (4 studies including active controls) stigma
On track for NDA and MAA submissions mid-2017 Improved treatment adherence – dose given is dose taken • FastTrack designation by FDA
14 Flexible and individualized opioid dependence treatment – across treatment stages
Weekly and monthly CAM2038 are administered as small dose volume subcutaneous (SC) injections by a prefilled syringe with a thin 23G needle
Monthly Weekly Initiation Weekly Maintenance or Weekly CAM2038 CAM2038 Stabilization - induction CAM2038 treatment
15 Extensive clinical program for CAM2038 in opioid dependence 7 Trial no. No. subjects Key results / Study design Status CLINICAL TRIALS Extended release of BPN suited for once COMPLETED 60 healthy volunteers weekly dosing. Dose proportional exposure. 6-8 HS-11-426 Phase 1 AND UNDER under naltrexone block times higher bioavailability versus SL BPN COMPLETION tablets.
Good safety Extended release suited for weekly respective 87 healthy volunteers monthly dosing. 6-8 times higher bioavailability. HS-13-487 Phase 1 and local under naltrexone block tolerability for Acceptability of CAM2038 dosing higher than CAM2038, SL tablets. +900 weekly and Dose proportional extended release further STUDY monthly supported by pharmacodynamics results for HS-07-307 Phase 2 41 patients PARTICIPANTS formulations withdrawal symptoms over time and time to DOSED WITH rescue medication. CAM2038 OR PLACEBO Randomized, placebo controlled opioid HS-14-478 Phase 2 47 patients challenge study of CAM2038 in opioid dependent patients (US).
HS-14-549 Phase 2 Repeat dose pharmacokinetic study of CAM2038 in opioid dependent pain patients (US), Positive results including injections in different subcutaneous injection sites.
Double blind, double dummy Phase 3 efficacy trial of CAM2038 versus sublingual HS-11-421 Phase 3 Positive results buprenorphine (US). N=428 Open label Phase 3 long-term safety trial in patients with opioid dependence (EU, US, HS-14-499 Phase 3 Under completion AUS). N=228
16 CAM2038 provides rapid and sustained opioid blockade Pivotal Phase 2 study
“At this moment, my liking for this drug is”
Qualification (Days 1-3) (Days 4-6) (Days 1-3) (Days 4-6) Strong Liking 100
90 CAM2038 q1w 24 mg CAM2038 q1w 32 mg 80 Weekly CAM2038 Weekly CAM2038 Injection 1 Injection 2 70
60 11 pt. difference Prespecified complete blocking Peak Score (mm) Score Peak Neutral 50 criteria
40
Strong Disliking 0 0 6 18 0 6 18 0 6 18 0 6 18 0 6 18 Hydromorphone (mg, IM)
Presentation, S27, ISAM & CSAM-SMCA 2016 Montreal, Canada Oct 20-22, 2016, Sharon L Walsh, Sandra Comer, Michelle Lofwall, Bradley Vince, Debra Kersh, Marion A Coe, Jermaine D Jones, Fredrik Tiberg, Behshad Sheldon, Sonnie Kim. http://www.csam-smca.org/resources-and-documents/past-annual-meeting-presentations/2016-abstracts/
17 CAM2038 also provides complete suppression of withdrawal
Effective suppression of clinical opiate withdrawal scale (COWS) scores from treatment initiation
44 CAM2038 24 mg COWS Withdrawal CAM2038 32 mg Score 12 Weekly CAM2038 Weekly CAM2038 – <5 Injection 1 Injection 2 Mild 5-12 9 Moderate 13-24 Moderate to 25-36 Severe 6
Severe >36 Total COWS Score COWS Total 3
0 BL 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Treatment Days
18 Phase 3 efficacy study of weekly and monthly CAM2038
Study design Key Primary and Secondary Outcomes
• 24-week, double-blind, double-dummy, • Primary Endpoint randomized, active-controlled Phase 3 study ‒ EMA: Negative Urines with NI margin of -11% ‒ Treatment-seeking patients with moderate to severe ‒ FDA: Response Rate* with NI margin of -10% opioid use disorder, not currently on medication assisted treatment (MAT) • Key Secondary Endpoint: ‒ Assessed from treatment initiation to maintenance ‒ EMA: Cumulative Distribution Function (CDF) ‒ Non-inferiority and superiority objectives of urines negative for illicit opioids from Week 5 to 25. (Sampling Weeks) ‒ CAM2038 vs. sublingual buprenorphine/naloxone BPN/NX – “Standard of Care” ‒ FDA: CDF of negative urines plus self-reports negative for illicit opioids from Week 5 to 25 (Sampling Weeks). ‒ Multiple additional secondary and explorative endpoints: retention; craving, morning cravings, withdrawal (SOWS and COWS)
* Responder defined as displaying negative urine samples, including self-reports, for; treatment week 12 and month 6, at least 2 of treatment weeks 9, 10 and 11 and 12, and at least 5 of the 6 samples obtained during treatment weeks 12 through 24.
19 CAM2038 met both FDA and EMA primary endpoints of non-inferiority versus SL BPN/NX – “Standard of Care” (ITT)
Non-Inferiority CAM2038 vs SL BPN/NX 95%CI Non-inferiority (NI) p-value NI margin EMA: 11% Primary Efficacy Endpoint (-0.1%, 13.3%) <0.001 - Mean % Urine Samples Negative for Illicit Opioids
NI margin 10% FDA: Primary Efficacy Endpoint (-3.5%, 10.4%) <0.001 - Response Rate
-0,2 -0,1 0 0,1 0,2
Favors SL BPN/NX Favors CAM2038 Difference (95% CI)
20 Statistical superiority met for CAM2038 versus SL/BPN/NX for secondary endpoint of CDF for negative urines +/- self-reports throughout the study (ITT)
Grace Period Treatment Sampling Superiority Superiority Weeks Weeks Weeks p-value (FDA) p-value (EMA)
0 1-24 2-25 0.006 0.011 1 2-24 3-25 0.005 0.010 3a 4-24 5-25 0.004 0.008 4b 5-24 6-25 0.001 0.003 6c 7-24 8-25 0.001 0.002
a Secondary endpoint for FDA and EMA; b Primary endpoint in RB-US-13-0001; c Including 2-week open label phase in RB-US-13-0001. CDF – cumulative distribution function
21 CAM2038 demonstrated non-inferior and superior efficacy across treatment phases versus daily SL BPN/NX
Robust efficacy versus “Standard of Care”
• Met both FDA and EMA primary endpoints • Statistical superiority for the key secondary endpoint of CDF for negative urines • Efficacy throughout treatment phases ‒ From initiation to maintenance • CAM2038 safety profile comparable to daily sublingual buprenorphine/naloxone ‒ Fewer SAEs (3.2% vs. 6%) ‒ No drug overdoses vs 4 overdoses ‒ Good local tolerability; no severe AEs • MAA and NDA submissions mid-2017
MAA – Market Authorisation Application
22 Global strategy for CAM2038 with build-up of own European commercial organization for opioid use disorder
Rationale Estimated 32 million opioid users globally
Specialist market in EU ~700 000 patients in treatment
CAM2038 addresses high unmet 1.3m need opioid problem users 2.5m 1.3m Sizeable socio-economic diagnosed opioid registered heroin users benefits dependent
On-going paradigm shift
Accessible and concentrated 187k market opioid dependent
Cost efficient roll-out and creation of significant value Braeburn markets Camurus markets Braeburn option right
Transformative new treatment can support pricing strategy and reimbursement on European markets
23 Significant interest in CAM2038 among European physicians
Country Physicians willingness to prescribe CAM20381 % patients*: q4w q1w
31% N=51 86% 30% 700k PATIENTS IN 36% TREATMENT IN N=50 94% EUROPE 25%
43% N= 48 N=50 86% 27%
39% N=50 96% 22% N= 47
Large markets with high willingness to prescribe weekly and monthly depots
Source. 1. Market access dynamics in opioid addiction, Decision Resources 2015 * % patients prescribers thought would be prescribed CAM2038 of those currently prescribed medication
24 Building the commercial organization in Europe
2016 2017 2018 • EU commercial leadership • Regional leadership teams • Regional leadership teams team in place early reimbursed markets 2nd wave markets • GMs in early reimbursed • GMs 2nd wave markets • Full key account teams for markets CAM2038 launch • Pricing, market access, medical affairs
Internationally experienced leadership team Pre-launch activities
Specialist pharma leadership HEOR, pricing and market access Market access Strategic marketing Medical affairs Medical affairs Global strategy Policy and education Opioid use disorder & pain Country operating models Stepwise build – right time, right place principles
25 CAM2029: Next generation subcutaneous octreotide depot for treatment of NET and acromegaly CAM2029 for treatment of acromegaly and neuroendocrine tumors
Overview of acromegaly and NET Strong market growth over 15 years1
• Acromegaly is a rare, chronic and insidious (USDm) CAGR 2004-2015: hormonal disorder 2 069 Somatuline® : 16% 2 032 ‒ Occurs when the pituitary gland produces excess 1 917 Sandostatin® : 7% 1 802 growth hormone (GH) and insulin-like growth factor-1 1 705 (IGF-1) 1 516
‒ Current gold-standard medical treatment include 1 350 1 300 somatostatin analogues 1 169
998 1 031 • Neuroendocrine tumors (NETs) are malignant 917
neoplasms 695 607 ‒ Somatostatin analogues constitute the current 488 412 standard of safe and effective medical therapy for 339 symptom control ‒ Somatostatin analogues also show anti-tumor effects 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Sandostatin® (Novartis) Somatuline® (Ipsen)
Significant potential in converting Sandostatin® LAR ® patients to CAM2029
Source1. Medtrack 27 CAM2029 is a convenient, safe and effective treatment option
CAM2029 overview CAM2029 key attributes
• Ready-to-use, long-acting octreotide for Easy subcutaneous administration treatment of acromegaly and neuroendocrine using prefilled syringe tumors (NETs) • Exclusive partnership with Novartis Self-administration option with significant convenience benefits and cost savings ‒ "Novartis Oncology continues its commitment to developing a new formulation of octreotide through a collaboration with Camurus” Increased bioavailability (500%) with potential for enhanced treatment efficacy1 • Positive Phase 2 results announced in July 2016 ‒ Well maintained control of disease symptoms and Thin needle and small injection volume biomarkers in NET and acromegaly patient when switching from Sandostatin® LAR® ‒ Good safety and local tolerability Room temperature stability avoiding cold chain distribution and conditioning before use • Phase 3 studies planned to start in 2017
1. Novartis Q2 and H1 Condensed Interim Financial Report
28 Pipeline expansion with new attractive preclinical candidates
PARTNERS PRODUCT STATUS PRECLIN PH 1/2 PH 3 REG
Rhythm preparing to enter CAM4072 Genetic obesity clinical development in 2017
CAM2043 PAH Phase 1 planned to start in 2017
CAM2046 Diabetes Formulation development
Early stage collaborations with Formulation development pharma and biotech partners
29 CAM2043 is a novel sustained release treprostinil under development for treatment of pulmonary arterial hypertension
• Pulmonary arterial hypertension (PAH) is a • Limitations of current parenteral progressive, life-threatening disease treatments • Orphan indication of 15-50 cases per ‒ Infusion site pain in 85% of patients million • Treatment limiting in 8% of patients ‒ Fewer than 200 treatment centers in the US ‒ Infections and sepsis relating to administration by continuous infusion • PAH market exceeded 4 billion USD with ‒ Need for extra-corporal pump device limiting aggregated treprostinil product sales of convenience and quality of life about 1.1 billion in 2015 • Requiring programming, drug dilution and filling ‒ Remodulin (United Therapeutics) sales of ~$572 with associated complications in 28% of million in 2015, ~12% CAGR1 patients • Pump not water resistant • Includes meta-cresol preservative
Source: 1. PharmaCircle
30 CAM2043 has multiple potential treatment benefits versus parenteral infusion for PAH patients
• Convenient SC depot CAM2043 pharmacokinetic profile ‒ Weekly target dosing ‒ Individualized treatment 100 • Steady exposure levels adjustable by dose treprostinil SC 22.5mg ‒ Within dose range of current products treprostinil SC 30 mg ‒ Maintain efficacy of parenteral infusion products 10 • Potential for improved local tolerability ‒ Less injection site pain 1 ‒ Reduced risks of infections and sepsis ‒ No need for meta-cresol preservative
Plasma TPN conc (ng/mL)Plasma TPN 0,1 24 48 72 96 120 144 168 Time (hours)
Source: Company data (dog PK)
31 Significant clinical news flow expected during 2017
PARTNERS PRODUCT EVENT TIME CAM2038 Opioid dependence Phase 3 results, long-term safety study Q2, 2017
NDA and MAA submissions Mid-2017 CAM2038 Chronic pain Phase 2 results Q2, 2017
Phase 3 efficacy results H2, 2017 CAM2029 Acromegaly & NET Phase 3 start 2017
CAM2047 CINV Phase 1 results Q2, 2017
CAM2048 Pain Phase 1 study results Q2, 2017 CAM2058 Pain, nausea and vomiting Phase 1 study results Phase 2 study start CAM2043 PAH Phase 1 study start H2 2017
32 Summary
• De-risked, late-stage, differentiated pipeline ‒ Opioid addiction, pain, cancer and acromegaly ‒ Successful Phase 3 study results in addiction ‒ Attractive multi-billion dollar specialty pharmaceutical markets ‒ Concentrated prescriber audiences and active patient advocacy groups • Strong collaborations with dedicated partners ‒ Novartis, Braeburn Pharmaceuticals, Rhythm, Solasia, R-Pharm US ‒ Early project collaborations with global pharma companies • Several levers for pipeline and business expansion ‒ New product candidates entering clinical development ‒ Growth opportunities via proven technology platforms as well as strong business development • European commercial organisation ‒ Leadership team established ‒ Pre-launch activities for CAM2038 ongoing • Solid financial position
33 Camurus AB, Ideon Science Park, SE-223 70 Lund, Sweden [email protected] www.camurus.com Solid financial position with increasing investments in late-stage development programs
2016 2015 Revenues Key figures, mUSD Q4 Q1-Q4 Q4 Q1-Q4 35 30 Revenues 4.1 12.5 4.0 17.1 25 License payments 20 Milestone payments Operating result -3.9 -12.3 -0,5 -3.3 15 10 Net sales; services 5 and products Cash 56.1 79.0 0 2012 2013 2014 2015 2016 Total assets 70.5 90.0 Operating expenses
Equity 62.2 70.6 35 30 25 20 Research & dev 15 Sales & marketing 10 Administration 5 0 2012 2013 2014 2015 2016
35