BioPharma BD Quarterly Newsletter Q2 2018

Syneos Health Consulting Commercial Strategy & Planning | Portfolio Strategy Solution Center Syneos Health BioPharma BD Quarterly Newsletter | Q2 2018

Q2 FDA Approvals | Q3 PDUFA Dates | Q2 Deal Summary | Q2 Mergers & Acquisitions | Q2 Partnerships | Q2 Asset Purchases

Q2 FDA Approvals1,2

In order of 2020 sales forecast No sales listed

Aimovig (erenumab) | Novartis / Amgen (co- Akynzeo IV (fosnetupitant) | Helsinn Group commercialize) . Prevention of acute and delayed nausea Migraine, first CGRP receptor blocker associated with cancer chemotherapy . 2020E Sales: $470M Bendamustine HCl Injection (bendamustine AndexXa (andexanet alfa) | Portola hydrochloride) | Spectrum Pharmaceuticals / Pharmaceuticals Eagle Pharmaceuticals (co-promotion Neel Patel . Used for uncontrolled bleeding in patients that agreement) used rivaroxaban and apixaban . Chronic lymphocytic leukemia Managing Director . 2020E Sales: $258M [email protected] Consensi (amlodipine besylate) | Kitov / Dexcel Fulphila (pegfilgrastim) | Mylan / Biocon Pharma Technology (cooperation agreement- (partnership) Dexcel will develop drugs final formulation-Kitov . Decrease incidence of infection, as manifested by pays Dexcel $3.5M for company’s facilities) febrile neutropenia . Amlodipine for hypertension and celecoxib for . 2020E Sales: $244M osteoarthritis

Lokelma (sodium zirconium cyclosilicate) | Crysvita (burosumab) | Ultragenyx AstraZeneca / Incyte (clinical trial collaboration) Pharmaceutical . Treatment of hyperkalemia in adults . X-linked hypophosphatemia . 2020E Sales: $225M EB178 (mirabegron) | Astellas Pharma Olumiant (baricitinib) | Eli Lily . Overactive bladder . Severe active rheumatoid arthritis . 2020E Sales: $214M Lucemyra (lofexidine hydrochloride) | Salix Nelson Azoulay Pharmaceuticals / US WorldMeds (co-partner) Director Crysvita (burosumab) | Kyowa Hakko Kirin . Opioid addiction

. X-linked hypophosphatemia [email protected] . 2020E Sales: $195M

2 Q2 FDA Approvals1,2, continued In order of 2020 sales forecast No sales listed

Doptelet (avatrombopag maleate) | Dova Plenvu (ascorbic acid) | Valeant Pharma / Norgine Pharmaceuticals (licensing agreement-Valeant to develop and . Thrombocytopenia in patients with chronic liver commercialize) disease . Cleansing of the colon in preparation for . 2020E Sales: $180M colonoscopy

Imvexxy (17-beta estradiol) | TherapeuticsMD Yonsa (abiraterone acetate) | Sun Pharmaceutical . Moderate to severe dyspareunia Industries / Churchill Pharmaceuticals (Sun Katya Magonova . 2020E Sales: $131M launches Yonsa due to licensing deal with Engagement Manager Churchill) Palynziq (phenylalanine ammonia lyase) | . Metastatic castration resistant prostate cancer [email protected] BioMarin Pharmaceutical . Treatment of phenylketonuria . 2020E Sales: $125M

Tavalisse (fostamatinib disodium) | Rigel Pharmaceuticals . Treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia . 2020E Sales: $93M

Retacrit (epoetin alfa) | Vifor Pharma Group / Fresenius / NovaQuest / Pfizer (commercialization agreement for certain channels) . Anemia due to chronic kidney disease and Jeff Tan zidovudine in patients with HIV-infection Analyst . 2020E Sales: $49M [email protected]

3 Q2 Deal Summary

Q2 2018 No. of Deals No. of Deals Tot. Deal Value Avg. Deal No. of Deals** Avg. Upfront Summary total with disclosed Value With upfront Payments finances payments

Mergers & 24 15* $19.90B $1.32B 5 $1.33B Acquisitions

Partnerships 108 24 $8.50B $0.35B 10 $0.04B

Asset Purchases & 14 6 $5.57B $0.93B 3 $0.87B Other

*One deal was removed due to rejection in merger **Comprised of only deals with disclosed finances Total Value of Deals by Therapeutic Area†

$14.0B

$12.3B $11.7B $12.0B

$10.0B

$8.0B

$6.0B $5.5B $5.4B $3.7B $4.0B Total Value of Deals ($B)

$2.0B

$0.0B Cancer Neurology Other Diagnostics Autoimmune M&A Partnerships Asset Purchases †Total value of deals is comprised of only deals with disclose finances. Deals that are indicated for multiple therapeutic areas have been double counted and those that are not indicated for a therapeutic area have been excluded 4 Q2 Deal Summary | Top Mergers & Acquisitions (by $)

Tot. Deal Upfront  Buyer Seller Deal Type Novartis was the largest spender in Q2 Value Payment with an upfront payment being the total deal value of $8.7B4 Novartis AG AveXis Inc. Full Acquisition $8.70B $8.70B • After the announcement of AveXis Inc. deal with Novartis’s board, Novartis AG Roche Foundation Medicine Inc. Full Acquisition $2.40B $2.40B acquired a potentially first-ever one-time Zoetis Inc. Abaxis Inc. Full Acquisition $2.00B $2.00B gene replacement therapy for spinal muscular atrophy, AVXS-101 Eli Lily & Co. Armo BioSciences Inc. Full Acquisition $1.60B - • AVXS-101 shows life-saving efficacy with all infants event free at 20 months Johnson & BeneVir Biopharm Inc. Full Acquisition $1.04B $0.14B • AVXS-101 is expected to be on the market Johnson by 2019, with an estimated multi-billion dollar peak sale Companies Deal Type Tot. Deal Value • Both companies supported the acquisition as it would allow Novartis AG to become Keryx Biopharmaceuticals Inc. and Akebia Therapeutics Merger $1.30B the leader in neurodegenerative diseases Inc. to merge to become Akebia Therapeutics Inc. Q2 Deal Summary | Top Partnerships (by $)

Tot. Deal Upfront  Licensee Licensor Asset Pfizer and Allogene Therapeutics entered Value Payment into an asset contribution agreement for Pfizer’s allogeneic CAR T immuno- Allogene 5 Pfizer Inc. Pharmaceutical Products $2.80B - oncology portfolio Therapeutics Inc • Pfizer participates financially to continue Axovant the development of allogeneic CAR T Oxford BioMedica plc Pharmaceutical Products $0.84B $0.03B Sciences Ltd. therapy through 25% ownership stake in Shionogi & Co. Sage Therapeutics Allogene Pharmaceutical Products $0.57B $0.09B Ltd. Inc. • The two companies will continue to develop CAR T both for children with acute Vifor Pharma Cara Therapeutics lymphoblastic leukemia and for adults with Ltd. / Fresenius Pharmaceutical Products $0.54B $0.05B Inc. advanced lymphomas SE & Co. KGaA  Oxford Biomedica and Axovant Sciences Daiichi Sankyo Zymeworks Inc. Discovery Technology $0.48B $0.02B entered into a $800M exclusive worldwide Co. Ltd. license agreement6 Sigilon Therapeutics • Axovant Sciences is going to help develop Eli Lilly and Co. Pharmaceutical Products $0.47B $0.06B Inc. and commercialize AXO-Lenti-PD, a gene CStone therapy treatment for Parkinson’s disease Agios Pharmaceuticals Pharmaceutical Products $0.42B $0.01B • Axovant will gain 7% - 10% tiered royalties Pharmaceuticals Inc. Co. Ltd. on the net sales of AZO-Lenti-PD

5 Q2 Deal Summary | Top Asset Purchases (by $)

Assets (by $)

Buyer Seller Asset Phase Tot. Deal Value Upfront Payment

Shire's cancer business, including Servier Shire Plc acute lymphoblastic leukemia (ALL) Marketed $2.40B $2.40B drug, Oncaspar pegaspargase

Advent International Zentiva Group A/S European generics Sanofi Not Applicable $2.30B $2.30B Corp. business

Spark Therapeutics a rare pediatric disease Priority Jazz Pharmaceuticals plc Not Applicable $0.11B $0.11B Inc. Review voucher

Guangzhou Industrial Investment Fund Takeda Management Co. Ltd. / 51% stake in JV Guangdong Pharmaceutical Co. Not Applicable $0.28B $0.28B Shanghai Techpool Bio-Pharma Ltd. Pharmaceuticals Holding Co. Ltd.

Biogen Inc. TMS Co. Ltd. TMS-007 and backup compounds Phase II $0.36B $0.04B

 Advent International entered into exclusive negotiations leading to the acquisition of Zentiva, Sanofi’s European generics business7 • Advent will work collaboratively with Sanofi to form a new independent operation, supporting the Zentiva management team to invest in the company’s operations and production facilities and R&D pipeline  Shire Plc, a leading global biotechnology company focused on rare diseases, entered into an agreement to sell its Oncology business to Servier8 • Shire’s Oncology business includes in-market ONCASPAR, a component of multi-agent treatment for acute lymphoblastic leukemia, and their rights to ONIVYDE, a component of multi-agent treatment for metastatic pancreatic cancer patients whose disease progressed after a gemcitabine-based therapy • Shire’s portfolio also includes Calaspargase Pegol which is under FDA review for the treatment of acute lymphoblastic leukemia in a multi-agent chemotherapeutic regimen. • Shire’s oncology business had sales of $262 million last year, putting the divestment on a respectable revenue multiple of 9.2 times

Royalties (by $)

Buyer Seller Asset Phase Tot. Deal Value Upfront Payment

HealthCare Royalty La Jolla Giapreza angiotensin II Marketed $0.13B $0.13B Partners Pharmaceutical Co.

6 Q3 FDA PDUFA Dates3, 7, 8

Drug Name Indication Date PDUFA Review

RISPERIDONE (RBP-7000) Schizophrenia Approved: 28-Jul Priority AZEDRA (Iobenguane) Pheochromocytoma Approved: 30-Jul Priority ORILISSA (Elagolix) Endometriosis Approved: 31-Jul Priority KALYDECO (Ivacaftor) Cystic fibrosis Approved: 07-Aug Omadacycline Acute bacterial skin infection Approved: 08-Aug Priority Familial amyloidotic polyneuropathy in patients with PATISIRAN Approved: 11-Aug Priority ATTR EYLEA (Aflibercept) Wet AMD Approved: 11-Aug GALAFOLD (Migalastat) Fabry disease Approved: 13-Aug Priority ORKAMBI (Lumacaftor / Ivacaftor) Cystic fibrosis 15-Aug OPDIVO (Nivolumab) Small cell lung cancer 16-Aug Priority Stannsoporfin Jaundice 22-Aug Priority PRALUENT (Alirocumab) For use with apheresis 24-Aug Post-operative inflammation and pain following INVELTYS (KPI-121) 24-Aug cataract surgery ALTRENO (IDP-121) Acne 27-Aug XERAVA (Eravacycline) Complicated intro-abdominal infections 28-Aug Priority WAYLIVRA (Volanesorsen) Familial chylomicronemia syndrome 30-Aug ESMYA (Ulipristal Acetate) Uterine fibroids 31-Aug Moxetumomab Cancer-leukemia 31-Aug Priority SYMJEPI (Epinephrine) Anaphylaxis 03-Sep Fremanezumab Migraine 16-Sep First line metastatic non-squamous non-small cell KEYTRUDA (Pembrolizumab) 23-Sep Priority lung cancer XYOSTED (Testosterone Testosterone deficiency 29-Sep Enanthate) EMGALITY (Galcanezumab) Migraine prevention 30-Sep Dacomitinib Non-small cell lung cancer 30-Sep Priority

7 Other News

 Akorn intends to sue Fresenius to force the closure of its $4.3B acquisition1 • Akorn’s sales have dropped nearly 30% since Fresenius alleged ‘material breaches’ of FDA data integrity standards in Akorn’s operations • Fresenius canceled its acquisition agreement, which increased its shares by 3.0% • If the breaches have occurred, Fresenius could potentially take over the third largest US ophthalmic company to boost its revenue by an estimated $500M  Pfizer announced to reorganize into three business units9 • Reorganized Pfizer will have an Established Medicines business, a Consumer Healthcare business, and an Innovative Medicines business • The largest of the three will be the Innovative Medicines business that includes a new Hospital Medicines unit in addition to all of the current Innovative Health business units • The creation of the Hospital Medicines unit, with a new channel for sterile injectable and anti-infective medicines, provided opportunity for the reorganization  Analogic was taken over by Altaris Capital Partners10 • Analogic was an oncology-focused biotech company with declining sales • Altaris Capital Partners purchased Analogic in June for $1.1B • Altaris Capital acquired leading-edge healthcare and security technology solutions from this deal including advanced imaging and real-time guidance technologies for disease diagnosis and treatments

1. Evaluate Pharma. Accessed 07/22/18 2. FDA Label. Accessed 07/22/18 3. https://www.biopharmcatalyst.com/calendars/fda-calendar. Accessed 07/22/18. 4. https://www.novartis.com/news/media-releases/novartis-enters-agreement-acquire-avexis-inc-usd-87-bn-transform-care-sma-and-expand-position-gene-therapy-and-neuroscience-leader. Accessed 07/22/18. 5. https://www.pfizer.com/news/press-release/press- releasedetail/pfizer_and_allogene_therapeutics_enter_into_asset_contribution_agreement_for_pfizer_s_allogeneic_car_t_immuno_oncology_portfolio. Accessed 07/22/18. 6. http://www.oxfordbiomedica.co.uk/news-media/press-release/oxford-biomedica-and-axovant-sciences-enter-8425-million-exclusive. Accessed 07/22/18. 7. https://www.adventinternational.com/advent-international-enters-exclusive-negotiations-acquire-zentiva-sanofis-european-generics-business. Accessed 07/22/18. 8. https://globenewswire.com/news-release/2018/04/16/1471737/0/en/Shire-plc-Shire-Announces-Sale-of-Oncology-Business-to-Servier-for-2-4-Billion.html. Accessed 07/22/18. 9. https://www.biospace.com/article/pfizer-to-reorganize-into-three-business-units/. Accessed 07/22/18. 10. https://www.analogic.com/press-release/analogic-to-be-acquired-by-an-affiliate-of-altaris-capital-partners-for-84-00-per-share-or-1-1-billion-in-cash/. Accessed 07/22/18.

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