Syneos Health Consulting BioPharma BD Quarterly Newsletter | Q4 and Full Year 2018

2018 | Full Year Analysis

The healthcare deal space has shown robust activity over the past few years. Fourth quarter 2018 disclosed deal activity was driven mainly by mega deals and early stage clinical partnerships, with focus on oncology, immunotherapy and infectious disease areas, involving both large and small scale companies. Syneos Health Consulting expects continued strong deal activity in 2019.

2018 Deal Summary | Value & No. of Deals by Year

2018 Deal Summary1

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

Mergers & 132 76 $147 B $1.94 B 62 $2.08 B Acquisitions

Partnerships 892 170 $84 B $0.49 B 118 $0.07 B

Asset Purchases & 104 44 $14 B $0.31 B 34 $0.32 B Others

Value & No. of Deals by Year

Value of Deals ($B) 329 Deals No. of Deals $320 $313B 500 375 Deals $275B 356 Deals 290 Deals $261B 312 Deals $245B 400 $240 303 Deals $185B $144B 300 $160 200

$80 100

$ 0 2013 2014 2015 2016 2017 2018 Asset Purchases & Others Partnerships M&A # Deal Count 1 Note: Data inclusive of worldwide Life Science deals with disclosed deal value between 2013 and 2018. Excludes payer / service provider transactions. Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 01/31/2019. 2018 | Q4 Analysis

Q4 Deal Summary | Q4 Mergers & Acquisitions | Q4 Partnerships | Q4 Asset Purchases | Q4 FDA Approvals | Q1 2019 PDUFA Dates

Q4 Deal Summary1

Q4 2018 No. of No. of Deals Tot. Deal Value Avg. Deal No. of Deals Avg. Upfront Summary Deals with Value With upfront Payments total disclosed payments finances

Mergers & 34 14 $15.75 B $1.05 B 13 $1.07 B Acquisitions

Partnerships 242 44 $30.06 B $0.68 B 38 $0.10 B

Asset Purchases & 29 10 $2.56 B $0.26 B 7 $0.36 B Others

Value & No. of Deals by Quarter Value of Deals ($B) No. of Deals 78 Deals $140 $131B 90 $130 80 $120 70 $110 60 $100 68 Deals 50 $48B $50 58 Deals 86 Deals 30 $40 $35B $31B 20 $30 $20 10 $10 $ 0 Q1 '18 Q2 '18 Q3 '18 Q4 '18 Asset Purchases & Others Partnerships M&A # Deal Count

Note: Data inclusive of worldwide Life Science deals with disclosed deal value. Excludes payer / service provider transactions.

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Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 01/31/2019. Q4 Deal Summary (cont’d)1

Value & No. of Deals by Therapeutic Area Value of Deals ($M) No. of Deals 16 Deals $16,855M $17,000 15

$13,700 13

$10,400 4 Deals 8 Deals 11 $6,708M $3,993M $7,100 6 Deals 9 $4,597M $3,800 5 Deals 7 $2,170M $2,000 6 $1,600 1 Deals $1,200M 4 $1,200 2 Deals $771M 2 Deals 2 Deals $800 $526M 1 Deals 1 Deals $202M $433M $371M 2 $400 $- 0

Asset Purchases & Others Partnerships M&A TA Deal Count

Value & No. of Deals by Development Phase Value of Deals ($M) No. of Deals 10 Deals $12,000 $11,073M 9 Deals 12 8 Deals $6,080M $9,375 $8,155M 7 Deals 10 6 Deal $4,018M $6,750 $2,812M 8 3 Deals $4,125 1 Deals $1,758M 2 Deals 6 $2,100M $1,760M $1,500 4 $1,000 3 $750 2 $500 1 Deals 1 $250 $68M $0 0

Asset Purchases & Others Partnerships M&A Phase Deal Count

Note: Therapeutic count was determined by the largest drug in the pipeline or the focus drug of the deal. The graph only includes deals with disclosed financing, and those consisting of biopharma products. Twenty (20) business unit or technology deals were not included. The development phase was determined by the development phase at the time deal sign of the biopharma products only. 3 Phases I/II were incorporated into Phase II, and Phase II/III were incorporated into Phase III counts.

Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 01/31/2019. Q4 Deal Summary | Top Mergers & Acquisitions (by $)1

Tot. Deal Upfront GSK acquires PARP inhibitor Buyer Seller Deal Type Value Payment developer TESARO in a $5.1 billion deal2,3 GlaxoSmithKline Full  GSK bought Waltham-based Tesaro Inc. $5.10 B $5.10 B Tesaro, acquiring its marketed plc Acquisition product Zejula (niraparib), a PARP inhibitor currently approved in the US and Europe Boston Scientific Full to treat ovarian cancer, along BTG plc $4.20 B $4.20 B Corp. Acquisition with several other oncologic pipeline assets including antibodies directed against PD- Full 1, TIM-3 and LAG-3 targets. AG Endocyte Inc. $2.10 B $2.10 B Acquisition  Ongoing trials are evaluating the potential benefit of Zejula in Pacific patients with the gBRCA Full mutations and those without Illumina Inc. Biosciences of $1.20 B $1.20 B Acquisition whose tumors are HRD-positive California Inc. or HRD-negative. GSK believes that the testing of Zejula in HRD Acquisition patients may unleash a number Leo Pharma A/S PellePharm $0.76 B -- Option of other opportunities to help cancer patients.

Q4 Deal Summary | Top Partnerships (by $)1

Therapeutic Phase of Tot. Deal Upfront Licensee Licensor Asset Area Development Value Payment Janssen Arrowhead Pharmaceutical Infectious (Johnson & Pharmaceuticals Phase II $3.70 B $0.18 B Product Disease Johnson) Inc. Swedish Orphan Pharmaceutical Infectious AstraZeneca plc Marketed $2.32 B $1.00 B Biovitrum AB Product Disease Pharmaceutical Eli Lilly and Co. AC Immune S.A. Neurology Preclinical $1.89 B $0.08 B Product Pharmaceutical Agenus Inc. Oncology Phase I $1.85 B $0.12 B Inc. Product Janssen Pharmaceutical (Johnson & Argenx S.E. Oncology Phase II $1.80 B $0.30 B Product Johnson)

Arrowhead and Janssen partner together to bring a functional cure to patients with chronic hepatitis B virus (HBV)4,5  Arrowhead will partner with Janssen to develop and commercialize ARO-HBV, an asset targeted to treat patients with chronic HBV, and potentially collaborate for up to three additional RNA interference (RNAi) therapeutics agents against new targets selected by Janssen.  Arrowhead’s Targeted RNAi Molecule, or TRiMTM, platform utilizes ligand-mediated delivery and is designed to enable tissue-specific targeting while being structurally simple.

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Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 01/31/2019. Q4 Deal Summary | Top Asset Purchases (by $)1

Tot. Deal Upfront Buyer Seller Asset Phase Value Payment

LifeScan Janssen (Johnson & Platinum Equity LLC diabetes Marketed $2.10 B $2.10 B Johnson) company

Trulance Synergy (plecanatide) Pharmaceuticals and other Marketed $0.20 B $0.20 B Companies Inc. Inc. selected assets

1315 Capital LLC & NeoGenomics Inc. Genoptix Inc. Marketed $0.13 B $0.13 B Ampersand Capital

Priority Siga Technologies Eli Lilly and Co. Review Undisclosed $0.08 B $0.08 B Inc. voucher

Cumberland Theravance Vibativ Marketed $0.03 B $0.03 B Pharmaceuticals Inc. Biopharma Inc. (telavancin)

NeoGenomics Signs Definitive Agreement to Acquire Genoptix for $126 million6  The acquisition of Genoptix enhances NeoGenomic’s leadership in the oncology test market, significantly expanding coverage into community oncology practices and driving additional value in complementary services to create an unprecedented offering.  The acquisition is expected to contribute $85 million of revenue and break-even EBITDA in year one, $25 million of cost synergies over time, and 25% EBITDA margin by the end of year three.

Asset Deals

Pharmaceutical Platform Business Royalty Regulatory Product Unit Vouchers

2 Deals 4 Deals 2 Deals 1 Deal 1 Deal $225M $32M $2,226M $1.6M $80M

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Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 01/31/2019. Q4 FDA Approvals7

In Order of 2020 US Sales Forecast

Udenyca (pegfilgrastim) | Coherus BioSciences . Decrease the incidence of infection, as manifested by febrile neutropenia . 2020E Sales: $203M

Bijuva (17-beta estradiol; progesterone) | TherapeuticsMD . Moderate to severe vasomotor symptoms due to menopause . 2020E Sales: $188M

Tegsedi (inotersen sodium) | Akcea Therapeutics / Ionis Pharmaceuticals (partnership) . Treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis . 2020E Sales: $111M

Firdapse (amifampridine phosphate) | Catalyst Pharmaceuticals . Lambert-Eaton myasthenic syndrome . 2020E Sales: $96M

Seysara (sarecycline hydrochloride) | Almirall . Treatment of moderate to severe acne . 2020E Sales: $57M

Truxima (rituximab) | Teva Pharmaceutical Industries . Treatment of Non-Hodgkin’s lymphoma . 2020E Sales: $49M

Nuzyra (omadacycline tosylate) | Paratek Pharmaceuticals . Treatment of community-acquired bacterial pneumonia . 2020E Sales: $45M

Aemcolo (rifamycin sodium) | Cosmo Pharmaceuticals . Travelers’ diarrhea caused by noninvasive trains of Escherichia coli . 2020E Sales: $30M

Yutiq (fluocinolone acetonide) | EyePoint Pharmaceuticals . Chronic non-infectious uveitis affecting the posterior segment of the eye . 2020E Sales: $29M

No Sales Listed

Gamifant (emapalumab) | Novimmune . Treatment of adult and pediatric patients with primary hemophagocytic lymphohistiocytosis with recurrent or progressive disease

Khapzory (levoleucovorin) | . Indicated for the rescue after high-dose methotrexate therapy in patients with osteosarcoma

Revcovi (elapegademase) | Leadiant Biosciences . Treatment of adenosine deaminase severe combined immune deficiency in pediatric and adult patients

Yupelri (revefenacin) | Theravance Biopharma . Maintenance treatment of patients with chronic obstructive pulmonary disease

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Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 01/31/2019. Q1 2019 FDA PDUFA Dates8

PDUFA Company Name Drug Name Indication Estimated Date Review

Cabozantinib Approved: Exelixis Inc. Advanced hepatocellular cancer (celestial) 01/14/2019 Evenity Approved: Inc. Osteoporosis (romosozumab) 01/16/2019 American Fluzone Quadrivalent Influenza A – children 6-35 months of Approved: Depositary Shares (influenza vaccine) age. 01/28/2019 ALKS 5461 Rejected: plc (buprenorphine and Major depressive disorder 01/31/2019 samidorphan) Aquestive Therapeutics Inc. APL – 130277 Parkinson’s Disease with motor Rejected: & Sunovion (apomorphine) fluctuations 01/31/2019 (partnership) DWP – 450 Evolus Inc. Glabellar lines 02/02/2019 (prabotulinumtoxinA) Acute bacterial skin and skin structure Motif Bio plc Iclaprim – REVIVE-2 02/13/2019 PRIORITY infections DUOBRII (halobetasol Bausch Health propionate and Psoriasis 02/15/2019 Companies Inc. tazarotene) KEYTRUDA – Merck & Company EORTC 1325 / Treatment of patients with unresectable 02/16/2019 Inc. KEYNOTE – 054 or metastatic melanoma (pembrolizumab) Treatment of patients with intermediate or high-risk myelofibrosis, including Incyte Corporation primary myelofibrosis, post- & Novartis AG Jakafi (ruxolitinib) 02/24/2019 PRIORITY polycythemia vera myelofibrosis and (partnership) post-essential thrombocythemia myelofibrosis Bausch Health Loteprednol Gel Ocular inflammation 02/25/2019 Companies Inc. 0.38% N8 – GP (turoctocog Nova Nordisk A/S Hemophilia A 02/26/2019 alfa pegol)

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Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 01/31/2019. Q1 2019 FDA PDUFA Dates8

PDUFA Company Name Drug Name Indication Estimated Date Review

Regeneron Pharmaceuticals Inc. & Sanofi American Dupixent (dupilumab) Atopic dermatitis 12-17 year-olds 03/11/2019 PRIORITY Depositary Chares (partnership) Celgene Corporation & Tecentriq Locally advanced or metastatic Roche Holding Ltd (atezolizumab) plus 03/12/2019 urothelial carcinoma ADR Abraxane (partnership) Aerie Roclatan (netarsudil / Reduction of elevated intraocular Pharmaceuticals latanoprost pressure in patients with open-angle 03/14/2019 Inc. ophthalmic solution) glaucoma or ocular hypertension Roche Holding Ltd Atezolizumab (atezo) Squamous non-small cell lung cancer 03/18/2019 PRIORITY ADR Sage Brexanolone (SAGE- Postpartum Depression – moderate 03/19/2019 PRIORITY Therapeutics Inc. 547) Jazz Solriamfetol (JZP – Excessive sleepiness associated with Pharmaceuticals 03/20/2019 110) narcolepsy plc Inc. & Sanofi Sotagliflozin (LX4211) Type 1 diabetes 03/22/2019 American Depositary Shares (partnership) Recro Pharma Intravenous Acute pain following bunionectomy 03/24/2019 Inc. meloxicam surgery Secondary progressive multiple Novartis AG Siponimod (BAF312) 03/31/2019 PRIORITY sclerosis Herceptin (trastuzumab / PF- Inc. Herceptin biosimilar 03/31/2019 05280014) BIOSIMILAR Total # 20 6 PRIORITY

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Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 01/31/2019. Authors

Neel Patel Nelson Azoulay Katya Magonova Managing Director Director Engagement Manager [email protected] [email protected] [email protected]

David Tannin Jeff Tan Nick Milazzo Senior Consultant Associate Consultant Analyst [email protected] [email protected] [email protected]

Sources

1. https://bciq.biocentury.com/deal/all-deals/insights. Accessed 01/15/2019. 2. https://www.forbes.com/sites/matthewherper/2018/12/03/gsk-buys-tesaro-for-5-billion-in-dramatic-bet-on-cancer- genetics/. Accessed 01/13/2019. 3. https://www.gsk.com/en-gb/media/press-releases/gsk-reaches-agreement-to-acquire-tesaro-an-oncology-focused- biopharmaceutical-company/. Accessed 01/13/2019. 4. https://arrowheadpharma.com/science/. Accessed 01/13/2019. 5. http://ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-enters-37-billion-license-and- collaboration-agreements. Accessed 01/13/2019. 6. https://ir.neogenomics.com/press-releases/detail/102/neogenomics-signs-definitive-agreement-to-acquire-genoptix. Accessed 01/13/2019. 7. Evaluate Pharma Approval Deals. Accessed 01/02/2019. 8. https://www.biopharmcatalyst.com/calendars/fda-calendar. Accessed 01/10/2019.

Note: Mergers & Acquisition deals include: full acquisition, majority acquisition, reverse merger, merger, and acquisition option. Partnership deals include: development and commercialization license, sales marketing and co-promotion, collaborative research and product license option, product license option, research and development only, partnership with company acquisition option, academic / foundational / govt. research, other unspecified partnership, and joint venture / consortium. Asset Purchases and Other deals include: business unit or division purchase, product pipeline or platform purchase, spin-out and company formation, royalty stream monetization, other unspecified asset purchase, settlement resulting in a license, and contract R&D and manufacturing service.

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Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 01/31/2019.