Syneos Health Consulting Biopharma BD Quarterly Newsletter

Syneos Health Consulting BioPharma BD Quarterly Newsletter

2019 | Q2 Analysis Newsletter Content . Q2 Deal Summary Similar to Q1, Q2 2019 Biopharma dealmaking has been marked by a continued pattern of high . Q2 Global & US Deals value low volume dealmaking, with activity slightly decreased from the previous quarter. High value . Q2 Ex-US Deals mega deals continue to drive headlines with major consolidation among large to mid-size . Q2 US IPOs biopharma companies. There were 7 novel drugs approved this quarter with most targeting varying . Q2 FDA Approvals indications within oncology. Q2 marked the highest quarter for IPOs (value and volume) compared . Q3 PDUFA Dates to recent years, as companies may be rushing to markets ahead of weaker global economic data. Q2 Deal Summary1

HIGHLIGHTS . AbbVie strikes deal to acquire Allergan for ~$63 billion to diversify its business and prepare for 2023 Humira US LOE.2 . Alnylam and Regeneron partner in a new industry-leading alliance aimed at realizing a significant opportunity for RNAi therapeutics to be potential transformative medicines for ocular and CNS diseases.3 . Takeda completes sale of XIIDRA to Novartis for an upfront payment of $3.4 billion and up to $1.9 billion in potential milestone payments. This will help service outstanding debt taken on by the recent acquisition of Shire.4

Q2 2019 # of Deals Tot. Deal Avg. Deal Value No. of Deals Avg. Upfront Q2 2018 Summary disclosed Value ($M) ($M) With upfront Payments Comparison finances of payments ($M) Tot. Deal Value total

Mergers & 10 of 11 $79,101 $7,300 7 $303  288% Acquisitions

Partnerships 14 of 34 $8,784 $627 12 $60  4%

Asset 4 of 7 $7,226 $1,817 2 $1,855  33% Purchases

Deals by Geography

WW 4 | 23 | 4

EU NA 3 | 1 | 1 5 | 1 | -- APAC 1 | 9 | 2

Legend: M&A Partnerships Asset Purchases 1

Note: M&As deals used the buyers HQ country. Partnerships deals listed through the licensing territory. Asset Purchases deals used either the HQ country or the licensing territory. Q2 Deal Summary (cont’d)1

Value & No. of Deals by Quarter Value of Deals ($B) No. of Deals

46 Deals $120 $112,393M 28 Deals 80 $106 $95,151M 70 $93 60 $79 50 $65 53 Deals 56 Deals 40 $37,559M $40 $34,937M 75 Deals $26,821M 30 $30 20 $20 $10 10 $ 0 Q2 '18 Q3 '18 Q4 '18 Q1 '19 Q2 '19

Value & No. of Deals by Therapeutic Area Value of Deals ($M) No. of Deals 2 Deals $63,135M 10 Deals $64,000 $16,880M 11 $49,000 9 $34,000 2 Deals $19,000 $5,404M 4 Deals 7 $4,000 $2,540M 5 1 Deal $2,800 2 Deals 2 Deals 4 $2,059M $2,100 $1,810M $1,795M 1 Deal 2 Deals 3 $1,035M $391M 1 Deal 1 Deal $1,400 $90M $12M 2 $700 1 $- 0

Value & No. of Deals by Development Phase Value of Deals ($M) No. of Deals 9 Deals $80,702M $80,000 10 9 $70,000 7 Deals $5,814M 8 $60,000 7 $50,000 6 3 Deals $6,000 3 Deals 2 Deals 5 1 Deal $3,654M $293M $2,573M 2 Deals 4 $835M $4,000 $1,167M 1 Deals 3 $113M $2,000 2 1 $0 0 Marketed Registration Phase III Phase II Phase I Preclinical Research Undisclosed

Legend: M&A Partnerships Asset Purchases Deal Count 2

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. The development phase was determined by the development phase at the time deal sign of the biopharma products only. Q2 Global & US Deals1

Select Mergers & Acquisitions

Tot. Deal Upfront Buyer Seller Summary Value ($M) Payment ($M)

Deal will help diversify business, grow sales and $63,000 - cushion impact of 2023 Humira LOE

Lead asset will increase company’s focus on colorectal $11,400 - cancer drugs

2 assets that will further bolster Merck’s oncology $2,200 $1,050 pipeline

SingleCut CRISPR gene editing platform that will $1,000 $245 enhance Vertex’s gene editing capabilities

Novel differentiated chemo-proteomic platform to $400 $250 discover new classes of drugs for broad spectrum of brain disease

DEAL HIGHLIGHT AbbVie Strikes Deal to Acquire Allergan for About $63 Billion2  Abbvie’s enhanced growth platform, comprised of growing and durable franchises across highly-attractive therapeutic areas, is expected to grow at a high-single digit annual growth rate, from more than $30 billion in 2020.  Humira is currently responsible for 60% of AbbVie's sales; this deal will help diversify its business, grow sales and mitigate the impact of the 2023 U.S. Humira LOE.

Select Partnerships

Tot. Deal Upfront Licensee Licensor TA Phase Asset Value ($M) Payment ($M)

Gilead $2,059 $50 Renal Research Undisclosed

Gilead $1,035 $15 Hepatic Research Undisclosed

$1,030 $400 CNS Phase II REGN3918

Pain $998 $48 Phase I CNTX-0290 Management

$560 - Agnostic N/A AI Technology

DEAL HIGHLIGHT Alnylam and Regeneron partner in a five year deal to discover, develop and commercialize RNAi therapeutics3  Collaboration will help discover, develop and commercialize new RNA interference (RNAi) therapeutics for a broad range of diseases by addressing disease targets expressed in the eye and central nervous system (CNS).  Regeneron will lead development and commercialization for all programs targeting eye diseases, with Alnylam entitled to potential milestone and royalty payments. The companies will jointly advance and alternate leadership on CNS programs.

3 Q2 Global & US Deals (cont’d)1

Asset Purchases

Tot. Deal Upfront Buyer Seller Phase Asset Value ($M) Payment ($M)

Xiidra lifitegrast for dry-eye disease and $5,300 $3,400 Marketed other ophthalmic indications

One clinical and two preclinical programs targeting NLRP3 inflammasome for $1,575 $310 Phase I treating several metabolic, fibrotic, autoimmune and neurological diseases

ZEMDRI (plazomicin) to address multi- drug resistant (MDR) gram-negative $16 $16 Marketed infections, purchased in U.S Bankruptcy court

DEAL HIGHLIGHT Takeda Completes Sale of XIIDRA to Novartis4  Xiidra® (lifitegrast ophthalmic solution) is a lymphocyte function-associated antigen-1 (LFA-1) antagonist indicated for the treatment of the signs and symptoms of dry eye disease (DED).  The multibillion dollar transaction will assist Takeda is servicing corporate debt taken on in part by the Shire acquisition, while optimizing key focus areas for the new company.

4 Q2 Ex-US Deals1

Mergers & Acquisitions

Tot. Deal Upfront Buyer Seller Region Summary Value ($M) Payment ($M)

$810 $340 EU Centered around TA-46 for achondroplasia

For assets including GRP78 inhibitor; IL- 17A inhibitor; NUE7770; RORgammaT $167 $166 EU agonist; and Neuvolutions drug discovery platform

DEAL HIGHLIGHT Pfizer Announces Acquisition of Theracon, a Rare Disease Biopharma Based in Basel Switzerland5  Pfizer will pay $340 million upfront with another $470 million in payments contingent on milestones for the development and commercialization of TA-46 for the treatment of achondroplasia.

Partnerships

Tot. Deal Upfront Licensee Licensor TA Phase Region Asset(s) Value ($M) Payment ($M) DC Vaccine $1,010 $10 AML Phase I/II Asia containing WT1/PRAME HRS7-SN-38, Unspecified sacituzumab $835 $65 Registered Asia Oncology govitecan (IMMU- 132)

Breast Nerlynx oral $405 $60 Marketed EU Cancer neratinib

Pancreatic $229 $3 Phase II Asia RX-3117 Cancer

Asset Purchases

Tot. Deal Upfront Buyer Seller Phase Region Asset(s) Value ($M) Payment ($M)

Vancocin vancomycin and Ceclor cefaclor for GI infections, as well as $375 $75 Marketed Asia a Ceclor manufacturing plant in Suzhou

5 Q2 US IPOs1

Value & No. of IPOs by Quarter Value of IPOs ($M) No. of IPOs

19 IPOs $2,500 $2,335M 30 17 IPOs 11 IPOs 19 IPOs $1,930M $1,855M $2,000 $1,767M 25 20 $1,500 11 IPOs $1,855M 15 $1,000 10

$500 5

$ 0 Q2 '18 Q3 '18 Q4 '18 Q1 '19 Q2 '19

Legend: Amount Raised No. Financing Deals

IPOs

Amount Raised Therapeutic Lead Product Date Company Ticker ($M) Area Status Complete

NGM Biopharmaceuticals NGM $120 Hepatic Phase II Apr 3 Inc. NASDAQ

HOOK Hookipa Pharma Inc. $84 Oncology Phase II Apr 17 NASDAQ

Turning Point Therapeutics TPTX $167 Oncology Phase II Apr 18 Inc. NASDAQ

TRVI Trevi Therapeutics Inc. $55 Dermatology Phase III May 7 NASDAQ

Milestone Pharmaceuticals MIST $95 Cardiovascular Phase III May 8 Inc. NASDAQ

NXTC NextCure Inc. $86 Oncology Phase I May 8 NASDAQ

CRTX Cortexyme Inc. $86 Neurology Phase I May 8 NASDAQ

AXLA Axcella Health Inc. $71 Neurology Preclinical May 8 NASDAQ

APLT Endocrine / Applied Therapeutics Inc. $40 Phase II May 13 NASDAQ Metabolic

6 Q2 US IPOs cont’d1

Amount Raised Therapeutic Lead Product Date Company Ticker ($M) Area Status Complete

BCYC Bicycle Therapeutics plc $61 Oncology Phase II May 22 NASDAQ

IDYA Ideaya Biosciences Inc. $58 Oncology Phase I May 22 NASDAQ

STOK Stoke Therapeutics Inc. $163 Neurology Preclinical Jun 18 NASDAQ

PRVL Prevail Therapeutics Inc. $125 Neurology IND Jun 19 NASDAQ

AKRO Akero Therapeutics Inc. $106 Hepatic Phase II Jun 19 NASDAQ

BCEL Atreca Inc. $125 Infectious Preclinical Jun 19 NASDAQ

PSNL Personalis Inc. $155 Genomics Marketed Jun 19 NASDAQ

Adaptive Biotechnologies ADPT $300 Diagnostic Marketed Jun 26 Corp. NASDAQ

BBIO BridgeBio Pharma Inc. $349 Oncology Phase III Jun 26 NASDAQ

MORF Morphic Holding Inc. $90 Inflammation Preclinical Jun 26 NASDAQ

7 Q2 FDA Approvals

Novel Drugs6 Approval Date

romosozumab | Amgen Apr 9 . Osteoporosis in postmenopausal women erdafitinib | Johnson & Johnson Apr 12 . Locally advanced or metastatic bladder cancer risankizumab | Abbvie Apr 23 . Moderate-to-severe plaque psoriasis tafamidis meglumine | Pfizer . Heart disease (cardiomyopathy) caused by transthyretin May 3 mediated amyloidosis (ATTR-CM) alpelisib | Novartis May 24 . Breast cancer polatuzumab vedotin | Genentech Jun 10 . Relapsed or refractory diffuse large B-cell lymphoma bremelanotide | Palatin Technologies . Hypoactive sexual desire disorder in premenopausal Jun 21 women

Biosimilars7 Approval Date

etanercept | Samsung Bioepis Eticovo Apr 29 . Rheumatoid arthritis and plaque psoriasis trastuzumab | Amgen and Allergan (partnership) Kanjinti Jun 13 . HER2-overexpressing breast and metastatic gastric cancer bevacizumab | Pfizer Zirabev Jun 28 . Metastatic colorectal cancer

First Generic8 Brand Product Approval Date naftifine Taro Pharmaceuticals hydrochloride gel Apr 10 . Interdigital tinea pedis topical cream

Mifepristone Topical cream | GenBioPro Apr 11 topical cream . Termination of early pregnancy loteprednol Hi-tech Pharmacal Co. etabonate . Steroid responsive inflammatory conditions of the palpebral Apr 17 topical eye drop and bulbar conjunctiva, cornea (i.e.) Valrubicin Custopharm Apr 19 injection . BCG-refractory carcinoma amoxicillin and clavulanate Aurobindo Pharma Apr 19 potassium . Multiple infections tablet naloxone Teva Pharmaceuticals hydrochloride Apr 19 . Opioid overdose intra-nasal spray Everolimus Mylan Apr 19 tablet . Subependymal giant cell astrocytoma (SEGA)

8 Q2 FDA Approvals (cont’d)

First Generic (cont’d)10 Brand Product Approval Date

Rufinamide Bionpharma Apr 23 topical cream . Seizures associated with Lennox-Gastaut Syndrome (LGS) pentamidine Seton Pharmaceuticals isethionate Apr 24 . Pneumocystis jiroveci pneumonia (PJP) IV injection Bosentan Amneal Pharmaceuticals Apr 26 tablet . Pulmonary arterial hypertension Penicillamine Amerigen Pharmaceuticals May 7 capsule . Wilson's disease and cystinuria Mesalamine Teva Pharmaceuticals May 9 capsule . Mildly to moderately active ulcerative colitis sapropterin Par Pharmaceuticals dihydrochloride May 10 . Hyperphenylalaninemia (HPA) tablet Fresenius Kabi USA Micafungin . Candidemia, acute disseminated candidiasis, candida May 17 injection peritonitis and abscesses dapiprazole Baradaina hydrochloride May 29 . Mydriasis Rev-Eyes topical eye drop

Sildenafil Novitium Pharma May 31 suspension . Pulmonary arterial hypertension (PAH) diclofenac sodium Mylan Jun 18 topical cream . Mild-moderate pain management dapsone Taro Pharmaceuticals Jun 26 topical gel . Acne vulgaris Tobramycin Inhaled aerosol | Teva Pharmaceuticals Jun 26 inhaled aerosol . Cystic fibrosis tramadol Rubicon Research hydrochloride Jun 28 . Severe pain management Ultram tablet No. of Drug Approvals by Quarter No. of Approvals 25 Generic 23 Generic 1 Biosimilar 4 Biosimilar 21 Novel 50 18 Novel 18 Generic 2 Biosimilar 20 Generic 40 14 Novel 3 Biosimilar 12 Generic 7 Novel 30 2 Biosimilar 7 Novel 20 67%

10 10% 23% 0 Q2 '18 Q3 '18 Q4 '18 Q1 '19 Q2 '19 Legend: Novel Biosimilar First Generic 9 Q3 FDA PDUFA Dates11

Estimated PDUFA Company Name Drug Name Indication Date Review

Autoimmune

Celgene Otezla Moderate to severe plaque psoriasis Jul 21

ABT-494 Abbvie Rheumatoid arthritis Aug 19 PRIORITY (upadcitinib) Tenapanor Ardelyx Inc Irritable bowel syndrome with constipation (IBS-C) Sep 12 (T3MPO-2)

Cardiovascular

Amarin Vascepa Severe hypertriglyceridemia Sep 28 PRIORITY Corporation

Central Nervous System (CNS)

Biohaven BHV-0223 ALS Jul 25 pharmaceuticals

Vanda Hetlioz Non-24-hour sleep–wake disorder Aug 16 pharmaceuticals (tasimelteon)

Sarepta Golodirsen - Duchenne muscular dystrophy (DMD) Aug 19 PRIORITY Therapeutics Exon 53

Intra-cellular Lumateperone Schizophrenia Sep 27 Therapeutics

Endocrinology & Metabolism

Xeris Glucagon Severe hypoglycemia Sep 10 Pharmaceuticals Rescue Pen

Novo Nordisk Semaglutide Type 2 diabetes Sep 20 PRIORITY

Johnson & INVOKANA - Lower blood sugar in adults with type 2 diabetes Sep 27 PRIORITY Johnson CREDENCE

Infectious Disease

Merck PRIMAXIN Bacterial infections Jul 16 PRIORITY

Nabriva Lefamulin Acute bacterial skin and skin-structure infections Aug 19 PRIORITY Therapeutics plc PIFELTRO Merck HIV-1 Aug 30 (doravirine)

10 Q3 FDA PDUFA Dates (cont’d)11

Estimated PDUFA Company Name Drug Name Indication Date Review

Oncology

Roche Entrectinib Non–small cell lung cancer (NSCLC) Aug 18 PRIORITY

TECENTRIQ (atezolizumab) Celgene and plus Roche Non–small cell lung cancer (NSCLC) Sep 2 chemotherapy (partnership) (carboplatin and Abraxane)

Celgene Fedratinib Myelofibrosis Sep 3

Ophthalmology

Kala KPI-121 (0.25%) Dry eye disease Aug 15 Pharmaceuticals

Pain Management

Intellipharmaceut ics International Rexista Moderate to severe pain Aug 28 Inc Nektar NKTR-181 Moderate to severe chronic low back pain Aug 29 Therapeutics

11 Authors

Neel Patel Nelson Azoulay Katya Magonova Senior 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 07/11/2019. 2. https://seekingalpha.com/article/4274213-abbvie-gets-even-complicated-allergan. Accessed 07/11/2019. 3. http://investors.alnylam.com/news-releases/news-release-details/alnylam-and-regeneron-announce-broad-collaboration-discover. Accessed 07/11/2019. 4. https://www.takeda.com/newsroom/newsreleases/2019/takeda-completes-sale-of-xiidra-to-novartis/. Accessed 07/11/2019. 5. https://www.biospace.com/article/pfizer-buys-theracon-for-810-million/. Accessed 07/11/2019. 6. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm629491.htm. Accessed 07/11/2019. 7. https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologic applications/biosimilars/ucm580432.htm. Accessed 07/11/2019. 8. https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/drugandbiologicapprovalreports/andage nericdrugapprovals/default.htm. Accessed 07/11/2019. 9. https://www.biopharmcatalyst.com/calendars/fda-calendar. Accessed 07/11/2019.

Note: Mergers & Acquisition deals include: full acquisition, majority acquisition, and merger. Mergers & Acquisition asset types include: company, and pharmaceutical products. Partnership deals include: development and commercialization license, collaborative research and product license option, partnership with company acquisition option, joint venture/consortium, sales marketing and co-promotion, cross-license, and public-private partnership. Partnerships assets include: company, facility, and pharmaceutical products. Asset Purchases deals include: business unit or division purchase, and product pipeline or platform purchase. Asset Purchases assets include: business unit or division, company, and pharmaceutical products. Deals and Assets filters have been included in previous quarters Deal Values have been rounded to the nearest million

Syneos Health makes no guarantee, warranty, or assurances concerning the information in this document. Data is based on latest information as of 07/18/2019. Syneos Health Consulting

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