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Report extract:Q3

2017 OUTLOOK REPORT

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Biomedtracker Q3 2017 Outlook Report

Summary In this report, we cover catalysts from 21 drugs expected to occur in Q3 2017. For each drug, the likelihood of Phase/PDUFA review success and overall Likelihood of Approval (LOA) given their particular phase, drug class, and disease group are provided. The results of the catalysts highlighted in our Q2 2017 Outlook Report can be found on Page 4. At the end of this report, we have included a list of Large Impact catalysts through Q3 2017. The catalyst list is also provided in Excel by downloading the supplemental material at the top of this page. Like our report? Have any questions or feedback? Please let us know at askanalyst@sagientresearch.com.

About the Author Biomedtracker is an independent research service that offers proprietary clinical assessments of developmental drugs within a comprehensive and intuitive drug information database. Clients from the pharmaceutical, biotech, and investment industries rely on Biomedtracker for its insight on the likelihood of approval, commercial potential, and future data and regulatory catalysts for drugs within the competitive landscape of every important disease and indication. Over recent years, Biomedtracker has become the leader in providing objective information alongside evidence-based clinical assessments and investment research on pipeline drugs worldwide. For more information on getting direct access to Biomedtracker, please email BioMedSupport@sagientresearch.com.

Disclaimer Copyright © 2017 Sagient Research This report is published by Sagient Research (the Publisher). This report contains information from reputable sources and although reasonable efforts have been made to publish accurate information, you assume sole responsibility for the selection, suitability and use of this report and acknowledge that the Publisher makes no warranties (either express or implied) as to, nor accepts liability for, the accuracy or fitness for a particular purpose of the information or advice contained herein. The Publisher wishes to make it clear that any views or opinions expressed in this report by individual authors or contributors are their personal views and opinions and do not necessarily reflect the views/opinions of the Publisher.

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Contents Outcomes of Biomedtracker's Large Impact Catalysts from the Q2 2017 Outlook Report ........................... 4

CTL019 for Acute Lymphocytic Leukemia (ALL) (NVS) ................................................................................... 6

Mylotarg for Acute Myelogenous Leukemia (AML) (PFE) .............................................................................. 7

Intepirdine for Alzheimer's Disease (AD) (AXON) .......................................................................................... 8

Biosimilar Trastuzumab (Mylan) for Breast Cancer (MYL) ............................................................................. 9

Nerlynx for Breast Cancer (PBYI) ................................................................................................................. 10

Lampalizumab for Dry Age-Related Macular Degeneration (Dry AMD) (Ophthalmology) (RHHBF) ............ 10

Translarna for Duchenne Muscular Dystrophy (DMD) (PTCT) ..................................................................... 11

Zorblisa for Epidermolysis Bullosa (FOLD) ................................................................................................... 13

ZYN-002 for Fragile X Syndrome (ZYNE) ...................................................................................................... 14

Vyzulta for Glaucoma / Ocular Hypertension (Ophthalmology) (VRX) ........................................................ 14

Nurelin for Levodopa-Induced Dyskinesia (ADMS) ...................................................................................... 15

OPN-375 for Nasal Polyposis (OptiNose) ..................................................................................................... 16

Imfinzi for Non-Small Cell Lung Cancer (NSCLC) (AZN) ................................................................................ 17

Sirukumab for Rheumatoid Arthritis (RA) (JNJ) ........................................................................................... 17

Upadacitinib for Rheumatoid Arthritis (RA) (ABBV) ..................................................................................... 18

Brexanolone for Seizure Disorders (Epilepsy) (SAGE) .................................................................................. 19

Endari for Sickle Cell Anemia (Emmaus) ...................................................................................................... 19

Omadacycline for Skin and Skin-Structure Infections (Antibacterial) (PRTK) ............................................... 20

Austedo for Tardive Dyskinesia (TEVA) ........................................................................................................ 21

Patisiran for Transthyretin (TTR)-related Hereditary Amyloidosis (Familial Amyloid Polyneuropathy) (ALNY) .......................................................................................................................................................... 22

Meropenem-Vaborbactam for Urinary Tract and Reproductive Tract Infections (Antibacterial) (MDCO) .. 23

Q3 2017 Large Impact Drug Catalysts……………..…..………………..…………………………………………………………………24

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Outcomes of Biomedtracker's Large Impact Catalysts from the Q2 2017 Outlook Report

Occurred Date

Lead Company Product Market Catalyst Did LOA Predict

Outcome

1-Day Perf

1-Week Perf

1-Month Perf

4/10/2017 OncoMed Demcizumab Oncology Phase II YOSEMITE - Top-

Line Results N/A1 N/A N/A N/A

4/18/2017 Mateon Zybrestat (Injectable) Oncology Phase II/III - FOCUS - Top-

Line Results Yes N/A N/A N/A

4/18/2017 Ultragenyx KRN23 Metabolic Phase III CL303 - Top-Line

Results No -0.91% 5.81% -3.97%

4/25/2017 Capricor CAP-1002 Metabolic Phase I/II HOPE-DUCHENNE

- Top-Line Results N/A1 N/A N/A N/A

5/1/2017 Aeterna Zentaris Zoptrex Oncology Phase III ZoptEC - Top-Line

Results N/A1 -73.13% -73.13% -68.06%

5/1/2017 AstraZeneca Durvalumab Oncology PDUFA for BLA - First

Review Yes 1.49% -0.07% 15.07%

5/1/2017 Neurotrope Bryostatin Neurology Phase IIb - Top-Line Results N/A1 -56.67% -54.01% -67.41%

5/8/2017 TherapeuticsMD Yuvvexy Endocrine PDUFA for NDA - First

Review No -6.42% -3.43% -8.78%

5/9/2017 SAGE SAGE-217 Neurology Phase II PoC - Top-Line

Results N/A1 -2.71% 2.90% 8.93%

5/17/2017 ImmunoGen Mirvetuximab Soravtansine

Oncology Phase Ib/II - FORWARD II -

Top-Line Results Yes 11.11% 4.73% 1.03%

5/18/2017 Shire SHP643 Autoimmune/ immunology

Phase III HELP - Top-Line Results

Yes 3.83% 1.45% -9.40%

5/22/2017 Celgene Ozanimod Neurology Phase II/III RADIANCE (Part

B) - Top-Line Results Yes 0.32% -1.54% 14.32%

5/24/2017 Aerie Roclatan Ophthalmology Phase III - MERCURY 2 Top-

Line Results Yes 32.97% 35.91% 34.31%

5/30/2017 Gilead Bictegravir Infectious Disease Phase III - Top-Line Results Yes 0.60% 0.54% 9.74%

5/31/2017 Novo Nordisk Nonacog Beta Pegol Hematology PDUFA for BLA - First

Review Yes 2.55% 1.96% 2.31%

6/8/2017 Actelion Cadazolid Infectious Disease Phase III - Top-Line Results N/A1 N/A N/A N/A

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6/13/2017 Alimera Iluvien Ophthalmology Phase III INDIA - Top-Line

Results Yes -2.96% 0.74% N/A

6/19/2017 Melinta Baxdela Infectious Disease PDUFA for NDA - First

Review Yes 0.71% 6.46% N/A

6/23/2017 Portola Betrixaban Hematology PDUFA for NDA - First

Review Yes 48.78% N/A N/A

6/27/2017 Alder Eptinezumab Neurology Phase III - PROMISE 1 - Top-

Line Results Yes -35.03% N/A N/A

1No previous LOA adjustment

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CTL019 for Acute Lymphocytic Leukemia (ALL) (NVS)

Drug Company Partner(s) Indication(s) Date Range Expected

Catalyst(s)

CTL019 Novartis AG bluebird; Celyad;

Oxford BioMedica; Regenerex; UPenn

Acute Lymphocytic Leukemia (ALL)

07/12/2017 FDA Advisory

Panel Meeting

Phase Disease Group

Drug Class Group/Class

Phase Success Group/Class

LOA (PTS) BMT LOA Opinion

BLA Oncology Biologic 93.95% 82.00% Above

CTL019 (tisagenlecleucel-T), first developed by the University of Pennsylvania, is an investigational chimeric antigen receptor T cell (CAR-T) therapy that uses the 4-1BB costimulatory domain to enhance cellular responses. CTL019 is unique from other targeted therapies in that CTL019 is manufactured for each individual patient. T cells are drawn from each patient's blood during treatment and reprogrammed to create T cells that are genetically coded to attack cancer cells and other B-cells expressing particular antigens. In 2012, Novartis and the University of Pennsylvania entered into a global collaboration to further research, develop, and commercialize CAR-T cell therapies, which included CTL019. The University of Pennsylvania first submitted for Breakthrough Therapy Designation and in July 2014, the United States Food and Drug Administration (FDA) granted Breakthrough status to CTL019 for the treatment of pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL). Subsequently, in March 2017, Novartis announced that the FDA granted Priority Review for the company's Biologics License Application (BLA) for CTL019 in the treatment of relapsed and/or refractory pediatric and young adult patients with B-cell ALL. The priority review designation and BLA submission for CTL019 are based on the results from the Novartis-sponsored pivotal Phase II ELIANA study, demonstrating CTL019 remission rates were maintained at six months in r/r ALL. These data for CTL019 show that 83% (n=63; P <.001) of patients achieved complete remission (CR) or CR with incomplete blood count recovery (CRi) within three months of infusion, therefore meeting the primary endpoint of the study. The study also showed that the relapse-free probability was 75% at six months and 64% at 12 months among responders suggesting durable responses, an important consideration for relapsed/refractory patients who may be unable to tolerate additional lines of therapy or have had prior stem cell transplantation. Forty-seven percent of patients in ELIANA experienced grade 3 or 4 cytokine release syndrome (CRS), a known complication and common side effect of CAR-T therapies that physicians are learning to manage with tocilizumab. The FDA’s Oncologic Drugs Advisory Committee will discuss the CTL019 BLA on July 12, 2017, and an expectedly positive vote should pave the way for an accelerated approval for this CAR-T therapy for the treatment of pediatric and young adult patients 3 to 25 years of age with r/r B-cell ALL.

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Mylotarg for Acute Myelogenous Leukemia (AML) (PFE)

Drug Company Partner(s) Indication(s) Date Range Expected

Catalyst(s)

Mylotarg Pfizer Inc. UCB; PDL

BioPharma Acute Myelogeneous

Leukemia (AML) 07/11/2017

FDA Advisory Panel Meeting

Phase Disease Group Drug Class Group/Class

Phase Success Group/Class

LOA (PTS) BMT LOA Opinion

BLA Oncology Biologic 93.65% 82.00% Average

On July 11th, 2017, the Food & Drug Administration will hold a meeting of the Oncologic Drugs Advisory Committee to discuss Wyeth Pharmaceuticals’ biologics license application (BLA) for Mylotarg (gemtuzumab ozogamicin) in combination with daunorubicin and cytarabine for the treatment of adult patients with previously untreated, de novo, acute myeloid leukemia (AML). The PDUFA goal date for the decision by the FDA is sometime in September 2017. Mylotarg was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in first-relapse patients with CD33-positive AML who were over 60 years old. In 2010, Pfizer voluntarily withdrew Mylotarg after a confirmatory post-approval Phase III trial failed to show a clinical benefit and revealed a significantly higher fatal induction toxicity rate. The current BLA application under review is based on additional data from the Phase III ALFA-0701 study as well as a meta-analysis of patient level data from five randomized Phase III studies. The ALFA-0701 study was a randomized, open-label study that evaluated the addition of Mylotarg to standard induction chemotherapy using an alternative fractioned dosing schedule in 280 adults, de novo, AML patients aged 50-70 years old. The primary objective of this study was event-free survival (EFS). Secondary objectives included response rate, disease-free survival (DFS), relapse-free survival (RFS), overall survival (OS) and safety. Results from the study showed that EFS and RFS benefits were observed with Mylotarg, with estimated 3-year EFS at 19% in the control arm versus 31% in Mylotarg arm (HR=0.66, p=0.0026) and 3-year RFS at 25% versus 38%, respectively (p=0.006). However, OS data did not confirm benefit with 3-year OS at 36% in control and 44% in Mylotarg arm (HR=0.82, p=0.18). The split dosage schedule avoids the toxicity seen with Mylotarg while retaining an EFS advantage. A meta-analysis of five randomized trials using various doses found an OS benefit for patients treated with Mylotarg and standard induction chemotherapy compared to chemotherapy alone (HR=0.89, p=0.01). There was a highly significant benefit for patients with favourable (HR 0.50, p=0.001) and intermediate (HR 0.85, p=0.007) risk cytogenetics, but no evidence of benefit for patients with adverse risk cytogenetics (HR 1.04, p=0.7). The meta-analysis suggested that excess early mortality was greater in patients given a higher dose of Mylotarg.

This upcoming FDA advisory panel meeting should shed light on the FDA’s thoughts of the ALFA-0701 study and the meta-analysis. Along with the upcoming FDA meeting and approval decision, the Company also announced that a Marketing Authorization Application (MAA) was validated for review by the

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European Medicines Agency (EMA) in December 2016, therefore anticipating a CHMP opinion between September 2017 and March 2018 with a European approval decision expected by May 2018.

Intepirdine for Alzheimer's Disease (AD) (AXON)

Drug Company Partner(s) Indication(s) Date Range Expected

Catalyst(s)

Intepirdine Axovant

Sciences, Inc. GlaxoSmithKline,

Roivant Alzheimer's

Disease 09/15/2017-09/30/2017

Phase III MINDSET - Top-Line Results

Phase Disease Group

Drug Class Group/Class

Phase Success Group/Class

LOA (PTS) BMT LOA Opinion

III Neurology NME 44.96% 36.95% Above

Intepirdine is a selective 5-hydroxytryptamine-6 (5-HT6) receptor antagonist being developed for adjunctive use with donepezil, a drug that inhibits cholinesterase from breaking down acetylcholine. Axovant is currently conducting the Phase III MINDSET trial, a double-blind, randomized study of interpirdine versus placebo when added to stable donepezil treatment in 1315 subjects with mild to moderate Alzheimer’s disease (AD). The MINDSET trial is being conducted pursuant to a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). Top-line results from this trial are expected in late September 2017. The MINDSET Phase III trial is designed to confirm the results of a similarly designed, Phase II, 684-patient, double-blind, placebo-controlled study in which patients on a stable background of donepezil therapy receiving 35 mg intepirdine demonstrated statistically significant improvements on the ADAS-cog and ADCS-ADL as compared to patients receiving donepezil alone. While intepirdine did not have a significant effect on CDR-SB (at 24 weeks, but effect was observed at 12 weeks), replication of this trial using the ADCS-ADL and ADAC-Cog endpoints could lead to regulatory approval. CDR-SB is a cognitive endpoint that was mentioned in the FDA early AD Guidelines, but this endpoint would likely be more relevant for detection of cognitive changes in prodromal or early AD. Earlier in 2017, a Phase III program for Lundbeck and Otsuka’s idalopirdine, also a 5-HT6 class receptor antagonist for the symptomatic treatment of patients with mild to moderate AD, was suspended due to data not demonstrating efficacy to support a regulatory submission. Idalopirdine’s failure leaves intepirdine as the leading pipeline candidate in the 5-HT6 receptor antagonist class. The drug’s new mode of action and Phase III clinical trial design would allow for positioning as an adjunct treatment, thereby avoiding generic competition. If the results of the MINDSET study are positive, Axovant plans to submit a new drug application (NDA) with the FDA for regulatory approval and commercialization of intepirdine in the U.S., followed by a marketing authorization application (MAA) with the European Medicines Agency (EMA).

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