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Biomedtracker Early 2018 Outlook Report

EARLY 2018 OUTLOOK REPORT EXTRACT

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Biomedtracker Early 2018 Outlook Report

Summary In this report, we cover catalysts from 21 drugs expected to occur in Early 2018. 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 Q4 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 Early 2018. The catalyst list is also provided in Excel by downloading the supplemental material at the top of this page.

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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.

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Contents for the full reportOutcomes of Biomedtracker's Large Impact Catalysts from the Q4 2017 Outlook Report ........................... 4

Azeliragon for Alzheimer's Disease (AD) (VTVT) ............................................................................................ 6

Exparel for Anesthesia (PCRX) ....................................................................................................................... 6

VB-111 for Brain Cancer (Malignant Glioma; AA and GBM) (VBLT) ............................................................... 7

Truxima for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL (TEVA) .. 8

VX-661 for Cystic Fibrosis (CF) (VRTX) ........................................................................................................... 9

ETC-1002 for Dyslipidemia / Hypercholesterolemia (ESPR)......................................................................... 10

Sollpura for Exocrine Pancreatic Insufficiency (ANTH) ................................................................................ 11

Bictegravir for HIV / AIDS (GILD) .................................................................................................................. 12

Ibalizumab for HIV / AIDS (THERF) ............................................................................................................... 13

Tavalisse for Immune Thrombocytopenic Purpura (ITP) (RIGL) ................................................................... 14

Esketamine for Major Depressive Disorder (MDD) (JNJ) ............................................................................. 15

Hydexor for Moderate to Severe Pain (Charleston) .................................................................................... 16

Azedra for Neuroendocrine Tumors (NET) (PGNX) ...................................................................................... 17

AM0010 for Pancreatic Cancer (ARMO) ...................................................................................................... 18

Apalutamide for Prostate Cancer (JNJ) ........................................................................................................ 19

Tildrakizumab for Psoriasis (Sun) ................................................................................................................. 20

CK-2127107 for Spinal Muscular Atrophy (CYTK) ........................................................................................ 21

Lupuzor for Systemic Lupus Erythematosus (SLE) (ImmuPharma) .............................................................. 22

Elagolix for Uterine Fibroids (ABBV) ............................................................................................................ 23

CLS-1001 for Uveitis (Ophthalmology) (CLSD) ............................................................................................. 24

KRN23 for X-Linked Hypophosphatemia (XLH) (RARE) ................................................................................ 25

Early 2018 Large Impact Drug Catalysts……………..…..………………..………………………………………………………………26

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Outcomes of Biomedtracker's Large Impact Catalysts from the Q4 2017 Outlook Report

Occurred Date

Lead Company Product Market Catalyst Did LOA Predict

Outcome

LOA Before Outcome

LOA After Outcome

10/4/2017 Motif Iclaprim (IV) Infectious disease Phase III REVIVE-2 - Top-Line

Results Yes

62% (1% Above Avg.)

71% (10% Above Avg.)

10/11/2017 Ardelyx Tenapanor Gastroenterology

(non inflammatory bowel disease)

Phase III - T3MPO-2 - Topline Results

Yes 69%

(7% Above Avg.) 72%

(10% Above Avg.)

10/12/2017 AcelRx Dsuvia Neurology PDUFA for NDA - First Review No 93%

(10% Above Avg.) 60%

(8% Above Avg.)

10/12/2017 Spark Luxturna Ophthalmology FDA Advisory Panel Meeting Yes 93%

(14% Above Avg.) 98%

(19% Above Avg.)

10/18/2017 Gilead Yescarta Oncology PDUFA for BLA - First Review Yes 90%

(8% Above Avg.) 100%

(Approved)

10/20/2017 Johnson & Johnson Simponi Aria (IV) Autoimmune/ immunology

PDUFA for sBLA - First Review (Axial Spondyloarthritis)

Yes 97%

(10% Above Avg.) 100%

(Approved)

10/20/2017 Johnson & Johnson Simponi Aria (IV) Autoimmune/ immunology

PDUFA for sBLA - First Review (Psoriatic Arthritis (PA))

N/A1 87%

(Same As Avg.) 100%

(Approved)

11/7/2017 Keryx Auryxia Hematology PDUFA for sNDA - First Review Yes 89%

(5% Above Avg.) 100%

(Approved)

11/8/2017 Merck Prevymis Infectious disease PDUFA for NDA - First Review Yes 98%

(10% Above Avg.) 100%

(Approved)

11/9/2017 Dynavax Heplisav-B Infectious disease PDUFA for BLA - Second Review Yes 89%

(1% Above Avg.) 100%

(Approved)

11/9/2017 Seattle Genetics Adcetris Oncology PDUFA for sBLA - First Review Yes 94%

(12% Above Avg.) 100%

(Approved)

11/14/2017 AstraZeneca Fasenra Respiratory PDUFA for BLA - First Review Yes 99%

(2% Above Avg.) 100%

(Approved)

11/15/2017 Ultragenyx Mepsevii Metabolic PDUFA for BLA - First Review No 88%

(1% Below Avg.) 100%

(Approved)

11/19/2017 Roche Hemlibra Hematology Phase III - HAVEN 3 - Top-Line

Results N/A1

100% (Approved)

100% (Approved)

11/21/2017 Cytokinetics Tirasemtiv Neurology Phase III VITALITY ALS - Top-Line

Results Yes

43% (9% Below Avg.)

0% (Suspended)

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11/27/2017 Catalyst Firdapse Autoimmune/ immunology

Phase III - LMS-003 - Top-Line Results

Yes 69%

(10% Above Avg.) 70%

(11% Above Avg.)

11/30/2017 Indivior Sublocade Psychiatry PDUFA for NDA - First Review Yes 93%

(8% Above Avg.) 100%

(Approved)

12/5/2017 Galectin GR-MD-02 Endocrine Phase II NASH-CX - Top-Line

Results Yes

15% (9% Below Avg.)

13% (11% Below Avg.)

12/20/2017 Strongbridge Macrilen Endocrine PDUFA for NDA - Second Review Yes 91%

(2% Above Avg.) 100%

(Approved)

1/8/2018 Axovant Intepirdine Neurology Phase IIb HEADWAY-DLB - Top-

Line Results No

17% (Same As Avg.)

0% (Suspended)

1No previous LOA adjustment

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Azeliragon for Alzheimer's Disease (AD) (VTVT)

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

Catalyst(s)

Azeliragon vTv Therapeutics

Inc. N/A

Alzheimer's Disease (AD)

03/16/2018-03/31/2018

Phase III STEADFAST - Top-Line Results (Part A)

Phase Disease Group Drug Class

Group/Class Phase Success

Group/Class LOA (PTS)

BMT LOA Opinion

III Neurology NME 43.75% 34.15% Above

In late March 2018, vTv Therapeutics is expected to announce data from the first part of a Phase III trial known as STEADFAST that is investigating Azeliragon in patients with mild AD. Azeliragon is an inhibitor of the receptor for advanced glycation end products (RAGE), which has been implicated in amyloid-β aggregation, tau fibril formation and chronic inflammation. Azeliragon was being developed by Pfizer, but was dropped by the company in 2011 following a Phase IIb trial in which safety issues led to study of a 20 mg per day dose being halted. However, a post-hoc subgroup analysis of this trial suggested that 18-month treatment with a 5 mg per day dose of Azeliragon added to an acetylcholinesterase inhibitor and/or memantine slowed the rate of cognitive decline in patients with mild AD. The 5 mg daily dose is being studied in the STEADFAST trial, which is being conducted under a Special Protocol Assessment (SPA), and Azeliragon has received U.S. Food and Drug Administration fast-track designation. Positive data from the initial phase III read-out could be an exceptional event given the long history of failed late-stage trials of AD drug candidates.

Exparel for Anesthesia (PCRX)

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

Catalyst(s)

Exparel Pacira

Pharmaceuticals, Inc. Vectura Anesthesia

02/12/2018-02/13/2018

FDA Advisory Panel Brief

Phase Disease Group Drug Class Group/Class

Phase Success Group/Class

LOA (PTS) BMT LOA Opinion

NDA Neurology NME 82.19% 70.00% Above

Pacira Pharmaceuticals’ Exparel (bupivacaine liposome injectable suspension) is a novel long-acting, sustained release formulation of bupivacaine HCl encapsulated in DepoFoam, the company's proprietary liposome drug delivery technology. Exparel was first approved by the U.S. Food and Drug Administration (FDA) in October 2011 for administration into the surgical site to produce postsurgical analgesia.

In May 2014, Pacira announced the submission of a supplemental New Drug Application (sNDA) to the U.S. FDA seeking expansion of the label to include administration via nerve block for prolonged regional analgesia. The sNDA was based on positive data from a Phase II/III study assessing the safety and efficacy of Exparel in femoral nerve block for total knee arthroplasty (TKA), and additional safety data from a Phase III study of Exparel used to perform an intercostal nerve block for thoracotomy. The FDA issued a

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complete response letter in March 2015 requesting an additional clinical trial to establish the efficacy of Exparel in an additional clinical setting beyond femoral nerve block for TKA. The FDA also requested a study following safety outcomes through the time to reach maximum concentration of Exparel.

In October 2017 Pacira announced that the FDA has accepted its resubmitted sNDA which includes new data from a Phase III study (C326) of Exparel in femoral nerve block for TKA (lower extremity) and a Phase III study (C327) of Exparel in brachial plexus block for shoulder surgeries (upper extremity). On November 14, 2017, the Anesthetic and Analgesic Drug Products Advisory Committee announced they will convene to discuss the sNDA and make recommendations on its safety and effectiveness. The meeting is tentatively scheduled for February 14-15, 2018, an unusually long day and a half meeting.

Topline results from C326 and C327 revealed that while Exparel met key primary and secondary endpoints in the shoulder surgery study (C327), Exparel did not demonstrate statistical significance in the Phase III femoral nerve block study (C326) due to a significant deviation from protocol identified at a single center. Although Exparel did previously meet the primary endpoint in an earlier Phase II/III femoral nerve block study, it does not bode well for Pacira’s claim that Exparel is broadly effective within the nerve block setting. Given the mixed results, the upcoming FDA Briefing Documents and subsequently, the advisory committee meeting, will delineate any potential concerns Exparel and Pacira Pharmaceuticals may face from the FDA. Pending voting outcome and approval decision, Exparel could potentially offer a new option for non-opioid, non-NSAIDs analgesics.

VB-111 for Brain Cancer (Malignant Glioma; AA and GBM) (VBLT)

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

Catalyst(s)

VB-111 VBL

Therapeutics NanoCarrier

Brain Cancer (Malignant Glioma; AA and GBM)

01/01/2018-03/31/2018

Phase III rGBM - Top-Line Results

Phase Disease Group Drug Class Group/Class

Phase Success Group/Class

LOA (PTS) BMT LOA Opinion

III Oncology Biologic 44.09% 41.32% Above

Top-line results from GLOBE, a pivotal Phase III study of VBL’s ofranergene obadenovec (VB-111) combined with bevacizumab in patients with recurrent glioblastoma multiforme (rGBM) are expected in the first quarter of 2018. VB-111 is a non-integrating, non-replicating, Adeno 5 vector engineered to express a pro-apoptotic Fas-chimera transgene in angiogenic blood vessels using VBL’s proprietary angiogenesis-specific promoter.

Patients with GBM have a poor prognosis, with only 3–5% of patients surviving for more than 3 years. In patients with recurrent disease, the median survival is between 3 to 6 months with bevacizumab treatment. In a non-randomized, open label Phase I/II study in patients with rGBM, the combination of VB-111 with bevacizumab following disease progression doubled median overall survival to 16 months compared to 8 months for bevacizumab alone (p=0.05).

VB-111 has received orphan drug designation for malignant glioma in the United States and Europe and was granted fast-track designation by the FDA for rGBM based on the promising survival results. GLOBE is

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being conducted pursuant to a Special Protocol Assessment (SPA) agreement from the FDA and pending positive results, the company may be able to file for approval based on this single study given the high unmet medical need in rGBM. Development of VB-111 in other solid tumor indications is ongoing with a pivotal Phase III trial initiated December 2017 evaluating VB-111 in combination with paclitaxel in ovarian cancer and an exploratory Phase I/II study in combination with a checkpoint inhibitor expected to initiate in non-small cell lung cancer in the first quarter of 2018.

Truxima for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL (TEVA)

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

Catalyst(s)

Truxima Teva

Pharmaceuticals Industries Ltd.

Celltrion; Nippon Kayaku

Chronic Lymphocytic Leukemia (CLL)/Small

Cell Lymphocytic Lymphoma (SLL) - NHL

02/15/2018-03/15/2018

BsUFA for 351(k) BLA - First Review

Phase Disease Group Drug Class Group/Class

Phase Success Group/Class

LOA (PTS) BMT LOA Opinion

BLA Oncology Biosimilar 100.00% 84.00% Average

On June 29, 2018, Teva and Celltrion announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for Truxima, a proposed monoclonal antibody biosimilar to Rituxan (rituximab), which is used to treat patients with non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis and microscopic polyangiitis.

The BLA for CT-P10 has been accepted for filing by the FDA for standard review, with FDA Regulatory Action expected between February 15, 2018 and March 15, 2018. The BLA compares Truxima and rituximab in terms of efficacy, safety, immunogenicity, pharmacodynamics and pharmacokinetics. These trials were conducted in over 600 patients and include up to 104 weeks of data.

In October 2016, Celltrion and Teva entered into an exclusive partnership to commercialize Truxima and a trastuzumab biosimilar, CT-P6 in the U.S. and Canada. Under the terms of the agreement, Celltrion has responsibility for completing all clinical development and regulatory activities while Teva is responsible for all commercial activities in the U.S. and Canada, pending regulatory approvals for both products.

In February 2017, the European Medicines Agency (EMA) approved Celltrion's Truxima for the treatment of NHL, CLL, Rheumatoid Arthritis and Granulomatosis with polyangiitis and microscopic polyangiitis. Celltrion consequently launched the product and started official sales of Truxima in the EU in April 2017.

Presently, Truxima is positioned to potentially be the first US approved Rituxan biosimilar. If approved, it could represent the entry of Teva and Celltrion into the US Rituxan market, pending the expiration of Rituxan’s primary patent protection in 2018.

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