Diplomat Specialty Pipeline Report

Q2 2020

Forward-Looking Statements This document contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements give current expectations or forecasts of future events or our future financial or operating performance. The forward-looking statements contained in this document are based on management’s good-faith belief and reasonable judgment based on current information, and these statements are qualified by important risks and uncertainties, many of which are beyond our control, that could cause our actual results to differ materially from those forecasted or indicated by such forward-looking statements. These risks include the number of patients prescribed such drug(s) currently and in the future, patient’s adherence to such drug(s), the number of distributors on panel and our relative distribution share, the timing of drug sales, the cost of such drug(s) and reimbursement rates by payers, drug competition, and the factors set forth in “Risk Factors” in Diplomat’s Annual Report on Form 10-K for the year ended Dec. 31, 2017, and in subsequent reports filed with or furnished to the Securities and Exchange Commission. Except as may be required by any applicable law, Diplomat assumes no obligation to publicly update such forward-looking statements, which are made as of the date hereof or the earlier date specified herein, whether as a result of new information, future developments, or otherwise.

Industry & Market Data Certain information in this presentation concerning our industry and the markets in which we operate is derived from publicly available information released by third-party sources, including independent industry and research organizations, and management estimates. Management estimates are derived from publicly available information released by independent industry and research analysts and other third-party sources, as well as data from our internal research, and are based on assumptions made by us upon reviewing such data and our knowledge of such industry and markets, which we believe to be reasonable. We believe the data from these third-party sources is reliable. In addition, projections, assumptions, and estimates of the future performance of the industry in which we operate and our future performance are necessarily subject to uncertainty and risk due to a variety of factors, as discussed in Diplomat’s reports filed with the Securities and Exchange Commission. These and other factors could cause results to differ materially from those expressed in the estimates made by these third-party sources.

Diplomat Specialty Pipeline Report | Q2 2020 | 2

Table of Contents

Preface Recent Approvals Ayvakit™ (avapritinib) Tepezza™ (teprotumumab-trbw) Tazverik™ (tazemetostat) Vyepti™ (eptinezumab-jjmr) Sarclisa® (isatuximab-irfc) Isturisa® (osilodrostat) Zeposia® (ozanimod)

Top Agents to Anticipate Risdiplam Pemigatinib Sacituzumab govitecan-hziy Inebilizumab Fintepla® (fenfluramine) Selumetinib Filgotinib

Recent Specialty Drug Approvals Late-Stage Pipeline Agents New Indications, Combinations & Formulations Glossary References

Diplomat Specialty Pipeline Report | Q2 2020 | 3

Preface1,2,3 ​ With thousands of clinical trials underway and only a fraction of agents reaching a rapidly evolving marketplace, strategic planning for specialty pharmaceuticals can be a challenging and daunting task. In our commitment to provide timely and valuable specialty medication news to our partners, Diplomat is pleased to provide you our Specialty Pipeline Report. This quarterly report, dedicated exclusively to specialty ​ products, provides insight on upcoming and recently approved medications expected to impact the specialty landscape and your business.

Each Specialty Pipeline Report begins by detailing selected Recent Approvals that have ​ ​ ​ ​ been approved by the U.S. Food and Drug Administration (FDA) during the previous quarter. The following section, Top Agents to Anticipate, targets specific promising ​ ​ specialty medications expected to have significant therapeutic and market impact after approval. The Recent Specialty Drug Approvals table is an overview of all specialty ​ ​ drugs approved in the previous quarter. A more comprehensive review of the pipeline is provided in the Late-Stage Pipeline Agents table, which includes agents in later stages ​ ​ of Phase 3 trials or those for which new drug applications (NDAs) or biologic license applications (BLAs) have been filed with the FDA. This table includes products expected to have an FDA approval decision within the year. The New Indications, Combinations & Formulations table provides information regarding currently approved specialty medications that are seeking approval for new indications, combinations, or formulations.

In each section, pipeline agents are presented with a description of an upcoming event, which is generally a Prescription Drug User Fee Act (PDUFA) date. PDUFA authorizes the FDA to collect fees from drug sponsors, thus generating funding to expedite the drug review and approval process. This establishes two tiers (standard versus priority) from which the FDA sets a target date, or PDUFA date, for its review.

Sales projections at the time of printing are reported in U.S. dollars (millions); global data may be substituted when U.S. information is unavailable.

The statuses below appear throughout the report and represent the medication’s classification within the FDA approval process.

The Accelerated Approval pathway permits earlier approval of therapies developed for ​ ​ serious conditions with a currently unmet medical need. This designation may be based on surrogate endpoints, with post-marketing trials to verify clinical outcomes.

Breakthrough Therapy designation provides for expedited development and review of ​ drugs that treat serious or life-threatening conditions and demonstrate impressive preliminary clinical data. Breakthrough Therapy designation holds the same advantages as Fast Track designation with the addition of intensive FDA guidance for efficient drug development.

Diplomat Specialty Pipeline Report | Q2 2020 | 4

The Fast Track designation is designed to increase patient access to critical drugs that ​ ​ treat serious conditions with a currently unmet medical need by facilitating a quick and efficient development and review process. Many Fast Track medications also receive a priority review.

Orphan drug status is granted to drugs and biologics which are intended to diagnose, ​ prevent, or treat rare diseases and disorders that affect less than 200,000 people in the United States. A product with a greater target population may also qualify if the sponsor is not expected to recover its development and marketing costs.

A Priority Review designation is granted to drugs that are considered major therapeutic ​ ​ advancements or those used to treat conditions currently lacking adequate therapy. This status shortens the goal for FDA review from 10 months to six.

Diplomat Specialty Pipeline Report | Q2 2020 | 5

Recent Approvals Ayvakit™ (avapritinib) 4,5,6 ​ Oncology

Indication Treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.

Approval Date January 9, 2020

Class Tyrosine kinase inhibitor (TKI)

Manufacturer Blueprint Medicines

Supply Method 100, 200, and 300 mg tablets

Storage 68-77°F (20-25°C) with excursions permitted from 59-86°F (15-30°C)

Population Approximately 5,000 new diagnoses of GIST are made in the United States yearly with platelet-derived growth factor alpha (PDGFRA) mutation present in approximately 10% of cases.

Clinical Trial Briefing The efficacy of Ayvakit™ was evaluated in a multi-center, single-arm, open-label clinical trial that included 81 patients with PDGFRA exon 18 or PDGFRA D842V genetic mutations. During the study, Ayvakit™ 300 or 400 mg was administered daily with a median duration of follow up of 10.6 months. Endpoints evaluated included overall response rate (ORR) and duration of response (DOR). NR - Not reached.

PDGFRA exon 18 PDGFRA D842V

ORR (95% CI) 84% (69%, 93%); N=43 89% (75%, 97%); N=38

Complete Response 7% 8%

Partial Response 77% 82%

DOR Median in months NR (1.9+, 20.3+); N=36 NR (1.9+, 20.3+); N=34

Patients with DOR ≥6 months 61% 59%

Diplomat Specialty Pipeline Report | Q2 2020 | 6

Dosing The recommended dosage is 300 mg taken orally once daily on an empty stomach (at least 1 hour before or at least 2 hours after a meal). Treatment should continue until the occurrence of disease progression or unacceptable toxicity. Dose reductions and modifications may be made based on adverse reactions and drug interactions. Please see the prescribing information for details.

Safety Adverse Events (>20%): edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased ​ appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness

Warnings and Precautions: intracranial hemorrhage, central nervous system effects, and embryo-fetal ​ toxicity

Other Agents in Therapeutic Area: Ayvakit™ is the first product to be FDA-approved for GIST specifically in ​ patients with PDGFRA exon 18 genetic mutation

Ayvakit™ Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Recent Approvals Tepezza™ (teprotumumab-trbw) 4,7,8 ​ Rare Disease

Indication Treatment of thyroid eye disease (TED).

Approval Date January 21, 2020

Class Insulin-like growth factor-1 receptor inhibitor

Manufacturer Horizon Therapeutics

Supply Method Single-dose vials containing 500 mg lyophilized powder for reconstitution

Diplomat Specialty Pipeline Report | Q2 2020 | 7

Storage 36-46°F (2-8°C). Store in the original carton until the time of use to protect from light. Do not freeze.

Population Approximately 15,000 to 20,000 diagnoses of TED yearly in the U.S.

Clinical Trial Briefing Tepezza™ was evaluated in two randomized, double-blind, placebo-controlled studies composed of 171 patients with TED. During the studies, patients received Tepezza™ (10 mg/kg at the initial infusion and 20 mg/kg for the following 7 infusions) or placebo every 3 weeks for 8 total infusions. Endpoints evaluated included proptosis responder rate at week 24 and average change in proptosis from baseline through week 24.

Study 1 Study 2

Teprotumumab Placebo Difference Teprotumumab Placebo Difference (N=42) (N=45) (95% CI) (N=41) (N=42) (95% CI)

Proptosis 71% 20% 51% (33, 83% 10% 73% (59, 88) responder rate 69) (week 24)

Average -2.5 -0.2 -2.3 (-2.8, -2.8 -0.5 -2.3 (-2.8, -1.8) proptosis -1.8) change from baseline through week 24 (mm)

Dosing The recommended dose of Tepezza™ is 10 mg/kg for the first dose, then 20 mg/kg every 3 weeks for 7 additional infusions.

Safety Adverse Events (≥5%): muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing ​ impairment, dry skin, dysgeusia, and headache

Warnings and Precautions: infusion reactions, exacerbation of preexisting inflammatory bowel disease ​ (IBD), and hyperglycemia

Other Agents in Therapeutic Area: Tepezza™ is the first product to be FDA-approved for thyroid eye ​ disease

Tepezza™ Sales Forecast

Diplomat Specialty Pipeline Report | Q2 2020 | 8

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Recent Approvals Tazverik™ (tazemetostat) 4,9,10 ​ Oncology

Indication Treatment of metastatic or locally advanced epithelioid sarcoma (ES) in patients ≥16 years of age who are not eligible for complete resection. This indication was granted under the accelerated approval program based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Approval Date January 23, 2020

Class Methyltransferase inhibitor

Manufacturer Epizyme

Supply Method 200 mg tablets

Storage Tazverik™ should not be stored above 86°F (30°C).

Population ES represent less than 1% of all soft tissue sarcomas, with most reported cases occurring in young men (2:1 male to female ratio) aged 10-45 years (median age 27 years).

Clinical Trial Briefing The efficacy of Tazverik™ was studied in an open-label, single-arm cohort of a multi-center study, composed of 62 patients with metastatic or locally advanced ES. Patients received Tazverik™ 800 mg twice daily, and tumor response assessments were conducted every 8 weeks. The median duration of follow up was 14 months. The major efficacy endpoints were confirmed overall response rate (ORR) and duration of response (DOR).

Diplomat Specialty Pipeline Report | Q2 2020 | 9

Endpoint Tazverik™ (N=62)

ORR (95% CI)* 15% (7%, 26%)

Complete Response 1.6%

Partial Response 13%

Duration of Response

% with Duration ≥ 6 months 67%

Range (months) 3.7, 24.5+

CI: confidence interval | *Time to response ranged from 2.4 to 18.4 months

Dosing The recommended dose of Tazverik™ is 800 mg taken by mouth twice daily with or without food until disease progression or unacceptable toxicity.

Safety Adverse Events (≥20%): pain, fatigue, nausea, decreased appetite, vomiting, and constipation ​ ​ ​

Warnings and Precautions: secondary malignancies and embryo-fetal toxicity ​

Other Agents in Therapeutic Area Tazverik™ is the first product to be FDA-approved for ES.

Tazverik™ Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Diplomat Specialty Pipeline Report | Q2 2020 | 10

Recent Approvals Vyepti™ (eptinezumab-jjmr) 4,11,12 ​ Migraine

Indication Preventive treatment of migraine in adults.

Approval Date February 21, 2020

Class Calcitonin gene-related peptide (CGRP) antagonist

Manufacturer Lundbeck Seattle BioPharmaceuticals

Supply Method Single-dose vials containing 100 mg/dL of Vyepti™ solution

Storage Prior to dilution, Vyepti™ should be stored at 36-46°F (2-8°C) in the original carton to protect from light until the time of use. Do not freeze or shake.

After dilution, Vyepti™ solution should be stored at 68-77°F (20-25°C) and administered within 8 hours of mixing.

Population Approximately 39 million people experience migraine in the U.S.

Clinical Trial Briefing The efficacy of Vyepti™ was evaluated in two randomized, multicenter, placebo-controlled studies, that each included a 6-month double-blind portion. Study 1 included patients with episodic migraine while Study 2 was composed of patients with chronic migraine. During the studies, Vyepti™ (100 or 300 mg) or placebo was given every 3 months. The primary endpoint in both studies was the change from baseline in mean monthly migraine days (MMD) over months 1-3.

Study 1 Vyepti™ 100 mg Vyepti™ 300 mg Placebo (n=221) (n=222) (n=221)

Change from baseline in MMD, -3.9 -4.3 -3.2 months 1-3

Difference from placebo -0.7 -1.1

p-value 0.018 <0.001

Diplomat Specialty Pipeline Report | Q2 2020 | 11

Study 2 Vyepti™ 100 mg Vyepti™ 300 mg Placebo (n=356) (n=350) (n=366)

Change from baseline in MMD, -7.7 -8.2 -5.6 months 1-3

Difference from placebo -2.0 -2.6

p-value <0.001 <0.001

Dosing The recommended dose is 100 mg given by IV infusion every 3 months. Some patients may benefit from receiving 300 mg every 3 months. Please see the prescribing information for details regarding preparation and administration procedures.

Safety Adverse Events (≥2% overall and ≥2% more than placebo): nasopharyngitis and hypersensitivity ​

Warnings and Precautions: hypersensitivity reactions ​

Other Agents in Therapeutic Area (CGRP antagonists for migraine) Ajovy® (fremanezumab) Ubrelvy™ (ubrogepant) Aimovig® (erenumab) Emgality® (galcanezumab)

Vyepti™ Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Diplomat Specialty Pipeline Report | Q2 2020 | 12

Recent Approvals Sarclisa® (isatuximab-irfc) 4,13,14 ​ Oncology

Indication The combination of Sarclisa® + pomalidomide + dexamethasone is approved for the treatment of adult patients with multiple myeloma (MM) who have received ≥2 prior therapies including lenalidomide and a proteasome inhibitor.

Approval Date March 2, 2020

Class CD38-directed cytolytic antibody

Manufacturer Sanofi-Aventis U.S.

Supply Method Single dose vials containing 100 mg/5 mL or 500 mg/25 mL (20 mg/mL) of Sarclisa® solution

Storage Prior to mixing, Sarclisa® should be stored at 36-46°F (2-8°C) in the original carton to protect from light and should not be frozen or shaken.

After dilution, Sarclisa® should be used within 48 hours when stored at 36-46°F (2-8°C), and used within 8 hours when stored at room temperature (including infusion time).

Population In 2020, approximately 32,270 new cases of MM are expected to be diagnosed in the U.S.

Clinical Trial Briefing Sarclisa®, in combination with pomalidomide and low-dose dexamethasone, was evaluated in a multicenter, multinational, randomized, open-label, phase 3 study composed of patients with relapsed/ refractory MM who had received ≥2 prior therapies including lenalidomide and a proteasome inhibitor. The primary endpoint was progression-free survival (PFS) as assessed by an independent response committee. Additionally, overall response rate (ORR) was evaluated.

Diplomat Specialty Pipeline Report | Q2 2020 | 13

® Sarclisa ​ + pomalidomide + Pomalidomide + ​ dexamethasone (n=154) dexamethasone (n=153)

Median PFS, months (95% CI) 11.53 (8.94-13.9) 6.47 (4.47-8.28)

Hazard ratio (95% CI) 0.596 (0.44-0.81)

p-value 0.0010

ORR 60.4% (52.2-68.2%) 35.3 (27.8-43.4%)

p-value <0.0001

Dosing The recommended dose is 10 mg/kg, based on body weight, in combination with pomalidomide and dexamethasone. During the first 28-day cycle, Sarclisa® should be given weekly (days 1, 8, 15, and 22). For the second cycle and thereafter, Sarclisa® should be given every 2 weeks (days 1 and 15) of each 28-day cycle. Sarclisa® should be administered by a healthcare professional. To reduce the risk and severity of infusion-related reactions, premedication with the following agents is recommended: dexamethasone, acetaminophen, H2 antagonists, and diphenhydramine. Please see the prescribing information for preparation instructions and other details.

Safety Adverse Events (≥20%): neutropenia, infusion-related reactions, pneumonia, upper respiratory tract ​ infection, and diarrhea

Warnings and Precautions: infusion-related reactions, neutropenia, second primary malignancies, ​ laboratory test interference, and embryo-fetal toxicity

Other Agents in Therapeutic Area Darzalex® (daratumumab) Empliciti® (elotuzumab) Farydak® (panobinostat) Kyprolis® (carfilzomib) Ninlaro® (ixazomib) Pomalyst® (pomalidomide) Revlimid® (lenalidomide) Thalomid® (thalidomide) Velcade® (bortezomib) Xpovio™ (selinexor)

Diplomat Specialty Pipeline Report | Q2 2020 | 14

Sarclisa® Sales Forecast ​ ​

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Recent Approvals Isturisa® (osilodrostat) 4,15,16 ​ Rare Disease

Indication Treatment of adult patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative.

Approval Date March 6, 2020

Class Cortisol synthesis inhibitor

Manufacturer Novartis

Supply Method 1, 5, and 10 mg tablets

Storage 68-77°F (20-25°C) with excursions permitted from 59-86°F (15-30°C). Protect from moisture.

Population Approximately 8 cases of Cushing’s disease per 1 million people in the U.S.

Clinical Trial Briefing Isturisa® was evaluated in a 48-week, multicenter study that included four study periods: (1) dose titration, (2) maintenance treatment, (3) double-blind, placebo-controlled, randomized withdrawal (used for efficacy analysis), and (4) an additional open label treatment period. A total of 137 patients with Cushing’s syndrome began the first study period at an initial dose of 2 mg twice daily. Titration was based on individual patient median urine free cortisol (UFC), and was increased up to a maximum of 30 mg twice daily. The primary endpoint was the percentage of complete responders remaining on Isturisa® compared to those switching to placebo at the end of period 3 of the study (8 weeks). A complete responder was defined as achieving a UFC at or below the upper limit of normal at week 24 and not requiring an increase in dose level beyond what was established in the titration period. Complete response was attained in 86% (95% CI: 71, 95) of the Isturisa® group compared to 29% (95% CI: 15, 47) for placebo (p<0.001).

Diplomat Specialty Pipeline Report | Q2 2020 | 15

Dosing The recommended initial dose of Isturisa® is 2 mg orally twice daily and may be taken with or without food. Titrate dosing (no more frequently than every 2 weeks) based on cortisol change, individual tolerability, and improvement in signs/symptoms of Cushing’s disease. Please see the prescribing information for additional details.

Safety Adverse Events (≥20%): adrenal insufficiency, fatigue, nausea, headache, and edema ​

Warnings and Precautions: hypocortisolism, QTc prolongation, and elevation in adrenal hormone ​ precursors and androgens

Other Agents in Therapeutic Area Korlym® ( mifepristone) Signifor® (pasireotide diaspartate)

Isturisa® Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Recent Approvals Zeposia® (ozanimod) 4,17,18 ​ Multiple sclerosis

Indication Treatment of relapsing forms of multiple sclerosis (including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease) in adults.

Approval Date March 26, 2020

Class Sphingosine 1-receptor modulator

Manufacturer Bristol-Myers Squibb

Supply Method 0.23, 0.46, and 0.92 mg capsules

Diplomat Specialty Pipeline Report | Q2 2020 | 16

Storage 68-77°F (20-25°C) with excursions permitted from 59-86°F (15-30°C)

Population Approximately 1 million people in the U.S. have multiple sclerosis (MS)

Clinical Trial Briefing Zeposia® was evaluated in two randomized, double-blind, double dummy, parallel group, active comparator-controlled clinical trials composed of 1,769 total patients with relapsing forms of MS. After the titration period, patients received Zeposia® 0.92 mg once daily or Avonex® (interferon beta-1a) 30 mcg once weekly. Treatment continued for at least 1 year in Study 1 and for 2 years in Study 2. The primary endpoint of both studies was annualized relapse rate (ARR).

Study 1 Study 2

Zeposia® (n=447) Avonex® (n=448) Zeposia® (n=433) Avonex® (n=441)

ARR 0.181 0.35 0.172 0.276

ARR relative 48% (p<0.0001) 38% (p<0.0001) reduction

% of patient 78% 66% 76% 64% without relapse

Dosing Prior to the initiation of treatment with Zeposia® the following should be completed: complete blood count, cardiac evaluation, liver function tests, ophthalmic assessment, and evaluation of current and prior medications. The recommended dosage of Zeposia® is listed below. Zeposia® may be taken with or without food.

Days 1-4 0.23 mg once daily

Days 5-7 0.46 mg once daily

Day 8 and thereafter 0.92 mg once daily

Safety Adverse Events (≥4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, ​ ​ ​ urinary tract infection, back pain, and hypertension

Warnings and Precautions: infections, bradyarrhythmia and atrioventricular conduction delays, liver injury, ​ fetal risk, increased blood pressure, respiratory effects, and macular edema

Other Agents in Therapeutic Area: Aubagio® (teriflunomide) Avonex® (interferon beta-1a) Betaseron® (interferon beta-1b) Copaxone® (glatiramer acetate) Extavia® (interferon beta-1b)

Diplomat Specialty Pipeline Report | Q2 2020 | 17

Gilenya® (fingolimod) Glatopa® (glatiramer acetate) Lemtrada® (alemtuzumab) Mavenclad® (cladribine) Mayzent® (siponimod) Novantrone® (mitoxantrone) Ocrevus® (ocrelizumab) Plegridy® (peginterferon beta-1a) Rebif® (interferon beta-1a) Tecfidera® (dimethyl fumarate) Tysabri® (natalizumab) Vumerity™ (diroximel fumarate)

Zeposia® Sales Forecast

Diplomat Specialty Pipeline Report | Q2 2020 | 18

Top Agents to Anticipate Risdiplam 4,19 ​ Rare Diseases

Target Indication Spinal muscular atrophy (SMA), types 1, 2, and 3

Manufacturer Roche and PTC Therapeutics

Class Survival motor neuron-2 (SMN-2) splicing modifier

Route Oral

Alias RG-7916, RO-7034067

Population 10,000 to 25,000 patients in the U.S.

Status FDA filing accepted - Nov. 2019

Clinical Trial Briefing Risdiplam was evaluated for the treatment of SMA in the FIREFISH trial, a two-part, open-label study composed of infants ages 1-7 months with SMA, type 1. In patients who received the dose level selected for part 2 of the study (n=17), 41% were able to sit without support for ≥5 seconds, 59% had the ability to roll, 53% had upright head control, and 6% (1 patient) was able to stand, after 12 months of treatment.

Additionally, the SUNFISH trial included patients 2-25 years of age with SMA type 2 or 3. Motor Function Measure-32 (MFM32) was assessed after 12 months of treatment. An improvement of ≥3 points from baseline occurred in 58% of patients (n=43) compared to 7.6% for a natural history group (n=39).

Safety In the FIREFISH study, the most commonly observed adverse events were pyrexia (52%), upper respiratory tract infection (43%), diarrhea (29%), vomiting (24%), cough (24%), pneumonia (19%), and constipation (19%).

In part 1 of the SUNFISH study, the most commonly observed adverse events were pyrexia (41%), cough (33%), vomiting (29%), upper respiratory tract infections (26%), oropharyngeal pain (22%), and nasopharyngitis (20%).

Upcoming Event PDUFA - May 24, 2020

FDA Designation(s) Orphan, Fast Track, and Priority Review

Diplomat Specialty Pipeline Report | Q2 2020 | 19

Risdiplam Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Top Agents to Anticipate Pemigatinib 4,20,21 ​ Oncology

Target Indication Relapsed/refractory locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements.

Manufacturer Incyte

Class Fibroblast growth factor receptor (FGFR) inhibitor

Route Oral

Alias INCB-54828, IBI-375

Population Approximately 8,000 people develop cholangiocarcinoma yearly in the U.S.

Status FDA filing accepted - Nov. 2019

Clinical Trial Briefing Pemigatinib was evaluated in a phase 2, open label, single-arm study composed of patients with previously treated locally advanced or metastatic cholangiocarcinoma. Cohort A included patients with FGFR2 gene rearrangements/fusions. During the study, pemigatinib 13.5 mg was administered daily in cycles of 2 weeks on and 1 week off. The primary endpoint was objective response rate (ORR) in cohort A of the study. Secondary endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). At the data cutoff point, 146 patients were enrolled in the study.

Diplomat Specialty Pipeline Report | Q2 2020 | 20

Endpoint Pemigatinib (cohort A)

ORR (95% CI) 35.5% (26.5-45.4%)

DoR [median in months] (95% CI) 7.5 (5.7-14.5)

DCR (95% CI) 82% (74-89%)

PFS [median in months] (95% CI) 6.9 (6.2-9.6)

OS [median in months] (95% CI) 21.1 (14.8, not reached)

Safety The most commonly observed adverse events were hyperphosphatemia (60%), alopecia (49%), diarrhea (47%), fatigue (42%), nail toxicities (42%), and dysgeusia (40%). Discontinuation rate was 9%. Dose reductions were made for 14% of patients, and dose interruption due to adverse events occurred in 42% of patients.

Upcoming Event PDUFA - May 30, 2020

FDA Designation(s) Breakthrough, Orphan, and Priority Review

Pemigatinib Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Top Agents to Anticipate Sacituzumab govitecan-hziy 22,23 ​ Oncology

Target Indication Triple negative breast cancer after ≥2 previous treatments.

Manufacturer Immunomedics

Diplomat Specialty Pipeline Report | Q2 2020 | 21

Class Antibody drug conjugate

Route IV

Alias IMMU-132, Anti-Trop-2-SN, hRS7 SN-38, isactuzumab govitecan

Population Approximately 15-20% of all breast cancers are triple negative.

Status FDA filing accepted - Dec. 2019

Clinical Trial Briefing Sacituzumab govitecan-hziy was evaluated in a phase 1/2 single-group, multicenter trial that included 108 patients with metastatic triple-negative breast cancer who had received ≥2 prior therapies. During the study, patients received sacituzumab govitecan-hziy 10 mg/kg of body weight on days 1 and 8 of each 21 day cycle. Treatment continued until the occurrence of disease progression or unacceptable toxicity. Endpoints evaluated included objective response rate (ORR) [according to Response Evaluation Criteria in Solid Tumors, version 1.1], duration of response (DoR), clinical benefit rate (CBR) [complete or partial response or stable disease for ≥6 months], progression-free survival (PFS), and overall survival (OS).

ORR Median DoR CBR Median PFS OS

33.3% (95% CI 7.7 months (95% CI 45.4% 5.5 months (95% CI 13.0 months (95% CI 24.6-43.1) 4.9-10.8) 4.1-6.3) 11.2-13.7)

Safety The most commonly observed adverse events (any grade, ≥50%) for patients receiving sacituzumab govitecan-hziy included gastrointestinal disorders (94%), nausea (67%), neutropenia (64%), diarrhea (62%), fatigue and asthenia (55%), and anemia (50%).

Upcoming Event PDUFA - June 2, 2020

FDA Designation(s) Breakthrough, Fast Track, and Priority Review

Sacituzumab govitecan-hziy Sales Forecast ​ ​

Diplomat Specialty Pipeline Report | Q2 2020 | 22

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Top Agents to Anticipate Inebilizumab 4,24,25 ​ Rare Disease

Target Indication Neuromyelitis optica spectrum disorder (NMOSD)

Manufacturer AstraZeneca, Viela Bio

Class CD19 antagonist

Route IV, Sub-Q

Alias MEDI-551

Population The incidence of NMOSD is 0.053 to 0.40 patients per 100,000 people

Status FDA filing accepted - Aug. 2019

Clinical Trial Briefing Inebilizumab was evaluated in a double-blind, randomized, placebo-controlled phase 2/3 study composed of 230 patients with NMOSD. During the study, patients received inebilizumab 300 mg by IV infusion or placebo on days 1 and 15. The primary endpoint was the time to onset of NMOSD attack. The randomized control period was ended earlier than scheduled due to demonstrated efficacy. The percentage of patients experiencing an NMOSD attack was 12% for inebilizumab compared to 39% for placebo (p<0.0001).

Safety Adverse events were observed in 72% of patients receiving inebilizumab compared to 73% for placebo. Serious adverse events occurred in 5% of the inebilizumab group compared to 9% for placebo.

Upcoming Event PDUFA - June 11, 2020

FDA Designation(s) Breakthrough, Orphan

Diplomat Specialty Pipeline Report | Q2 2020 | 23

Inebilizumab Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Top Agents to Anticipate Fintepla® (fenfluramine) 4,26,27 ​ Rare Disease

Target Indication Seizures associated with Dravet syndrome

Manufacturer Zogenix

Class Mechanism of action is not fully understood. Some evidence of acting as a serotonin reuptake inhibitor.

Route Oral

Alias ZX-008, Brabafen

Population An estimated 1 in 15,700 individuals in the U.S. have Dravet syndrome

Status FDA filing accepted - Nov. 2019

Clinical Trial Briefing Fintepla® was evaluated in two double-blind, parallel-group, placebo-controlled phase 3 studies composed of 206 patients with Dravet syndrome. During the studies, patients received Fintepla® 0.2 to 0.7 mg/kg/day. Additional concomitant antiepileptic treatments were allowed, including stiripentol (STP), clobazam (CLB), valproate (VPA) and valproate + clobazam (CLB/VPA). The studies included a titration period of 2-3 weeks. Change in monthly convulsive seizure frequency (MCSF) from baseline was evaluated during the titration and maintenance phases of the studies.

Diplomat Specialty Pipeline Report | Q2 2020 | 24

Dose regimen Change in MCSF compared to placebo

Fintepla® - STP -62.3*

Fintepla® + STP -54.0*

Fintepla® - CLB -73.6*

Fintepla® + CLB -62.1*

Fintepla® - VPA -39.6 (p=0.012)

Fintepla® + VPA -74.5*

Fintepla® - CLB/VPA -51.6 (p=0.018)

Fintepla® + CLB/VPA -68.7* *p<0.001

Safety The most frequently observed adverse events (≥25%) were fatigue (39%), appetite suppression (37%), lethargy (34%), and somnolence (29%)

Upcoming Event PDUFA - June 25, 2020

FDA Designation(s) Orphan, Priority Review

Fintepla® Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Diplomat Specialty Pipeline Report | Q2 2020 | 25

Top Agents to Anticipate Selumetinib 4,28,29 ​ Rare Disease

Target Indication Neurofibromatosis, type 1 (NF 1)

Manufacturer AstraZeneca

Class MEK 1/2 inhibitor

Route Oral

Alias AZD-6244, ARRY-142886

Population 1 case of NF 1 per 3,000 to 4,000 people

Status FDA filing accepted - Nov. 2019

Clinical Trial Briefing Selumetinib was evaluated in an open label phase 2 study composed of 50 pediatric patients (2-18 years of 2 age). During the study, selumetinib 25 mg/m ​ was administered twice daily for a median of 19.5 cycles of ​ 28 days each. After 1 year of treatment, pain intensity, pain interference, strength, and range of motion scores improved compared to baseline (p<0.01). Additional outcomes are described below.

Endpoint Selumetinib

Median change in plexiform neurofibromas from -27.7% baseline

Best response (partial response) 72%

Stable disease 24%

Safety The most frequently occurring adverse events included nausea/vomiting, diarrhea, asymptomatic creatine kinase increase, acneiform rash, and paronychia.

Upcoming Event FDA decision expected - Q2 2020

FDA Designation(s) Breakthrough, Orphan, and Priority Review

Diplomat Specialty Pipeline Report | Q2 2020 | 26

Selumetinib Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Top Agents to Anticipate Filgotinib 4,30,31 ​ Immunology

Target Indication Rheumatoid arthritis (RA)

Manufacturer Gilead

Class Janus kinase 1 (JAK 1) inhibitor

Route Oral

Alias GLPG-0634, GSK-2586184, G-146034

Population 1.3 million people in the U.S. have RA

Status FDA filing completed - Dec. 2019

Clinical Trial Briefing Filgotinib was evaluated in three randomized, double-blind, placebo or active-controlled Phase 3 studies (FINCH 1, FINCH 2, and FINCH 3). The studies were composed of >3,000 total patients with RA who had a variety of previous experience with methotrexate (MTX) and other disease modifying anti-rheumatic drugs (DMARDs). During the studies, patients received filgotinib (100 or 200 mg daily), adalimumab (40 mg every 2 weeks), or placebo. Additionally, some patients received concomitant MTX. Endpoints evaluated included American College of Rheumatology (ACR) 20%, 50%, and 70%, Disease Activity Score C-Reactive Protein 28 (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and Modified total Sharp/van der Heijde (mTSS) scores. Results of the FINCH 3 study after 24 weeks of treatment are presented below.

Diplomat Specialty Pipeline Report | Q2 2020 | 27

Filgotinib 200 mg Filgotinib 100 mg Filgotinib 200 mg MTX (n=416) + MTX (n=416) + MTX (n=207) monotherapy (n=210)

ACR20 81.0*** 80.2* 78.1 71.4

ACR50 61.5*** 57.0** 58.1** 45.7

ACR70 43.8*** 40.1*** 40.0*** 26.0

DAS28 (CRP) <2.6 54.1*** 42.5*** 42.4*** 29.1

HAQ-DI change -0.94*** -0.90** -0.89* -0.79

mTSS change 0.20 0.22 -0.04** 0.52 *** p<0.001; * p<0.05; ** p<0.01 (filgotinib compared to MTX alone)

Safety In the FINCH 3 study, serious adverse events were observed in 4.1, 2.4, 4.8, and 2.9% of patients receiving filgotinib 200 mg + MTX, filgotinib 100 mg + MTX, filgotinib 200 mg monotherapy, and MTX alone, respectively. The most commonly observed adverse event was infection, particularly of the upper respiratory tract and nasopharyngitis.

Upcoming Event FDA decision expected in mid-2020

FDA Designation(s) Priority Review

Filgotinib Sales Forecast

BioPharm Insight: Accessed March 24, 2020 USDm: U.S. dollars, millions

Diplomat Specialty Pipeline Report | Q2 2020 | 28

Recent Specialty Drug Approvals 32 ​ DRUG NAME APPROVED DRUG CLASS / ROUTE APPROVAL DATE MANUFACTURER(S) INDICATION(S) MECHANISM

Oncology

Opdivo® (nivolumab) + PD-1 inhibitor, CTLA-4 Yervoy® (ipilimumab) Hepatocellular carcinoma IV Mar. 10, 2020 blocker Bristol-Myers Squibb

Sarclisa® (isatuximab-irfc) Relapsed/refractory Anti-CD38 antibody IV Mar. 2, 2020 Sanofi, ImmunoGen multiple myeloma

Nerlynx® (neratinib) HER2+ breast cancer* Tyrosine kinase inhibitor Oral Feb. 25, 2020 Puma

Mesothelioma, Pemfexy™ (pemetrexed) non-squamous, non-small Antimetabolite IV Feb. 7, 2020 Eagle cell lung cancer*

Tazverik™ (tazemetostat) Soft tissue sarcoma EZH2 inhibitor Oral Jan. 23, 2020 Epizyme

Gastrointestinal stromal Ayvakit™ (avapritinib) tumors (GIST) with Tyrosine kinase inhibitor Oral Jan. 9, 2020 Blueprint PDGFRA exon 18 genetic mutation

Keytruda® BCG-unresponsive, (pembrolizumab) high-risk, non-muscle PD-1 inhibitor IV Jan. 8, 2020 Merck invasive bladder cancer*

Rare Diseases

Chronic fibrosing Ofev® (nintedanib) interstitial lung disease Kinase inhibitor Oral Mar. 9, 2020 Boehringer Ingelheim with a progressive phenotype*

Isturisa® (osilodrostat) Aldosterone synthase Cushing’s disease Oral Mar. 6, 2020 Novartis inhibitor

Severe diarrhea/flushing associated with metastatic Bynfezia® (octreotide carcinoid tumors, acetate) Somatostatin analog Sub-Q Jan. 28, 2020 acromegaly, diarrhea Sun associated with vasoactive intestinal peptide tumors*

Tepezza™ Insulin-like growth factor-1 (teprotumumab-trbw) Thyroid eye disease IV Jan. 21, 2020 receptor antagonist Roche, Horizon

Other Conditions

Zeposia® (ozanimod) Relapsing forms of multiple Sphingosine 1-phosphate Oral Mar. 25, 2020 Bristol-Myers Squibb sclerosis receptor modulator

Epclusa® (sofosbuvir, NS5A inhibitor, nucleotide Hepatitis C in pediatric velpatasvir) NS5B polymerase Oral Mar. 19, 2020 patients* Gilead inhibitor

Symtuza™ (darunavir, cobicistat, emtricitabine, Protease inhibitor, CYP3A HIV in pediatric patients* Oral Mar. 2, 2020 tenofovir alafenamide) inhibitor, NRTI Gilead, Janssen

Diplomat Specialty Pipeline Report | Q2 2020 | 29

Nurtec™ ODT (rimegepant) Acute treatment of Bristol-Myers Squibb, CGRP inhibitor Oral Feb. 27, 2020 migraine Biohaven

Vyepti™ (eptinezumab-jjmr) Prevention of migraine CGRP inhibitor IV Feb. 21, 2020 Lundbeck

Palforzia™ (peanut allergen powder-dnfp) Peanut allergy Allergen immunotherapy Oral Jan. 31, 2020 Aimmune

*New formulation, new combination, or expanded indication.

4,32 Late-Stage Pipeline Agents ​ DRUG NAME PROPOSED DRUG CLASS / ROUTE UPCOMING EVENT MANUFACTURER(S) INDICATION(S) MECHANISM

Oncology

FP-001 (leuprolide Prostate cancer as GnRH agonist Sub-Q FDA decision: Early 2020 mesylate) palliative care Foresee

Mitomycin-C Urothelial cancer DNA synthesis antagonist Intravesical PDUFA: Apr. 18, 2020 Urogen

Pemigatinib Cholangiocarcinoma FGFR inhibitor Oral PDUFA: May 30, 2020 Incyte

Sacituzumab Triple negative breast TROP-2 inhibitor IV PDUFA: Jun. 2, 2020 govitecan-hziy cancer Immunomedics

Margetuximab Her2+ breast cancer Fc-domain optimized IgG IV PDUFA: Jun. 19, 2020 Macrogenics monoclonal antibody

Selumetinib Neurofibromatosis, type 1 MEK kinase inhibitor Oral FDA decision: Mid-2020 Mesoblast

Belantamab mafodotin Multiple myeloma Anti-B-cell maturation IV PDUFA: Jul. 21, 2020 GlaxoSmithKline antigen

Capmatinib Non-small cell lung cancer C-met inhibitor Oral Estimated PDUFA: Aug. Novartis with MET exon 14 skipping 2020 mutation

KTE-X19 Mantle cell lymphoma CAR-T IV PDUFA: Aug. 10, 2020 Gilead, Kite

Ripretinib Gastrointestinal stromal CD117 and PDGF-A Oral PDUFA: Aug. 13, 2020 Deciphera tumors (GIST) inhibitor

Lurbinectedin Small cell lung cancer RNA polymerase inhibitor IV PDUFA: Aug. 16, 2020 PharmaMar

Lisocabtagene maraleucel Large B-cell lymphoma CAR-T IV PDUFA: Aug. 17, 2020 (JCAR017) Juno, Bristol-Myers Squibb

Tucatinib HER2+ breast cancer Tyrosine kinase inhibitor Oral PDUFA: Aug. 20, 2020 Seattle Genetics

Tafasitamab Diffuse large B-cell CD-19 inhibitor IV PDUFA: Aug. 30, 2020 Morphosys lymphoma

Selpercatinib RET+ non-small cell lung RET kinase inhibitor Oral FDA decision: Q3 2020 Eli Lilly, Loxo cancer, RET+ thyroid

Diplomat Specialty Pipeline Report | Q2 2020 | 30

cancer

Vicinium Non-muscle invasive Epithelial cell adhesion Intravesical Estimated PDUFA: Oct. 9, Sesen Bio bladder cancer molecule binder 2020

Rolontis® (eflapegrastim) Chemotherapy-induced G-CSF Sub-Q PDUFA: Oct. 24, 2020 Spectrum neutropenia

Naxitamab Neuroblastoma 3F8 bispecific antibody, IV FDA decision: Mid/late Y-Mabs GD2 antagonist 2020

Umbralisib Marginal zone lymphoma PI3K inhibitor Oral FDA decision: Q4 2020 TG Therapeutics or follicular lymphoma

Rare Diseases

Bronchitol® Cystic fibrosis and Chloride channel regulator Inhalant FDA decision: Early 2020 (mannitol) bronchiectasis Pharmaxis, Chiesi

Risdiplam Spinal muscular atrophy SMN2 modulator Oral PDUFA: May 24, 2020 PTC

Trevyent® Pulmonary arterial Prostacyclin analogue Sub-Q PDUFA: Apr. 27, 2020 (treprostinil) hypertension United

Fosdenopterin Molybdenum cofactor Cyclic pyranopterin IV PDUFA: Jun. 3, 2020 BridgeBio deficiency, type A monophosphate

Inebilizumab Neuromyelitis optica CD19 antagonist IV PDUFA: Jun. 11, 2020 AstraZeneca

Fintepla® (fenfluramine) Dravet syndrome Serotonin reuptake Oral PDUFA: Jun. 25, 2020 Zogenix inhibitor

Mycapssa™ (octreotide) Acromegaly Somatostatin analog Oral PDUFA: Jun. 26, 2020 Chiasma

Triheptanoin Long chain fatty acid Triglyceride Oral PDUFA: Jul. 31, 2020 Ultragenyx oxidation disorders

Satralizumab Neuromyelitis optica IL-6 inhibitor Sub-Q PDUFA: Aug. 2020 Chugai, Roche

Valoctocogene Hemophilia A Gene therapy IV PDUFA: Aug. 21, 2020 roxaparvovec BioMarin

Narsoplimab Hematopoietic stem-cell MASP-2 inhibitor Sub-Q PDUFA: Aug. 28, 2020 Omeros transplant-associated thrombotic microangiopathy

Terlipressin Hepatorenal syndrome, Vasopressin V1B and V2 IV PDUFA: Sep. 2020 Mallinkrodt type 1 receptor agonist

Lonafarnib Progeria and progeroid Farnesyltransferase Oral Estimated PDUFA: Oct. 16, Eiger laminopathies inhibitor 2020

JZP-258 Narcolepsy Acts on GABA B receptors Oral FDA decision: Q3 2020 Jazz

Berotralstat Hereditary angioedema Kallikrein inhibitor Oral PDUFA: Dec. 3, 2020

Diplomat Specialty Pipeline Report | Q2 2020 | 31

BioCryst (HAE)

Viltolarsen Duchenne muscular Antisense oligonucleotide IV FDA decision: Q4 2020 NS Pharma dystrophy

Lumasiran Primary hyperoxaluria, RNA interference targeting Sub-Q FDA decision: Q4 2020 Alnylam type 1 glycolate oxidase

Immunology & Multiple Sclerosis

Bafiertam™ (monomethyl Relapsing forms of Nrf2 activator Oral PDUFA: Jun. 2020 fumarate) multiple sclerosis Banner

Filgotinib Rheumatoid arthritis JAK inhibitor Oral FDA decision: Mid-2020 Galapagos, Gilead

Ponesimod Relapsing forms of S1P1 agonist Oral FDA decision: Q1 2021 Actelion multiple sclerosis

Voclosporin Lupus nephritis Calcineurin inhibitor Oral FDA decision: Q1 2021 Aurinia

Other Conditions

Leronlimab HIV CCR5 antagonist Sub-Q FDA decision: Q2 2020 Cytodyn

Viaskin peanut Peanut allergy Epicutaneous Topical PDUFA: Aug. 5, 2020 DBV Technologies immunotherapy

Remestemcel-L Graft vs host disease Mesenchymal stem cell IV FDA decision: Mid/late Mesoblast formulation 2020

Fostemsavir HIV Attachment inhibitor Oral FDA decision: Q4 2020 Bristol-Myers Squibb

Roxadustat Anemia associated with HIF-PH inhibitor Oral PDUFA: Dec. 20, 2020 AstraZeneca, Fibrogen chronic kidney disease

Remune (HIV-1 HIV Vaccine IM FDA decision: Q4 2020 immunogen) Immune Response BioPharma

PDUFA listed when available; estimated PDUFA is based on the FDA filing date; “FDA decision” is used when no exact PDUFA or filing date can be located.

Diplomat Specialty Pipeline Report | Q2 2020 | 32

Potential New Indications, Combinations & Formulations4,32 ​ DRUG NAME CURRENT PROPOSED EXPANDED ROUTE UPCOMING EVENT MANUFACTURER(S) INDICATION(S) INDICATION

Oncology

Imbruvica® (ibrutinib) + Imbruvica - CLL/SLL in Previously untreated CLL/SLL Oral + IV FDA decision: Early 2020 rituximab adults as monotherapy, in younger patients as a Janssen, Pharmacyclics multiple additional combination therapy indications

Braftovi® (encorafenib) + Melanoma with Colorectal cancer with Oral + IV PDUFA: Apr. 2020 cetuximab BRAFV600E or V600K BRAFV600E mutation Array mutation in combination with Mektovi® (binimetinib)

Reblozyl® (luspatercept-aamt) Anemia associated with Myelodysplastic syndromes Sub-Q PDUFA: Apr. 4, 2020 Acceleron, Celgene beta thalassemia

Ayvakit™ (avapritinib) Gastrointestinal stromal GIST in a 4th line setting Oral PDUFA: May 15, 2020 Blueprint tumors (GIST) with regardless of mutation PDGFRA exon 18 mutation

Rubraca® (rucaparib) Epithelial ovarian, Metastatic Oral PDUFA: May 15, 2020 Clovis fallopian tube, or primary castration-resistant prostate peritoneal cancer cancer with BRCA 1/2 mutation

Tazverik™ (tazemetostat) Epithelioid sarcoma Follicular lymphoma Oral PDUFA: Jun. 18, 2020 Epizyme

Alunbrig® (brigatinib) ALK+ non-small cell lung ALK+ non-small cell lung Oral PDUFA: Jun. 23, 2020 Ariad, Takeda cancer, 2nd line setting cancer, 1st line setting

Xpovio® (selinexor) Multiple myeloma Diffuse large B-cell Oral PDUFA: Jun. 23, 2020 Karyopharm lymphoma

Lynparza® (olaparib) Ovarian, breast, and HRR+ prostate cancer Oral FDA decision: Q2 2020 AstraZeneca pancreatic cancers

Zejula® (niraparib) Epithelial ovarian, Epithelial ovarian, fallopian Oral FDA decision: Mid-2020 Tesaro fallopian tube, or primary tube, or primary peritoneal peritoneal cancer, after cancer, 1st line setting previous treatment

Darzalex® (daratumumab) Multiple myeloma New formulation Sub-Q FDA decision: Q3 2020 Janssen

ASTX727 (decitabine + Myelodysplastic New Oral Estimated PDUFA: Aug. cedazurine) syndrome and chronic formulation/combination 2020 Astex myelomonocytic leukemia

Nurtec™ (riluzole) Amyotrophic lateral New formulation Oral film FDA decision: Mid/late Biohaven sclerosis 2020

Herceptin® (trastuzumab) + HER2+ breast cancer New formulation Sub-Q PDUFA: Oct. 18, 2020 Perjeta® (pertuzumab) Genentech/Roche

Rare Disease

Crysvita® (burosumab-twza) X-linked Osteomalacia Sub-Q PDUFA: Jun. 18, 2020

Diplomat Specialty Pipeline Report | Q2 2020 | 33

Ultragenyx hypophosphatemia

Epidiolex® (cannabidiol) Lennox-Gastaut Tuberous sclerosis complex Oral FDA decision: Q4 2020 GW Pharma syndrome, Dravet syndrome

Immunology

Cosentyx® (secukinumab) Psoriasis, psoriatic Axial spondyloarthritis Sub-Q FDA decision: Q2 2020 Novartis arthritis, ankylosing spondylitis

Stelara® (ustekinumab) Psoriasis, psoriatic Psoriasis in younger pediatric Sub-Q + IV PDUFA: Aug. 2020 Janssen arthritis, Crohn’s disease, patients ulcerative colitis

Tremfya™ (guselkumab) Psoriasis Psoriatic arthritis Sub-Q PDUFA: Jul. 2020 Janssen, Morphosys

Other Conditions

Dupixent® (dupilumab) Atopic dermatitis in Atopic dermatitis in patients Sub-Q PDUFA: May 26, 2020 Genzyme, Sanofi patients ≥12 years old, 6-11 years old asthma, nasal polyposis

Arzerra® (ofatumumab) Chronic lymphocytic Relapsing forms of multiple CLL: IV PDUFA: Jun. 20, 2020 Novartis leukemia (CLL) sclerosis (MS) MS: Sub-Q

Ocaliva® (obeticholic acid) Primary biliary Non-alcoholic steatohepatitis Oral FDA decision: Jun. 26, Intercept cholangitis/primary biliary 2020 cirrhosis

Rilpivirine + cabotegravir HIV-1 infection, daily oral HIV-1 infection, long acting IM FDA decision: Mid/late Janssen, Viiv dose IM dose 2020

PDUFA listed when available; estimated PDUFA is based on the FDA filing date; “FDA decision” is used when no exact PDUFA or filing date can be located.

Diplomat Specialty Pipeline Report | Q2 2020 | 34

Glossary Accelerated Approval — Permits earlier approval of therapies developed for serious ​ conditions with a currently unmet medical need; this designation may be based on surrogate endpoints, with post-marketing trials to verify clinical outcomes. Adverse Event — Any undesirable experience associated with the use of a medical product in a patient. Black Box Warning — Appears on the label of a prescription medication to alert the ​ patient and health care provider about any important safety concerns, such as serious side effects or life-threatening risks. Breakthrough Therapy — Provides for expedited development and review of drugs that ​ treat serious or life-threatening conditions and demonstrate impressive preliminary clinical data; Breakthrough Therapy designation holds the same advantages as Fast Track designation with the addition of intensive FDA guidance for efficient drug development. Double-Blind Study — A clinical trial designed so that neither the participant nor the ​ researcher knows whether the treatment or a placebo has been administered. Fast Track — Designed to increase patient access to critical drugs that treat serious ​ conditions with a currently unmet medical need by facilitating a quick and efficient development and review process; many Fast Track medications also receive a priority review. Orphan Drug Status — Granted to drugs and biologics which are intended to diagnose, ​ prevent, or treat rare diseases and disorders that affect less than 200,000 people in the United States; a product with a greater target population may also qualify if the sponsor is not expected to recover its development and marketing costs. Placebo-Controlled Studies — A study in which the effect of a drug is compared with the ​ effect of a placebo (an inactive substance designed to resemble the drug). Priority Review — Granted to drugs that are considered major therapeutic advancements ​ or those used to treat conditions currently lacking adequate therapy; this status shortens the goal for FDA review from 10 months to six. Randomized Study — A study design that randomly assigns participants into an ​ experimental group or a control group; as the study is conducted, the only expected difference between the control and experimental groups in a randomized controlled trial (RCT) is the outcome variable being studied. REMS (Risk Evaluation and Mitigation Strategy) — A strategy to manage known or ​ potential serious risks associated with a drug or biologic product; REMS programs included medication guides, package inserts, and communication plans.

Diplomat Specialty Pipeline Report | Q2 2020 | 35

References

1. U.S. Food and Drug Administration, “Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review,” fda.gov/forpatients/approvals/fast/default.htm. 2. U.S. Food and Drug Administration, “Developing Products for Rare Diseases & Conditions,” fda.gov/forindustry/developingproductsforrarediseasesconditions/default.htm. 3. U.S. Food and Drug Administration, “Frequently Asked Questions: Breakthrough Therapies,” fda.gov/regulatoryinformation/lawsenforcedbyfda/significantamendmentstothefdcact/fdasia/ucm341027.ht m. 4. BioPharm Insight GlobalData, biopharminsight.com. Accessed March 2020. 5. Ayvakit™ (avapritinib) [prescribing information]. Cambridge, MA: Blueprint Medicines; January 2020. 6. National Institute of Health Genetics Home Reference. “Gastrointestinal stromal tumor”. https://ghr.nlm.nih.gov/condition/gastrointestinal-stromal-tumor 7. Tepezza™ (teprotumumab-trbw) [prescribing information]. Lake Forest, IL: Horizon Therapeutics; January 2020. 8. Smith T, Kahaly G, Ezra D, et al. “Teprotumumab for thyroid-associated ophthalmopathy”. N Engl J Med 2017; 376:1748-1761. May 4, 2017. 9. Tazverik™ (tazemetostat) [prescribing information]. Cambridge, MA: Epizyme, Inc.; January 2020. 10. Needs T, Fillman EP. “Cancer, Epithelioid Sarcoma”. StatPearls. June 22, 2019. https://www.ncbi.nlm.nih.gov/books/NBK532911/. ​ 11. Migraine Research Foundation. “About Migraine.” http://migraineresearchfoundation.org/about-migraine/migraine-facts/ 12. Vyepti™ [prescribing information] Bothell, WA: Lundbeck Seattle BioPharmaceuticals; February 2020. 13. American Cancer Society. “What is multiple myeloma”. https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html 14. Sarclisa® [prescribing information]. Bridgewater, NJ. Sanofi-Aventis U.S. March 2020. 15. Broder MS, Neary MP, Chang E, et al. “Incidence of Cushing’s syndrome and Cushing’s disease in commercially-insured patients <65 years old in the United States”. Pituitary. 2015 Jun;18(3):283-9. 16. Isturisa® [prescribing information]. Lebanon, NJ. Recordati Rare Disease, Inc; March 2020. 17. Zeposia® [prescribing information]. Summit, NJ. Celgene. March 2020. 18. National Multiple Sclerosis Society. “MS Prevalence”. https://www.nationalmssociety.org/About-the-Society/MS-Prevalence 19. PTC Therapeutics. “Data from pivotal FIREFISH and SUNFISH studies demonstrate clinical benefit of risdiplam in type 1, 2, & 3 spinal muscular atrophy patients.” http://ir.ptcbio.com/news-releases/news-release-details/data-pivotal-firefish-and-sunfish-studies-demonstrat e-clinical. ​ 20. Vogel A, Sahai V, Hollebecque A, et al. “LBA40 - FIGHT-202: A phase II study of pemigatinib in patients (pts) with previously treated locally advanced or metastatic cholangiocarcinoma (CCA).” Annals of Oncology. Volume 30, Supplement 5, October 2019, Page v876. 21. Cholangiocarcinoma Foundation. “Key Statistics”. https://cholangiocarcinoma.org/key-statistics/ ​ 22. Susan G. Komen. “Triple negative breast cancer”. https://ww5.komen.org/BreastCancer/TripleNegativeBreastCancer.html 23. Bardia A, Mayer IA, Vahdat LT, et al. “Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer”. N Engl J Med 2019;380:741-51.

Diplomat Specialty Pipeline Report | Q2 2020 | 36

24. Marrie RA, Gryba C. “The incidence and prevalence of neuromyelitis optica: a systematic review”. Int J MS Care. 2013 Fall; 15(3): 113–118. 25. Cree BAC, Bennett JL, Kim HJ, et al. “Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomized, placebo-controlled phase 2/3 trial.” The Lancet. Volume 394, issue 10206, P1352-1363. 26. Knupp KG, Lagae L, Thiele EA, et al. “ZX008 (fenfluramine hydrochloride oral solution) provides clinically meaningful reductions in seizure frequency irrespective of concomitant AEDs commonly used in Dravet Syndrome: pooled analysis of two phase 3 trials.” Presented at American Epilepsy Society (AES) Annual Meeting, December 6–10, 2019, Baltimore, MD, USA. https://www.zogenix.com/wp-content/uploads/2019/12/03.-FINAL-52350-Conmeds-AEDs-AES-poster-2019- 12-02v3.pdf 27. National Organization for Rare Disorders (NORD). “Dravet syndrome”. https://rarediseases.org/rare-diseases/dravet-syndrome-spectrum/. ​ 28. National Institute of Neurological Disorders and Stroke. “Neurofibromatosis Fact Sheet”. Available from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Neurofibromatosis-Fact-She et 29. Gross AM, Wolters P, Baldwin A, et al. “SPRINT: Phase II study of the MEK 1/2 inhibitor selumetinib (AXD6244, ARRY-142886) in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN).” Journal of Clinical Oncology. https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.10503 30. American College of Rheumatology. “Prevalence Statistics”. https://www.rheumatology.org/Learning-Center/Statistics/Prevalence-Statistics 31. NIHR Health Technology Briefing, May 2019. “Filgotinib for moderate to severe active rheumatoid arthritis”. http://www.io.nihr.ac.uk/wp-content/uploads/2019/06/6638-Filgotinib-for-Moderate-to-Severe-Active-Rheu matoid-Arthritis-V1.0-MAY2019-NON-CONF-1.pdf 32. IPD Analytics. “Recent Brand Approvals” ipdanalytics.com. March 24, 2020. ​ ​

Diplomat Specialty Pipeline Report | Q2 2020 | 37

Visit diplomatpharmacy.com

Medical Advice – The information herein is for educational purposes only and may not be construed as medical advice. Diplomat ​ Pharmacy Inc. takes no responsibility for the accuracy or validity of the information herein, nor the claims or statements of any manufacturer. Intellectual Property – Copyright © 2020 by Diplomat Pharmacy Inc. Diplomat is a registered trademark of Diplomat Pharmacy Inc. All ​ rights reserved. All other brand names referenced are the trademarked property of their respective owners. Such references are for informational purposes only.

Diplomat Specialty Pipeline Report | Q2 2020 | 38