Biohaven Pharmaceutical Holding Co Ltd
Biohaven Pharmaceutical — Investor Presentation (September 2021)
89 slides from Biohaven Pharmaceutical's investor presentation, Sep 27, 2021
Slide 1: Investor Presentation | September 2021
NYSE:BHVN Ellie, living with migraine © 2021 Biohaven Pharmaceuticals. All rights reserved. Investor Presentation | September 2021 neuroinnovation
Slide 2: Disclaimer
Disclaimer This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including: statements about Biohaven Pharmaceutical Holding Company Ltd. (The ”Company”) and our plans relating to the commercialization and sales of NURTEC® O
Slide 3: Innovative pharmaceutical solutions to address unmet needs in neuroscience
Innovative pharmaceutical solutions to address unmet needs in neuroscience PIPELINE INCLUDES 6 products across multiple technology platforms COMMITTED TO IMPROVING THE LIVES OF PATIENTS by advancing first-in-class and best-in-class therapies PROVEN LEADERSHIP in industry & academic settings with uni
Slide 4: Company Achievements
Company Achievements BIOHAVEN INVESTOR PRESENTATIONSEPTEMBER 2021 4 >875,000 TRxs of NURTEC to Date 61.5% New to Brand Share $93M Net Sales 2Q2021 $200M Total Net Sales Since Launch
Slide 5: First and only medication proven to treat and prevent migraine
y 4 i § Nurt BREAKING NEWS we FIRST & ONLY | MEDICATION PROVEN TO TREAT & mae PREVENT q. MIGRAINES Ellie W Actual Nurtec O1 OT Patient TAKE CONTROL OF MIGRAINE WITH one medication
Slide 6: The First and Only Medication Proven to Treat and Prevent Migraine
The First and Only Medication Proven to Treat and Prevent Migraine SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 6 ACUTE Treatment PREVENTIVE Treatment DUAL-THERAPY MIGRAINE TREATMENT Dissolving the line between acute and preventive treatment
Slide 7: SEPTEMBER 2021 Patient
SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 7 Patient
Slide 8: SEPTEMBER 2021
SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 8
Slide 9: SEPTEMBER 2021
SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 9
Slide 10: SEPTEMBER 2021
SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 10
Slide 11: SEPTEMBER 2021
SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 11
Slide 12: Oral CGRP Class Continues to Show Robust Market Growth
3/ 13 3/ 27 4/ 10 4/ 24 5/ 8 5/ 22 6/ 5 6/ 19 7/ 3 7/ 17 7/ 31 8/ 14 8/ 28 9/ 11 9/ 25 10 /9 10 /2 3 11 /6 11 /2 0 12 /4 12 /1 8 1/ 1 1/ 15 1/ 29 2/ 12 2/ 26 3/ 12 3/ 26 4/ 9 4/ 23 5/ 7 5/ 21 6/ 4 6/ 18 7/ 2 7/ 16 7/ 30 8/ 13 8/ 27 9/ 10 Oral CGRP Class Continues to Show Robust Market Growth, Nurtec
Slide 13: Nurtec ODT Has Gained Significant Market Share Post Prevention Approval
40.0% 45.0% 50.0% 55.0% 60.0% 4/ 23 4/ 30 5/ 7 5/ 14 5/ 21 5/ 28 6/ 04 6/ 11 6/ 18 6/ 25 7/ 2 7/ 9 7/ 16 7/ 23 7/ 30 8/ 6 8/ 13 8/ 20 8/ 27 9/ 3 9/ 10 9/ 17 Total Rx Share (9/17)¹ 35% 40% 45% 50% 55% 60% 4/ 23 4/ 30 5/ 7 5/ 14 5/ 21 5/ 28 6/ 04 6/ 11 6/ 18 6/ 25 7/ 2 7/ 9 7/ 16 7/ 23 7/ 30 8/ 6 8/ 1
Slide 14: Oral CGRPs Have Significant Growth Opportunity Ahead vs Triptans
476,222 3,924,354 Oral CGRPs Have Significant Growth Opportunity Ahead vs Triptans BIOHAVEN INVESTOR PRESENTATION 14 2Q21 TriptansCGRP orals3 Quarterly TRx volume 2Q21 TRx Volume vs Triptans¹ 11% SEPTEMBER 2021 Source: 1. TRX numbers cover 2Q2021, IQVIA SMART, accessed 8/4/21. 2. NBRx numbers cover
Slide 15: Oral CGRPs Have Driven CGRP Growth in 2020 and 2021 (vs mAbs)
Orals CGRPs Have Driven CGRP Growth in 2020 and 2021 (vs mAbs) 0 20,000 40,000 60,000 80,000 100,000 120,000 140,000 5/25/1 8 6/25/1 8 7/25/1 8 8/25/1 8 9/25/1 8 10/2 5/18 11/2 5/18 12/2 5/18 1/25/1 9 2/25/1 9 3/25/1 9 4/25/1 9 5/25/1 9 6/25/1 9 7/25/1 9 8/25/1 9 9/25/1 9 10/2 5/19 11/2 5/19 12/2 5/
Slide 16: Significant Unmet Need
Significant Unmet Need SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 16 PREVENTION = TOO FEW, TOO LATE DESPERATION FOR BETTER OPTIONS THE INJECTION BARRIER IS REAL 15% of people who meet clinical criteria for Preventive treatment actually use it 84% of people taking a Preventive treatment wish there
Slide 17: Redefining the Prevention Market Opportunity
SEPTEMBER 2021 17 39M People with Migraine in US 19.5M Diagnosed with Migraine 500KNovel Injectables 1.1M Topiramate, Gabapentin, Tcas 7.0M Rx Therapy CURRENT INJECTIBLE PREVENTIVE MIGRAINE MARKET BROADER PREVENTIVE MARKET OPPORTUNITY ACUTE PLUS ACUTE AUGUST 2021 Redefining the Prevention Market Opp
Slide 18: Perceptions of CGRPs' Advance Over Triptans Continues to Rise
Perceptions of CGRPs’ Advance Over Triptans Continues to Rise Through 1Q21 BIOHAVEN INVESTOR PRESENTATION 18 13% 12% 16% 15% 12% 33% 32% 42% 38% 51% 0% 41% 51% 53% 58% Q1 2020 (n=98) Q2 2020 (n=101) Q3 2020 (n=101) Q4 2020 (n=101) Q1 2021 (n=106) Percent of Respondents Who Indicate That Recently Lau
Slide 19: Specialists and PCPs Rate Nurtec ODT Better Than Ubrelvy
Specialists and PCPs Rate Nurtec ODT Better Than Ubrelvy on Pain Freedom, Duration and Tolerability BIOHAVEN INVESTOR PRESENTATION 19 7% 5% 5% 11% 8% 12% 43% 24% 27% 39% 28% 33% Duration of effect Tolerability Pain freedom at two hours Duration of effect Tolerability Pain freedom at two hours Attrib
Slide 20: Unparalleled CGRP-Antagonist Franchise
Unparalleled CGRP-Antagonist Franchise Biohaven’s CGRP Platform SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 20 ORAL Ph 3 prevention Started 1Q21 Zavegepant RAPID DISSOLVING Launched 1Q20 Nurtec® ODT MULTIPLE FORMULATIONS BHV-3100 Ph 1 started 2Q21 Advanced Leads 4 Oral Follow-Ups INTRANASAL 2nd Ph
Slide 21: Patent Awarded for ODT Formulation, Extends IP into 2039
Product Patent Awarded for ODT Formulation, Extends Company's IP for CGRP Platform into 2039 SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 21 New patent awarded to the Company by the United States Patent and Trademark Office for our drug product, Nurtec ODT (rimegepant), in an ODT form Covers rimege
Slide 22: CGRP Franchise: Near-Term Value Inflection Milestones
CGRP Franchise: Near-Term Value Inflection Milestones BIOHAVEN INVESTOR PRESENTATION SUBMISSION 4Q21 TOP-LINE 4Q22 MIGRAINE ACUTE APPROVED MIGRAINE PREVENTION APPROVED MIGRAINE PEDIATRIC PHASE 3 START MIGRAINE ULTRA- RAPID ACUTE INTRANASAL MIGRAINE CHRONIC ORAL QDZAVEGEPANT ZAVEGEPANT SEPTEMBER 2021
Slide 23: Rimegepant Global Regulatory Expansion in Migraine
United Arab Emirates Acute | APPROVED Israel Acute | APPROVED Kuwait Acute | 4Q20 Europe Dual | 1Q21 Saudi Arabia Acute | 1Q21 Lebanon Acute | 3Q21 Qatar Acute | 3Q21 Bahrain Acute | 4Q20 Japan Ph 2/3 | 4Q21China Ph 3 | 4Q20 Korea Ph 3 | 4Q20 Rimegepant Global Regulatory Expansion in Migraine SEPTEM
Slide 24: Neuroinnovation Pipeline: Near-Term Milestones
Neuroinnovation Pipeline: Near-Term Milestones BIOHAVEN INVESTOR PRESENTATION OBSESSIVE COMPULSIVE DISORDER TOP-LINE 2H22 TRORILUZOLE AMYOTROPHIC LATERAL SCLEROSIS VERDIPERSTAT COMPLETE ENROLLMENT 4Q21 SPINOCEREBELLAR ATAXIA TRORILUZOLE TOP-LINE 1H22 SEPTEMBER 2021 24
Slide 25: Nurtec ODT Provides New Hope
Nurtec® ODT Provides New Hope SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 25 THE HALO FOR ACUTE IS REAL HCPS ARE LIKELY TO RX FOR MULTIPLE USES DESIRE FOR FLEXIBILITY ACUTE 67% of patients say they want a drug that treats and prevents 85% of HCPs will Rx more for Acute as a result of Preventive in
Slide 26: Broad Commercial Coverage: High Impact PBM and Health Plan Wins
Broad Commercial Coverage: High Impact Commercial PBM and Health Plan Wins 89% COVERAGE 235M+ TOTAL COVERED LIVES IN ALL CHANNELS SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 26
Slide 27: Net Sales Progress
Net Sales Progress BIOHAVEN INVESTOR PRESENTATION 27 $10M $18M $35M $44M $93M 2Q20 3Q20 4Q20 1Q21 2Q21 $200M Launch to date approximate net product revenue1 SEPTEMBER 2021 1. 7/7/2021 Press Release - NURTEC® ODT achieved preliminary net product revenue of approximately $93 million for the second qua
Slide 28: Nurtec Maintained a Competitive Share of Voice With Far Less Budget
20% 2% 17% 20% 1% 14% 27% 14% 1% 17% 16%26% 26% Throughout 2020, Nurtec Maintained a Competitive Share of Voice, With Far Less Budget BIOHAVEN INVESTOR PRESENTATION 28 Source: Nielsen AdIntel January through December Nurtec ODT Ubrelvy 2020 total share of voice 2020 total share of spend Nurtec ODT S
Slide 29: Expansion of CGRP Portfolio: Following the Science of CGRP
Expansion of CGRP Portfolio: Following the Science of CGRP SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 29 GLOBAL EXPANSION CGRP MEDIATED: NON-MIGRAINE DISEASES Europe Japan China Korea Middle East and Israel Psoriasis Asthma Undisclosed MIGRAINE ADJACENCIES ACUTE AND PREVENTION EXPANSION INTO PEDI
Slide 30: Multiple Opportunities Across Multiple Platforms
Multiple Opportunities Across Multiple Platforms SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 30 PLATFORM DRUG NAME OPPORTUNITIES CALCITONIN GENE-RELATED PEPTIDE (CGRP) Rimegepant Small molecule/NCE • US NURTEC ODT | Acute Migraine • US NURTEC ODT | Migraine Prevention • EX-US (EU, Japan, China, Ko
Slide 31: Company Achievements
Company Achievements BIOHAVEN INVESTOR PRESENTATIONSEPTEMBER 2021 31 >875,000 TRxs of NURTEC to Date 61.5% New to Brand Share $93M Net Sales 2Q2021 $200M Total Net Sales Since Launch
Slide 32: Take Control of Migraine With One Medication
TAKE CONTROL OF MIGRAINE WITH one medication Ellie W Actual Nurtec® ODT Patient
Slide 33: Orphan Disease Opportunities
Orphan Disease Opportunities BIOHAVEN INVESTOR PRESENTATION 33 Amyotrophic Lateral Sclerosis Spinocerebellar Ataxia 2 Devastating Diseases 2 Phase 3 Readouts Over Next Year Targeting 2 Global Orphan Drug Approvals 2022/2023 SEPTEMBER 2021
Slide 34: Clinical-Stage Milestones
DRUG NAME INDICATION 1H2021 2H2021 1H2022 2H2022 Migraine prevention Migraine acute/prevention Migraine acute (China/Korea) Zavegepant Small molecule/NCE Migraine (intranasal) Migraine (oral) Undisclosed Troriluzole NCE prodrug of riluzole Spinocerebellar ataxia Obsessive-compulsive disorder Verdipe
Slide 35: Biohaven Labs: Chemistry and Discovery
Biohaven Labs: Chemistry and Discovery Next-Generation Bispecific Platforms for Pipeline Growth BIOHAVEN INVESTOR PRESENTATION 35 Binds liver (ASGPR) Binds protein target Bifunctional small molecule Target Binder Reactive group Directing group Binding to IgG1/2/4 antibody Conjugation and release of
Slide 36: Biohaven 2021 Growth Drivers
Biohaven 2021 Growth Drivers BIOHAVEN INVESTOR PRESENTATION 36 Nurtec (rimegepant) • Treating migraine continuum • Single simple clear dosing with ODT • Significant lifecycle expansion Zavegepant • Intranasal ultrarapid formulation • Oral formulation for chronic migraine • Multiple additional nonmig
Slide 37: Thank You!
THANK YOU!
Slide 38: Appendix
Appendix & biohaven (jpharmaceuticals
Slide 39: Innovative Chemistry & Discovery Initiatives for Next-Generation Bispecific Compounds
Innovative Chemistry & Discovery Initiatives to Advance Next-Generation Bispecific Compounds for Neuroscience, Immunology & Oncology
Slide 40: Next-Generation Bispecific Compounds – MATEs, ARMs & MoDEs
Binds liver (ASGPR) Binds protein target Bifunctional small molecule Next-Generation Bispecific Compounds – MATEs, ARMs & MoDEs BIOHAVEN INVESTOR PRESENTATION 40 Target Binder Reactive group Directing group Binding to IgG1/2/4 antibody Conjugation and release of directing group Endogenous IgG Antibo
Slide 41: ARM, MATE and MoDE Technologies: Synergies across platforms
PRECLINICAL VALIDATION STUDIES: MATE PEPTIDE (HGM) ARM, MATE and MoDE Technologies: Synergies across platforms 41 Synthetic Degraders Immune Cell Engagers Antibody-based Degraders M o D E A R M M AT E Phagocytic Based Degraders Bispecific immune degraders IVIG Conjugates (HGM) MoDe Bind to target pr
Slide 42: Chemical Reengineering of Antibodies to Enhance Their Function
Chemical Reengineering of Antibodies to Enhance/ Improve their Function Site-directed, chemical conjugation to off-the-shelf therapeutic monoclonal antibodies (mAbs), or therapeutic intravenous immunoglobulin (IVIG) pooled from healthy donors. MATE™ Multimodal Antibody Therapy Enhancer Bioengineerin
Slide 43: Examples of MATE applications to create Next Generation Antibodies
Examples of MATE applications to create Next Generation Antibodies BIOHAVEN INVESTOR PRESENTATION 43 Attachment of anti-CD3 scFV to recombinant antibodies Attachment of targeting peptide to plasma-derived antibodies (IVIG) Attachment of small molecule degrader to recombinant antibodies SEPTEMBER 202
Slide 44: MATE HGM: COVID-19 Three Potential Mechanisms of Action
MATE™ HGM: COVID-19 Three Potential Mechanisms of Action Against SARS-CoV-2 BIOHAVEN INVESTOR PRESENTATION 44 Direct virus neutralization/killing: Blocks virus entry SARS-CoV-2 Spike protein FcγR binding Immune-mediated virus killing HUMAN CELL FcγR binding Long-term vaccination effect NK CELLS Infe
Slide 45: MATE Peptide (HGM) Prototype: Convert inert IVIG into anti-COVID19 agent
PRECLINICAL VALIDATION STUDIES: MATE PEPTIDE (HGM) MATE Peptide (HGM) Prototype: Convert inert IVIG into potent anti- COVID19 agent (partnered with Bill and Melinda Gates Foundation) BIOHAVEN INVESTOR PRESENTATION 45 Spike Trimer and RBD Binding Antibody Dependent Cellular Phagocytosis Viral Inhibit
Slide 46: ARM Antibody Recruiting Molecules
Endogenous IgG Antibody (polyclonal) Macrophages NK cells ARM binds to disease target and induces antibody binding Antibody Recruiting Molecules (ARMs) are bispecific molecules that recruit endogenous antibodies to target cancer, virally infected cells, and disease-causing microorganisms for immune
Slide 47: MoDEs Molecular Degraders of Extracellular Proteins
Uptake and degradation of target proteins mediated by MoDE bifunctional molecules MoDEs Molecular Degraders of Extracellular Proteins Utilizes the patients liver to clear unwanted, disease causing proteins BIOHAVEN INVESTOR PRESENTATION 47 ASGPR N-acetyl galactosamine Target protein Target protein l
Slide 48: MoDEs Prototype Preclinical Validation Studies
In vitro evalutiona of cellular updake of cytokine • Cytokine levels are reduced within concentration dependence • Potent activity in nM range Analysis of cell culture supernatants after the addition of MODA-002 • Cytokine disappears from supternatant after MODA-002 treatment SUMMARY • MODA-002 elim
Slide 49: Metallothionein Blockade: A Novel Anti-Inflammatory Therapeutic
METALLOTHIONEIN BLOCKADE A Novel Anti-Inflammatory Therapeutic
Slide 50: Metallothionein Can Alter Immune Response by Influencing Cellular Trafficking
Metallothionein Can Alter Immune Response by Influencing Cellular Trafficking BIOHAVEN INVESTOR PRESENTATION Healthy tissue Stress-causing cell damage Metallothionein production and release as a “danger signal” Extracellular MT recruits inflammatory cell Disease propagation cycle: more stress and mo
Slide 51: Metallothionein: A Novel Target in the Immune Cascade
Metallothionein: A Novel Target in the Immune Cascade • Metallothionein (MT) is an intracellular protein in non-stressed conditions • MT is released from cells/tissues that are stressed, damaged, or killed • Extracellular MT can act as a pro-inflammatory agent • MT acts as an agent of disease progre
Slide 52: UC1MT Reduces Inflammation in the Adoptive T Cell Transfer Model of IBD
UC1MT Reduces Inflammation in the Adoptive T Cell Transfer Model of IBD BIOHAVEN INVESTOR PRESENTATION Anti-MT performance exceeded conventional anti-TNF therapeutic UC1MT: monoclonal antibody targeting extracellular metallothionein; Anti-MT, anti-metallothionein monoclonal antibody; Anti-TNF, anti-
Slide 53: UC1MT: First in Class Metallothionein Antagonist
UC1MT: First in Class Metallothionein Antagonist for a Novel Pro-Inflammatory Target • UC1MT is a high affinity monoclonal antibody that recognizes both mouse and human MT1 and MT2 • Confirmed the role of MT involvement in multiple disease models with better activity than anti-TNF • Evidence of mole
Slide 54: Commercial and Launch Readiness
Commercial and Launch Readiness
Slide 55: Doing things differently…
Doing things differently… 15 sec
Slide 56: Nurtec ODT 'Surround Sound' Marketing Plan
Key Characteristics: • Competitive share of voice • Highly targeted • Modern, ‘social first’ mindset Nurtec™ ODT ‘Surround Sound’ Marketing Plan Peer-2-Peer (Engagement & Education) Core HCP Rep Promotion >500 HCP Omni-Channel (Awareness & Engagement) Consumer Omni-Channel (Awareness & Activation) B
Slide 57: Launch Payer Mix versus CGRP Migraine Prevention Class
Launch Payer Mix versus CGRP Migraine Prevention Class (6 Months) BIOHAVEN INVESTOR PRESENTATION 57 Payment Type Commercial / Assistance Programs 88.3% 89.3% 89.3% 87.1% Medicare 6.0% 4.2% 5.2% 6.0% Cash 2.8% 3.7% 2.8% 3.7% Medicaid 2.6% 2.9% 2.7% 3.2% Totals 100% 100% 100% 100% *Ubrelvy data throug
Slide 58: Managed Markets Customer Engagements
Managed Markets Customer Engagements BIOHAVEN INVESTOR PRESENTATION 58SEPTEMBER 2021
Slide 59: Acute Migraine Treatment Options: Triptans, NSAIDs, Opioids
Triptans NSAIDs Opioids Examples Sumatriptan, naratriptan, zolmitriptan1 Diclofenac, ketoprofen, flurbiprofen2,3 Butorphanol, morphine, hydromorphone2,5 Migraine-specific treatment? Yes1 No3 No6 Use • Moderate or severe attacks OR2 • Mild-to-moderate that respond poorly to NSAIDs or caffeinated comb
Slide 60: REYVOW (Lasmiditan) Label Information
Schedule V CNS DEPRESSION, SEROTONIN SYNDROME & MEDICATION OVERUSE HEADACHES (detoxification may be necessary) DRIVING IMPAIRMENT Advise patients not to drive for 8 hours LABEL INDICATION: ACUTE TREATMENT OF MIGRAINE REYVOW™ (Lasmiditan): Serotonin (5-HT) 1F Receptor Agonist BIOHAVEN INVESTOR PRESEN
Slide 61: CGRP Receptor Antagonist Platform: Zavegepant
CGRP Receptor Antagonist Platform: Zavegepant
Slide 62: Zavegepant: First and Only Third-Generation, Intranasal CGRP Receptor Antagonist
Zavegepant: First and Only Third-Generation, Intranasal CGRP Receptor Antagonist BIOHAVEN INVESTOR PRESENTATION 62 FIRST INTRANASAL FORMULATION OF A SMALL MOLECULE CGRP RECEPTOR ANTAGONIST • Superior chemical attributes • Potent antagonist at the human CGRP receptor • Highly soluble and high free fr
Slide 63: Zavegepant Phase 2/3 Study BHV3500-201
ZAVEGEPANT PHASE 2/3 — STUDY BHV3500-201, 10MG & 20MG INTRANASAL Zavegepant 10 mg and 20 mg Demonstrated Early Separation From Placebo at 15, 60 and 120 Minutes, Durable Through 24–48 Hours BIOHAVEN INVESTOR PRESENTATION 63 1. Pain Relief is defined as patients who have either mild-pain or no-pain d
Slide 64: Glutamate Platform
GLUTAMATE PLATFORM Therapies for Neurologic and Neuropsychiatric Indications
Slide 65: The Role of Glutamate: Present in 90% of Brain Synapses
NORMAL FUNCTION Healthy State The Role of Glutamate: Present in 90% of Brain Synapses BIOHAVEN INVESTOR PRESENTATION 65 EXCITOTOXICITY Diseased State AMYOTROPHIC LATERAL SCLEROSIS SPINOCEREBELLAR ATAXIA DEMENTIA NEURODEGENERATION NEUROTOXICITY SEIZURES DEPRESSION ANXIETY STRESSCANCER PAIN STROKE MEL
Slide 66: Glutamate Mechanisms of Action in CNS
Glutamate Mechanisms of Action in CNS BIOHAVEN INVESTOR PRESENTATION 66 Glutamate Transporter Modulation • Troriluzole Glutamate NMDA Receptor Antagonism • BHV-5000 Third-party clinical trials provide basis for exploration of troriluzole and BHV-5000 in multiple neurologic and neuropsychiatric disor
Slide 67: Riluzole (Rilutek): Use and Limitations
Riluzole (Rilutek®) is approved for the treatment of patients with amyotrophic lateral sclerosis (ALS) and proven to extend survival • Originally marketed by Sanofi, received FDA approval in 1995 • In 2013, the FDA approved the first generic versions of riluzole • Doses above 100 mg for efficacy not
Slide 68: Troriluzole: Rational Drug Discovery to Optimize Therapy
Troriluzole: Rational Drug Discovery to Optimize Therapy BIOHAVEN INVESTOR PRESENTATION 68 • Improved absorption • Enhanced bioavailability • Reduced drug burden • Reduced first pass metabolism • Favorable safety profile • Once-daily dosing SEPTEMBER 2021
Slide 69: Peptide Transporter Enhances Absorption of Troriluzole
Peptide Transporter 1 Enhances Absorption of Troriluzole BIOHAVEN INVESTOR PRESENTATION 69 PepT1 PepT1 = Peptide Transporter 1 ACTIVE ABSORPTION IN INTESTINAL TRACT BY PEPT1 SEPTEMBER 2021
Slide 70: Troriluzole: Targeted Lead-Indication Development Strategy
Troriluzole: Targeted Lead-Indication Development Strategy BIOHAVEN INVESTOR PRESENTATION 70 Lead indications across an array of potential neurologic and neuropsychiatric indications Cerebellar Disorders Spinocerebellar Ataxia (SCA) Friedreich’s Ataxia Sporadic Ataxia Other Ataxias Essential Tremor*
Slide 71: Cerebellar Ataxias
Cerebellar Ataxias • Characterized by: • Poor balance with falls • Dysarthria / dysphagia • Incoordination of limbs • Cognitive impairment • Postural or kinetic tremor • Oculomotor dysfunction • Spinocerebellar ataxia (SCA; >40 subtypes) • Affects 1–5.6 per 100,000 (estimated 3,200–18,000 in US) • N
Slide 72: Troriluzole Study in Spinocerebellar Ataxia vs Natural History
• Post-hoc analysis of patients enrolled in long-term extension of Phase 2b/3 troriluzole SCA trial • Primary efficacy endpoint: change from baseline in the Total SARA Score after 48 weeks • Patients from BHV4157-201 trial versus eligibility criteria matched Ashizawa Natural History cohort: • SCA Ge
Slide 73: Troriluzole Study BHV4157-206 Randomized Controlled Trial in SCA
Key Entry Criteria • SCA genotypes (SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10) Design • Sample size: 230 subjects • Randomization: 1:1 • Stratification: by SCA genotype • Dose: Troriluzole 200 mg QD vs. Placebo QD • Primary Outcome: Modified SARA Scale • FDA aligned outcome measure Status • Phase 3
Slide 74: OCD Treatments Are Limited and Need Is Vast
• Few FDA-approved treatments • Serotonin reuptake inhibitors (SSRIs and clomipramine) are the only approved monotherapy • No new mechanisms for 30 years • With limited efficacy1,2 • <50% of patients respond well • 25–30% are refractory • Many of those categorized as ‘responders’ continue to suffer
Slide 75: Accumulating Evidence for Glutamatergic Dysfunction in OCD
Accumulating Evidence for Glutamatergic Dysfunction in OCD BIOHAVEN INVESTOR PRESENTATION 75 GENES ANIMAL MODELS NEURAL NETWORKS PATIENTS IN THE CLINIC Genetic association studies: Glutamate transporter gene (SLC1A1 on chromosome 9p24) associated w/OCD1 GWAS studies are focusing attention on DLGAP1,
Slide 76: Neurochemical Evidence for Glutamate Dysregulation in OCD
Neurochemical Evidence for Glutamate Dysregulation in OCD BIOHAVEN INVESTOR PRESENTATION 76 Rosenberg et al. 2000 Consistent with pathologic hyperactivity in cortico-striatal circuit Suggests clinical testing of agents that enhance glutamate uptake Healthy Control Subjects n = 11 Treatment Naïve OCD
Slide 77: Neurochemical Evidence for Glutamate Dysregulation in OCD
Neurochemical Evidence for Glutamate Dysregulation in OCD BIOHAVEN INVESTOR PRESENTATION 77 Consistent with pathologic hyperactivity in cortico-striatal circuit Suggests clinical testing of agents that enhance glutamate uptake CSF Glutamate Concentrations Bhattacharyya et al. 2009 SEPTEMBER 2021
Slide 78: Randomized Controlled Trial with Riluzole Augmentation
• Outpatients with moderate-to-severe OCD severity (Y-BOCS score ≥ 21) and free of medication treatment for at least six weeks • Randomized to receive fluvoxamine (up to 200 mg/day) plus either placebo or riluzole (50 mg twice daily) • Robust benefit on primary outcome measure (change in Y-BOCS scor
Slide 79: Troriluzole Phase 2/3 Study in OCD (Completed)
KEY ENTRY CRITERIA • Moderate-to-severe OCD and inadequate response to standard of care DESIGN • Sample size: 226 subjects • Randomization: 1:1 • Dose: Troriluzole 200 mg QD vs. Placebo QD (in patients on standard of care) • Primary Outcome: Y-BOCS, a precedented outcome measure accepted by FDA Tror
Slide 80: Troriluzole Phase 2: Strong signal for efficacy
Troriluzole Phase 2: Strong signal for efficacy and served as basis for powering two ongoing Phase 3 trials needed for approval BIOHAVEN INVESTOR PRESENTATION 80 SOC, standard of care Y-BOCS, Yale-Brown Obsessive Compulsive Scale SEPTEMBER 2021
Slide 81: Troriluzole Phase 3 Program in Obsessive-Compulsive Disorder
• TWO PHASE 3 STUDIES • BHV4157-302 (US only) • BHV4157-303 (global) • KEY ENTRY CRITERIA • Moderate-to-severe OCD • Inadequate response to SOC • DESIGN (identical for each Ph 3 study) • Sample size: 600 subjects • Randomization: 1:1 • Treatment: • Troriluzole 280 mg vs. placebo, 1x daily • Adjuncti
Slide 82: MPO Platform: Therapies for Neuroinflammation
MPO PLATFORM Therapies for Neuroinflammation
Slide 83: Amyotrophic Lateral Sclerosis (ALS)
• Rare, rapidly progressive and fatal neurodegenerative disease • Prevalence: 4–8 per 100,000 • Clinical • Characterized on autopsy by degeneration of • Upper motor neurons (brain) • Lower motor neurons (brainstem/spinal cord) • Leads to weakness and paralysis of voluntary muscles • Prognosis • Most
Slide 84: Rationale for Studying Verdiperstat in ALS
BIOHAVEN INVESTOR PRESENTATION 84 • Targets well accepted ALS disease mechanisms (oxidative stress / nitrosative stress, microglial activation / neuroinflammation) in a physiologically relevant manner • MPO may also play a role in increasingly recognized ALS disease mechanisms mediated by peripheral
Slide 85: Neuroinflammation in ALS Indicated by TSPO Imaging
Neuroinflammation in ALS Indicated by [11C]-PBR28 TSPO Imaging BIOHAVEN INVESTOR PRESENTATION 85 TSPO, translocator protein - positron emission tomography Increased in ALS vs. controls Co-Localizes with Cortical Thinning Correlates with ALS Disease Severity Alshikho MJ, et al. Ann Neurol. 2018 Jun;8
Slide 86: Verdiperstat Selected for First-Ever Platform Trial in ALS
SEPTEMBER 2021 BIOHAVEN INVESTOR PRESENTATION 86 Verdiperstat Selected for First-Ever Platform Trial in ALS FDG,
Slide 87: Verdiperstat Phase 3 Healey ALS Platform Trial
• DESIGN • Sample size: 160 subjects • Randomization: 3:1 • Dose: 600 mg BID vs. Placebo • Primary outcome measure: ALS Functional Rating Scale – Revised (ALS-FRS-R) • Sites: 50 sites (North East ALS Consortium) • STATUS • Study initiated 3Q2020 and recruiting rapidly • Complete Enrollment: expected
Slide 88: Verdiperstat Summary
• Licensed from AstraZeneca • BHV-3241, AZD3241 • Studied in Ph1/Ph2 in ~250 subjects • 4 Phase 1 studies in healthy volunteers • 2 Phase 2a studies in Parkinson’s disease • Generally safe and well tolerated • Achieves target engagement in plasma • ↓ MPO activity • Achieves target engagement in brai
Slide 89: www.biohavenpharma.com
neuroinnovation WWW.BIOHAVENPHARMA.COM | NYSE: BHVN Zydis® is a registered trademark of Catalent. Rilutek® is a registered trademark of Covis Pharma B.V. Reyvow is a trademark of Eli Lilly and Company
Biohaven Pharmaceutical Holding — Investor Presentation (September 2021) on 6ix