Biohaven Ltd. · NYSE:BHVN
Biohaven — 42nd Annual J.P. Morgan Healthcare Conference (January 2024)
56 slides from Biohaven's conference presentation, Jan 8, 2024
Slide 1: 42nd Annual J.P. Morgan Healthcare Conference
TIA, Living with OCD AND HELPING RECRUIT IN BIOHAVEN CLINICAL TRIALS 42nd Annual J.P. Morgan Healthcare Conference Vlad Coric, M.D. Chairman and Chief Executive Officer January 8, 2024 © 2024 Biohaven, Ltd. All rights reserved.
Slide 2: Forward-Looking Statement
Forward-Looking Statement This presentation includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements about Biohaven Ltd. (the “Company”) and our planned and ongoing clinical trials, the timing of and the availability of data
Slide 3: Groundbreaking Legacy of Success in Migraine
GROUNDBREAKING LEGACY OF SUCCESS IN MIGRAINE Biohaven has reemerged for countless patients and is growing one of the most innovative portfolios in life sciences. NEUROSCIENCE | IMMUNOLOGY | ONCOLOGY
Slide 4: Top Areas of Innovation: Biohaven Portfolio
Top Areas of Innovation BIOHAVEN PORTFOLIO Positioned for Future Value Creation for Patients and Investors IgG Degrader TYK2/JAK1 Kv7 Activator TRPM3 Antagonist Troriluzole Taldefgrobep Alfa Trop2 CD30 β1-AR Degrader IgA Degrader RARE DISEASE RENAL CARDIOVASCULAR ONCOLOGY OBESITY NEUROLOGY IMMUNOLOG
Slide 5: Pipeline by program and indication
PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MARKET GLUTAMATE Troriluzole BHV-4157 Obsessive-Compulsive Disorder MYOSTATIN Taldefgrobep Alfa BHV-2000 Spinal Muscular Atrophy Obesity ION CHANNEL Kv7 Activator BHV-7000 Focal Epilepsy Generalized Epilepsy Bipolar Disorder Major Depressive Disorder TRPM3 Antagon
Slide 6: Ion Channels: BHV-7000 Kv7.2/7.3 Activator
Ion Channels BHV-7000 Kv7.2/7.3 Activator Potassium (K+) Ion Channel
Slide 7: BHV-7000 Selective Kv7 Activator
BHV-7000 SELECTIVE Kv7 ACTIVATOR Kv7 is Breakthrough Target in Neurology and Neuropsychiatry • Selective Kv7 activation avoids unwanted CNS side effects • Clinically validated in epilepsy and major depressive disorder BHV-7000 is Potentially Best-in-class Selective Kv7 Activator with Blockbuster Pot
Slide 8: BHV-7000: Epilepsy Update
BHV-7000: Epilepsy Update ION CHANNELS
Slide 9: Dialing Out GABAA Receptor Activation Reduces CNS Side Effects
Dialing Out GABAA Receptor Activation Now Clinically Proven to Reduce CNS Side Effects Pooled CNS AEs BHV-7000 MAD Pooled N=29 XEN1101 MAD Pooled N=18 Somnolence 0% 39% Headache 21% 39% Balance disorder/ dizziness 10% 34% Memory impairment 0% 28% Sensory disturbance 0% 11% Speech disorder 0% 33% BHV
Slide 10: BHV-7000 CNS Target Engagement Confirmed
BHV-7000 CNS Target Engagement Confirmed at Concentrations Well-Tolerated and Exceeding Predicted Therapeutic Target Levels 10 Biohaven | 42nd Annual J.P. Morgan Healthcare Conference January 8, 2024 Demonstrated CNS target engagement in EEG spectral power across all frequency bands, in a dose propo
Slide 11: Epilepsy Phase Studies in Focal and Generalized Epilepsy
Epilepsy Phase 3 Studies in Focal and Idiopathic Generalized Epilepsy January 8, 2024Biohaven | 42nd Annual J.P. Morgan Healthcare Conference11 BHV-7000 Focal Design Generalized Design Focal Epilepsy Study — 110 global clinical sites selected, FPFV 1Q24 KEY POINT DESIGN Randomized, double-blind, pla
Slide 12: BHV-7000: Neuropsychiatry Updates
BHV-7000: Neuropsychiatry Updates ION CHANNELS
Slide 13: Kv7 Activation Validated in the Clinic for MDD
Kv7 Activation Validated in the Clinic for Major Depressive Disorder 13 0 1 2 3 4 5 -20 -15 -10 -5 0 C ha ng e in M AD R S sc or e Weeks • 7.9-point benefit vs. placebo on MADRS (p<0.001) • 6.9-point benefit vs. placebo on SHAPS (p<0.001) • Dose-limiting side effects in 20% of study subjects Ezogabi
Slide 14: Potential for Ketamine and Psilocybin-Like Anti-Depressant Effect
BHV-7000: Potential for Ketamine and Psilocybin-Like Anti-Depressant Effect January 8, 2024Biohaven | 42nd Annual J.P. Morgan Healthcare Conference14 BHV-7000 Kv7 (KCNQ2) Mediates Therapeutic Benefits of Ketamine1 • Chronically stressed mice show downregulation of Kv7 gene expression • Kv7 mediated
Slide 15: BHV-7000: Phase Study in Major Depressive Disorder
BHV-7000: Phase 2 Study in Major Depressive Disorder January 8, 2024Biohaven | 42nd Annual J.P. Morgan Healthcare Conference15 DESIGN Randomized, double-blind, placebo-controlled trial POPULATION Subjects with Major Depressive Disorder (MDD) with at least one prior depressive episode who are current
Slide 16: Human Genetics Links Kv7 to Risk of Bipolar Disorder
Human Genetics Links Kv7 to Risk of Bipolar Disorder ASMs Such as Lamotrigine Are Cornerstone Bipolar Treatments Kv7 Activation With Ezogabine Normalizes Hyperactive Locomotion and Brain Hypermetabolism in Mania Model Compelling Evidence for Targeting Kv7 in Bipolar Disorder • HUMAN GENETICS ANK3 ge
Slide 17: BHV-7000 Phase 2/3 Study in Mania in Bipolar Disorder I
BHV-7000: Phase 2/3 Study to Evaluate Safety and Efficacy for the Acute Treatment of Mania in Bipolar Disorder I January 8, 2024Biohaven | 42nd Annual J.P. Morgan Healthcare Conference17 DESIGN Randomized, double-blind, placebo-controlled trial POPULATION Subjects with Bipolar Disorder I with at lea
Slide 18: BHV-2100 TRPM3 Antagonist
BHV-2100 TRPM3 ANTAGONIST • Biohaven is back in migraine with novel agent, BHV-2100 • Phase 1 SAD study ongoing • Phase 2 in migraine and neuropathic pain planned 2H 2024 BREAKING NEWS Despite the CGRP Revolution, Significant Unmet Need Remains for 40M Migraine Sufferers in the US and 1B Worldwide •
Slide 19: Myostatin
Myostatin TALDEFGROBEP / MYOSTATIN COMPLEX ACTIVIN TYPE II RECEPTOR ACTIVIN TYPE I RECEPTOR SKELETAL MUSCLE CELL SURFACE
Slide 20: Taldefgrobep Alfa: Differentiated Profile Balancing Efficacy and Safety
TALDEFGROBEP ALFA (Anti-myostatin) Differentiated Profile Balancing Both Efficacy and Safety • Taldefgrobep alfa inactivates free myostatin (GDF-8), an inhibitor of muscle growth • Pharmacology uniquely sustained by taldefgrobep alfa/myostatin complex • Taldefgrobep alfa/myostatin complex inhibits s
Slide 21: Muscle Is an Important Endocrine Organ in Metabolic Activity
Muscle Is an Important Endocrine Organ in Metabolic Activity January 8, 2024Biohaven | 42nd Annual J.P. Morgan Healthcare Conference21 Taldefgrobep MYOKINES play an important role in regulating fat metabolism, inflammation, appetite, glucose control, bone density, and basal metabolic rate LEAN MUSCL
Slide 22: Inhibiting Myostatin Increases Muscle Mass and Metabolic Health
Increased lean mass Reduction in total body fat mass Improved insulin sensitivity Reduction in visceral fat Reduction in intramuscular fat Reduction in intrahepatic fat Increased basal metabolic rate Improved bone mineral density Inhibiting Myostatin Increases Muscle Mass and Metabolic Health Taldef
Slide 23: Taldefgrobep Alfa: Differentiated Therapeutic Approach
Taldefgrobep Alfa: A Differentiated Therapeutic Approach Balances Efficacy and Safety January 8, 2024Biohaven | 42nd Annual J.P. Morgan Healthcare Conference23 Taldefgrobep ALK4 ALK5 ActRIIB SKELETAL MYOCYTE SMAD2/3/4 SIGNALING Signal transduction of muscle growth inhibition through ALK4/5 and ActRI
Slide 24: SC Taldefgrobep Suppresses Free Myostatin in Healthy Adults
SC Taldefgrobep Effectively Suppresses Free Myostatin in Healthy Adults January 8, 2024Biohaven | 42nd Annual J.P. Morgan Healthcare Conference24 Free Myostatin Levels Myostatin Complex Levels Taldefgrobep LAST DOSE LAST DOSE Complex sustains activity • Robust lowering of free myostatin after admini
Slide 25: Fat Reduction While Improving Lean Mass in Healthy Adults
Taldefgrobep Taldefgrobep Alfa: Demonstrates Fat Reduction While Improving Lean Mass in Healthy Adults Taldefgrobep Alfa Demonstrates Continued Improvement in Lean Mass in Healthy Adults at 30 Days Post-dosing Taldefgrobep Alfa Continued to Decrease Total Fat Mass Beyond the Dosing Period -10 -8 -6
Slide 26: Phase Study of Taldefgrobep +/- Semaglutide in Obesity
Taldefgrobep Alfa: Phase 2 Study to Evaluate Taldefgrobep +/- Semaglutide in the Treatment of Overweight and Obesity Innovative study design allows for early insight into a number of key clinical questions • Impact of Taldefgrobep monotherapy on changes in body composition, total body weight, and me
Slide 27: Troriluzole in OCD
3M+ OCD Patients in US With High Unmet Medical Need • 40–60% do not respond to first line treatment • 10–40% are treatment refractory potentially requiring ablative neurosurgery or deep brain stimulation Phase 2 Troriluzole Trial in OCD Demonstrated Efficacy Signal Consistent numerical benefits vs.
Slide 28: Degraders
Degraders DEGRADATION TARGET BIFUNCTIONAL MoDE™ DEGRADER ASGPR RECEPTOR ON HEPATOCYTE
Slide 29: Potent Extracellular Pan-IgG Lowering Agents
Potent Extracellular Pan-IgG Lowering Agents • Degrading and depleting pathogenic IgG presents multiple disease opportunities • BHV-1310 has further optimized properties over first-generation BHV-1300 Innovative Mechanism of Action • Protein degradation rather than inhibition • Low projected human d
Slide 30: First-in-Class Mechanism: Hepatic ASGPR Receptor
A First-in-Class Mechanism: Hepatic ASGPR Receptor Harnessed for Efficient and Safe Removal of Circulating Pathogenic Targets subcutaneous or intravenous injection MoDEs™ are administered via *Stylistic representation ASGPR, asialoglycoprotein receptor; MoDE™, molecular degrader of extracellular pro
Slide 31: Transformational Drug Platform: MoDE
Precisely balanced components selected for optimal efficacy, safety and product profile A Transformational Drug Platform: Molecular Degraders of Extracellular Proteins (MoDE™) January 8, 2024Biohaven | 42nd Annual J.P. Morgan Healthcare Conference31 TARGET BINDER STABLE LINKER ASGPR BINDER COMPOUND
Slide 32: MoDE Degraders: Multiple Asset Opportunities and Timelines
K E Y I N F L E C T I O N P O I N T S 2023 2024 2025 IgG RA-Autoimmune BHV-1300 IgG BHV-1310 IgA IgA Nephropathy BHV-1400 β1-AR Cardiomyopathy BHV-1600 Novel autoantibody targets MoDE™ Degraders: Multiple Asset Opportunities and Potential Timelines Realization of value inflection points will be proj
Slide 33: BHV-1300 Degraders
BHV-1300 DEGRADERS
Slide 34: BHV-1300: Potential for Superiority Over Competition
BHV-1300: Shows Potential for Superiority Over Competition BHV-1300 demonstrated faster depletion of IgG in non-human primates 0 50 100 150 0 5 10 15 % Ig G , b as el in e Days after start of infusion 10 mg/kg 75 mg/kg 250 mg/kg Vehicle BHV-1300 NHP Pharmacodynamics 2–3 days to reach 80% depletion E
Slide 35: Unique Properties of BHV-1300 and BHV-1310
Unique Properties of BHV-1300 and BHV-1310 Matched to Indications BHV-1300 35 Biohaven | 42nd Annual J.P. Morgan Healthcare Conference January 8, 2024 BHV-1310 Preclinical Pharmacodynamics (single dose) BHV-1300 Preclinical Pharmacodynamics (multiple dose) Dose Administered 60% DEPLETION 90% DEPLETI
Slide 36: Pan-IgG Degraders Allow Co-Administration with mAbs
Biohaven Pan-IgG Degraders Allow for Co-Administration with mAbs January 8, 2024Biohaven | 42nd Annual J.P. Morgan Healthcare Conference36 BHV-1300 * Adapted from BLA 761154, IND 116471, Study no. r-fkb327-01 Humira 3 mg/kg SC, After a 30 mg/kg SC Dose of BHV-1300 to NHP Time (days) M ea n co nc en
Slide 37: BHV-1600 Degrader Targeting β1-AR Autoantibodies
BHV-1600, Next-Generation Selective Degrader Targeting β1-AR Autoantibodies DEGRADERS
Slide 38: Selective Targeting of β1-AR Autoantibodies for Dilated Cardiomyopathy
Selective Targeting of β1-AR Autoantibodies for Dilated Cardiomyopathy BHV-1600 Cardiac beta-adrenergic receptors (β1-AR) Inducibly increases heart rate, contractility and cardiac output Agonistic autoantibodies to β1-AR increase basal heart rate Sustained β1-AR agonism ▶ dilated cardiomyopathy ▶ he
Slide 39: BHV-1600 In Vitro and In Vivo Properties
IND Filing and FIH Phase 1 Study 2H 2024 KEY UPDATE Ternary Complex and Endocytosis Marked Degradation of Anti-β-1AR Antibody in Mice BHV-1600: In Vitro and In Vivo Properties Ideal for Degrading β-1AR Abs BHV-1600 High Affinity to the Target High affinity for monoclonal mouse anti-b1-AR antibody an
Slide 40: BHV-8000 TYK2/JAK1 Inhibitor
First-in-Class Oral, Selective, Brain-Penetrant TYK2/JAK1 Inhibitor • Uniquely potent, TYK2/JAK1 selective, brain-penetrant inhibitor • Selectivity profile should avoid class risks associated with JAK2/3 inhibition Breaks the Cycle of Neuroinflammation Reduces inflammatory impacts of microglia, astr
Slide 41: BHV-8000: TYK2/JAK1 in Neuroinflammatory Disorders
BHV-8000: TYK2/JAK1 in Neuroinflammatory Disorders Cytokine Receptor JAK FAMILY Microglia IFN-γ, IFN-⍺, IFN-β Astrocytes IFN-γ, IFN-⍺ and IFN-β Lymphocytes and Other Leukocytes IL-23, IL-17 downstream of IL-23 CELLULAR DRIVERS IN NEUROINFLAMMATION Inflammation plays a key role in the pathogenesis of
Slide 42: Real-World Analytics: Parkinson's Risk Reduction with IL-17/TNF Therapies
Biohaven's Real-World Analytics of Large Healthcare Database: Parkinson's Disease Risk Reduction with IL-17/TNF Targeting Therapies • Biohaven conducted analysis using Komodo Health database (over 320 million patients since 2012) examining treatment with Anti-TNF or Anti-IL17 and incidence of PD • M
Slide 43: BHV-8000: Unique Clinical Trial Approach in Parkinson's Disease
Provides a highly-sensitive supportive secondary efficacy endpoint Novel Composite Endpoint Parkinson’s Disease Composite Score (PARCOMS) • Based on established methodology (i.e., Alzheimer’s Disease Composite Score [ADCOMS]) • Leverages PPMI and placebo-arm clinical trial data (C-Path) • Comprises
Slide 44: ARIA: A Potential Therapeutic Target for TYK2/JAK1 Inhibition
Severe ARIA-E (Edema) in a Patient Receiving Anti-Amyloid Therapy for AD ARIA: A Potential Therapeutic Target for TYK2/JAK1 Inhibition ARIA events typically occur early (8–12 weeks) after initiation of anti- amyloid mAb therapy1 and can complicate the benefit-risk assessment in certain patient group
Slide 45: BHV-8000: A Potential Therapy for Prevention of ARIA
BHV-8000: A Potential Therapy for the Prevention of ARIA Therapeutic hypothesis: • TYK2/JAK1 inhibition reverses activated glial- and T-cell mediated pathology and general inflammation • Corticosteroids and other immunosuppressive drugs show benefit in treating and reducing the risk of ARIA1,2,3 • T
Slide 46: Oncology Payload
Oncology Payload IgG 1, 2 and 4 antibody NK cell Macrophage Cancer cell Targeted cancer cell antigen Fab fragment Fc Fc receptor
Slide 47: ADC Platform Conjugation Chemistry
Biohaven chemistry Stable, physicochemically benign amide linkage O Payload N H N PayloadS O O Poorly stable linkage Industry standard maleimide Conjugation Chemistry Superior to Industry Standard Maleimide and lipophilic click chemistry Attached to Two Specific Lysines Provides stable and consisten
Slide 48: BHV-1510 is a Potential Best-in-Class TROP2 ADC
BHV-1510 is a Potential Best-in-Class TROP2 ADC TROP2 IS A HIGHLY VALIDATED TARGET WITH LARGE MARKET OPPORTUNITY • Trodelvy® only drug approved with 2022 actual sales of $680M (+65%y/y) • Significant opportunities for indications beyond current approvals and in anti-PD1 combination BHV-1510 HAS POTE
Slide 49: BHV-1510: Improved Efficacy, Cell Killing and Linker Stability
Superior Bystander Activity vs. DS-1062 Superior Immunogenic Cell Death with Topolx Compared to Other Payloads (DxD and SN38) Highly Stable Linker vs. DS-1062 High Payload Delivery to Tumor BHV-1510: Improved Efficacy, Cell Killing and Linker Stability BHV-1510 49 Biohaven | 42nd Annual J.P. Morgan
Slide 50: BHV-1510 + Anti-PD1 Combination Shows Synergy
BHV-1510 BHV-1510 + Anti-PD1 Combination Shows Compelling Synergy in Syngeneic Models and is Superior to DS-1062 • Preclinical profile of BHV-1510 positions it for superiority in ADC therapy with anti-PD1 • Landscape open for TROP2 combinations with safer more efficacious ADCa January 8, 2024Biohave
Slide 51: BHV-1500 Improved Survival in Mouse Compared to Adcetris
BHV-1500 Improved Survival in Mouse Compared to Adcetris® BHV-1500 BHV-1500: Compares Favorably to Adcetris and Potential Best-In-Class Profile BHV-1500 Demonstrates Superior Efficacy to Adcetris® in a Mouse Xenograft Model 0 500 1000 1500 2000 2500 Day 1 Day 4 Day 8 Day 11 Day 15 Day 18 Day 22 Day
Slide 52: BHV-1500: Improved PK and Decreased Payload Release
Free MMAEADC BHV-1500: Improved PK and Decreased Payload Release Compared to Adcetris® • Markedly improved PK • Increased exposure does not increase risk • Marked reduction in release of free payload • Free payload drives toxicity BHV-1500 52 Biohaven | 42nd Annual J.P. Morgan Healthcare Conference
Slide 53: Capitalization Updates
Capitalization Updates CASH SHARES O UTSTA NDIN G POTENTIAL R OYA LT IES ~$495M1 81.1M2 CGRP Pfizer will make royalty payments in low- to mid-teens% in respect of annual US net sales of rimegepant and zavegepant >$5.25B, subject to annual cap ($400M/year)3 1. As of October 5, 2023, including cash fr
Slide 54: BioCentury Survey: Patient Populations by Indication
BIOCENTURY SURVEY1 1. Adapted from BioCentury survey: https://www.biocentury.com/article/ 650883/move-over-oncology-i-i-will-write-the-next-big-stories-in-innovation#. 2. Patient numbers are US prevalence from Biohaven market research; 3. With amyloid therapy; 4. Disease modifying PATIENTS 2 INDICAT
Slide 55: 2024 Milestones: Potential for Multiple Value Inflection Points
1Q 2024 2Q 2024 2H 2024 Troriluzole | BHV-4157 Obsessive-Compulsive Disorder Taldefgrobep Alfa | BHV-2000 Spinal Muscular Atrophy Obesity Kv7 Activator | BHV-7000 Focal Epilepsy Generalized Epilepsy Bipolar Disorder Major Depressive Disorder TRPM3 Antagonist | BHV-2100 Migraine Neuropathic Pain TYK2
Slide 56: Our Commitment: Building Value for Patients and Shareholders
Our Commitment: Building Value for Patients and Shareholders
Biohaven — 42nd Annual J.P. Morgan Healthcare Conference (January 2024) on 6ix