Biohaven Ltd. · NYSE:BHVN
Biohaven — Investor Presentation (March 2023)
48 slides from Biohaven's investor presentation, Mar 24, 2023
Slide 1: Investor Presentation March 2023
Investor Presentation March 2023
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 trials for our BHV-2100, troriluzole, BHV- 5500, BHV-1100,
Slide 3: Pfizer Acquisition of CGRP Platform $13B
Pfizer Acquisition of CGRP Platform $13B
Slide 4: Because we are passionate about the work we do everyday
Because we are passionate about the work we do everyday — FRANCINE Through state- of-the-art drug discovery and passionate scientists — LARRY With a powerful R&D engine — JAVIER We never forget patients need us. — JEREMY With a commitment to transforming patients’ lives — KATRINA
Slide 5: High Value Platforms, Innovative Portfolio, Proven Business Formula
HIGH VALUE PLATFORMS INNOVATIVE PORTFOLIO PROVEN BUSINESS FORMULA Pursuing novel paths of science to transform the treatment of neurological and neuropsychiatric diseases A broad therapeutic portfolio addressing patient needs with intention. Formula for continued growth built upon past success of ex
Slide 6: Pipeline by indication and phase
6 INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 FILED ION CHANNEL: Kv7 ACTIVATOR Kv7 ION CHANNEL: TRPM3 INHIBITOR TRPM3 INFLAMMATORY: TYK2/JAK1 INHIBITOR TYK2/JAK1 GLUTAMATE PLATFORM Troriluzole MYOSTATIN PLATFORM BISPECIFIC TARGETED CELL THERAPY CD-38 DISCOVERY RESEARCH IgG Degrader IgA Degrader N
Slide 7: Key Programs
¥ TAIYE | Assoclete Scientist , / . Key Programs
Slide 8: Kv7 Ion Channels: Key Regulators of Neuronal Function
Kv7 Ion Channels: Key Regulators of Neuronal Function 5 FAMILY SUBTYPES Primary localizations: • Kv7.1: cardiac • Kv7.2: CNS BHV-7000/7010 activator • Kv7.3: CNS BHV-7000/7010 activator • Kv7.4: smooth muscle and inner ear • Kv7.5: vascular tissue, neurons, skeletal muscle Kv7 Stria Vascularis Organ
Slide 9: Kv7 Potassium Channels Regulate Neuronal Excitability and Loss of Function Causes Epilepsy
Kv7 Potassium Channels Regulate Neuronal Excitability and Loss of Function Causes Epilepsy Biohaven | Investor Presentation9 Impaired Kv7 Channel Activity Causes Certain Types of Epilepsy Kv7 Activation Normalizes Action Potential Firing Loss-of-function mutations in Kv7.2 channel Abnormal EEG with
Slide 10: Kv7 Platform: Focal Epilepsy
Biohaven | Investor Presentation10 Kv7 PLATFORM Focal Epilepsy Potential Best-in-Class, Fast-Follower Approach Clinically validated mechanism of action Pursuing Differentiation Preclinical data suggests wide therapeutic index in the clinic by dialing out GABA risk (somnolence, sedation, dizziness) T
Slide 11: 1st and 2nd Gen Kv7 Activators vs 3rd Gen Differentiation
BHV-7000 is chemically stable to photo-oxidation BHV-7000 is selective for Kv7 over GABAA receptors a BHV-7000 has a wide therapeutic index preclinically a 1st and 2nd Gen Kv7 Activators Show Clinical Anti-seizure POC, But Off-target Activities, Opportunity for 3rd Gen Kv7 Differentiation XEN1101 •
Slide 12: BHV-7000 Exhibits Highly Differentiated Preclinical Profile
BHV-7000 Exhibits Highly Differentiated Preclinical Profile Biohaven | Investor Presentation12 Wide Therapeutic Index Kv7.2/7.3 Activator GABAA Activity “dialed-out” Ezogabine XEN1101 BHV-7000 Activator, clinical and preclinical anti-seizure activity Activator, clinical and preclinical anti-seizure
Slide 13: BHV-7000 Phase I SAD/MAD Study Update: Dosing Completed
BHV-7000 Phase I SAD/MAD Study Update: Dosing Completed Preliminary Safety • Single doses up to 100 mg and multiple doses up to 40 mg daily x15 days generally well-tolerated • Most AEs mild and resolved spontaneously • No serious or severe AEs • No dose limiting toxicities Preliminary Pharmacokineti
Slide 14: BHV-7000 Favorable CNS-Associated AE Profile Compared to Xen1101
BHV-7000 Shows Favorable CNS-Associated AE Profile Compared to Xen1101 Across Pooled MAD Cohorts 14 1MedDRA® Preferred Term within the System Organ Class of “Nervous System Disorders” 2Data from 2019 73rd Annual American Epilepsy Society Meeting poster, Abstract # 3.31, published 11.25.19 Data prese
Slide 15: Maximal Electroshock Seizure Model: Predictive Translation to the Clinic
Maximal Electroshock Seizure Model: Strongly Positive Predictive Translation to the Clinic Predictive Efficacy: Efficacy results from the maximal electroshock (MES) model are predictive of efficacy in the epilepsy patient population. Other CNS diseases have not benefitted from such similarly predict
Slide 16: Role for Kv7 in Bipolar Disorder and Depression
Kv7 In mania models, Kv7 activation reduces hypermetabolism and hyperactive behavior1 Robust MDD efficacy likely to translate to bipolar disorder2 fMRI study: ezogabine effects mediated by the limbic system Preclinical and Clinical Data Suggest a Role for Kv7 in Bipolar Disorder and Depression Bioha
Slide 17: Blockbuster Peak Sales Potential for Kv7 Platform
Epilepsy Blockbuster Peak Sales Potential for Kv7 Platform Mood Disorders Biohaven | Investor Presentation17 ✓ Easy to Prescribe Convenient dosing, no titration, no food effect ✓ Safe/Tolerable Side effects negatively impacted other recent epilepsy launches ✓ Biohaven Proven Commercial Expertise in
Slide 18: TRPM3 (BHV-2100): A Novel Peripheral Target for Neuropathic Pain
TRPM3 (BHV-2100): A Novel Peripheral Target for Neuropathic Pain Biohaven | Investor Presentation18 Differentiated from existing programs targeting TRPV1 and TRPA1 • Current SoC comes with liabilities — addiction (opioids), sedation • Pre-clinical data shows reversal of pain in various models, witho
Slide 19: TRPM3 (BHV-2100) Reduces Pain in Preclinical Models
TRPM3 (BHV-2100) Reduces Pain in Preclinical Models of Chemotherapy and Diabetic Neuropathy Encouraging evidence of pain reduction without the sedation observed with high dose tramadol/gabapentin Biohaven | Investor Presentation19 BHV-2100 5 mg/kg BHV-2100 25 mg/kg Tramadol 5 mg/kg BHV-2100 1 mg/kg
Slide 20: BHV-8000: TYK2/JAK1 in NeuroInflammatory Disease
BHV-8000: TYK2/JAK1 in NeuroInflammatory Disease BHV-80001 has potential for first- in-class and best-in-class dual TYK2/JAK1 inhibition ü Most advanced, selective TYK2/JAK1 inhibitor with good brain penetration in animal models, to the best of our knowledge ü Dual inhibition of TYK2 and JAK1 can ef
Slide 21: Cellular Drivers In Neuroinflammation
Cellular Drivers In Neuroinflammation: Predominant TYK2/JAK1 Effects TYK2/JAK1 cytokines • IFN-g • IL-b • TNF downstream of IFN-g • IL-8 • GM-CSF, MCP-1 Microglia are the resident macrophages of the CNS, playing an important role in neuroinflammation, repair and maintenance Microglia • IFN-g • IL-12
Slide 22: Properties of TYK2/JAK1 Selective Inhibitors for Neuroinflammation
Properties of TYK2/JAK1 Selective Inhibitors Ideal for Treatment of Neuroinflammation Brain penetrance • Biologics are not brain penetrant • Requires specially designed small molecule to reach site of action • Existing agents exclude all lymphocytes from the CNS • TYK2/JAK1 inhibitor expected to sel
Slide 23: BHV-8000: Phase-1 Ready, Brain-Penetrant TYK2/JAK1 Inhibitor
BHV-8000: Phase-1 Ready, Brain-Penetrant TYK2/JAK1 Inhibitor for Neurological Disorders BHV-8000 ü The most advanced brain-penetrant, selective, dual TYK2/JAK1 inhibitor • Good brain penetration in pre-clinical species • Excellent selectivity over JAK2 and JAK3, avoiding associated toxicities • Wide
Slide 24: TYK2/JAK1 Pathways in Parkinson's Disease
TYK2/JAK1 Pathways in Parkinson’s Disease • a-synuclein aggregates in dopaminergic neurons of substantia nigra • Microglia present a-syn fragments with MHC-II leading to immune response, and activated T cells entering the CNS • T cells release IFN-g, activating microglia which release further proinf
Slide 25: TYK2/JAK1 Inflammatory Pathways in Multiple Sclerosis
TYK2/JAK1 Inflammatory Pathways in Multiple Sclerosis • Multiple sclerosis is an inflammatory disease in which humoral immune and cell-mediated immune responses target CNS antigens • IL-17A-defective mice are highly resistant to induction of EAE • PKM2 activators mediate potent inhibitory effects in
Slide 26: TYK2/JAK1 Pathways in Other Neuroinflammatory Disorders
TYK2/JAK1 Inflammatory Pathways in Other Neuroinflammatory Disorders • Alzheimer disease • Neuroinflammation is a key event in AD pathogenesis • Cytokines and chemokines affect TAU phosphorylation and amyloid deposition • Ab induces the glial cell expression of several pro- inflammatory cytokines, s
Slide 27: BHV-8000 Summary
BHV-8000 Summary CNS immunomodulation in neuroinflammatory disorders will interrupt the cycle of inflammation, neuronal injury and demyelination, and will complement other approaches directly addressing neurodegeneration such as amyloid, a-synuclein, tau and mitochondrial targeting therapies Strong
Slide 28: Troriluzole: SCA and OCD
Biohaven | Investor Presentation28 TRORILUZOLE SCA and OCD SPINOCEREBELLAR ATAXIA (SCA) • Reduction in fall risk + treatment effect in SCA3 genotype • Safe and well-tolerated profile • Regulatory engagement planned for H1 2023 OBSESSIVE COMPULSIVE DISORDER (OCD) • Compelling mechanistic rationale fo
Slide 29: Troriluzole Phase 3 Results: Treatment Effect in SCA3 Genotype
Troriluzole Phase 3 Results: Treatment Effect in SCA3 Genotype • Post-hoc analysis suggests troriluzole has disease-stabilizing effect in SCA3 genotype (most common genotype, pre- identified randomization stratum) • In SCA3 patients (N=89 / 41%), numerical treatment benefit observed on change from b
Slide 30: Troriluzole Treated OCD Patients: Strong Signal in Phase 2
BHV-4157 Troriluzole Treated OCD Patients: Strong Signal Observed in Phase 2 POC Supports Advancement to Phase 3 STUDY BHV-4157-202 Patients with moderate-to-severe OCD (Y-BOCS score ≥ 19) and inadequate response to standard of care SAMPLE SIZE 226 subjects RANDOMIZATION 1:1 DOSE Troriluzole 200 mg
Slide 31: Taldefgrobep Alfa SMA: Pivotal Phase 3 Study Initiated
Biohaven | Investor Presentation31 TALDEFGROBEP ALFA SMA Pivotal Phase 3 Study Initiated July 2022 • Large pre-clinical and clinical safety package licensed from BMS • Limited additional work needed to support BLA submission • 34 sites total, ~20 open POC for Mechanism of Action Supported by clinica
Slide 32: T-Alfa: Targeting a Differentiated Regulatory Pathway of Muscular Growth
T-Alfa: Targeting a Differentiated Regulatory Pathway of Muscular Growth The Most Advanced Phase 3 Ready Myostatin Inhibitor Safety studied with more than 300 subjects dosed in prior clinical studies in pediatric and adult populations Non-clinical studies showed muscle and bone improvements POC for
Slide 33: Bispecific Platform: IgG Degradation via MoDE
• Harnesses the body’s own machinery for degrading proteins • Extracellular protein targets are eliminated via the asialoglycoprotein receptor (ASGPR) • Protein targets are degraded via endolysosomal proteolysis * formerly BH 2640 Bispecific Platform: IgG Degradation via MoDE™ March 2023Biohaven | I
Slide 34: Hepatic ASGPR Receptor Harnessed for Removal of Pathogenic Targets
Hepatic ASGPR Receptor Harnessed for Efficient and Safe Removal of Pathogenic Targets – Pan IgG Degradation March 2023Biohaven | Investor Presentation34 02 03 BHV-1300 administered by subcutaneous or IV BHV-1300 binds circulating IgG to ASGPR on hepatocyte* Internalized IgG is rapidly degraded in ly
Slide 35: BHV-1300: Optimized ASGPR Binder Advancing as Drug Candidate
Hepatic ASGPR Receptor Harnessed for Efficient and Safe Removal of Pathogenic Targets • High capacity ASGPR hepatocellular receptors internalize plasma proteins with specific motifs • Bispecific ASGPR-binders with target-binder effectively removes [pathogenic] target from the circulation • IgG may b
Slide 36: BHV-1300 Mediates Removal, Uptake and Degradation of IgG
HepG2 cells internalize IgG-BHV-1300 complexes In vitro BHV-1300 Mediates Removal, Uptake and Degradation of IgG March 2023Biohaven | Investor Presentation36 1 10 100 1000 0 20000 40000 60000 80000 nM M FI Uptake of IgG in HepG2 EC50 110 BHV-1300 125nM BHV-1300 Untreated Uptake of IgG in HepG2 1 10
Slide 37: BHV-1300 Efficiency in Removal of Human IgG in Mouse Screen
BHV-1300 human IgG depletion in mice, single dose 12 mg/kg BHV-1300 Selected for Remarkable Efficiency in Removal of Exogenously Administered Human IgG in Mouse Screen Approximately 40% IgG removal achieved in 2 hours with a molar ratio of drug-to-target = 1.0 March 2023Biohaven | Investor Presentat
Slide 38: IgG is Specifically Depleted: IgA and IgM Unchanged
IgG is Specifically Depleted: IgA and IgM Levels Remain Unchanged March 2023Biohaven | Investor Presentation38 0 100 200 300 400 0 100 200 300 Hours Ig M % T 0t IgM % change by group 0 mg/kg 10 mg/kg 30 mg/kg 75 mg/kg 150 mg/kg 250 mg/kg • Preliminary BHVN data and literature consistent with an abse
Slide 39: BHV-1300 SC, IM or IV Routes Have Comparable Bioavailability
BHV-1300 Administered by SC, IM or IV Routes has Comparable Bioavailability March 2023Biohaven | Investor Presentation39 Potentially allows at- home, self administration with subcutaneous injection 0 10 20 30 10 100 1000 10000 100000 Hours ng /m l BHV-1300 levels in plasma after a SD of 10 mg/kg in
Slide 40: Pan-IgG Degrader (BHV-1300) and Efgartigimod Primate Data
Pan-IgG Degrader (BHV-1300) and SoC (Efgartigimod) Primate Data Efgartigimod: Cynomolgus Pharmacodynamics 0 5 10 15 0 25 50 75 100 125 Days % Ig G , ba se lin e vehicle 10 mg/kg 75 mg/kg 250 mg/kg BHV-1300: Cynomolgus Pharmacodynamics 3 days 75% depletion 5–7 days 50% depletion March 2023Biohaven |
Slide 41: Bispecific Platform: IgA Degrader for IgA Nephropathy
DISCOVERY RESEARCH Bispecific Platform: IgA Degrader for IgA Nephropathy Therapeutic Hypothesis: Galactosyl deficient-IgA (Gd-IgA) containing-immune complexes drive glomerular injury in IgA nephropathy.1 Specific removal of this pathogenic Gd-IgA with preservation of “normal” IgA (and other Ig’s) pe
Slide 42: Bispecific Degrader Platform Summary
BHVN Bispecific Degrader Platform Summary • Pan-IgG degrader (BHV-1300) in nonclinical development with anticipated 2023 IND • Mechanism with potential for “pipeline in a product” • Highly optimized chemistry, drug delivery potential, and differentiated mechanism of action compared to standard of ca
Slide 43: Bispecific Platform: CD38 Targeted Cell Therapy for Multiple Myeloma
Bispecific Platform: CD38 Targeted Cell Therapy for Multiple Myeloma CD38 Antibody Recruiting Molecule (ARM™) • Modular bispecific molecules with two moieties, each designed for non-covalent binding to a specific target • Redirect endogenous antibodies to target cancerous or virally infected cells f
Slide 44: Ex Vivo Patient Study: Reduction in Plasma Cells
Ex Vivo Patient Study: 4 Out of 5 Patients Showed Reduction in Plasma Cells (Multiple Myeloma) Biohaven | Investor Presentation44 ARM Using patient bone marrow and a combination therapy % reduction in plasma cells in patient bone marrow +/- autologous CIML NK cells in presence of BHV-1100 0 20 40 Pa
Slide 45: Bispecific Platform: Next-Generation Site-Specific ADCs
Second-generation ADC-linker technologiesBiohaven third-generation technology DISCOVERY RESEARCH Bispecific Platform: Advancing Next-Generation, Site-Specific Antibody Drug Conjugates (ADCs) Potential for best-in-class A single residue per heavy chain is available for conjugation • Controlled DAR* r
Slide 46: Capitalization Considerations
Capitalization Considerations CGRP royalties: Pfizer will make royalty payments in low- to mid-teens% in respect of annual U.S. net sales of rimegepant and zavegepant >$5.25B, subject to annual cap ($400M/year)3 ~$465.3 million2 SHARE O/S CASH & MARKETABLE SECURITIES POTENTIAL ROYALTIES 1. Excludes
Slide 47: Near-Term Milestones (Anticipated)
File IND Near-Term Milestones (Anticipated) 47 DRUG NAME INDICATIONS 2H 2022 1H 2023 2H 2023 BHV-7000 Kv7 channel activator Focal Epilepsy Bipolar Disorder BHV-7010 Kv7 channel activator Epilepsy and Mood Disorders BHV-2100 TRPM3 Chronic Pain BHV-8000 TYK2/JAK1 Immune-Mediated Brain Disorders Troril
Slide 48: Pursuing novel paths of science
Pursuing novel paths of science A broad therapeutic portfolio Formula for continued growth HIGH VALUE PLATFORMS INNOVATIVE PORTFOLIO PROVEN BUSINESS FORMULA