Biohaven Ltd. · NYSE:BHVN
Biohaven — Investor Presentation (September 2023)
83 slides from Biohaven's investor presentation, Sep 27, 2023
Slide 1: Investor Presentation
Investor Presentation
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: 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 In-house scientific expertise to enable a broad therapeutic portfolio addressing patient needs with intention Formula for continu
Slide 5: Pipeline by platform and phase
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 Next-Gen ADC P
Slide 6: Kv7 Platform Is Broadly Applicable to Hyperexcitability Disorders Beyond Epilepsy
Kv7 Platform Is Broadly Applicable to Hyperexcitability Disorders Beyond Epilepsy Kv7.1: cardiac Kv7.2: CNS BHV-7000 activator Kv7.3: CNS BHV-7000 activator Kv7.4: smooth muscle and inner ear Kv7.5: vascular tissue, neurons, skeletal muscle Stria Vascularis Organ of Corti Vascular tissue Gastrointes
Slide 7: Significant Unmet Needs Remain for Patients Living with Epilepsy
Significant Unmet Needs Remain for the 3.5 Million Patients Living with Epilepsy in the US After starting an ASM, 80% of patients experience burdensome adverse events, which can include: • Somnolence • Dizziness • Cognitive dysfunction • Mood disturbances 80% 1/3 people are treatment refractory desp
Slide 8: Third-Gen Kv7 Differentiation: BHV-7000 vs XEN1101 and Ezogabine
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 9: BHV-7000: First Kv7.2/7.3 Activator Designed to Exclude GABAA Activation
Rat Rotarod BHV-7000: First Kv7.2/7.3 Activator in Clinical Development Designed Specifically to Exclude GABAA Receptor Activation No impact on motor function observed with BHV-7000 across effective dose range Ti m e to fa ll - R ot ar od Vehicle 0.3 1 3 10 30 0 50 100 150 200 250 BHV-7000 (mg/kg) P
Slide 10: BHV-7000 Exhibits Highly Differentiated Preclinical Profile
BHV-7000 Exhibits Highly Differentiated Preclinical Profile Biohaven | Investor Presentation10 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 11: BHV-7000: Well-Tolerated Across Phase 1 SAD/MAD Cohorts
BHV-7000: Well-Tolerated Across Phase 1 SAD/MAD Cohorts MedDRA System Organ Class Placebo (N=15) n (%) BHV-7000 (N=46) n (%) Nervous system disorders 1 (6.7) 7 (15.2) Gastrointestinal disorders 1 (6.7) 6 (13.0) Musculoskeletal disorders 0 5 (10.9) Infections 0 2 (4.3) Investigations 1 (6.7) 2 (4.3)
Slide 12: BHV-7000: Phase 1 CNS TEAEs by Dose and Cohort
BHV-7000: Phase 1 SAD/MAD CNS TEAEs by Dose and Cohort CNS AEsa Placebo N=10 4 mg N=6 10 mg N=6 25 mg (Fasted) N=6 25 mg (Fed) N=6 50 mg N=6 100 mg N=5 BHV-7000 Overall N=29 Headache 0 0 1 (16.7) 1 (16.7) 0 1 (16.7) 0 3 (10.3) Dizziness 0 0 1 (16.7) 0 0 0 0 1 (3.4) Myoclonus 0 0 0 1 (16.7) 0 0 0 1 (
Slide 13: BHV-7000: Not Associated with CNS AEs Typical of Other ASMs
BHV-7000: Not Associated with CNS AEs Typical of Other ASMs 80% 80% of patients will experience an AE after starting an ASM1 Challenges with Existing ASMs GABAA pathway activated by other ASMs is associated with AEs such as somnolence and dizziness2 Several ASMs cause behavioral (irritability, anger
Slide 14: BHV-7000: Summary and Clinical Program Status
BHV-7000: Summary and Clinical Program Status • Potent, selective activator of Kv7.2/Kv7.3 potassium channels • Structurally/pharmacologically distinct from other K+ channel activators • Designed to “dial out” GABAA receptor activation, improve tolerability • Potent in MES epilepsy model without adv
Slide 15: BHV-7000: Phase 1 EEG Study in Healthy Volunteers
BHV-7000: Phase 1 EEG Study in Healthy Volunteers Study Objective: • Demonstrate BHV-7000 target engagement in the cerebral cortex and refine dose selection for Phase 3 Study Measures: • Continuous EEG monitoring & PK sampling • Evaluation of changes in EEG spectral power post dose Study Design Base
Slide 16: EEG Spectral Power Increases After 10 mg Dose of BHV-7000
Increases Observed in EEG Spectral Power Across Beta and Gamma Bands After a 10 mg Dose of BHV-7000 in Subjects With Drug Concentrations >EC50 PREDOSE POST DOSE G AM M A BE TA AL PH A TH ET A D EL TA FR E Q U N E C Y B A N D S E E G S P E C TR A L P O W E R BHV-7000: Spectral Power Changes Observed
Slide 17: BHV-7000: Spectral Power Increases After 50 mg Dose
BHV-7000: Increases in Spectral Power Were Observed in all Frequency Bands and all Brain Regions After 50 mg Dose SEPTEMBER 2023Biohaven | Investor Presentation17 HOT OFF THE PRESS Increases Observed in EEG Spectral Power Across All Frequency Bands After a 50 mg Dose of BHV-7000 Demonstrating Centra
Slide 18: BHV-7000: Predicted Concentration vs. Time Profiles for Extended Release
BHV-7000: Mean Predicted Concentration vs. Time Profiles of BHV-7000 Extended Release (ER) For 25 mg ER, 50 mg ER, 75 mg ER Once Daily Dosing at Steady State SEPTEMBER 2023Biohaven | Investor Presentation18 *EC20 and EC50 values from preclinical maximal electroshock seizure (MES) model M ea n Pr ed
Slide 19: BHV-7000: Phase 3 Trials in Focal Epilepsy
BHV-7000: Phase 3 Trials in Focal Epilepsy Two multicenter, international, placebo-controlled, double-blind studies to evaluate the efficacy of BHV-7000 in adolescents and adults with refractory focal epilepsy Randomization 1:1:1 Double-Blind Phase 8 and 12 weeks Extension Study 1+ years Placebo 25
Slide 20: Kv7 Platform Summary
Kv7 PLATFORM Summary Proprietary Chemical Library of Novel Kv7 Activators In-house synthesis with differentiated pharmacological and structural profiles and potential for multiple indications Kv7.2/7.3 Activation Clinically validated mechanism of action in epilepsy BHV-7000: Potential Best-in-Class
Slide 21: Bipolar Disorder Affects Millions of Adults in the US
Bipolar Disorder Affects 11 Million Adults in the US While characterized by mania, patients largely suffer from depression, yet few effective options for BPD and maintenance treatment1-4 ~50% of patients are medication nonadherent; discontinuations commonly due to poor tolerability4,5~50% No new moo
Slide 22: Compelling Evidence for Kv7 Activation in Bipolar Disorder Treatment
Compelling Evidence for Kv7 Activation in Bipolar Disorder Treatment Overlapping molecular, cellular mechanism in bipolar disorder ü ANK-3: highly implicated gene in bipolar disorder; codes for a protein that anchors Kv7 channels to the cell membrane1 ü Kv7.2/7.3 channels among most dysregulated pro
Slide 23: BHV-7000: Potential for Clinical Translation of Kv7 Activation in Bipolar Disorder
BHV-7000: Demonstrates Potential for Clinical Translation of Kv7 Activation in Bipolar Disorder Kv 7. 2 Kv 7. 3 BHV-7000 Retigabine1 Increased M-current Reduced neuronal hyperactivity Lamotrigine2 Lithium3 indirect BHV-7000 shares mechanistic overlap with cornerstone bipolar treatments indirect Reti
Slide 24: BHV-7000: Potentially Addresses Key Unmet Needs in Bipolar Disorder
BHV-7000: Potentially Addresses Key Unmet Needs in Bipolar Disorder by Reducing Stress-Related Hyperactivity While Enhancing Resilience • Patients change / discontinue medication after ~2 months • >50% of patients discontinue at 6 months due to intolerance1 ü Favorable safety and tolerability over c
Slide 25: BHV-7000: Potential to Overcome Challenges With Existing Therapies
BHV-7000: Potential to Overcome Challenges With Existing Therapies Potential for best-in-category tolerability and safety • Low burden to patients and providers, enabling safer, easier long-term treatment • No expected long-term metabolic side effects, no “switching” risk, no titration, and no drug
Slide 26: TRPM3: A Novel Peripheral Target for Neuropathic Pain
TRPM3: A Novel Peripheral Target for Neuropathic Pain Oral class terminated for hyperthermia No new molecules in this class despite promising Multiple TRPA1 programs terminated Conflicting data for pro- and anti-nociceptive role; remains in active drug development Promising as a novel target: broade
Slide 27: 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 Presentation27 BHV-2100 5 mg/kg BHV-2100 25 mg/kg Tramadol 5 mg/kg BHV-2100 1 mg/kg
Slide 28: BHV-2100: A Versatile Agent for Multiple Pain Conditions
Molecular Characteristics Molecular characteristics predict convenient, safe molecule with optimal target product profile for a daily oral medicine BHV-2100: A Versatile Agent for Treatment of Multiple Pain Conditions Unmet Need in Neuropathic Pain Disorders >50% of patients with common neuropathic
Slide 29: TYK2 (BHV-8000) Overview
TYK2 (BHV-8000) Overview First-in-Class Oral Brain-Penetrant TYK2/JAK1 Inhibitor Uniquely potent, TYK2/JAK1 selective, brain penetrant inhibitor Breaks the Cycle of Neuroinflammation Reduces inflammatory impacts of microglia, astrocytes, & infiltrating T-lymphocytes Potential in Multiple Neuroinflam
Slide 30: BHV-8000: TYK2/JAK1 in Neuroinflammatory Disease
BHV-8000: TYK2/JAK1 in Neuroinflammatory Disease • Dual inhibition of TYK2 and JAK1 can effectively block Th17 cell generation, Type I IFN signaling, and inflammation • JAK inhibitors are more efficacious anti-inflammatory agents than anti-TNFs JAK2JAK3JAK1 IFNγ IL-6 TYK2 Type I IFN IL-23 → IL-17 IL
Slide 31: Cellular Drivers in Neuroinflammation: Predominant TYK2/JAK1 Effects
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 32: BHV-8000: Summary
BHV-8000: Summary Selectivity is a differentiator • Selective inhibition of TYK2/JAK1 provides potential for best-in-class immunomodulation in neuroinflammatory disorders • Selectivity for TYK2/JAK1 mitigates non-selective JAK class liabilities, largely related to JAK2 and JAK3 inhibition, and offer
Slide 33: Properties of TYK2/JAK1 Selective Inhibitors Ideal 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 34: BHV-8000: Targets Both Axes of Neuroinflammation in Parkinson's Disease
BHV-8000: Targets Both Axes of Neuroinflammation in Parkinson’s Disease Dopaminergic neuron 1. a-syn aggregates in dopaminergic neurons Microglia 5. Microglia present α-syn to T cells with MHCII Th1/Th17 cells 3. Microglia release chemokines to recruit T cells to CNS 6. T cells release IFN-γ, which
Slide 35: 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 EAE model due to Th17 cell effects • In a meta-analys
Slide 36: TYK2/JAK1 Inhibition Reduces Key Cytokines Driving Alzheimer's Pathology
TYK2/JAK1 Inhibition Reduces Several Key Cytokines Driving Alzheimer’s Disease (AD) Pathology Neuroinflammation is a key event in AD pathogenesis, suggesting that a combination of anti-amyloid β (Aβ)/tau and anti-inflammation therapies is necessary1,2 Neuroinflammation Aβ plaque deposition + tau acc
Slide 37: OCD Summary: Troriluzole Glutamate Platform
Biohaven | Investor Presentation37 OBSESSIVE COMPULSIVE DISORDER (OCD) • Compelling mechanistic rationale for cortico-striatal glutamate abnormalities in OCD patients • Strong PoC in Phase 2 • Well-characterized in 1,000+ patients • Two Phase 3 studies ongoing; enrollment completion anticipated YE 2
Slide 38: Troriluzole in OCD: Framing the Unmet Need
Troriluzole in OCD: Framing the Unmet Need OCD Affects 1.2% of the US population, but only 1 in 6 people with OCD are treated with a pharmaceutical medication Limited ongoing investigations in the treatment of OCD, predicting a paucity of new approved agents in the near future Ketamine shown to have
Slide 39: Troriluzole in OCD: Strong Signal Observed 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 40: Myostatin Platform: Taldefgrobep Alfa
Myostatin Platform TALDEFGROBEP ALFA BHV-2000 Non-Clinical • Well characterized in over 20 animal studies for safety and models of disease • Includes juvenile animals permitting the safety down to 2 years of age Clinical • In prior studies, 359 participants received taldefgrobep: 179 healthy partici
Slide 41: Myostatin and Activin A are Potent Muscle Regulators
Myostatin and Activin A are Potent Muscle Regulators SEPTEMBER 2023Biohaven | Investor Presentation41 Blocking Myostatin and Activin A Leads to Muscle Hypertrophy • Myostatin is a secreted protein belonging to the TGF-ß superfamily of signaling molecules • Myostatin signals by binding initially to t
Slide 42: Taldefgrobep Alfa: Differentiated Mechanism of Action
Taldefgrobep Alfa: Differentiated Mechanism of Action SEPTEMBER 2023Biohaven | Investor Presentation42 • Taldefgrobep is a fusion protein designed to have optimal affinity for myostatin and not other members of TGF-ß pathway • Non-clinical studies show that taldefgrobep binds to myostatin at activin
Slide 43: Taldefgrobep Alfa: Activity Confirmed in Human Studies
Myostatin Free and Drug Bound Levels Taldefgrobep Alfa: Activity Confirmed in Human Studies SEPTEMBER 2023Biohaven | Investor Presentation43 • Healthy volunteers showed dose dependent increases in exposure and lowering of free myostatin when administered subcutaneously on a weekly basis for 4 weeks
Slide 44: Myostatin: Strong Scientific Rationale in Spinal Muscular Atrophy
Myostatin: Strong Scientific Rationale in Spinal Muscular Atrophy SEPTEMBER 2023Biohaven | Investor Presentation44 COMBINATION THERAPY STUDIES OF SMN UPREGULATION IN SMA DISEASE MOUSE MODEL DEMONSTRATED: ü Improved life span and strength, along with improved muscle function ü Increased nerve branchi
Slide 45: Phase 3 RESILIENT Study Overview
Phase 3 RESILIENT Study Overview RESILIENT is a randomized, placebo-controlled trial testing the effectiveness and safety of taldefgrobep as an adjunctive treatment Taldefgrobep, or a placebo, will be given while the participant is: • Already taking a stable dose of nusinersen and/or • Already takin
Slide 46: RESILIENT Study Population
RESILIENT Study Population • We include a broad population given high unmet need across SMA population, and changing treatment paradigms • Field has evolved with disease modifying therapies and widespread newborn screening, early treatment, and potentially combinations of therapies • Shift to focus
Slide 47: Obesity is a Public Health Crisis
Obesity is a Public Health Crisis • Obesity is a DISEASE of excess and/or abnormal adipose tissue § Cardio-metabolic risk is closely correlated with visceral adiposity • By 2030, it is estimated that 1 billion people worldwide will be living with obesity, including ~50% of American adults1 § Obesity
Slide 48: Entering a New Era of Hope and Opportunity for Adults Living with Obesity
Entering a New Era of Hope and Opportunity for Adults Living with Obesity • This is a time of rapid change and renewed excitement in the weight management space • Highly potent anti-obesity medications (AOMs) and combination therapies are approaching efficacy outcomes comparable to bariatric surgery
Slide 49: Comparative Efficacy Outcomes in Adults Living with Overweight and Obesity
Comparative Efficacy Outcomes in Adults Living with Overweight and Obesity • In the clinic, anti-myostatin therapies have repeatedly demonstrated the ability to increase lean mass, reduce fat mass, and improve glucose metabolism across diverse patient populations • Improvements in body composition a
Slide 50: Inhibiting Myostatin Signaling Demonstrates Important Physical and Metabolic Change
Inhibiting Myostatin Signaling Demonstrates Important Physical and Metabolic Change Myostatin as a Pharmacologic Target Improved bone mineral density Increased basal metabolic rate Improved insulin sensitivity Reduction in intramuscular fat Reduction in intrahepatic fat Reduction in total body fat m
Slide 51: Advancing Taldefgrobep in Obesity
Advancing Taldefgrobep in Obesity • Leveraging available pre-clinical and early clinical data allows for significant acceleration of development timelines • Pre-IND meeting for obesity completed with FDA • Proof-of-concept trial in adults living with overweight and obesity NOVEL MECHANISM TARGETING
Slide 52: Myostatin Platform: Novel Mechanism of Blocking Myostatin and Activin A
Myostatin Platform TALDEFGROBEP ALFA BHV-2000 Novel Mechanism of Blocking Myostatin and Activin A Signaling • Human data showing potent reduction in free myostatin and accumulation of myostatin-taldefgrobep complex • Short duration clinical studies demonstrated improvement in lean body mass and loss
Slide 53: Degrader Platform Overview
DEGRADER PLATFORM Overview A Pipeline of Therapies Potential to support numerous clinical candidates spanning across a wide range of indications by targeting pathogenic proteins and antibodies Potential First-in-Class Targeted Protein Degradation MOA Provides unique advantages, e.g. accelerated path
Slide 54: MoDE Degraders: Multiple Asset Opportunities and Efficient Timelines
MoDE™ Degraders: Multiple Asset Opportunities and Efficient Timelines Key Value Inflection Points IgG and IgA antibodies are the first targets for Biohaven’s powerful degradation platform PROGRAM 2023 2024 2025 2026 2027 Discovery targets Realization of value inflection points will be project specif
Slide 55: 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™ SEPTEMBER 2023Biohaven
Slide 56: A First-in-Class Mechanism: Hepatic ASGPR Receptor Harnessed
A First-in-Class Mechanism: Hepatic ASGPR Receptor Harnessed for Efficient and Safe Removal of Circulating Pathogenic Targets SEPTEMBER 2023Biohaven | Investor Presentation56 MoDE™ binds circulating target and efficiently delivers it to ASGPR on hepatocytes • Internalized target is rapidly degraded
Slide 57: Hepatic ASGPR Receptor Harnessed for Removal of Pathogenic Targets
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 be
Slide 58: 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 SEPTEMBER 2023Biohaven | Investor Presentation58 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
Slide 59: BHV-1300 Selected for Efficiency in Removal of Human IgG in Mouse
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 SEPTEMBER 2023Biohaven | Investor Prese
Slide 60: IgG is Specifically Depleted: IgA and IgM Levels Unchanged
IgG is Specifically Depleted: IgA and IgM Levels Remain Unchanged SEPTEMBER 2023Biohaven | Investor Presentation60 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
Slide 61: BHV-1300 Administered by SC, IM or IV Has Comparable Bioavailability
BHV-1300 Administered by SC, IM or IV Routes has Comparable Bioavailability SEPTEMBER 2023Biohaven | Investor Presentation61 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
Slide 62: BHV-1300: Potential for Superiority Over SOC (Efgartigimod)
BHV-1300: Shows Potential for Superiority Over SOC (Efgartigimod) Biohaven | Investor Presentation The Journal of Clinical Investigation 2018:128(10):4372-4386. httos://doi.org/10.1172/JC197911. IgG, immunoglobulin G; NHP, non-human primate; SOC, standard of care BHV-1300 demonstrated faster depleti
Slide 63: BHV-1300: Repeat Dosing Allows for Deep Reductions
BHV-1300: Repeat dosing allows for deep reductions of over 90% -200 200 400 Day 0 ↓ Day 8 ↓ Day 15 ↓ 0 50 100 150 Hours % c ha ng e / T 0 IgG: % by group:1:200K Control BHV1300, 75mg/kg BHV1300, 250mg/kg BHV1300, 375mg/kg BHV1300, 500mg/kg Day -7 0 Dose BHV-1300: NHP Pharmacodynamics Combined result
Slide 64: BHV-1300: Specific and Rapid Pathogenic Target Removal
BHV-1300: Specific and Rapid Pathogenic Target Removal • Mechanism not expected to cause hypoalbuminemia or dyslipidemia • Improved and optimizable potency for target removal • Deeper target removal when required • Improved pharmacodynamics with faster onset of action than FcRn inhibition • Improved
Slide 65: BHV-1300 Differentiated From FcRn Class Competitors
BHV-1300 DIFFERENTIATED FROM COMPETITORS in FcRn class such as efgartigimod and nipocalimab with a unique MOA, faster onset, and predicted to have improved safety PHASE 2 STUDY Start in 2024 BHV-1300: Has Potential to Add Significant Value Across Rare And Common Diseases With a Differentiated Profil
Slide 66: Rheumatoid Arthritis Is a Heterogenous Autoimmune Disorder
Rheumatoid Arthritis Is a Heterogenous Autoimmune Disorder Marked by Autoantibodies of Various Classes 1. Adapted from Van Delft and Huizinga, An overview of autoantibodies in rheumatoid arthritis; J Autoimmun 2020. 2. UpToDate accessed Jan 2023. At risk Rheumatoid Arthritis Transition to symptomati
Slide 67: Autoantibody Presence is a Main Feature of Rheumatoid Arthritis
• Rheumatoid Factor (RF) antibodies are primarily IgM but form immune complexes with IgG • Anti-citrillunated protein antibodies (ACPAs) including anti- cyclic citrullinated peptide-2 (anti-CCP2) are primarily IgG, but some IgA and IgM species exist • All immune complexes can cause damage in joints,
Slide 68: Gd-IgA1-Specific MoDE Selectively Degrades Gd-IgA1
Preclinical Studies Show the Gd-IgA1–Specific MoDE™ Selectively Degrades the Gd-IgA1 Present in IgAN Ab, antibody; EC50, half maximal effective concentration Gd, galactose-deficient; Ig, immunoglobulin; IgAN, IgA nephropathy; MoDE™, molecular degrader of extracellular proteins • Reduces only pathoge
Slide 69: MoDE Shows Rapid Reduction of Pathogenic AutoAb
Greatly Reduced Half-life Compared to Controls Treatment Half-life (h) Antigen-MoDE™ <2 Antigen (Neg. Control) 27.5 PBS 29.7 Study Design Leveraging Known AutoAb Epitope–MoDE™ Shows Rapid Reduction of Pathogenic AutoAb Day -1 0 1 2 3 4 Antibody injection Blood draw Drug injection 0 1 2 3 4 0 20 40 6
Slide 70: Summary: Biohaven MoDE Extracellular Degraders Provide Optionality
Summary: Biohaven MoDE™ Extracellular Degraders Provide Optionality Subcutaneous or intravenous injection ü Numerous extracellular and circulating targets are involved in pathology and make excellent targets ü IND 2H 2023 for lead program BHV-1300 which has “pipeline in a product” potential • BHV-13
Slide 71: 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 72: 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 Presentation72 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 73: Advancing Next-Generation, Site-Specific Antibody Drug Conjugates
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 74: Biohaven's Next-Generation Site-Specific ADCs
Biohaven’s Next-Generation Site-Specific ADCs ü ADAPTABLE Complements and improves multiple existing ADC payload-linker technologies ü STABLE Improved ADC plasma stability with controlled DAR potentially improves therapeutic index ü EFFECTIVE Improved efficacy in mouse tumor model also suggests pote
Slide 75: Challenges of Alternate ADC Protein Engineering and Chemistry
• Nearly all existing methods involve extensive antibody manipulation or engineering • Potential impact on activity, clearance, immunogenicity, and COGs • Drug linkage can reverse over time, “leaking” free payload Challenges of Alternate ADC Protein Engineering and Chemistry N Payload S O O N Payloa
Slide 76: Potential Best-in-Class Site-Specific ADCs
N N N N O Payload Click chemistry to engineered antibody Undesirably large, lipophilic linkage Biohaven chemistry Stable, physicochemically benign amide linkage O Payload N H Potential “Best-in-class” Site-specific ADCs N PayloadS O O Industry standard maleimide Poorly stable linkage IMPROVED LINKER
Slide 77: BH3973: Improved Plasma Stability Over Adcetris
Time, h Mouse Time, h % C ha ng e Human Time, h MouseHuman % C ha ng e RT 37C RT 37C Time, h BH3973: Improved Plasma Stability Over Adcetris® • ADC toxicity/tolerability directly relates to free payload • Enhanced stability reduces free payload, and potentially allows for higher drug concentration a
Slide 78: Adcetris and BH3973 Demonstrate Comparable PK
Adcetris® and BH3973 Demonstrate Comparable PK • BH3973 half-life 7-8 days across all doses • Adcetris® half-life 5-6 days across all doses BH3973 Adcetris® SEPTEMBER 2023Biohaven | Investor Presentation78
Slide 79: BH3973: Potential for Superior Efficacy to Adcetris
BH3973: Demonstrates Potential for Superior Efficacy to Adcetris® Biohaven | Investor Presentation 0 500 1000 1500 2000 2500 1 4 8 11 15 18 22 25 29 32 37BH3973 3.0 mg/kg Adcetris® 0.3 mg/kg BH3973 0.3 mg/kg Tu m or v ol um e (m m 3 ) Days Isotype control Adcetris® 3.0 mg/kg BH3973 1.0 mg/kg (8/10 r
Slide 80: BH3973: Improves Survival in Preclinical Model
BH3973: Improves Survival in Preclinical Model Compared to Adcetris® With Half the Payload Biohaven | Investor Presentation 0 5 10 15 20 25 30 35 40 45 50 55 60 0 10 20 30 40 50 60 70 80 90 100 Effect of Treatment on Survival (Dose @ 0.3 mg/kg + Controls) Study Day Su rv iv al (% ) No Treatment BH39
Slide 81: BH3973: Summary
BH3973: Summary üExisting, highly effective ADC formats such as Adcetris® and optimized warheads may potentially be enhanced with improved safety, efficacy, manufacturability and patent life üDifferentiated in vivo efficacy and safety results of BH3973 compared to Adcetris® üBroad patent coverage BI
Slide 82: 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 ~$349.0 million2 SHARE O/S CASH & MARKETABLE SECURITIES POTENTIAL ROYALTIES 1. Excludes
Slide 83: Anticipated Near-Term Milestones
INDICATIONS 1H 2023 2H 2023 2024 BHV-7000 Kv7 Channel Activator Focal Epilepsy Bipolar Disorder BHV-7010 Kv7 Channel Activator Epilepsy and Mood Disorders BHV-2100 TRPM3 Chronic Pain Disorders BHV-8000 TYK2/JAK1 Neuroinflammatory Disorders Troriluzole NCE Prodrug of Riluzole Obsessive-Compulsive Dis