advancing innovative therapies for neurological diseases

NYSE: BHVN© 2018 Biohaven Pharmaceuticals. All rights reserved.

November 01, 2018

Advancing Innovative Therapies for Neurological Diseases

Biohaven Investor Presentation

Disclaimer

This presentation contains forward-looking statements, including: statements about our plans to develop and commercialize our product candidates, our planned clinical trials for our rimegepant, BHV3500, troriluzole, BHV0223, BHV5000 and BHV3241 development programs, the timing of the availability of data from our clinical trials, the timing of our planned regulatory filings, the timing of and our ability to obtain and maintain regulatory approvals for our product candidates and the clinical utility of our product candidates, alone and as compared to other treatment options. These statements involve substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements in this presentation represent our views as of the date of this presentation. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation. For further information regarding these risks, uncertainties and other factors you should read the “Risk Factors” section of the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the ”SEC”) on August 14, 2018 and the Company’s other periodic reports filed with the SEC.

This presentation also contains market data and other statistical information that are based on independent industry publications, reports by market research firms or published independent sources. Some market data and statistical information are also based on the Company's good faith estimates, which are derived from management's knowledge of its industry and such independent sources referred to above. While the Company is not aware of any misstatements regarding the market and industry data presented herein, such data involve risks and uncertainties and are subject to change based on various factors.

NOVEMBER 2018 ADVANCING INNOVATIVE THERAPIES FOR NEUROLOGICAL DISEASES 2


BIOHAVEN CORPORATE OVERVIEW

Positioned For Near-Term Milestones and Long-Term Success

CGRP PLATFORM

Three Novel Small-Molecule Platforms

GLUTAMATEPLATFORM

MPOPLATFORM

Migraine and Pain Two positive Phase 3 trials

Alzheimer’s and AnxietyFour Phase 2/3 trials

NeuroinflammationPhase 2 study in MSA

Strong intellectual property protection; exclusive license agreements

Deep experience across all platforms

Cost-efficient R&D< 60 full-time employees

Biohaven’s Advanced Pipeline


Preclinical Phase 1 Phase 2 Phase 3 Approval

RIMEGEPANT (BHV3000-301 and -302) | Acute Treatment of Migraine Tablet

RIMEGEPANT (BHV3000-303) | Acute Treatment of Migraine Rapid Dissolving

Data inRIMEGEPANT (BHV3000-201) | Open Label Long-Term Safety Study Tablet

RIMEGEPANT (BHV3000-305) | Prevention of Migraine Tablet

NURTEC™ (BHV0223) | Amyotrophic Lateral Sclerosis (ALS)* Rapid Dissolving

TRORILUZOLE (BHV4157-203) | Alzheimer’s Disease (AD) † Capsule

TRORILUZOLE (BHV4157-202) | Obsessive-Compulsive Disorder (OCD) Capsule

TRORILUZOLE (BHV4157-206) | Spinocerebellar Ataxia (SCA) Capsule

BHV-5000 | Neuropsychiatric Indications Capsule

CGRP PLATFORM FOR MIGRAINE

GLUTAMATE PLATFORM FOR NEUROPSYCHIATRIC INDICATIONS

Delivery

BHV-3500 | Acute Treatment and Prevention of Migraine Nasal Spray

TRORILUZOLE (BHV4157-207) | Generalized Anxiety Disorder (GAD) Capsule Anticipated start 1Q2019

Anticipated start 4Q2018



MYELOPEROXIDASE INHIBITION PLATFORM FOR NEUROINFLAMMATION BHV-3241 | Multiple System Atrophy (MSA) Tablet

* 505(b)(2) † External collaboration with Alzheimer’s Disease Cooperative Study (ADCS) group

Anticipated start Mid 2019

CGRP PLATFORMTherapies for Migraine

CGRP Platform for Migraine


Preclinical Phase 1 Phase 2 Phase 3 Approval

Data in

RIMEGEPANT (BHV3000-301) | Acute Treatment of Migraine Tablet

RIMEGEPANT (BHV3000-303) | Acute Treatment of Migraine Rapid Dissolving

RIMEGEPANT (BHV3000-302) | Acute Treatment of Migraine Tablet

RIMEGEPANT (BHV3000-201) | Open Label Long-Term Safety Study Tablet

RIMEGEPANT (BHV3000-305) | Prevention of Migraine Tablet

Delivery

Submit NDA in 2019

Submit NDA in 2019

Initial results expected 4Q2018

Topline results expected 4Q2018

Start Phase 3 in 4Q2018

Zydis® ODT Fast Dissolve Technology

BHV3500 | Acute Treatment and Prevention of Migraine Nasal Spray

File IND and commence Phase 1 in 2018 Aptar UDS Single shot technology

Historical Segmentation of Migraine Therapy: Time to Revisit and Rethink

ADVANCING INNOVATIVE THERAPIES FOR NEUROLOGICAL DISEASES

PREVENTIVE TREATMENT

• Indicated based on headache frequency & headache related impairment, including:• Chronic Migraine (CM) patients (~3.6M) • Patients appropriate for prevention

without CM diagnosis (~10.4M) • These patients also need acute treatment• CGRP agents targeting indication:

• Antibodies: Alder, Amgen, Lilly, Teva• Small molecules: Biohaven, Allergan

~36M People with Migraine

in the U.S.1

1. American Migraine Foundation2. ICHD-3b International Classification of Headache Disorders3. Lipton RB, Bigal ME, Diamond M, et al. Neurology. 2007;68(5):343-349.

~14M (39%3)~36M (100%)

ACUTE TREATMENT• 100% of patients need acute therapy• Diagnosis: Migraine with/without aura2

• Take as needed to abort attack• CGRP agents targeting indication:

• Small molecules: Biohaven, Allergan

Biohaven is disrupting the historical two segment migraine paradigm by advancing novel treatments with potential dual-therapy action (acute and preventive treatment)

Stylized pie-chart: NOT brain anatomy

NOVEMBER 2018 7

Multiple Formulations, Meeting Patient Needsfrom Acute Treatment to Prevention of Migraine


NOJECTION™ CGRP Drug Delivery Platform

* Exclusive World-Wide License with Catalent for use of Zydis® Fast Dissolve Technology in our migraine product candidates** Aptar Pharma Unit-Dose System (UDS) single shot nasal technology

Oral Rapid Dissolving* Intranasal**

Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist: Mechanism of Action in Migraine1

Inhibition of Pain Transmission

Decreasing Artery Dilation

Blocking Neurogenic Inflammation


1 From N Engl J Med, Durham PL, CGRP-Receptor Antagonists — A Fresh Approach to Migraine Therapy? 350:1073-1075, Copyright © 2018 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society."

Rimegepant: Well Tolerated in Phase 1 and Phase 2b

10

Testing of very high doses in Phase 1 and 2b provides evidence of acceptable tolerability for 75 mg dose

Phase 2b Safety Data

• Phase 1: Well tolerated at high doses– Ultra-high exposures up to 1,500 mg well tolerated – high

doses achieved daily exposures >50-fold therapeutic dose– 600 mg administered for up to 14 days

• Phase 2b: Well tolerated at all doses– Most AEs of mild or moderate severity– 75 mg dose with comparable AEs to placebo– AEs of chest discomfort only reported in sumatriptan group– No clinically important findings on ECG,

physical exam, lab assessments or vital signs• Preclinical: Large safety multiples at 75 mg (AUC)

– 23x below rat NOEL (3)

– 56x below monkey NOAEL (4)

Number (%) of Patients Reporting a Commonly Occurring Adverse Event within 48 Hours Post-Dose (1)(2)

Rimegepant Sumatriptan Placebo

Patients, n (%)

10 mg n=72

25 mg n=62

75 mg n=86

150 mg n=86

300 mg n=112

600 mg n=84

100 mg n=100 n=209

Nausea 1 (1) - 3 (3) 3 (3) 5 (4) 7 (8) 2 (2) 5 (2)

Dizziness 2 (3) 1 (2) 1 (1) 2 (2) - 3 (4) 1 (1) 2 (1)

Vomiting - 2 (3) 2 (2) - - 2 (2) 1 (1) 5 (2)

Diarrhea 4 (6) - - - 1 (1) - - -

Paresthesia - - - - - - 2 (2) 2 (1)

Dysgeusia 2 (3) - - - - - - -

Chest Discomfort - - - - - - 2 (2) -

Myalgia 2 (3) - - - - - - -

(1) Marcus R, et al. (2014). Cephalalgia 34(2): 114-125(2) Adverse events occurring in ≥2% of patients in any treatment group; ordered by

frequency in the rimegepant 600 mg group. n: number (%) of patients who took at least one tablet of study drug

(3) NOEL = no observable effect level (4) NOAEL = no observable adverse effect level

Summary of Clinical Safety Data

NOVEMBER 2018 ADVANCING INNOVATIVE THERAPIES FOR NEUROLOGICAL DISEASES

Rimegepant: Comprehensive and Durable Treatment Effect Observed in Phase 2b

0

25

50

75

100

Placebo 10 25 75 150 300 6000

25

50

75

100

Placebo 10 25 75 150 300 600

Overview of Phase 2b Trial (1)

• Double-blind, randomized, placebo-controlled, dose-ranging clinical trial completed by BMS

• 812 patients suffering from migraine attacks received either placebo, sumatriptan 100 mg or rimegepant dosed at 10, 25, 75, 150, 300 or 600 mg

• Rimegepant dosed at 75 mg was observed to have comprehensive and durable treatment effect

203 61 86 85 111 82100 71Patients (n)Rimegepant (mg)

**

Sustained Pain Freedom and Pain Relief 2-24 Hours Post-Dosing

**

**

**

**

**

****

**

**

*

**

Nausea, Phonophobia and Photophobia Freedom Two Hours Post-Dosing

203 61 86 85 111 82100 71Patients (n)

** ****

** ****

****

****

**

Patie

nts

(%)

Rimegepant (mg)203 61 86 85 111 82100 71Patients (n)

Pain Freedom Two Hours Post-Dosing

** **** **

Sumatriptan, 100 mg

Sumatriptan, 100 mg

Sumatriptan, 100 mg

Rimegepant (mg)

(1) Marcus R, et al. (2014). Cephalalgia 34(2): 114-125

*

* p < 0.05 ** p < 0.01

0

10

20

30

40

50

Placebo 10 25 75 150 300 600

Patie

nts

(%)

Pain Freedom Pain Relief

Patie

nts

(%)

Nausea Freedom Phonophobia Freedom Photophobia Freedom

11NOVEMBER 2018 ADVANCING INNOVATIVE THERAPIES FOR NEUROLOGICAL DISEASES

RIMEGEPANT (BHV-3000) PHASE 3 HIGHLIGHTS

Rimegepant Demonstrates Comprehensive and Durable Efficacy across Two Pivotal Phase 3 Trials with a Single Dose


• Primary endpoints achieved in two pivotal Phase 3 trials• Pain freedom at two hours• Freedom from most bothersome symptom (MBS) at two hours

• Clinically important drug benefit across multiple outcome measures• Majority of patients achieved pain relief within two hours (speed of onset)• Sustained efficacy out to 48 hours on multiple measures (durable benefit)• High proportion of patients achieving normal function• Low use of rescue meds

• Placebo-like safety and tolerability• Safety profile similar to placebo including liver function tests• Adverse events profile similar to placebo and favorable compared to historical triptan experience

• Consistent results across endpoints and efficacy trials

RIMEGEPANT (BHV-3000) PHASE 3 – STUDY 302

Increasing Benefit Over Time on Pain Freedom After Single Dose


Single Dose of Rimegepant, No Rescue Meds

0

20

40

60

80

100

2 hr 3 hr 4 hr 6 hr 8 hr

% o

f Pat

ient

s Pa

in F

ree

Pain Freedom 2-8 HoursPost-Single Dosing with Rimegepant 75 mg

Time

Rimegepant 75 mg (n=537)Placebo (n=535)

20%

66%

33%

43%

54%

Data are Kaplan-Meier estimates of Pain Freedom; subjects were censored (not included) who took rescue medication or were lost to follow-up during the specified interval



Durable Pain Freedom Benefit through 48 Hours After Single Dose

Sustained Pain Freedom

Rimegepant n=537

Placebo n=535 p-value

2 to 24 hrs 12.3% 7.1% 0.0040

3 to 24 hrs 19.9% 10.8% <0.0001

4 to 24 hrs 26.8% 14.4% <0.0001

2 to 48 hrs 9.9% 5.6% 0.0181

3 to 48 hrs 16.2% 9.7% 0.0015

4 to 48 hrs 21.4% 12.2% <0.0001

Sustained Pain Freedom1 from 2, 3, & 4 to 24 or 48 hours

24 hr

48 hr


1. Sustained Pain Freedom is defined as having no headache pain during the specified interval, with no use of rescue medication


Pain Relief1: Early Separation and Continued Improvement Without Additional Dosing or Rescue Medications

Prob

abilit

y of

Pai

n R

elie

f

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.00 30 60 90 120 180 240 300 360 420 480 520

Time (minutes)

Rimegepant (n=537)Placebo (n=535)

63%

79%

91%

Kaplan-Meier Curve of Time to Pain Relief

up to 8 Hours Post Single Dose

Single Dose of Rimegepant,

No Rescue Meds


1. Pain Relief is defined as patients who have either mild-pain or no-pain during the specified interval. Data are Kaplan-Meier estimates of Pain Relief; subjects were censored (not included) who took rescue medication or were lost to follow-up during the specified interval.



Durable Pain Relief Through 48 Hours After Single Dose

Sustained Pain Relief

Rimegepant n=537

Placebo n=535 p-value

2 to 24 hrs 42.6% 26.5% <0.0001

3 to 24 hrs 49.5% 29.9% <0.0001

4 to 24 hrs 52.9% 36.1% <0.0001

2 to 48 hrs 36.3% 22.6% <0.0001

3 to 48 hrs 42.3% 25.0% <0.0001

4 to 48 hrs 45.1% 29.9% <0.0001

Sustained Pain Relief1 from 2, 3, & 4 to 24 or 48 hours

24 hr

48 hr


1. Sustained Pain Relief is defined as patients who have either mild-pain or no-pain pain during the specified interval, with no use of rescue medication



Increasing Proportion of Patients Are Free from Most Bothersome Symptom (MBS)1 Following Single Dose of Rimegepant, No Rescue Meds

Prob

abilit

y of

MBS

Fre

edom

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.00 30 60 90 120 180 240 300 360 420 480 520

Time (minutes)


Kaplan-Meier Curve of Time to MBS Freedom up to 8

Hours Post Single Dose


No Rescue Meds

1. Freedom from Most Bothersome Symptom defined by each patient as either photophobia, phonophobia or nausea for this attack. Data are Kaplan-Meier estimates of MBS Freedom; subjects were censored (not included) who took rescue medication or were lost to follow-up during the specified interval



Freedom from Functional Disability: Greater Proportion of Patients Achieving Normal Function on Rimegepant

Data are Kaplan-Meier estimates of Functional Disability Freedom; subjects were censored (not included) who took rescue medication or were lost to follow-up during the specified interval

Four Point Scale: • Normal Function• Mild Impairment • Severe Impairment • Required Bedrest

Prob

abilit

y of

Fun

ctio

nal D

isab

ility

Free

dom

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.00 30 60 90 120 180 240 300 360 420 480 520

Time (minutes)

Kaplan-Meier Curve of Time to Functional Disability Freedom up to 8 Hours Post

Single Dose


No Rescue Meds



Rescue Medicine Use: Rimegepant Treated Patients Had Lower Use of Rescue Medicine and Delayed Time to Use

Data are Kaplan-Meier estimates of Rescue Medicine Use; subjects were censored (not included) at the time of taking rescue medication, and those lost to follow-up were censored at the end of the specified interval

Prob

abilit

y of

Res

cue

Med

icin

e U

se

0.5

0.4

0.3

0.2

0.1

0.00 2 4 6 8 10 12 14 16 18 20 24

Time (hours)


22

Kaplan-Meier Curve of Time to Rescue Medicine Use up to 24 Hours Post

Single Dose


No Rescue Meds



More Than 3x of Subjects Who Responded to TreatmentPreferred Rimegepant Over Their Previous Treatment

62% Preferred Rimegepant over Prior

Standard of Care

Preferred Previous Treatment, 17%

No Preference, 21%

n=232 who responded to treatment and provided a response (Study 302); Placebo Responders (n=176) 47% preferred study medication, 28% previous treatment, 24% no preference.


Preference of Medication at 24 Hours in Subjects Who Responded to Treatment

RIMEGEPANT (BHV-3000) PHASE 3 – STUDY 301 & 302

Rimegepant was Well Tolerated in Phase 3: No Single Adverse Event Occurring > 2%

PERCENT (NUMBER) OF PATIENTS REPORTING AN ADVERSE EVENT WITHIN 48 HOURS POST-DOSE ≥ 1% INCIDENCE

Adverse Event Placebon=1092

Rimegepantn=1089

≥ 1 On-Study AE* 12.5% (136) 14.9% (162)

Nausea 1.1% (12) 1.4% (15)

UTI 0.7% (8) 1.0% (11)

SAEs** 0.3% (3) 0.3% (3)

* No other individual AEs ≥ 1% than listed in table. Includes all AEs without attribution to drug relatedness. ** No drug-related Serious Adverse Events (SAEs). 2 of the subjects with SAE in rimegepant group and 1 in placebo group had not been dosed before onset of SAE.

Pooled Adverse Event (AE) Safety Data from Study 301 and Study 302



Rimegepant Ph 3 Pooled Liver Function Test (LFT) Profile: Rimegepant was Similar to Placebo in Both Studies

COMPLETE DATASET OF LFT RESULTSFROM STUDY 301 AND STUDY 3021

ALT or AST Placebo n=1092

Rimegepant n=1089

> ULN2 32 (2.9%) 24 (2.2%)

> 3x ULN 1 (0.1%) 1 (0.1%)

> 5x ULN 0 0

> 10x ULN 0 0

> 20x ULN 0 0

1. No bilirubin elevations >2x ULN across both Studies 301 and 3022. ULN: upper limit of normal; ALT: alanine aminotransferase; AST: aspartate aminotransferase



Rimegepant Met Both Primary Endpoints and Achieved Benefits Over Placebo in 11 of 13 Primary and Secondary Endpoints in 2 Pivotal Trials

Study 301 (n=1084)PRIMARY ENDPOINTS BHV PBO P-VALUE

Pain @ 2hrs 19.2% 14.2% 0.0298

MBS @ 2hrs 36.6% 27.7% 0.0016

SECONDARY ENDPOINTS BHV PBO P-VALUE

Photophobia @ 2 hours 34.9% 24.8% 0.0005

Phonophobia @ 2hours 38.6% 30.9% 0.0299

Pain Relief @ 2 hours 56.0% 45.7% 0.0006

Nausea @ 2 hours 46.9% 41.6% 0.1815Prob of Rescue Meds in 24 hours 20.4% 31.8% <0.0001

SP Freedom 2 to 24 hours 14.0% 8.1% 0.0020

SP Relief 2 to 24 hours 38.9% 27.9% 0.0001


SP Relief 2 to 48 hours 33.7% 23.9% 0.0003

Pain Relapse 2 to 24 (*n=181) 40.1% 50.0% 0.1798Functional Disability at 2 hours 33.3% 21.8% <0.0001

Study 302 (n=1072)PRIMARY ENDPOINTS BHV PBO P-VALUE

Pain @ 2hrs 19.6% 12.0% 0.0006

MBS @ 2hrs 37.6% 25.2% <0.0001

SECONDARY ENDPOINTS BHV PBO P-VALUE

Photophobia @ 2 hours 37.4% 22.3% <0.0001

Phonophobia @ 2hours 36.7% 26.8% 0.0039

Pain Relief @ 2 hours 58.1% 42.8% <0.0001

Nausea @ 2 hours 48.1% 43.3% 0.2084Prob of Rescue Meds in 24 hours 21.0% 37.0% <0.0001


SP Relief 2 to 24 hours 42.6% 26.5% <0.0001


SP Relief 2 to 48 hours 36.3% 22.6% <0.0001

Pain Relapse 2 to 24 (*n=169) 49.6% 50.0% 0.9648Functional Disability at 2 hours 32.6% 23.4% 0.0007

* Represents only approximately 16% of sample size


Rimegepant Potential to Be the Favored Choice for Acute Treatment of Migraine


RIMEGEPANT UBROGEPANT LASMIDITAN CGRP ANTIBODIES

Mechanism of Action CGRP receptor antagonist CGRP receptor antagonist 5-HT1F receptor agonist

Antibody against CGRP receptor (Amgen) or CGRP peptide (Alder,

Lilly, Teva)

Stage of Development Phase 3 Phase 3 Phase 3 Aimovig approved; Others

Phase 3: BLA filed & earlier

Effectiveness in Acute Treatment of Migraine

Met both registrational endpoints (2 hr pain free & MBS) in two pivotal Phase 3 Trials

Comprehensive treatment effect: pain relief, photophobia and phonophobia at 2 hours post-dose;

Durable treatment effect: 2 to 24 and 2 to 48 hour sustained pain freedom

Met both registrational endpoints (2 hr pain free & MBS) at 50 mg in two pivotal Phase 3 trials (multi-dose submission?)

Inconsistent effect on MBS across studies and doses

Durable treatment effect: did not show 2 to 48 hour sustained pain freedom

Met both registrational endpoints (2 hr Pain Free & MBS) in two pivotal Phase 3 Trials

Phase 2 — Durable treatment effect: headache recurrence at 24 hour not different from placebo

No data showing 2 to 24 hour or 2 to 48 hour sustained pain freedom or sustained pain relief

Preventive use only Durable treatment effect: vast

majority of patients show residual ongoing migraine attacks

Safety / Tolerability

No sig difference from Placebo on LFTs > ULN No single AE > 2% Tolerability profile similar to placebo without

difference from placebo on triptan AEs of interest Long-term safety study: up to daily dosing —

ongoing (started Aug 2017)

Imbalance 6 cases of LFTs > 3x ULN, 5 on ubrogepant vs 1 on placebo; 2 cases of LFTs > 5x ULN on ubrogepant (1 case > 10x ULN attributed to pancreatitis)

nausea, somnolence dry mouth >2.5% No single AE > 5%; treatment AEs appear to

increase with dose Long-term safety study: up to 8 doses per month

— pending 4Q2018; Planned 2nd LTS study≥ 15 doses per mo for 2 mo at 100 mg

Higher rates of treatment-emergent AEs compared to placebo (dizziness, paresthesia, somnolence, nausea, fatigue, lethargy and vertigo)

Phase 2 — Higher rates of severe AEs and treatment-emergent AEs compared to placebo (dizziness, fatigue, vertigo, paresthesias, somnolence and sensation of heaviness)

Ongoing study of effect on driving

Well tolerated Cumbersome route of

administration (IV, SC)

Benefits /Unknowns ofMechanism

Novel MOA targeting patients not satisfied with triptan efficacy or who are triptan intolerant or unresponsive

No reason to expect headache recurrence phenomena

Novel alternative for patients who are triptan intolerant or unresponsive

No reason to expect headache recurrence phenomena

Mechanism represents an advance on triptans Uncertainty regarding triptans — e.g., rebound Uncertain appeal in triptan

non-responders

Relatively long duration of action (1 dose per month or 1 dose per 3 months)

Lack of CV effect on exercise-induced angina (Amgen)

PREVENTION ONLY

Rimegepant Value Proposition


Oral Availability

Single dose & durable effect

Low cost of goods

Well tolerated

Effective on pain & MBS

Ultra-high potency

BHV-3500 HIGHLIGHTS


• Superior chemical attributes; • potent antagonist at the human CGRP receptor• highly soluble• high free fraction

• Multiple potential routes of delivery• nasal, inhalation, subcutaneous and oral• potential for rapid onset

• Optimized safety profile in preclinical studies even at very high doses• Low cost of goods, higher value to patients and payors• Pursuing development for the acute treatment and prevention

of migraine• Phase 1 started October 2018• Topline phase 2/3 data anticipated 4Q2019

BHV-3500: Third Generation CGRP Receptor Antagonist

Aptar Pharma Unit-Dose System (UDS) single shot nasal technology

CGRP Platform Development Milestones & Next Steps


4Q2018 Preliminary data from long-term safety study with rimegepant to support NDA submission

4Q2018 Top-line results from Phase 3 rimegepant Zydis® ODT trial for acute treatment of migraine*

4Q2018 Initiate Phase 3 rimegepant trial for prevention of migraine

4Q2019 Topline phase 2/3 data anticipated for intranasal BHV-3500 trial in acute treatment of migraine

2019 Submit New Drug Application (NDA) for rimegepant to the FDA

2020 Anticipated rimegepant LAUNCH!

* ODT trial results are not required for NDA filing (bioequivalence criteria met for ODT and tablet)

GLUTAMATE PLATFORMTherapies for Neurologic and Neuropsychiatric Indications

Glutamate Platform for Neuropsychiatric Indications


Preclinical Phase 1 Phase 2 Phase 3 ApprovalDelivery

NURTEC (BHV0223) | Amyotrophic Lateral Sclerosis (ALS) Rapid Dissolving

Submit NDA 505(b)(2) expected 2H2018

TRORILUZOLE (BHV4157-202) | Obsessive-Compulsive Disorder (OCD) Capsule

Enrollment Active

TRORILUZOLE (BHV4157-206) | Spinocerebellar Ataxia (SCA) Capsule

FPFV expected 4Q2018

TRORILUZOLE (BHV4157-203) | Alzheimer’s Disease (AD) Capsule

6-month Futility Analysis 4Q2019

BHV5000 | Neuropsychiatric Indications Capsule

Complete Phase 1 in 2018

TRORILUZOLE (BHV4157-207) | Generalized Anxiety Disorder (GAD) Capsule

FPFV expected 1Q2019

TRORILUZOLE (BHV4157-201) | SCA Long-Term 96-Week Ext Capsule

Topline Results at 48-Weeks Expected 4Q2018

The Role of Glutamate: Present in 90% of Brain Synapses


Biohaven is focused on normalizing glutamate to treat disease

EXCITOTOXICITYDiseased State

NORMAL FUNCTIONHealthy State

GLUTAMATE REGULATION

AMYOTROPHIC LATERAL SCLEROSIS

SPINOCEREBELLAR ATAXIADEMENTIA

NEURODEGENERATION

NEUROTOXICITY SEIZURES

STRESS

DEPRESSION ANXIETY

STROKE

CANCERPAIN

MELANOMA

ABNORMAL CELL GROWTH

RETT SYNDROME

NEUROTRANSMISSION

MEMORY

CELL SURVIVAL

SYNAPTOPLASTICITY

LEARNING

NEUROTROPHIC

STRESS RESILIENCE

ACTION POTENTIAL COGNITION

MOODNEURONAL CONNECTIONS

Glutamate Mechanisms of Action in CNS


Glutamate Transporter Modulation

• Troriluzole• BHV0223

Glutamate NMDA Receptor Antagonism

• BHV5000

Third-party clinical trials provide basis for exploration of riluzole-related candidates, troriluzole and BHV0223, in multiple neurologic and neuropsychiatric disorders

1

2

1

2


Riluzole is approved for the treatment of patients with amyotrophic lateral sclerosis (ALS) and proven to extend survival

• Originally marketed by Sanofi, Rilutek® (riluzole) received FDA approval in 1995

• In 2013, the FDA approved the first generic versions of riluzole

• Doses above 100 mg for efficacy not approved due to dose-dependent liver effects

BENEFITS Mechanism of action well understoodNeuroprotective, survival benefit in ALSWell tolerated, safe in clinical settings at approved dose

LIMITATIONS ✘Twice daily dosing, low bioavailability✘Fasting required for 6 hours/day,

can’t be taken with meals✘Dose dependent LFT liability(1)

✘Marked PK variability ✘High drug burden relative to efficacy(2)

✘Only one approved indication (ALS)

Riluzole: Use and Limitations

1. LFT = liver function test2. Poor oral bioavailability results in a high liver burden relative to efficacy as ~40% is either not absorbed or is metabolized in the liver

Troriluzole: Rational Drug Discovery to Optimize Therapy


• Improved absorption• Enhanced bioavailability• Reduced drug burden• Reduced first pass metabolism• Favorable safety profile• Once-daily dosing

Peptide Transporter 1 Enhances Absorption of Troriluzole

PepT1

PepT1 = Peptide Transporter 1

ACTIVE ABSORPTION IN INTESTINAL TRACT BY PEPT1


TRORILUZOLE


Troriluzole: Targeted Lead-Indication Development Strategy

* = Third-party study / collaboration ongoing or planned (ADCS Collaboration for AD; ET Study Group Collaboration for ET)

Pending further evaluation of Phase 2/3 SCA data

Lead indications across an array of

potential neurologic and neuropsychiatric

indications

Neurodegenerative Disorders

Mild-to-Moderate Alzheimer’s Disease*

Prodromal Alzheimer’s Disease

ALS (High Dose)

Neuropsychiatric Disorders

Obsessive-Compulsive Disorder

Social Anxiety Disorder

GAD

Bipolar Depression

Cerebellar Disorders

Spinocerebellar Ataxia (SCA)

Friedreich’s Ataxia

Sporadic Ataxia

Other Ataxia

Essential Tremor*

TRORILUZOLE

Rationale for Troriluzole in Alzheimer’s Disease (AD)


• Validated glutamate mechanism for treating neurodegenerative disease• Multimodal activity goes beyond simply targeting tau or amyloid• Therapeutic and pharmacologic effects of troriluzole in AD models

rescues cognitive symptoms and reverses hippocampal gene expression changes found in human AD tissue

• Potential to improve AD symptoms and reduce disease progression • Relevant to all stages of AD

Hallmarks of Human Alzheimer’s Disease• Cognitive and

behavioral symptoms• Loss of hippocampal

synapses (highly correlated with AD severity)

• Impairments in glutamate synapse structure and function

• Amyloid and tau pathology

GLIAL CELL FAILURE IS AN EARLY MARKER OF PATHOPHYSIOLGY


• Glial cells protect and support neurons• Glial cell failure is associated with neuronal cell death

in AD animal models• Glial fibrillary acidic protein expression (GFAP+) can

be used to mark glial cell failure• GFAP+ is reported to increase in animal models of AD

and aging (and occurs earlier than amyloid deposits and brain atrophy)

• Key feature of glial cell failure is impaired glutamate transporter (GLT-1) function

Glia Dysfunction in Aging and Alzheimer’s Disease1

1 Ugbode et al 2016 Biochemical Journal (2017) 474 333–355


Glutamate Transporter (GLT-1) Implicated in Pathophysiology of AD

GLT-1: glutamate transporter-1 is the dominant astrocytic glutamate transporter in the cerebral cortexGlutamine synthetase (GS): converts glutamate to glutamine in astrocytes* Human autopsy observations from AD and controls (n=13)

A. Hosi et al. Neuropathology and Applied Neurobiology (2018)

HUMAN PATHOPHYSIOLOGY IN AD

Healthy Brain

Alzheimer’sBrain


GLT-1 immunoreactivity (IR) in each temporal neocortex area in the AD group is significantly weaker than that in the control group

Glutamate Transporter (GLT-1) Implicated in Pathophysiology of AD

**P < 0.01 vs. control

GLT

-1 IR

Control AD

INFERIOR TEMPORAL

GLT

-1 IR

Control AD

MIDDLE TEMPORAL

GLT

-1 IR

Control AD

SUPERIOR TEMPORAL

A. Hosi et al. Neuropathology and Applied Neurobiology (2018)

I

Attenuates Impairments in Hippocampal Glutamate Synapses

Rescues Cognitive Symptoms(Learning and Memory)


Riluzole Rescues Symptoms, Function and Pathology in AD Animal Models

Pereira Proc Natl Acad Sci 2014; Hunsberger J Neurochem 2015; Hunsberger, Metab Brain Dis 2016; Pereira Molecular Psychiatry 2017; Okamoto Transl Psychiatry 2018

Reduces Amyloid and Tau Pathology

Reduces amyloid plaque

Reduces p-tau

Increases Glutamate Transporter(GLT-1)

Control TauP301L Riluzole + TauP301L

CP-

13/A

ctin

(R

elat

ive

Rat

io)

Wat

er M

aze

Erro

rs

ControlTauP301LRiluzole + TauP301L

Morris water maze

Time (min)

Expl

orat

ion

Tim

e (s

ec)

Aged-control

Young-control

Aged-treated

Y-maze

Aged-controlYoung-control Aged-treated

Normal Spine Density

Reduced Spine Density

Restored Spine Density

Increases neuronal

spine density

Riluzole-treated aged

animals perform like

young-controls

Riluzole-treated tau-

overexpressing animals

perform like controls

TRORILUZOLE (BHV-4157) PHASE 2/3


• Key entry criteria• Diagnosis of mild to moderate Alzheimer’s disease

with Mini-Mental State Exam (MMSE) score of 14–24

• Co-primary efficacy endpoints• Alzheimer's Disease Assessment Scale (ADAS)-Cog11• Clinical Dementia Rating-Sum of Boxes (CDR-SB)

• Secondary efficacy endpoints• Brain volumes: MRI imaging• Activities of daily living: ADCS-ADL• Neuropsychiatric: NPI• Neuropsychological: NTB• Cognitive: MMSE/MoCA

• Sample size: 292 subjects• Randomization: 1:1• Collaborator: Alzheimer’s Disease Cooperative Study

Troriluzole Phase 2/3 Clinical Trial Design in AD

Troriluzole280 mg qd

Placebo

Interim Futility Analysiswhen first 100 subjects reach week 24

Screening Phase

6 weeks

Randomized Double-Blind, Placebo-Controlled Phase

48 weeks

R

-2.00

-1.00

0.00

1.00

2.00

8 weeks

Cha

nge

in S

ARA

Scor

e

1. Ristori et al., Neurology 2010; 74: 839-845. 2. Romano et al., Lancet Neurol 2015; 14: 985–91. 3. Scale for the Assessment and Rating of Ataxia



• Two double-blind(1,2), placebo-controlled academic trials with riluzole show therapeutic effects (p<0.05)• Biohaven Phase 2/3 SCA trial with troriluzole failed to separate from placebo at 8 week time point; extension phase ongoing

Troriluzole in SCA: Signal-to-Noise Challenges at 8 Weeks

• This was the first multi-center randomized clinical trial in North America for SCA. High variability observed in primary rating scale (SARA) and unexpected high placebo response rates at 8 weeks.

• At 8 wks, troriluzole with improvement of -0.81 points [95% CI: -1.4 to -0.2] on the SARA vs. -1.05 points [95% CI: -1.6 to -0.4] in placebo, p-value = 0.52.

• Troriluzole demonstrated a favorable safety and tolerability profile, with no drug-related SAEs and low discontinuation rates due to adverse events.

• Long-term, open-label, extension phase is ongoing. This extension phase will allow for potential signal detection at later time points. Topline data from the extension phase is expected in 4Q2018.

0%

20%

40%

60%

8 weeks

% o

f Pat

ient

s

Trigriluzole (n=63) Placebo (n=68)

% of Patients with Improved SARA Score ≥1 pt

p = 0.52

Change in SARA Scores

Biohaven Multicenter Phase 2/3 (Oct 2017)

-2.00

-1.00

0.00

1.00

2.00

3 Months 12 months

Cha

nge

in S

ARA

Scor

e

0%

20%

40%

60%

3 Months 12 months

% o

f Pat

ient

s

Riluzole (n=28) Placebo (n=27) ** p < 0.01

Romano et al. 2015 (2)

• Study on the use of riluzole in patients with hereditary cerebellar ataxias over a 12-month period• Multi-center, double-blind, placebo-controlled trial with 60 subjects diagnosed with either SCA or

Friedreich’s ataxia (enrolled 2:1) • Subjects randomized to receive 12 months of treatment with either placebo or 100 mg riluzole (50 mg

riluzole tablets, BID)• Primary endpoint was the proportion of patients with a minimum 1-point improvement on the SARA(3)

after 12 months• Demonstrated statistically significant efficacy in patients with hereditary cerebellar ataxia (both SCA and

Friedreich’s ataxia)

** **

% of Patients with Improved SARA Score ≥1 pt Change in SARA Scores

48-Week Extension Phase Ongoing to Assess Efficacy (Topline 4Q2018)

Num

ber o

f Sub

ject

s

Δ SARA [Screening SARA – Baseline SARA] Points

+ 2pt- 2pt



• Based upon available literature, a 1 point change in total SARA was believed to be clinically relevant • In this trial, 2 point change was unexpectedly observed

between screening and baseline in over 1/3 patients• Limits ability to detect 1pt efficacy signal at 8 weeks

• Observations from 8-week randomization phase• High scale variability between screening and baseline

without drug on-board, limits signal detection at 8 weeks• Placebo response for progressive neurodegenerative

disease unexpectedly high• Site rater experience appears critical to reducing variance

and placebo response• Cannot rule out short term efficacy signal• Troriluzole well tolerated with favorable safety profile

• Full dataset analysis and ongoing extension to be presented at medical conferences• Favorable trends identified in subpopulations defined to reduce variability

Additional analyses of dataset, interactions with FDA ongoing

Scale Learnings Inform SCA Analyses and Trial Considerations

36% of patients with ≥ 2pt change in SARA between screening and baseline

TRORILUZOLE (BHV-4157) PHASE 2/3 DATA


Biohaven’s Long-Term Data Supports Efficacy to Natural History Cohort

Natural History Cohort

Troriluzole-Treated

Tota

l Mod

ified

SAR

A(M

ean

Cha

nge

±SE

)

SE: Standard Error

NURTEC (BHV-0223)

DESIGN • Double–blind, placebo

controlled crossover trial with two Impromptu Speech Task sessions

• Subjects diagnosed with Social Anxiety Disorder

• N=22 randomized (21 completed)

• BHV-0223 vs PBO, dosed 1 hour prior to public speaking stress task; separated by two to ten days to allow for medication washout

Yale POC Study: Anti-Anxiety Effects of Nurtec (BHV-0223)

Primary outcome: trial powered at 80%, to detect an effect size of 0.58, at an alpha of p=0.10; prespecified analysis showed p=0.056 and likelihood-based analysis showed p=0.0259


RILUZOLE PRECLINICAL

Yale Human POC Study Is Consistent with Preclinical Models Showing Riluzole’s Anti-Anxiety Effects and Enhancement of Recognition Memory

Sugiyama et al 2017 (Brain Behavioral Research)


Anti-Anxiety Effects

%Ti

me

Spen

t in

Ope

n Ar

m

Saline Riluzole

Enhances Recognition Memory

Dis

crim

inat

ion

Inde

x

Saline Riluzole

Treatment with riluzole increases amount of time spent in open arms and number of entries

(Diazepam used as active anxiolytic control)

Sugiyama et al 2012 (Psychopharmacology)

RILUZOLE PRECLINICAL


Anti-Anxiety Effects of Riluzole Appear Similar to Benzodiazepines in Preclinical Models

%Ti

me

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Ent

ry

Riluzole(mg/kg, p.o.)

Diazepam (mg/kg, p.o.)

Riluzole(mg/kg, p.o.)

Diazepam (mg/kg, p.o.)

TRORILUZOLE (BHV-4157) PHASE 2/3 TRIAL DESIGN

GENERALIZED ANXIETY DISORDER

• Chronic or excessive worry, restlessness, fatigue, difficulty concentrating, insomnia

• Impairs ability to function socially or at work

• Irritable bowel-like gastrointestinal issues

• GAD has a 12-month prevalence in the United States of 3%

• 3,500,000 (est. treatment resistant in U.S.)

RILUZOLE PHASE 2/3 TRIAL DESIGN

• Multicenter (US only), randomized, double-blind, placebo-controlled trial in outpatients with GAD

• Troriluzole 140 mg QHS* & 60 mg QAM* vs Placebo BID*, N=260

• Primary Outcome: Change on HAM-A from baseline to Week 8

• Significant unmet need

• Yale IP protects riluzole in GAD, SAD & Panic Disorder

Expanding Biohaven’s glutamate modulating platform into Generalized Anxiety Disorder (GAD)

NBC New, 28-JUL-18


* QHS: every bedtime, QAM: every morning, BID: twice daily

NURTEC (BHV-0223)


• Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that causes muscle weakness, difficulties with breathing and swallowing and death

• Generic riluzole has been proven to extends survival in ALS• Yet, swallowing is a challenge for patients with ALS

• About 1/3 of patients have dysphagia at diagnosis; over 80% during advanced disease • Many crush riluzole tablet and mix with food, yet label cautions results in lower drug

levels• Fasting required 3 hours per dose (fast 2 hours before and one hour after meals)

• Nurtec is a proprietary, novel formulation of riluzole optimized for sublingual administration

• Nurtec rapidly dissolves when placed under tongue• Active ingredient efficiently absorbed by sublingual mucosa• No need to swallow tablet with liquid

NURTEC is Optimized to Address Riluzole Delivery Limitations for ALS

Only Riluzole Oral Dissolving Tablet meets needs with difficulty swallowing

Cau

tion:

New

Dru

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imite

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Uni

ted

Stat

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se

NURTEC (BHV-0223)

NURTEC Phase 1 Single Dose PK Results


Observations• Sublingual (SL) 35 mg

dose of BHV0223 vs. 50 mg dose of oral Rilutek(riluzole)

• BHV-0223 associated with less PK variability

• Oral Rilutek associated with large PK variability• Lower exposures in

some patients• Attributed to poor

bioavailability and first-pass metabolism of oral dosing

0

50000

100000

150000

200000

250000

300000

350000

400000

0.0 0.5 0.1 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

0

50000

100000

150000

200000

250000

300000

350000

400000

0.0 0.5 0.1 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

Rilutek (50 mg tablet)

BHV-0223 (35 mg SL)

Actual Time (h)A

Mea

n Pl

asm

a R

iluzo

leC

once

ntra

tion

(pg/

mL)

Mean

Individual Results

Mean

Individual Results

A

Mean Plasma Concentrations with

Individual PK Profiles Superimposed

Single Dose

Time Post-Dose (h)

NURTEC (BHV-0223)


EASE OF ADMINISTRATION • An early symptom of ALS is difficulty swallowing; makes use of riluzole

tablets challenging

• BHV0223 uses fast-dissolving technology that does not require swallowing or administration of liquids

NO FOOD EFFECT • Prescribing instructions for riluzole tablets state that it should be taken

at least an hour before, or two hours after, a meal to avoid food-related decreases in bioavailability

• Patients who do not strictly adhere to these fasting requirements or administer crushed riluzole in food, may not be obtaining desired therapeutic levels of riluzole

• BHV0223 was designed to be absorbed sublingually; since absorption of BHV0223 occurs in the vasculature under the tongue, fasting requirements are not anticipated

• This will be particularly beneficial to patients who require a continuous feeding tube for nutrition

NURTEC Offers Potential Advantages Over Conventional Riluzole Tablets for ALS Patients

MORE PREDICTABLE PHARMACOKINETIC PERFORMANCE • Some patients with ALS crush their solid riluzole tablets and

take with food to ease administration(1)

• With BHV0223, patients will not have to crush or alter the form of administration

• In Phase 1 trial, observed less pharmacokinetic variability with BHV0223 compared to 50 mg riluzole

REDUCED DRUG LOAD AND LIVER EXPOSURE • Riluzole associated with dose-dependent liver issues

resulting from high dose loads / extensive liver metabolism

• BHV0223 is sublingually absorbed, bypassing first-pass liver metabolism and reducing the dosage size that needs to be administered, thereby reducing potential risk for hepatic enzyme elevations

1. Leads to uncertain pharmacokinetic performance as well as oral numbness

BHV-5000


• Potential first-in-class, next-generation NMDA receptor antagonist • Exclusive license from AstraZeneca• Low-trapping agent • Orally bioavailable prodrug of the IV drug lanicemine

• NMDA modulation has the potential for applicability across a number of CNS disorders• BHV-5000 demonstrate markedly mitigated risk of dissociative effects in the clinic • Attributed to its distinct ability to uncouple from the NMDA receptor more freely than other agents

• Well tolerated in a Phase 1 single and multiple ascending dose trial• BHV-5000 doses up to 95 mg studied to date in Phase 1• Active metabolite, lanicemine, has been administered to ~770 subjects in single or multiple doses

in 18 clinical trials; generally well tolerated

BHV-5000: A Novel Low-Trapping NMDA Antagonist

BHV-5000 MOA


Lanicemine vs. Ketamine

NMDA receptor / ion channel complex exists in an open or closed state

Blockers bind to the open state but may be “trapped” if they do so deep within the channel

High trapping agents narrow the therapeutic window; low trapping agents expand it

BHV-5000: Novel Low-trapping NMDA Channel Blocker

82% trapping 52-59% trapping

LanicemineKetamine

A clinically meaningful advantage over ketamine-like agents

LANICEMINE


• Lanicemine (active metabolite of BHV-5000) studied in 2 single-dose RCTs and 2 multiple-dose RCTs in depressed patients

• POC demonstrated in both single-dose studies

BHV-5000: Demonstration of Target Engagement

Improvement of ~5 Points on MADRS:Superior to Adjunctive Atypicals (~3 Points)Sustained CGI-I Response After Treatment Period

RCT: randomized controlled trial

• Efficacy demonstrated in one multiple dose study in Treatment Resistant Depression (Study 9) on primary endpoint (Week 3 MADRS) and multiple secondary endpoints, with effects sustained beyond dosing period

% P

atie

nts

with

CG

I-I s

core

≤2

3-week treatment -------- 5-week follow-up ---------

Phase IIb (Study 9):

Very-much-improved or

much-improved

measured by CGI-I

CGI-I: Clinical Global Impression – Global Improvement scale

--- 3-week treatment --- -------- 5-week follow-up ---------

weeks

weeks

Phase IIb (Study 9): Change in MADRS score as adjunct in MDD

MAD

RS

scor

e ch

ange

MADRS: Montgomery–Åsberg Depression Rating Scale

Sanacora ACNP 2012; Sanacora et al., 2013

Glutamate Platform Development Milestones & Next Steps


2H2018 Submit NDA via 505(b)(2) pathway for Nurtec in ALS

4Q2018 Continue enrollment in a Phase 2/3 trial of troriluzole in AD

4Q2018 Continue enrollment in a Phase 2/3 trial of troriluzole in OCD

4Q2018 Begin Phase 2/3 trial of troriluzole in spinocerebellar ataxia

4Q2018 Complete Phase 1 trial for BHV-5000

1Q2019 Begin Phase 2/3 trial of troriluzole in GAD

ALS: amyotrophic lateral sclerosis, AD: Alzheimer’s Disease, OCD: Obsessive-Compulsive Disorder, GAD: Generalized Anxiety Disorder, SCA: Spinocerebellar Ataxia

MPO PLATFORMTherapies for Neuroinflammation

BHV-3241


• Rare, rapidly progressive and fatal neurodegenerative disease • Clinical symptoms:

• Parkinsonism: characteristic tremor (not responsive to L-DOPA), rigidity, dysarthria, falls• Cerebellar ataxia• Autonomic failure: orthostatic hypotension, urinary dysfunction, erectile dysfunction• REM sleep behavior disorder

• Prevalence: 2–5 per 100,000• Pathology: glial cytoplasmic inclusions containing alpha-synuclein• Prognosis: more rapidly progressive than Parkinson’s disease

• Time to loss of ambulation: 3.5–5 years• Mean survival from symptom onset: 6–10 years

• No approved disease modifying treatments• Managed symptomatically

Multiple System Atrophy (MSA)

BHV-3241


• Potent myeloperoxidase inhibitor (MPO-I) developed by AstraZeneca (formerly AZ3241)

• Effective neuroprotection in MSA animal models• Reduces intracellular aggregates of alpha-synuclein • Suppresses microglial activation, rescues

neurodegeneration • Promotes functional (motor) improvements (motor score,

flex field, pole test, and stride length test)

• Clinical experience• Studied in approximately 250 subjects (healthy volunteers,

Parkinson’s disease, multiple system atrophy)• Safe and well tolerated• Demonstrated target engagement (blood MPO activity)• Reduced neuroinflammation on Positron Emission

Tomography study (TSPO) in Parkinson’s disease

BHV-3241 Compound Background

Baseline AZD3241, 4w AZD3241, 8w

BHV-3241


• Phase 2 study: randomized double-blind controlled trial• N=61 subjects (MSA-C, 34; MSA-P, 24)• Randomized to 12 weeks treatment • Placebo BID vs BHV3241 300 mg BID vs BHV3241 600

mg BID• Outcome measures: UMSARS*, PET, safety (labs, AE’s,

ECGs, vitals)

• Safe and well tolerated• Emerging efficacy signals warrant further study in MSA

• Dose proportional benefit on mean UMSARS decline• Dose proportional rates of clinically meaningful

improvement• 600 mg dose with statistical trends (p<0.10) for superiority

over placebo on multiple UMSARS items (cutting food/handling utensil, dressing, arising from chair)

• 600 mg dose shows numerical improvement on MSA Quality of life scale

Phase 2 Study in MSA Completed by AstraZeneca

* UMSARS, Unified MSA Rating Scale

Mean Change on UMSARS Total Score

Number of Subjects by Categorical UMSARS Changes

UM

SAR

S To

tal C

hang

e fro

m B

asel

ine

Driving Investor Value NYSE: BHVN

Biohaven’s Deep Therapeutic, Clinical and Commercial Experience

Robert Berman, M.D.Chief Medical Officer

Jim EngelhartChief Financial Officer

John TiltonChief Commercial Officer

Cliff BechtoldChief Operating Officer

Charlie Conway, Ph.D.Chief Scientific Officer

Robert Croop, M.D.Chief Development Officer —

Neurology

Elyse Stock, M.D.Chief Portfolio Strategy

and Development

Donnie McGrath, M.D. MPHChief of Corporate Strategy and

Business Development


Vlad Coric, M.D.Chief Executive Officer, Director

PRIOR PROFESSIONAL ROLES

SELECTED DEVELOPMENT EXPERIENCE

Licenses and Intellectual Property

• Founded on intellectual property from Yale University focused on glutamate modulation

• Licensed lanicemine prodrugs from AstraZeneca• Expanded glutamate patent portfolio with licenses from Rutgers, MGH

and ALSBiopharma• Licensed CGRP antagonist program from Bristol-Myers Squibb• Collaboration with Catalent on ZYDIS ODT technology across

glutamate and CGRP antagonist programs• Kleo Pharmaceuticals investment to develop small molecule

immuno-oncology platform


Financial Summary

IPO on NYSE at $17/share in May 2017

COMPANY OWNERSHIP• Top-tier institutional investors and company founders among

long-term shareholders• $500MM raised since inception

• raised $150M with Royalty Pharma CGRP platform transaction

• Cash on hand as of June 30, 2018 = $217.5M• Top 15 Institutional Investors (38%), Insiders (33%), Other (29%)1

NOVEMBER 2018 ADVANCING INNOVATIVE THERAPIES FOR NEUROLOGICAL DISEASES 631. Data based on latest available information per Thomson and SEC Filings; institutional investor ownership as of 4Q2017

4Q18: Tablet Initial results from 12-month long-term safety study4Q18: ODT Phase 3 topline results (bioequivalence of Zydis® ODT to oral tablet established 1Q18)

RimegepantAcute Treatment

of Migraine

2018: Complete Phase 1 trial with oral solid-dose formulation BHV-5000Neuropsychiatric

Indications 2

4Q18: Initiate Phase 1 clinical trial with intranasal BHV-3500 for acute treatment of migraine4Q19: Topline phase 2/3 data anticipated for intranasal BHV-3500 trial in acute treatment of migraine

BHV-3500Acute Treatment and Prevention

of Migraine

2019: 4 Phase 2/3 trials in AD (started 3Q18), OCD (active), GAD (expected 1Q19) & SCA (expected 4Q18)4Q18: Topline results of SCA long term extension phase to assess drug signal at one year

TroriluzoleAlzheimer’s disease

(AD), Spinocerebellar Ataxia (SCA)

2H18: Submit NDA for treatment of ALS — 505(b)(2) regulatory pathwayNurtec

Amyotrophic Lateral Sclerosis (ALS)

1. Alzheimer's Disease Cooperative Study2. Pain, Treatment Resistant Depression, RETT Syndrome

2018 Development Milestones and Next Steps


BHV-3241Multiple System Atrophy (MSA)

Mid 2019: Commence Phase 2/3 trial in Multiple System Atrophy

AD: Alzheimer’s Disease, OCD: Obsessive-Compulsive Disorder, GAD: Generalized Anxiety Disorder, SCA: Spinocerebellar Ataxia

BIOHAVEN CORPORATE OVERVIEW

Biohaven Well Positioned for Growth


Advancing Late-Stage Clinical Programs from Three Novel Neurology Small-Molecule Platforms

Well positioned to deliver potential best-in-class therapies to patients and grow company value

GLUTAMATE PLATFORM• Alzheimer’s and Anxiety• Initiated Phase 2/3 trials in ALS, Alzheimer’s,

ataxia, anxiety, depression and OCD• Nurtec: submit NDA for ALS in 2018

CGRP PLATFORM• Migraine and pain • Two positive Phase 3 trials• Program for acute to prevention• Rimegepant: submit NDA in 2019

MPO PLATFORM• Neuroinflammation• Phase 2 Study in Multiple System

Atrophy (MSA) Completed by AZ 1• BHV-3241: Complete Phase 3 in 2019

1. ASTRAZENECA

advancing innovative therapies for neurological diseases

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