Neuroinnovation Meeting patient needs and growing value - Investor Presentation | January 2021 - Biohaven Pharmaceuticals
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Investor Presentation | January 2021
neuroinnovation
Meeting patient needs and growing value
Ellie, living with migraine
© 2021 Biohaven Pharmaceuticals. All rights reserved.
NYSE:BHVN
Disclaimer This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including: statements about Biohaven Pharmaceutical Holding Company Ltd. (The ”Company”) and our plans relating to the commercialization and sales of NURTEC ODT, the potential approval and commercialization of other product candidates, the effect of the ongoing COVID-19 pandemic on the Company, the expected timing, commencement and outcomes of the Company's planned and ongoing clinical trials for our rimegepant, zavegepant (BHV-3500), troriluzole, BHV-5500, verdiperstat and KP-1237 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, the clinical potential utility of our product candidates, alone and as compared to other existing or potential treatment options, and the potential advancement of our early phase programs including ARMs, MATEs and MoDEs. 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 and from the Company's current expectations. 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. The forward-looking statements in this presentation represent our views as of the date of this presentation. Subsequent events and developments may cause our views to change. However, the Company does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by 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. Additional important factors to be considered in connection with forward-looking statements are described in the "Risk Factors" section of Biohaven's Annual Report on Form 10-K for the year ended December 31, 2019, filed with the Securities and Exchange Commission on February 26, 2020, and Biohaven's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020 filed with the Securities and Exchange Commission on November 9, 2020 and the Company’s other reports filed with the SEC. References to www.biohavenpharma.com in this presentation are not intended to, nor shall they be deemed to, incorporate information on such website into this presentation by reference. 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. Safety information and the full prescribing information for Nurtec ODT can be found at Nurtec.com. JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 2
Innovative pharmaceutical solutions to
address unmet needs in neuroscience
COMMITTED TO IMPROVING THE LIVES OF PATIENTS
by advancing first-in-class and best-in-class therapies
PIPELINE INCLUDES
6 products across multiple technology platforms
PROVEN LEADERSHIP
in industry & academic settings with unique development approach
FULL COMMERCIAL OPERATIONS
to support bringing multiple pipeline assets to market
3
Nurtec ODT Commercial Achievements in Less Than 8 Months From Launch
$28.5M >80% >330,000
1–3Q20 net increase in 3Q20 net TRxs of Nurtec
sales sales from 2Q20 since launch
Nurtec ODT Prevention 200M+ >89%
sNDA accepted covered lives commercial
4Q2020 all channels coverage
TRx, Total Rx; sNDA, Supplemental New Drug Application; NBRX, New to Brand Rx
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 4
Oral CGRP Class Continues to Show Robust Market Growth
1 Total Rx — Time Aligned (12/25) 2 New to Brand Rx Share (12/18)
Ubrelvy
16,234
Ubrelvy
14,251
48.7%
Nurtec ODT Nurtec ODT
1
3
5
7
9
11
13
15
17
19
21
23
25
27
29
31
33
35
37
39
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49
3/ 3
4/ 7
4/ 0
24
22
19
17
8/ 1
8/ 4
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9/ 1
10 5
1 0 /9
11 6
12 4
8
5
3
3
0
8
5/
6/
7/
/2
/
/2
/
/1
1
2
1
3
1
2
1
2
11
12
3/
5/
6/
7/
7/
Weeks since launch
Week ending
KEY INSIGHTS
• Time-aligned Nurtec TRx launch curve shows strong growth consistent with the class, despite competitor’s
pre-COVID launch 2 months earlier
• Oral CGRP market for migraine on track to reach blockbuster status in U.S. market alone
TRx, Total Rx; NBRX, New to Brand Rx; Source: NBRx through 12/18, Symphony PrescriberSource, accessed 1/7; TRx through 12/25, Symphony PHAST, accessed 1/7
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 5
Orals CGRPs Have Driven CGRP Class Growth in 2020 (vs mAbs)
CGRP Weekly TRx
140,000
120,000
100,000
80,000
Acute oral
60,000
mAb
40,000
20,000
0
11 /18
12 /18
1/ 18
11 /19
12 /19
1/ 19
11 /20
20
6/ 18
7/ 18
8/ 18
9/ 18
10 / 18
2/ 19
3/ / 19
4/ 19
5/ 19
6/ 19
7/ 19
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9/ 19
10 / 19
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5/
5/
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5
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5
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5
/2
/2
/2
/2
/2
/2
/2
/2
5/
Symphony Prescribersource Database: TRx Volume to 12/18/2020, accessed 1/7/2021
* CGRP acute orals = Ubrelvy, Nurtec ODT; CGRP mABs = Emgality, Ajovy, Aimovig
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 6
“New to Rx” and “Dissatisfied Rx” Patients
Fueling Large Market Growth
~24%*
Not currently
taking Rx
Two different
patient segments
driving initial oral
CGRP growth
~76%
Patients switching
from triptans
*Symphony PrescriberSource 12/22/20
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 7
Oral CGRPs have Significant Growth Opportunity Ahead
2,104,859
16%
14%
328,076
11%
1-2Q20 1-3Q20 1-4Q20 1-4Q20
CGRP Orals Triptans
Source: Symphony PrescriberSource Database: Cumulative NBRx Volume (1/24/20 – 12/18/20), accessed 1/7/2021
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 8
Neurologists’ Preference for Nurtec ODT exceeds
Ubrelvy and Reyvow
Anticipate Using Brand as Preferred Acute
Migraine Therapy
Vast Majority of
Percent of respondents
Neurologists
49%
rank Nurtec
33%
ODT as an
10%
advance over
Reyvow Ubrelvy Nurtec ODT Triptans, and
Majority View Nurtec ODT as Advance Over Triptans that perception
No advance (1-3) Somewhat of an advance (4-7) Significant advance (8-10) has grown over
Q4 2020 (n=101) 43% 53%
time
Q3 2020 (n=101) 46% 51%
Q2 2020 (n=101) 6% 53% 41%
0% 20% 40% 60% Percent of 80% 100%
respondents
Source: Spherix Global Insights, Q4 Real Time Dynamix Study, Neurologists
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 9
Nurtec ODT outranks Ubrelvy on several key attributes, notably duration of
effect, speed and need to redose
100%
11% 10% 12%
16% 15% 14%
18% 18% 21%
22%
32% 31% 29%
35%
80%
43%
60%
68%
73%
77% 85% 87% 83%
77% 76%
40% 75% 75%
62% 63%
58% 65%
52%
20%
18%
12%
5% 7% 7% 8% 5% 6% 7% 5%
0%
Duration of Need for Speed of Administration: Rapid pain relief Pain freedom at Pharmaceutical Professionalism Freedom from Pharmaceutical Tolerability Supported by Good long-term Accessibility on My familiarity/
effect redosing efficacy onset Patient and return to two hours company /value brought most company strong clinical safety profile formularies or comfort
convenience function in as little support for by sales bothersome support for data insurance plans
as one hour health care representative symptom at two patients
providers hours
Ubrelvy is better (1-2) Equivalent (3) Nurtec ODT is better (4-5)
Source: Spherix Global Insights, Q4 Real Time Dynamix Study, Neurologists: “In your opinion, how does Nurtec ODT compare to Ubrelvy on the following metrics?” (n=101)
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 10Broad Commercial Coverage: High Impact Commercial PBM and
Health Plan Wins
April – June 2020 July – October 2020
89%
COVERAGE
200M+ Total
Covered Lives in
all Channels
PBM, Pharmacy Benefit Manager
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 11A Defining Launch, Future Growth Potential Across the Pipeline
2020 pivotal growth year for oral CGRPs
sNDA for Nurtec ODT Prevention
accepted by FDA, 2Q2021 PDUFA Date
Neuroinnovation pipeline poised to
deliver multiple NDAs
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 12Common Disease Pipeline Opportunities
Nurtec ODT™ ACUTE MIGRAINE Global filings 2021, China and
Korea clinical study started in Oct 2020
Acute and Prevention
MIGRAINE PREVENTION PDUFA 2Q21, launch
preparation underway while awaiting approval decision
Multiple INTRANASAL ULTRA-RAPID ONSET Second pivotal
acute migraine & 1yr Safety study initiated Oct 2020
Zavegepant Blockbuster
Small molecule/NCE ORAL Oral formulations of zavegepant confirmed
Potentials target exposure in human PK trial and Phase 3 to begin
NON-MIGRAINE INDICATIONS 3 POC studies in 2021
ALZHEIMER'S DISEASE Topline expected Jan 2021
Glutamate Modulation
OCD Phase 3 program initiated 4Q2020
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 13Rare Disease Opportunities
3 2 >$5B
Devastating Phase 3 Potential Global
Diseases Readouts Peak Revenue
in 2021
Multiple System Atrophy Targeting 3 Combined Potential
Global Rare Disease Across 3 Indications
Amyotrophic Lateral Sclerosis
Drug Launches by 2023
Spinocerebellar Ataxia
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 14Biohaven Labs: Chemistry and Discovery
Next-Generation Bispecific Platforms for Pipeline Growth
M AT E ™ M O N O C L O N A L A N T I B O D Y T H E R A P Y E N H A N C E R
Reactive group
Directing
Target Binder
group
Binding to Conjugation and release
IgG1/2/4 antibody of directing group
ARM™ ANTIBODY MoDEs MOLECULAR DEGRADERS
RECRUITING MOLECULES OF EXTRACELLUAR PROTEINS
Binds protein target
Binds liver
ARM™ binds to (ASGPR)
disease target and
induces antibody Bifunctional small molecule
binding
Macrophages
NK cells
Endogenous IgG
Antibody
(polyclonal)
N-acetyl Target Target protein
ASGPR
galactosamine protein ligand
ASGPR-binding Target-binding
terminus terminus
JANUARY 2021 IgG, Immunoglobulin G; NK, Natural Killer cells BIOHAVEN INVESTOR PRESENTATION ASGPR, Asialoglycoprotein Receptor 15Pipeline Milestone Events
DRUG NAME INDICATION 2H2020 1H2021 2H2021 2022
Migraine prevention sNDA Accepted Approval
Migraine acute/prevention PMDA Meeting Europe Filing 1Q
Migraine (intranasal) Filing 4Q Approval
Zavegepant
Small molecule/NCE
Migraine (oral) Start Phase 3 1Q
Alzheimer's Topline Jan 2021
Troriluzole Spinocerebellar ataxia Topline 4Q
NCE prodrug of riluzole
Obsessive-compulsive disorder Topline
Multiple system atrophy Topline 4Q
Verdiperstat
NCE oral MPO inhibitor
Amyotrophic lateral sclerosis Topline
sNDA, supplementary new drug application (U.S. FDA); PMDA, Pharmaceuticals and Medical Devices Agency (Japan); NCE, new chemical entity; MPO, myeloperoxidase
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 16Biohaven Targeting 3 Global Orphan Drug Launches By 2023
US targeted approval EU targeted approval
2020 2021 2022 2023
Verdiperstat- Ph3 trial completed Ph3 topline
MSA enrollment1 data expected
Verdiperstat- Ph3 trial first Ph3 top line
ALS patients enrolled2 data expected
Troriluzole- Ph3 enrollment
Ph3 top line
completion
SCA data expected
anticipated3
Note: Assumes 1 year for Ph1, 2 years for Ph2, 3 years for Ph3, and 1 year for filing and FDA approval.
1. https://www.prnewswire.com/news-releases/biohaven-completes-enrollment-ahead-of-timelines-in-international-phase-3-clinical-trial-of-verdiperstat-in-multiple-system-atrophy-301096602.html
2. BioSpace. Biohaven Announces Enrollment Of First Patients In Pivotal HEALEY ALS Platform Trial Including Verdiperstat Conducted By Healey Center For ALS At Massachusetts General Hospital. Accessed September 7, 2020.
https://www.biospace.com/article/releases/biohaven-announces-enrollment-of-first-patients-in-pivotal-healey-als-platform-trial-including-verdiperstat-conducted-by-healey-center-for-als-at-massachusetts-general-hospital/
3. BioSpace. BIOHAVEN ENROLLS FIRST PATIENT IN PHASE 3 SPINOCEREBELLAR ATAXIA CLINICAL TRIAL OF TRORILUZOLE. Accessed September 7, 2020. BIOHAVEN ENROLLS FIRST PATIENT IN PHASE 3
SPINOCEREBELLAR ATAXIA CLINICAL TRIAL OF TRORILUZOLE. https://www.biohavenpharma.com/investors/news-events/press-releases/03-14-2019
MSA, multiple system atrophy; ALS, amyotrophic lateral sclerosis; SCA, spinocerebellar ataxia
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 17Filing for Approval
PLATFORM | DRUG NAME PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MARKETED
US NURTEC ODT | Acute Migraine
ISRAEL | Acute Migraine
MIDDLE EAST | Acute Migraine
CHINA | Acute Migraine
Rimegepant NURTEC US | Migraine Prevention
Small molecule/NCE
EUROPE | Migraine (Acute and Prevention)
CALCITONIN GENE-
RELATED PEPTIDE (CGRP)
JAPAN | Migraine (Acute and Prevention)
UNDISCLOSED | Planned Migraine Adjacencies
UNDISCLOSED | Planned Non-Migraine Indications
US | Acute Migraine/Prevention
Zavegepant COVID19 US | Respiratory Complications
Small molecule/NCE
UNDISCLOSED | Planned Non-Migraine Indications
Alzheimer’s Disease (AD)
Troriluzole Spinocerebellar Ataxia (SCA)
NCE prodrug of riluzole
GLUTAMATE
Obsessive-Compulsive Disorder (OCD)
BHV-5000/5500 Neuropsychiatric Indications
NCE NMDA antagonist
Multiple System Atrophy (MSA)
MYELOPEROXIDASE (MPO) Verdiperstat
NCE oral MPO inhibitor
Amyotrophic Lateral Sclerosis (ALS)
UC1MT Not Disclosed
Metallothionein
NOVEL PROGRAMS
TDP43 ALS
JANUARY 2021 NCE, new chemical entity; TDP-43: TAR DNA-binding protein 43 BIOHAVEN INVESTOR PRESENTATION UC1MT: monoclonal antibody targeting extracellular metallothionein 18Nurtec ODT Commercial Achievements in Less Than 8 Months From Launch
$28.5M >80% >330,000
1–3Q20 net increase in 3Q20 net TRxs of Nurtec
sales sales from 2Q20 since launch
Nurtec ODT Prevention 200M+ >89%
sNDA accepted covered lives commercial
4Q2020 all channels coverage
TRx, Total Rx; sNDA, Supplemental New Drug Application; NBRX, New to Brand Rx
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 19THANK YOU! w w w. b i o h a v e n p h a r m a . c o m NYSE:BHVN
Appendix
Next-Generation
Chemistry & Discovery:
Bispecific
Next-Generation
Compounds Bispecific CompoundsNext-Generation Bispecific Compounds – MATEs, ARMs & MoDes
M AT E ™ M O N O C L O N A L A N T I B O D Y T H E R A P Y E N H A N C E R
Reactive group
Directing
Target Binder
group
Binding to Conjugation and release
IgG1/2/4 antibody of directing group
ARM™ ANTIBODY MoDEs MOLECULAR DEGRADERS
RECRUITING MOLECULES OF EXTRACELLUAR PROTEINS
Binds protein target
Binds liver
ARM™ binds to
(ASGPR)
disease target &
induces antibody Bifunctional small molecule
binding
Macrophages
NK cells
Endogenous IgG
Antibody
(polyclonal)
ASGPR N-acetyl Target Target protein
galactosamine protein ligand
ASGPR-binding Target-binding
terminus terminus
JANUARY 2021 IgG, Immunoglobulin G; NK, Natural Killer cells BIOHAVEN INVESTOR PRESENTATION ASGPR, Asialoglycoprotein Receptor 23MATE™ Monoclonal Antibody Therapy Enhancer
Chemical Reengineering of Antibodies to Enhance/ Improve their Function
Biohaven’s monoclonal antibody therapy enhancer (MATE) platform enables site-directed, chemical
conjugation to off-the-shelf therapeutic monoclonal antibodies (mAbs), or therapeutic intravenous
immunoglobulin (IVIG) pooled from healthy donors.
Reactive group
Directing
Target Binder
group
Binding to Conjugation and release
IgG1/2/4 antibody of directing group
IgG, Immunoglobulin G
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 24ARM™ Antibody Recruiting Molecules
Antibody Recruiting Molecules (ARMs) are bispecific
ARM™ binds to molecules that recruit endogenous antibodies to target
disease target cancer, virally infected cells, and disease-causing
and induces
antibody binding microorganisms for immune destruction. They are comprised
Macrophages
of two distinct binding domains connected by a tunable linker
domain. One binding domain attaches to circulating
antibodies and the other attaches to disease cells. These
molecules are engineered with modular components that are
readily interchangeable, giving the platform tremendous
NK cells
flexibility to target a variety of disease cells and tumor types.
Endogenous IgG
Antibody The ARM's target-binding domain binds tightly to specific
(polyclonal) molecules expressed on the disease cell's surface. Its
antibody-binding domain attaches to antibodies already
present in the patient's body and the micro-environment of
the disease cells. By creating this “bridge”, ARMs enable
endogenous antibodies to coat the cell, leading to the
destruction of the disease cell through the body’s innate
IgG, Immunoglobulin G; NK, Natural Killer cells antibody-mediated immune mechanisms.
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 25MoDEs Molecular Degraders of Extracellular Proteins
Uptake and degradation of Binds protein target
target proteins mediated by Binds liver
(ASGPR)
MoDE bifunctional molecules Bifunctional small molecule
N-acetyl Target Target protein
ASGPR
galactosamine protein ligand
ASGPR-binding Target-binding
terminus terminus
ASGPR, Asialoglycoprotein Receptor
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 26METALLOTHIONEIN BLOCKADE A Novel Anti-Inflammatory Therapeutic
Metallothionein Can Alter Immune Response by
Influencing Cellular Trafficking
Stress-causing cell damage
Healthy tissue Disease propagation
cycle: more stress and
Extracellular MT more inflammation
recruits
Metallothionein production and inflammatory cell
release as a “danger signal”
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 28Metallothionein: A Novel Target in the Immune Cascade
• Metallothionein (MT) is an intracellular protein in non-stressed conditions
• MT is released from cells/tissues that are stressed, damaged, or killed
• Extracellular MT can act as a pro-inflammatory agent
• MT acts as an agent of disease progression in multiple inflammatory models
• MT elevations demonstrated in patients with Inflammatory Bowel Disease (IBD)
• MT is elevated in diabetes, multiple brain disorders, inflammatory liver disease, inflammatory skin disease,
pulmonary arterial hypertension, neoplasia, etc.
• Anti-MT monoclonal antibody (UC1MT) significantly reduces disease severity in multiple models
Pro-inflammatory Progressive
Inflammatory MT induction and
effects of inflammation and
stress release
released MT MT synthesis
UC1MT blockade
UC1MT: monoclonal antibody targeting extracellular metallothionein
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 29UC1MT Reduces Inflammation in the Adoptive T Cell Transfer Model of IBD
Anti-MT performance exceeded conventional anti-TNF therapeutic
UC1MT: monoclonal antibody targeting extracellular metallothionein; Anti-MT, anti-metallothionein monoclonal antibody; Anti-TNF, anti-tumor necrosis factor monoclonal antibody; IBD, inflammatory bowel disease
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 30UC1MT: First in Class Metallothionein Antagonist for a Novel Pro-Inflammatory Target • UC1MT is a high affinity monoclonal antibody that recognizes both mouse and human MT1 and MT2 • Confirmed the role of MT involvement in multiple disease models with better activity than anti-TNF • Evidence of molecular mechanism • Demonstrated the ability reduce markers of inflammation by UC1MT • Strong global patent protection of Anti-MT antibody therapeutic in several disease areas UC1MT: monoclonal antibody targeting extracellular metallothionein; Anti-TNF, anti-tumor necrosis factor monoclonal antibody JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 31
CGRP Receptor Antagonist Platform: Redefining the Treatment of Migraine
Migraine Significantly Impairs Patients’ Lives
Migraine affects ~15% of the US population1 with prevalence highest
during peak employment years (25–55 years of age)3
1 in 5 women2
20,000 per 100,000 women
1 in 16 men2
6,250 per 100,000 men
• Chronic neurological disease characterized by disabling attacks2
• Reduced functionality, disrupting daily lives, work productivity, and
social interactions2,4
• Severity, frequency, and characteristics of migraine vary among
patients, and often within the same patient over time2
Regardless of frequency, severity, or use of preventative treatment, all
patients require effective acute treatment for their migraine attacks.
References: 1. Burch R, Rizzoli P, Loder E. Headache. 2018;58(4):496–505. 2. The American Headache Society. Headache.
2019;59(1):1–18. 3. Bonafede M, Cai Q, Capell K. JMCP. 2017;23(11):1169–1176. 4. Martelletti P et al. J Headache Pain. 2018;19(1):115.
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 33Migraine Attacks: A Leading Cause of Economic Burden in US
Annual total costs for migraine in the US are estimated at $27 BILLION 1
~25% OF ER VISITS FOR MIGRAINE were followed by a second ER visit for
headache inPatients Report Low Satisfaction With Current Acute Treatments and
High Abandonment Rates Across the Spectrum of Therapies
A B A N D O N M E N T R AT E S O F A C U T E M I G R A I N E T R E AT M E N T S 1
PRESCRIPTION
NSAIDs TRIPTANS ERGOT DERIVATIVES
ANALGESICS
50% 45% 38% 35%
§ In a large survey, only 40% reported satisfaction with their current migraine treatment plan 2
§ Migraine patients twice as likely to use opioids, and had 1.8x the number of opioid scripts per patient3
References: 1. Migraine.com. https://migraine.com/infographic/migraine-is-more-than-a-headache-its-a-life-ache/. Published August 30, 2016. Accessed September 9, 2019. 2. Data on file, Biohaven
Pharmaceuticals 3. Bonafede M, Cai Q, Cappell K. JMCP. 2017;23(11):1169-1176.
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 35Oral CGRP Receptor Antagonists Address Unmet Needs of Current Acute Treatments
Cardiovascular Medication Overuse
Nonresponders Cannot tolerate Recurrence
Contraindications Headache (MOH)
Up to 55% of people do not 17% to 40% experience
Overuse of many current
have sufficient relief with 43% experience AEs return of migraine Approximately 2.6M
acute therapies can
currently available within 24 hours2 pain/symptoms within in the US4
cause MOH5
treatments1 24 hours3
References: 1. Lipton RB et al. Headache. 2017;57(7):1026-1040. 2. Derry CJ et al. Cochrane Database Syst Rev. 2012;2(2):CD008615. 3. Géraud G et al. Headache. 2003;43(4):376-388. 4. Buse DC et al.
Headache. 2017;57(1):31-44. 5. Schwedt TJ et al. J Headache Pain. 2018;19(1):38.
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 36The Only
Quick-Dissolve Oral
eliminate migraine pain
CGRP Receptor in minutes
Antagonist
That Can… get you back to normal
function by one hour, and
lasts 48 hours after a single dose
Nurtec ODT [prescribing information]. New Haven, CT: Biohaven Pharmaceuticals, Inc; Croop R et al. Lancet. 2019;394(10200):737-745. Data on File 001. Biohaven Pharmaceuticals, Inc.
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 37Nurtec ODT Blister Pack (8-count) JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 38
1. Nurtec ODT [prescribing information]. New Haven, CT: Biohaven Pharmaceuticals, Inc; 2. Croop R et al. Lancet. 2019;394(10200):737-745. 3. Data on File 001. Biohaven Pharmaceuticals, Inc. JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 39
of migraine 1. Nurtec ODT [prescribing information]. New Haven, CT: Biohaven Pharmaceuticals, Inc; 2. Croop R et al. Lancet. 2019;394(10200):737-745. 3. Data on File 001. Biohaven Pharmaceuticals, Inc. JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 40
of migraine 1. Nurtec ODT [prescribing information]. New Haven, CT: Biohaven Pharmaceuticals, Inc; 2. Croop R et al. Lancet. 2019;394(10200):737-745. 3. Data on File 001. Biohaven Pharmaceuticals, Inc. JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 41
of migraine 1. Nurtec ODT [prescribing information]. New Haven, CT: Biohaven Pharmaceuticals, Inc; 2. Croop R et al. Lancet. 2019;394(10200):737-745. 3. Data on File 001. Biohaven Pharmaceuticals, Inc. JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 42
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 43
“In our analysis of the cost effectiveness…we found
that for patients for whom triptans are not effective,
not tolerated, or are contraindicated…rimegepant…[is]
cost effective at commonly used thresholds.”
ICER Report Feb 25th 2020, Page ES18
Atlas S, Touchette D, Agboola F, Lee T, Chapman R, Pearson S D, Rind D M. Acute Treatments for Migraine: Effectiveness and
Value. Institute for Clinical and Economic Review, February 25, 2020. http://icer-review.org/material/acute-migraine-evidence-report/
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 44Top Tier Medical Journals Publish Rimegepant Acute and Prevention Pivotal Trials • Croop, R., et al. (2021). "Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double- blind, placebo-controlled trial." Lancet. 397(10268): 51-60. • Lipton, R. B., et al. (2019). "Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine." N Engl J Med 381(2): 142-149. • Croop, R., et al. (2019). "Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial." Lancet 394(10200): 737-745. JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 45
Well-tolerated across clinical trials1
LOW RATES OF AES1,2 LONG-TERM SAFETY MAINTAINED
THROUGH 52 WEEKSImportant Safety Information
INDICATION
Nurtec™ ODT (rimegepant) is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use
Nurtec ODT is not indicated for the preventive treatment of migraine.
IMPORTANT SAFETY INFORMATION
Contraindications: Hypersensitivity to Nurtec ODT or any of its components.
Warnings and Precautions: If a serious hypersensitivity reaction occurs, discontinue Nurtec ODT and initiate appropriate therapy. Serious
hypersensitivity reactions have included dyspnea and rash, and can occur days after administration.
Adverse Reactions: The most common adverse reaction was nausea (2% in patients who received Nurtec ODT compared to 0.4% in patients
who received placebo). Hypersensitivity, including dyspnea and rash, occurred in less than 1% of patients treated with Nurtec ODT.
Drug Interactions: Avoid concomitant administration of Nurtec ODT with strong inhibitors of CYP3A4, strong or moderate inducers of CYP3A
or inhibitors of P-gp or BCRP. Avoid another dose of Nurtec ODT within 48 hours when it is administered with moderate inhibitors of CYP3A4.
Use in Specific Populations: Pregnant/breast feeding: It is not known if Nurtec ODT can harm an unborn baby or if it passes into breast milk.
Hepatic impairment: Avoid use of Nurtec ODT in persons with severe hepatic impairment. Renal impairment: Avoid use in patients with end-
stage renal disease.
Please see full Prescribing Information available at www.nurtec.com
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 47Rimegepant 1-Year Long-Term Safety to Capture Real World Patient Usage
Patients Received Free
SCREENING/ TREATMENT PERIOD END of Treatment
Access to Daily Supply1
BASELINE up to 52 Weeks or Early D/C Visit
of Rimegepant for 1 year
• Assess Long-Term Safety
30-day • Determine Patient Utilization
Observation
Phase
• Assess Migraine Frequency and Disability
Dispense Start treatment Stop treatment
1. Patients were dispensed open label rimegepant 75 mg in bottles containing 30 tablets; A maximum of 1 tablet per calendar day was permitted
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 48Median Monthly Usage: < 8 pills/month over 1-Year with PRN Dosing
• PRN protocol allowed dosing up to once per calendar day
Rimegepant 75 mg Tablets Treated Subjects
Average rimegepant exposure [tablets per 4 weeks]
PRN Dosing PRN Dosing
2–8 cohort {attack history/mo} 9–14 cohort {attack history/mo}
(n=1031) (n=481)
Mean (SD) 5.6 (3.50) 8.5 (4.20)
Median 4.9 7.8
• To further test safety, patients in additional EOD+PRN group received scheduled every other day
dosing (EOD) and could also dose PRN on nonscheduled dosing days for up to 3 months (n=286):
median usage = 14.2 tablets per month (based on 28-day month)
Tablets per 4 weeks are based on 4-week (28-day) intervals in the long-term treatment period. Data on file. Study 201: Biohaven Pharmaceuticals; 2019.
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 49Rimegepant Reduced Total Migraine Disability (MIDAS) by ~50%
in 1-Year Study
Migraine Disability Assessment Score
Severe
35
Mean MIDAS Total Score
33 33.9 PRimegepant 75 mg Up to Once Daily Reduces Lost Productivity Time by
Approximately 50%
Absenteeism Days Mean Item Score
of missed work, 20 17.8
school, household, 18
social or leisure 16
PRimegepant Shows Reduction in Moderate-to-Severe Migraine Days
Irrespective of Baseline Migraine Frequency
RIMEGEPANT LONG-TERM SAFETY – STUDY 201, INTERIM ANALYSIS 21FEB2019
48.4% of subjects in the EOD+PRN
Moderate-to-Severe Migraine Days/Mo
Patients Showing ≥50% Reduction in
cohort during month 3 achieved ≥50% 60%
reduction from baseline of moderate- 48.4% 48.6%
50% 46.2%
to-severe migraine days per month
with rimegepant 75 mg (n=244)
40%
30%
20%
10%
0%
AllBiohaven Achieves Positive Results in Pivotal Trial of Oral NURTEC™, Dosed Every Other Day, for the Preventive Treatment of Migraine • Rimegepant 75 mg, dosed every other day, demonstrates statistically significant superiority, compared to placebo, on the primary endpoint of reduction in the mean number of migraine days per month • Orally administered rimegepant 75 mg, approved earlier this year for the acute treatment of migraine, is the only CGRP targeting therapy to demonstrate efficacy in both the acute and preventive treatment of migraine • Biohaven plans to engage the FDA and European Medicines Agency to submit a sNDA and MAA, respectively, for rimegepant for the indication of preventive treatment of migraine JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 53
Study BHV3000-305: Phase 3 Randomized Study Investigating the Safety and
Efficacy of Rimegepant 75 mg for Preventive Treatment of Migraine
Rimegepant 75 mg EOD Dosing Baseline Treatment Phase
Observation Period Dosed Every Other Day (EOD) End of Study Visit
28 Day Up to 12 Weeks
Rimegepant 75 mg
(n=370)
Study 305 History of 4 to 18
migraine days R End of Study
(N=741) per month 1:1 Visit
Placebo
(n=371)
R randomization
Objective: Assess Rimegepant 75 mg versus placebo on safety,
efficacy and tolerability in the preventive treatment of migraine
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 54Rimegepant Met Primary Endpoint – Showed Superiority to Placebo in Reduction
of Monthly Migraine Days (MMD) with 75 mg Every Other Day (EOD) Dosing
Placebo Rimegepant 75 mg
Every Other Day Every Other Day
N=347 N=348
Monthly Migraine Days at 3 Months
-1
Mean Change from Baseline in
• Rimegepant 75 mg EOD
treated patients demonstrated
-2 4.3 day reduction from
baseline in monthly
migraine days at month 3
compared to a 3.5 day
-3 reduction in the placebo
group, p < 0.01.
• Baseline MMDs = 10.1
-4 during observation period
-3.5 across all evaluable
subjects
-5 -4.3
p < 0.01 a
-6
a
Figure shows model-based estimates of the change from baseline for evaluable mITT cohort. MMD monthly migraine days. EOD every other day dosing
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 55Rimegepant EOD Met Key Secondary Endpoint – Superiority to Placebo in %
Patients with ≥50% Reduction from Baseline in Moderate-Severe MMDs at 3 Months
Placebo Rimegepant 75 mg
Every Other Day Every Other Day
N=347 N=348
0
% Patients Showing ≥50% Reduction in
Moderate to Severe Migraine Days/moa
-10 • 49.1% of rimegepant-treated
subjects achieved ≥50%
reduction, from baseline, in
-20 moderate to severe migraine
days per month at month 3,
compared to 41.5% for
placebo, p < 0.05
-30
• Baseline MMDs = 10.1
during observation period
-40 across all evaluable
subjects
-41.5
-50
-49.1
-60 p < 0.05
a
Figure shows model-based estimates of the change from baseline for evaluable mITT cohort. Moderate-Severe pain intensity. MMD monthly migraine days. EOD every other day dosing
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 56Oral NURTEC™ is First CGRP Targeting Medication to Show “Dual-
Therapy Action” with Both Acute and Preventive Treatment Benefits
• Patients treated with oral NURTEC (rimegepant 75 mg), dosed every other day, demonstrated
superiority over placebo on the primary endpoint of reduction in the mean number of migraine days
per month, and key secondary outcome measure assessing the proportion of patients who achieved a
≥50% reduction in moderate-to-severe migraine days at month 3
• Patients receiving the drug every other day experienced a statistically significant 4.3 day reduction from
baseline in monthly migraine days, compared to 3.5 day reduction in the placebo group, p < 0.01
• 49.1% of patients treated with NURTEC 75 mg showed a ≥50% reduction from their baseline number of
moderate-to-severe migraine days at month 3 compared to 41.5% of placebo-treated patients, p < 0.05
• Nurtec™ ODT 75 mg was approved earlier this year for the acute treatment of migraine showing rapid
onset within 60 minutes and durable benefits out to 48 hours with a single dose
• Nurtec is part of Biohaven’s NOJECTIONTM CGRP receptor antagonist platform and is the first
therapy to complete pivotal trials that demonstrate efficacy in both acute and preventive treatment of
migraine
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 57Commercial and Launch Readiness
Doing things
differently…
15 secNurtec™ ODT ‘Surround Sound’ Marketing Plan
Key Characteristics: Core HCP
• Competitive share of voice Rep Promotion
>500
• Highly targeted
• Modern, ‘social first’ mindse
Consumer
Omni-Channel Peer-2-Peer
(Awareness & Activation) (Engagement & Education)
HCP Omni-Channel
(Awareness & Engagement)
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 60Launch Payer Mix for CGRP Migraine Prevention Class (6 Months)
Payment Type
Commercial / Assistance
88.3% 89.3% 89.3% 87.1%
Programs
Medicare 6.0% 4.2% 5.2% 6.0%
Cash 2.8% 3.7% 2.8% 3.7%
Medicaid 2.6% 2.9% 2.7% 3.2%
Totals 100% 100% 100% 100%
*Ubrelvy data through 3 weeks of launch ending 2/7/20
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 61Managed Markets Customer Engagements JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 62
Established Treatments: Options for Acute Treatment of Migraine
Triptans NSAIDs Opioids
Butorphanol, morphine,
Examples Sumatriptan, naratriptan, zolmitriptan 1 Diclofenac, ketoprofen, flurbiprofen 2,3
hydromorphone 2,5
Migraine-specific
Yes 1 No 3 No 6
treatment?
• Moderate or severe attacks OR 2 Mild-to-moderate attacks 2 Used for moderate-to-severe migraine 7
• Mild-to-moderate that respond poorly
Use
to NSAIDs or caffeinated
combinations 2
Use with caution in patients who have:1,2 • Can cause serious gastrointestinal • Short-acting opioids have the
• Coronary artery disease and cardiovascular side effects 4 potential for physical dependence
• Peripheral vascular disease • May be associated with delays in and/or psychological addiction 7
Shortcomings • Uncontrolled hypertension absorption due to gastric hypomotility • May worsen patient's primary
• Other vascular risk factors and during migraine attacks 3 migraine disease through overuse 7
disorders
• Concomitant SSRI use
*Excedrin Migraine contains NSAID and nonNSAID ingredients.
References: 1. Rothrock JF, Friedman DI. American Headache Society website. https://americanheadachesociety.org/wp-content/uploads/2018/05/John_Rothrock_and_Deborah_Friedman_-
_Triptans.pdf. Accessed September 9, 2019. 2. The American Headache Society. Headache. 2019;59(1):1-18. 3. Pardutz A, Schoenen J. Pharmaceuticals. 2010;3:1966-1987. 4. Varga Z,
Sabzwari SRA, Vargova V. Cureus. 2017; 9(4):e1144. 5. Dodson H, Bhula J, Eriksson S et al. Cureus. 2018;10(4):e2439. doi:10.7759/cureus.2439. 6. Franklin GM. Neurology. 2014;83:1277-
1284. 7. American Migraine Foundation website. https://americanmigrainefoundation.org/resource-library/opioid-therapy-migraine/. Published October 12, 2007. Accessed September 9, 2019.
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 63REYVOW™ (Lasmiditan): Serotonin (5-HT) 1F Receptor Agonist
LABEL INDICATION: ACUTE TREATMENT OF MIGRAINE
DRIVING IMPAIRMENT CNS DEPRESSION, SEROTONIN SYNDROME
Advise patients not to drive & MEDICATION OVERUSE HEADACHES Schedule V
for 8 hours (detoxification may be necessary)
5.2 Central Nervous System Depression
Driving Impairment
REYVOW may cause central nervous system (CNS) depression, including
REYVOW may cause significant driving 9.1 Controlled Substance
dizziness and sedation.
impairment. In a driving study, administration Because of the potential for REYVOW to cause sedation, other cognitive REYVOW contains lasmiditan, a
of single 50 mg, 100 mg, or 200 mg doses of and/or neuropsychiatric adverse reactions, and driving impairment, Schedule V controlled substance.
REYVOW significantly impaired subjects’ REYVOW should be used with caution if used in combination with alcohol
ability to drive. or other CNS depressants. 9.2 Abuse
…With all doses of REYVOW,
Patient who cannot follow this advice should Serotonin Syndrome subjects reported statistically
not take REYVOW. In clinical trials, reactions consistent with serotonin syndrome were
significantly higher “drug liking”
reported in patients treated with REYVOW who were not taking any other
drugs associated with serotonin syndrome. Serotonin syndrome may also scores than placebo, indicating that
Prescribers and patients should be aware that REYVOW has abuse potential….
occur with REYVOW during coadministration with serotonergic drugs…
patients may not be able to assess their own
driving competence and the degree of
Medication Overuse Headache
impairment caused by REYVOW. Overuse of acute migraine drugs (e.g., ergotamines, triptans, opioids, or
a combination of these drugs for 10 or more days per month) may lead to
exacerbation of headache…
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 64Zavegepant: First and Only Third-Generation,
Zavegepant Structural
Intranasal CGRP Receptor Antagonist Diversity vs. Rimegepant
FIRST INTRANASAL FORMULATION OF A SMALL MOLECULE CGRP RECEPTOR ANTAGONIST
Zavegepant
• Superior chemical attributes
• Potent antagonist at the human CGRP receptor
• Highly soluble and high free fraction
• US composition of matter protection to March 20311
• Multiple potential routes of delivery hCGRP Ki = 23 pM
• Nasal, inhalation and oral
• Zavegepant Achieved Positive Topline Results in
Pivotal Phase 2/3 Study Rimegepant
• 10 and 20 mg achieved statistical superiority to placebo
on regulatory endpoints of pain freedom and freedom
from most bothersome symptom at 2 hours
• Zavegepant showed evidence of rapid onset with pain
relief as early as 15 minutes, return to normal function hCGRP Ki = 32 pM
at 30 min and sustained benefits through 48 hours
1. Patent expiration, not including patent term adjustment or any potential patent term extensions
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 65Zavegepant 10 mg and 20 mg Demonstrated Early Separation From
Placebo at 15, 60 and 120 Minutes, Durable Through 24–48 Hours
ZAVEGEPANT PHASE 2/3 — STUDY BHV3500-201, 10MG & 20MG INTRANASAL
Pain Relief to 2 Hours1 & Sustained Pain Relief 2-24/48 Hours2
Post-Single Dosing with Zavegepant Intranasal
% of Patients with Pain Relief Placebo (n=401) 61% 61%
Zavegepant 10 mg (n=391)
60 Zavegepant 20 mg (n=402) 50%
46% 45%
50 54% 43%
40% 39%
40
30% 42%
27%
30 36%
33%
18%
20 15% 25%
10
10%
0 //
15 min 30 min 60 min 120 min 2-24 hr 2-48 hr
Time
Single Dose of Zavegepant, No Rescue Meds
1. Pain Relief is defined as patients who have either mild-pain or no-pain during the specified interval. 2. Sustained Pain Relief is defined as patients having mild-to-no-pain at 2 hours and continuing to the end of the specified interval.
Estimates computed using the mITT population and CMH methods (mean ± Alpha’s Standard Error). Subjects using rescue medications at or before the assessment, and subjects not providing data, are classified as failures.
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 66GLUTAMATE PLATFORM Therapies for Neurologic and Neuropsychiatric Indications
The Role of Glutamate: Present in 90% of Brain Synapses
EXCITOTOXICITY NORMAL FUNCTION
Diseased State Healthy State
STRESS
DEMENTIA
RESILIENCE MEMORY
AMYOTROPHIC LATERAL SCLEROSIS
LEARNING SYNAPTO-
DEPRESSION ANXIETY PLASTICITY
NEURONAL
ABNORMAL CELL GROWTH
CONNECTIONS
NEURO-
STROKE MELANOMA
TRANSMISSION
MOOD
NEURODEGENERATION
NEUROTROPHIC
CANCER STRESS PAIN
SPINOCEREBELLAR ATAXIA ACTION
POTENTIAL
CELL
RETT SYNDROME
SURVIVAL
COGNITION
NEUROTOXICITY SEIZURES
Biohaven is focused on normalizing glutamate to treat disease
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 68Glutamate Mechanisms of Action in CNS
1 Glutamate Transporter Modulation
• Troriluzole
2 Glutamate NMDA Receptor Antagonism
• BHV-5000
1
Third-party clinical trials provide basis for
exploration of troriluzole and BHV-5000 in
2 multiple neurologic and neuropsychiatric
disorders
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 69Riluzole (Rilutek®): Use and Limitations
Riluzole (Rilutek®) is approved for the treatment of BENEFITS
patients with amyotrophic lateral sclerosis (ALS) ü Mechanism of action well understood
and proven to extend survival
ü Neuroprotective, survival benefit in ALS
ü Well tolerated, safe in clinical settings at approved dose
• Originally marketed by Sanofi, received FDA
approval in 1995
LIMITATIONS
• In 2013, the FDA approved the first generic ✘ Twice daily dosing, low bioavailability
versions of riluzole
✘ Fasting required for 6 hours/day,
• Doses above 100 mg for efficacy not approved can’t be taken with meals
due to dose-dependent liver effects
✘ Dose dependent LFT liability1
✘ Marked PK variability
✘ High drug burden relative to efficacy2
✘ Only one approved indication (ALS)
1. LFT = liver function test; 2. Poor oral bioavailability results in a high liver burden relative to efficacy as ~40% is either not absorbed or is metabolized in the liver
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 70Troriluzole: Rational Drug Discovery to Optimize Therapy • Improved absorption • Enhanced bioavailability • Reduced drug burden • Reduced first pass metabolism • Favorable safety profile • Once-daily dosing JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 71
Peptide Transporter 1 Enhances Absorption of Troriluzole
ACTIVE ABSORPTION IN INTESTINAL TRACT BY PEPT1
PepT1
PepT1 = Peptide Transporter 1
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 72Troriluzole: Targeted Lead-Indication Development Strategy
Neurodegenerative Obsessive-Compulsive Cerebellar
Disorders & Related Disorders Disorders
Lead indications Mild-to-Moderate Obsessive-Compulsive Spinocerebellar
Alzheimer’s Disease* Disorder Ataxia (SCA)
across an array of
potential neurologic
and neuropsychiatric
indications
Prodromal
Trichotillomania Friedreich’s Ataxia
Alzheimer’s Disease
ALS
(High Dose) Hoarding Disorder Sporadic Ataxia
Other Ataxias
Essential Tremor*
* Third-party study / collaboration ongoing or planned (ADCS Collaboration for AD; ET Study Group Collaboration for ET)
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 73Troriluzole Phase 2/3 Clinical Trial Design in AD
• Key entry criteria
• Diagnosis of mild to moderate Alzheimer’s disease Screening Randomization Extension
with Mini-Mental State Exam score of 14–24 Phase Phase Phase
6 weeks 48 weeks 48 weeks
• Co-primary efficacy endpoints
• Alzheimer's Disease Assessment Scale Cog11
Troriluzole
• Clinical Dementia Rating-Sum of Boxes 280 mg QD
Troriluzole
• Secondary efficacy endpoints R 280 mg QD
• Brain volumes: MRI imaging
Placebo QD
• Activities of daily living: ADCS-ADL
• Neuropsychiatric: NPI
• Neuropsychological: NTB
• Cognitive: MMSE/MoCA
• Sample size: 350 subjects Passed interim Futility Analysis December 2019
• Randomization: 1:1 Topline Data Expected January 2021
• Collaborator: Alzheimer’s Disease Cooperative Study
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 74Cerebellar Ataxias No FDA-Approved
Medications for SCA
• Characterized by:
• Poor balance with falls • Dysarthria / dysphagia
• Incoordination of limbs • Cognitive impairment
• Postural or kinetic tremor • Oculomotor dysfunction
• Spinocerebellar ataxia (SCA; >40 subtypes)
• Affects 1–5.6 per 100,000 (estimated 3,200–18,000 in US)
• Neurodegeneration of cerebellum and input/output tracts
• Relentlessly progressive, often fatal (aspiration)
• Increasing disability over time (requiring wheelchair, assistance with
activities of daily living)
• The 6 most common genotypes caused by triplet repeat expansion
mutations, sharing many phenotypic features Spinocerebellar Ataxia type 2
• Genetic anticipation in some: subsequent generations affected at earlier Cerebellar and brainstem volume loss
ages and with greater severity
• Other ataxias have similar core features
• Can be recessive, dominant, immune, mitochondrial, post-stroke, e.g.,
Friedreich’s ataxia, ataxia telangiectasia, multiple system atrophy —
cerebellar type
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 75Troriluzole Treated SCA Patients Treated for 1 Year Compared to
Matched Ashizawa Natural History Cohort
• Post-hoc analysis of patients enrolled SCA Patients on Troriluzole vs. Natural History Cohort
in long-term extension of Phase 2b/3
troriluzole SCA trial
Least Squares Mean2 Change in Total
• Primary efficacy endpoint: change
SARA Score (from baseline ± SE)
from baseline in the Total SARA Score
after 48 weeks
• Patients from BHV4157-201 trial
versus eligibility criteria matched Difference: -1.41 ± 0.411
Ashizawa Natural History cohort: (95% confidence interval of
• SCA Genotype -2.22 to -0.60) suggesting
• SCA1, SCA2, SCA3, SCA6 therapeutic benefits of
troriluzole (p=0.0007)
• Age at baseline
• 18 to 75 years of age
• Gender 1. Matched on eligibility criteria
2. ANCOVA model with fixed effects for cohort,
• SARA Score at baseline sex, & SCA genotype with age and baseline
SARA scores as covariates
• ≥ 8 and ≤ 30, and
• Initial SARA gait item score ≥ 2
Troriluzole Study (BHV4157-206) in Spinocerebellar Ataxia (SCA) Achieved Phase 2/3 start in 1Q19
SARA: Scale for the Assessment and Rating of Ataxia
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 76Troriluzole Study BHV4157-206 Randomized Controlled Trial in SCA
Key Entry Criteria
• SCA genotypes (SCA1, SCA2,
SCA3, SCA6, SCA7, SCA8, SCA10) Screening Randomization Extension
Phase Phase Phase
Design 6 weeks 48 weeks 48 weeks
• Sample size: 230 subjects
• Randomization: 1:1 Troriluzole
200 mg QD
• Stratification: by SCA genotype
Troriluzole
• Dose: Troriluzole 200 mg QD vs. R 200 mg QD
Placebo QD
• Primary Outcome: Modified SARA Placebo QD
Scale
• FDA aligned outcome measure
Status
• Phase 3 (initiated 1Q19)
SARA: Scale for the Assessment and Rating of Ataxia
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 77OCD Treatments Are Limited and Need Is Vast
• Few FDA-approved treatments
• Serotonin reuptake inhibitors (SSRIs and clomipramine) are the only approved monotherapy
• No new mechanisms for 30 years
• With limited efficacy1,2
•Accumulating Evidence for Glutamatergic Dysfunction in OCD
ANIMAL NEURAL PATIENTS
GENES IN THE CLINIC
MODELS NETWORKS
Genetic association ↑Glutamatergic activity Multiple neuroimaging Preliminary efficacy
studies: worsens OCD behaviors: studies: evidence:
Glutamate transporter SAPAP3 knockout mice (- Increased activity in Glutamate modulating
gene (SLC1A1 on /-) exhibit OCD-like cortico-striatal-thalamic agents show promise in
chromosome 9p24) behaviors2 (CST) pathway3 OCD patients
associated w/OCD1
SAPAP3 is an ortholog of MRS studies:
GWAS studies are DLGAP3, in the same Glutamate dysfunction
focusing attention on family as a gene in OCD suggested by
DLGAP1, a post-synaptic implicated by OCD GWAS some studies4,5
scaffolding molecule at studies
glutamate synapse Spinal fluid studies:
Increased glutamate in
OCD patients6
1. Arnold et al 2006; 2. Aida et a; 2015; 3. Baxter et al 1987, 1988, 1992; Nordhal et al 1989; Swedo et al 1989; Sawle et al 1991; Rubin et al 1992, 1995; Adams et al 1993; Perani
et al 1995; Adams et al 1993; Perani et al 1995; McGuire et al 1994; Breiter et al 1996; Rausch et al 1996; 4. Rosenberg et al 2000; 5. Bolton et al 2001; 6. Chakrabarty et al 2005
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 79Neurochemical Evidence for Glutamate Dysregulation in OCD
Concentration (x104/water)
Caudate Glutamatergic
Healthy Control Treatment Naïve
Subjects OCD Patients
n = 11 n = 11
Rosenberg et al. 2000
Consistent with pathologic hyperactivity in cortico-striatal circuit
Suggests clinical testing of agents that enhance glutamate uptake
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 80Neurochemical Evidence for Glutamate Dysregulation in OCD
CSF Glutamate Concentrations
Bhattacharyya et al. 2009
Consistent with pathologic hyperactivity in cortico-striatal circuit
Suggests clinical testing of agents that enhance glutamate uptake
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 81Randomized Controlled Trial with Riluzole Augmentation
• Outpatients with moderate-to-severe OCD
severity (Y-BOCS score ≥ 21) and free of
medication treatment for at least six weeks
• Randomized to receive fluvoxamine (up to 200
Y-BOCS Total Score
mg/day) plus either placebo or riluzole (50 mg
twice daily) *
• Robust benefit on primary outcome measure
Placebo (n=25)
(change in Y-BOCS scores)
Riluzole (n=25)
*, pTroriluzole Study BHV4157-202 in Randomized Controlled Trial in OCD
KEY ENTRY CRITERIA
• Moderate-to-severe OCD Screening Randomization Extension
and inadequate response to Phase Phase Phase
standard of care 42 days 12 weeks 48 weeks
DESIGN
SOC + Troriluzole
• Sample size: 226 subjects 200 mg QD
SOC + Troriluzole
• Randomization: 1:1 R 200 mg QD
• Dose: Troriluzole 200 mg SOC +
Placebo QD
QD vs. Placebo QD (in
patients on standard of care)
Subjects (n=226) with Moderate to severe OCD and inadequate response to standard of care
• Primary Outcome: Y-BOCS,
a precedented outcome SOC, standard of care
measure accepted by FDA
Y-BOCS, Yale-Brown Obsessive Compulsive Scale
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 83Troriluzole OCD Phase 2/3 Topline Results
SOC, standard of care
Y-BOCS, Yale-Brown Obsessive Compulsive Scale
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 84Troriluzole Phase 3 Program in Obsessive-Compulsive Disorder
• TWO PHASE 3 STUDIES
• BHV4157-302 (US only)
• BHV4157-303 (global) Screening Randomization Extension Study
Phase Phase (BHV4157-209)
• KEY ENTRY CRITERIA 42 days 10 weeks 48 weeks
• Moderate-to-severe OCD
• Inadequate response to SOC SOC + Troriluzole
280 mg QD
• DESIGN (identical for each Ph 3 study)
SOC + Troriluzole
• Sample size: 600 subjects R 280 mg QD
• Randomization: 1:1
SOC +
• Treatment: Placebo QD
• Troriluzole 280 mg vs. placebo, 1x daily
• Adjunctive therapy to SOC
Subjects (n=600) with moderate-to-severe OCD and inadequate response to SOC
• Primary Outcome: Y-BOCS
• FDA accepted outcome measure
• STATUS
• Phase 3 initiated 4Q2020
OCD, obsessive-compulsive disorder; SOC, standard of care; Y-BOCS, Yale-Brown Obsessive-Compulsive Scale
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 85MPO PLATFORM Therapies for Neuroinflammation
Multiple System Atrophy (MSA)
• 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
• 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
• Pathology: glial cytoplasmic inclusions (GCIs) containing alpha-synuclein
• Disease mechanisms: oxidative stress and neuroinflammation
• No disease modifying treatments
• Symptomatic and palliative management
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 87Verdiperstat (BHV-3241) is a Myeloperoxidase Inhibitor
• Myeloperoxidase (MPO) enzyme
• Key mediator of oxidative and inflammatory
processes that lead to neurodegeneration
• Promotes alpha-synuclein aggregation
• Increased in human MSA brains in areas of
neurodegeneration1
• Verdiperstat
• Potent, first-in-class, brain-penetrant MPO inhibitor
• Developed by AstraZeneca (formerly AZ3241)
1. Neurotox Res 2012;21(4):393-404
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 88Verdiperstat Neuroprotective Effects in MSA Animal Model1
Suppresses microglial activation Reduces GCIs of alpha-synuclein Rescues neurodegeneration
Promotes functional (motor) improvements
RLZ treated
1. Neurotox Res 2012;21(4):393-404
JANUARY 2021 BIOHAVEN INVESTOR PRESENTATION 89You can also read
