Next Wave of Medicines August 2019 1 Proprietary & - - PowerPoint PPT Presentation

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Next Wave of Medicines August 2019 1 Proprietary & - - PowerPoint PPT Presentation

(NASDAQ: BTAI) Next Wave of Medicines August 2019 1 Proprietary & Confidential BioXcel Therapeutics, 555 Long Wharf Drive, New Haven, CT 06511 | www.bioxceltherapeutics.com Forward-Looking Statements This presentation includes


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Proprietary & Confidential

1 BioXcel Therapeutics, 555 Long Wharf Drive, New Haven, CT 06511 | www.bioxceltherapeutics.com

Next Wave of Medicines

August 2019

(NASDAQ: BTAI)

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Forward-Looking Statements

This presentation includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this presentation include, but are not limited to, statements that relate to the advancement and development of BXCL501 and BXCL701, the commencement of clinical trials, the availability and results of data from clinical trials, BioXcel Therapeutic, Inc.'s (“BTI”) submission of its first New Drug Application with the FDA and other information that is not historical information. When used herein, words including “anticipate”, “being”, “will”, “plan”, “may”, “continue”, and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon BTI's current expectations and various assumptions. BTI believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. BTI may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, its limited operating history; its incurrence of significant losses; its need for substantial additional funding and ability to raise capital when needed; its limited experience in drug discovery and drug development; its dependence on the success and commercialization of BXCL501 and BXCL701 and other product candidates; it ability to receive regulatory approval for its product candidates; its ability to enroll patients in its clinical trials; its approach to the discovery and development of product candidates based on EvolverAI is novel and unproven; its exposure to patent infringement lawsuits; its ability to comply with the extensive regulations applicable to it; its ability to commercialize its product candidates; and the other important factors discussed under the caption “Risk Factors” in its Quarterly Report on Form 10-Q for the period ended March 31, 2019 as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SEC's website at www.sec.gov. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this

  • presentation. Any such forward-looking statements represent management's estimates as of the date of this presentation. While BTI may elect to

update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing BTI's views as of any date subsequent to the date of this presentation.

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BXCL701

Targeting Rare Cancers Clinical Partnerships

BioXcel Therapeutics Investment Highlights

  • Phase 3 Pivotal Trial Initiation

− 4Q 2019

  • Phase 3 Data Readout

− 1H 2020

  • 3 Ongoing Trials

− Pancreatic Cancer: (2 trials) − Neuroendocrine Prostate Cancer (tNEPC)

  • Data Readouts Expected in

2H 2019 and 1H 2020

BXCL501

Sublingual Thin Film for Acute Treatment of Agitation

  • Improves R&D Economics
  • Increases Development Efficiency
  • Maximizes Probability of Success

Innate Immunity Based Approach Neuro Symptoms Based Approach AI-powered Drug Development

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T R A N S L A T I O N A L T E A M M U L T I P L E C A N D I D A T E S

NDA

C L I N I C A L D E V E L O P M E N T T E A M

3 2 1

Registration Filings Candidate Validation Human Proof Of Concept Selection of Best Candidates

R E G U L A T O R Y T E A M

BXCL501 BXCL701 AI Powered Drug Development 4-5 Year Development Cycle

Unleashing the Power of AI Across the Entire R&D Value Chain

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Pipeline To Rapid Human PoC and Development Path

Phase 1/2 Phase 2/3 Anticipated Milestones Product Candidate

BXCL701

(DPP 8/9 & FAP Inhibitor)

Immuno- Oncology Pancreatic Cancer

(triple combination)

Treatment of Acute Agitation

BXCL501

(Selective α2a Adrenergic Receptor Agonist)

Additional Discovery Through an Exclusive AI Relationship with BioXcel Corporation (parent)

Future Programs

Worldwide Rights

  • Phase 3 schizo/bipolar trial

initiation (4Q 2019)

  • Phase 3 schizo/bipolar data

readout (1H 2020)

  • Schizo/bipolar NDA

submission (2H 2020)

  • Dementia trial initiation (2H 2019)
  • tNEPC data readouts

(2H 2019)

  • Pancreatic data readouts

(1H 2020)

*Bioavailability (BA) study for optimizing BXCL501 sublingual thin film dose for Phase 3 registration trials

Schizophrenia/Bipolar Geriatric Dementia

Phase 1b Completed

  • New indications & geography

expansion (2019)

Pipeline Expansion BXCL501 BXCL701

Opioid Withdrawal, Delirium Exploring Multiple Tumor Types

Program

Proof of Concept Trial Initiating

Neuroendocrine Prostate Cancer (tNEPC)

(double combination)

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Clinical Programs

BXCL501: First in Class Sublingual Thin Film Dexmedetomidine (Dex) for Acute Treatment of Agitation

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Agitation is an Unmet Medical Need

  • Common and expensive phenomenon associated

with multiple psychiatric conditions − 8.3 million suffer each year in the US − $40 billion per year health care burden

  • Rapid symptom relief with a non-invasive approach

is desired

  • Patients experience multiple episodes per year

8.3M 5M

~19M At Risk

Suffer Agitation Mild to Moderate Agitation

BXCL501

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Current Treatments are Suboptimal:

  • Dementia: Antipsychotic drugs (black-box warning) for elderly
  • Psychiatric: Invasive with severe side effects

Proprietary Sublingual Thin Film of Dex# for Acute Treatment of Agitation

Fast Track Designation

  • Non-invasive
  • Calmness without sedation
  • Easy to administer
  • Rapid onset
  • Non-traumatic / non-coercive
  • Good safety profile
  • Favorable tolerability
  • Patient preference

Consensus Opinion* Treatment Options

BXCL501: Novel Mechanism of Action (MoA) üNon-Invasive, easy to administer sublingual thin film designed for rapid onset of action

#Dexmedetomidine *Martinez-Raga, J., et al. (2018). "1st International Experts' Meeting on Agitation: Conclusions Regarding the Current and Ideal Management Paradigm of Agitation."

BXCL501

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Proprietary Formulation and Scale Up Manufacturing

  • Transitioned to Automated Manufacturing for Scale Up

− GMP manufacturing initiated − Scale up and supply phase 3 in 2H 2019 and commercial readiness in 2020

  • Extensive Formulation Development Completed for Clinical Studies

− Multiple dose strengths − Immediate release film with muco-adhesion properties − Proprietary technology delivers low dose ranges

118 subjects dosed: Healthy volunteers (28) and Agitated Schizophrenia patients (90)

BXCL501

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Predictable and Dose Proportional PK in Phase I Study

1 2 3 4 5 6 7 8 0.1 1 10 100 1000

Time (hours) Mean Concentration (ng/L) 10 µg 40 µg 20 µg

28 active : 14 placebo Phase I clinical studies in 42 healthy volunteers

BXCL501

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BXCL501 (20, 60, 80, 120, 180 mcg)

Phase 1b Clinical Trial in Agitated Schizophrenia Patients

Assessing Agitation Episodes in Schizophrenia

Primary Endpoint: Change from baseline in PEC score (PANSS-Excitatory Component) ✔ Initiated May 2019 → ✔ Completed July 2019 Evaluation Period (6 hours)

0 min 60 min 120 min 180 min 240 min 300 min 360 min

* Placebo

R

2:1 Randomization (n = 135)

n=90 n=45

BXCL501

Screening Period Agitated Schizophrenia Patients

* Patients Dosed

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Primary Endpoint: Change in PEC Score from Baseline

Drug/Dose #

% Responders (Reduction in PEC of ≥ 40%) Mean Change in PEC Score P-Value Placebo N=36 28%

  • 4.5

BXCL501 (180 mcg) N=18 89%

  • 10.8

< 0.0001 BXCL501 (120 mcg) N=18 67%

  • 9.2

0.0003 BXCL501 (80 mcg) N=18 56%

  • 7.1

0.0152 BXCL501 (60 mcg) N=18 39%

  • 6.0

0.1227

*The lowest dose tested, 20 mcg (not shown) was repeated in subjects who did not achieve response criterion

Time = 120 Min (Primary Endpoint)

Change in PEC Score from Baseline (Least Squares means)

60 120 180 240 300 360

  • 12
  • 10
  • 8
  • 6
  • 4
  • 2

Time Post Dose (Minutes)

** *** *** *** *** *

Placebo 180 mcg 80 mcg

* * * * ** *

* = p < 0.05 ** = p < 0.001 *** = p < 0.0001

BXCL501

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Secondary Evaluation: Change in ACES from Baseline

Drug/Dose # Mean Change in ACES Score From Baseline P-Value Placebo N=36 1.20 BXCL501 (180 mcg) N=18 3.94 < 0.0001 BXCL501 (120 mcg) N=18 3.11 0.0005 BXCL501 (80 mcg) N=18 2.33 0.0156 BXCL501 (60 mcg) N=18 2.11 0.0750

*The lowest dose tested, 20 mcg (not shown) was repeated in subjects who did not achieve response criterion The ACES consists of a single item that rates overall agitation and sedation at the time of evaluation, where 1 indicates marked agitation; 2, moderate agitation; 3, mild agitation; 4, normal behavior; 5, mild calmness; 6, moderate calmness; 7, marked calmness; 8, deep sleep; and 9, unarousable.

Placebo 80 mcg 180 mcg 1 2 3 4 5

Dose Change in ACES Score from Baseline (Least Squares Mean) p = 0.0156 p = <0.0001

BXCL501

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BXCL501 (2 Doses)

Phase 3 Pivotal Trial: Potential Design

Assessing Agitation Episodes in Schizophrenia and Bipolar Disorder

Primary Endpoint: Change from baseline in PEC score (PANSS-Excitatory Component) Expected to Initiate 4Q 2019

Placebo

1:1 Randomization (n = 600-700)

BXCL501 Evaluation Period (6 hours)

0 min 60 min 120 min 180 min 240 min 300 min 360 min

*

R

Trial 2: Agitated Bipolar Patients

Screening Period

Trial 1: Agitated Schizophrenia Patients

* Patients Dosed

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Potential To Capitalize on Large US Commercial Opportunity

2 4 6 8 10 12 14 16 18 20 AT RISK WITH AGITATION MILD TO MODERATE AGITATION

Schizophrenia Bipolar Disorder Dementia Opioid Use Disorder Delirium

Patients (Millions)

18.9M 5.0M 8.3M

Sources: Internal Company Estimates

  • https://www.sccm.org/Communications/Critical-Care-Statistics
  • https://psychiatryonline.org/doi/pdf/10.1176/appi.books.9780890426807
  • https://www.samhsa.gov/data/
  • https://www.nimh.nih.gov/health/statistics/index.shtml
  • 5 Million Patients With Mild to Moderate Agitation
  • Multiple Episodes Per Year

0.53 1.34 0.45 1.71 0.94 BXCL501

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Key Targeted Milestones for Value Creation

BXCL501

Anticipated Timeline

Schizophrenia / Bipolar Disorder

Phase 3 Pivotal Trial Initiation First NDA Submission Phase 1b Data Announced (July 22, 2019) Phase 3 Data Readout 3Q’19 4Q’19 1H’20 2H’20 2021 Commercial Launch

BXCL501

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Clinical Development Plan Across Multiple CNS Conditions

1H 2020 INDICATION 1H 2019 2H 2019 2H 2020 2021 2022

Phase 3: Schizophrenia & Bipolar Disorder

Schizophrenia/ Bipolar Disorder

(Acute Agitation)

Alzheimer’s/ Dementia

(Acute Agitation) Opioid Withdrawal

(Symptoms)

NDA Submission Phase 1b: Schizophrenia

Delirium

(Acute Agitation)

Phase 1b Trial Planning Trial Planning BXCL501

Commercial Launch

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Clinical Programs

BXCL701: First-in-Class Oral IO Therapy Targeting Pancreatic Cancer and tNEPC

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Potential First-in-Class Oral I/O Therapy

Orally Administered Activator of Systemic Innate Immunity Pathway Dual MoA Inhibits DPP 8/9 & FAP Established clinical proof of mechanism & tolerable safety profile (>700 patient data)

ü Ongoing Clinical Trials: Pancreatic (2), tNEPC

(1) Nature Chemical Biology, volume 13, pages 46–53 (2017)

Validation of AI Approach1

Pancreatic Cancer Melanoma

BXCL701

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FAP

Human Proof of Concept & Mechanism of Action

Inflammasome ↓ Caspase-1 ↓ Pyroptosis & IL-18 release Breaks Fibrotic Barrier

DPP 8/9

IMMUNE EVASION IMMUNE ACTIVATION

>700

Patient Data

BXCL701 Human Proof of Concept

ü Single Agent Activity in Melanoma ü ~10% Response Rate (CR/PR) ü Comparable to Yervoy (anti-CTL4)

BXCL701

BXCL701

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Pancreatic Cancer: Mechanistic and Triple Combination Trial

YES Activity

Stop

NO

2 Weeks of BXCL701 Treatment Before Surgery (Pre and Post Tissue Available (N=10-15)) Efficacy Trial in Metastatic Patients after First-line Treatment Triple Combination Phase 2 Expansion

(N=30)

Simon 2-stage: 15+15 Primary Endpoint: ORR Combination: > 15% Secondary Endpoint: DoR, PFS, OS Exploratory Endpoint: Effect on immune cells (MDSC, T-cells, neutrophils)

Demonstration of Immune Cell Infiltration/Activation to Validate MoA Louis Weiner, M.D. Director

BXCL701 NKTR-214 Avelumab

Proof of Mechanism Trial

Global* Pivotal Study

BXCL701

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tNEPC Clinical Development Plan: Combination with Keytruda

*Expect to commence global

development planning during Phase 2 Focus on EU and Japan

Simon 2-stage: 15+15 Primary Endpoint: ORR Combination: > 15% Secondary Endpoint: DoR, PFS, OS Exploratory Endpoint: Effect on immune cells (MDSC, T-cells, neutrophils)

✔ Patient Recruitment Ongoing

Safety Run-in

Safety/PD/Immune-phenotyping (N=6)

Phase 2 Expansion

(N=30)

✔ CTA Accepted 2Q19

Eric Small, M.D. Chief, Division of Hematology/Oncology Johann de Bono, M.D., Ph.D. Head, Division of Clinical Studies

Global* Pivotal Study

BXCL701

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Key Targeted Milestones for Value Creation

BXCL701

Anticipated Timeline

Neuroendocrine Prostate Cancer (tNEPC) Pancreatic Cancer (PDA)

Combination Trial Initiated (BXCL701+Keytruda)

tNEPC Data Readout Registration Trial

Mechanism Trial Initiated Triple Combination Trial Initiated

2H’18 1H’19 2H’19 1H’20 2H’20 Beyond

Pancreatic Data Readouts Registration Trial BXCL701

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Total Cash and Cash Equivalents: ~30.0 million as of June 30th, 2019 Major Shareholders:

Artemis (6.25%)* Fidelity (5.37%)* DNCA Finance (5.11%)

Analyst Coverage:

Geoff Meacham (Barclays) Carter Gould (UBS) Do Kim (BMO Capital Markets) Sumant Kulkarni (Canaccord Genuity) Ram Selvaraju (H.C. Wainwright)

Optimally Positioned for Execution

Funded to Reach Multiple Inflection Points

* As of July 2019 * As of March 2019

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Appendix

Management Team Board Profile Clinical Advisory Boards

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World-Class Leadership Team

VIMAL MEHTA

CEO & Member of Board

FRANK YOCCA

Chief Scientific Officer

VINCENT J. O’NEILL

Chief Medical Officer

RICHARD I. STEINHART

Chief Financial Officer

CHETAN D. LATHIA

Senior Vice President, Head of Translational Medicine

Corporate

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World-Class Leadership Team

Strategic Advisors Board of Directors

SHEILA GUJRATHI

CEO, Gossamer Bio

PETER MUELLER

Chairman of Board

STEVE LAUMAS

Member of Board

KRISHNAN NANDABALAN

Member of Board

MICHAL VOTRUBA

Member of Board

STEVEN PAUL

CEO, Karuna Therapeutics

Corporate

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Neuroscience Clinical Advisory Board

John Krystal, M.D. Chair, Department of Psychiatry Maurizio Fava, M.D. Director, Division of Clinical Research Thomas Laughren, M.D. Director, Regulatory Affairs Sheldon H. Preskorn, M.D. Professor of Psychiatry Thomas Kosten, M.D. Director, Division of Alcohol and Addiction Psychiatry Stephen R. Marder, M.D. Director, Section on Psychosis George Grossberg, M.D. Director, Geriatric Psychiatry Alan Breier, M.D. Professor of Psychiatry, Vice-Chair for Clinical Research

Corporate

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Immuno-Oncology Clinical Advisory Board

Louis M. Weiner, M.D.

Director, Georgetown Lombardi Comprehensive Cancer Center

Daniel Von Hoff, M.D., F.A.C.P.

Physician in Chief, Distinguished Professor at the TGen

Eric J. Small, M.D.

Chief, Division of Hematology/Oncology

Emmanuel S. Antonarakis, M.D.

Associate Professor of Oncology and Urology

Johann de Bono, M.D., Ph.D.

Head, Division of Clinical Studies

Corporate

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  • Dr. Vimal Mehta, CEO

BioXcel Therapeutics, New Haven, CT 06511 vmehta@bioxceltherapeutics.com

T H A N K Y O U !