Slide 1: BXCL701 Key Opinion Leader Day
NASDAQ: BTAI ® BXCL701 Key Opinion Leader Day February 21, 2023 BioXcel Therapeutics | 555 Long Wharf Drive, 12th Floor | New Haven, CT 06511 | www.bioxceltherapeutics.com
Slide 2: Forward-Looking Statements
2 Forward-Looking Statements This presentation includes "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. We intend such forward- looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section
Slide 3: Agenda and Speakers
3 Agenda and Speakers • BioXcel Therapeutics: Corporate Overview • Prostate Cancer Overview and Challenges with Current Immunotherapy Vimal Mehta, Ph.D. Vincent J. O’Neill, M.D. • BXCL701 Mechanism Founder and CEO Chief R&D Officer BioXcel Therapeutics OnkosXcel Therapeutics of Action • Results of P
Slide 4: BioXcel Therapeutics: Corporate Overview
4 BioXcel Therapeutics: Corporate Overview Vimal Mehta Founder & CEO ®
Slide 5: Building a Unique Biopharmaceutical Business Model
5 Building a Unique Biopharmaceutical Business Model Transformative Drug Re-innovation Approach Using AI BioXcel Therapeutics: Targeting High Unmet Continuing Mission of Developing Needs in Neuroscience and Immuno-Oncology Transformative Medicine in Hard-to-Treat Tumors • Optimize R&D, accelerate de
Slide 6: Innovation Shaping the Immunotherapy Cold Solid Tumor Market
6 Innovation Shaping the Immunotherapy “Cold” Solid Tumor Market Similar to Hematological Market in the 2000s Multiple Myeloma BXCL701 Transformative Potential Leadership in DPP8/9 “The first effective new drug to treat MM in decades, inhibition to turn “cold” Thalomid launched a new era of "novel t
Slide 7: Disruption is in Our DNA
7 Disruption is in Our DNA Developing Transformative Medicines in Two Underserved Therapeutic Areas Neuro franchise Poised to potentially capture 139-million- episode1 U.S. agitation market2 Delivering Disrupting First drug $260m strategic innovation drug development approved and financing in paradi
Slide 8: First AI Derived Human POC for Oral Innate Immune Activator
First AI Derived Human POC for Oral Innate Immune Activator 8 Utilizing Extensive Data from 11 Prior Clinical Trials and ~700 Subjects 2H 2023* Q1 2023 Q3 2022 Q1 2022 Q1 2021 Phase 2B Q4 2020 SCNC full initiation Q2 2020 Phase 2a Durability of efficacy/ Q4 2018 Phase 2a interim safety data SCNC Pha
Slide 9: BXCL701: Strong Value Proposition in Hard-to-Treat Tumors
9 BXCL701: Strong Value Proposition in Hard-to-Treat Tumors Mechanism of Action Full Phase 2 Data for SCNC Data Published in JITC Presented at ASCO GU • Composite response rate: 25% One of the most clinically advanced oral innate immune activators, designed to activate inflammasome • Median duration
Slide 10: Prostate Cancer Overview and Challenges with Current Immunotherapy
10 Prostate Cancer Overview and Challenges with Current Immunotherapy Daniel P. Petrylak, M.D. Speaker is acting on behalf of and is a paid consultant to BioXcel Therapeutics, Inc. This material is intended for an investor audience only. The information contained in the following material is intende
Slide 11: Prostate Cancer 2023
11 Prostate Cancer 2023 • Leading male US cancer, 2nd cancer deaths (lung #1) • New: 288,300 Deaths: 34,700 • Prevalence of metastatic disease: 100,000 • Lifetime US risk: – Diagnosis: ~17% Death: ~3% • Every 2 Minutes an American is diagnosed with prostate cancer and every 18 Minutes an American di
Slide 12: What Was the Path to mCRPC?
12 What Was the Path to mCRPC? Recurrent ADT nmCRPC BCR ADT primary ADT no ADT prostate cancer mCRPC mHSPC ADT ADT De Novo de novo mHSPC
Slide 13: Differing Natural Histories
13 Differing Natural Histories n = 2859 mCRPC from Prostate Cancer Metastatic European Prostate Localized Hormono Sensitive Cancer Registry (PrCA (mHSPC) Metastatic Castration Resitant (mCRPC) 1.2 yrs 35% [0.1;5.2] 1.4 yrs [0.9; 2.7] Death Castration Resistant • OS comparable after 5.2 yrs 1.2 yrs p
Slide 14: Treatment of Metastatic Prostate Cancer
14 Treatment of Metastatic Prostate Cancer Androgen blockade + Abiraterone Abiraterone + Docetaxel Enzalutamide + Apalutamide Cabazitaxel + Enzalutamide Radium-223 Daralutamide Abiraterone Tumor Enzalutamide volume and Sipuleucel-T activity Docetaxel Time
Slide 15: Classes of Agents
15 Classes of Agents • Immunotherapeutic – Sipuleucel-T – Pembrolizumab MSI-high • Hormonal – Enzalutamide, apalutamide, darolutamide, abiraterone • Cytotoxic – Docetaxel, cabazitaxel • DNA damage – Rad223 – Olaparib, rucaparib
Slide 16: Updated WHO Classification in Prostate Cancer
16 Updated WHO Classification in Prostate Cancer Table 1 - The 2022 WHO classification of the Prostate and Seminal Vesicle Epithelial tumors of the prostate Glandular neoplasms of the prostate 8440/0 Cystadenoma 8148/2 Prostatic intraepithelial neoplasia, high grade 8500/2 lntraductal carcinoma 8140
Slide 17: Neuroendocrine Prostate Cancer Terminology
17 Neuroendocrine Prostate Cancer Terminology • Morphology-based definition – Small cell carcinoma, large cell carcinoma, mixed/NED, other NE Epstein et al, Am J Surg Path 2014; Mosquera, Beltran et al, Neoplasia 2013
Slide 18: Neuroendocrine Prostate Cancer Terminology
18 Neuroendocrine Prostate Cancer Terminology • Morphology-based definition – Small cell carcinoma, large cell carcinoma, mixed/NED, other NE • IHC not required for diagnosis but is often: – (+) for at least 1 NE marker ▪ e.g., INSM1, SYP, NSE – (-) androgen receptor (AR) – (-) Luminal markers ▪ Eg,
Slide 19: Current Diagnosis of NEPC is Imperfect
19 Current Diagnosis of NEPC is Imperfect POSSIBLE EXPLANATIONS: Some people report never or rarely seeing a • Repeat biopsies are not standardly case of NEPC done in mCRPC • Variability amongst pathologists – Others report up to evaluation and nomenclature not 15–20% of CRPC tumors standardized • I
Slide 20: Tumors Exhibiting a T Cell–Inflamed or Non-T-Cell-Inflamed Phenotype
20 Tumors Exhibiting a T Cell–Inflamed or Non-T-Cell-Inflamed Phenotype
Slide 21: Sipuleucel-T: Autologous APC Cultured with PAP-Cytokine Fusion Protein
21 Sipuleucel-T: Autologous APC Cultured with PAP-Cytokine Fusion Protein Recombinant Prostatic APC takes up Antigen is processed Fully activated, the APC Acid Phosphatase (PAP) the antigen and presented on is now sipuleucel-T antigen combines with surface of the APC resting antigen INFUSE PATIENT p
Slide 22: IMPACT Overall Survival
22 IMPACT Overall Survival Intent-to-Treat Population 100 P = 0.032 (Cox model) HR = 0.775 [95% CI: 0.614, 0.979] Percent Survival 75 Median Survival Benefit = 4.1 months 50 Sipuleucel-T (n = 341) Median Survival: 25.8 months 25 Placebo (n = 171) Median Survival: 21.7 months 0 0 6 12 18 24 30 36 42
Slide 23: Key Data From Anti-PD-1 / PD-L1 Alone in mCRPC
23 Key Data From Anti-PD-1 / PD-L1 Alone in mCRPC • Phase I atezolizumab study in mCRPC cohort 1 – Unresectable or recurrent patients with prior treatment with sipuleucel-T or enzalutamide – ORR (RECIST 1.1) 0%, ORR (irRECIST) 7.0%, mPFS 3.4 months, and mOS 18.6 months – 60% of patients had TRAEs (2
Slide 24: Subtypes of Prostate Cancer Sensitive to Checkpoint Inhibitors
TABLE. Subtypes of Prostate Cancer Sensitive to Checkpoint Inhibitors INTERVENTION TRIAL TYPE PATIENTS OUTCOME KEYNOTE-028" Pembrolizumab 10 mg/kg 1V/2 wk Phase Ib 23 DORI4mo OS8mo ORR TR KEYNOTE-199° Pembrolizumad 200 mg/kg IV/3 wi Phase2 133 DOR IT mo OS9.5mo SO Antonorakis et al" Pembrolizumab Re
Slide 25: MSI in Castration-Resistant Prostate Cancer
25 MSI in Castration-Resistant Prostate Cancer Patient No. P-0011155 PR -99.9 Best PSA Response From Baseline, % P-0008682 PR -81.3 P-0025952 PR -99.9 P-0000755 SD -40.8 P-0018147 PD +88.1 Treatment duration P-0012928 Inevaluable (toxic effects) Death -18.3 P-0000964 PD Treatment ongoing -60.3 Anti-
Slide 26: Primary Endpoint: OS at Final Analysis, ITT Population
26 Primary Endpoint: OS at Final Analysis, ITT Population Events/Participants Hazard Ratio (95% CI) 100 Pts w/ Median, mo Overall 563/1030 0.92 (0.78-1.09) Event (95% CI) Age 90 Pembrolizumab + <65 years 123/225 0.95 (0.66-1.35) 275 19.6 (18.2–20.9) 65 years 440/805 0.91 (0.75-1.09) docetaxel Age (
Slide 27: TAM Kinase, VEGFR2 and MET Inhibition
27 TAM Kinase (TYRO3, AXL, MER) Inhibition VEGFR2 Inhibition + Increases numbers of Decreases number/function circulating and of regulatory T cells and MDSCs tumor-infiltrating CD8+T cells + Promotes macrophage fee MET Inhibition foe phenotype transition + Blocks MET-induced from M2 (immune- tumor e
Slide 28: Atezolizumab / Cabozantanib
28 Atezolizumab / Cabozantanib
Slide 29: CONTACT-02 Trial Design
29 CONTACT-02 Trial Design Patients Key eligibility Cabozantinib Efficacy Endpoints • Prior treatment with one, and only (40 mg daily) R Atezolizumab one, NHT (e.g., abiraterone, A apalutamide, darolutamide, or (1200 mg /20 mL q3w) Primary: N (n = 290) enzalutamide) D • PFS per RECIST 1.1 O • Surgic
Slide 30: Bi-Specific T Cell Engager (BiTE)
30 Bi-Specific T Cell Engager (BiTE®)… • Once T cells are activated by a BiTE molecule, the T cells may induce further T-cell proliferation and cytokine production • Induces apoptosis; activated T cells release cytokines and produce additional perforin/granzymes that may allow T cells to target surr
Slide 31: Two flexibly linked, single-chain antibodies
31 Two flexibly linked, single-chain antibodies, with one that is specific for a selected tumor-associated antigen and the other that is specific for CD3 found on T cells
Slide 32: Pasotuxizumab
T cell binding Peptide linker domain (CD3) Pasotuxizumab Tumor specific antigen binding domain Hummel HD et al. Immunotherapy. 2021;13(2):125-141
Slide 33: Therapeutic Targets
33 Therapeutic Targets • DLL3 in NEPC (AMG 757) • STEAP1 (AMG 509) • Human Kallikrein-2 (KLK2) • TMEFF2: ESMO 2022 poster • PD-1 x CTLA-4 (Vudalimab = XmAb20717) • PSMA • PSCA
Slide 34: BiTE Molecules
34 BiTE Molecules • Pasotuxizumab - AMG 212 = BAY 2010112 • Acapatamab - AMG 160: half-life extended • HPN424 • JNJ-081 • REGN5678
Slide 35: PSCA Targeted CAR T
35 PSCA Targeted CAR T Phase 1 Study
Slide 36: P-PSMA-101
36 P-PSMA-101 PSMA Targeted CAR T, Phase 1 Study CAR encodes intracellular 4-1BB signaling domain and a T-cell receptor (TCR) ζ chain signaling domain expresses three • P-PSMA-101 is an autologous CAR-T therapy major components from a transposed transgene that is stably integrated into the genome ta
Slide 37: P-PSMA-101 Clinical Response Data
37 A B Baseline 12 weeks Baseline (SUV 28.5) 4 weeks (SUV 8.3) 12 weeks (SUV 2.8) D CD4 CD8 C Baseline 12 weeks E 40 10 5 P-PSMA-101 / mg DNA PSA 30 PSA (ng/mL) 10 4 P-PSMA-101 copies/mg DNA in 20 peripheral blood 10 3 P-PSMA-101 10 10 2 copies/mg DNA in biopsy tissue 50 0 -70 0 20 40 60 80 100 120
Slide 38: Conclusions
38 Conclusions • Sipuleucel-T is FDA approved for CRPC in patients who are minimally symptomatic/asymptomatic with non-hepatic metastases • Checkpoint inhibition therapy is effective in the MSI high subgroup, results in unselected patients are disappointing • Further treatment should be designed to
Slide 39: BXCL701 Mechanism of Action
39 BXCL701 Mechanism of Action Louis M. Weiner, M.D. Speaker is acting on behalf of and is a paid consultant to BioXcel Therapeutics, Inc. This material is intended for an investor audience only. The information contained in the following material is intended to provide background and educational in
Slide 40: Disclosures
40 Disclosures • I receive no monetary compensation from BioXcel Therapeutics* • My laboratory has a contract for work that will be discussed • Co-PI of open clinical trial of BXCL701 + pembrolizumab in metastatic pancreatic adenocarcinoma *Travel was arranged by BioXcel Therapeutics
Slide 41: BXCL701 (Talabostat): Biochemical Activities
41 BXCL701 (Talabostat): Biochemical Activities OH DPP8 DPP9 DPPIV FAP O IC50 (nM) IC50 (nM) IC50 (nM) IC50 (nM) B Val C N OH 3 3 1 30
Slide 42: Mechanism of Action of BXCL701
42 Mechanism of Action of BXCL701 BXCL701 Modulates the Tumor Microenvironment by Activating the Innate Immunity Followed by Adaptive Immunity Leading to Cancer Cell Death BXCL701 • DPP8/9 inhibition by BXCL701 DPP8/9 DPP4 activates inflammasome leading to TUMOR proinflammatory cytokines, Th1 cytoki
Slide 43: DPP Inhibition by BXCL701 Reduces Tumor Growth in Murine PDAC Model
43 DPP Inhibition by BXCL701 Reduces Tumor Growth in a Murine Pancreatic Ductal Adenocarcinoma (PDAC) Model End Treatment End Treatment Tumor Growth Curves Survival curves of mice Journal for ImmunoTherapy of Cancer 2021; 9:e002837. doi:10.1136/jitc-2021-002837
Slide 44: BXCL701 Synergizes with Anti-PD-1 in Reducing Tumor Growth
44 BXCL701 Synergizes with Anti-PD-1 in Reducing Tumor Growth in a Murine Pancreatic Ductal Adenocarcinoma (PDAC) Model Tumor growth curve mT3-2D 2000 Tumor Volume (mm3) PBS BXCL701 1500 PD1 Ab 1000 BXCL701+PD1Ab 500 0 15 20 25 30 35 40 45 Days After Tumor Inoculation Journal for ImmunoTherapy of Ca
Slide 45: BXCL701 Increases Circulating Inflammasome and Th1-Related Cytokines
45 BXCL701 Increases Circulating Inflammasome and Th1-Related Cytokines in a Syngeneic PDAC Mouse Model of Pancreatic Cancer Journal for ImmunoTherapy of Cancer 2021; 9:e002837. doi:10.1136/jitc-2021-002837
Slide 46: BXCL701 Increases Tumor Levels of CXCR3+ and Innate Immune Cells
46 BXCL701 Alone and in Combination with Anti-PD-1 Increases Tumor Levels of CXCR3+ and Innate Immune Cells in a Syngeneic Mouse Model (mT3-2D) of Pancreatic Ductal Adenocarcinoma Journal for ImmunoTherapy of Cancer 2021; 9:e002837. doi:10.1136/jitc-2021-002837
Slide 47: BXCL701 + Anti-PD-1 Engages Both NK and CD8+ T Cells
47 BXCL701 + Anti-PD-1 Engages Both NK and CD8+ T Cells in a Syngeneic Mouse Model (mT3-2D) of Pancreatic Ductal Adenocarcinoma • NK and CD8+T cells both contribute to tumor growth inhibition by PD-1 / BXCL701combination treatment • Depletion of either immune cell type or especially both types simul
Slide 48: NK Cell and T Cell Depletion Influences Treatment Outcomes
48 NK Cell and T Cell Depletion Influences Treatment Outcomes for 701 Treatment Alone Day 18 after treatment Day 28 after treatment
Slide 49: BXCL701 + Anti-PD-1 Induces Memory Response Against Rechallenge
49 BXCL701 + Anti-PD-1 Induces Memory Response Against Rechallenge • Tumor-free mice from previous experiment (BXCL701 + anti-PD-1 Ab) were re-challenged with 5-fold excess (i.e., 5 x 105) tumor cells compared with original challenge • 5 tumor-naive mice used as controls • Tumor growth was monitored
Slide 50: Effector Memory T Cells Increased in Re-Challenged Mice
50 Percentage of CD45+ Cells (Effector Memory T Cells) Were Increased in Re-Challenged Mice 60 60 47 % o f C D 4 5 + C e lls % o f C D 4 5 + C e lls 40 40 23.5 24.0 20 20 7.0 0 0 e e ic ic m m e e e ic e ic iv g m m n a e n e e ll iv g g a n h n a ri -c e n a ll e e g a R b n h ri r -c o a e m e R b
Slide 51: Well-Understood Mechanism of Action of BXCL701 and Pembrolizumab Combination
51 Well-Understood Mechanism of Action of BXCL701 and Pembrolizumab Combination Adapted from Journal for ImmunoTherapy of Cancer 2021; 9:e002837. doi:10.1136/jitc-2021-002837
Slide 52: BXCL701 Treatment Reduces Fibrosis in Tumor Micro-Environment
52 BXCL701 or BXCL701 + PD1 Antibody Treatment Reduces Fibrosis in Tumor Micro-Environment A B PBS PD-1 Ab BXCL701 Combination (A) Masson’s Trichrome stain demonstrating intense fibrosis formation in a representative mT3-2D pancreatic tumor from a PBS treated mouse, while BXCL701 or combined Rx mark
Slide 53: BXCL701: Potential Combination Opportunities in Addition to Anti-PD-1
53 BXCL701: Potential Combination Opportunities in Addition to Anti-PD-1 ®
Slide 54: BXCL701 Synergizes with Multiple T Cell Activating Therapies
54 BXCL701 Synergizes with Multiple T Cell Activating Therapies S u r v iv a l p r o p o r tio n s - M C 3 8 Tumor growth curve mT3-2D 2000 PBS Tumor Volume (mm3) 100 BXCL701 1500 P e r c e n t s u r v iv a l PD1 Ab V e h ic le BXCL701 1000 BXCL701+PD1Ab a n ti-P D -1 + B X C L 7 0 1 50 a n t i- P D
Slide 55: BXCL701 Induces Antibody Dependent Cell Cytotoxicity Effect In Vitro
55 BXCL701 Induces Antibody Dependent Cell Cytotoxicity (ADCC) Effect In Vitro PBMC+SKOV3 (E:T =15:1)+Trastuzumab PBMC+A431 (E:T =15:1)+Cetuximab 1 0 0 1 0 0 PBMC 8 0 8 0 PBMC+Ab % Lysis % Lysis 6 0 6 0 4 0 4 0 2 0 PBMC 2 0 PBMC+Ab 0 0 0 .0 0 .1 0 .2 0 .3 0 .4 0 .5 0 .6 0 .7 0 .8 0 .9 1 .0 0 .0 0 .1
Slide 56: BXCL701: Potential Predictive Biomarker
56 BXCL701: Potential Predictive Biomarker ®
Slide 57: DPP9 Copy Number Correlates with BXCL701 Cytotoxicity in Leukemic Cell Lines
DPP9 Copy Number Correlates with BXCL701 Cytotoxicity in 57 Leukemic Cell Lines and is a Potential Predictive Biomarker in Leukemias Out of total 13 cell lines 10 were AML cell lines 120% y = 0.1357x - 0.0415 R² = 0.8131 100% % Cytotoxicity 80% 60% 40% 20% 0% 0 2 4 6 8 10 Copy Number (DPP9) *** p-va
Slide 58: Results of Phase 2 Trial of BXCL701 in SCNC
58 Results of Phase 2 Trial of BXCL701 in SCNC Rahul Aggarwal, M.D. Speaker is acting on behalf of and is a paid consultant to BioXcel Therapeutics, Inc. This material is intended for an investor audience only. The information contained in the following material is intended to provide background and
Slide 59: BXCL701 with Pembrolizumab in mCRPC SCNC: Phase 2a Final Results
59 First-in-class Oral Innate Immune Activator BXCL701 Combined with Pembrolizumab in Patients with Metastatic Castration- resistant Prostate Cancer (mCRPC) of Small Cell Neuroendocrine (SCNC) Phenotype: Phase 2a Final Results Rahul R. Aggarwal1, Jingsong Zhang2, Paul Monk3, Xinhua Zhu4, Rob Jones5,
Slide 60: Background
60 Background • De novo and treatment-emergent BXCL701 SCNC are associated with adverse survival outcomes DPP8/9 DPP4 TUMOR • BXCL701 modulates tumor microenvironment by activating innate immunity followed by adaptive CXCL9/10 immunity leading to cancer cell death • Phase 1b safety lead-in tested 2
Slide 61: High Unmet Need in SCNC with no FDA Approved Therapy
61 High Unmet Need in SCNC with no FDA Approved Therapy and Incidence is Increasing 288,300 Men Diagnosed with Prostate Cancer in U.S. in 2023*; ~20% Expected to Progress to More Aggressive mCRPC • ~20% of these mCRPC patients will develop SCNC phenotype, characterized by poor prognosis and low surv
Slide 62: Methods
62 Methods KEY INCLUSION CRITERIA KEY EXCLUSION CRITERIA • Histologically confirmed de novo SCNC or treatment- • >2 cytotoxic chemotherapy regimens for mCRPC emergent SCNC • Prior treatment with anti-PD-1, anti-PD-L1, • ≥1 prior line of systemic therapy anti-programmed death-ligand 2 (PD-L2) agent o
Slide 63: Baseline Characteristics
63 Baseline Characteristics Phase 2a Cohort (n = 34) n (%) Median Age, years (range) 67.5 (54 – 80) 0 16 (47%) ECOG Performance Status (%) 1 16 (47%) 2 2 (6%) Any site 21 (62%) Visceral Metastases (%) Liver 11 (32%) Median number of lines of prior 3 (1 – 8) systemic therapy (range) Androgen signalin
Slide 64: Treatment Duration
64 Treatment Duration • Median duration of Patient Identification Number follow up = 30.8 weeks (range 1.9 – 86.9 weeks) • Median duration of treatment = 9 weeks (range: 0.7 to 73 weeks) 28 Evaluable Patients - Data as of 19-DEC-22
Slide 65: Best Overall Response
65 Best Overall Response n (%) RECIST Evaluablea (%) 25 (89) Objective Response Rate (%) 5 (20) Confirmed Partial Response (%) 4 (16) Unconfirmed Partial Response (%) 1 (4) Objective response rate: 20% SD (any duration) 7 (28) • 4 confirmed partial responses + PD 13 (52) 1 unconfirmed partial respon
Slide 66: Change in Tumor Size from Baseline
66 Change in Tumor Size from Baseline RECIST 1.1 Best Response n = 25 60 % Change in Target Lesion SoD* from Baseline 40 Confirmed Response 20 0 • All responders are -20 MSS and/or TMB low -40 Prior Platinum Chemotherapy -60 -80 120-946 106-976 101-982 101-962 108-966 102-901 106-964 108-978 106-972
Slide 67: Safety
67 Safety Treatment-Emergent n (%) Adverse Events (n = 34) Any Grade 33 (97) Attributed to BXCL701 29 (85) Attributed to Pembrolizumab 23 (68) Grade 3 16 (47) Attributed to BXCL701 6 (18) Attributed to Pembrolizumab 6 (18) Grade 4 0 Grade 5 1* (3) AE Leading to Treatment Discontinuation 6 (18) BXCL7
Slide 68: Response in a Patient with Treatment-Emergent SCNC with Liver Metastases
68 Response in a Patient with Treatment-Emergent SCNC with Liver Metastases Cytokine expression in the circulation • Prior systemic therapies: LHRH agonist, abiraterone 4000 Cytokine concentration + prednisone, cisplatin + etoposide 3000 • Microsatellite stable, low TMB 2000 • 58% reduction in targe
Slide 69: Results from Adenocarcinoma Cohort
69 Results from Adenocarcinoma Cohort BXCL701 + Pembrolizumab 2022 Best Tumor Response (n = 18) 100 80 60 Composite response rate: 21% % change from baseline 40 • RECIST-defined PR*: 22% 20 0 • Disease control rate: 83% -20 • PSA50: 17%—including 5 -40 patients with -100% to -57% -60 PSA decrease -8
Slide 70: Conclusions
70 Conclusions • BXCL701 + pembrolizumab demonstrated encouraging activity with durable responses observed in a subset of patients with platinum pre-treated, small cell neuroendocrine prostate cancer – All responders were MSS and/or TMB low, with low probability of response to pembrolizumab monother
Slide 71: Acknowledgements
71 Acknowledgements • Patients and their families • Co-Investigators and study staff • BioXcel Therapeutics
Slide 72: BXCL701 Current Trials and Future Direction
72 BXCL701 Current Trials and Future Direction Vincent J. O’Neill, M.D. ®
Slide 73: BXCL701: Pipeline Within a Product Plan and Next-Generation Candidate
73 BXCL701: Pipeline Within a Product Plan and Next-Generation Candidate Expected Compound Proposed Indication Preclinical Phase 1 Phase 2 Upcoming Collaborator Milestone Small Cell Neuroendocrine Initiate Prostate Cancer (SCNC) Phase 2b Small Cell Lung Cancer Initiate (SCLC) Phase 1b/2 BXCL701 Acut
Slide 74: Frequency of DPP Alterations in Solid Tumors
74 Frequency of DPP Alterations in Solid Tumors Pancreatic SCNC SCLC TCGA Data; AACR 2017
Slide 75: SCNC Phase 2a Results Support Further Development of BXCL701 + KEYTRUDA
75 SCNC Phase 2a Results Support Further Development of BXCL701 + KEYTRUDA Phase 2b Potential Registrational Trial in SCNC Expected to Initiate in 2H 2023* Primary endpoint*: Objective Response by RECIST 1.1 criteria Pembrolizumab 200 mg IV Day 1 q3week + BXCL701 0.3 mg PO BID Days 1-14 2:1 N = 40 P
Slide 76: SCNC Clinical Development Timeline
76 SCNC Clinical Development Timeline* 2023 2024 2025 1H 2H 1H 2H 1H 2H NDA SCNC Phase 2b pivotal study Submission Under AA Program *Initial discussions with the FDA regarding the development pathway and registrational strategy for BCXL701 in SCNC expected in mid-2023. | AA = Accelerated Approval
Slide 77: BXCL701: Extensive Stage Small Cell Lung Cancer (SCLC)
77 BXCL701: Extensive Stage Small Cell Lung Cancer (SCLC) Current Therapy Remains Sub-optimal • SCLC is an aggressive disease with early metastasis U.S. Patients 2023 • 2 CPIs approved in combination with carboplatin / etoposide for New SCLC patients Extensive Stage SCLC 36K1 – TECENTRIQ® (atezolizu
Slide 78: Planned Phase 1b/2 SCLC Clinical Trial Design
78 Planned Phase 1b/2 SCLC Clinical Trial Design* Determine Recommended Phase 2 Dose (RP2D) Atezolizumab IV 1,200 mg Day 1 q3week + ES-SCLC Patients in BXCL701 0.2 mg BID 14 days Screening Cohort 1 Maintenance n=3+3 Atezolizumab IV 1,200 mg Day 1 q3week + Cohort 2 BXCL701 0.3 mg BID 14 days n=3+3 Pr
Slide 79: SCLC Clinical Development Timeline
79 SCLC Clinical Development Timeline 2023 2024 2025 1H 2H 1H 2H 1H 2H End of Phase Phase 1b SCLC PoC 2 meeting
Slide 80: BXCL701: Acute Myeloid Leukemia (AML)
80 BXCL701: Acute Myeloid Leukemia (AML) Significant Underserved Patient Population • BXCL701 is directly cytotoxic in AML cell lines1 U.S. Patients 2023 • Conventional chemotherapy is a mainstay in AML therapy, response rates 35-75% New AML Patients • Standard of care for patients unfit for inducti
Slide 81: Initiating Phase 1b/2 AML Clinical Trial
81 Initiating Phase 1b/2 AML Clinical Trial 81 3 + 3 Dose Escalation Study Design n = 12 - 30 Level (-1) BXCL701 0.2 mg BID Pulse Dosing Starting Screening Level 1 BXCL701 0.3 mg BID Pulse Dosing Dose Primary objective Level 2 BXCL701 0.4 mg BID Pulse Dosing Determine MTD and establish recommended P
Slide 82: BXCL701: Pancreatic Cancer
82 BXCL701: Pancreatic Cancer Significant Underserved Patient Population • Pancreatic cancer has among the highest levels of overexpression U.S. Patients 2023 and amplification of DPPs • Preclinical models demonstrate synergy between DPP inhibition New Pancreatic Cancer Patients with BXCL701 and ant
Slide 83: Initiating Phase 2 Pancreatic Clinical Trial
83 Initiating Phase 2 Pancreatic Clinical Trial Safety Lead-In n = 6 Screening + pre-treatment core tumor Pembrolizumab 200 mg IV q3w Day 1 + biopsy BXCL701 0.3 mg PO BID Days 1-14 of 21-day cycle Simon’s 2-stage, single-arm, open label n = 19-43 Primary objective Determine 18-week progression-free
Slide 84: BXCL701 Potential Pipeline Within a Product in Cold Tumors
84 BXCL701 Potential Pipeline Within a Product in Cold Tumors SCNC SCLC Pancreatic* Breast GBM BXCL701 Sensitizing cold tumors to CPI Colorectal Sarcoma* * Ovarian
Slide 85: Conclusions
85 Conclusions • BXCL701 is an oral innate immune activator with a novel mechanism of action, described in peer- reviewed publication • BXCL701 has demonstrated clinical POC, in combination with KEYTRUDA, in two cold tumor settings – Adenocarcinoma – SCNC • Initial discussions with the FDA regarding
Slide 86: Panel Discussion
Panel Discussion ® BioXcel Therapeutics | 555 Long Wharf Drive, 12th Floor | New Haven, CT 06511 | www.bioxceltherapeutics.com