Bioatla, Inc. · NASDAQ:BCAB
Bioatla — Investor Presentation (December 2024)
49 slides from Bioatla's investor presentation, Dec 20, 2024
Slide 1: Conditionally Active Biologics: Transforming Cancer Therapy
Exhibit 99.1 Conditionally Active Biologics: Transforming Cancer Therapy Investor Presentation Non-Confidential December 2024
Slide 2: Important Notices & Disclaimers
Important Notices & Disclaimers This presentation (the “Presentation”) by BioAtla, Inc. (“we”, “us”, “our”, “BioAtla”, or the “Company”) contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations and financial
Slide 3: BioAtla Overview
BioAtla Overview Clinical stage company harnessing the tumor microenvironment for targeted cancer therapy • Advancing a platform of targeted “Conditionally Active Biologics (CAB)” monoclonal antibodies that bind epitopes exposed in the acidic pH microenvironment of tumor cells, but are otherwise shi
Slide 4: Leadership Team
Leadership Team Eric Sievers, M.D. Richard Waldron, M.B.A. Jay Short, Ph.D. Sheri Lydick Chief Medical Officer Chief Financial Officer Chairman, CEO and Cofounder Chief Commercial Officer GeneMedicine, Inc. William Boyle, Ph.D. Monica Sullivan Susie Melody Sr. Research Fellow Sr. VP, Intellectual Pr
Slide 5: Board of Directors and Scientific Advisors
Board of Directors and Scientific Advisors Jay Short, Ph.D. Lawrence Steinman, MD Mary Ann Gray, Ph.D. Sylvia McBrinn Chairman, Chief Executive Officer & Cofounder Lead Director Director Director Director Susan Moran, MD, MSCE Scott Smith Eddie Williams Director Director Director James Allison, Ph.D
Slide 6: CAB Technology Summary
CAB Technology Summary ➢ All cancer cells are acidic (pH5.3-pH6.7) • The most acidic regions are oxygenated, not anaerobic • Acidity is a result of the need for precursor molecules from glycolysis for continuous cell replication • Cancer cells use acidity promote metastasis and defend against immune
Slide 7: Pre-clinical Evidence Summary
Pre-clinical Evidence Summary ➢ Preclinical evidence of CAB selectivity • Differential EGFR tumor vs. skin binding (12.6-fold improved TI) • AXL-ADC reduced TMDD yielding ⁻ T and exposure in NHP (>2-fold increase in T ) 1/2 1/2 ⁻ Reduced liver enzymes (>10-fold in ALT levels) • CTLA4 reduction of pe
Slide 8: Clinical Evidence Summary
Clinical Evidence Summary ➢ Clinical evidence of CAB selectivity • AXL-ADC good risk/benefit ratio ⁻ Two non-CAB AXL-targeting ADCs terminated in P1 ⁻ Potent and durable response in mKRAS NSCLC patients • ROR2-ADC good risk/benefit ratio ⁻ Good tolerability with only 7% treatment-related discontinua
Slide 9: Selective and Targeted CAB Technology Widens Therapeutic Window
Selective and Targeted CAB Technology Widens Therapeutic Window Thus has the potential to enhance clinical outcomes in multiple tumor types Acidic Cancer Cell Membrane Alkaline Healthy Cell Membrane BioAtla discovered that acidic pH at the cancer cell surface unveils binding sites that are shielded
Slide 10: CAB Antibodies Bind Selectively and Reversibly Based on the TME
CAB Antibodies Bind Selectively and Reversibly Based on the Tumor Microenvironment (TME) Enhancing exposure and reducing toxicity CABs Bind Selectively in the Lower pH TME Non-CABs Bind to Normal Tissues, Causing Toxicity Non-CAB Normal Cells Focused Selective Tumor CABs Preserved Binding Tumor Kill
Slide 11: CAB ADCs Show Strong Selectivity and Improved Therapeutic Window
CAB ADCs Show Strong Selectivity and Have an Improved Therapeutic Window vs Traditional ADCs Unlike prodrugs, CABs are reversible and selective enhancing the therapeutic index 10000 Enhanced ADC Therapeutic Exposure Enhanced ADC Tumor Selectivity (12.6-fold increase in TI) 1000 AXL ADCs- 1mg/kg dose
Slide 12: Broad Applicability of BioAtla's CAB Platform Across Antibody Types
Broad Applicability of BioAtla’s CAB Platform Across Several Antibody Types ADCs I/O Antibodies Bispecific TCE Targets: ROR2, AXL Target: CTLA-4 Target: EpCAM & CD3 Widely expressed in a variety of tumor CTLA-4 blockade activates effector Bispecific antibodies bridge cancer types, ROR2 and AXL overe
Slide 13: Focused Pipeline with Broad Applicability of Differentiated CAB Assets
Focused Pipeline with Broad Applicability of Differentiated CAB Assets Designed to Deliver Near-term value IND Enabling Phase 1 Phase 2 CAB Program Target Indications Pre-Clinical Clinical Clinical Mecbotamab Vedotin NSCLC AXL BA3011 UPS CAB-ADCs Ozuriftamab Vedotin ROR2 SCCHN BA3021 Evalstotug Mela
Slide 14: BioAtla's Near-Term Catalysts
BioAtla’s Near-Term Catalysts 2025 2026 Readout BA3011 (AXL-ADC) – Phase 2 (n=50) mKRAS NSCLC Readout Readout BA3182 (EpCAM-TCE) – Phase 1 Dose Phase 2 Extension (n=40) Escalation (n=30) Adenocarcinomas BCAB OPEX (including G&A, IP, etc.) Operations BioAtla | Overview 14
Slide 15: Near-Term Catalysts with Potential Partnering Opportunities
BioAtla’s Near-Term Catalysts with Potential Partnering Opportunities 2025 2026 BA3021 (ROR2-ADC) – Phase 2 Extension (n=40) Phase 3 SCCHN BA3071 (CTLA4-IO) – Phase 2 (n=60) Phase 3 Melanoma Submission BA3362 (Nectin4-TCE) – Pre-clinical and IND-enabling Studies Solid Tumors Out-Licensed to Context
Slide 16: Mecbotamab Vedotin (CAB-AXL-ADC): mKRAS NSCLC
Mecbotamab Vedotin (CAB-AXL-ADC): mKRAS Non-Small Cell Lung Cancer (NSCLC)
Slide 17: Mecbotamab Vedotin: CAB-AXL-ADC
Mecbotamab Vedotin: CAB-AXL-ADC AXL is expressed in a variety of tumor types, with overexpression associated with metastasis, tumor resistance to chemotherapy, and poor prognosis BA3011 pH binding inflection point adjusted for tumor CAB-tumor cell target microenvironment selectivity 100 Non-CAB AM C
Slide 18: Co-expression of Mutant KRAS and AXL is Significant and Functionally Linked
Co-expression of mutant KRAS and AXL is Significant and Functionally Linked • In lung cancer cells, AXL over-expression is involved in resistance to chemotherapy and targeted therapies and drives epithelial to mesenchymal transition • Prevalence of AXL expression in KRAS mutant NSCLC is significant,
Slide 19: AXL Plays a Crucial Role in Survival of KRAS G12C NSCLC Cells
AXL Plays a Crucial Role in the Survival of KRAS G12C mutant NSCLC Cells Treated with KRAS G12C Inhibitors AXL driving resistance to KRAS inhibitors • KRAS inhibition leads to upregulation and activation of AXL expression o Autocrine/paracrine of increased GAS6 expression • AXL inhibition alone does
Slide 20: Docetaxel has modest efficacy in 2L+ NSCLC
Docetaxel (expected control arm) has modest efficacy in 2L+ NSCLC Codebreak and Krystal has G12C docetaxel 2L+ data • 234,580 new cases of NSCLC expected in US for 2024 No pan-KRAS docetaxel 2L+ data Timing relative to Study with • 30% or 70,374 new cases of NSCLC with RAS Median Median Immune Docet
Slide 21: Emerging Opportunity for Mecbotamab Vedotin in mKRAS Variants
Emerging Opportunity for Mecbotamab Vedotin in Patients with Mutated KRAS (mKRAS) Variants mKRAS constitutes 30% of all NSCLC patients mutant KRAS; all NSCLC (SQ+NSQ); median of approximately 3 prior lines of tx for both mKRAS and wtKRAS Total (N=78) Age, y, mean (range) 67 (46-82) KRAS Status, n (%
Slide 22: Confirmed Responses with Mecbotamab Vedotin Across mKRAS Variants
Confirmed Responses with Mecobotamab Vedotin Across mKRAS Variants - ongoing N=21 of 24**; 1.8 mg/kg Q2W, 2Q3W, and Q2W+nivo Best % Change in TL Median of mKRAS 3 prior lines of tx N=21 BOR all 5 (24%) G12R G12R G12S G12A Q61H G12C G12D G12S G12V G12C^ G12A G12V G12C Q61H G12D BOR confirmed 4 (19%)
Slide 23: Improved Overall Survival in mKRAS NSCLC Patients
Improved Overall Survival with Mecbotamab Vedotin among NSCLC Patients with Tumors Expressing mutant KRAS Variants Compared to KRAS Wildtype Median of 3 prior lines of tx Events n (%) Median (95% CI) mKRAS 9 (37.5) NR (6.5 - NE)* wtKRAS 29 (58.0) 8.7 (5.8-10.2) *Ongoing, >50% survival @ 1yr. BioAtla
Slide 24: Overall Survival Comparison vs Competition
Overall Survival comparison between mecbotamab vedotin vs competition mKRAS median of 3 prior lines of tx Median (95% CI) mecbotamab vedotin NR (6.5 – NE) mecbotamab RMC- Treme/Durv Sotorasib vedotin 6236 a/Chemo RMC-6236 17.7 (13.7 – NE) RMC-6236 Population mKRAS RAS G12X mKRAS G12C Number of mecbo
Slide 25: Ph2 Mecbotamab Vedotin: Overall Safety Summary
Ph2 Mecbotamab Vedotin: Overall Safety Summary of NSCLC patients Generally well-tolerated 1.8 mg/kg 1.8 mg/kg 1.8 mg/kg Total Q2W 2Q3W Q2W + Nivo (N=78) (N=26) (N=33) (N=19) Any Adverse Events (AEs) 26 (100) 33 (100) 19 (100) 78 (100) 1 2 Related AEs with CTCAE Grade 3 or 4 10 (39) 12 (36) 4 (21) 28
Slide 26: Mecbotamab Vedotin: Phase 2 Safety Data of NSCLC Patients
Mecbotamab Vedotin: Phase 2 Safety Data of NSCLC patients Most frequent treatment-emergent adverse events irrespective of causality (≥15%) BA3011 Q2W + Nivo BA3011 Q2W BA3011 2Q3W TOTAL (N=78) (N=26) (N=33) (N=19) Preferred Term All Grades Grade 3-4 All Grades Grade 3-4 All Grades Grade 3-4 All Grad
Slide 27: Mecbotamab Vedotin NSCLC Summary
Mecbotamab Vedotin NSCLC Summary Median of 3 prior lines of tx • Promising anti-tumor activity among patients whose tumors express KRAS mutations o mKRAS represents 30% of all NSCLC patients and is associated with increased AXL expression o Improved overall survival observed among treated patients w
Slide 28: BA3182 (EpCAM x CD3 Bispecific T-Cell Engager): Adenocarcinoma
BA3182 (EpCAM x CD3 Bispecific T-Cell Engager): Adenocarcinoma
Slide 29: CAB-EpCAM x CAB-CD3 Bispecific T-Cell Engager (BA3182)
CAB-EpCAM x CAB-CD3 Bispecific T-Cell Engager (BA3182) Significant opportunity for safe and effective EpCAM x CD3 bispecific • EpCAM is an attractive therapeutic target because it’s expressed in most solid tumors, as well as in normal epithelial tissues, well suited for CAB technology 1 • BA3182 exh
Slide 30: EpCAM is Widely Expressed Across Solid Tumors
EpCAM is Widely Expressed Across Solid Tumors 4 most common new cases of cancers from American Cancer Society and EpCAM Expression ACS estimate for 2024 EpCAM Expression in US (TIS 1 to 12) Breast Cancer 310,720 81% Prostate Cancer 299,010 99% Lung Cancer 234,580 93% NSCLC/ 80% SCLC Colon Cancer 106
Slide 31: Overview of the Structure and Activity of BA3182
Overview of the Structure and Activity of BA3182 Dual CAB EpCAM x CAB CD3 Bispecific antibody • BA3182 humanized anti-EpCAM IgG1 antibody with a humanized anti-CD3ε scFv fused to the C-terminus of the IgG1 kappa light chain constant domain. • H1-L1 expression configuration • CHO product MW = 198,981
Slide 32: MonoCAB and BA3182 DualCAB Inhibit Tumor Growth in vivo
MonoCAB and BA3182 DualCAB Inhibit Tumor Growth in vivo BA3182 BA3182 BioAtla | Overview 32 Source: MABS 2024, VOL. 16, NO. 1, 2322562 https://doi.org/10.1080/19420862.2024.2322562
Slide 33: BA3182 DualCAB Reduces Immunotoxicity in Cynomolgus Monkey
BA3182 DualCAB Shows Significant Reduction of Immunotoxicity and Highly Increased Tolerability in Cynomolgus Monkey * BA3182 BA3182 BA3182 BA3182 BioAtla | Overview 33 Source: MABS 2024, VOL. 16, NO. 1, 2322562 https://doi.org/10.1080/19420862.2024.2322562
Slide 34: Amgen Discontinued Development of Solitomab Due to DLTs
Amgen Discontinued Development Of Solitomab Due to DLTs Which Precluded Dose Escalation to Potentially Therapeutic Levels Solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting EpCAM • Sixty-five patients received solitomab at doses between 1 and 96 µg/day for ≥28 days • Overall
Slide 35: BA3182 Phase 1 Study Design
BA3182 - Phase 1 Study Design BioAtla | Overview 35 Abbreviations: AE, adverse event; CRS, cytokine release syndrome; DL, dose level; DLT, dose-limiting toxicity; MABEL, minimum anticipated biological effect level.
Slide 36: EpCAM Expression in Adenocarcinoma
EpCAM Expression in Adenocarcinoma Validated commercial antibody for EpCAM EpCAM expression was assessed in 2,291 primary tumor tissues and in 108 metastases using the EpCAM-specific antibody. J Clin Pathol 2011;64:415e420. doi:10.1136/jcp.2011.090274 BioAtla | Overview 36
Slide 37: Frequent High-Level Expression of EpCAM in Colon, Stomach, Prostate and Lung Cancers
Frequent High-Level Expression of the Immunotherapeutic Target EpCAM in Colon, Stomach, Prostate and Lung Cancers BioAtla | Overview 37
Slide 38: In vitro Characterization of BF-588-WT, MonoCAB and BA3182-DualCAB
In vitro Characterization of BF-588-WT, BF-588-MonoCAB and BA3182-DualCAB BA3182 BA3182 BA3182 BA3182 BioAtla | Overview 38 Source: MABS 2024, VOL. 16, NO. 1, 2322562 https://doi.org/10.1080/19420862.2024.2322562
Slide 39: BA3182 Has >80-fold Higher Therapeutic Index Compared to non-CAB Bispecific
BA3182 Bispecific TCE Antibody has >80-fold Higher Therapeutic Index Compared to non-CAB Bispecific Maximum Tolerated Dose • Minimal effective dose (MED) determined in the mouse-based animal models • MTD/Highest Non-severely Toxic Dose (HNSTD) determined in non-human primate (NHP)* 2 TI = HNSTD (mg/
Slide 40: BA3142 (B7H3 x CD3 Bispecific T-Cell Engager): Pre-clinical
BA3142 (B7H3 x CD3 Bispecific T-Cell Engager): Pre-clinical
Slide 41: B7H3 Background
B7H3 Background Large commercial potential High expression across many different solid tumors B7-H3 Expression in Prostate • B7H3 is a member of B7 family of immunoregulatory transmembrane glycoproteins expressed by T cells. • B7H3 is overexpressed on many solid cancers and displays relatively high
Slide 42: B7H3 is Exceptional for CAB Targeting
B7H3 is exceptional for CAB targeting Enhances the Warburg effect in tumors • B7H3 expression increases tumor cell aerobic glycolysis and acidic pH in TME • Regulates the expression of HIFa leading to elevated LDH and PDK1 MDA-MB-468 B7-H3 overexpressing breast cancer cells (468 B&-H3) or transduced
Slide 43: BA3142 in vivo Efficacy
BA3142 in vivo Efficacy BA3142 dosed at 2mg/kg led to significant tumor regression in Detroit 562 and A375 humanized mouse model of human pharyngeal and melanoma cancers, respectively. The in vivo anti-tumor activity of BA3142 was comparable to the Non-CAB B7H3/CD3 TCE. In vivo efficacy studies. Tri
Slide 44: Competition Limited for Differentiated TCE as a Result of Clinical Failures
Competition Limited for Differentiated TCE as a Result of Clinical Failures ▪ Terminated programs- ▪ Macrogenics terminated MGD009 (B7H3 x CD3) in Phase 1 a partial clinical hold due to hepatic safety concerns. Program discontinued in 2019. ▪ Daiichi-Sankyo discontinued the development of its fucosy
Slide 45: BA3142 NHP Tox and PK Study
BA3142 – NHP Tox and PK study • BA3142 was well-tolerated in non-human primates at 25 mg/kg; MTD not reached • Sporadic elevations of IL-6 cytokine was observed without a clear relationship with BA3142 dosing. • Systemic exposure was dose-proportional with no significant gender differences in TK par
Slide 46: BA3142 CAB B7H3 TCE Summary
BA3142 – CAB B7H3 TCE Summary • B7H3 tumor expression correlated with exceptionally high glycolytic activity and acidity, making this target well suited for CAB technology • Potent B7H3 x CD3 bispecific TCE with good safety profile and wide therapeutic margin o Exceptional HNSTD 25 mg/kg in NHPs; MT
Slide 47: BA3142 CAB B7H3 TCE Path to IND
BA3142 – CAB B7H3 TCE Path to IND - Potential IND submission 2Q 2025 • cGMP manufacturing completed • Material for clinical trials available • Tox lot in vitro characterization (in progress) o pH Affinity ELISA o Specificity ELISA o Promega T cell activation Assay o pH Range ELISA o pH SPR analysis
Slide 48: BioAtla Is a Clinical Stage Company Focused on Transforming Cancer Therapy
© BioAtla Is A Clinical Stage Company Focused on Transforming Cancer Therapy with Conditionally Active Biologics (CABs) Proprietary technology with Clinical stage assets: Clinical readouts for Completed out-licensing P2 CAB-ROR2-ADC over 500 issued patents multiple indications / transaction with Con
Slide 49: Appendix
Appendix