Bioatla, Inc. · NASDAQ:BCAB
Bioatla — Technical Presentation (October 2024)
14 slides from Bioatla's technical presentation, Oct 11, 2024
Slide 1: Evalstotug (BA3071): a potent conditionally active biologic anti–CTLA-4 antibody
Evalstotug (BA3071): a potent conditionally active biologic (CAB) anti– CTLA-4 antibody designed to enable high exposures, extended dosing, and reduced immune-mediated toxicity William J. Boyle, PhD October 11, 2024 Abbreviation: CTLA-4, cytotoxic T-lymphocyte associated protein 4.
Slide 2: Disclosures
Disclosures ● William J. Boyle is an employee of BioAtla, Inc. Confidential 2
Slide 3: CAB technology widens the therapeutic index
CAB technology widens the therapeutic index ● Minimally altered in CDRs to permit binding only within the acidic TME1 ● CABs are not masked or caged by a blocking peptide and do not require enzymatic cleavage for activation ● Designed to reduce immune-related AEs, enhance antitumor immunity, avoid t
Slide 4: Evalstotug (CAB CTLA-4) selectively active in the acidic TME to reduce irAEs
Evalstotug (CAB CTLA-4) Selectively active in the acidic TME1 to reduce irAEs Non-CAB CTLA-4 Normal cell (alkaline) CAB CTLA-4 inhibitors (tumor selective binding) anti–CTLA-4 anti–CTLA-4 CAB CTLA-4 CAB CTLA-4 Tumor (acidic) • CTLA-4 blocked from B7.1 and B7.2 binding • Increased CD8+ T cells Minimi
Slide 5: Evalstotug is a CAB-derivative of ipilimumab
Evalstotug is a CAB-derivative of ipilimumab Preserved efficacy with reduced toxicity in combination with PD-1 ● Ipilimumab (ipi) CDR’s modified to bind at tumor cell acidic pH, but not at normal pH leading to evalstotug: Tumor Normal Tumor Normal ⎼ Preserved affinity and epitope ⎼ Equivalent EMax a
Slide 6: Reversible binding in the TME
Reversible binding in the TME Comparison of evalstotug binding to CTLA-4 in different pH conditions Abbreviations: CTLA-4, cytotoxic T-lymphocyte associated protein 4; ICI, immune checkpoint inhibitor; IgG, immunoglobulin G; OD450, optical density at 450 nm; TME, tumor microenvironment. Note: Figure
Slide 7: Tumor regression with dose response
Tumor regression with dose response Preclinical model with human CTLA-4 knock-in micea IgG control 10mg/kgb BIW Evalstotug 10mg/kg BIW Abbreviations: BIW, twice a week; CTLA-4, cytotoxic T-lymphocyte associated protein 4; IgG, immunoglobulin G. Note: Figures modified from Chang HW, et al. Proc Natl
Slide 8: Modulated T cells in the TME and periphery
Evalstotug modulated T cells in the TME and periphery Potential mechanism for reduced immune-related toxicities Tumor infiltrating lymphocytes Normal tissue lymphocytes % CD4eff of CD4 T cells Peripheral blood % CD8 of T cells MC38 syngeneic tumor xenograft models in hCTLA4 knock- in mice at % CD4ef
Slide 9: Reduced GI toxicity in primates
Evalstotug reduced GI toxicity in primates Vehicle Control GI Symptoms Ipilimumaba + nivolumab Liquid feces 15 mg/kg + 20 mg/kg Non-formed feces Other GI symptoms Evalstotuga + nivolumab 15 mg/kg + 20 mg/kg 20 15 KI67+ CD4+ T cells Ratio to Baseline Vehicle 10 Ipilimumab + nivolumab 5 Evalstotug + n
Slide 10: Ph1 dose escalation of evalstotug; 70 mg to 1000 mg cleared
Ph1 dose escalation of evalstotug; 70 mg to 1000 mg cleared Most related AEs were low grade; no grade 4/5 related AEs were observed Most frequent AEs of any grade (≥15% of patients) All AEs Related AEs Fatigue 9 2 7 3 3 Chills 8 8 8 8 Vomiting Only 2 patients with 7 7 3 3 grade 3 related immune- Dia
Slide 11: Intra-patient dose escalation of anti-CTLA-4 leads to increased response in melanoma patients
Intra-patient dose escalation of anti-CTLA-4 leads to increased response in melanoma patients CAB-CTLA-4 (evalstotug) enables higher dosing to (~5 mg/kg); not possible with ipi • 2 patients with cutaneous melanoma As of October 4, 2024: • Ongoing, approaching 2 years • Phase 1 dose escalation study
Slide 12: Confirmed PR associated with increased dosing
Confirmed PR associated with increased dosing 75-year-old female with stage IV cutaneous melanoma (BRAF+) 70 mg evalstotug 210 mg (SD) 350 mg (PR) November 2022 August 2023 March 2024 Baseline Tumor assessment – SD Tumor assessment – PR First dosed at 70 mg evalstotug Therapy well-tolerated. Became
Slide 13: Conclusions
Conclusions ● Preclinical & clinical data demonstrate that ipi & evalstotug are similar, i.e. epitope, affinity, T1/2 and tumor exposure, and efficacy ● Preclinical & clinical data demonstrate that ipi & evalstotug are NOT similar with respect to normal tissue environment and safety; e.g., reduced i
Slide 14: Questions?
Brita Questions?