Agenus Inc. · NASDAQ:AGEN
Agenus — Technical Presentation (November 2022)
18 slides from Agenus's technical presentation, Nov 15, 2022
Slide 1: Phase 1A/1B Study of Botensilimab Plus Balstilimab in Sarcoma
A PHASE IA/IB STUDY OF BOTENSILIMAB, A NOVEL INNATE/ADAPTIVE IMMUNE ACTIVATOR, PLUS BALSTILIMAB FOR THE TREATMENT OF PATIENTS WITH SARCOMA Breelyn A. Wilky, MD University of Colorado Cancer Center Director of Sarcoma Medical Oncology Deputy Associate Director for Clinical Research Aurora, Colorado,
Slide 2: Disclosures
DISCLOSURES Consultant/Advisory Role: Adaptimmune, Adcendo, Daiichi Sankyo, Deciphera, Epizyme, Polaris, Springworks Institutional Coordinating PI: Agenus
Slide 3: Recent I-O Trials in Sarcoma
RECENT I-O TRIALS IN SARCOMA Summary of Responses in All-comer Soft-Tissue Sarcoma Patients Study Agents Study N Median Prior ORR Range Median OS Range Treatments Range (All-Comers) Range PD-(L)1 as Monotherapy1-3 40-79 2 16-37% 11.3-13.0 months PD-1 + CTLA-44-7 16-48 2-3 12-16% 13.1-NR months Chemo
Slide 4: Standard ICIs Ineffective for Majority of Sarcoma Patients
STANDARD ICIS INEFFECTIVE FOR MAJORITY OF SARCOMA PATIENTS 20% of common adult type sarcomas have high expression of immune related genes, correlating with to response to checkpoint inhibitor monotherapy 1. Petitprez F, et al. Nature. 2020;577:556-560. 2. Progression-free survival graph based on the
Slide 5: Novel Immunotherapy Agents
NOVEL IMMUNOTHERAPY AGENTS botensilimab balstilimab Fc-enhanced CTLA-4 Inhibitor PD-1 Inhibitor Active in cold and I-O refractory tumors1: Safety and efficacy analogous to approved anti-PD-1 mAbs4,5 • ↑ T cell priming, expansion, memory2,3 • >750 patients treated; 10 ongoing trials / 2 completed • ↑
Slide 6: C-800-01 Study
C-800-01 STUDY NCT03860272: First-in-human trial of botensilimab (bot) ± balstilimab (bal) in patients with advanced cancer1,2 POPULATION DESIGN Key Eligibility bot* Monotherapy every 3 weeks • Refractory to standard treatment [Fc-enhanced CTLA-4] • Prior I-O therapy allowed 0.1, 0.3, 1, 2, 3 mg/kg
Slide 7: Botensilimab/Balstilimab Efficacy in Cold and I-O Resistant Tumors (N=125)
BOTENSILIMAB/BALSTILIMAB EFFICACY IN COLD AND I-O RESISTANT TUMORS (N=125)* 130 Best Percent Change From Baseline (%) 120 110 100 ORR DCR 90 80 20% 66% 70 95% CI, 13-28% 95% CI, 57-74% 60 50 40 30 20 20% Tumor 10 Growth 0 -10 -20 -30 30% Tumor -40 Reduction -50 -60 -70 -80 -90 -1000 -1100 0 6 12 18
Slide 8: Clinical Responses in Select Expansion Cohorts
CLINICAL RESPONSES IN SELECT EXPANSION COHORTS Select Expansion Cohorts* MSS CRC Ovarian Anti-PD-(L)1 R/R NSCLC (n=59) (n=19) (n=5) ORR, % 22% (95% CI, 12-35%)* 26% (95% CI, 9-51%)* 60%† BOR, n (%) CR 1 (2) 1 (5) 0 (0) PR 12 (20) 4 (21) 3 (60)‡ SD 30 (51) 7 (37) 1 (20) PD 16 (27) 7 (37) 1 (20) DCR (
Slide 9: C-800-01 Sarcoma Analysis Population
C-800-01 SARCOMA ANALYSIS POPULATION NCT03860272: First-in-human trial of bot ± bal in patients with advanced cancer1,2 POPULATION DESIGN Evaluable Combination Patients* bot† Combination therapy + bal† 13 treated with 1 or 2 mg/kg bot + bal as of [Fc-enhanced [PD-1] 16 June 2022 with ≥1 Q6W imaging
Slide 10: Patient Characteristics (N=13)
PATIENT CHARACTERISTICS (N=13) Characteristic Overall (N=13) Age, median (range) 54 (41-80) Sex, n (%) Male 7 (54) Female 6 (46) ECOG PS at baseline, n (%) 0 9 (69) 1 4 (31) Prior lines of therapy, n (%) Median (range) 3 (0-4) 2 1 (8) 3 4 (31) 4 4 (31) Prior I-O, n (%)* 4 (31) Microsatellite stable
Slide 11: Efficacy (N=13)
EFFICACY (N=13) Characteristic Overall (N=13) ORR, % 46% (95% CI, 19-75%) BOR, n (%) CR* 1 (8) PR 5 (38) SD 3 (23) PD 4 (31) DCR (CR + PR + SD), % 69% (95% CI, 39-91%) Median DOR, months NR (95% CI, 1.9-NR) Median OS, months NR (95% CI, 3.2-NR) 12-months OS, months 77% (95% CI, 35-94%) Median F/U, m
Slide 12: Botensilimab Promotes Responses in Subtypes Unresponsive to I-O (N=13)
BOTENSILIMAB PROMOTES RESPONSES IN SUBTYPES UNRESPONSIVE TO I-O (N=13) 130 Best Percent Change in Target Lesions (%) 120 • All Sarcoma (n=13) 110 100 90 • ORR: 46%; DCR: 69% 80 70 • (1 CR, 5 PRs, 3 SDs) 60 50 • Ongoing Responses: 4/6 (67%) 40 30 20 20% Tumor 20% Tumor Growth 10 Growth 0 -10 • Angios
Slide 13: Botensilimab Promotes Responses in Subtypes Unresponsive to I-O (N=13)
BOTENSILIMAB PROMOTES RESPONSES IN SUBTYPES UNRESPONSIVE TO I-O (N=13) 130 Best Percent Change in Target Lesions (%) 120 • All Sarcoma (n=13) 110 Subtypes Unresponsive to I-O 100 90 • ORR: 46%; DCR: 69% 80 70 • (1 CR, 5 PRs, 3 SDs) 60 50 • Ongoing Responses: 4/6 (67%) 40 30 20% Tumor 20% Tumor Growt
Slide 14: Botensilimab Promotes Durable Responses in Multiple Subtypes (N=13)
BOTENSILIMAB PROMOTES DURABLE RESPONSES IN MULTIPLE SUBTYPES (N=13) 120 110 Sarcoma Tumor Subtype Type 100 Cutaneous Angiosarcoma • All Sarcoma (n=13) 90 Visceral Angiosarcoma Best Percent Change From Baseline (%) 80 • ORR: 46%; DCR: 69% Leiomyosarcoma 70 60 Liposarcoma • (1 CR, 5 PRs, 3 SDs) 50 Ple
Slide 15: Safety
SAFETY TRAES OF ANY GRADE IN ≥2 PATIENTS (N=13) Characteristic All Grade Grade 3 Any TRAE 12 (92) 3 (23) GASTROINTESTINAL Diarrhea/colitis 6 (46) 2 (15) Nausea 3 (23) 0 (0) CONSTITUTIONAL Fatigue 5 (38) 1 (8) Chills 4 (31) 0 (0) Similar safety profile to the larger trial Decreased appetite 3 (23) 0
Slide 16: Summary
SUMMARY • Botensilimab plus balstilimab demonstrates a high ORR with durability and clinical benefit in patients with advanced sarcoma, including subtypes that have been unresponsive to I-O • The combination is well tolerated and appears differentiated from first-gen CTLA-4- based regimens, with les
Slide 17: Acknowledgements
ACKNOWLEDGEMENTS Agenus Inc. funded and is the sponsor of this study. The authors would like to thank the patients and their families for participating in the C-800-01 study, as well as the trial coordinators and investigators for their contributions.
Slide 18: Abbreviations
ABBREVIATIONS AE, adverse event irAE, immune-related adverse event APC, antigen presenting cell ITT, intention-to-treat bal, balstilimab mAb, monoclonal antibody BOR, best overall response MSS, microsatellite stable bot, botensilimab NK, natural killer CPS, combined positive score NR, not reached CR