Agenus Inc. · NASDAQ:AGEN
Agenus — ESMO World Congress on Gastrointestinal Cancer 2022
22 slides from Agenus's conference presentation, Jun 29, 2022
Slide 1: World Congress on Gastrointestinal Cancer 2022
| sy, WORLD CONGRESS ON “74 Gastrointestinal © Cancer 29 JUNE-—2 JULY 2022
Slide 2: Botensilimab plus balstilimab for metastatic heavily pretreated MSS colorectal cancer
Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer Anthony B. El-Khoueiry University of Southern California Norris Comprehensive Cancer Center Los Angeles, California, United States 2
Slide 3: Botensilimab plus balstilimab for MSS CRC: authors and affiliations
Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer Andrea J. Bullock,1 Joseph E. Grossman,2 Marwan G. Fakih,3 Heinz-Josef Lenz,4 Michael S. Gordon,5 Kim Margolin,6 Breelyn A. Wilky,7 Daruka Ma
Slide 4: Declaration of Interests
Declaration of Interests Anthony B. El-Khoueiry Advisory Role/Honoraria: Agenus, AstraZeneca, Bayer, Bristol-Myers Squibb, CytomX Therapeutics, Eisai, EMD Serono, Exelixis, Gilead, Merck, MedImmune Research Funding: Astex Pharmaceuticals, AstraZeneca, MedImmune, Merck, Pieris Pharmaceuticals, Roche
Slide 5: Limited Efficacy in 3L+ MSS CRC
Limited Efficacy in 3L+ MSS CRC 100 • ~95% of metastatic colorectal 80 Standard of Care cancer is microsatellite stable (MSS CRC) Percent (%) 60 mPFS ~2 months • Limited efficacy with regorafenib mOS ~6 months and TAS-102 in 3L+ setting1-3 40 Investigational 20 0 Rego 1,2 TAS-1023 PD-(L)1 Ipi/ Nivo8
Slide 6: Limited Efficacy in 3L+ MSS CRC
Limited Efficacy in 3L+ MSS CRC 100 • ~95% of metastatic colorectal 80 Standard of Care cancer is microsatellite stable (MSS CRC) Percent (%) 60 mPFS ~2 months • Limited efficacy with regorafenib mOS ~6 months and TAS-102 in 3L+ setting1-3 40 Investigational 20 • IO-only responses are rare4-11 • PD-
Slide 7: Novel Immunotherapy Agents: botensilimab and balstilimab
Novel Immunotherapy Agents botensilimab balstilimab Fc-enhanced CTLA-4 Inhibitor Design: PD-1 Inhibitor • Improved binding to activating FcγRs on APCs and NK cells • Reduced complement binding Function (relative to first-gen CTLA-4)2,3: • ↑ Frequency of activated Balstilimab DCs (IgG4) • ↑ T cell pr
Slide 8: Novel Immunotherapy Agents: botensilimab and balstilimab
Novel Immunotherapy Agents botensilimab balstilimab Fc-enhanced CTLA-4 Inhibitor PD-1 Inhibitor Active in cold and IO refractory tumors1: Safety and efficacy analogous to approved anti-PD-1 mAbs3,4 • ↑ T cell priming, expansion, memory2 • > 650 patients treated; 8 ongoing trials / 2 completed • ↑ Tr
Slide 9: C-800 Study Design
C-800 Study Design NCT03860272: First-in-human trial of botensilimab ± balstilimab in patients with advanced cancer1,2 KEY ELIGIBILITY TREATMENT (Up to 2 years) ENDPOINTS Dose Escalation Efficacy Monotherapy every 3 weeks • Advanced solid • ORR bot* • DCR (SD, CR or PR) tumors refractory to standard
Slide 10: C-800 Study Design
C-800 Study Design NCT03860272: First-in-human trial of botensilimab ± balstilimab in patients with advanced cancer1,2 KEY ELIGIBILITY TREATMENT (Up to 2 years) ENDPOINTS Dose Escalation Efficacy Monotherapy every 3 weeks • Advanced solid • ORR bot* • DCR (SD, CR or PR) tumors refractory to standard
Slide 11: C-800 Study Design
C-800 Study Design NCT03860272: First-in-human trial of botensilimab ± balstilimab in patients with advanced cancer1,2 KEY ELIGIBILITY TREATMENT (Up to 2 years) ENDPOINTS Dose Escalation Efficacy Monotherapy every 3 weeks • Advanced solid • ORR bot* • DCR (SD, CR or PR) tumors refractory to standard
Slide 12: C-800 Study Design: MSS CRC
C-800 Study Design: MSS CRC NCT03860272: First-in-human trial of botensilimab ± balstilimab in patients with advanced cancer1,2 KEY ELIGIBILITY TREATMENT (Up to 2 years) ENDPOINTS Dose Escalation Efficacy Monotherapy every 3 weeks • Advanced solid • ORR bot* • DCR (SD, CR or PR) tumors refractory to
Slide 13: MSS CRC Patient Characteristics
MSS CRC Patient Characteristics Characteristic Overall (N=41)* Age, median (range) 57 (36-82) Sex, n (%) Male 17 (41) Female 24 (59) ECOG PS at baseline, n (%) 0 17 (41) 1 24 (59) Prior lines of therapy, n (%) Evaluable patients Median (range) 4 (2-10) treated with Bot + Bal 2 5 (12) had ≥1 Q6W imag
Slide 14: Efficacy: Durable Objective Responses
Efficacy: Durable Objective Responses Overall (N=41) ORR, % (95% CI) 24% (14-39) BOR, n (%) CR 0 (0) • 8/10 objective responses ongoing PR 10 (24) • 3 responses >1 year SD 20 (49) • Median DOR not reached PD 11 (27) DCR (PR + SD), % (95% CI) 73% (58-84) Median Follow-up, mo. (range) 5.8 (1.6-24.4) 1
Slide 15: Waterfall Plot: Change in Target Lesions (%)
Waterfall Plot (N=41) ORR DCR 24% 73% 95% CI, 14-39 95% CI, 58-84 Change in Target Lesions (%) Patients 15 + =Ongoing PR/SD × =Progression of non-target lesions * =Complete metabolic response by PET
Slide 16: Safety: TRAEs in ≥10% of Patients
Safety TRAEs in ≥10% of Patients (N=41) TRAE, n (%) Any Grade Grade 1-2 Grade 3 Any 31 (76) 21 (51) 10 (24) No hypophysitis GASTROINTESTINAL Diarrhea/colitis 16 (39) 12 (29) 4 (10) Pneumonitis is rare Nausea 7 (17) 7 (17) 0 (0) Vomiting 4 (10) 4 (10) 0 (0) No grade 4 or 5 TRAEs CONSTITUTIONAL Fatigu
Slide 17: Exploratory Analysis by Liver Involvement
Exploratory Analysis by Liver Involvement Enriched responses in patients without active liver metastases (n=24) ORR DCR 42% 96% 95% CI, 25-61 95% CI, 80-99 Change in Target Lesions (%) Patients 17 + =Ongoing PR/SD × =Progression of non-target lesions * =Complete metabolic response by PET
Slide 18: Summary
Summary • Botensilimab plus balstilimab is a novel Fc-enhanced CTLA-4/PD-1 combination • In heavily pretreated patients with MSS CRC: • Deep objective responses with evidence of durability • Well tolerated with a differentiated safety profile • Enriched responses in patients without active liver met
Slide 19: Acknowledgements
Acknowledgements • Agenus Inc. funded and is the legal entity responsible for 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 19
Slide 20: Abbreviations
Abbreviations 3L, third line Nivo, nivolumab AE, adverse event NK, natural killer APC, antigen presenting cell ORR, objective response rate Bal, balstilimab OS, overall survival Bot, botensilimab PD-1, programmed death receptor-1 CR, complete response PD-L1, programmed death-ligand 1 CRC, colorectal
Slide 21: Q&A Session
/ORLD CONGRESS ON ESMD er Gastrointestinal snes Cancer Q&A Session 21
Slide 22: Declaration of Interests (Full)
Declaration of Interests (Full) • AJ Bullock: Advisory Role: Exelixis, Geistlich Pharma. • JE Grossman: Employee of Agenus with stock/stock options. • MG Fakih: Advisory Role: Array, Bayer, GlaxoSmithKline, Incyte, Mirati, Pfizer, Seattle Genetics, Taiho, Zhuhai Biotech; Honoraria: Amgen; Speakers'
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