Agenus Inc. · NASDAQ:AGEN
Agenus — Investor Presentation (October 2026)
33 slides from Agenus's investor presentation, October 2026
Slide 1: Botensilimab & Balstilimab: Redefining Immunotherapy in Cold Tumors
Botensilimab & Balstilimab: Redefining Immunotherapy in Cold Tumors Agenus Corporate Overview | October 2026
Slide 2: Forward-Looking Statement
Forward-Looking Statement This presentation contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws. These forward-looking statements include, but are not limited to, express or implied statements relating to the Company’s expectations,
Slide 3: Registration Enabling Opportunity for Neoadjuvant BOT+BAL in MSS Colon Cancer
Registration Enabling Opportunity for Neoadjuvant BOT+BAL in MSS Colon Cancer The Set-Up • Agenus’ focus has been development of a next-gen Fc-enhanced anti–CTLA-4 (BOT) and anti–PD-1 (BAL) combination in late- line, metastatic MSS CRC and other advanced, metastatic solid tumors • Two separate ISTs
Slide 4: Example of 100% tumor regression from Neoadjuvant BOT+BAL in MSS Colon Cancer
Novel Immunotherapy Example of 100% tumor regression from Approach with BOT+BAL Neoadjuvant BOT+BAL in MSS Colon Cancer After 1 dose of BOT + 2 doses of BAL with no concurrent nor prior therapy; from NEST1 Phase 2 trial ▪ Chemotherapy-free option ▪ Manageable safety profile MSS Colorectal Cancer ▪ O
Slide 5: Colorectal Cancer Faces Two Urgent Challenges: Rising Burden and Limited Innovation
Colorectal Cancer (CRC) Faces Two Urgent Challenges: Rising Burden of Disease and Limited Innovation – Especially in Microsatellite Stable (MSS) Disease Most CRC lacks effective 1 Rising CRC Burden 2 immunotherapy options • Colorectal cancer (CRC) is now the • Microsatellite stable (MSS) accounts le
Slide 6: Clinical Precedent Supports Next-Generation CTLA-4 in Neoadjuvant Treatment of Cold Tumors
Clinical Precedent Supports Next-Generation CTLA-4 in Neoadjuvant Treatment of “Cold” Tumors Building on Clinical Success Long-term EFS “tails” have been observed with Neoadjuvant PD-1 and CTLA-4 blockade have dual checkpoint blockade demonstrated durable event-free survival (EFS) tails in "hot" tum
Slide 7: Botensilimab: A Differentiated Anti–CTLA-4 Designed to Overcome Resistance
Botensilimab (BOT): A Differentiated Anti–CTLA-4 Designed to Overcome Resistance and Activate Anti-Cancer Immunity1,2 BOT's Fc-enhanced design supports multifaceted immune activation: Botensilimab APCs Complement X Factors T Cell Treg NK Cell Fc-Enhanced Activates Reduces Avoids Difficult- via point
Slide 8: BOT+BAL Converts Tumors from Cold to Hot
BOT+BAL Is Uniquely Effective in Driving Durable Anti-Cancer Immunity and Converting Tumors from “Cold” (Immune Evading) to “Hot” (Immune Activated) “Cold” Tumors1 “HOT” Tumors2 • Hidden from the immune system • Detectable by the immune system • Poor/no response to approved immunotherapy • Sensitive
Slide 9: BOT+BAL Phase 1b: Clinical Activity Across Multiple Metastatic Solid Tumor Settings
BOT+BAL Phase 1b: Clinical Activity Observed Across 339 Efficacy-Evaluable Patients and Multiple Metastatic Solid Tumor Settings1 140 120 100 80 Percent Change From Baseline (%) 60 40 20% tumor growth 20 0 -20 30% tumor reduction -40 -60 -80 -100 0 12 24 36 48 60 72 84 96 108 120 132 144 156 Time on
Slide 10: Pan-Tumor Phase 1b: Expanded Safety Dataset Shows Manageable Tolerability Profile
Pan-Tumor Phase 1b: Expanded Safety Dataset Shows Manageable Tolerability Profile Equals Selected ROBBIN Dose (75mg) Safety event, n (%) 1 mg/kg (n=228) 2 mg/kg (n=183) Overall (N=411) Any grade TRAE 85% 86% 85% Grade 1-2 TRAEs 57% 48% 53% Grade ≥3 TRAEs 28% 38% 32% Grade 1 or 2 Grade ≥3 Grade 1 or
Slide 11: Rationale for Strategic Pivot From Metastatic CRC to Neoadjuvant MSS Colon Cancer
Rationale for Strategic Pivot From Metastatic CRC to Neoadjuvant MSS Colon Cancer FROM TO Late-line, refractory metastatic CRC High-risk Stage II/Stage III MSS colon cancer BOT provides a significant benefit, but in a smaller and more No advances in treatment of this patient population in over 20 ye
Slide 12: Significant Market Opportunity for BOT+BAL in Locally Advanced MSS Colon Cancer
Significant Market Opportunity for BOT+BAL in Locally Advanced MSS Colon Cancer ~85,000 people are diagnosed with Stage I-III colon cancer in the US every year Exclude Stage I and • Stage I colon cancer is excluded from ROBBIN low-risk Stage II ; • 15-20% of Stage I and II Patients are MSI-H, and 8-
Slide 13: Understanding the Value of Cure in the Context of Early-Stage Colon Cancer
Understanding the Value of Cure in the Context of Early-Stage Colon Cancer ILLUSTRATIVE Current oncology therapies in the metastatic setting often deliver 2-6 months of incremental mOS Measuring the value of immune activation, memory, and Conventional Targeted Incremental Improvement in Median Total
Slide 14: Current Treatment Paradigm for Stage I to Stage III MSS Colon Cancer
Current Treatment Paradigm for Stage I to Stage III MSS Colon Cancer Adjuvant Therapy1-4 T1-2,N0 Observation T3,N0 Observation or 6m 5FU/LV or Capecitabine Resectable Colon Surgery & 6m 5FU/LV or Capecitabine ROBBIN T4,N0 Eligible Cancer Pathologic Staging or FOLFOX/CAPEOX T3,N1 CAPEOX or cT4a,N0 FO
Slide 15: Precedent for Pathologic Response Correlating with EFS: FOxTROT Study
Precedent for Pathologic Response Correlating with Event-Free Survival (EFS) in Stage II/III MSS Colon Cancer: FOxTROT Neoadjuvant Chemotherapy Study • FOxTROT (N=1,053) established that the depth of pathologic regression is associated with improved recurrence rates (notably no recurrences in patien
Slide 16: Pathologic Complete Response Rates Correlate with EFS
Pathologic Complete Response Rates (pCR) Correlate with EFS: pCR Rates with BOT+BAL in NEST & UNICORN Provide a Strong Signal for Success in ROBBIN pCR Rate Projected EFS METHODOLOGY: Delta Hazard Ratio Expected pCR rate in Control arm for ROBBIN = 0% • 21 neoadjuvant/perioperative trials evaluated
Slide 17: Precedent for I/O-Driven Pathologic Response and EFS: NICHE Study
Precedent for I/O-Driven Pathologic Response and EFS: Ipilimumab + Nivolumab Neoadjuvant Treatment in MSS Colon Cancer (NICHE Study) • The NICHE study evaluated neoadjuvant ipilimumab + nivolumab ± celecoxib in 31 patients with MSS Colon Cancer • 30 patients underwent surgery and were assessable for
Slide 18: Neoadjuvant CRC: BOT±BAL Evaluated Across Multiple Pre-Surgical Treatment Schedules
Neoadjuvant CRC: BOT±BAL Evaluated Across Multiple Pre-Surgical Treatment Schedules NEST (N=24)1 UNICORN (N=56)2 NEST 1 (~4 weeks to surgery) ~5 weeks to surgery BOT (75mg) BOT (75mg) BAL BAL Surgery Surgery 0 2 0 2 WEEKS WEEKS NEST 2 (~8 weeks to surgery) ~5 weeks to surgery BOT (75mg) BOT (75mg) B
Slide 19: Neoadjuvant CRC: Patient Populations Reflect Clinically Advanced Stage II and III Disease
Neoadjuvant CRC: Patient Populations Reflect Clinically Advanced Stage II and Stage III Disease Across MSS and MSI-H Settings NEST1 UNICORN2 NEST-1 NEST-2 pMMR pMMR Characteristic (n=10) (n=14) BOT BOT + BAL Age, median, years 57 69 Characteristic (n=14) (n=14) (Q1, Q3) (35, 69) (59, 75) Age, median
Slide 20: NEST Trial: Marked Tumor Reductions with BOT Dose + 2-4 BAL Doses
NEST Trial: Marked Tumor Reductions with 1 BOT Dose + 2-4 BAL Doses Stage II/III (Pre-Surgery and/or Chemo or “Neoadjuvant”) Patients Treated with BOT+BAL MSS/pMMR (“Cold”) MSI-H/ Topline Results dMMR (1 dose BOT + 2-4 doses BAL) NEST-1 NEST-2a (“Hot”) ~4 weeks to surgery ~8 weeks to surgery 0% MSS
Slide 21: UNICORN Trial: Consistent Demonstration of Benefit with BOT+BAL
UNICORN Trial: Consistent Demonstration of Benefit with BOT+BAL 56 Patients Treated with BOT Mono (n=28) and BOT+BAL Combo (n=28) ; Further Support for Contribution of Components MSS/pMMR (“Cold”) MSI-H/dMMR (“Hot”) BOT+BAL BOT BOT+BAL BOT 0% Pathologic tumor regression (%) −25% Pathological Respons
Slide 22: No Disease Recurrence Reported in BOT+BAL Treated Patients Across NEST and UNICORN
No Disease Recurrence Reported in 38 BOT+BAL Treated Patients Across NEST and UNICORN NEST1 UNICORN2 Event-Free Survival (N=24) Event-Free Survival (N=14) 100% BOT + BAL (MSS/pMMR) 75% NEST-1 Median follow-up: 32.2 months EFS Probability Median follow-up: NEST-2 Median follow-up: 23.5 months 50% 8.6
Slide 23: No ctDNA Recurrences Observed in NEST
No ctDNA Recurrences Observed in NEST ctDNA Levels 100 75 pre-surgical sample ctDNA (MTM/ml) post-surgical sample 50 25 0 0 100 200 300 400 500 Time post treatment (days) 23 Shah M et al. Neoadjuvant Botensilimab/Balslimab for localized mismatch repair proficient and deficient colon cancer…
Slide 24: NEST Safety Summary: Favorable Safety Profile With No Surgical Delays
NEST Safety Summary: Favorable Safety Profile With No Surgical Delays and No Unresolved High-Grade irAEs1,2 Treatment-Related Adverse Events NEST-1 (n=10) NEST-2 (n=14) • There were no grade 4 irAEs, and no unresolved high-grade irAEs Treatment-Related Adverse Event* Grade 2 Grade 3 Grade 2 Grade 3
Slide 25: UNICORN Safety Summary: Manageable Safety Profile with Limited High-Grade irAEs
UNICORN Safety Summary: Manageable Safety Profile with Limited High-Grade irAEs and Minimal Impact on Surgical Timing Immune-Mediated Adverse Events Botensilimab + Balstilimab (N=56) Any grade Grade ≥3 N (%) N (%) • Timely surgery was performed in all but 1 patient Any IMAE 22 (39%) 1 (2%) • 10-day
Slide 26: NEST and UNICORN Safety Summary: Favorable Toxicity Profile
NEST and UNICORN Safety Summary: Favorable Toxicity Profile with Low Incidence of High-Grade irAEs and No Significant Surgical Delays NEST1 UNICORN2 BOT+BAL BOT+BAL Treatment-Related Grade 3 (n=24) Immune-mediated AE Grade ≥3 (N=28) Fatigue 1 (4%) Hyperthyroidism 1 (2%) Colitis/Diarrhea 3 (13%) No d
Slide 27: Setting the Stage for the ROBBIN Phase 3 Study
Setting the Stage for the ROBBIN Phase 3 Study: Neoadjuvant BOT+BAL Demonstrates Deep and Durable Responses in Stage II/III MSS CRC No Disease Recurrence Depth of Pathologic Response in MSS CRC Reported with BOT+BAL BOT+BAL Neoadj Chemo IPI/NIVO (NEST1) (UNICORN2) (FOxTROTa) (NICHEb) BOT+BAL1,2 Adju
Slide 28: ROBBIN Phase 3: Neoadjuvant BOT+BAL in High-Risk Stage II and Stage III MSS Colon Cancer
ROBBIN* Phase 3: Neoadjuvant BOT+BAL in High-Risk Stage II and Stage III MSS Colon Cancer Trial Size • N=850 ~ 8 weeks BOT (1 dose; 75 mg) + SOC adjuvant chemotherapy Patient • High Risk Stage II (cT4aN0M0) and Stage III BAL (3 doses; 240 mg Q2W) S or observation† Population (cT3-T4Na+M0) resectable
Slide 29: ROBBIN Phase 3 Trial Design Aligned with FDA Feedback
ROBBIN Phase 3 Trial Design Aligned with FDA Feedback The following key elements of the Phase 3 study are aligned with FDA feedback: • The proposed patient population of Stage II (cT4aN0M0) and Stage III (cT3-T4Na+M0) colon cancer that is not MSI-H/dMMR • The proposed experimental arm of neoadjuvant
Slide 30: Projected Timeline for ROBBIN Phase 3 Study
Projected Timeline for ROBBIN Phase 3 Study 2026 2027 2028 2029 2030 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 ROBBIN Phase 3 RCT N = 850 (R 1:1) IA (EFS) FA (EFS) 2H’29 2H’30 FDA FPI Q1’27 50 patients LPI Meeting BOT/BAL treated 2H’28 (for interim path response) Interim Readout (P
Slide 31: Consistent Adoption of BOT+BAL in Paid Compassionate Access Programs
Consistent Adoption of BOT+BAL in Paid Compassionate Access Programs (AAC & NPP) Program Expansion High Interest Regulatory context AAC Expanded to 3 Tumor Documented HCP and Patient Unmet Need Remains Evident Types, NPP to New Markets Interest The French regulatory authority approved France AAC and
Slide 32: Fully Funded, FDA-aligned Phase 3 Trial Testing Neoadjuvant BOT+BAL in MSS Colon Cancer
Fully Funded, FDA-aligned Phase 3 Trial Testing Neoadjuvant BOT+BAL in MSS Colon Cancer, a Multi Billion-Dollar Opportunity in the US • July financing of $85M upfront and up to $340M in total, focused on BOT+BAL opportunity in high-risk Stage II and Stage III MSS Colon Cancer, >$7 Billion TAM in the
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