CheckMate-8HW Trial

[Slide 1] CheckMate 8HW 1L NIVO + IPI vs chemo Summary 1L NIVO + IPI demonstrated superior PFS vs chemo in patients with centrally confirmed MSI-H/dMMR mCRC (HR, 0.21 [97.91% CI, 0.13-0.35]; P < 0.0001) - 24-month PFS rates for NIVO + IPI vs chemo: 72% vs 14% - PFS benefit across all prespecified subgroups, including patients with BRAF or RAS mutations PFS2 favored NIVO + IPI vs chemo (HR, 0.27 [95% CI, 0.17-0.44 ]) despite a high crossover rate, suggesting clinical benefit is maintained after subsequent therapy - 24-month PFS2 rates for NIVO + IPI vs chemo: 83% vs 52% The safety profile of NIVO + IPI was different compared with chemo, with fewer grade 3/4 TRAEs despite longer treatment duration - Safety of NIVO + IPI was consistent with the known profiles of each individual component, with no new safety signals These results provide further evidence to support NIVO + IPI as a standard-of-care 1L treatment option for patients with MSI-H/dMMR mCRC Copies of this slide deck obtained through Quick Response for personal and may not be reproduced without from ASCO this slide --- [Slide 2] CheckMate 8HW 1L NIVO + IPI vs chemo PFS2: progression-free survival after subsequent therapy 12-month rate 100 89% 24-month rate 90 83% 80 Patients who are progression-free after first subsequent therapy (%) 70 65% NIVO + IPI 60 52% 50 dee 40 1L centrally confirmed NIVO IPI Chemo 30 MSI-H/dMMR (n 171) (n 84) Chemo Median PFS2, a,b,c mo NR 29.9 20 95% CI NE-NE 14.8-NE 10 HR (95% CI) 0.27 (0.17-0.44) 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 No. at risk Months NIVO IPI 171 161 155 147 135 127 117 103 94 85 71 64 45 30 25 10 1 0 Chemo 84 77 65 54 45 40 35 31 27 26 21 17 13 9 7 2 0 0 PFS2ᵃ favored NIVO + IPI vs chemo with a 73% reduction in the risk of death or disease progression after first subsequent therapy "Defined as time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death. Per investigator. Median follow-up in patients with centrally confirmed MSI-H/dMMR, 31.6 months. 10 --- [Slide 3] CheckMate 8HW 1L NIVO + IPI vs chemo Progression-free survival 1L centrally confirmed NIVO IPI Chemo MSI-H/dMMR (n 171) (n 84) Median PFS,ᵃ,ᵇ mo NR 5.9 100 95% CI 38.4-NE 4.4-7.8 90 12-month rate HR (97.91% CI) 0.21 (0.13-0.35) 24-month rate P value < 0.0001 80 Progression-free survival (%) 70 79% 60 72% 50 NIVO + IPI 40 30 21% 20 14% 60 10 Chemo 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 No. at risk Months NIVO IPI 171 144 132 122 108 95 92 77 64 53 42 37 22 10 9 1 0 Chemo 84 53 29 20 10 6 5 5 3 2 0 0 0 0 0 0 0 PFS benefit with NIVO + IPI vs chemo was robust and consistent across the sensitivity and supportive analyses, including PFS by BICR in 1L all randomized patients (HR, 0.32; 95% CI, 0.23-0.46) "Per BICR. Median follow-up in patients with centrally confirmed MSI-H/dMMR, 31.6 months. 7 --- [Slide 4] CheckMate 8HW 1L NIVO + IPI VS chemo CheckMate 8HW study design CheckMate 8HW is a randomized, multicenter, open-label phase 3 studyᵃ Dual primary endpoints in patients with Key eligibility criteria: NIVO 240 mg Q2W for 6 doses, centrally confirmed MSI-H/dMMR Histologically confirmed followed by NIVO 480 mg Q4Wb status: unresectable or metastatic CRC PFS by BICR (NIVO + IPI vs chemo in MSI-H/dMMR status by local the 1L setting) testing ECOG PS 0 or 1 R NIVO 240 mg + IPI 1 mg/kg Q3W for 4 doses, PFS by BICR (NIVO + IPI VS 2:2:1 1L setting: followed by NIVO 480 mg Q4Wb NIVO across all lines) n 202 Stratification factors: Other select endpoints: Prior lines of treatment Investigator's choice chemoc (0 VS 1 vs > 2) Safety (mFOLFOX6 or FOLFIRI + bevacizumab or Primary tumor location 1L setting: OS; PFS2 by investigatore; ORR by cetuximab) (right vs left) n = 101 BICRe; PROs Treatment until disease progression, unacceptable toxicity, withdrawal of consent (all arms), or a maximum treatment duration of 2 years (NIVO and NIVO + IPI arms only) At data cutoff (October 12, 2023), the median follow-up was 31.5 months (range, 6.1-48.4) ClinicalTrials.gov. NCT04008030. Patients with 2 2 prior lines are randomized only to the NIVO or NIVO IPI arms. Patients receiving investigator's choice of chemotherapy are eligible to receive NIVO IPI upon progression (crossover treatment). "Confirmed using either immunohistochemistry and/or polymerase chain reaction-based tests. "Evaluated using RECIST v1.1. Time between randomization and data cutoff. 4

[Slide 1] A Centrally confirmed microsatellite instability-high Nivolumab plus Nivolumab or mismatch repair-deficient status ipilimumab (n=296) (n=286) 100 Median progression-free survival (months) NR 39-3 95% CI 53-8-NE 22-1-NE HR (95% CI) 0-62 (0-48-0-81) 80 P value 0.0003 Progression-free survival (%) 60 40 20 Nivolumab plus ipilimumab Nivolumab 0 Number at risk CM-8HW (number censored) Nivolumab plus ipilimumab 296 248 234 225 214 207 200 180 164 146 136 134 121 102 100 61 54 29 23 0 0 (0) (5) (7) (10) (12) (13) (18) (34) (49) (62) (72) (74) (85) (98) (100) (138) (144) (169) (173) (195) (195) Nivolumab 286 210 191 179 169 164 158 141 124 109 98 95 81 72 69 39 31 15 12 1 0 (0) (5) (9) (11) (12) (13) (16) (25) (39) (50) (58) (60) (73) (81) (83) (111) (119) (135) (138) (149) (150) B All randomised Nivolumab plus Nivolumab 100 ipilimumab (n=354) (n=353) Median progression-free survival (months) 54.1 18-4 95% CI 44-0-NE 9.2-28-2 80 HR (95% CI) 0.64 (0-52-0-79) Progression-free survival (%) 60 40 20 Nivolumab plus ipilimumab Nivolumab 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 Time (months) Number at risk (number censored) Nivolumab plus ipilimumab 354 271 253 240 227 216 208 187 170 152 141 139 126 106 104 63 56 29 23 0 0 (0) (7) (10) (13) (15) (16) (21) (38) (54) (67) (78) (80) (91) (105) (107) (147) (153) (180) (184) (206) (206 Nivolumab 353 230 202 187 177 172 166 146 128 112 101 98 84 75 72 39 31 15 12 1 0 (0) (7) (11) (13) (14) (15) (18) (28) (43) (54) (62) (64) (77) (85) (87) (118) (126) (142) (145) (156) (157) --- [Slide 2] KN-177 100 Hazard ratio for progression or death, 90 0.60 (95% CI, 0.45-0.80) P=0.0002 80 Patients with Progression-free 70 Survival (%) 60 50 Pembrolizumab 40 30 20 Chemotherapy 10 0 0 4 8 12 16 20 24 28 32 36 40 44 48 Months No. at Risk Pembrolizumab 153 96 77 72 64 60 55 37 20 7 5 0 0 Chemotherapy 154 100 68 43 33 22 18 11 4 3 0 0 0

[Slide 1] Nivolumab plus ipilimumab versus nivolumab in W CrossMark microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial Thierry André, Elena Elez, Heinz-Josef Lenz, Lars Henrik Jensen, Yann Touchefeu, Eric Van Cutsem, Rocio Garcia-Carbonero, David Tougeron, Guillermo Ariel Mendez, Michael Schenker, Christelle de la Fouchardiere, Maria Luisa Limon, Takayuki Yoshino, Jin Li, Jose Luis Manzano Mozo, Laetitia Dahan, Giampaolo Tortora, Myriam Chalabi, Eray Goekkurt, Maria Ignez Braghiroli, Rohit Joshi, Timucin Cil, Francine Aubin, Elvis Cela, Tian Chen, Ming Lei, Lixian Jin, Steven Blum, Sara Lonardi A Centrally confirmed microsatellite instability-high Nivolumab plus Nivolumab or mismatch repair-deficient status ipilimumab (n=296) (n=286) 100 Median progression-free survival (months) NR 39-3 95% CI 53-8-NE 22-1-NE HR (95% CI) 0-62 (0-48-0-81) 80 P value 0.0003 Progression-free survival (%) 60 40 20 Nivolumab plus ipilimumab Nivolumab 0 Number at risk (number censored) Nivolumab plus ipilimumab 296 248 234 225 214 207 200 180 164 146 136 134 121 102 100 61 54 29 23 0 0 (0) (5) (7) (10) (12) (13) (18) (34) (49) (62) (72) (74) (85) (98) (100) (138) (144) (169) (173) (195) (195) Nivolumab 286 210 191 179 169 164 158 141 124 109 98 95 81 72 69 39 31 15 12 1 0 (0) (5) (9) (11) (12) (13) (16) (25) (39) (50) (58) (60) (73) (81) (83) (111) (119) (135) (138) (149) (150) B All randomised Nivolumab plus Nivolumab 100 ipilimumab (n=354) (n=353) Median progression-free survival (months) 54-1 18-4 95% CI 44-0-NE 9-2-28-2 80 HR (95% CI) 0-64 (0-52-0-79) Progression-free survival (%) 60 40 20 Nivolumab plus ipilimumab Nivolumab 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 Time (months) Number at risk (number censored) Nivolumab plus ipilimumab 354 271 253 240 227 216 208 187 170 152 141 139 126 106 104 63 56 29 23 0 0 (0) (7) (10) (13) (15) (16) (21) (38) (54) (67) (78) (80) (91) (105) (107) (147) (153) (180) (184) (206) (206) Nivolumab 353 230 202 187 177 172 166 146 128 112 101 98 84 75 72 39 31 15 12 1 0 (0) (7) (11) (13) (14) (15) (18) (28) (43) (54) (62) (64) (77) (85) (87) (118) (126) (142) (145) (156) (157)

[Slide 1] April 08, 2025 CheckMate-8HW Nivolumab/Ipilimumab FDA Approval in MSI-H Indications Nivolumab with Ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer. Trial: Randomized, Phase III, N=707 Nivolumab + Ipilimumab VS. Nivolumab Primary Endpoint Median PFS NR HR 0.62 (95%CI, 0.48-0.81, p = 0.0003) 39.3 mos Secondary Endpoint ORR 71% (p=0.0011) 58 % Side effects:* fatigue, nausea/vomiting, musculoskeletal pain, immune- mediated adverse events hypothyroidism, hyperthyroidism, colitis, pneumonitis, hepatitis, pancreatitis, hypophysitis. Disclaimer: *Please note that we are only listing the most common toxicities; this is not an exhaustive list of side effects. For a comprehensive overview, please refer to the official package insert or relevant clinical guidelines. Dosage: Nivolumab 240 mg + Ipilimumab 1 mg/kg every 3 weeks (max of 4 doses) Followed by Nivolumab 480 mg every 4 weeks ONC othel Website: www.oncbrothers.com X @OncBrothers

[Slide 1] ASCO FDA Alerts --- [Slide 2] On April 8, 2025, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for adult and pediatric patients 12 years of age and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). The FDA also converted the accelerated approval to regular approval for single agent nivolumab for adult and pediatric patients 12 years of age and older with MSI-H or dMMR metastatic CRC, that has progressed following fluoropyrimidine, oxaliplatin, and irinotecan. --- [Slide 3] The analysis of nivolumab + ipilimumab versus chemotherapy in the first line setting was conducted in 255 patients with centrally confirmed MSI-H/dMMR status of 303 patients based on local testing. Median PFS was not reached (NR) (95% Cl: 38.4, not estimable [NE]) in the nivolumab + ipilimumab arm and 5.8 months (95% Cl: 4.4, 7.8) in the chemotherapy arm (Hazard ratio 0.21 [95% Cl: 0.14, 0.32] p-value <0.0001). Comparative results of ORR and OS between arms were not available at the time of the interim PFS analysis due to statistical testing strategy.