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2945P: Expanded Safety and Efficacy of Givastomig, a Claudin 18.2/4-1BB Bispecific Antibody, in Combination with Nivolumab and mFOLFOX6 in 1L Metastatic Gastroesophageal Carcinoma (mGEC) S. Klempner1, F . Dayyani2,J . K r a t z3,N . U b o h a3, K. Spencer4,S . K i m5,S . L e e6,J . J e o n6,C . X u7, C. Ahlers7, P . Dennis7,G . K u8 1Medical Oncology, MGH - Massachusetts General Hospital, Boston, MA, United States of America, 2Medical Oncology, UCI - University Of California Irvine - Health Manchester Pavilion, Orange, CA, United States of America, 3Medical Oncology, University of Wisconsin - School of Medicine and Public Health, Madison, WI, United States of America, 4Medical Oncology, NYU Langone Laura and Isaac Perlmutter Cancer Center, New York, NY , United States of America, 5Medical Oncology, UCHealth Cancer Care - Anschutz Medical Campus - University of Colorado Cancer Center, Aurora, CO, United States of America, 6Clinical Development, ABL Bio, Seongnam, Republic of Korea, 7Clinical Development, NovaBridge Biosciences, Rockville, MD, United States of America, 8Gastrointestinal Oncology Service, Department of Medicine, MSKCC - Memorial Sloan Kettering Cancer Center, New York, NY , United States of America Background • Gastric cancer is the fifth most common cause of cancer related death worldwide, and existing standards of care only provide modest benefit in gastric/GEJ cancers. Therefore, there remains a high unmet need for novel agents in the first line (1L) metastatic setting for these tumors. • CLDN18.2 is a validated biomarker expressed in gastric cancers and several other tumor types. • Givastomig/ABL111 is a first-in-class, bispecific antibody targeting Claudin (CLDN) 18.2 that engages 4-1BB on T cells within tumors that express CLDN18.2, which results in localized T-cell activation designed to limit systemic immune toxicity and liver toxicity. 1 • The ongoing study (NCT04900818) is an open-label, first-in-human, phase 1 study with givastomig in patients with advanced solid tumors. Part 2 was designed to evaluate safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of givastomig in combination with nivolumab and mFOLFOX6 in CLDN18.2+ gastric, gastroesophageal and esophageal adenocarcinomas (GEA). • Encouraging efficacy and safety data from dose escalation were reported at ESMO GI 2025.2 • Here we report longer follow up and additional data from expansion cohorts treated with the combination of givastomig, nivolumab, and mFOLFOX6 as of August 6, 2026. Study Schema/Method Figure 3: Spider Plot highlighting response duration at 8 and 12 mg/kg Table 4: TRAE Related to Givastomig and IRAE Study Design: • Multi-center, dose-escalation and expansion phase 1b study • Enrolling US patients • Bayesian optimal interval escalation design with at least four subjects per dose Eligibility: • 1L unresectable or metastatic GC/GEJ/EAC (GEA) • HER2-negative • CLDN18.2 ≥1+ on ≥1% of tumor cells • Any PD-L1 CPS Givastomig Molecular Design 4-1BB scFv CLDN18.2 High binding affinity to tumor cells with a broad range of CLDN18.2 expression Reduced Fc-effector function to minimize CLDN18.2 or 4-1BB mediated toxicity Potent intra-tumor 4-1BB activation upon binding to CLDN18.2 on tumor cells Results Table 1: Overall Response Rates across CLDN18.2 and PD-L1 Subgroups Givastomig 8 mg/kg + Nivolumab + mFOLFOX6 (n=31) Givastomig 12 mg/kg + Nivolumab + mFOLFOX6 (n=40) Response-evaluable (n)^ 29 40 Median follow up (mo., 95% CI) 17.8 (15.1, 18.9) 10.1 (7.8, 11.5) Median DOR (mo., 95% CI) 15.2 (8.8, NC) 12.1 (5.6, NC) ORR* [confirmed and unconfirmed] % (n) 79% (23/29) 70% (28/40) SD 17% (5/29) 25% (10/40) DCR* (CR+PR+SD) % (n) 97% (28/29) 95% (38/40) PD-L1 CPS ≥1* 77% (20/26) 72% (21/29) PD-L1 CPS <1* 100% (3/3) 64% (7/11) CLDN18.2 ≥75%*# 82% (14/17) 60% (9/15) CLDN18.2 1–74%*# 75% (9/12) 76% (19/25) CLDN18.2 ≥75%# and PD-L1 CPS ≥1* 80% (12/15) 73% (8/11) CLDN18.2 1-74%# and PD-L1 CPS ≥1* 73% (8/11) 72% (13/18) ^at least one evaluable on-treatment scan; *includes confirmed and unconfirmed responses (unconfirmed includes only those with one follow-up scan at the time of DCO); #CLDN18.2 ≥75% includes 2+/3+ only, CLDN18.2 1–74% inclusive of 1+/2+/3+; DOR: Duration of Response Table 2: Progression-Free Survival across PD-L1 Subgroups Givastomig 8 mg/kg + Nivolumab + mFOLFOX6 (n=31) Givastomig 12 mg/kg + Nivolumab + mFOLFOX6 (n=40) Median PFS (mo., 95% CI) 16.9 (7.3, NC) 10.4 (8.6, NC) events n (%) 13 (41.9%) 14 (35.0%) censored n (%) 18 (58.1%) 26 (65.0%) PD-L1 CPS ≥1 16.9 (6.8, NC) 9.1 (8.4, NC) PD-L1 CPS <1 18.0 (10.5, NC) 15.6 (4.0, NC) • As of August 6, 2026, 71 GEC patients received givastomig 8 mg/kg (n=31) or 12 mg/kg (n=40) with nivolumab and mFOLFOX6. • The median duration of follow up was 17.8 mo. (8 mg/kg) and 10.1 mo. (12 mg/kg). Dose cohorts were enrolled sequentially leading to the differences in follow-up duration between cohorts; cross-cohort comparisons should be interpreted with caution. • Objective response rate (ORR) was 79% and 70%, with DCR 97% and 95%, respectively (efficacy evaluable population, confirmed and unconfirmed responses, see Table 1). • Responses were rapid: median time to response was 2 and 3.6 mo. in the 8 and 12 mg/kg groups, respectively, and deepened over time. • The median duration of response was 15.2 mo. (8 mg/kg) and 12.1 mo. (12 mg/kg). • Median progression-free survival (PFS) was 16.9 mo. at 8 mg/kg and 10.4 mo. at 12 mg/kg (one PD event reclassified from earlier data cut-off). • Median overall survival (OS) data are immature, available in the Supplemental Data file: see QR code, bottom left of this poster. • 34 patients remain on treatment with the longest treatment duration being 26 months (Figure 1). Lead author disclosures: Consulting: Astellas Pharma US Inc, Merck & Co Inc, Daiichi Sankyo Inc, Natera Inc, Novartis Pharmaceuticals Corporation, AstraZeneca Pharmaceuticals LP, Mersana Therapeutics Inc, BeOne, Gilead Sciences Inc, Elevation Oncology Inc, Eisai Inc, Taiho Oncology Inc, Boehringer Ingelheim Corp USA, NovaBridge Biosciences, Sanofi, Signet Therapeutics, EsoBiotec; DSMB: Sanofi Aventis. Board, Society, Committee, or Advocacy Group (uncompensated): Debbies Dream Foundation, Hope for Stomach Cancer; Other: NCCN Guidelines Committee (uncompensated), Research to Practice (CME lecture). Email: sklempner@mgb.org Study sponsored by: NovaBridge Biosciences and ABL Bio, ClinicalTrials.gov Identifier: NCT04900818 Acknowledgements: NovaBridge Biosciences thanks all patients, their families, & participating clinical sites. • The most common givastomig treatment- related adverse events (TRAEs, all grade) were nausea, fatigue and gastritis in the 8 mg/kg cohort, and nausea, vomiting, decreased appetite and gastritis in the 12 mg/kg cohort. • The incidence of grade 3 givastomig-related nausea remains low across both doses. There was no grade 3 vomiting at 8 mg/kg; the incidence of grade 3 vomiting at 12 mg/kg was 5%. The incidence of grade 3 ALT/AST elevation was 1%. • There were no givastomig-related grade ≥4 AEs. • Immune-related AEs were uncommon, except for gastritis, the majority of which were Grade 2 events. • A table of TRAEs attributed to any study treatment is available in the Supplemental Data file: see QR code, bottom left of this poster. • The most common any-drug TRAEs (all grade) were fatigue (71% at 8 mg/kg, 65% at 12 mg/kg), nausea (61% at 8 mg/kg, 60% at 12 mg/kg), neutropenia (52% at 8 mg/kg, 50% at 12 mg/kg) and vomiting (39% at 8 mg/kg, 50% at 12 mg/kg) • The most common any-drug grade 3 TRAEs were neutropenia (26% at 8 mg/kg and 22% at 12 mg/kg), fatigue (6% at 8 mg/kg, 10% at 12 mg/kg) and decreased appetite (6% at 8 mg/kg, 10% at 12 mg/kg). • The most common grade 4 any-drug TRAE was neutropenia (6% at 8 mg/kg, 5% at 12 mg/kg). There were no grade 5 any-drug TRAEs. GC = gastric cancer; GEJ = gastroesophageal junction; EAC = esopha geal adenocarcinoma; mFOLFOX6 = 5FU, Oxaliplatin, Leucovorin; Q2W = every two weeks; ORR = objective response rate; PK = pharmacokinetic; PD = pharmacodynamic; BOR = best overall response; DOR = duration of response; PFS = progression-free survival; OS = overall survival; 1L = first line Primary: • Safety Dose Expansion (n=80) Dose Level 3 (n=40) Givastomig 12 mg/kg + nivolumab 240 mg + mFOLFOX6 Q2W Enrollment Ongoing Dose Escalation (n=17) Dose Level 2 (n=40) Givastomig 8 mg/kg + nivolumab 240 mg + mFOLFOX6 Q2W Dose Level 1 (n=5) Givastomig 5 mg/kg + nivolumab 240 mg + mFOLFOX6 Q2W Dose Level 2 (n=6) Givastomig 8 mg/kg + nivolumab 240 mg + mFOLFOX6 Q2W Dose Level 3 (n=6) Givastomig 12 mg/kg + nivolumab 240 mg + mFOLFOX6 Q2W Endpoints Secondary: • Response: ORR, BOR, DOR • Survival: PFS, OS • PK/PD Givastomig 8 mg/kg + Nivolumab + mFOLFOX6 (n=31) Givastomig 12 mg/kg + Nivolumab + mFOLFOX6 (n=40) TEAE 97% 100% TRAE givastomig 90% 92% TRAE any drug 97% 100% SAE 58% 55% Related SAE givastomig 10% 30% Related SAE any drug 26% 30% Grade ≥3 TEAE 68% 80% Grade ≥3 TRAE givastomig 23% 40% Grade ≥3 TRAE any drug 55% 62% TRAE any drug Æ givastomig delay 55% 68% TRAE any drug Æ givastomig interrupted 23% 15% TRAE any drug Æ givastomig discontinued 26% 18% TRAE any drug Æ any drug discontinued 48% 42% TRAE any drug Æ death –– Table 3: AE Overview Enrollment Ongoing 20 patients ongoing treatment at 12 mg/kg 14 patients ongoing treatment at 8 mg/kg Figure 1: Duration of Study Treatment – 34 Patients on Treatment 0 100 200 300 400 500 600 700 800 Study Day 8 mg/kg 12 mg/kg −100 −80 −60 −40 −20 20 40 Percent change from baseline 0 100 200 300 400 500 600 700 800 Study Day 0 Figure 4: Kaplan-Meier Estimate of Progression-Free Survival All treated patients (N=71) 0 5 10 15 20 25 30 0.0 0.2 0.4 0.6 0.8 1.0 Survival Probability + Censored Month 31 19 14 11 1 1 08 mg/Kg 40 27 10 3 0 0 012 mg/Kg Dose 8 mg/Kg 12 mg/Kg Figure 2: 99% Subjects Experienced Tumor Shrinkage −100 −80 −60 −40 −20 0 20 Best Change in Sum of target diameter from Baseline (% ) Dose CPS 3< 1 0 1 51 5 130 25 20 60 10 30 7 0 15-20 40 0 5 <1 30 1-4 3 25 5 20 30 5 30 30 5 75 00 10 2 15 0 20 011 10 8 32 7 0 16 2 20 20 17 5 2 20 20 10 1 53 0 0 10 80 20 10 CL DN 18.2 85 80 75 93 95 40 10 5 85 35 2 85 80 15 55 80 53 0 90 90 95 10 50 40 2 40 90 85 10 15 2 40 60 80 30 5 1 2 5 95 85 60 83 95 95 90 35 7 5 99 95 75 70 90 70 77 93 10 0 95 30 90 82 70 30 80 70 4 60 60 SD SD * SD SD SD * SD * SD * PD * SD uPR SD PD PR uPR PR PD PR PR SD PR PR PR PR PR uPR PR PR PR uPR SD * PR PR PR uP R PR SD PR PR SD PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR SD * PR CR SD * 8 m g/kg 12 m g/kg Re d fo nt: CPS<5 or CL DN18 .2=1-74 TRAE givastomig in ≥10% in either dose (n=71) Adverse Event Grades ≤ 2 Grade 3 All Grades mg/kg: 8 (n=31) 12 (n=40) 8 (n=31) 12 (n=40) 8 (n=31) 12 (n=40) Any event 68% 52% 23% 40% 90% 92% Nausea 48% 45% 10% 8% 58% 52% Vomiting 35% 42% – 5% 35% 48% Gastritis 32% 32% 6% 15% 39% 48% Fatigue 45% 25% 3% 10% 48% 35% Decreased appetite 23% 38% 6% 10% 29% 48% IRR 19% 20% 3% – 23% 20% Weight decreased 19% 12% 3% 8% 23% 20% Abd pain/discomfort 13% 10% – 8% 13% 18% Diarrhea 13% 12% – – 13% 12% Dyspepsia 6% 10% – – 6% 10% Dysgeusia 10% 8% – – 10% 8% Headache 10% – – – 10% – Immune-related adverse events (n=71) Adverse Event Grades ≤ 2 Grade 3 All Grades mg/kg: 8 (n=31) 12 (n=40) 8 (n=31) 12 (n=40) 8 (n=31) 12 (n=40) Any event 39% 42% 16% 18% 55% 60% Gastritis 32% 32% 6% 15% 39% 48% Rash maculo-papular 3% 12% 6% – 10% 12% Pneumonitis –5 %–2 %–8 % Hyperthyroidism 6% – – – 6% – Hypothyroidism 6% 2% – – 6% 2% Immune nephritis –– 3 % – 3 % – Immune neurologic disorder –––––– Conclusions • With longer follow-up, givastomig 8 mg/kg plus nivolumab and mFOLFOX6 demonstrated encouraging and durable clinical activity across CLDN18.2 and PD-L1 subgroups, with a manageable safety profile supporting 8 mg/kg for Phase 3 development in 1L metastatic GEA. • The overall AE profile of the combination is generally similar to that observed with IO/chemo alone. • The rates of immune-related AEs do not appear to be increased over the rates seen with nivolumab + chemo in other studies, with the exception of gastritis. • Gastritis was manageable and had a rare incidence of grade 3 events (and no grade 4 or 5 events) at 8 mg/kg. • Follow-up continues, as well as enrollment in CLDN18.2 positive pancreatic and biliary tract cancer cohorts. References 1. Gao J, et al. CLDN18.2 and 4-1BB bispecific antibody givastomig exerts antitumor activity through CLDN18.2-expressing tumor-directed T-cell activation. J Immunother Cancer. 2023;11:e006704. 2. Klempner et al. Preliminary safety and efficacy of givastom ig, a novel claudin 18.2/4-1BB bispecific antibody, in combination with nivolumab and mFOLFOX in metastatic gastroesophageal carcinoma (mGEC) Annals of Oncology, 36, S151-S152.
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CONFIDENTIAL I Treatment emergent AE related to any drugs occurring in ≥15% of participants at 8mg/kg or 12mg/kg • DCO Aug 6, 2026 Adverse Event Grades ≤ 2 Grade 3 Grade 4 All Grades 8 (n=31) 12 (n=40) 8 (n=31) 12 (n=40) 8 + 12 (n=71) 8 (n=31) 12 (n=40) 8 (n=31) 12 (n=40) 8 + 12 (n=71) Any Event 42% 38% 42% 55% 49% 13% 8% 97% 100% 99% Fatigue 65% 55% 6% 10% 8% -- -- 71% 65% 68% Nausea 52% 52% 10% 8% 8% -- -- 61% 60% 61% Neutropenia* 19% 22% 26% 22% 24% 6% 5% 52% 50% 51% Vomiting 39% 45% -- 5% 3% -- -- 39% 50% 45% Decreased appetite 29% 45% 6% 10% 8% -- -- 35% 55% 46% Gastritis 32% 32% 6% 15% 11% -- -- 39% 48% 44% IRR 16% 32% 6% 2% 4% -- -- 23% 35% 30% Peripheral neuropathy 45% 58% -- 2% 1% -- -- 45% 60% 54% Diarrhea 19% 28% -- 2% 1% -- -- 19% 30% 25% Dysgeusia 35% 22% -- 2% 1% -- -- 35% 25% 30% Temp intolerance 10% 20% -- -- -- -- -- 10% 20% 15% Weight decreased 29% 12% 3% 8% 6% -- -- 32% 20% 25% Platelets decreased 23% 10% 3% 2% 3% -- -- 26% 12% 18% AST increased 10% 8% 6% 2% 4% -- -- 16% 10% 13% Constipation 13% 15% -- -- -- -- -- 13% 15% 14% Pruritus 19% 12% 3% -- 1% -- -- 23% 12% 17% Abdominal pain 10% 10% -- 8% 4% -- -- 10% 18% 14% Paresthesia 16% 12% -- -- -- -- -- 16% 12% 14% ALT increased 13% 8% 3% 2% 3% -- -- 16% 10% 13% Stomatitis 19% 15% -- -- -- -- -- 19% 15% 17% Anemia 13% -- 3% 5% 4% -- -- 16% 5% 10% *PT neutrophil count decrease and neutropenia 1
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CONFIDENTIAL I 2 DCO Aug 6, 2026 Kaplan-Meier Estimate of Overall Survival, Givastomig 8 mg/kg or 12 mg/kg