Adlai Nortye Group Ltd. · NASDAQ:ANL
Adlai Nortye — AACR-NCI-EORTC 2025
11 slides from Adlai Nortye's conference presentation, Oct 25, 2025
Slide 1: Discovery of AN4035: A Novel CEACAM5-Targeting ADC Armed with a Pan-RAS(ON) Inhibitor Payload
Discovery of AN4035: A Novel CEACAM5-Targeting Antibody Drug Conjugate (ADC) Armed with a Proprietary Pan-RAS(ON) Inhibitor Payload, Designed to Broaden the Therapeutic Window Xiaojun Han, Qingchong Qiu, Xin Chang, Yao Wang, Haige Li, Ling Zhang, Hao Ye, Ying Pan, Junying Li, Meng Chen, Xiaoli Zhu,
Slide 2: Disclosure Information
Disclosure Information Archie Tse MD PhD I have the following relevant financial relationships to disclose: Employee and Stockholder of: Adlai Nortye Ltd. (Nasdaq: ANL)
Slide 3: Pan-RAS(ON) inhibitor as a next-generation ADC payload
Pan-RAS(ON) inhibitor as a next-generation ADC payload ▪ Background: Tricomplex pan-RAS(ON) inhibitors (e.g. RMC-6236) are a promising class of therapeutics against RAS-driven cancers ▪ Potential limitations: on-target, off-tumor toxicities may restrict dose and limit safety in combinations ▪ Our Hy
Slide 4: Payload is a proprietary highly potent pan-RAS(ON) inhibitor
Payload is a proprietary highly potent pan-RAS(ON) inhibitor MOA of Payload: Binary Tri-complex (KRAS) KD2 (nM) Pan-RAS(ON) molecular glue Compound (CYPA) KD1 (nM) G12C G12D G12V WT Payload 14.9 4.7 30.5 14.0 18.6 RMC-6236 12.5 19.1 174 45.9 52.8 RAS Mutation Payload 72h CTG Cancer Cell Line Indicat
Slide 5: AN4035 demonstrated favorable drug-like characteristics
AN4035 demonstrated favorable drug-like characteristics Stable Conjugator Human Plasma Compound LC-MS DAR Incubation Time Day 0 8.04 AN4035 Day 7 7.85 Stable Linker-Payload Plasma Payload Released Rate % Compound Incubation Time Human Mouse Rat Monkey Day 0 <0.05 <0.05 0.02 <0.05 CEACAM5: Overexpres
Slide 6: AN4035 achieved superior target-mediated intracellular payload retention
AN4035 achieved superior target-mediated intracellular payload retention ADC drugs media Cell supernatant (10 μg/mL) conc. lysis buffer Cancer Cell 20 min, 2, 4, 24, 48 h Cell lysate PBS wash payload conc. HPAC cancer cell AN4035 RASi ADC (10 μg/mL) Isotype-control ADC (10 μg/mL) CEACAM5C Top1 ADC (
Slide 7: AN4035 demonstrated potent cytotoxicity and a robust bystander effect
AN4035 demonstrated potent cytotoxicity and a robust bystander effect in CEACAM5-positive, RAS-addicted cancer cell models 6-day CTG Cancer Cell CEACAM5 RAS AN4035 showed a superior bystander killing effect Indication Mutation AN4035 Isotype ADC Line mRNA nTPM Type compared to CEACAM5 Top1-based ADC
Slide 8: AN4035 demonstrated robust anti-tumor activity in CDX models
AN4035 demonstrated robust anti-tumor activity in CDX models HPACKRAS G12D model (PDAC, CEACAM5 mRNA 714): CTG1 ΔRTV1 (%) on Compound Dose (mg/kg) (IC50, nM) Day 25 3, single dose -78% AN4035 0.10 10, single dose -85% (1) CTG = cell-titer glow in vitro assay (2). ΔRTV = relative tumor volume; relati
Slide 9: AN4035 exhibited compelling activity in single-mouse PDX trials
AN4035 exhibited compelling activity in single-mouse PDX trials AN4035 10 mg/kg QW Indication CR PR SD PD ORR DCR CRC 1 8 2 0 82% 100% PDAC 0 6 0 1 86% 86% NSCLC 3 1 0 4 50% 50% Total 4 15 2 5 73% 81% PDX, patient-derived xenograft The response was determined by comparing tumor volume change at time
Slide 10: AN4035 demonstrated favorable PK and tolerability in monkeys
AN4035 demonstrated favorable PK and tolerability in monkeys AN4035 showed an antibody-like PK profile, comparable AN4035 achieved high exposure with good tolerability (no skin or GI to CEACAM5 mAB in mice1 toxicities) in monkey1, 2 AN4035 HNSTD has not been reached AUC AUC Compound Dose C0 (μg/mL)
Slide 11: Preclinical Summary of AN4035
Preclinical Summary of AN4035 ⚫ First-in-class CEACAM5-targeting ADC armed with a highly potent pan-RAS(ON) inhibitor payload ⚫ Favorable thermal and plasma stability with desirable pharmacokinetic properties ⚫ Strong intracellular payload retention, driving nanomolar to picomolar cytotoxicity in CE