Adlai Nortye (ANL) investor relations material

Pipeline highlights

• Lead program AN9025 is a pan-RAS inhibitor in phase I dose escalation, with completion expected in the first half of 2027.

• AN4035 is a CEACAM5-targeting ADC, aiming to selectively deliver payloads to tumors and address ADC resistance, with IND filing planned for mid-2026.

• Next-generation IO program A025, a PD-L1/LAG-3 variant, is in phase I with phase I-A completion targeted by year-end 2026.

• Both RAS programs are advancing in the US, China, and Australia, with key data releases anticipated in 2027.

• Strong cash position of $290 million provides runway through 2028, supporting ongoing development.

Scientific and clinical insights

• AN9025 demonstrates over 34-fold higher potency biochemically and up to 274-fold in vivo compared to market leaders.

• Preclinical models show comparable or better therapeutic index versus divarasib, supporting both daily and intermittent dosing strategies.

• Intermittent (weekly) dosing may widen the therapeutic window, potentially improving safety and enabling higher efficacy.

• GTP hydrolysis is not deemed critical for efficacy if the inhibitor is sufficiently potent, as shown by preserved cytotoxicity across RAS mutants.

• Data from both daily and weekly dosing arms are expected in the first half of 2027.

ADC platform and differentiation

• ADC approach (RASiCA) enables selective tumor delivery, reducing systemic toxicity and enhancing efficacy.

• ADC payloads show 44-fold enrichment in tumor cells and robust bystander killing effects.

• ADCs outperform free payloads in preclinical models, achieving higher efficacy without weight loss.

• ADCs enable rational combinations, especially with EGFR inhibitors in colorectal cancer.

• ADC and small molecule programs are viewed as complementary, not competitive, broadening therapeutic options.