Adlai Nortye (ANL) Investor Presentation summary

Background and scientific rationale

• RAS mutations are implicated in about 30% of human cancers, especially pancreatic, lung, and colorectal types, representing a major unmet need.

• Pan-RAS (ON) inhibitors like RMC-6236 act by forming a tri-complex with cyclophilin A and RAS (ON) protein, inhibiting downstream signaling.

• AN9025 is a novel, orally bioavailable pan-RAS (ON) inhibitor with improved potency and pharmacokinetic/pharmacodynamic (PK/PD) profile.

Preclinical efficacy and mechanism of action

• AN9025 shows 3- to 8-fold higher tri-complex binding affinity and 1.5- to 2-fold greater maximum response than RMC-6236.

• Demonstrates approximately 100-fold greater potency in inhibiting viability of RAS-mutant cancer cell lines compared to RMC-6236.

• Exhibits a similar RAS-mutant sensitivity pattern as RMC-6236, with highest activity against G12X mutations.

• Achieves potent anti-tumor activity and tumor regression in multiple xenograft models with RAS mutations.

• Shows more sustained DUSP6 inhibition and tumor suppression after drug withdrawal compared to RMC-6236.

Pharmacokinetics, tolerability, and development status

• AN9025 binds cyclophilin A with a 4-fold stronger affinity and slower dissociation rate than RMC-6236.

• Demonstrates favorable PK/PD and tolerability in vivo, supporting potential for intermittent dosing.

• Induces deep tumor regression, with efficacy comparable to or exceeding RMC-6236 in mouse models.

• Currently advancing through IND-enabling studies and seeking strategic partnerships for further development.