AN9025 Key Features - AN9025 is a novel pan-RAS(ON) inhibitor developed by Adlai Nortye with improved potency and a favorable PK/PD profile[8, 16] - AN9025 strongly binds to cyclophilin A (CypA) with a dissociation constant (KD1) of 3.2 nM, exhibiting a 4-fold stronger binding affinity compared to RMC-6236[3, 4, 8] - AN9025 exhibits a 3- to 8-fold higher binding affinity for tri-complex formation compared to RMC-6236[5] - AN9025 demonstrates approximately 100-fold greater potency in inhibiting cell viability across RAS-mutant cell lines compared to RMC-6236[8] - AN9025 shows potent anti-proliferative activity in RAS-addicted cancer cell lines with picomolar IC50 values[7, 8] In Vivo Efficacy and PK/PD - In vivo studies show that AN9025 induces deep tumor regression, with efficacy comparable to or exceeding RMC-6236 in mouse CDX models[8, 9] - AN9025 demonstrates a favorable pharmacokinetic (PK) and pharmacodynamic (PD) profile in vivo[8] - AN9025 exhibits more sustained DUSP6 inhibition compared to RMC-6236 across all tested doses[8] Clinical Development - The prolonged tumor DUSP6 suppression following AN9025 administration suggests the potential for an intermittent dosing regimen to optimize tolerability and efficacy[8] - AN9025 is advancing through the IND-enabling stage[8] - Adlai Nortye is actively seeking strategic partnerships to advance the development of AN9025[18]

Adlai Nortye Ltd. announced topline results from its Phase III BURAN trial evaluating buparlisib (AN2025), a PI3K inhibitor, in combination with paclitaxel for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The study did not meet the primary endpoint of improving overall survival compared to paclitaxel alone. The safety profile of buparlisib was consistent with previous findings, with no new safety signals observed.Detailed results will be presented at ...