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]

Group 1 - 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) [1] - The study did not meet the primary endpoint of improving overall survival compared to paclitaxel alone [1] - The safety profile of buparlisib was consistent with previous findings, with no new safety signals observed [1] Group 2 - Detailed results from the Phase III trial will be presented at an upcoming medical conference [2] - AN8025 is a next-generation tri-specific antibody fusion protein derived from an approved PD-L1 antibody, optimized for PD-1-based immunotherapy [2] - Preclinical studies have demonstrated that AN8025 enhances both the quantity and quality of antigen-presenting cells (APCs) while inducing robust PD-L1-dependent T cell activation and anti-tumor efficacy in vivo [3] Group 3 - The company plans to submit the IND application for AN8025 in mid-2025 [3] - AN9025 is an in-house developed oral small molecule pan-RAS(ON) inhibitor designed to target a broad spectrum of RAS mutations across various tumor types [3] - Preclinical studies have shown that AN9025 effectively inhibits RAS-mutant cancers, including pancreatic, lung, and colorectal adenocarcinomas, with potent and durable efficacy [4] Group 4 - The company plans to submit an IND application for AN9025 in the second half of 2025 [4] - AN4005 is an orally available small-molecule PD-L1 inhibitor that demonstrates antitumor activity by blocking PD-1/PD-L1 interaction [4] - Preliminary results from the Dose-Escalation Phase presented at SITC 2024 demonstrated that AN4005 exhibits favorable safety and tolerability in patients with advanced tumors [5]