China-based Haisco Pharmaceutical Group Co., Ltd (SHE: 002653) has announced that it has received clinical trial approval from the National Medical Products Administration (NMPA) for its oral small molecule EGFR-PROTAC, HSK40118. The drug is targeted for the treatment of advanced non-small cell lung cancer (NSCLC).
Drug Mechanism and Pre-Clinical Results
HSK40118 is a Category 1 drug and a proteolysis-targeting chimeric (PROTAC) small-molecule inhibitor that targets the EGFR protein. It recruits the ligand of E3 ubiquitin ligase, while a linker connects the two parts. Pre-clinical studies have shown that HSK40118 has good inhibition and degradation activity on mutant EGFR protein and excellent selectivity for wild-type EGFR.
Potential Impact on Drug Resistance
Additionally, HSK40118 has demonstrated a significant inhibitory effect on the growth of EGFR L858R-T790M double mutation and ex19del (or L858R) – T790M-C797S triple mutation in vivo. This suggests that HSK40118 is effective against the acquired drug resistance mutation induced by the third generation of EGFR TKI, and is expected to delay or even overcome the problem of EGFR drug resistance mutation caused by long-term use of EGFR TKI.
Market and Development Context
There is currently no similar product marketed anywhere in the world, while some fourth-generation EGFR TKI targeting the EGFR C797S mutation are in the early stages of clinical development. HSK40118’s approval for clinical trials highlights Haisco Pharmaceutical’s commitment to innovation and addressing unmet needs in lung cancer treatment.-Fineline Info & Tech
