SHANGHAI FOSUN PHARMACEUTICAL (GROUP) CO., LTD. Insilico Medicine ("Insilico"), an end-to-end artificial intelligence (AI)-driven drug discovery and development company, announced that it has used its proprietary AI platform to nominate a preclinical candidate compound (PCC) for innovative cancer immunotherapy for its QPCTL program. Notably, this is the first major milestone achieved by Insilico in the strategic collaboration with Fosun Pharma. Insilico Medicine and Fosun Pharma are working together on IND-enabling studies to advance PCCs in the QPCTL program to clinical trials.
ISM004-1057D, Insilico's first PCC for its QPCTL program, is a potential first-in-class small molecule inhibitor that targets QPCTL. QPCTL is responsible for CD47 pyroglutamate formation, which is the modification essential for the interaction of CD47 with its ligand SIRPa. CD47, a cell surface protein over-expressed in a wide variety of cancers, provides a "don't eat me" signal to protect tumor cells from innate immune system surveillance by interacting with SIRPa on the surface of immune cells.
The small molecule inhibitors of QPCTL mimic the therapeutic effect of CD47 antibodies by attacking tumor cells via blockage of this "don't eat me" signal. In completed in vivo preclinical studies, ISM004-1057D showed anti-tumor activity in both liquid and solid tumors and demonstrated favorable pharmacokinetics and an acceptable safety profile. As a small molecule inhibitor of QPCTL, ISM004-1057D not only provides high tumor penetration but also reduces potential hematologic and antigen sink side effects.
Due to the broad expression of CD47 beyond tumor cells, antigen sink is commonly caused by treatment with most of the current CD47 antibodies. Insilico leveraged its end-to-end Pharma.AI platform including target identification engine PandaOmics and small molecule generation engine Chemistry42 to develop the target hypothesis for oncology and design compounds with good drug-like properties, respectively. After synthesizing and testing 71 compounds, Insilico nominated a PCC within 9 months of project initiation.
