Partnership Uses AI to Identify Compound That Could Block Cancer’s ‘Don’t Eat Me’ Signal

PRESS RELEASE — Insilico Medicine, an end-to-end artificial intelligence (AI)-driven drug discovery and development company, said it used 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.

Using AI, the process — from announcing the collaboration to nominating a preclinical compound — took less than 40 days, according to leadership.

ISM004-1057D, Insilico’s first preclinical candidate compound 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 SIRPα. 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 SIRPα 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.

“Innovation has always been the core driving force of Fosun Pharma. We believe that innovative AI platform technology has the potential to improve the efficiency of discovery and development of new medicines, providing strong support for pharmaceutical innovation,” said Dr. Aimin Hui, Executive President, President of Global R&D Center, Chief Medical Officer of Fosun Pharma. “We believe that both Fosun Pharma and Insilico will make persistent efforts that may enable us to leverage advantages in technology and clinical development from each side to benefit more patients worldwide.”

“It has been a phenomenal experience working together with Fosun Pharma to so efficiently achieve the PCC nomination milestone for the QPCTL program,” said Feng Ren, Ph.D., CSO of Insilico. “During the collaboration, we have been hugely impressed by the Fosun team’s professionalism as well as their expertise in both science and project management. We are committed to working closely together to potentially progress the PCC into clinical trials.”

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.

“The world needs innovative and effective first-in-class therapeutics. In this QPCTL collaboration with Fosun Pharma, we believe we are setting records in speed and novelty with AI. I am delighted that in less than 40 days since our collaboration announcement, we managed to nominate a preclinical candidate and start IND-enabling studies for the QPCTL program. We are committed to our goal of bringing speed, quality and innovation to all our drug discovery programs and moving them into clinical development as fast as we can” said Alex Zhavoronkov, Ph.D., CEO of Insilico Medicine.

Insilico announced its strategic collaboration with Fosun Pharma in January 2022, which combines Insilico’s end-to-end AI-driven drug discovery platforms and Fosun Pharma’s clinical development and commercial expertise, to discover and develop a portfolio of novel therapeutics. Insilico is working to advance ISM004-1057D to the IND stage, and if it is achieved, Fosun Pharma would be responsible for conducting clinical trials. Both parties will share commercialization profits from the QPCTL program.