Lilly shines light on protein-protein interaction, inking backloaded $660M Prism drug discovery pact

Eli Lilly has joined Prism BioLab’s stable of Big Pharma partners, striking a deal worth up to $660 million to collaborate on the discovery of oral inhibitors of protein-protein interaction (PPI) targets.

Prism, a Japanese biotech specializing in PPI targets, has landed deals with Boehringer Ingelheim, Merck KGaA and Roche in recent years. In those deals, Prism, which raised an Eisai-backed 1.4 billion yen ($9.5 million) series C round in 2021, provided its library of peptide mimetic small molecules for screening against its partners’ targets in exchange for upfront and success-based payments of undisclosed size. 

Working with Lilly, Prism will use its PepMetics technology to discover small molecule inhibitors of a PPI target selected by its partner. Lilly has the option to add up to two more PPI targets to the deal, which features an upfront fee and up to $660 million in milestones. 

The PepMetics technology underpinning the deal is a method for quickly synthesizing peptide mimetic molecules. Working with a library of side chains and scaffolds, Prism creates fragments that it combines to form intermediates and ultimately PepMetics molecules. The method enables the generation of large numbers of molecules for screening against drug targets. 

A drug candidate co-created by Prism and Eisai, dubbed E7386, is in phase 1/2 development in solid tumors. The molecule is designed to inhibit interactions between β-catenin, a protein deemed “undruggable,” and CBP to suppress tumor growth dependent on Wnt signaling. The phase 1/2 trial is testing the idea that the oral candidate may enhance the effect of a checkpoint inhibitor, namely Merck & Co.’s Keytruda. 

PPI dysfunction is implicated in a wide range of diseases but only a tiny fraction of the interactions are targeted by approved drugs, largely because identification of drug-like molecules capable of disrupting the proteins has proven challenging. Prism’s technology represents an attempt to overcome the barriers to PPI inhibition—and a bid to unlock the potential of a mostly untapped area of biology.