Sanofi has teamed up with Exscientia to discover and develop bispecific small molecules that treat diabetes and its comorbidities. The agreement will see Sanofi hand over up to €250 million ($274 million) in return for small molecules designed to hit two targets involved in glucose control, NASH, weight management and other areas relevant to diabetics.
Exscientia’s role is to identify pairs of targets and generate bispecific small molecules against them. These drugs will have properties similar to those of typical small molecules—weight of under 500 daltons, suitable for oral delivery—but be designed to hit two different targets. The potential of such a dual-pronged attack is said to have turned heads at Sanofi.
“What they were excited by was the possibility of really being creative about the target product profile,” Exscientia CEO Andrew Hopkins, D.Phil., said.
Some of the drugs could hit two targets in the same pathway to trigger a synergistic effect. Others could go after targets associated with distinct pathways to help diabetics manage two aspects of their health. Hopkins gave the example of a drug that controls glucose levels while also helping the patient to manage their weight to show the potential of the approach. The range of conditions common to diabetics means many other such combinations are theoretically possible.
Sanofi will provide research funding, up to €250 million in milestones and royalties as the drug candidates advance. The Big Pharma is putting up the cash in a bid to unearth small molecules that stand out in the congested diabetes space and in doing so deliver drugs that improve outcomes and reduce the pill burden on patients.
The partners will work together at the discovery stage, with Exscientia handling compound design and Sanofi providing chemical synthesis support. Sanofi will then take full control of candidates that are promising enough to push forward, handling further assays, preclinical development and clinical trials solo.
The work is made possible by the algorithms Exscientia has created and the drug hunters it has brought on board to build on their output. In the case of the Sanofi deal, the research process entailed listing targets relevant to diabetes and associated conditions. Having identified around 45 individual targets, Exscientia and Sanofi had close to 1,000 possible pairs. Exscientia then used its technology to filter out the many combinations that are chemically intractable.
“The algorithm is actually designing novel molecules,” Hopkins said. “This is the big difference between the platform Exscientia has been developing and many previous computational chemistry approaches.”
Earlier attempts to apply algorithms to drug discovery typically limited themselves to screening databases of existing drugs for hits against targets or providing support to drug designers. Exscientia’s goal is to have a platform that explores the chemical space and proposes molecules, beyond which humans step in to assess the robustness and drug-like properties of the candidates. The chief chemist overseeing this second stage of the process at Exscientia is Andy Bell, co-inventor of Pfizer’s Viagra.
Exscientia and Sanofi are now moving molecules discovered by the platform into the experimental phase. And, with an earlier CNS collaboration with Sumitomo Dainippon on the cusp of moving a bispecific small molecule into the clinic, Exscientia has decided to to break cover after a low-profile first four years of existence. Having done so, Exscientia is looking to keep itself in the limelight.
“This is the first of several deals which we're announcing this year,” Hopkins said.
The deals will allow Exscientia to apply its technology to a wider range of therapeutic areas than its internal operation can handle. Exscientia is focusing its own pipeline on immuno-oncology, notably through a collaboration with Evotec that gives it access to the medicinal chemistry capabilities of the Toulouse, France, site the CRO picked up from Sanofi. As the platform is applicable outside of this niche, Exscientia plans to partner to apply it to other therapeutic areas.