Daiichi finds line of attack on once-undruggable CNS target by penning $182M Confo collaboration

Daiichi finds line of attack on once-undruggable CNS target by penning $182M Confo collaboration

Confo Therapeutics’ business development team is on a roll. Weeks after licensing its lead candidate to Eli Lilly, the Belgian biotech has landed a 168 million euro ($182 million) deal with Daiichi Sankyo to discover small molecule agonists of a central nervous system (CNS) target.

Daiichi has committed the cash, in an undisclosed mix of upfront and milestone payments, to get Confo to apply its platform to “a previously undruggable G-protein coupled receptor (GPCR) target in an area of high unmet medical need.” The project is expected to generate a series of small-molecule compounds that Daiichi will have an exclusive option to license globally and take into the clinic.

Confo, part of the Fierce 15 class of 2019, landed the deal on the strength of technology for stabilizing GPCRs. The membrane receptors are flexible proteins that function through conformational changes to transmit a signal inside the cell. The shape shifting makes GPCRs hard to isolate and find hits for using biophysical methods.

While a significant minority of drugs on the market target GPCRs, most of the membrane proteins are yet to be drugged. The upshot is that the industry is yet to develop drugs against targets that are thought or known to play a role in diseases with major unmet needs.

Brute force can help overcome the challenges, with companies sometimes able to find hits by exposing GPCRs to large compound libraries during high-throughput screening, but Confo has tried to develop a more reliable method that is less prone to delivering false positives.

Using VHH fragments, the technology that turned Ablynx into a 3.9 billion euro biotech, Confo stabilizes GPCRs in their active state. Once the proteins are stabilized, Confo uses biophysical, competition and biosensor-type screening assays to generate hits. The model allows the biotech to find hits using a library of small-molecule fragments that is far smaller than those used in alternative approaches to GPCRs.

Attracted by the platform, Regeneron signed up to collaborate with Confo in 2021. The Belgian biotech took its lead candidate, neuropathic pain prospect CFTX-1554, into the clinic the following year. At the start of March, Lilly struck a deal to license CFTX-1554 and associated backup compounds for $40 million upfront and up to $590 million in milestones. Confo last publicly disclosed a financing round in 2019.

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