Plexxikon

Plexxikon was founded in 2001 by Joseph Schlessinger of Yale and Sung-Hou Kim of Berkeley — two academic structural biologists whose premise was that the crystallographic methods on which their careers had been built could be turned into an industrial engine for small-molecule drug discovery. From offices in South San Francisco, the firm developed Scaffold-Based Drug Discovery, a structure-first pipeline that produced two FDA-approved oncology therapies over the twenty years the company was in operation. Plexxikon was acquired by Daiichi Sankyo in April 2011 for approximately $935 million; the Japanese parent wound down Plexxikon’s offices on 31 March 2022 as part of a shift in its oncology strategy.

The firm designed small-molecule kinase inhibitors for oncology and inflammation, working from a proprietary drug-discovery platform that used high-throughput crystallographic screening to identify promising chemical scaffolds and then optimise them into drug candidates. Two of its molecules received FDA approval: Zelboraf (vemurafenib), a BRAF inhibitor approved in 2011 for BRAF V600E-mutant melanoma, and Turalio (pexidartinib), a CSF1R inhibitor approved in 2019 for tenosynovial giant-cell tumour. Zelboraf, in particular, is often cited as one of the earliest clinical demonstrations of precision oncology, in which a patient’s tumour is genotyped and matched to a targeted therapy.

Among the drug-discovery firms of its era, Plexxikon was notable for two things: the structural-biology depth of its founding team, and the frequency with which its molecules reached approval. Joseph Schlessinger had been a foundational figure in signal-transduction biology since the 1970s; Sung-Hou Kim brought a parallel career in crystallography from Berkeley. That combined pedigree produced an unusually high hit rate for a firm of its size — two FDA approvals in twenty years, one of them the BRAF inhibitor Zelboraf, which was approved in 2011 alongside a companion diagnostic in one of the first such regulatory pairings in oncology.