The SHP2 ship sails

The quiet termination of a licensing deal between Roche and Relay Therapeutics leaves Bristol Myers Squibb and Pfizer as perhaps the only remaining western developers of SHP2 inhibitors. Roche’s decision – Relay revealed the termination of the deal, covering the SHP2 inhibitor migoprotafib, in a low-key SEC filing yesterday – follows AbbVie’s ending of two Jacobio-derived SHP2 inhibitors, the scrapping of Erasca’s similarly acting project ERAS-601, and several other discontinuations. Such moves have followed clinical setbacks, as the SHP2 mechanism failed to live up to its initial promise as a combination partner for KRAS inhibition. In the case of migoprotafib no clinical data were ever published, though technically three combo trials remain ongoing. Though the Relay/Roche tie-up was one of several in SHP2 inhibition the deals’ relatively cautious financial terms suggested that this mechanism was always seen as a long shot. Bristol came to this party relatively late, paying $90m in 2022 for rights to BridgeBio’s BBP-398 (now coded BMS-986466), and while this deal remains listed in Bristol’s pipeline several trials of this molecule have been terminated. The SHP2 inhibitor pipelineProjectCompanyStatusNoteStill in development...BR790Shanghai Blueray BiopharmaPh1/2 tislelizumab combo–BMS-986466/ BBP-398Bristol Myers Squibb/ BridgeBioPh1 Opdivo combo in NSCLCMay 2022 deal, $90m up front; several other trials terminated on CT.govHMPL-415/ HMPL-415S1HutchmedPh1 in solid tumours–PF-07284892/ ARRY-558Pfizer (ex Array)Ph1 combo study in solid tumours–ET0038Etern TherapeuticsPh1 in solid tumours–HS-10381Jiangsu Hansoh PharmaceuticalPh1 in solid tumours–ICP-189InnoCare PharmaPh1 PD-1 MAb combo, not yet recruiting–BPI-442096Xcovery/ BettaPh1 IND accepted 2022, not yet recruitingLong-standing deal covering various projects...and those with setbacksJAB-3312Jacobio PharmaceuticalsPh3 starting in NSCLC in Q3 2024Feb 2020 deal with AbbVie, $45m up front, terminated Jul 2023Migoprotafib (GDC-1971/ RLY-1971)RelayPh1 Tecentriq combo in solid tumours ongoingDec 2020 deal with Roche, $75m up front, terminated Jul 2024JAB-3068Jacobio PharmaceuticalsDiscontinued in ph1/2Feb 2020 deal with AbbVie, $45m up front, terminated Jul 2023RMC-4630/ SAR442720Revolution MedicinesDiscontinued in ph2Jul 2018 deal with Sanofi, $50m up front, terminated Dec 2022ERAS-601ErascaDiscontinued in ph1Feb 2020 deal with NiKang, $12m up frontTNO155NovartisDiscontinued in ph1Some trials still ongoing, but Novartis says filing is no longer plannedSource: OncologyPipeline.