The gist of GSK's move is to follow Ono

Less than a year after Ono bought Deciphera for $2.4bn, the latter company's main competitor, privately held IDRx, has been acquired for $1bn by GSK. The reason for both moves is KIT inhibitors for treating gastrointestinal stromal tumours (GISTs): here Deciphera developed Qinlock, and IDRx is working on IDRX-42, a molecule that appears to be more promising.

The move sees GSK taking another step back into oncology, after deals with the likes of DualityBio, Hansoh, iTeos, Ideaya, Sierra and Tesaro. For IDRx this is an especially positive outcome, the biotech having been founded just four years ago, and having apparently raised only $122m and $120m from venture capitalists in respective series A and B rounds.

The trigger looks to have been data IDRx presented at last November's Connective Tissue Oncology Society meeting, where the Strategist-1 study of IDRX-42 showed a 20% response rate among 10 fourth-line or later GIST patients given the recommended dose. Qinlock is approved in this setting, and the corresponding number on its label is 9%.

Early use

However, IDRx already made it clear that it was gunning for earlier use, citing a 46% response rate in second-line GIST patients – a setting in which Qinlock's Intrigue study failed. The cross-trial comparator here is Sutent (18% ORR), and IDRx earlier revealed plans to start a phase 3 in second-line GISTs, using Sutent as control.

If this weren't enough, IDRx also started enrolling patients into a first-line cohort of Strategist-1. A third KIT inhibitor competing for the GIST market is Blueprint's Ayvakit, but importantly this secured approval only in a small population, namely in patients with PDGFRA exon 18 mutations, including PDGFRA D842V.

Cross-trial comparison in GIST

Source: Qinlock prescribing information & CTOS 2024 presentation.

In addition to the $1bn GSK is paying up front, the takeover includes a small future milestone fee, $150m, relating to regulatory approval. GSK is also taking on responsibility for royalties owed to Merck KGaA, the originator of IDRX-42, from which IDRx licensed this molecule in 2022.

At the same time IDRx also licensed another project, the follow-on KIT inhibitor IDRX-73 (BLU-654), from Blueprint; this molecule targets KIT exon 13 mutations. The deal involved up to 15% of IDRx's series A preferred stock, up to $217.5m in milestones, and royalties.

However, IDRX-73 no longer appears in IDRx's pipeline, having presumably been dropped once IDRx saw the potential for broad GIST treatment with IDRX-42 rather than targeting mutation-specific niches. Nevertheless, Blueprint should benefit from the GSK acquisition by virtue of its equity stake in IDRx.

Blueprint's own development path for Ayvakit has shifted to indolent systemic mastocytosis, which has proved to be a far more lucrative indication than mutant GIST. This space includes another KIT inhibitor, Cogent's D816V-specific bezuclastinib (acquired from Daiichi Sankyo), and it's not clear whether pursuing this indication might now be of interest to GSK.

Securing a lucrative buyout at such an early stage marks a success for IDRx management after an earlier setback: the company's chief executive, Tim Clackson, finance chief Brad Dahms and chief medical officer David Kerstein all held the same roles at the small-molecule player Theseus, which discontinued its GIST project THE-630 and was sold to Concentra Biosciences for its cash balance.