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Relay passes on the lirafugratinib baton

The US subsidiary of South Korea’s HLB will take on the selective FGFR2 inhibitor.

Relay Therapeutics had already signalled its desire to divest the FGFR2 inhibitor lirafugratinib, but the just revealed choice of partner might raise eyebrows. Elevar Therapeutics, the US arm of the South Korean biotech HLB, is taking the project off Relay’s hands in a deal worth $75m in up-front payments and regulatory milestones.

Elevar, which gains worldwide rights, will now have to navigate an FDA filing that has shifted from cholangiocarcinoma to a broad tumour-agnostic approach, and back to cholangiocarcinoma again. Relay, meanwhile, will be able to focus on its PI3Kα inhibitor RLY-2608, which has shown promise in breast cancer.

More selective

Two FGFR inhibitors, Incyte’s Pemazyre and Taiho’s Lytgobi, have US accelerated approvals for cholangiocarcinoma, but are associated with high levels of toxicity, specifically ocular issues and hyperphosphataemia.

It’s thought that these adverse events are associated with hitting the 1 and 4 receptor subtypes, and that they could be avoided with more selective compounds like lirafugratinib. So far, that seems to have been borne out with data on the Relay project.

Still, lirafugratinib’s path to approval has been tortuous. Relay had originally been targeting cholangiocarcinoma, before switching to a tumour-agnostic approach around a year ago.

But this September the group disclosed that the FDA had suggested first filing for cholangiocarcinoma, followed by a tumour-agnostic supplemental NDA for FGFR2-altered solid tumours, using data from more patients. This is the path that Elevar will now presumably take. 

An analysis of OncologyPipeline shows that lirafugratinib is ahead in the selective FGFR inhibitor race, but several groups are also trying to avoid FGFR4; notably Tyra Biosciences' TYRA-200 is in phase 1. That group has already impressed with an FGFR3-specific project, TYRA-300, in bladder cancer.

Meanwhile Elevar has, until now, been focused on the VEGFR-2 inhibitor rivoceranib, which is awaiting an FDA approval decision by March 2025, alongside the PD-1 blocker camrelizumab; the combo was knocked back last May over manufacturing and inspection site issues.

 

FGFR inhibitors in cholangiocarcinoma

ProjectDescriptionCompanyStatus
Pemazyre (pemigatinib)FGFR inhibitorIncyteAccelerated approval 2020 for 2nd-line, FGFR2 fusion cholangiocarcinoma
Lytgobi (futibatinib)FGFR inhibitorTaihoAccelerated approval 2022 for 2nd-line, FGFR2 fusion cholangiocarcinoma
Truseltiq (infigratinib)FGFR inhibitorBridgeBio/Helsinn (ex Novartis)Accelerated approval 2021 for 2nd-line, FGFR2 fusion cholangiocarcinoma; withdrawn 2024
Tasfygo (tasurgratinib)FGFR inhibitorEisaiApproved in Japan 2024 for 2nd-line, FGFR2 fusion cholangiocarcinoma
LirafugratinibFGFR2 inhibitorElevar (ex Relay)Ph2 Refocus; NDA planned for accelerated approval in cholangiocarcinoma, then FGFR2-altered tumours
HMPL-453FGFR1/2/3 inhibitorHutchmedChina ph2 completes Jun 2025
3D185FGFR1/2/3 inhibitor3D MedicinesChina ph2 completes Dec 2025
GunagratinibPan-FGFR inhibitorInnoCareChina ph2 completes May 2026
TYRA-200FGFR1/2/3 inhibitorTyraPh1 Surf-201 completes Sep 2026

Source: OncologyPipeline.