Two more companies try to outdo Rybrevant

Developing bispecifics that target EGFR and cMet, as does Johnson & Johnson’s marketed drug Rybrevant, is turning into a popular strategy, judging by recent initiations of first-in-human studies. The latest listings on clincialtrials.gov reveal two such molecules, from Jiangsu Simcere and Qilu.

While Rybrevant is a naked MAb, however, both of the new clinical assets, SIM0610 and QLS5316 respectively, use an antibody-drug conjugate modality. The moves are relevant in light of recent developments at Genmab, which has ditched its ProfoundBio-originated anti-EGFR x cMet ADC, and has a legacy interest in Rybrevant.

That apparent discontinuation, of a molecule coded GEN1286, emerged a few days ago. For Genmab the paradox of developing a potential competitor to Rybrevant continues, given the Danish company’s ownership of another asset derived from an acquisition, namely MCLA-129, a naked anti-EGFR x cMet MAb originated by Merus; still, it might only be a matter of time before this too is discontinued.

SIM0610 and QLS5316 are both China-originated ADCs that use topoisomerase 1 inhibitor payloads, and both start phase 1 this month, according to clinicaltrials.gov. They join numerous anti-EGFR x cMet ADCs already in the clinic, including AstraZeneca’s tilatamig samrotecan and BeOne’s BG-C0902.

Astra stands out for also having a naked MAb against these two targets, though this asset, FPI-2053, has yet to enter human trials. Another notable naked MAb is BioNTech’s PM1080, and that came courtesy of Biotheus. Chia Tai, meanwhile, boasts both a naked MAb and an ADC, and both assets, TQB2922 and TQB6411 respectively, are in clinical trials.

Recently disclosed first-in-human studies*

Note: *these projects were first listed on the clinicaltrials.gov database between 8 and 22 Jan 2026.

What other projects newly into the clinic are notable? One is FORX-428, a PARG inhibitor from FoRx Therapeutics, given that this has become the private Swiss company’s first clinical-stage asset.

OncologyPipeline reveals five other clinical-stage PARG inhibitors, most importantly perhaps Ideaya’s IDE161. FoRx closed a $50m series A financing round in December, and while FORX-428 actually started phase 1 last July it’s only now that its clinicaltrials.gov listing has gone live and revealed this study’s design.

Meanwhile, two other targets, FGFR2b and ATR, have delivered disappointments, the first amounting to the high-profile setback of bemarituzumab, a MAb Amgen acquired through its $1.9bn takeover of Five Prime Therapeutics; bema’s Fortitude-102 and Fortitude-101 trials last year disappointed, casting doubt on the logic of Amgen’s move.

But 3H Pharmaceuticals is undeterred, taking 3H-10000 into the clinic this month. However, 3H-10000 uses an ADC modality.

ATR inhibitors that have delivered setbacks include Astra’s ceralasertib, Repare’s camonsertib (once partnered with Roche), Bayer’s elimusertib and Merck KGaA’s berzosertib. Fosun Pharma is next to try its luck with this mechanism, having taken FXS887 into a phase 1 solid tumour trial.