Genmab formalises the challenge against its partner

Genmab's challenge against Johnson & Johnson's Rybrevant, mooted by the Danish company just two weeks ago, is now official: the anti-EGFR x cMet ADC PRO1286, which Genmab got through its acquisition of ProfoundBio, has entered human studies, according to the latest new listings on the clinicaltrials.gov registry.

New first-in-human trials also include two other anti-EGFR approaches, one being a degrader from BeiGene, a company keen to distance itself from its Chinese roots. There's also a new twist from Aptamer Science on hitting GPC3, a target that this year emerged as especially promising, albeit when hit with cell therapy rather than a conjugate, which is what Aptamer will try to do.

Excitement about GPC3 was driven by AbelZeta’s Car-T project C-CAR031 in liver cancer at ASCO, but other approaches haven't fared as well. Aptamer, a listed South Korean group, focuses on aptamer-drug conjugates, which use a short, artificial nucleic acid molecule – rather than an entire MAb, as typical ADCs do – bound to a linker and payload.

The anti-GPC3 project AST-201 looks like Aptamer's first into the clinic. ADCs against GPC3 haven't done well; OncologyPipeline lists Miracogen's MRG006A as the only one in clinical trials, Bristol Myers Squibb having terminated a phase 2 study of BMS-986183 some years ago.

ADC focus

For followers of novel ADCs, however, the focus will be the ProfoundBio-originated PRO1286, which Genmab now codes GEN1286, and which starts a phase 1 solid tumour trial this month.

This is relevant because J&J's Rybrevant, a naked MAb against EGFR and cMet, had been originated through a long-standing discovery alliance with Genmab. It hadn't been disclosed whether that 2012 tie-up allows Genmab to work on a competing project with the same targets (albeit using the ADC modality), but the Danish group has evidently decided that it does.

Meanwhile, degradation hasn't yielded highly promising clinical data beyond the BTK target, but BeiGene is continuing to try, having highlighted the EGFR degrader BG-60366 in its third-quarter earnings presentation. The group called this a truly differentiated mechanism "to completely abolish EGFR signalling", with broad coverage of EGFR mutations.

Now this will be tested in the clinic, with BG-60366 in December starting its first human trial; this concerns EGFR-mutant NSCLC relapsed after third-generation tyrosine kinase inhibitors, with expansion cohorts in documented EGFR resistance mutations like C797S. BeiGene recently announced plans to change its name to BeOne Medicines, with its Nasdaq ticker changing from "BGNE" to "ONC".

Companies with far clearer links to China include LaNova Medicines – the subject of last week's high-profile licensing deal with Merck & Co for a bispecific MAb – and Jiangsu Simcere. Both feature among first-in-human trial entrants, with LM-2417 and SIM0508 respectively.

The latter molecule is of special interest as it inhibits the synthetic lethality target DNA Pol theta, which has seen buy-in from Repare Therapeutics and GSK, via a deal with Ideaya, among others. A phase 1 study of SIM0508, with or without Lynparza, starts this month, but includes no hospitals beyond China.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 12 and 14 Nov 2024.