Spurned by Sanofi, Orano turns to Roche

It’s a good job that Orano Med, a key player in radiotherapeutics using the isotope lead-212, isn’t entirely reliant on Sanofi as a partner, otherwise the French group’s reluctance to move forward would have hit it hard. However, Orano has in place a long-standing deal with Roche, and that tie-up looks like it’s now taking pride of place in Orano’s pipeline.

The first asset from the Roche tie-up is about to enter a human study, new listings on clinicaltrials.gov reveal. Recent entries to the registry also show imminent first-in-human trials for a highly unusual tetraspecific anti-DLL3 T-cell engager from Shangai Henlius, and for CTX-10726, an anti-PD-1 x VEGF bispecific highlighted last year by Compass Therapeutics.

There’s a lot riding on CTX-10726, which Compass has described as having anti-PD-1 activity comparable to Keytruda and superior to Akeso/Summit’s ivonescimab. Such bold claims helped Compass raise $120m from investors last August, and now they will be put to the test in a clinical trial starting in April; the group has floated the possibility of data from this coming as early as this year. 

Radiotherapeutics

The radiotherapy space was this month hit by Sanofi’s quiet deprioritisation of the lead-212-based, SSTR-targeting radioconjugate AlphaMedix, to which the group had gained rights in 2024 in a three-way tie-up with Orano and Radiomedix.

That asset hasn’t formally been discontinued, and remains the most advanced in Orano’s pipeline of radiotherapeutics using lead-212, an emitter of beta and alpha radiation. But surely its days are numbered, putting the spotlight on the first fruit of a 2012 alliance between Orano and Roche: the CEA-targeting 212Pb CEA-PRIT.

This, according to its new clinicaltrials.gov listing, will enter phase 1 in microsatellite-stable/MMR-proficient colorectal cancer at the end of March. The Roche deal has been quite low-key, but it has seen the establishment of a French research lab focused on lead-212, and was last year said to have entered its “next phase”; clinical development of 212Pb CEA-PRIT is key to that.

Recently disclosed first-in-human studies*

Note: *these projects were first listed on the clinicaltrials.gov database between 13 and 19 Feb 2026.

Elsewhere, DLL3-targeting therapeutics recently saw Zelgen take a biparatopic T-cell engager, alveltamig, into a pivotal trial in relapsed small-cell lung cancer. This hits two DLL3 domains in addition to the T-cell anchoring CD3 protein, and is meant to improve on Amgen’s approved Imdelltra.

Now Shanghai Henlius wants to go better still, with HLX3901; not only does this molecule target two DLL3 epitopes and CD3, it also hits the co-stimulatory protein CD28. The big caveat here is that co-stimulatory approaches have a poor track record, but Henlius’s move is relevant for Zymeworks, whose ZW209 is a trispecific (DLL3 x CD28 x CD3) T-cell engager in preclinical development.

First-in-human study initiations also include another T-cell engager, the CD24-targeting ONC-783, from OncoC4. CD24 is a fairly unusual target, said to be a novel immune checkpoint expressed on macrophages, and is the subject of Pheast Therapeutics’ recent phase 1 entrant, PHST001. OncoC4 is probably best known as the originator of BioNTech’s anti-CTLA-4 MAb gotistobart.