RemeGen cools on DR5
A pipeline update reveals the dropping of RC248, after cMet and Claudin18.2 ADCs disappeared earlier.
A pipeline update reveals the dropping of RC248, after cMet and Claudin18.2 ADCs disappeared earlier.
China's RemeGen has left the way slightly clearer for Inhibrx, one of the few biotechs still active in DR5 blockade, by deprioritising its own shot at this mechanism. The RemeGen molecule in question, RC248, was also notable for being the only anti-DR5 project to use an antibody-drug conjugate modality.
RC248's only clinical trial is investigator-initiated, in DR5-positive lung cancer, and the fact RemeGen never sponsored a study suggests that the company had been lukewarm on this asset. Not so two other ADCs on which RemeGen has gone quiet; the anti-cMet RC108 and the anti-Claudin18.2 RC118 were in a combined seven company-sponsored trials before dropping off RemeGen's R&D pipeline.
RemeGen last mentioned RC248 in its nine-month report in October, but by the time it published its 2024 annual report last month the project was missing. The company didn't respond to a request to confirm whether these projects were indeed discontinued, but their removal from the pipeline suggests at best that they are no longer a priority.
DR5 difficulty
It has proved difficult to turn DR5 into a viable oncology target, and the approach has seen discontinuations of projects from Genmab, Roche and others.
However, at ASCO-GI Inhibrx saw some promise in a small study of ozekibart, a tetravalent MAb that remains its lead pipeline asset. Among other competitors, the status of Innovent's IBI3004 is unclear; IBI3004 has never appeared in an Innovent pipeline listing, but it entered phase 1/2 last August, and the NCI later disclosed it as being an anti-CEA/anti-DR5 bispecific MAb.
No longer in RemeGen’s R&D pipeline
| Project | Mechanism | Studies |
|---|---|---|
| RC108 | cMet ADC | Ph1/2 furmonertinib combo +/- toripalimab in EGFR+ve, cMet+ve post-EGFRi NSCLC |
| Ph2 in cMet+ve solid tumours | ||
| Ph1/2 toripalimab combo in cMet+ve solid tumours (CTR20232828) | ||
| Ph1 in solid tumours | ||
| Ciletatug vedotin (RC118) | Claudin18.2 | Ph1/2 toripalimab combo in solid tumours |
| Ph1/2 monotherapy in solid tumours | ||
| Ph1 in solid tumours completed | ||
| RC248/ Oba01 | DR5 ADC | Ph1 investigator-sponsored trial in DR5+ve relapsed NSCLC |
Source: OncologyPipeline.
Meanwhile, the anti-Claudin18.2 ADC RC118 last appeared in a RemeGen pipeline listing a year ago, but by August it too was gone. This is despite the fact that in the meantime RemeGen applied for and received an INN for this molecule: ciletatug vedotin.
In mid-2023 the company announced a clinical trial collaboration to study RC118 in combination with Shanghai Junshi's toripalimab, and technically this continues, as does a phase 1/2 monotherapy study. Though at last year's ESMO RC118 was said to have shown promising efficacy and safety in its first-in-human trial, RemeGen's cooling on it might not be a complete surprise given how crowded the field of Claudin18.2-directed ADCs has become.
RemeGen also started two toripalimab combo trials of the anti-cMet ADC RC108, but hasn't mentioned this asset for some time. Two phase 1/2 studies are still marked on clinicaltrials.gov as recruiting patients.
Industry approaches to targeting cancers expressing wild-type cMet feature, most prominently, AbbVie, which has two late-stage ADCs: the first-generation telisotuzumab vedotin is awaiting an imminent FDA verdict on its approvability (the precise PDUFA date hasn't been disclosed), while the next-generation telisotuzumab adizutecan recently started phase 3.
However, this space has increasingly become the domain of bispecifics, most notably Johnson & Johnson's anti-EGFR x cMet MAb Rybrevant, and not long ago Regeneron discontinued a cMet x cMet bispecific ADC, REGN5093-M114, in favour of a separate biparatopic project, davutamig.
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