Regeneron gets another bispecific blow

Not long after an FDA rejection for odronextamab, Regeneron has been hit by a complete response letter for another key T-cell engager, linvoseltamab. As telegraphed during the group's recent earnings call, the decision was due to third-party manufacturing issues.

However, Regeneron previously couched the setback as a mere delay; a CRL seems a more serious blow to the company's bispecific ambitions. And things don’t look too rosy for some of its other bispecific MAbs either, reading between the lines of recent updates.

Linvo lag

It’s unclear when linvoseltamab might be refiled. Regeneron said during its second-quarter earnings only that the findings from an inspection – which related to another company’s candidate – had now been resolved, but that a re-inspection would be needed.

The group added that the FDA had not raised any issues relating to safety, efficacy, or the status of its ongoing confirmatory trial of linvoseltamab – likely a reference to the problems it’s had with odronextamab, which was knocked back because its confirmatory trials were still in their dose-finding stages.

Regeneron looks unlucky with the latest news, but contract manufacturing issues are cropping up throughout biopharma, raising the question of what companies can do to address them.

Whatever the reason, Regeneron has now fallen behind in both the BCMA and CD20 T-cell engager races, leaving the way clear for competitors like Johnson & Johnson, Pfizer, Roche and AbbVie.

Pipeline questions

There are also questions about some of Regeneron’s other bispecific hopefuls. A case in point is nezastomig, a project targeting PSMA and the CD28 co-stimulatory domain. Regeneron had been testing this asset alongside its anti-PD-1 MAb Libtayo, but saw two immune-mediated deaths and abandoned efforts with nezastomig and full-dose Libtayo.

Now it seems that hopes for nezastomig rest on a combination with the PSMA x CD3 project REGN4336. Regeneron said during its second-quarter call that this approach “may maintain the efficacy observed with the Libtayo combination, but may improve the safety and tolerability profile”.

In addition, the group’s EGFR x CD28 asset dalmitamig disappointed at this year’s ASCO meeting, with a Libtayo combo producing an ORR of just 6% among 51 patients with microsatellite-stable colorectal cancer in phase 1. Regeneron will have to hope for better as it enrols dose-expansion cohorts in various solid tumours including NSCLC, colorectal and head and neck cancers.

The jury is still out on harnessing co-stimulatory domains such as CD28 – an approach where Regeneron is particularly exposed.

The company has been an antibody powerhouse, but it still looks some way from becoming a bispecifics contender.

Regeneron’s notable bispecifics

Source: OncologyPipeline & company Q2 2024 presentation.