Chimerix's cancer transformation

Chimerix could be on the verge of receiving its second US approval in 12 years as a Nasdaq-listed company, closing up 10% on Tuesday's acceptance of a US filing for accelerated approval of the DRD2 antagonist dordaviprone for H3K27-mutant diffuse glioma.

Remarkably, both dordaviprone and Chimerix's first approved drug, the smallpox antiviral Tembexa, are the results of pivots the company has made in the face of setbacks. If approved dordaviprone would follow Day One's Ojemda with a label for a childhood brain cancer, and mark Chimerix's move away from its 2013 flotation as an antiviral player focused on a proprietary lipid technology.

That vision evaporated back in 2015, when Chimerix's then-lead, brincidofovir, failed in a cytomegalovirus infection study, and the group's shares crashed 80%. Chimerix then switched this molecule to smallpox, and managed to get it approved as Tembexa, though that asset was then divested to Emergent BioSolutions.

Oncoceutics

As such the stroke of genius was Chimerix's acquisition in mid-2021 of the private cancer biotech Oncocoutics, for just $39m in cash and $39m in stock.

It was Oncoceutix that brought dordaviprone, then coded ONC201. Despite some questions as to the patentability of ONC201, aired 10 years ago, this molecule is now Chimerix's lead; it and several other Oncoceutics projects effectively now comprise Chimerix's R&D pipeline.

The dordaviprone filing is based on findings from uncontrolled trials, showing a 28% overall response rate, plus median overall survival of 13.7 months in a cohort of 50 patients with recurrent H3K27-mutant diffuse midline gliomas. The standard treatment for these cancers is radiotherapy, and historical data suggest median OS of around 5 months, the company says.

Key to a successful accelerated approval is the status of a potentially confirmatory trial, and Chimerix points to the fact that its phase 3 Action study, which tests dordaviprone in the front-line setting, is substantially enrolled.

If dordaviprone is approved by its 18 August PDUFA date (the filing has priority review, and no adcom is planned) it would join Day One's Ojemda with a nod in a childhood brain cancer. Ojemda was greenlit last year for second-line BRAF-positive low-grade glioma, also on an accelerated basis, with the phase 3 Firefly-2 trial to serve as confirmation.

Ojemda too has had a far from straightforward path to approval, having been originated at least 20 years earlier, and having initially targeted a different indication. Chimerix will be hoping to add dordaviprone to the tally of biotech pivots that do end up working out.