Sanofi, BioNTech cull mRNA clinical cytokine cancer candidate based on early data

Sanofi and BioNTech’s vision of using mRNA to prime anti-cancer immune attacks has failed to hold up to clinical scrutiny. After running an interim analysis of early-phase data, the partners have jointly decided (PDF) to scrap development of the candidate as an intratumoral therapy.

The candidate, also known as BNT131, is made of four mRNAs that encode for IL-12sc, IL-15sushi, IFN-α and GM-CSF. By expressing the cytokines in the tumor microenvironment, the partners aimed to help the immune system to recognize and attack cancer cells. The mechanism is theoretically complementary to checkpoint inhibitors, and that cocktail improved survival and tumor regression in mice. 

Buoyed by the preclinical data, Sanofi and BioNTech began a phase 1 trial of SAR441000 as a single agent and in combination with Libtayo, a PD-1 checkpoint inhibitor that the French drugmaker developed with Regeneron. The partners shared interim data on 17 solid tumor patients in 2020.

The results were strong enough to encourage BioNTech and Sanofi to enroll 77 patients in the study. Yet, one year after passing the primary completion date, the partners’ enthusiasm for the mRNA program has waned. BioNTech and Sanofi jointly terminated development of the intratumoral candidate based on the clinical results seen so far. 

Sanofi removed another candidate from its phase 1 pipeline between its first and second quarter results. The asset, SP0274, is a mRNA vaccine for respiratory syncytial virus (RSV) in older adults. Sanofi no longer includes SP0274 on its phase 1 pipeline but it has added SP0256, another mRNA vaccine for RSV in older adults, to the list of early-phase programs. 

The switch comes weeks after Sanofi made SP0256 a focus of its vaccine investor event. At the event, the drugmaker presented phase 1/2 data that, in its view, position SP0256 as the backbone of a combination respiratory vaccine that protects against RSV, human metapneumovirus and parainfluenza virus. Sanofi plans (PDF) to start a phase 2b trial and a phase 1/2 combination trial this year.