BioNTech swiftly axes oral mRNA vaccine project after tech flunks early test

BioNTech has swiftly rejected an oral mRNA delivery technology. Barely one year after signing up to work with Matinas BioPharma, BioNTech found an initial mouse study failed to show preclinical activity—leading it to join Gilead Sciences on the list of companies to dump the biotech in recent months.

In April 2022, Matinas revealed BioNTech had paid $2.75 million for exclusive use of a lipid nanocrystal (LNC) platform in the delivery of mRNA vaccines. BioNTech agreed to fund Matinas’ research related to the collaboration, which covered formulation, optimization and in vitro testing, and entered into talks about a potential licensing agreement. 

The collaboration made it as far as a study in mice. Thursday, Matinas revealed that the study of the oral mRNA candidate failed to show activity. With the single study now over, BioNTech and Matinas have ended their collaboration.

Matinas’ summary of the collaboration offers insights into the challenges of delivering mRNA orally. The April 2022 statement about the deal said the collaboration would “evaluate the combination of mRNA formats and Matinas’ proprietary LNC platform technology.” However, the mouse study tested a non-LNC formulation of a BioNTech-supplied reporter mRNA.

As Matinas explained, it developed a “nano-formulation, distinct from traditional LNCs” to cope with the “physical complexity and biological fragility of mRNA.” The formulation worked in vitro, Matinas said, “and because of the timelines required under the BioNTech collaboration was brought forward for oral in vivo evaluation.”

While BioNTech is walking away, Matinas made the case that its approach may work, stating that internal in vivo studies of similar non-LNC mRNA formulations “showed activity when administered systemically.” The formulations are stable for at least 17 weeks at 4 degrees Celsius, suggesting they may be easier to ship and store than existing mRNA vaccines based on lipid nanoparticles.

The conclusion of the BioNTech deal comes five months after Gilead pulled out of a deal with Matinas to develop an oral COVID-19 antiviral to focus on its internal candidate. Roche's Genentech unit recently extended its alliance with Matinas for another year, although, with the biotech completing its obligations related to a third and final molecule in the first quarter, the longer-term prospects remain uncertain.