A rush of activity in vaccines to protect against COVID-19 has brought with it renewed enthusiasm for mRNA as a therapeutic modality- though the real test will be if the therapeutics can hold their own without the urgent enthusiasm supplied by a global pandemic.
While FDA review of non-pandemic treatments is a major uncertainty for the biopharma sector, those directed against SARS-CoV-2 are progressing into clinical development at a record pace. That includes a candidate vaccine from Moderna Therapeutics that this week began dosing in an NIH-sponsored trial in healthy patients. The rapid progress of the candidate includes just 42 days between identification of the SARS-CoV-2 sequence and delivery of its drug candidate to the NIH, and 38 days between manufacture of a clinical batch of mRNA-1273 and patient dosing.
In fact, the coronavirus pandemic has been the time to shine for mRNA drug development, given the uniquely rapid turnaround time for the modality. In addition to Moderna, CureVac and BioNTech have been churning through their own vaccine candidates; BioNTech said on March 16 that it had partnered with Fosun Pharmaceutical to develop a SARS-CoV-2 vaccine that it expects in the clinic in late April.
That news followed a disclosure from Pfizer that the pharma was also on the board the mRNA train, saying it had partnered with BioNTech "on a potential mRNA coronavirus vaccine."
CureVac, meanwhile, had apparently drummed up enough enthusiasm for its mRNA vaccines that it became entangled in global tug-of-war for access to its hypothetical medicines, with Germany and the US apparently at odds over the latter's desire to secure exclusive access to the company's pipeline.
The bigger picture
There have never been so many cheerleaders for mRNA-based therapies, which could have knock-on effects to support programmes across the spectrum of mRNA-encoded protein therapies- should the current candidates show signs of life in the clinic. Moderna says that the NIH-sponsored trial of mRNA-1273 will follow safety and reactogenicity in healthy patients for 12 months, while a Moderna-sponsored Phase II study "could begin in a few months."
Evercore ISI's Umer Raffat speculates that immunogenicity data could be available from the Phase I trial in June.
Moderna has been the poster child for the mRNA movement in recent history, seeking to restore optimism for the modality in the face of known difficulties around delivery of the oligonucleotides and management of immunogenic reactions. Outside of the current coronavirus vaccine push, it has shown preliminary de-risking data for its programmes in cytomegalovirus (CMV) and chikungunya vaccination- results that Raffat notes helped to inform the design of the current Phase I trial.
But despite the multi-billion potential that Moderna attaches to its vaccine platform, analysts tend to be more excited about other aspects of the pipeline at mRNA players like Moderna, BioNTech, or CureVac- namely, the perpetual money maker that is oncology. BioNTech and CureVac are each advancing mRNA candidates as neoantigen therapies, along with a diverse array of antibody and cytokine-encoding technologies- and could see some new-found confidence in those approaches should rapid-fire efforts against SARS-CoV-2 show signs of efficacy.
Despite significant investments necessary for clinical development, SARS-CoV-2 vaccines and therapeutics aren't necessarily expected to be major revenue drivers for biopharma. However, companies are clearly assigning value to their coronavirus assets nonetheless; BioNTech will receive up to $135 million from Fosun for China rights to BNT162, while Vir Biotechnology will owe Alnylam Pharmaceuticals up to $15 million for each RNA candidate it in-licenses under the terms of their newly expanded deal.
How the companies arrived at those economics remains to be seen, and will likely be a key feature as the candidates advance towards patient use- likely to occur in the backdrop of a hostile political environment that won't be sympathetic towards drug development costs that are sunk during a pandemic.
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