With a global pandemic to fight, the speed, efficacy, and efficiency of mRNA vaccine research, development, and manufacturing have been proven invaluable. While the Moderna (mRNA-1273) and BioNTech (Comirnaty) COVID-19 vaccines are notable steps forward with respect to containing the pandemic, the implications for mRNA as a therapeutic modality are even broader and more substantive. These vaccines are notable because they represent the first mRNA assets authorized for use in humans, were developed in record time, and show high efficacy. These achievements resoundingly demonstrate the power of the platform for the first time and have lead to heightened focus and investment in the space.  So how does this renewed interest impact the biopharma landscape? How will newcomers adapt to the highly technical and complex development and manufacturing requirements for mRNA? And how will supply chain expansion and consolidation look, as a result of the monumental rush to increase vaccine output capacity? While we have written this to spark discussion, we will briefly cover some potential paths forward for these market-shifting trends here.

Delivery, Delivery, Delivery

Landmark emergency use approvals for the Moderna and BioNTech COVID-19 vaccines have propelled mRNA technology from a growing area of interest for those studying rare diseases to a household topic of discussion. No mRNA therapeutic had been approved prior and the most advanced program is still a few years away from FDA approval.  While there have been considerable strides made in the supply chain, manufacturing, and formulation of mRNA at global scales, there persist fundamental challenges, the most significant of which, is delivery. mRNA is exceedingly difficult to deliver into cells in vivo given its size and charge. The ability for an mRNA-based therapy to replace a traditional biologic, for example, would require extremely high doses that are not possible today. The importance of delivery is highlighted by the recent M&A in the space, with Beam Therapeutics having acquired Guide Therapeutics, Sanofi having acquired Tidal Therapeutics, and Arcline having just acquired Polypeptide Therapeutic Solutions (PTS). All these transactions were driven by the need for improved delivery solutions. In the meantime, infectious diseases and vaccines represent a logical use-case for mRNA given the relatively low doses required. Beyond infectious disease, mRNA could also have a substantial role in the cell and gene therapy revolution, another space where relatively minuscule amounts of delivered mRNA may be sufficient. This can include the use of mRNA to encode for CRISPR enzymes for knockout / knock-in therapies under development by companies like Verve Therapeutics and Intellia Therapeutics, which focus on cardiovascular and rare disease indications, respectively. Beyond the issue of getting mRNA into cells, is the related issue of “regulating” its function once within the cell, which can also impact efficacy. Genetic control may offer extremely precise control of delivery based on (de)activation of the mRNA without the requirement that the mRNA be guided precisely to the right location. Utilizing cell-specific promoter sequence, companies like Strand Therapeutics are able to ensure that even with the imperfect targeting of currently available lipids, the therapeutic will not be active unless it has reached its proper target. Though these genetic control techniques offer great promise, they are a more nascent technology that will require significant development before we see widespread clinical use. For now, widespread clinical use is left to those applications where targeted delivery is unnecessary, i.e., vaccines. However, harnessing the power of these next-gen delivery systems could be the key to the success of future mRNA assets outside of vaccine applications.Be on the lookout for part II of this COVID mRNA vaccine blog collection where we discuss the necessity for experience and quality in mRNA therapeutic manufacturing and take a deeper dive into some recent M&A activity in the space. If you appreciate content like this, we track the mRNA therapeutics / gene / cell therapy space constantly (via an interactive tracker) and would love to discuss this area with you further. Please reach out to schoellhammer@decibio.com and braverman@decibio.com to get more of our thoughts on this topic.