Moderna (MRNA): Its little known genomics & enzymatics work is quite possibly the future of Moderna

I‘ve read a heck of a lot about Moderna & listened to loads of podcasts, however for whatever reason I didn’t come across their genomics work a great deal. If like me you don’t have any medical training, (basically) genomics is focused on studying the DNA of an organism (i.e. its genome) while enzymatics is about enzymes, which are proteins that accelerate chemical reactions (without enzymes speeding things up, the cell is stuffed!). All in all, enzymatics is advancing the genomics industry, with gene editing performed using enzymes.

Compared to Moderna’s work in it’s drug modalities & news of its ever expanding drug pipeline, there is a distinct lack of publicly available information on its genomics business. I find this a bit puzzling, as from what I have come across they clearly have VERY high hopes for its potential. I didn't invest in Moderna for this, but I like it!

Consider the following:

1. 31May22 "111 Extraordinary leaps need solid foundations part 2 – Stephane Bancel" (38mins) pod.. at33.40 Our goal is to vastly improve gene editing techniques.. We think there is a lot of ways to improve gene editing technology to basically go & cut your DNA inside your body to put in a better piece of DNA to make you healthier or to cure a disease. That will take a bit longer, but it might have a much more profound impact on life.
2. 22Mar23 “Founder Stories: Stéphane Bancel, CEO of Moderna” (17mins) pod.. at13.00 Think 3-5yrs, what are the big Moderna leaps coming….. at15.15 I believe we're going to become the biggest genomics company on the planet, because we're going to leapfrog the "Crispr cas9" companies because we now have huge investment in gene editing we're looking at 3rd & 4th generation of gene editing enzymes that we code with our mRNA technology [BB: rather than using mRNA to code for a protein]….Once we get the right enzymes you're going to see this company flying, we're going go from zero gene editing programs to 40.

Interestingly, the only acquisition they have ever made was in genomics, granted in part to improve their core mRNA-coding-for-a-protein business. On 04Jan23 they spent $85m buying OriCiro Genomics, which is now called Moderna Enzymatics. A press release said "we obtain best-in-class tools for cell-free synthesis & amplification of plasmid DNA" [Note: And they’re quietly working on their mRNA-coding-for-a-enzyme business, which if they succeed could quite possibly play a huge part in Moderna’s future]

1. A 27Mar24 Pod.. at2hr11min shed a little line on what that means .. "Most of the [manufacturing] process for most of [Moderna’s] life was chemistry based enzymatic, not cells, & the first steps were still using cells to make the plasmid & through the OriCiro acquisition we removed that so we can go 100% synthetic"
2. Bancel in a 04Jan23 FiercePharma article described the technology as "a critical upgrade in the conveyor belt like path that is Moderna's clinical development" giving them "faster product to clinic, faster product to market.. And then the research part is: We can iterate much faster." Essentially, every drug that they will ever produce through their platform will benefit from this highly strategic fit, in terms of accuracy, speed & cost efficiency.. Seriously, quite the acquisition!
3. For perspective, I'm guessing traditional pharma are still using the old, but established, DNA cloning process (employing E.coli bacteria), which could take several days & requires purification afterward. While OriCiro’s amplification process can take just a few hours, reducing Moderna's large-scale manufacturing time, apparently by, up to 30%.

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In addition to the above, they created Moderna Genomics to tackle what they call "blue sky challenges." This division is "developing, characterizing, & optimizing a toolbox of gene-editing medicines to achieve our mission of individualized gene therapies for [genetic disease] patients." Essentially, they are looking to develop tailor-made systems targeting genetic mutations specific to a patient’s genome, which they call “n-of-one” individualized genetic treatments. I reckon another way of saying all this, is that they are looking to create a platform for gene editing, reminiscent of their INT cancer treatment.

Moderna also has "Strategic Collaborators." These are signed deals with specialists in their field:

1. Metagenomi (02Nov21): Is a CRISPR gene editing company. The partnership will look to accelerate the development of in vivo gene editing therapeutics for serious genetic diseases (Note: “in vivo” means directly in the body, rather than older methods requiring laboratory work then back in the body). Metagenomi will offer up access to its gene editing tools while Moderna will bring the expertise in mRNA & LNP delivery technologies. Moderna is interested in improving delivery mechanisms in gene editing with its mRNA technology.
2. Life Edit Therapeutics (22Feb23): Is focused on next-generation gene editing technologies & therapeutics. They announced a strategic R&D collaboration to discover & develop in vivo mRNA gene editing therapies. A Fierce Biotech 22Feb23 said "Life Edit’s gene editing platform includes a large library of base editors and RNA-guided nucleases (RGNs). The RGNs are smaller than other conventional nucleases—such as those currently used for CRISPR-Cas9—which could boost versatility for delivery."

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My take on all this, goes back to Bancel's comments above on the huge potential Moderna sees in gene therapies (mRNA coding for enzymes, possibly a future income stream) & obviously does for cell therapies (It’s current business of mRNA coding for missing proteins etc).

1. Currently Moderna is using mRNA to code for a missing protein, the idea is that you would perhaps need an injection once a month (perhaps more often, perhaps less). However, using mRNA to code an enzyme to gene edit you could possibly permanently cure patients.
2. Both treatments would significantly reduce future healthcare costs, however the gene edit would have a much more profound financial impact.
3. What price is appropriate for a “one & done” treatment, quite likely $millions versus an annuity like stream from a series of injections possibly over a life time.

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Moderna clearly recognizes the risk gene editing could have on its business, so decided to invest heavily in it itself. Given that Crispr-Cas9 arrived back in 2012, yet it was only last year that UK & US regulators approved drugs based on Crispr technology (e.g. sickle cell), its clear that regulators are cautious but open to the technology.

So if Moderna Enzymatics & Moderna Genomics are successful & Bancel is correct in his 3-5yr forecast in getting possibly 40 drug prospects…. Then this warp speed business, that you’ve possibly never heard of, could be massively financially lucrative for Moderna.

[If you’re aware of any other genomic information, please add in the comments below for all to see rather than sending it direct to myself. Many thanks, BB]