Codexis, Inc. 12th Annual Cantor Fitzgerald Global Healthcare Conference

Thanks, Kristen. Great to be here. Love to have the opportunity.

Yeah. Codexis generates manufacturing solutions using highly engineered enzymes. We've been doing that successfully over the last 15 years. Every year, we supply metric tons of enzymes to the pharmaceutical industry. But what we're most excited about is in the last several years, rather than working with single enzymes, we've created a manufacturing platform that is comprised of enzymes that generates siRNA. It generates oligonucleotides. We're focused on optimizing it for the generation of siRNA, and we call that the ECO Synthesis manufacturing platform, eco being enzyme catalyzed oligonucleotide synthesis.

Yeah. siRNA as a modality, I think, is really starting to shine. siRNAs were commercialized initially in smaller indications, but with the approval of inclisiran, have moved into much larger indications. There are 3 phase III cardiovascular trials ongoing, very large trials. We're seeing the pharmaceutical industry really take that step towards the very large opportunities. I think that siRNA as a modality has been proven now across several indications to be safe, effective, at very attractive dosing frequency, either quarterly or half yearly. What's fantastic about the modality is the whole transcriptome is, in theory, available and tractable as drug targeting.

Yeah. I think that my own experience in advanced medicines and working on manufacturing technologies over the last decade, I think that we've had some groundbreaking fundamental science. However, in some of these precision or advanced medicines, maybe the production technologies have actually been lagging. Patients that could benefit from these transformative technologies and the commercial success that these technologies could achieve is maybe not quite where it needs to be for us really to have the medicines of the future that you're referring to in that big uptick. But I think all of the metrics indicate, so estimates are somewhere between 400 and 600 siRNA assets in various stages of development. There's more than 100 in the FDA database of clinical trials.

I think what we are looking at is a lot of breadth in terms of indication, a lot of appetite for looking at very significant indications. I already mentioned cardiovascular, but also obesity related, a lot of interest in CNS targeting. I really do think that of all of the ways that we have been looking to advance medicine, siRNA is one of the most powerful modalities.

Yes. Traditional chemical synthesis has a long history, 40-year history, and the practitioners of that chemistry are very familiar with that chemistry, and it has become highly optimized. Yes, there are people scaling products, and there are large products such as inclisiran, so there are people in the market working with existing production technologies, of course. However, these technologies have some significant challenges. The maximum batch size for solid phase organic synthesis is about 7 to 10 kilos. If you are making product for phase I clinical trial, you probably do not even notice that there is an issue. But if you have a successful commercial asset and you need to produce 1 metric ton of product a year, this becomes a very, very significant challenge.