04.10-11.24-HST-Startups-Gensaic

UYANGA TSEDEV: Thank you, everyone, for having me today. I am Uyanga, CSO and co-founder at Gensaic. All right, here we go. So Gensaic was founded out of MIT in 2021 with the three of us co-founders here. And we're very lucky to have with us an extremely experienced board, as well as a growing team of expert scientific advisory, some of whom are all up there on the slides right now.

And so currently in the field of therapeutics development, we are faced with a challenge in terms of the number of options that are available for us in order to deliver therapeutics outside of the liver. At Gensaic, we're very much interested in delivery of therapeutics beyond the liver and even at the subcellular scale. So specifically, we're looking at precision delivery at all scales in vivo. So thinking about accuracy for the right organ, for the right cell type, as well as the right subcellular compartment.

And so to address such dimensional-- oh, OK. Let's go back. Dimensional delivery, which is delivery across all of in vivo dimensions or barriers, we at Gensaic build multifunctional-- OK. We're going to have to imagine that there's a beautiful graphic. A video that's playing of our multifunctional protein that's being generated using generative AI, where we're scaffolding functional sequences that have the ability to direct our material to the right tissue or cell type, as well as facilitate the transport of our material to the right subcellular compartment so that the therapeutic payload can have the most effect at the final destination.

And so the way we do this is by using our FORGE discovery engine, which has three major pillars of activity. Here we have FORGE-Target, where we utilize unbiased barcode of protein libraries to discover sequences that have tissue and cell specificity. We have FORGE-Transport where we utilize high content imaging to track in an arrayed format barcode of proteins that may have intracellular function. And then we have FORGE-ML, where we take our discovered sequences and are able to then scaffold that onto a single structure that can then preserve all of the delivery functions, as well as optimize for drug like properties such as low immunogenicity and stable folding.

So here is a data sampler of what it looks like for us when we succeed in FORGE-Target or FORGE-Transport. So here, we're demonstrating sample sequences that have specificity for human primary cells of the lung, BBB, skeletal muscle, as well as adipose variety. We're also here showing you that FORGE-Transport can elucidate for us the function of these sequences in the context of a cell, whether we're only decorating the surface of the cell, whether we're internalizing, or we're actually driving delivery to subcellular places such as the nucleus and the mitochondria.

And so, as we mentioned, what we do then is take our sequences that we've discovered through our Transport and Target screens. And we're able to then use generative AI-- the latest diffusion models-- to create structures that hold both of these functions on them. When we have our structures, we are then able to identify and ID sequences that can then enable these structures to fold properly, as well as allow for in vivo characteristics that we care for, such as proper PK and, again, folding.

So when we have our libraries of multifunctional protein vehicles, we then test them for delivery potential with a variety of payloads. And again, you can imagine that there's a beautiful video showing you-- oh, this time it's working-- showing you the generative process where we are scaffolding the novel sequences that we've discovered for delivery potential. Here we go. So you can see a few examples of what this process looks like.

Ultimately, the winning sequences that we discover, as well as the multifunctional vehicles that we create, are payload agnostic and can transition forward with any therapeutic modality that would benefit from tissue to subcellular level specificity. Right now at Gensaic, we are very much concerned with the translation of oligonucleotides-- so ASOs and siRNAs-- for our CNS and adipose programs.

So very quickly, I just want to give you a sampler of what it looks like for us to conjugate our cell internalizing adipose specific peptide onto a standard ASO against the MALAT1 gene. And both in the in vitro and in vivo context, we can see that we get very adipose specific enhancement in the knockdown of the target gene. And ultimately, even in vivo context, we can see that we drive very specific knockdown in the white adipose tissue over other target tissues, and even detarget clearance organs like the kidney.

So right now, we're very excited about driving forward our adipose peptides for the enhancement of white adipose browning and enhanced energy expenditure. And this would be for the treatment of obesity and other metabolic diseases. We are very quickly following this with our first muscle and CNS oligo conjugates. And so if you are interested in discussing therapeutics development in any of these areas, please do come find our table during the lunch exhibit.

And of course, we're always excited about research collaborations for other target organs, as well as compartment specific delivery and then, obviously, optimization for alternative payloads. So thank you again for everyone's attention, and I'll pass the mic forward.

[APPLAUSE]