11.15-16.23-RD-Gensaic

LAVI ERISSON: Good afternoon, everyone. Thank you so much for this wonderful opportunity to present Gensaic. My name is Lavi Erisson. I'm the co-founder and CEO of Gensaic. We are a genomic medicines company with a singular mission to decode the language of intracellular delivery. So Gensaic was founded out of MIT by three MIT alums back in 2021. We got our first pharma collaboration in 2022, and then subsequently won five innovation and grant awards.

Over the last two years we grew to a team of about 10 physicians and scientists supported by a highly entrepreneurial world class scientific advisory board and a highly experienced deeply experienced board of directors chaired by Dr. Jeremy Levin. The pain we're trying to solve is the selective delivery of biomedicine. This is the single largest therapeutic bottleneck of our era. There is a graveyard of potent medicines that have never made it to patients due to limited therapeutic window. And in fact, to this day there is no FDA approved IV delivered oligonucleotide therapy that is targeting a non liver tissue.

The potential of selective delivery is endless. But in order to realize it, we first need to understand and rebuild delivery from the bottom up. So you see tissues are actually an atomically dispersed and comprised of heterogeneous cell populations. Each cell is a universe or an ecosystem of subcellular specialized organelles. And the proteome that governs access into and outside of these subcellular universe is largely unknown. It is waiting to be discovered and translated into transformative genomic medicines that can treat diseases with dominant cell or subcellular phenotype, like late disease or myotonic dystrophy.

And to do that, we build FORGE. FORGE is a machine guided unbiased protein evolution platform with access to over 10 to the power of 50 protein variants. The FORGE platform is quite simple. We produce and then we screen billions scale libraries generating in this process imaging sequence and pharmacokinetic data that we use to train generative machine models. We then use these machine models to create new novel proteins and a second round of evolution. And with that, we repeat and do it again. In the end, FORGE discovers novel cellular targets which we then translate to genetic medicines.

And with that, let's go and look at some real data. So this is a short cyclic peptide selected against skeletal muscle. On the left, you're seeing live imaging data from different protein families, and we look at how they behave within cells. We ingest this data alongside sequence data into an autoencoder model represented in this video as a latent space and generate a second round of evolution gaining us 10x selectivity in skeletal muscle.

The next step is to understand can we actually translate this to real genomic medicines? So and this is the right experiment we're looking at right now. We took three candidates, one against skeletal muscle and two against white adipose tissue. And we conjugated them to an antisense oligonucleotide that knocks down MALAT1 one. It is a commonly used nuclear target. We then administered or reduced those candidates intravenously into wild type mice using two controls and negative PBS or buffer control and a positive active but non-targeted antisense oligonucleotide.

As you can see on the right bar in the middle, we were able to achieve potent knock down in muscle 70% against the buffer and 63% better than the active control. But what really exciting for us is actually the bar graph on the left showing the selectivity of our variant in skeletal muscle against other tissues going as far as targeting cardiomyocytes in the heart, which is another type of striated tissue. The same thing is shown in terms of knock down and selectivity in the lower row for white adipose tissue, opening up a really exciting therapeutic space for us in obesity related indications.

The future of forge is actually redirecting and bringing all different genetic and non-genetic medicines to the right compartment they need to be in. However, in the near future we are racing to patients. And we want to be there by 2026 with two oligonucleotide therapies that are targeting white adipose tissue and skeletal muscles. And at the heels of that, we have gene delivery programs for CNS and lung that are taking a reducible 20 KB DNA vector that is proprietary to us and is derived from a phage species we engineered in house.

In summary, Gensaic is the first company in the world to systematically decode and map the subcellular universe. And it is also the first to show this level of selectivity in skeletal muscle and white adipose tissue allowing us to position as best in class for multiple genetic and metabolic diseases. Our go to market is simple. We want to be in patients in 2026 and we need your help to do so. We are currently actively seeking partners that are therapeutically committed and have a clear vision for delivery.

Thank you so much for your time and I look forward to talking with you directly after the session.