1.23.24-Japan-Gensaic

LAVI ERISSON: Konnichiwa. My name is Lavi Erisson. I'm the CEO and co-founder of Gensaic, decoding the subcellular delivery of genetic medicines. Gensaic was spun out of MIT by three MIT alums. We are supported by an extraordinary scientific advisory board, led by Professor Angie Belcher from MIT, and a wonderful corporate board chaired by Dr. Jeremy Levin, the previous CEO of Teva Pharmaceuticals.

The pain we are solving is systemic extrahepatic and subcellular delivery of biomedicines, the single largest therapeutic bottleneck of our era. Now targeted delivery is not a novel concept, far from it. But until now, we have never considered delivery as its own system biology. You see, tissues are in fact anatomically dispersed. Subcutaneous fat is different from visceral fat. Each tissue is consisting of heterogeneous cell populations, and within each cell we have a subcellular ecosystem of organelles where disease truly takes place.

In order to create a subcellular therapeutic window, we need to think deeply about the proteome that governs the journey of molecules in our body and decode the language that our endogenous proteins actually use to gain access into the right tissue cell and subcellular dimension. If we can do that, we can transform the way drugs are developed. Think about the clinical and commercial upside of antibody drug conjugates, and now multiply that by every drug modality that we know.

To get to that future we need to step outside the limits of rational protein design, and actually look back at our own biology. When you do that, the solution is in plain sight. We need to design multifunctional proteins. However, designing multifunctional protein was previously impossible due to computational limits. Now with the advent of generative diffusion models, that future is rapidly becoming available and that is exactly where Gensaic is pioneering the way.

Our discovery engine is made of three components-- access to a massively large, diverse protein space from which we can sample protein sequences; an unbiased protein evolution engine where we discover the proteomic code of delivery using integrated genomic and spatial biology data sets; and then finally a generative protein design algorithm that ingests these data sets and produces multifunctional proteins, which we can test for subcellular delivery.

Now seeing is believing. Moving from left to right, you can see some in vitro validation data, showing protein motifs that initially from left enrich in tissue, but do not internalize into cells. Then enrich in tissue and internalize efficiently into cells. And finally enrich in tissue, internalize into cells, and deliver a reporter protein to the nucleus and mitochondria.

Shifting gears, I'd like to share with you some early in vivo data we've generated in skeletal and white adipose tissue. So in this mouse experiment, we tested whether we could actually knock down nuclear protein expression of MALAT1 using a MALAT1 antisense oligonucleotide that's conjugated to three different protein moieties we've discovered. The first data point on the right side is that we can achieve 70% knockdown using low dose with IV access. That's not unique.

What is unique is actually the second side on the left hand, showing that both are skeletal and white adipose tissue moieties are unusually selective in terms of cell selectivity. It's going as far as the targeting cardiac myocytes while still selecting skeletal myocytes for knockdown. Excitingly, we now also have novel mechanistic for CNS uptake, which we are now advancing in coming weeks.

Our clinical vision is obviously to unlock large indication baskets where differentiation can be achieved with our platform. Concentrating on cell selectivity in white adipose tissue, our lead program is in browning thermogenesis where we go beyond GLP-1 therapeutics by tuning our own body's basal metabolic rate. Our second indication cluster is nuclear delivery and RNA aggregate disease, which is a class of diseases with a huge unmet clinical need, including Alzheimer's, ALS, and myotonic dystrophy.

Before we conclude, I'd like to share my excitement about the future of our platform. Our journey is the beginning of a new era in drug development, an era where cellular machines create subcellular therapeutic window matching the right payload and novel payload with the right disease etiology. In conclusion, I'd like to leave you with three takeaways.

The first is that we are the first and only protein design company that's focused on subcellular delivery of genetic medicines. The second is that our goal is to be in patients by 2026. And finally, I'm here to collaborate with you. Over the two years, I've had the opportunity to start dialogue with multiple Japanese pharma and sign two US pharma on deals. I've been impressed so far by your excellent scientific acumen and emphasis on relationship building. I believe in this culture. And I think now is the time to move from dialogue to true partnership.

Thank you for your listening, Arigato gozaimasu.

[APPLAUSE]

ARIADNA RODENSTEIN: Well, thank you very much to all the startups. Thank you all again for joining us for the startup lightning talks. And now I would like to invite everyone to the lunch exhibit across the hall. The tables will be hosted by MIT faculty and ILP program directors, so look for those names in the center of the tables. And please also engage with all the startups. You will be able to see demos, have conversations, and see if there's a good fit for potential for collaboration. And please join us back here at 2:00 PM for the next session. Thank you very much.