4.4.23-Health-4M-Therapeutics

BEN WILLIAMS: It's an honor being here. Thank you so much. I went to Harvard but I'm a huge MIT fanboy. I just got to throw that out there. I have two sons. I keep pushing them, like no Harvard rattles, only MIT rattles.

Let me see, so our founders have done this before, real quick on the MIT affiliation. So Steve runs chemical neurobio at MGH. He's a senior member at the Broad. A lot of our pits and leads and assets came from his work at the Broad. Li-Huei Tsai is an Alzheimer's expert. As you guys might know, she runs the Picower Learning and Memory Institute at MIT, neuroscience professor. She's awesome.

We also licensed a use patent on our parent molecule from MIT. The molecule was in clinical trials for a different indication and Steve found out that it was a GSK3 beta inhibitor. And we're advancing the primary metabolite, a unique salt form crystal structure of that so we can get some composition of matter protection.

Don used to be president at Bristol-Myers Squibb. He ran the global pharmaceuticals business. He met Pablo, our CEO, there. They've done the blockbuster drug thing in CNS before so we hope to do it again. Don in particular, in licensed Abilify from Otsuka, for example. And he and Pablo worked on that.

I am a lowly tech guy with a science background. I'd be remiss to not mention Larry and Randy. Randy did the famous inject, went into a tadpole embryo, get the two headed tadpole thing back in the day. I remember reading about that in AP biology in high school, and he's a co-founder of Fate Therapeutics. Larry, co-founder of Cytokinetics, a lot of great folks involved.

So a big part of our innovation is studying the effects of drugs on living human brain cells derived from stem cells. We have a lot of small molecule opportunities before us, our first program in bipolar mania. We're all about these conserved mechanisms around neuroplasticity and neurogenesis. So we think what we're doing applies very widely in CNS.

You guys are familiar with this, so I won't belabor it. But basically, you can take a cell from an adult, turn it into a stem cell, and then turn it into neurons and test it. So in particular, we looked a lot at how lithium affects uncovering the mechanism of action of lithium by looking at its effects on folks with bipolar, without, folks who are traditionally responsive to lithium, those who aren't, that kind of thing.

So, main problem, lithium and a lot of other drugs in bipolar mania have black box warnings. They're pretty horrible. So we're trying to develop more targeted therapies by understanding the underlying MOA.

One way to look at it is in anxiety, depression, schizophrenia, there's many, many different variants of common drugs. In bipolar, there are no lithium analogs and lithium really is kind of a wonder drug. And it's a very dirty drug. It does a lot of things but we think in bipolar in particular, potentially future applications in dementia, its GSK3 beta inhibition.

Our lead compound seems to be better than lithium in a lot of different respects. We recently demonstrated efficacy in an animal model of bipolar mania. So basically, our compounds are chilling out rats to the same extent that lithium does. And there's some dose response as well.

Sorry for flying through this, would love to chat with anyone that's interested in learning more. We're about two years away from the clinic. So we're currently doing IND enabling studies right now on our lead. And the encouraging data from the parent compound was in clinical trials all the way to phase III. 2,000 patients took it for over a year, no serious adverse events.

The traditional difficulty in targeting GSK3 has been side effects, so we don't think it's specific to GSK3. We think it's scaffold specific. So we think we found the one or a few, actually.

Again, the stem cell thing, we did a bunch of high throughput screening, cross screening, all that kind of stuff. I think this is perhaps the largest high throughput screen on neuroprogenitor cells in academia. Not sure, but we looked at 320-some-thousand compounds. And that's essentially our pipeline.

We have a second asset that's perhaps the most potent GSK3 beta inhibitor, most specific perhaps ever created. And we have a bunch of other assets in the pipeline.

The IP coverage is pretty extensive. We think for our lead compound, it's kind of the best of both worlds. It's been in clinic, but we also have composition matter of protection coming.

And yeah, we're looking for partners interested in helping us advance our lead asset in particular. But of course, if you're interested in our second and third, even better. We'd love to chat with anyone interested in learning more. We've kind of been stealth but now that our IP position is pretty solid, we're kind of coming out to party and chat with folks. Well, thank you for your time.