11.15-16.23-RD-Bilayer-Therapeutics

THOMAS COLLET: Hi. Well, thank you very much for the invitation to present. Bilayer Therapeutics, as Tricia mentioned, is developing first-in-class therapies for the treatment of obesity, diabetes, and motility disorders with superior tolerability. We have strong ties to MIT. The technology is out of Bob Langer's and Gio Traverso's lab, co-invented at Brigham's. And we have as a senior advisor Michael Camilleri from the Mayo Clinic.

I myself am a serial entrepreneur, and also have an MIT degree. So we have nearly only MIT represented. Not that that's really the objective, but nonetheless.

So in terms of the problem we're trying to solve, we're looking at obesity. 42% of US adults are obese. I usually don't have a problem convincing people that that's an unmet need. But what most of you probably have heard is that there's now a class of drugs that's available that significantly lowers body weight. And these are typically called GLP-1 receptor agonists. The most well known one, arguably, is Ozempic, and they now achieve body weight reductions up to 24% to 26% over 72 weeks, which is, of course, tremendous.

And that, in general, is acknowledged to be a roughly $100 billion opportunity, and people are talking about 100 million Americans going on to this drug. So the fly in the ointment is that these compounds have significant side effects. And these range from GI side effects, such as constipation, diarrhea, nausea, gastrointestinal blockage, all the way to interactions with other drugs, as well as loss of lean muscle mass.

And obviously, when you want to lose weight, you want to lose fat, not muscle. So that becomes a significant issue. And the commercial problem is that this is causing a significant number of-- significant percentage of patients to stop taking these drugs.

So the numbers, the columns on the right show you that out of 100 patients who start on these drugs, a year later, roughly 50% will have dropped off, and two years later, roughly 70% will have dropped off. So there's some debate over the magnitude of those numbers because this is more than in clinical trials, but that seems to be the real-world evidence.

So basically, we've set out a solution to enable healthy weight loss. And this consists of us using what I call bile acids. These are naturally-occurring compounds that are made in the liver, and that have the tendency to increase the levels of seven nutrient-stimulated hormones.

So not just GLP-1, as in Ozempic, or maybe GLP-1, glucagon and GIP as in Eli Lilly's new drug, but this actually stimulates seven different mechanisms of action. And because bile acids have been used in human clinical trials and in clinical practice before, we actually know that they have a benign side effect profile. Typically, transient and benign per product label.

And we're combining this with a delivery platform that's coming out of MIT's labs which basically targets a bilayer tablet-- hence, the company name-- to the colon and then generates a what's called biphasic PK profile, which is a fancy way of saying that we think it coats the inside of the colon evenly for maximum efficiency. So this is basically the graphic representation. So far, what has borne out is that more hormones is better because it inactivates more mechanisms to actually lead to weight loss. And that's the route that we're leading down with our lead molecule, BL-050.

The bilayer tablet they described here, I'd encourage you to go to our website. There's a nice animation that shows how it works. But it's basically, as I mentioned, coated with an enteric coating that makes sure that the tablet does not dissolve in your stomach, but only in your colon. Once it's in the colon, it dissolves and it actually then evens coats all of the colon, so what are called the proximal and distal parts. So not just the beginning of the colon, but also, the middle, and the end towards the rectum. And that's really key for maximum efficiency.

So there's a human study. Actually, there are several human studies that academics have undertaken because they wanted to see whether bile acids work. And this is one shot, a screenshot or an excerpt from a publication that shows that if you infuse the three hormones, GLP-1, OXM, and PYY, in healthy volunteers, you achieve a roughly 30% reduction in caloric intake.

So if you look at the dark blue columns on the right, the taller column is volunteers who are taking saline solution. The one on the right are the ones that are getting the drug solution, and their appetite is reduced in such a way that they're eating 1/3 less. So quite significant impact.

This is the safety profile of sodium CDC. As I said, it's been used before in approved drugs. Side effects are considered transient, even at doses that are higher than what we intend to use. And we also have some animal data indicating that these active ingredients will protect muscle mass.

Our IP is licensed from MIT and Brigham's, and we started creating our first IP. And in terms of attendance at this conference, we're hoping to talk to companies that have scientific and clinical and medical expertise that would like to figure out with us how to get this compound into humans and to show a first-in-human study, which is called the phase I PK study, that this actually works. So thank you very much.