Welcome to Piper Sandler's 37th Healthcare Conference. I'm going to date myself. This is actually my 20th Healthcare Conference since joining Piper, so it's kind of crazy to recognize and celebrate that milestone. I've got to say, over the last two-plus decades, I've seen my share of downturns, including the genomics bubble, 9/11, the 2008 financial crisis, and most recently this post-COVID bear market. I've got to say, biotech's back. We're witnessing a biotech recovery with the Nasdaq Biotech Index up over 40% off the bottom since April. My coverage universe is up over 90% in that time frame, which is a little bit more skewed to small caps. I believe this recovery has legs driven by unprecedented innovation, new product approvals, and launches.
Our first presenting company really fits this bill is Biomea Fusion, which is developing an oral menin inhibitor, icovamenib, and an oral GLP-1 agonist, BMF-650. Here with us today is Ramses Erdtmann, Founder, Chief Operating Officer, and President, and also Dr. Steven Morris, who's the Chief Development Officer. Thank you both for making the trip, and thanks for being with us today.
Yeah, thanks for the invitation.
Ramses, perhaps you can start off by describing menin. What role does it play, and how does inhibiting menin benefit diabetes patients?
Good. Very good question. If we lean back and we ask ourselves, what function does menin have in the pancreas? It's a scaffold protein, and it controls—and Steve can add to my answer because he's the physician—but what we've learned about menin is it controls, in the pancreas, the beta cell proliferating effect. Meaning, if menin is inhibited, beta cells are allowed to proliferate. If menin is not inhibited, beta cells are under control. You do not need new beta cells in general physiological conditions. If you are obese, the body responds. Menin is inhibited, and these beta cells are proliferating to overcome the resistance of the obesity. You can see in patients who are obese, they have high levels of insulin production, and they have a lot of beta cell regeneration. In pregnancy, we see the same thing.
The mother downregulates menin through prolactin, and that's validated in animal experience. It's very difficult to do that in humans. Validated in animal experiences. When the pregnant mother downregulates menin, these beta cells respond to what? To the queue of glucose. Because the glucose now has to be brought through resistance to the cells. She needs more power to do that, and the body responds in a very elegant way. That's why most of the people who are obese are not diabetic, and that's why most of the women do not get diabetes. We saw this data, and it was fascinating. I mean, literally fascinating when you read the early research, and you see a guy crispering out menin from mice and then giving it glucose.
The glucose is absorbed in these really fat mice that are "diabetic." In the controlled arm, the glucose is not being absorbed. When you read that research, you think, "If I could safely help the diabetic person downregulate, or in our case, inhibit menin, could this effect be replicated?" We did it in cells, we did it in animals, and then we went to the human. Now in our human study, we see exactly what I just described.
It's a perfect segue. Walk us through some of the data so far that you've reported that really supports that mechanism of action and really the downstream effects in patients.
I'd like to take a step back and ask myself, why on earth do we even need another agent? If you go on clinicaltrials.gov, I invite you to do that for fun and look at how many agents are there under development, not for obesity, but for diabetes, and how many have been approved. You come to a number that is astounding. Just for this audience here, we've been in development for a long time. It takes you eight years to get through if you're lucky. You're one out of ten who makes it through. There are 60 approved agents in diabetes, and all they're doing, they're chronic agents, and they're addressing the symptoms that come from diabetes, which is glucose toxicity. They're trying to help the body overcome the symptom.
None of these agents addresses the root cause, which is your body's incapability to manage through the beta cells, addressing the glucose toxicity naturally through insulin production. When we saw this pathway, we said, "This would be the first agent that is addressing the root cause and allows the body to rebuild itself naturally." If that were to be true, then could we potentially cure diabetes? That is how we started. The results were now showing that those patients—we did an Alzheimer's study where we took any diabetic patient, the guy who is obese, BMI of 40—I mean, think about that—and BMI of 25, which are completely different phenotypes of diabetes. We took patients of all races, and by the way, Asians respond very differently. We took patients of all ages, etc., etc.
We had an Alzheimer's study, and before we read out, we said, "Let's segmentize these patients into their insulin deficiency," because we believe that higher insulin deficiency could potentially be a better patient profile.
Sure.
Why should I help an obese person who has a very high production of insulin, is not compensating for the glucose, has diabetes, but why do I add another little bit of insulin on top of it when the core problem of his diabetic situation is resistance, meaning fat? If he gets a GLP-1, perfect. He reduces his weight, and the resistance is reduced, and the insulin production is now matching the glucose toxicity. However, the guy who's insulin deficient, who has a BMI of 25, who has a reduced pool of beta cells, function is depleted, that could be potentially our responder. We had four subcategories. We read out the four subcategories, and as I just described, the insulin deficient patients were the ones that responded profoundly. I mean, what was most fascinating is we would have wished for this, but obviously you don't know.
You dose a patient for X amount of weeks, you stop dosing, and then you say, "Nine months later, let's see if your A1C is still under control because we should have recovered your beta cell pool, right?" We passed that test. In our sort of—in most of their various arms, we had to test various dose ranges. It was a very complex study, but in these patients, we showed up to 1.8% placebo-adjusted A1C reduction, which is up there with GLP-1s.
Yeah, absolutely. Why only dose for 12 weeks, and what's the benefit of that?
Yeah. It is very simple. We only had toxicity for 12. The FDA said, "You can only go for 12." We are now working on chronic dosing. We should be able to be allowed to chronically dose a patient starting next year. We can do a lot more work on understanding what longer dosing does for maybe the patients who are more resistant. We found that the guy who is severe insulin deficient actually does not need more than 12 weeks. We found 8 weeks is insufficient, but 12 weeks was delivering beautiful results. We take 12 weeks into the next set of studies addressing those patients.
Yeah. It's almost like a reset then for those severe insulin-dependent diabetics.
Yeah.
Now, I know you have some upcoming data. Maybe you can kind of tell us what to expect from this next data readout, just I think in the next couple of weeks here.
Yeah, there is a data readout on this Friday at the World Congress for Insulin Resistance and Diabetes Care. It's a very interesting congress because it has all these high-profile endocrinologists presenting. We were invited because Juan Pablo Frias, who's helped us for these past three years in the clinical development, he's presenting for us.
That's great.
We're presenting the 52-week data set, and we will add mechanistic backgrounds to why we think it is working the way it's working. C-peptide is one of the things we're going to show more of. C-peptide is a surrogate for insulin. You can't really measure insulin, but you can measure C-peptide, which goes stepwise with insulin. C-peptide would be what you want to see in these patients, right? We're going to show some of the C-peptide data.
That's great. We will look forward to that on our day off after the conference. We will be sure to look into that. Tell us, you mentioned about the next trials. Tell us about sort of the development plan from here.
Yeah. Being in our seat is super exciting, but it's also super difficult because you need funders, investors to support a pathway. You can have, on the one hand, pharma that is excited about your pathway, but it sort of depends upon where the excitement goes to. Right now, obesity is a big topic, and we have an obesity drug, as you know, 650. We're going to get to that. Our clinical development plan is driven by the funding that we have. The easiest shot on goal is the severe insulin deficient patients. There's about every fifth diabetic patient. You can identify them. They have low BMIs. They have high A1Cs. It's not a difficult-to-find phenotype. We're going to go after those first. Why? Because it's definable. There's a clear path because they become insulin-dependent the quickest.
The FDA, if we were to help these patients, can see the need. If this is not a chronic agent, it's a fast path to approval. Okay. The next group where we saw results are the ones that are on a GLP-1, but the GLP-1 is not controlling your diabetes. Wow. Why is that? Because when you inhibit menin, the receptors on the surface of these beta cells are more expressed. This expression leads to a better interaction with the GLP-1 receptor agonist. We also increase the GLP-1 expression. That study, we also have data that we just showed on the GLP-1 uncontrolled patients. That study is also a very easy, clear for us to do phase two study. There are other areas. There's type 1. There is the effect we've seen on obesity when you add icovamenib to a GLP-1 receptor agonist.
There is weight loss, the quality of the weight loss, the preservation of muscle that we have seen in animals. These are all areas where we—big studies where you need help. We either do those studies later. We do them with investigators where the investigator takes a share of the work, and we just fund drug supply and similar things, or we do it with pharma.
Yeah. I think the way you've prioritized this makes a lot of sense just in terms of lowest hanging fruit and really best application. It really shows you when you've got an entirely new class of metabolic drugs.
That is the problem.
There is a lot that you can do in this.
There's a lot you can do, but there's also a lot of skepticism. The academic world is solidly behind us. What they really like is they like the fact that you avoid this chronic treatment. You can take a guy and say, "You don't have to be on drug for the rest of your life." When we do these, we have a scientific advisory board. We update them. There are 20 folks on there. When we have these sessions with them, they are most excited about that aspect, which I am too, because the core problem of diabetes care is persistence, meaning patients taking their medicine. You don't want to take a medicine every day, and you have side effects.
Absolutely. I'm going to pause and just see if there's any questions from the audience on icovamenib. I'm going to switch gears to BMF-650, which is your oral GLP-1. How does your agent differ from what's being developed and what's sort of getting ready to be approved?
Yeah. Let's check with our Chief Development Officer here to my left. Chief, do you want to answer that?
Happy to do so. First of all, BMF-650 is based on the orfo scaffold. Now, orfo is a wonderful drug, but arguably, if anything, it's too potent for its own good. The high potency of orfo means that many patients have tolerability issues. Another aspect of that high potency is the fact that you have to ramp up as you initiate therapy with orfo with a patient. That ramp-up period takes weeks. Some patients simply don't tolerate orfo at all. BMF-650, by design, was created to be actually less potent than orfo, to have a smaller peak-to-trough ratio than orfo. That's another problem that orfo has that leads to issues with tolerability. We think that 650, because it's somewhat less potent, smaller peak-to-trough ratio, will be better tolerated than orfo.
We also think, and this is based in part on cynomolgus monkey studies that we've done with BMF-650, that we won't have that protracted ramp-up period. In monkeys dosed with BMF-650, we started on day one with that dosing at the therapeutic dose, and we had minimal side effects, almost no nausea, no vomiting, and also very good weight loss in that cynomolgus monkey study. Now, we didn't do a head-to-head comparison of 650 in those studies. We may be doing that in the future, but what we can do in a cross-study comparison is compare it, for example, with the Carmot GLP-1 receptor agonist cynomolgus study. At equal doses, 650 versus Carmot, we actually saw greater weight loss with 650 compared to Carmot. The Carmot compound, you'll recall, was acquired by Roche. We are in the clinic already.
We started dosing recently with BMF-650 in the GLP-131 study. This is a study that is enrolling obese, otherwise healthy individuals. We will have a 28-day efficacy readout from that study, but we've also built in an additional two weeks, so we'll be able to follow the patients having dosed for a total of six weeks to get an idea as to continued weight loss, the weight loss, whether it plateaus, for example. Those data will be available the first half of 2026.
That's great. That's really exciting. I guess, again, you guys have a wealth of challenges here, right? Because you've got two of arguably the biggest drug classes and biggest disease areas that you're going after. Where do you really see another and hopefully differentiated oral GLP-1 fitting in? Do you see the opportunity to combine with icovamenib or other mechanisms?
All the injectables will have to, or all the orals will have to compete with the injectables, and people will make their choices. When you look at surveys, it's very clear that people want an oral, not an injectable. We think the class is moving to orals over time. That's why we wanted to develop an oral. We believe safety and side effect profile, because so many people take a GLP-1, is key. If you look at the dropout rates that are not based on finances, it's seven out of 10 within the first year. Now, you see studies where it's five out of 10. I've seen them where there's seven out of 10, but it's very, very high.
Safety, side effect profile, and what we're trying to do and what we have seen is if you combine one with the other, meaning a GLP-1, our GLP-1, or a GLP-1 with icovamenib, you can reduce the potential load of the GLP-1 because icovamenib has this synergistic effect where we also increase the weight reduction. We have seen it in animals. We are going to explore that in humans. These are all exciting contributions to the space, and that is where we see ourselves fit in. 650 is a perfect drug. Let's say it comes out with good data, which we think it could. There are a lot of pharma players that need one and that have maybe bet on the wrong scaffold, that have maybe bet on injectables versus orals, etc., etc.
There is a place for us to work together with pharma, very likely, to develop 650. What I think is more interesting from our perspective and our contribution to the space is that, one, we're going for curing a disease, diabetes, and two, we're going for reducing side effects that are already established. Muscle loss is a problem. The dropout rate is a problem. The safety is a problem. These are all three areas that we would address in combination with icovamenib because we can reduce GLP-1.
What would next steps be for 650 beyond the data that you receive in the first half of next year? Where would you really go next to continue to prove out that differentiation?
I think a development path for 650 is very, very expensive. The difference is, and you've got to go into a little bit of what the FDA is thinking. The FDA says, "If you're on an agent chronically, you have to show me X many patient lives. You have to show me these more age groups. I want to see that you don't hurt these age groups, blah, blah, blah, blah, blah." It is a, "Look at Viking. Look at how much money they're spending." It is an ongoing effort to adjust your dilutionary impact. You're looking at it, you're thinking, "Wow, is that really what we want to do?" First, let's look at the results when we get them. Two, let's see what is pharma's interest in collaborating with us. Three, can we afford to do another study?
I think the last question is probably the most important one. I think our contribution has been so far where we are developers. We come up with new ideas. We have come up with a new idea. When we developed, as you remember, the Pharmacyclics days, people were on our tail to come up with a better PCI-32765, and they did. Now you can see how the volume of more precise BTK inhibition is taking over. That is good. That is good for the space. We are doing the same thing to offer GLP-1, not because we like offer GLP-1.
With menin too, pioneering that pathway as well.
That's a little more difficult because we are the first. We are in the space. We have to go through all the, "Hey, what are you doing? What does menin do?" The FDA concerns, we had to handle all those. We are now past all that. We have identified our home, and we are now looking on the sides and say, "Is there prediabetes space? Is type 1? Is obesity?" These are all areas that are worthwhile to explore, maybe most likely with investigators because they have great interest in doing it, and they do not cost a lot.
Yep. If you think about kind of the scenario you laid out, especially around 650 and the cost of developing it, what would be an ideal partnership? Do you want to just simply license it out and focus on icovamenib? Do you want to retain some skin in developing 650? What would be the ideal partner from your perspective?
Yeah. First of all, any of the above. Any of the above is great, particularly in our current situation. We have cash until the first quarter of 2027. I have to deliver a lot of things until then. One of them is 650, show me the results. Another one is show me, and this is 26 weeks readout on the GLP-1 uncontrolled patients, 60 enrolled. You have to handle enrollment. You have to get to the readout. You have to get FDA on board. You have to do the same thing for the severe insufficient patients, plus, plus, plus. The delivery line is high. The people are very motivated. We have a good group. We can do that, I believe.
When 650 data reads out, and it is, let's say, according to our expectations, I think there's a lot of pharma interest, and pharma dictates what they're willing to do. Ideal for us is a pharma partner. The negotiations then will have to see. Look at the deal we did with J& J. Everybody likes that deal, obviously, because it had an ongoing stream. As you did another phase three, you got another milestone payment, which kept you alive. That's how we actually were able to do 13 phase three studies. I mean, that was amazing, right? If you look at those structures, if I could get that structure, obviously, that would be very exciting. It has to work for both sides, not only for us as Biomea, but also for the partner.
Brilliant. It is going to be an exciting 12-plus months, 15 months here. Stick close and keep a close eye on this one. Ramses, thank you so much for being with us today.
Thank you very much.
Steven, thanks for being with us.
Thank you.