All right, welcome to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I am one of the senior biotech analysts here at JPMorgan. I'm joined by my squad: Priyanka Grover, Joyce Zhao, and Rathi Pintai. Our next presenting company is Biomea Fusion, and presenting on behalf of the company, we have CEO Mick Hitchcock.
Thank you.
I'll call it an ovation, man. It's a lot of pressure.
Yeah, thanks a lot. Good afternoon, everybody. Thanks for coming. I want to thank JP Morgan for putting on the conference and for inviting us to give our presentation so that everyone can see what we're doing. Also, just for context, my name's Mick Hitchcock. I'm CEO of the company. I've been on board since about March, and I'll jump right into the presentation. First, of course, is the legal disclaimer, and I think you've probably seen enough of these after three days that I don't need to dwell on it. I think everybody knows what it says, so in terms of what Biomea Fusion is working on currently, we are developing two assets, and we believe that they're both significant contributors to our new focus, which is diabetes and obesity. Icovamenib, specifically at this point, is targeted at diabetes. It's an oral small molecule.
What I'll talk to you about is some data that we got out of this COVALENT- 111 study, and then tell you about the two patient populations that we have significant activity in, and then talk about where we're going next. On the other hand, more recently moving into the clinic is a program with an oral GLP-1 receptor agonist, and this is called BMF-650. It's targeted for weight loss. It's an oral, again, oral small molecule. We're in a study, a phase I study now called GLP-131. We are looking at enrolling obese patients so that we can study weight loss. Just in terms of giving you some background in terms of what we're looking at, the existing Type 2 diabetes treatments tend to address the symptoms and not the disease progression itself.
And what we have here is a plethora of names, different drugs that have been developed over the last 30, 40 years, and they all address the symptoms but not the root cause of diabetes. And you've seen all these things like metformin and dipeptidyl peptidase inhibitors, DPP-4, I can't even say it, thiazides, et cetera, and GLP-1s. And I think there's a lot of drugs out there. There's been 60 that have been developed, but they all address symptoms. Icovamenib, on the other hand, is a selective and partial menin inhibitor, targets a pathway that has not been addressed to date. Now, the root cause of diabetes is driven by progressive beta cell failure.
In this graph, what we show is that your beta cells that you're given after you get to about age two, they increase maybe a little bit up until you're age 20, and then they go into a decline. You can see this number going down over time. By the time you're diagnosed with diabetes, you've usually lost about 50% of the cells, and you will continue to lose them even when you're on these particular therapies. Now, diabetes itself is a big health problem. In the U.S., about $1 in every four is now currently spent for healthcare of diabetes patients. There's about 35 million with Type 2 diabetes, and of those, 7 million are considered insulin deficient, and they're one of the targets that we'll be looking at in this presentation. Let's start with the results.
This is really where I want to sort of engage you and get you excited about what we're doing. You can see the green bar at the left. This is the treatment period. We actually treat orally once a day with 100 mg just for three months. And then we follow the A1C over time. You can see it goes down over the 12-week period. But then when you stop dosing, it continues to go down. Now, every other drug that I showed you previously, if you stop dosing, basically the A1C will return to baseline in no time, certainly within a month or two. So the fact that it goes down by 26 weeks was pretty special, and we announced that data earlier in the year. Of course, the expectation was then, well, okay, if you follow them for longer, it'll either flatten out or go back up.
But in fact, as you can see here, the 52-week data show that it continues to go down and that you get overall about a 1.5 reduction when you consider the placebo-adjusted rate. So that's pretty significant, and it's pretty similar to many drugs that have been approved. And we feel that for that reason, this gives us a lot of credibility around dosing. Now, what you'll notice here is that there's not a lot of patients, and these were pulled out of the trial that I showed you earlier. And so I'll show you later how we're addressing that particular criticism. Now, why does it work? Well, this is a measure of insulin production. It's called C-peptide. It's the piece that gets cleaved off of insulin after insulin is made. Insulin gets used up, but the C-peptide remains.
And so it becomes a measure of how much insulin has been secreted. You can see it goes up over time, and it continues to go up after we finish dosing. And so we believe that that is based on the fact that we increase the number and the productivity of these beta cells in the pancreas. Now, obviously, it's a great theory and all the rest of it, but what leads us to have credibility around that is actually a couple of things, and I'll talk about them in the next slides. Menin, which is the target for our drug, it suppresses beta cell proliferation and function. And so if we inhibit menin, what it's going to do is to lift that brake on the replication.
A short 12-week dosing period is good enough to allow beta cell regeneration, and that continues post-treatment and drives the sustained A1C picture that we showed. Now, there's also the question of, well, does this work? How does this work in normal situations? Well, one of the situations that we looked at in terms of where menin controls the beta cell proliferation is in pregnancy. And you can see this particular publication that was put out talks about how when you have a pregnancy, because of the extra mass in the pregnant woman, we do get occasional cases of, I'm sorry, I'm blanking on the name. We do get diabetes in pregnant women, but it's not very often. And the reason it doesn't happen mostly is because menin is being suppressed and we get the extra cells being produced.
This has also been showed by studying cadavers of pregnant women, and you can actually see in the pancreas that there are more beta cells. So icovamenib has been shown to directly inhibit menin. And so what it's doing here is essentially recapitulating what happens in a normal pharmacologically relevant process, and it enables us to give us a sort of rationale for why our drug is working. Now, obviously, in the people, we can't go in and pull out their pancreas and look at their beta cells. But what we have done here is in two studies that are shown in this slide. On the left-hand side, you see the studies in rats where you can show that if you give icovamenib, you increase the number of beta cells.
And unfortunately, I don't think you can see the little red dots on the bottom right-hand corner of that four-panel block. But insulin production is increased in those situations when you give icovamenib, and that's because you're actually causing proliferation because you're inhibiting menin. On the right-hand side, what we've done is a similar type of experiment, but these are with human isolated islets, and what we can see there is from two different donors. If you just add the solvent, you get a certain amount of insulin production. The insulin production is shown by the green stain. On the right-hand side, when we've treated the cells with icovamenib, you can see much more insulin production.
While we can't actually show that these cells are replicating in the humans, we have enough preclinical data and evidence that, in fact, that's what the situation is happening, and that's why when we give the drug for three months, you see an increase in production of insulin, and then it's maintained going out through 52 weeks, even nine months after you've stopped dosing. Now, within the study that we did, COVALENT- 111, there was another group of patients where we found significant effect. This is a different group of patients, but these patients came into that study on a GLP-1 agent. In order to get into the study, they were considered failing their regimen because the target dose that you're trying to get to is 7% A1C, and these guys came in at 7.5 or above. They're all failing the GLP.
We found these 12 patients who were on GLPs. We kept them on the GLPs, and we gave them three months' dosing of icovamenib. You can see again there's a decrease in terms of the A1C in the icovamenib group compared with the placebo, and then again, once the drug is stopped, the effect continues, and it goes down at 26 weeks, and it goes down at 52 weeks, and again, a significant drop, minus 1.2 there. And when you look at other drugs in this therapeutic area, if you can get anything greater than a 0.5 effect over six months, that's usually considered enough for registration. If you look at some of the other drugs, they might have a 1.0 or 1.5, but I think we're in the similar ballpark to some of the other drugs in terms of potential registration.
Now, again, the rationale for why does this work? Icovamenib, you can see on the left-hand panel there, if you give icovamenib, you increase the amount of GLP-1 receptors on the pancreatic beta cells. And on the right-hand panel, you can see that it also increases insulin production. Now, what about the safety? It's all very well to look at the efficacy of the drug, but it's safety also that's required to get you onto the commercial front. So if you look at the first two columns here, this is looking at the whole study. We had 267 patients, 66 on the placebo, 201 on the icovamenib combined arms. And you can see here that the adverse event rate is pretty similar between placebo and icovamenib. There's nothing there that would suggest any issues.
When we get to the next slide, what we're looking at now is not necessarily AEs, but specific events, and in this case, looking at ALT and AST increase, we do see some ALT and AST increases. These are monitors of liver function, and what we found with those is that they do increase a little bit while on therapy, but if you continue therapy, they go away, and you can see the bottom line there, resolution of those without interruption of study treatment, 100%, so they all resolved over time, so we feel pretty comfortable that we have a safe product too, so looking at the overall effects, we have a durable treatment effect in severe insulin-deficient Type 2 diabetes. That was the first group I showed you. What I haven't shown you is higher icovamenib exposure leads to improved responses.
What we did was we actually segmented the patients into groups of A1C reduction, and the ones with the higher A1C reduction had higher exposures to icovamenib, so we thought about that and decided, okay, we need to do another study to figure out how we make sure that all the patients going forward get a higher exposure, and we've just finished a study. It's called 121. It's a study looking at food effect, and we showed that if you give the drug without food, you get a certain exposure. But if you give it with food, and it doesn't matter whether it's a high-fat meal or a low-fat meal or half an hour after or one hour after the meal, then you get twice the exposure, and so for our future studies, we now have dosing instructions that will require the patients to be dosed with food.
On the third bullet point, icovamenib increased insulin secretion as measured by C-peptide. I showed you those data. The treatment effect in GLP-1 failures continued to improve, and those again are going out to 52 weeks. And we have a favorable safety profile through week 52. Now, somebody asked me before the talk, what is the most underappreciated fact? And I think this is it. COVALENT- 111, the two patient populations that we showed, we have an effect. It highlights the potential to restore endogenous insulin production capacity in patients who would otherwise progress to chronic insulin therapy. And anybody who knows anybody who does insulin therapy knows that that's not a great thing. So we are now offering, with this treatment, the possibility of short-term oral treatment, i.e., three months' daily oral pills rather than lifelong injectable management. And we think that's pretty significant.
We're moving forward with two studies to take these populations forward and make sure that we can repeat the outcome of these two studies. The first one is called COVALENT- 211. This is the insulin deficient patients. And you can see there we're taking patients with HbA1c between 7.5 and 10.5. Their BMI is not massive. They're a little bit obese or a bit smaller. So anything under 32, we're taking. And then it's basically by looking through the data, we found that the effect is better in patients who've been pretreated with one to three antidiabetic medications. They'll come into the study. They'll be randomized to arm A or B. It's 40 patients on treatment versus 20 on placebo. And we'll get those enrolled and then followed up for six months. And so the primary endpoint's at week 26 and the secondary endpoint at week 52.
Now, the parallel study, which we'll be doing at the same time, is COVALENT- 212. And this will take the patients who come on with a GLP-1-based therapy. We're restricting it in this case to, I don't know if you call it semaglutide or semaglutide. I'm not sure what the correct pronunciation is. But these are larger patients, tend to have a BMI in the 25-40 range. And we bring them in with A1Cs greater than 7.5, i.e., not meeting target. And they will stay on their GLP-1 therapy through the trial. And we have the same makeup in terms of 40 patients on treatment and 20 patients on placebo. And so these two studies will run in parallel, and we're in the process of getting those going right now. So what we've showed you is the mechanism of action of icovamenib.
There's the dual effect on beta cell function, increase in beta cell mass, and increase in insulin synthesis and secretion, and then the GLP-1 receptor expression, which is increased expression and increased release of the enhanced incretin effect. We also get enhanced weight loss, but we are not exploring that further at this time. Now, the second product I wanted to talk to you about is our GLP-1 receptor agonist, BMF-650. It was designed for better bioavailability, and so that with better bioavailability, you should get more consistent efficacy. I think one of the problems with the orforglipron compound that's also an oral GLP-1 receptor agonist, it tends to have a lot of GI side effects, and so you have to titrate up slowly.
Now, the data that we produced around the mid-year was a monkey study, and what I've shown you here is the results from the monkeys in terms of body weight change over time. There's five monkeys in each group. The gray group at the top is the monkeys getting the vehicle. Then there's the orange group, which get 12, sorry, 10 mg per kilo, and then the green group, which get 30 mg per kilo. And you can see after a 28-day dosing period, and this is significant in terms of the reduction in body weight is associated with a reduction in food intake. By the time you get to the 28 days, the top dose has given you a 15% reduction in body weight, and the mid-dose or the lower dose has given you a 12% reduction.
So armed with these data and all the associated toxicology, we looked at how to get in the clinic. We have a chemotype, which is similar to the Chugai chemotype, orforglipron. And so that drug has not shown any LFT signals, and we've not shown any LFT signals. And as you know, the other Pfizer chemotype has had a number of LFT abnormalities that have led to discontinuation of development of those drugs. So daily oral dose in cyno monkeys, healthy and obese for up to six weeks has led to no ALT and AST elevations. And the first in-human study, which is ongoing, I'll show you in a second, also to date has shown no ALT or AST elevations. This is the design of the phase I study.
On the left-hand side, you can see the single ascending dose, the SAD, and we go up 10 mg, 25 mg, 50 mg, et cetera. And you can see where we are now by the red arrow. In each of those dose groups, there are six of the blue patients. They're the ones getting the active drug. The two gray ones are the placebos. And so for us to go through the rest of the cohorts, we'll end up with 40 patients getting single doses. And then we'll move into the multiple ascending dose. And in the multiple ascending dose, we will have overweight or obese patients, and they will have come into the trial with a BMI of 30-45. So we'll have some extra weight to be able to see them lose it in the study. We are in the process of getting ready to start the MAD first cohort.
That should be in the next week or two, and then we'll escalate from there. And the outcome is body weight, and we'll look at reduction in body weight over time. We'll get both a 28-day normal type of outcome, but we'll also get a day 42 because during the toxicology, we decided we would do a six-week toxicology study, and the FDA allowed us to translate that into a six-week in-human study. And so we'll be hoping that we get good results from that. We've got eight patients there who are on active and two on placebo, and we'll get the data shortly.
The overview and the key milestones, I think, are presented in this part of the program: the COVALENT- 211 insulin-deficient first patient enrollment planned in 1Q, 26-week readout expected in 4Q this year; COVALENT- 212, which is the GLP-1 patients who are not meeting target. The first patient, again, will be enrolled in 1Q, and the 26-week data readout in 4Q. And then for the GLP-1 study, using obese, otherwise healthy volunteers, we're still in the updose in for the single ascending dose, but we expect to have the 28-day weight loss results in the second quarter of 2026. That's my presentation. Thank you very much for your attention.
Thank you. Yeah. I'll ask the first couple of questions, but there's an opportunity for others in the audience to get their questions in. Just raise your hand when I prompt.
Just wondering, for both COVALENT- 211 and COVALENT- 212, first patient enrollment is in this quarter in Q1. So what are the final kind of gating factors to getting that first patient enrolled?
So we've done most of the preparation. We've got the protocol approved. We've got a CRO on board for both studies. We've got the place that's going to look at all the blood work. And so now what we need to do is to do a final selection on the sites and send them drugs so that they can start dosing patients. So we're pretty close.
And just I know the data is in Q4, but broadly speaking, for each study, how would you kind of define a win scenario?
I think a win for both studies would be to come up with the data that's similar to what we saw in the 111 study.
Anything above a 0.5 reduction at week 26 is considered approvable. So from 0.5 up, we'd see 0.5 as good because it was approvable, but we'd like it to be better so that it's more competitive with what type of reductions have been seen with other agents, maybe in the 1.8- 2 range.
Questions from the audience? So let's say you get kind of your win scenario, and it's compelling enough to move to the next stage. What does that look like from a clinical perspective, but as well as a strategic perspective?
I think from a clinical perspective, once we get the 26-week data, we'll be pursuing discussions with the FDA to build out a phase III program.
The big issue that everybody talks about with a phase III program is how many patients are you going to need, and how long is it going to take you to enroll them? We had discussions with the FDA early on about the three months of dosing. They basically said, "If you do three months of dosing, you will not be considered a chronic agent, and you will not have to put in thousands of patients and do all the long-term work, studying cardiovascular outcome, et cetera." We feel it's a smaller subset of patients that we would need to put into a phase III. Obviously, we'd like to have those discussions and get that nailed down after we get the phase II data.
Maybe a quick one on 650.
Just thinking about the MAD portion and the efficacy portion, what would you be looking for in terms of weight loss? What's a win scenario given the competitive landscape?
Yeah. If you look at the other things that are out there at the moment, the general perspective is you need after 28 days a 5% weight loss. If we get a 5% weight loss, that'll be great. If we get a little less than that, then it'll be, well, how well is the tolerance? How well is the up-titration dealt with? One of the challenges with the GLP-1s currently is that they do take a long time to up-titrate, and I think we've seen recently some of the drugs take as long as six months to actually get up to the weight loss dose.
I don't know about you, but if I want to lose weight, I don't want to wait six months. So I think having a faster up-titration period would be beneficial. In terms of the general development, provided the safety is good and we do see weight loss, I think what we're looking for, as much as anything, is not just how to maximize the weight loss, but how to give somebody weight loss that's maintained over time. And I think a better strategy than what we've seen clinically from the agents so far is to actually use a dose that gives you a slower weight loss. But then when you get to the weight you want to be at, maybe back off on the amount of drug so that you go into a maintenance phase rather than going off the drug and gaining all the weight back again.
Any final questions from the audience? I have one more. Can you just remind us of your cash position and runway?
Yeah. Right now, we don't have the 4 Q numbers yet, but if you look at 3Q and you add on the $27 million that we raised, we were about $70 million at the end of the third quarter, and we're spending somewhere around $12 million, plus or minus a couple, for each quarter. So as we lay out the runway right now, it gets us sort of into early 2027.
All right. Thank you.