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Thanks, operator. Thanks for everyone for joining the call. My name is Anupam Rama. I'm one of the senior biotech analysts here at JP Morgan. I'm joined on the call by Joyce Zhou, Rati Pinheiro, and Priyanka Grover from the team. Today, we're continuing our 2026 JP Morgan Biotech Conference call series with Biomea Fusion. We have Mick, Ramses, and Thorsten should be joining here in a second from the team. Guys, we have a lot to get through here in the next 30 minutes, so maybe we'll just hop straight into the Q&A. Phase I data for BMF-650, the oral GLP-1 receptor agonist is expected in Q2, which is technically tomorrow. Just to set the stage here for 650, this is a compound that's built upon the orforglipron scaffold.
What are the key attributes of the molecule itself that translate to potentially addressing the unmet need clinically and commercially in obesity?
Thanks, Anupam. I would turn this question over to Thorsten in a minute. He was the guy who actually was responsible for putting this molecule together, and he's running the program. What we're trying to get out of this molecule is number one, oral, which is similar to orforglipron, but number two, better pharmacokinetics, which could lead to better tolerability. We are testing that in our phase I program. Is Thorsten available?
We are currently trying to make Thorsten a speaker so that they can speak.
Yeah.
Should I go on?
They can go ahead and talk. Their lines are open.
Thorsten. Okay, Thorsten, are you on?
Yeah, Thorsten, you have to unmute yourself.
Thank you. Yes, I unmuted myself. Thank you very much for letting me in and letting me be part of this discussion. Yes. BMF-650, the upside of the molecule. When we looked at the chemical space, we believed that in the orforglipron chemical space, the PK of that lead compound really wasn't optimal. A key attribute of BMF-650 is very good, smooth PK and a high oral bioavailability, which leads to less inter-patient variability down the road. That's what we designed into the compound, so we are hoping for this. We're seeing this. We also looked at the intrinsic potency of compounds of this chemotype, and we believe that this 1 milligram starting dose in a 2.7-meter intestine will never distribute it well.
We took a little bit the potency out so that the edge when people are being introduced to the compound for the first time is off. I think this is a very good design, better PK and slightly less intrinsic potency at the beginning of the titration phase. We believe that people will very quickly get to a pharmacologically relevant dose and that the titration is not such a drawback for a compound of this class. We believe that's an asset and a design feature of the compound.
Can you remind us what is the size and scope of the phase I update that we're expecting here in Q2 for 650? Just remind us of the key tenets of the trial design.
Yes. Thank you very much for this question. Any compound that goes into the clinic first will actually have an SAD, so a single ascending dose phase, and it will have a multiple ascending dose phase. Our single ascending dose phase essentially has five cohorts where we dose titrate up single-dose-wise from 10 mg to 200 mg, single doses. We will there already then establish safety tolerability for the compound and also the PK that we wanted to see for the compound. This phase has actually already concluded. The MAD portion of the clinical trial is ongoing. Here we are dosing in four cohorts, 10 individuals per cohort. It will be eight and two active versus the placebo. We have here healthy individuals that are overweight or obese, so non-diabetic.
Then we will track the weight loss in what in the end amounts to be a six-week single daily dosing strategy, where we have essentially a two-week uptitration phase and a four-week hold as a titration target. We have titration target of 100, 200, 300, and 400 milligrams. We'll be able to read out essentially the normal four-week weight loss period when you titrate. We also have essentially the weight loss when we hold for four weeks a titration target. This will be giving us multiple dimensions of data readouts. How does the titration look, and how good is four weeks at titration target already with respect to weight loss?
We believe we will be extracting a very good amount of data out of our very, very first-in-human study for BMF-650 here with this design.
With all that being said, Thorsten-
Yeah
Can you just how many patients we're gonna be getting in this initial Q2?
Yeah. Okay, sorry, I may have run past this. In the SAD portion, we'll have 40 individuals over the five groups. Those are split into six who get the drug and two placebo. More importantly for the MAD in our four cohorts, overall we will have 40 people, so every cohort has 10, which we'll be splitting into eight on active and two placebo. Sorry if I ran past this too quickly.
What is a win scenario from your perspective in this initial kind of phase I update for 650? What are the reference comps that we should be considering in the competitive landscape?
Yes. Also a very good question, and I feel, people sometimes think about this one-dimensionally, just, you know, how much weight loss do you get over the time. This would be a key feature. I think there are two other features that needs to be in this triangle of balance. One is how quickly can you dose uptitrate, right? And how much, you know, GI disturbances do you see on your way up to the titration target. Those three things need to be looked at then in weighted balance. I do believe though that orforglipron in its originally reported four-week uptitration and weight loss study will be a good reference point. There the placebo group lost essentially 2 kilograms.
We never know how much percentage it was, but it was only reported absolute, and then the highest dose lost five. You could argue either you are looking around 5 kilograms or 3 kilograms placebo adjusted. In this range, I think one should look, but then very much have an eye on the side effects observed towards generating these weight loss numbers.
You'd point us to the actual absolute magnitude versus a percentage?
Yes. I have pointed in this direction because there is this paper that one can easily point to, and it's essentially on very solid ground saying at least compared to this. The field has certainly evolved to a degree, multiple GLP-1 small molecule receptor agonists are out there. Essentially the 5 kg, 5% weight loss mark is kind of where you have your eye on. I think it's not the only parameter to look for. You kind of need to be in that range. I mean, weight loss need to occur. Really check, you know, GI side effects largely and how quickly could you get there, and how quickly how high was your entry point of your titration versus target. Because this will in the end unfold to either 6 months titration strategy like orforglipron has it, or potentially just two.
If patients essentially see the weight loss earlier because they didn't need to titrate so slowly, they might be much more happy with the product that they are actually using.
I think a key element is, you know, patients with more weight tend to lose more weight, and so this is why people have generally moved towards percentages. In terms of a comparator, we only have the orforglipron study in which they did not give percentages, they only gave actual kilos.
Yep. Okay. The other ways to think about a win would be just, you know, did you titrate faster, and I think you said GI AE.
Yeah. Exactly.
Yeah.
Let's say pending positive data here in the initial phase I study for 650, how are you thinking about the potential range of next steps in studies?
Yeah. There's a lot of pieces and, you know, we have obviously to go into a longer term trial. I think if we can uptitrate quickly, you can look at the longer term effects fairly quickly. I think the goal ultimately, however, is to sort of not just look at how much weight can you lose over time, but maybe how you can keep it off. Because most of the studies that have been done so far, you go on the drug and then you stop it, and all the weight comes back.
I think what we wanna do is think about more sensibly how do you lose the weight at an appropriate rate, and then think about how do you back titrate in a way that keeps people at the weight they wanna be, rather than taking them off drug and seeing them jump back to where they were in the first place.
Okay. Maybe switching gears a little bit. Broadly speaking, what would you say are the top, you know, two or three most misunderstood aspects of the icovamenib program by the street?
Yeah. I'm gonna turn this one over to Ramses. He's put a lot of thought and effort into this and there's a lot of moving parts, but I think he can address them nicely.
Yeah. Two to three is difficult. I'll go fast. Let's start with the space overall. Does this space need a new agent? We have a lot of agents out there. They're all chronic. Every agent that you take in diabetes is a chronic agent. They all address one way or another the effect of too much glucose in your blood. None of them are addressing the function or the dysfunction your body has in conquering this problem in a healthy person. A healthy person has a sufficient pool of beta cells, and the beta cells produce insulin, and they take up the glucose. That's how it should be. We're doing symptom management, and half of the patients out there are uncontrolled, meaning they're on these drugs, but their HbA1c is too high.
About a third of all patients move into insulin dependency as the last resort. First point that is misunderstood is that this diabetes care is leading to an insulin dependency for a third of the patients, and we as a new mechanism of action are addressing exactly that. We don't play into the initial treatment phase, but we try to help a patient not to get there. When all standard of care fails, icovamenib steps in and takes your pool of beta cells, and that's the goal of the drug, improves the dysfunctional pool of beta cells and enhances them, restores the capacity so that you do not have to end up on insulin. It's a non-chronic agent, very, very key. You don't have to be on the agent.
We restore the healthy or the functioning pool within 12 weeks, and you end up with a benefit that you otherwise can't achieve, right? We're basically giving you a new lease here that you could, if your lifestyle changes, could potentially lead to a long-term benefit. Now, many people will not do that. They will need another dose of icovamenib over time, but the drug is designed for complete restoration, and we're designing studies right now where the endpoint is 26 weeks primary, 52 weeks secondary endpoint. With that body of data from those two studies that we're doing right now, we go to the FDA for an end-of-phase II meeting, and we're planning to go into phase III next year. That's not easily understood that that's how far we are along in this.
We have biologic clarity that this is happening in the pancreas, not from us, since about 20 years. You can read up on papers where people see menin is the culprit or is the checkpoint. We have evidence in animals that we can show to you, and we have the islets, the human pancreatic islets, where we've done the experiments. Now we're in the humans, and we see the same effect. We have a very solid base of why we're doing what we're doing, and we can predict the outcome.
I'm gonna turn it over to Joyce Zhou from the team.
Sure.
She's gonna ask a few questions.
Thanks, Anupam. Digging deeper into icovamenib, 52-week follow-up data from the COVALENT-112 study in type 1 diabetes is expected in 2Q.
Yeah.
What would you have us look at within that update?
Yeah, that is sort of a program that comes out of nowhere, right? Because everybody's looking at type 2 diabetes. This is a proof of concept study that we started, and we have two cohorts there. We're looking at patients zero to three years since diagnosis and three to 15. There is hardly any study out there that looks at patients zero to three and three to 15. They all look at early onset. What we wanted to see is what benefit can we give to these patients in general in type 1 diabetes at various doses with these two different subsets of patients, and it's about 20 patients overall, meaning these increments where we hope to see responses, likely in the zero to three and likely at the higher dose, is a handful of patients.
Overall, we will show you 20 patients.
Got it. Going back to type 2 diabetes.
Yeah
How is enrollment going in both COVALENT-211 in type 2 diabetes and COVALENT-212 in type 2 diabetes in patients not controlled on a GLP-1? Where are you in terms of site activation on both? I believe your guidance for data from both studies is Q4 of this year.
Yeah, that's correct. All that is correct. We are still holding on to that guidance, which is a tough one, but we do think, because of all the experience, the understanding we have of the market, of the investigators, of the sites, we will achieve this target. Right now we have engaged with about 20-plus sites. They're all up and running, and we're now getting site initiation visits, all these workflows done so that we will start enrolling in Q2 and hope to finish enrollment of these two studies in Q2 so that we have a readout by year-end. Everything is going per plan at this moment. Yeah.
Great. I will hand it back over to Anupam.
Sure.
Ramses, maybe you could expand a little bit about outlining what a win scenario looks like?
Yeah
in COVALENT-211 and COVALENT-212 programs in this 4Q update.
Yeah. We have quite a few updates that are really meaningful. It's 1, the type 1 update coming in Q2. It's the 650 that we talked about earlier, also in Q2. At the end of the year, we will show those 2 Phase II studies that are now going after type 2 patients, that those are identified to go into Phase III. Those studies, typically in type 2 diabetes, your endpoint is reduction in HbA1c. When you look at what FDA has approved in the past, they have approved 0.5 as one of the benchmarks. Our studies have shown 1.5, 1.8% placebo-adjusted in an all-comer study. If we hit anything above 0.5, we're good, meaning we feel that's a win. Now, how far can I get it?
It depends on the patient, depends on the numbers, on the type, et cetera. You can't get it as precise as you wanted. 0.5 and above for an agent that is not chronic would be a win for me.
The other part of that I think is really, you know, we've seen in the two patient populations that we've showed today that we have a reduction at 26 weeks and then there's a reduction at 52 weeks, which is even bigger. What we don't know is how long that persists for. I think that's part of what we wanna show as a follow-up study to COVALENT-211 and COVALENT-212.
The win will be ultimately if it's still coming down at week 52 weeks, which would be a sort of recap of the data that we've just produced in our COVALENT-111 study. Then we think that that's a win too, because then there is a very strong probability that this is gonna be utilized significantly instead of injectable insulin to sort of bridge that gap between when you're failing on all the other agents that are currently out there and when you have to go onto insulin.
Just to clarify.
Mm-hmm.
The 0.5 that you're talking about as a win scenario, that's for COVALENT-211 and COVALENT-212?
Each one, yeah. Either one. Yeah.
You get that type of reduction.
Above, I mean, 0.5 is your bottom hurdle that you have to clear. A DPP4 was approved for that. They look at risk, and they look at what do you give to the disease and what do you take from it. So if I truly keep somebody off insulin, right? This is your next step, meaning I take the last line, and I say, "This patient, standard of care has failed him. HbA1c is rising." We can bring that down by 0.5 and continuing over time, not being on a chronic agent. It's a win. I mean, it's a win for the patients, it's a win for the FDA. Obviously our goal is that this trend continues and improves even further. My minimum hurdle would be 0.5. Yes.
Can you speak to that? You talked about your, I think recently, in your press releases, talked about data from some of the chronic toxicology studies, right?
Yeah.
Trending the data that you see in COVALENT-211 and COVALENT-212, and Mick has kind of alluded to this, how does your chronic tox work evolve your thoughts on the development program?
Yeah. It's an interesting question because you're kinda you're hinting towards now that you can do longer term dosing because we were limited by the tox we had. Now we have shown in two species that longer tox is okay. We don't see signals there, or we think we don't, and the FDA would probably agree with us. Do we need it? I think there will be subsets of patients, not the two that we have in our phase II studies right now. We feel 12 weeks is fine. The results are stellar if you just look at those subsets. There could be subsets where, for instance, in type 1, where longer dosing does make sense, or redosing does make sense, or where there are patient subsets where it could be beneficial to have longer dosing.
Like, the focus that we're currently on is not limited by the tox, but it's the outcome that we're achieving we think is sufficient, it's continuing, and it's beneficial to a large degree for those two subsets in type 2 diabetes. In future patient populations, particularly like type 1 diabetes, I believe a longer term dosing could make sense, and that's in the discussion.
Okay.
Yeah.
To round out the call here, can you remind us of your cash runway and position, and just remind us what key milestones are assumed?
Anupam, you have it in your report. You're one of the staunch criticizers so far of cash position. It's always a balance, right? Over raise, under raise, and you don't wanna dilute too much. You still wanna produce good, valuable data for everyone, and we're all shareholders. Our cash today that we have is $56 million at the end of last year, and it will last into 2027. What does that mean? Somewhere in Q1, based on what our auditors have identified as our spending plan, we're running out of cash. But what do I buy for that cash? I buy type 1 data readout, which could be transformational. I'm not saying it is.
I'm just saying it gives a new potential, which is big, and there is nothing approved in type 1, as we all know, at least not in phase III. Type 1, can we open a door there? Yes, no, we will see. We have BMF-650. It's an oral agent. It has new PK. Pfizer has just paid for an Asian compound that is also oral, over $100 million as an upfront, not just now, but recently.
Yeah.
So-
Pre-clinical.
Pre-clinical. We have to see what the value of that is, but that's an interesting update, which is coming at the end of Q2. Then you have the two updates coming before year-end in our phase II, which are 26 weeks primary endpoint data. All that is part of the current cash. Now, the cash is always tight in biotech companies. We've reduced the size of this operation from spending a lot to spending really only for those programs I just mentioned. We're not doing any more groundwork research. We think we're done with that. We have released those former employees just to focus on clinical development, quality, CMC, and all those key departments. We're right now running lean at 40 people. The spend is really focused. When do we raise is probably one of your next question.
The question is always, it depends, right? We have enough power to get to where we need to get to. If things work out the way I think they will, we will raise along the way, obviously.
Mick, Ramses, Thorsten, I wanna thank you guys so much for taking the time. You guys have got plenty of updates coming here.
Yeah
imminently in Q2, which is tomorrow.
Mm-hmm.
So, um-
Yeah
you know, we look forward to the updates, and I hope you guys have a great rest of the week.
Okay. Thank you.
Thank you, Anupam.
Thank you very much.
Very good.
Thank you.
Thanks a lot.
Thank you, everyone, for joining.
That concludes today's call. Thank you all for joining. You may now disconnect your lines.