Is somebody closing the door?
Yeah, someone will run and do it. Okay, good afternoon, everybody. Thanks for joining us for day one of the Citizens Life Sciences Conference. My name is Jon Wolleben. I'm pleased to introduce Biomea Fusion and President Ramses Erdtmann, who's gonna run us through a presentation. We'll have some time for Q&A towards the end too in the room. If not, I'll just ask some hard-hitting questions.
Perfect. Okay, thank you very much, and thank you for hosting us here. It's a great pleasure to be here. I have a lot to talk about. I can run through it fast. I can high-level it. We can have meetings later on if you have further questions. I'll gladly answer them either today or afterwards. Just look me up, and then we'll set up a time. Okay. Biomea Fusion, if you think of us, think of us as a company focused on diabetes and obesity, period. We have two assets. One is something that nobody has ever tried before, yet, all pre-clinical and early clinical data indicates that it's working. The other one is an asset that everybody knows, but not quite, there is consumer satisfaction with what we know from the GLP-1 space, and we're trying to improve upon that.
The markets in both are huge. We don't need to go there. The way we're doing either one of those two assets, they were both in-house developed. The way we're targeting the pathway that is required to achieve the necessary effect is slightly different than others are doing it. We're funded through Q1 of 2027, so what you see today in terms of milestones, et cetera, is basically achievable for us without further funding necessary. Okay, let's go into the program. The first program is icovamenib. It's a potential first-in-class menin inhibitor. The word potential is a legal word that the lawyers made me do it. Yeah, I think it is the first in class. I know it is the first in class, but potentially because we're not approved yet. Obviously, it's investigational. The market for diabetes is huge.
You can find these slides on our website, and you can read up on it. It is much bigger than I had thought. I come from the oncology side about 10 years ago, and going into diabetes has been very interesting and challenging. The market is very big. It's ever-growing. $1 in $4 of our U.S. healthcare system is spent on diabetes-related diseases. The number I would like you to focus on is this one down here that says one out of three people in the U.S. with Type 2 diabetes are using insulin. What we're doing is we're helping these folks that have failed all standard of care to now have another option before having to go to insulin. Insulin, if you think about it, is sort of the last resort of what you can do to your body.
You're taking the mechanics out, and you're saying, "I'm going to give you something now." That pump is so smart with AI and everything, it still doesn't do what your body does inside naturally. Typically, you find people die, and they lose 12 years- 14 years even though they are on insulin. The disease has tremendous side effects. Okay, this is how diabetes is understood so far before we came along. What everybody's trying to do is they try to address the hyperglycemia, which basically means too much sugar in your blood. It causes toxicity, and your body is not able to overcome this sugar. Why is that?
Because your pancreas makes cells, they're called beta cells, they produce insulin, and your body looks around and says, "How much insulin do you need?" Well, if you overburden the system every day with the wrong food, with no exercise, with American lifestyle, I'm American even though I come from Germany, you end up potentially, and a lot of people do with prediabetes, it's one out of every third American, but those guys that are depicted here, which is about 38 million in America, end up with hyperglycemia. They have too much glucose. We address that with targeted agents that address that symptom. They do not address the reason. The reason for this problem is that you lose capacity on your beta cells. They do not. They wear out, they die, they lose function, and by the time you get diagnosed, you lost 50% of them.
That's the root cause. What do we do? What we do is something that mother nature has sort of guided us. When we started about 10 years ago, we looked at the target menin, as you can see here, and we thought, "God, menin is such an interesting protein. What does it do?" Well, if you go into the literature, menin has been identified through pre-clinical and human data consistently. If menin is reduced, it improves beta cell mass and function. Now, our website is full of articles, you can read up on them, where that is being shown as a mechanism the body uses to address problems when you're pregnant. You have a problem, you need more insulin. How do you do that? Menin is the pathway that the body is using.
Now these studies are showing here on the right, they have done that in pregnant mice and in animals just to see, is this the right pathway? Karnik has shown that in 2007. It's not very well known. It's not known for a long time that menin is an interesting target for diabetes, but all the data leads to it. Now what we have done is we said, "Okay, if a person shows up with a depleted pool of beta cells and becomes potentially insulin dependent, what can I do for them?" If I could rebuild the pool through our drug, the pool is growing, and as the pool has matured later on, and this time frame here is up to whatever, about a year potentially, and then your production of insulin has gone up, and your glucose has come down.
That is the postulated pathway of what we had hoped for. We have checked that in animals and in human islet cells, and I'm going to show you those results here. These are just the two pathways of what we see menin does when you inhibit it. Not only do we produce beta cells, but we also enhance the whole metabolic system by giving you more GLP-1. That's not because of us, because of this pathway, and more GLP-1 receptors, which leads to improved beta cell function , decreased blood glucose, but also the synergies with GLP-1 based therapies. We have explored both sides, but what I would like to show you is this experiment that we did. On the right-hand side, we used pancreatic beta islets, which are cadaver islets that you culture and you hold and you keep alive, and you test your theory.
You can see here the green bar is a maximum amount of icovamenib is increasing only with the stimulus of glucose. The body responds when there is high glucose. Menin on the right side is inhibited through icovamenib. The more menin you inhibit, the more the body responds with the beta cell mass responds. That's in human islets. We've done the same experiment in animals, and we came to the conclusion this is working. Now, on the left-hand side, you can see that we're actually addressing menin. Menin is being downregulated, not to zero. You don't want to go to zero with anything. The body needs menin. We're only reducing it to about 50%, 60%. Okay, now that we've known this, we then ask the question, what does it do for the GLP-1 receptors? You remember I showed you both pathways.
Here we can see on the left-hand side that the receptors, the protein, is upregulated. Interesting. Insulin is upregulated the more icovamenib you use. That's a very interesting finding. Down here in combination with semaglutide, this is semaglutide alone, we improve the insulin response of semaglutide. Same thing. Again, these are islet studies. You could argue, well, not everything translates. Islets is pretty close to human body, so we were very excited when we saw these results for the first time. If you go now into a human, this data was presented last year in December. You can see the green shaded area shows you the dosing period of 12 weeks, and you can see here the purple curve is the HbA1c, the blood glucose, as it comes down.
The most exciting part about this graph is not only the amount, 1.2%, which is huge in just looking at all drugs out there, but also that it comes off drug. You're not on drug. 12 weeks is sufficient to restore the pool, and the body is responding accordingly. These were patients that were identified as severe insulin deficient. If you are obese and your BMI is 40, the pathway of resistance is so strong that even if I give you more beta cells, very likely you're not responding well enough to overcome the resistance. Here I have typically a patient with BMI either overweight or normal weight, and you can see a beautiful response. This graph is probably the second most exciting graph because we show you that the body is making C-peptide as a surrogate for insulin. The body is making insulin.
There are cells that are making insulin, and they're making more insulin than at baseline, and they're continuously making it even though you're off drug. This is very, mechanistically important for us, our scientific advisory board, for people that are in this space. They find this extremely exciting. Okay, here now we're looking at all patients we enrolled, and we ask the question, of all these patients, there were 12 patients that were on a GLP-1. By the way, all of these patients were obese. Were we able to control sugar in an obese person? Well, we were if you were on a GLP-1, because the GLP-1 is stimulating this pathway and we're giving the GLP-1 an extra boost, even though when the patients were enrolling, they had high HbA1c.
We brought it down because the GLP-1 was on board or because of us having this synergistic effect. You can see here the same thing. The HbA1c reduction is driven by an insulin response off drug. Also super exciting. Now, the company had gone through a lot of, how shall I say, difficulties in its early stages. Why? Because we were dose escalating and the FDA said, "Look, guys, you're dose escalating, but we see liver responses that we have to put you on hold for because we don't understand them." At that time, we were dose escalating. We don't need to dose escalate. All our studies are done currently with 100 milligrams. If you stay at 100 milligrams and you escalate after and you go to 200 milligrams, you don't see those liver enzyme increases.
Here you can see AST, ALT, all Grade I except for one Grade II, which is mild and moderate. This is a very, from my perspective, good safety profile. I couldn't have asked for something much better because these percentages are quite similar between us and placebo, except AST, ALT, but that is at the Grade I, Grade II level. We have updosed, just as a point of reference, and I made it down here, we've updosed to 500 milligrams in our cancer study where we tested the menin pathway in cancer. There we have seen a well-tolerated safety profile. We feel very comfortable with 100 milligrams.
We get the efficacy we want with a very, very good safety profile. Okay, now comparing ourselves to all the other guys in the space, even though all of these guys are chronic agents, we're the only non-chronic agents. Even though they're dosed for nine months longer than we have in this experiment, we're achieving similar results as the best-performing agent. You should say you would argue, "Why aren't you in phase II studies?" Well, we are in phase II studies now. These were early phase II studies. We're now doing a phase IIb . What do we know? We know 100 milligram does the job. Our food effect study confirms at what time point you should take it. When we started dosing, we didn't know, is there a food effect? We didn't know at what dose concentration can I go?
At what dose duration? What is the heterogeneity of these patients? We have answered all these questions. We understand the patient. We understand 12 weeks does a very fine performance. We don't need longer dosing. It's a non-chronic agent. We have strong clinical data in two groups of failing, meaning when standard of care fails, these two subsets are very prominent. We don't really have treatment-emergent AEs. Okay, so we started these two studies that are now going through their phase II's. We're funded up to the primary endpoint. They're gonna read out by the end of the year, and we can go into the details of these studies, but they basically resemble our learnings from the first larger study I just showed you.
This is probably one of the most important graphs in the deck because it shows where do we fit in. If we pass this phase II advancement of two studies, and we go into phase III, what is the benefit we give to a patient, to society, to the healthcare system? It's about $20,000 a patient per year. Why is that? The minute a patient moves over here, and by the way, 1/3 of all these patients that are diabetic will end up here. The minute they move over here, they cost the healthcare system $20,000+ every year. The earlier they become diabetic, the longer this $20,000 is accumulating. Icovamenib will prevent will give patients another option and will potentially prevent, that's probably the better term, from somebody from ending up here. How long can we do that?
How long is the effect lasting? We're still at the very beginning of understanding this effect, but just the chance you can prevent, one, the expense and two, the benefit for somebody that is not chronically on an agent. He can potentially reduce the agents he's on while having had icovamenib. Okay, I don't know how familiar you are with this space, but if you go through the studies with GLP-1 agents, you can see that 15%-45%, depending on the study and whatever drug was used, are not getting to an HbA1c target of less than seven. We're estimating about 30% of all GLP-1 patients will end up requiring insulin. That's the other group. On the one hand, we have the insulin-deficient ones.
On the other ones, we have the obese patients that are on a GLP-1. Okay, there's a second compound. Well, we still have good time. There's a second compound that we have started to work on about four years ago. We're now in the clinic. It's our own compound. We are actually our background, we are drug developers, not myself, but the team that I'm with. So we look for how can I do things better. If you look at the GLP-1 space, you say, "God, the numbers are big." Obviously, they're huge. What are the drugs that you're taking? If you ask all your colleagues in New York and you say, "Hey, are you on a GLP-1?
It looks so good." "Yeah, but I'm titrating, and I've tried something different, and I'm not doing this, and I can't use it anymore." It's not quite easy to get your body to agree that you're full when you're not, right? It's a game that you're playing with yourself, which is mentally driven, but also through the drugs, gives you an edge whereby you could lose weight. That's true, but seven out of ten patients are not staying on, even though the drug is free. That's from a study in the U.K. Something's not quite right with these drugs, even though the pathway we all agree is phenomenal. What we felt was required is to improve the profile of these drugs, so potentially you don't have to dose that high, but you can stay longer on drug.
You can overcome the desire to leave the drug by having an improved PK profile, which is we have tried to achieve that with better bioavailability, with potentially a longer half-life, with not having this peak to trough hit you, but just to make it easier for the body to absorb the drug. So generally, we're aiming for a more patient-friendly design, and that's what we started with when we all got together. We now have a drug that is oral. That was a number one criteria for us, make it oral, and come up with a scaffold that will survive. The Pfizer scaffold didn't survive. Luckily, we didn't follow that scaffold. What you see now here is our first animal data. We're comparing here to Carmot.
They were one of the few who published their monkey data. We've used these similar monkeys. We've gotten a little bit better of a weight reduction than Carmot. I don't know. No, I don't have that slide in here. What's interesting here is if you look at those cohorts, this is a mean. The tighter the mean is with all the monkeys, the more you know you're doing the right thing, there's less variability. We have a chart in our corporate deck that shows that very nicely. We feel we're kind of where we wanted to be in terms of weight reduction. The variability is gone.
We also feel from a safety perspective, even though it's very difficult to do with a monkey, but from what we saw from a safety perspective, we're getting where we hoped to be at this stage of the game. Right now we're going through this study, which is a phase I. You basically, you go through a single ascending dose and you test, and then you go through a multiple ascending dose with cohorts of 10 patients each, two placebo just to see the results, and we're in the middle of this exercise on the right, and we hope to read out data by the end of Q2 of this year. That's. If this reads out the way we hope it would, and it's a very acute value driver coming very soon. These are the things we're working on.
One, the top line I hadn't talked about, which is Type I. Because of the hold, the company had not finished dosing in many of the intended Type I patients. We do have some that finished their dosing, and we're gonna show those data in Q2 when the study fully has been vetted and reads out. That's exciting for me because Type I is the ultimate insulin deficiency you can think of, so do we have a response there? Type II are the two studies that I talked about. They're gonna read out in Q4. Then you have the obesity trial, which is gonna read out in Q2 of this year. That's.
Perfect timing.
Pretty much on time.
Yeah.
Okay.
You wanna throw the pipeline back up.
Yeah
for reference?
Of course.
Any questions in the room? Okay, Catherine, I can repeat.
Oh, I have a quick question.
Yeah
about just generally how you're thinking about dosing some patients 'cause, like, I don't assume that you're thinking this would be, like, a cure for diabetes, so, like, I'm like assuming the beta dysfunction may continue.
Mm-hmm.
Can you redose this? Like, let's say.
Yeah
Somebody gets off insulin.
Yeah
Like, it comes back. There are-
Yeah
HbA1c increases. Can
Yeah. Well, we don't know that quite yet. What we're trying to do is we're gonna roll these patients over in a follow-on study. They're less expensive, and you then try to stay in touch with a patient to understand his A1C and understand the need for redosing. He has to come back in. We're gonna check his A1C. We're gonna see over a follow-on year is what you're describing happening, or maybe is he stable? What did he change? They're very well controlled in the study. They can't change their lifestyle. They can't just go on a diet. They can't do all these things, so you have a real comparison in the trial. Once they roll over, you still wanna be in touch to understand your question, and we don't have the answer. We don't know how long they last.
A beta cell, just for reference, lasts decades, so that would be best case. Worst case is these are, they're not as healthy as the regular cells. We have no reason to think either one of the two other than let's do the experiment and find out. Right now, you can see the trend is continuing. We believe that trend potentially could continue until you're below seven, but we don't know. We're gonna test it. Our goal is, however, to be a non-chronic agent, which means one and done. If there is a need for redosing, we're gonna test that in a second trial because we want to get through. Our focus is get through the FDA, have a solid meeting with them after the phase II, get an agreement on a phase III, and become a phase III company next year.
Now, that's a super high goal, I get it, and you can question that, but that's our goal internally. If we get into Phase III on this one indication, we can then check later on redosing as an add-on with future studies. For instance, take the 100 million patients that are prediabetic. Shouldn't they be on a drug like this? In my mind, they should. But, you know, that, to test that takes a lot of money. Yeah.
A couple quick hitters on the data.
Yeah.
Background meds, like any reason these patients would keep improving when you stop your drug?
They keep improving.
Yep
when they stop my drug.
Yep. You guys dose for 12 weeks. We saw the curves continue to improve.
Yeah.
I'm guessing they're still on background meds.
Yes.
Medics-
They have to be.
Okay.
They can't change anything because we don't wanna introduce another variable.
Okay.
You stay, you fail, and when you fail, the clinician says, "Okay, you need an investigational compound-
Yep
Because your A1C is high, I have no other drug." They come on our drug, they come down, but they have to stay on whatever they're on.
Okay. Well-balanced between that and the control arm?
Yeah.
Okay.
Yeah.
You showed us one curve, but dose response, dose exposure, did you guys see anything in the phase-
Yes.
Okay.
Higher exposure, better response. How do you get higher exposure? Not easy. That's why we did the food effect study. The food effect study showed if you dose within 1/2 an hour of food, you get a really good exposure, and it's controlled, and it's the same, and it's a main food, it's not a quick breakfast. We're trying to get you into a comparable behavior so I know I'm gonna get the best response.
Can you and did you measure menin?
Yes.
With the-
We did. There's a chart there.
Oh, in diabetics?
In diabetics, yes. We also measured menin in our oncology study.
Mechanistically we're
Mechanistically, we're on target.
Okay.
You can, we can go very deep into that, but the fact that, and maybe we got lucky there, if you hit menin down to zero, it's a tougher response on your body than what you want. The fact that we're downgrading menin with 100 milligram, the way we're seeing it about 50%ish-
Mm-hmm
is exactly what gives us this beautiful safety profile.
Maybe last one, big picture-wise, you guys showed, you know, 1.2%.
Yeah
1.5% reductions. In your next studies, you know, you're talking about percent reduction, but it matters where you start, where you end.
Yeah.
Are you trying to get patients to 7%, or is any benefit good, or is it?
Any benefit is.
1/2 a percentage is.
I think any benefit is good, but one of the endpoints is how many patients got below seven, which basically means to the FDA you've got them controlled.
Mm-hmm.
We want to know that as well, obviously. The higher you start, the more you have to drop, so there's a trade-off. We're kind of where everybody is. Our all comers p-study had eight point two. They go up to eight point five. I think the studies now with insulin deficient patients will probably be higher when they come in, but our goal is to get as many below seven as we can.
Last one, anything in terms of, like, baseline menin levels or patients who may not be responders for some reason?
That's a good one. No, it's not an enrollment criteria.
Okay.
It would be.
Interesting to see.
Very interesting to see. Yeah.
Okay. Well, you got a lot coming soon.
Yeah.
A very busy Q4 .
Yeah.
Ramses, thanks so much for joining us.
Yeah
giving us the story.
Thank you. Thanks for your interest.