We're here.
Yes.
Good to see you.
Good to see you.
Yeah.
You want to sit down or?
Sitting down works for me because you have questions, right?
Do you want to have a couple of presentations or you just want to?
I have slides just in case we need to.
Okay. Yeah, you can reference what you like.
Okay.
Got it.
Why don't I stay here just to see the slides?
Okay.
Okay. Perfect.
All righty. Okay. Welcome, everyone, to Jefferies London Healthcare Conference 2025. My name is Roger Song, one of the senior health cover clinical biotech in the U.S. It's my pleasure to have the fireside chat with our Biomea CEO, Ramses. Good to see you.
Yes. Thank you. Thank you for inviting us and thank you for giving us a chance to present.
Absolutely. Okay. All right. We, you know, Biomea is a very unique play in the metabolic space, including diabetes and obesity, which is the two hottest areas in the biotech space. Ramses, can you just give us a little bit high-level overview of Biomea? What's the recent kind of strategic pivoting? What's the focus right now? We can dive a little bit deeper into that.
Sure. Maybe it's important to understand when you say these are the two very hot areas in the metabolic space. Overall, if you look at obesity, it is probably the biggest disease area we will see in our lifetimes.
Unfortunately, so far.
Yeah, I know, I know.
Hopefully, we can address that.
When you look at diabetes, diabetes is being addressed with about 60, I mean, think about that, 60 approved agents or a combination of agents in America that can be chosen to help somebody with diabetes. All of them are chronic agents, and they do symptom management. If you look at the symptoms that we're trying to manage, these are all symptoms that come from the disease. What is the reason for the disease? When you look at it a little bit more deeper, you will find that we all have pancreatic, we all have a pancreas. The pancreas produces insulin. When those cells in the pancreas are running their course and are actually depleting over time at about 50% of their capacity, we have not sufficient insulin to overcome the glucose toxicity.
That's when you go to the doctor and you have side effects, and the doctor says, "I'm sorry, you have diabetes." At that stage, you then fight the disease for a couple of years. You get on a drug. You have the first drug, the second drug, the third drug. At some point, you become insulin-dependent. Those patients that are insulin deficient, which are not the obese ones that are diabetic, there are more than 50% in the U.S. that are actually phenotypically not obese. Those diabetic patients get on insulin quick within one to five years if you're severe insulin deficient. Those are the patients we address because we're looking at the root cause of their problem, which is the insufficient beta cell capacity. We're growing or regenerating this pool of beta cells in the pancreas.
The only reason why we're doing it or why we're so smart is because Mother Nature has shown us how to do it. When a pregnant woman tries to overcome the need for more insulin, she upregulates prolactin. Prolactin downregulates a protein called menin. When you look at this pathway, you're saying, "What if I were to drug menin, inhibit it? Could I have the same effect?" That is basically what we're doing with icovamenib. On the one hand, we're addressing diabetes at the core level. We do believe we have more impact also on the other non-insulin deficient patients, the more resistant patients. That comes over time with more money and a bigger partnership. Right now, we're focusing where we see the best response, which is in insulin deficient patients.
The secondary category are those patients, and we've seen data there as well, that when the mother upregulates prolactin to downregulate menin as a target, she also achieves that the receptors on the surface of the beta cells are more expressed. We knew that. We saw it in preclinical experiments. Now we're looking at it in the clinic, and we see, is there a patient that we had dosed that was on a GLP-1 that required the interaction of the GLP-1 receptor with the agonist? We had 11 of them. There we also saw beautiful responses. Two target populations, one insulin deficient, the other one failing or not being controlled on a GLP-1 therapeutic. That's in diabetes. In obesity, the company has started about three years ago an effort to come up with a next-generation oral GLP-1 receptor agonist.
That's based on the orforglipron scaffold. Orforglipron is a wonderful molecule, but it's very potent, and it has a high peak-to-trough ratio. We're making the drug less potent when it hits the body. We're giving it a longer, higher bioavailability and a more patient-friendly PK profile. That's the other area. We will have 28-day weight reduction in the first half of next year where we can show in an obese patient population, how do we compare against the other players that have a GLP-1? We then actually will compete against the whole space. Now, what are the next steps after? We have to see. We're not Metsera, I know, but we are right behind Metsera with our drug.
Awesome. All right. Great. Yeah, I think that's a good level set. Maybe we focus probably most of the conversation today is on the icovamenib for the menin inhibitor, but we'll touch on the obesity as well, the small molecule. Maybe I understand the biology. I understand the target population for deficiency and then GLP-1 fail. Take a step back. How do you think icovamenib is designed differently from other menin inhibitors? I also cover a couple of other menin inhibitor companies. They are most focused on oncology, just like you before, right? Why do you think icovamenib can be better suited for diabetes versus oncology? What clinical and maybe mechanistic kind of molecular design support that?
Yeah. I mean, you have to go back to the way the molecules were structured or designed. The other players in the menin space, they started by inhibiting the rearrangement of MLL from docking on or interacting with the protein menin. And they tried to prevent this connection to occur. They built large molecules to prevent this interaction. When we saw that as drug developers, we said, that's actually quite difficult and causes potential side effects. As we now know, they do cause side effects. Let us try to see if we could, if we were to find a way to target menin directly. Menin is a fairly large protein. If we are able to address menin directly, could this be more elegant, more precise, and could we have a different effect profile?
Now, after we have found a way to do that, and we're doing it covalently, now that we see the outcome, we actually see by just taking out menin, we do not fall into the same side effect profile as the other players in the space. They will have to prove themselves in diabetes. I mean, this is a very broad disease category where the safety standards are fairly high. We'll have to see. They're not in the space yet, but they're certainly working on it.
Which means you have a less, like a differentiation syndrome or also the dose?
We do not see that. I mean, that is also dependent on the disease that you are in. In diabetes, what we see in the safety profile, and you can see the table that we have in our presentation, which is, I mean, I do not know if people online can see it, but if you go to the deck that we have online, look at the safety profile, which is phenomenal in my mind. And right here. If you see here, overview of treatment emergent AEs, you compare us against placebo, you do not see a lot of the difference. If you dig a little deeper and you say, "Okay, show me everything that is greater than 5%," you will see, okay, we have a little bit of nausea, but placebo has as well. We have maybe more diarrhea, but then placebo has more headaches or less headaches, right?
It's sort of the disease itself carries some side effects. I find our safety profile extremely supportive of the next stage of development. We're only dosing for 12 weeks. We're not chronically dosing. I mean, think about that. When have you seen a therapeutic that is designed to recover or replenish or help the body recapture its own capacity? Twelve weeks. You stop the drug. Nine months later, you test whether that purposeful treatment over 12 weeks has still an effect. I've never seen that before in medicine. Now we are testing ourselves a year later, and we're saying, "Wow, look at these curves." If you look at these curves that we are producing, and just here, this is our best performing on this, 1.8%. That compares to the strongest drugs we have there. This is nine months post-dosing.
Yeah, I think the HbA1c, the data is very impressive. Maybe you just find that those can get to this beta proliferation and then get to the HbA1c, but not causing any menin associated side effects, but with the differentiation on the binding and then the targeting of the menin, the way you target. Makes sense. Just stick on this. I know your phase II is having multiple dose cohort. Can you just tell us about the dosing finding and then what is the foot effect you think you need to address before you can move into the next stage?
Every drug developer wants to see one thing. That is, I showed to you here. You want to see that the target you're inhibiting is actually having an effect as you're inhibiting. The more you inhibit, the more response you want to see. We can see that here. It also shows that we have variability. Meaning, why have some patients achieved this amount of inhibition and others this amount or this amount of exposure in the blood, right? There's variability. You try to avoid variability, and you try to get into this bar. You try to improve outcome. In an effort for the phase II that we're now embarking upon to read out more consistently with less variability, we're doing a food effect study to take away all potential variable items. If you have food in the stomach, the exposure is higher.
If some patients did take our drug in the last study without food or with less food, we want to make sure that we understand what kind of food, when, and give clear food instructions. That is what we are learning here. We did it at PharmaCyclix as well. I mean, this is a common thing you do if you want to get into getting persistently good responses. That is the intent.
When are we going to see the data? What's the expectation?
You're going to see it in Q1. You're probably going to see it. The expectation is we have found our now defined, not sweet spot. It's basically we have tightened up the food instructions. We can now provide to patients in these new two studies that we're enrolling very clear tight food instructions to decrease variability. That you will see in Q1 because we're enrolling our first patient in Q1. That's the plan.
Got it. By the way, it is a QD, right? Whatever the food effect, you're going to be around the timing of the dosing. If it's, let's say, fasting or no drink, no food.
That's the point. You try to clear that because the difference between fasting and non-fasting can be huge.
Yeah. Okay. Not going to be too convincing in terms of you do not want to overcomplicate this, saying what kind of food you should take and why not just fasting.
Yeah. You reduce the complications and you make it as easy as possible and as clear as possible. The better you do that, the less variability. With variability, we had incredibly good responses in this study. I was very, very happy. I did not expect. I have to show this to you. I mean, think about it. When we read out here, we thought, "This is good." It actually improved. Meaning, I would have been very happy with stable responses not improving further. The fact that the body is now taking over these beta cells and are producing more insulin to cover the glucose that this person or these people are exposed to is wonderful. We are trying to tighten up the instructions just to even improve upon those results. That is the goal.
We have shown here 0.5 as what we think is a benchmark for a government or the FDA where they say, "Okay, you got to hit that." That is kind of when they approved a DPP-4 in our space.
Got it. Okay. Yes, I think you are in the conversation with the FDA to start the phase II. I think you say one Q next year. Outside of food effects, any other alignment you need to get with the FDA in terms of the population, I believe one of the dosing regimen, the length of the study? I know you're probably not going to disclose much today, but what are the key topics you wish to get alignment with the FDA?
You will not get alignment, by the way. You will get alignment after an end of phase II meeting. What you are trying to do is you are trying to anticipate from the viewpoint of the FDA what would be good, solid, scientifically smart drug design or drug development. What you are trying to cover is type of patient, is it clearly defined? Length of dosing, is it clearly defined? Dosing exposure, is it validated? And the amount of drug you are giving these patients. Can the FDA agree with you on the 100 milligrams we are doing for 12 weeks with a follow-up of 26 weeks as a primary, 52 weeks as a secondary? We think they will, but that is an assumption. There is a residual risk you always carry with the FDA. We have to give them the deliberation upon seeing everything to say yes or no.
They have not seen it yet. They have seen some of what we are doing, and they are saying, "Go do it phase II." Of course, we want everybody wants patients to do better, we as well as the government. For us, if we show them patients are doing better on our drug, that is first. Now show me that you are doing it safe, right? We had a hiccup. We have to be very mindful of producing safe, very safe and solid responses. That is what we are doing.
Yeah. Yeah. Okay. Can you just, what's your expectation for the phase II cost and the timing? What will be the profile can support the phase III? Because as you said, right, FDA not going to give you definitive alignment, say, "Okay, this will get approval," which means it's a phase III profile. What are the target profile for phase II before you can move into?
What we're trying to achieve is in these, so first of all, is the patient in need? Yes, the patient is in need because these patients typically go to insulin therapy if they continue to fail. If the FDA agrees with a need, which is in our case, somebody who has BMI less than 30-ish, high A1c, which means your body is not producing enough insulin, so you have insulin deficiency, even though you do not have much of a resistance. You are trying to get to the patient who is not resistant, insulin deficient, and has tried a prior therapy and is not producing the response. He is failing a prior therapy. That is a patient population we can define, and we can show with 60-100 patients.
Here is a body of evidence in a predefined patient population that you FDA should look at because their alternative would be insulin therapy. The other alternative or the other trial that we're doing is a study in GLP-1 failing patients, meaning they're not controlled in the HbA1c. The HbA1c is rising upon enrollment, and we take this patient who is on background GLP-1, and we add icovamenib, and we reduce or try to produce this response here. And that's kind of what we did in our prior phase II, and we're now going after these patients pre-specified and enrolling another 60-100 patients. We believe both studies can be enrolled in one to two quarters. We're starting next year, Q1. By end of Q2, we should have all of these patients enrolled.
By the end of Q4, we should have 26 weeks primary endpoint of this study, the readout. We are funded until the beginning of 2027. We should be able to fund all the studies that we're talking about here. The study for BMF-650, which is our own oral next generation GLP-1 receptor agonist. That data is coming in the first half. These two studies will read out before the end of the year, at least to us. We have to release it to the public.
Got it. Okay. Great. So that seems to be your funding is sufficient for all of those data readout, which will be very critical next year. I think this is faster than I saw you get to phase II from icovamenib.
You got to be very focused. I mean, we know the centers, right? We know the physicians, we know the investigators, we know the centers. I feel fairly confident that these are manageable timelines, but that's the goal that we're publicly stating.
Because this is, as you said earlier, the population is big, right? Even 50% of diabetes, they are insufficient patients, and then also millions of people. How do you think about the safety database FDA want to see before you can get approval?
Yeah. If you look at it through our eyes, this study had about 250 plus patients. That is in the safety database. They looked at all the narratives of those patients. On the oncology side, we had quite a few patients there as well. Our safety database covers about 400 plus patients already that have been touched with a menin inhibitor, icovamenib. We are now getting into hundreds, and we are getting to large numbers. With these additional studies, with the food effect, which is another base of patients that are exposed to the drug, you can show quite a bit of patients. This is not a chronic agent. The studies that are required to satisfy the needs by the FDA to go into a chronic treatment are much larger. We should not apply those because we are not chronic. That is pretty clear.
What is the standard? I believe with the data that we will give to the FDA at the end of these two studies, we will have sufficient information for them to make a judgment call on safety and efficacy.
Got it. Okay. So the current plan, including food effect and the phase II with all the existing safety database, you think that's sufficient to start a phase III program with the data?
I think that's the goal, yes.
Got it. Okay. Great. I think that's a pretty good kind of discussion. Anything else in terms of early pipeline, maybe the oral GLP-1? I know you mentioned a couple of differentiation, but the first half next year, the data readout, what you want to see and then to be able to move forward.
Yeah. We're going through the multiple ascending doses. At first, single ascending, then multiple ascending. You become with that data in the first half. Let's say in the second quarter, somewhere there, you will have a comparable set of data that you can now look at. What did Orforglipron do in their phase I readout? What did Carmot do? When you look at our animal data, nobody publishes their obese monkey data. We all went through it. Nobody publishes. Carmot did. We compared ourselves against Carmot. If you look at that data, which is here, and that is quite fascinating how wonderful we did it. These are all individual patients. Look how clean everybody's responding. That's the goal. Less variability. We achieved that here. This is our drug at two doses. This is placebo. We're achieving really beautiful responses here.
When you compare them against Carmot, which is this graph here, you can see Carmot did about 12% at their high dose. We're doing about 15% at our high dose. Those are great results in animals, and these are obese monkeys. We're now hoping to show similar responses with good safety in the first half, at the end of the first half. What is interesting to know is it's an effect I would like to show you. There is a benefit that we have seen, which is this data. People are not quite in tune yet with this. I think you are, but not everybody is. This is half of Sema, and this is Sema together with icovamenib. This is appetite suppression just by adding icovamenib to semaglutide. If you look at the weight reduction, semaglutide is here at half the dose or at the 1 milligram dose.
This is us. We fourfold weight reduction just by adding icovamenib. If you then look at what kind of weight did we lose, this is all fat mass. This is animal data. I'm aware of this. As researchers, this is what you want to see. You want to see in animals, you're reducing fat, not muscle. We believe there is a benefit icovamenib has to the weight loss need in America. If you add us into a GLP-1, not only in diabetes, but also in obesity. We're talking to investigators right now about this data and what they think and what our scientific advisory board thinks we should do. You're going to see us do a lot more work in obesity with icovamenib. That's not in our pipelines, but it'll be preclinical and then clinical.
Yeah. Got it.
Lastly, Roger.
Sure.
Type 1. Yes, Type 1. It was disrupted by the clinical hold we had, and we do not have good data yet to show. Type 1 with this response here, if you have a response like this, these patients.
A certain amount, but we stay close to the closest one.
Sure. No problem. Their pool of beta cells is very depleted. It's very much phenotypically like a Type 1. For us to now explore Type 1 makes total sense from a developer's perspective. We will come out with more activities around Type 1 also in the next year. You don't see it in the pipeline because we don't have the studies up and running, but we do a lot of work in the background on obesity as well as on Type 1.
Excellent.
Yep.
Great. Thank you, Dr.
Thank you.
Thank you, everyone.
Thank you.