Alright. Hi, everyone. I'm Yigal Nochomovitz, biotech analyst at Citi here in Tribeca in downtown Manhattan. We do this virtual C-suite fireside chat periodically. We've had many over the summer. We have many on the schedule. You can check your email if you want the full lineup. Today, we have the pleasure of having the senior leadership from Biomea here with me. I have Ramses Erdtmann, who is the Chief Operating Officer and President, and I have Thorsten Kirschberg, who is the Head of Research at Biomea. If you are listening and you want to ask questions, then you have to email me, please. yugal.nahsamovitz@citi.com and I will line up. I will relay if I can over to Ramses and Thorsten. With that being said, Ramses, I think it would be good if you could start with an overview, please, of the company's pipeline. What is the, you know, the key objective in the short term? Maybe highlight just some of the upcoming catalysts. Okay. You go straight to the heart of it. Okay. So, and you go, we know each other since a long time. The company was started in 2017. It went public in 2021. We're about 40 people here in California. We have a focus on two key areas, and these are very, very relevant areas. It's diabetes and obesity. There is a program in each area that we're pursuing. The size of this problem is of magnitude because what you're thinking of when you think of diabetes, you say, oh, you know, there's a lot of solutions out there that you can get in the public markets. The doctor has over 60 available therapies, but at the end of the day, half of the patients that are diabetic today in America are uncontrolled, meaning their HbA1c is above the marker of toxicity, meaning they are now in the range where there is a problem that is occurring over time. Their HbA1c, their level of glucose toxicity, is not controlled. That's something we've seen over the years, even though therapies have come on and new therapies have been sort of created. What we're focused on is we're focused on the root cause of the problem, which is in the pancreas, you have cells that are depleted over time. As they hit a low mass of about 50%, that's when the function and the mass together are not capable of managing the toxicity of glucose in your system, and the insulin production that you have has been reduced to a level that you now have what we call an HbA1c that is uncontrolled, meaning above seven. That is the problem in diabetes. What we have done is we've created a drug, and that is, just think about the idea that we would be the first company that is addressing the reason why you have this problem is because of this depleted pool of beta cells. We've now created a drug that takes away the control function, meaning there is a protein that controls the growth of these beta cells. When you inhibit this protein, just like a pregnant woman does or an obese person does, when they do not get diabetes, in both instances, their hormone called prolactin is downregulating this protein called menin, and when it's downregulated, these beta cells are allowed to grow again. We've seen it in cell experiments, we've seen it in animals, and we're now doing clinical studies. That's the study that just read out a few weeks ago where we have shown that we did control this function, and we have seen a reduction of this glucose toxicity from above seven all the way down. Post-dosing, there is a period where we dose patients for 12 weeks, and then we have seen it, I mean, literally dramatically go down 1.5%, 1.8% versus placebo. That is severe, and that is significant, and that people have to recognize. This is a pathway. We're the first to do it, which is the menin inhibition pathway in diabetes program one that has now been, in my eyes, validated to a point where we're now starting a study, phase II, just designed for patients that have what we call insulin deficiency. It's about a fifth of all diabetic patients in the U.S. that are insulin deficient, and they look like you and me, and their pancreas is not producing enough insulin. Those are the patients we would enroll in the next study. We're also focused with a second program on obesity. We all know obesity is the biggest pharma market today. It's not resolved. 36% of the U.S. is obese. 25% of the world, patients or people, are obese. If you look at that, it's the fastest growing segment. We're going to hit $100 billion in sales sometime 2030 +. We are focused on a program there where we also looked at it strategically, and we asked the question, what is needed here? At the time we started, all drugs were injectables that were going after obesity. We're looking at a non-injectable, an oral agent. The pathway that people have sort of validated is called the GLP-1 receptor agonist pathway. We are using the same GLP-1 receptor agonist-based sort of drug structure. We're looking at, in this case, a chemotype that is similar to Lilly's, and we have improved it to a point where one of the side effects you can see in the GLP-1 space is people are having a lot of nausea and adverse events while on drug. About seven out of ten patients drop out of drug over the course of the first year. We're trying to solve that with an oral agent that is more next generation-like, that is more body harmonious. Toss, keep going to that as we go through this Q&A. The company is focused on these two areas with programs in the making there. We have a phase I that is about to read out in Q1. Okay. You mentioned the fifth of the diabetes patient market that's the so-called insulin deficient. Can you tell us, tell us more about those people? How are they identified? What did you see in the studies that made you believe that that was the right place to focus for the later stage? Yeah. When you look at diabetes as a segment, you will find very quickly that there's a large degree of heterogeneity. There is, on the one hand side, the heavy set diabetic who is obese, BMI 27, overweight, 30, obese to 40 and higher. Those patients typically have an overproduction of insulin. Their body is trying to compensate and compensate and compensate. What we're doing is we're giving you more insulin, meaning for those patients, the benef`it of icovamenib is not as profound, even though they will also, over time, have a failing pool of their beta cells. When you catch them in the early stages of their disease, we haven't seen such a profound impact on those patients. However, because the study that we just read out enrolled everybody, we found in patients that you can quickly identify by just using BMI, which is less, typically not obese, and an HbA1c, which is the level of glucose in your system, HbA1c above 8%. Those are indicators that show you're not resistant and you have a failing beta cell pool because you're not hitting sufficiently the glucose. If that's the case, those are the criteria that we would go for. We found in the readout of the study that those, to a large degree, characterize the severe insulin deficient patients. There are other criteria you can use that are more technical, but we found those two, plus having failed a prior agent, which is obviously everybody who goes to the doctor. The doctor says, look, use metformin. It's something that we've used for the last, you know, how many decades, and it's a very good agent. We're coming after that. You have failed that agent, and that's where we come in and when we will apply our drug. Okay, you just had the recent 52-week data. Yeah. What do you need to show then, you know, having looked at that and understand that, especially in the SPEG segment you're talking about, in the high HbA1c, and then I think it's the lower BMIs? Correct. What will be good enough, additional reduction on top of all the prior therapies you're talking about in a pivotal trial that will convince the diabeticians across America and others that they should be adding this menin inhibitor to everything else to further push the HbA1c? I think the number one thing or the number one problem, if you talk to an endocrinologist, is persistence. Patients have to take these drugs every day, all day, meaning you have to have drug on board every single day for the rest of your life. One, two, all drugs have a shelf life. They all work and then they stop working. Then, they get stacked on top of each other. A third of all diabetic patients end up on insulin, meaning ending up on insulin, which is now the thing that your body should produce, that you're now giving yourself through injections on a day-to-day basis, is the last thing you want to have. You're having to control your food, you're having to do all these things, and you're still not controlling the levels of glucose toxicity, and it has huge side effects. Do we have a transmission problem? I think maybe Ramses had a freezing. Thank you, Yigal. I just lost you. I think we lost you there for a moment. Okay, no problem. Can you hear me now? Yes, yes. Okay. When you get diagnosed with diabetes, that's the thing the doctor wants to avoid. Your question was, what is it that a physician wants from us? The physician wants the problem solved. What we believe is that we have seen first indicators that we're actually solving the core problem, as we're rebuilding your pool of beta cells in three months. That's it. We stop dosing. You don't need to be on a chronic agent. You don't need to have icovamenib every day. We have rebuilt your pool. We have seen the effects of this pool now being active. Your HbA1c is coming down post-dosing. We have read out nine months post-dosing. There's not one drug in America that has been in a clinical study that has shown you can be on this, you can have effects off therapy. We're the first one. We have shown these effects to a degree of nine months post the last dose, and we have shown an HbA1c reduction, our best performing arm of 1.5%. Compare that to any other agent and you'll see we're in the upper end of the spectrum without being on drug. We believe the hurdle is much lower than what we have shown. The hurdle, actually, if you look at FDA's approvals, is 0.5%. I have threefold that hurdle, meaning at 0.5%, DPP-4 inhibitors were approved by the agency. Now, I'm just looking at the benefit we're creating, and the benefit is you can be off drug. The persistence, meaning patients having to take a drug every day, will stop because if we truly rebuild the pool of beta cells, over time, you may not need other agents anymore. We have to obviously prove these things out. We're an investigative compound. We're in clinical trials. That's the goal. The goal is to reconstitute your pool of beta cells, and you can be done. We hope to show that with benefits as measured in HbA1c. We have shown huge benefits. If we think our hurdle rate in a phase II, then going into III, then later on will be roughly around that 0.5% level. That's the comparator that we see in earlier studies. Obviously, we're talking for above 1%. We as a company. Okay. What's the, tell us a little more specifically. You finished this phase II now. You mentioned the data and the potentially, you know, promising results there. Are you going to have a meeting with the FDA to discuss the next study? What will the next study look like? I guess you would, my guess is you would probably have to do another study just in these high BMI, sorry, the low BMI, high HbA1c people. Is that the plan? Yeah. There are two patient categories that we have identified. One is about every fifth patient in the U.S. So just 38 million have diabetes, roughly 2+ million have type 1. The rest have type 2. It's about 7 million patients in the U.S. that we're targeting with the profound effect that we have seen in what we call severe insulin deficient patients. However, the study that we enrolled was all comers. We have also seen a subset of patients when we looked at the all comers, and we asked the question, this is another effect. When you inhibit this protein, the body has the receptors in these beta cells are now more expressed. We knew this from preclinical studies. We asked the question, if a GLP-1 is on board in a patient, would a patient have a benefit if these receptors are more expressed and the GLP-1 receptor agonist is now interacting? We found out of 11 patients enrolled in our study that were on a GLP-1, they had a profound 1.1% on drug and 1.8% placebo-adjusted effect on their HbA1c. There are two subgroups: one was pre-specified, the other was a post-hoc analysis. In both subgroups, we're starting designated phase II studies because they're both large patient populations. If you look at the one I just mentioned that are on a GLP-1, about 40% of all GLP-1 studies in type 2 diabetes have patients that are uncontrolled, that are not reaching the 7% target. That's a study. In the real world, that number is bigger. There are a lot of patients out there that are on a GLP-1 that don't quite get to 7%. Those patients, we would help and boost their responses because of these receptors being more expressed. In both these groups, we would do a phase II study and would then, after the study results, go to the FDA. Sorry. They're basically not overlapping populations. I mean, the people that are the post-GLP-1s are not the people that are the low BMI, high HbA1c. Actually, it's the opposite. Patients who are obese are typically on a GLP-1. Patients who are insulin deficient are typically not on a GLP-1. Yeah, I'm just making sure everyone understands this. These are distinct populations. Yeah. Okay. Now, what? All right. When these two studies are going to start, are they going to run concurrently? What's the plan? It's pretty clear. We know the centers. We've just enrolled a study. When you start something, obviously, the first hurdle is people are very skeptical. What is this doing? What is the side effect profile, et cetera, and the FDA as well? I think we've passed that point. We have hundreds of patients now on drug that we can point to from a safety perspective. Look at the profile that we published. It's really, really good, meaning I have now a drug that is safe for the three months dosing that we have shown, or in our eyes, safe, and that has shown tremendous benefits for patients in a desired, in a very highly needed patient population. These patients that we're dosing with icovamenib, both groups go on insulin as one of their next choices. That's the tough part. If you're insulin deficient, within five years, you're insulin dependent. Those patients that we characterized early on in this conversation, their choice is insulin, shit, or hey, I could use icovamenib. The enrollment we don't see as a problem. These patients are typically looking for us. There's quite a few centers in the U.S. that we know. We're starting both of these protocols right now. We're going to submit them to the FDA. We hope to have an IND very early in the next year. When these patients come on board, we anticipate 60 to 100 patients in each of these trials are sufficient. We're going to run through this fairly quickly with a 26-week primary readout. We're going to take that data to the FDA. A secondary readout will be the 52 weeks. That's still not quite the pivotal trial. That's a next group. I know. It's a, yes, true. Yeah. But it's enough. For instance, we're doing something that hasn't been done before. There is a lot of skepticism, as you know, one, not only from investors, but also from pharma. The more data points we can show to this data is profound. There is a lot of interest in looking at our data and understanding how did you guys do that? Because it hasn't been done before. Nobody has stopped dosing and shown this effect on HbA1c. As that benefit is better understood, people will come and help us to broaden our clinical pipeline. Right now, what we're doing is what we can fund ourselves. If you think about it, we should be in pre-diabetes, truly. I mean, you should prevent the disease right up front. If we can, you know, if we would have more funds, we would be in pre-diabetes. We also have type 1 diabetes that you're probably going to ask me about. That is another big area where we will initiate more work in because the study was disrupted last year, the type 1 D study. There's more for us to do. What I just showed to you or what we just discussed is what we're funding ourselves. Okay, you start them first patient in, you said, I guess, early next year. Twenty-six weeks you have to enroll. The data then would be, what have you said? For people who can plan for their data calendars, when could we? I think, yeah, the 26 weeks readout, half a year later, take one to two quarters to enroll, and then half a year later, you have the readout. End of next year, early 2027, maybe. End of next year, yeah. I mean. What are they comparing to? Is every day they stay on their background therapies, and then you just do versus placebo, I guess? Is that how this goes? Is it different? That's how it goes. You have to really manage that they do not change anything. Otherwise, the signal is not, you have to really control the study well. We know how to do that. Now then, okay. The GLP-1, tell us more about that because that was a very interesting finding. I don't know whether the people at, you know, Novo or, you know, the Lilly, if they even knew, made this observation about what happens in the menin upregulation. Was this your observation? How did you come to even figure this out? Do we even know why this happens, why you get this receptor upregulation with the menin blockade, which would make it such that, I guess, your argument is you can have more GLP-1 receptors, so you can lower the dose, I guess. That's one of the benefits that you could potentially lower the dose. There are two categories where GLP-1s are used. One is diabetes, one is obesity. So far, what we have shown, preclinical work in obesity, which is the poster that we showed at ADA and EASD. In the poster, you can see the gene, the MEN1 gene goes up. The protein goes up when you introduce Icovamenib. These are cell experiments. This is not our work. This is known in the literature that menin has that impact. We just put it into an organic environment like a cell or now a human. Obviously, we can't measure in a human as well as we can in cells. We have validated what academia has identified prior. We knew what to hunt for. As we read out, we thought, gee, we should check that because we know it should be there. Nobody knew the impact. The impact is that with three months of dosing, so 12 weeks of dosing, the patient is on a GLP-1 background. That GLP-1, which failed to control sugar, meaning the HbA1c was going up in these patients. Now that GLP-1 is actually working again for this patient. What could be the impact is not only that his HbA1c came down. That's what we measured because we know when you inhibit menin, the insulin production goes up because of this effect. The GLP-1 works good. What could it do in obesity? We've done a study in obesity where we looked at rats. These are ZDF rats. They look like rabbits. They come into the clinic. What we did is we said half a dose of sema in this arm, half a dose of sema in this arm, plus icovamenib. You can see that this arm has a four-fold increase in weight loss, literally four-fold if you look at the poster. You ask the question, what else happened? Insulin better controlled, da, da, da, da, da. The things we already knew from the diabetes side, but also muscle preservation. That's a new finding, which you can read up in the literature. There are references for that, that when you inhibit menin, you have muscle impact, a preservative impact. We have shown a little bit of that from other studies. At the end of the day, now the question is, can menin potentially be a combination partner to a GLP-1 therapy just for its benefits of the quality of weight loss? New question. We have more studies in the making that are preclinical that will fine-tune this finding further. When it's further, you know, for us validated, then we'll take it into the clinic. You get more updates from us throughout this year and beginning of next year with our experiments. That's a true killer finding because the GLP-1 space is the backbone of obesity. You go to ADA, which is a diabetes conference, everybody's talking about obesity. Everybody's talking about GLP-1. All of them have a problem. What is that? The quality of weight loss. It's the side effects of the GLP-1s. It's the muscle loss and other negative impacts on the human body. Menin seems to have a natural way of dealing with these resistance problems, pregnancy, obesity, where menin is by the body downregulated in order to overcome these two problems. When you ask the professors from Joslin, and they do all these studies on beta cells, that's the first thing they've shown to us. They said, look at obesity, look at pregnancy. This is where you can see a natural occurrence of what you guys are trying to do with your drug. Look at the benefits that you're creating that in both instances are being sort of upheld. No muscle loss in either one of them when there is no diabetes, right? When the body is able to overcome these two problems. That's why we think, why we knew something was there. Now we're exploring it further. It's pretty profound. Yeah. Okay. That idea of the combo, right, with the menin inhibitor and the GLP-1, that's one aspect. The fact that you're going into the post-GLP-1 in the current study, in the one we were talking about a moment ago, that's what was the, what did you discover? Why did those people behave better in terms of response in the post-GLP-1? What was the conclusion? Yeah. In diabetes, what you see is when menin is inhibited, these receptors are more expressed. We know GLP-1 has an impact on the function of beta cells. It doesn't proliferate them, but it makes them, it has an impact on their production of insulin. When menin is inhibited, more insulin gets produced. With more insulin produced, the GLP-1 works better, and more insulin gets produced. That was a cascade of effects we were aware of. As we interrogated our database, we saw that it had this impact on these patients. We didn't quite know how much HbA1c to expect. When we saw the effect and the continuation of the effect post-dosing, it's not us who does that. It's the combination of us with the GLP-1 who does this. When we look at our obese patients, we don't really have that much of an HbA1c impact on obese patients per se. When they're on a GLP-1, the impact is profound. Okay. Because you know, back many years ago, when you first made this observation, everyone was studying, you know, everyone at the company and the investors, we were all trying to understand this phenomenon of the beta cell mass. We were asking all the normal questions around, it's more beta cells, but maybe then they also, the ones that were there that survived are working better, right? All these sorts of things. Now part of that is a little bit, you're saying part of that is a little clarified because by the upregulation of the GLP-1, the ones that are preserved may be working better. We have more. You did a long, long time ago, you did all those cell spheroid models, and I remember those slides. Is there anything, I think people would be very curious if you have like the, it's maybe not possible to do, you know, to actually show the imaging, to show that there's more of the beta cells, to prove it even further. We were, but yeah, we had a whole SAB. If you look on our website, the SAB is pretty deep. We had a whole SAB, meaning a meeting with all these members trying to assess function mass. How could I validate either one of the two? Obviously, we've done all the preclinical experiments. When it boils down to it, imaging isn't up to a point where it could, and one of them told me, the whole pool of beta cells that you have is the size of your thumb. Go try to find them. Meaning the imaging technology in the pancreas is not up to a point where you could find the proliferative effect of an agent. You can only measure it by the outcome right now. We're measuring outcome, which is insulin production, which is, you know, transcripts of genes, which is those kinds of things. We can't go into the human body as well as we can in an animal. In animals, we've shown size increase. You have, okay. We have. The other thing you can look at, which is super, is when a woman goes through pregnancy, where I've said earlier, during pregnancy, the mother downregulates the protein menin in order for the pancreas to enlarge and produce more insulin. Women who died during pregnancy have an enlarged pancreas. We have those images, and I can send you that research where women who've gone through lactation, women who've had pregnancies have less probability of getting diabetes 30 years out. Meaning this effect is a known effect. Okay, you're going to do these two studies, the insulin deficiency and the low BMI, high HbA1c, and then the post-GLP-1. You're going to get that data, I guess, like we said, end of next year, early 2027. What do you have from the, you know, in terms of the funding and the runway to go beyond that? Would you pick one of those to do the pivotal trial for the approval or what? How would you think about that? I know that's going to require more capital. Yeah. Okay. You need for both and for all the work that we're doing, obviously, we need agreement with the FDA, and the need and the benefit need to be clarified. That's why we're doing these studies so that the benefit and the risk that a person is taking when using icovamenib, which we think is benign at this moment, that's all that we can see in our clinical data, that the FDA is in agreement. We believe that in both cases, the FDA, with sufficient phase II data, will be in agreement for us to go into an end of phase II meeting with the data and then see how we progress from there into phase III. We would try to pursue both. Why? Because the demand in both is very high. The identification of the patient is not that difficult. In one, you're on a GLP-1, your HbA1c is uncontrolled. Pretty clear. Meaning you're failing an existing therapeutic agent and your HbA1c is high. That gives rise for, hey, what are we doing there? There is no therapy. GLP-1 agents are the best therapeutic agents for obese patients. What do you do now? There we have a solution for these patients. The need in both is there. We believe if we can show safety over time, then the agency, and obviously that needs a meeting and needs for them to look at the data, but we can find agreement with the agency that that's worth pursuing in both categories in phase IIIs. Until that point, we have a few more updates that we will be doing. We will provide you more updates on the impact of menin inhibition in obesity, which could become its own clinical path because we would then look at how can we be an add-on agent to existing agents. Would there be an interest to do a study that we just shown in animals, semaglutide at half the dose, with semaglutide at half the dose in icovamenib? Is that a study that could entice people and investigators and potentially pharma? We're working on all these things that we can support ourselves going to those phase III studies with data points we will bring up in obesity, data points we will bring up in type 1 diabetes, and data points we will bring up with our second molecule, 650, which Thorsten is on the line here. He can answer. Talk about that in a minute. Can we just finish on the type 1? I know you meant, you know, that one you pursued it and then you paused. What is the latest update on the type 1? Yeah. With the data that we came out with just two weeks ago, the interest really spiked from academia because we're showing that in a type 1-like patient, a severely insulin deficient patient is almost like a type 1. Your beta cell pool is depleted and there is not enough production. We do not have an autoimmune attack, obviously, in severely insulin deficient patients. In theory, what we were thinking of, and that's why we went into type 1, is that every type 1 patient still has some form of C-peptide production, which is a surrogate for insulin. We can still measure that insulin production after a meal in a type 1. If the immune system of the person that has type 1 would have attacked those cells, there shouldn't be a production of insulin. These cells are still alive and working. If I were to regrow those cells, what impact could I have on this patient? That was the question when we started the exercise. Unfortunately, we were disrupted by the FDA. The data that we have now that we read out this one study, we're going to look at this data and see is there anything useful in there. With the incoming interest from investigators, we need to do a study in type 1, which we as a company completely agree with. We will probably restart a study fairly quickly together with academic centers. We will fine-tune the impact potential that we have on a type 1. Also, an important data point for you is we believe by the end of the year, we should be allowed to do chronic dosing. Could it make sense for us to go into a type 1 study where we not only dose for 12 weeks, but maybe for longer because the pool could be so heavily depleted that it needs longer dosing? In diabetes, we don't think so. In type 1, it may. We will have likely chronic dosing ability coming next year. We could dose, start a new study, chronically dose type 1, and have one arm just icovamenib and another arm icovamenib and an agent that suppresses the immune system so that we have a chance in case there is an attack to still have proliferation of beta cells. Those are thoughts that we have right now together with investigators. You will hear us engage further in the near future. Okay. Let's bring Thorsten into the conversation a little bit. Do you want to, you know, you have a totally different program, the BMF-650, the oral GLP-1. You mentioned it at the top of the hour, Ramses, just in a little bit about the chemotype similarity to orforglipron, but it's not orforglipron, obviously. Tell us what it is and what is different about it and why is it interesting maybe for pharma to look at this one? Thank you. Thank you very much. I will just start then on BMF-650. Ramses is giving me the floor. I can see this. Thank you very much. Yes, BMF-650 is essentially a product of our internal program to discover a small molecule GLP-1 receptor agonist. We started the program, now that we're at the doorsteps of the clinic, obviously, roughly two years ago. Two years ago, the landscape was still a little different. There were two scaffold types out there. There was a Pfizer scaffold type, to just colloquialize it, and the Chugai chemotype. We looked at the properties of both chemical worlds, so to speak. We believe that the Chugai chemotype offered the higher likelihood of delivering a very successful GLP-1 receptor agonist. We focused our attention to this side of the world. We did analyze the data also for this chemotype, for the Chugai compound, as it was disclosed then already. We felt the PK properties of the compound were not ideal. Before I go maybe into further detail, this is really a phenomenal molecule that that group has actually produced there. As a medicinal chemist, I really, really think that was a great effort. A few things are not perfect. I think that is the PK. One could maybe also argue that the intrinsic potency of that compound is actually a little bit too high. It is an oral drug. The gut is immediately exposed to the drug. It is a daily dosing. You will have peak to trough, which is very different from a weekly dosing scheme in semaglutide. We wanted to shallow out the peak to trough ratio, have better PK overall and slightly less potency, resembling a little bit what happened when liraglutide actually was improved and it became semaglutide. The compound had longer half-life and actually less free fraction that would have a sharp edge to really agonize and lead to side effects. This was the goal when we set out to have a compound in this class. We tested the optimized compounds in preclinical species for PK properties. We saw that both in the Pseudomonas monkey and in the rat, our oral bioavailability is two to three-fold better than orforglipron when we compared it side by side. Our intrinsic potency is essentially tenfold less than orforglipron, which is easily adjusted for the higher up-titration target dose. It is actually an advantage when you start dosing the compound at the titration starting dose, where you do not hit the patient in particular parts of the GI with super efficacious doses versus other parts that do not see anything. Just to try to distribute a milligram in the GI tract is almost impossible to get it homogeneously done. We believe we have a much better titration entry point for the compound generated with these properties. The program advanced to many steps to show that we have a very good incretin effect in Pseudomonas monkeys. At the end of the optimization program was our obese Pseudomonas monkey weight loss study, where in a daily dosing regime for 28 days, in a very nice and balanced group, we saw very significant and dose-dependent weight loss that showed no sign of plateauing at the end of the dosing interval. We had 12% and 15% for low and high dose group weight reduction at the end of the study. We believe this data, because of the similarity of this receptor in the Pseudomonas monkey and in human, is very guiding towards what we're going to see in the clinic with this compound. As a side remark, the amount of emesis that was seen for those monkeys on the studies without an up-titration scheme was actually rather minimal. We are very happy that we achieved all goals that we had set out to achieve for this compound preclinically. We are now truly at the doorsteps of the clinic to actually translate this now into human data. Okay, the goal is to have an equally effective but safer, more tolerable. Is that correct or no? The more you want to condense, yes, that is correct. The efficacy, we do not want to sacrifice anything that has been seen for orforglipron. That is essentially handled by a slightly higher up-titration target dose. We do believe that our up-titration timeframe could actually be shorter so that you actually harvest in weight loss earlier in your titration. That we will need to see in humans, but it is a distinct possibility based on the data that we have generated. Okay. You said you're about to start a phase I. What is the status there? Have you got the relevant clearances and so on? When do we see the data for that study? Yes. Okay. Thank you for asking it this way. Yes. The package has been submitted to the FDA, has been cleared. We are ready to go. At the end stage, there's always a certain amount of CR optimization. When can we dose? We are really at the doorsteps. I don't want to give the date, but we are right there. The study will essentially be falling into two parts. There's the SAD, so single ascending dose study, and then there's the MAD, where we will really then measure the weight loss. The MAD is really scheduled to happen at the beginning of next year. Q1 is a very, very important quarter for us with respect to BMF-650 data. Yeah, yeah, Q1 to Q2, where we read out. The additional information here. Q1 to Q2 of 2026, we would have Q2. Yes, next year, the first half of next year until we do the official data release, but we will be in Q1. Oh, MAD that we will go into a phase II with, it's a comparable. How many people are going to be in this little starting study? The SAD part will have 40, and the MAD will also have 40. The group size is not the same for either one, but for the MAD, which is most likely the one you are more interested in, this will be for those groups with 10 people each. The ratio is 2 to 1. What level of obesity are they going to be? Are these just healthy volunteers for the first part? They are all healthy, overweight, and overweight or obese. For the, yeah, that's essentially the criteria. I'm not sure if you want the exact BMI right now that we have as the entity. We'll take it if you have it. I think it was 27. 27 to 30 is overweight. 30+ is obese. Okay. Now, what about, I mean, of course, you've been asked about combining, eventually, maybe combining this with ico. I mean, is that something that's possible or you just don't know that yet? Our long-term goal is that we do want to have a combo of those two internal compounds as well. We will read out the beneficial additive effect first in this study that Ramses has described. The long-term goal very much would be having a combo pair here as well. Yeah. Have you looked at it in the cell models? I'm like combining the icovamenib with 650 preclinically in any sense or not yet? Yes. We have eyelid data where we have combined icovamenib and we have used orforglipron and we have used BMF-650, and we see the anticipated beneficial effect of the combinations. All right. After that, is this the type of thing that you would want to have more funding to do your own trial? If you get good proof of principle in the single ascending and multi-ascending, what's the order of priorities for the company, Ramses? I mean, you have to. You have options. You need to create optionality. That's the moment when you have optionality. Having a pharma partner, and based on my experience with pharma partners, is beneficial, is not as dilutive as people may think because it's a long way, as we know. icovamenib is we look as a non-chronic agent, meaning that all the regulations for chronic dosing that we have in diabetes and in obesity, but in diabetes in particular, there are very tough requirements. Look at Viking, how much money they're spending to get through their studies. You have to raise a ton of money to get through. We feel this, we would like the optionality at that time point to look at alternatives. Obviously, one route is to build up the company again and do all these things like others have done, or go with a pharma partner who's just faster, bigger, and more forceful. Those are options we would love to have, but I can't make a decision now on which one is the best. There are certain views I have because of my experience, but that may not be the best solution at that time. Okay, all right. Creating that optionality is we are drug developers. Our goal is to show the value that this compound may have. You know from the BTK days, you can always improve a compound. We have looked at orforglipron over the last two and a half plus years, and we believe it's a very, very good compound. However, as we now know from all the data they have published, there are deficiencies. We will attempt to improve those deficiencies to show the next guy this market opportunity that is there, it's $100 billion. This market opportunity will be won with better patient-friendly compounds, no question. It will be won by somebody who is willing to invest in that. Even though there are struggles at the top, you can get in there. That's kind of what we're doing. We're showing early on that this potentially is possible. By the way, I was just curious, in the phenomenon you observed with the menin inhibition upregulating the GLP-1 receptor, did you see that? That's not just like in the type 2. Like you would see that in the type 1s as well, right? I would think. Yeah, if there's something there, I mean, the cells are. That's why I was thinking about you because you have such a less smaller pool. Is the biology somehow impaired in a different way that it doesn't do the same thing? It's very difficult for us to be definitive, but if there are cells there, which we know they're there, we should have the same effect. We couldn't yet measure it in the type 1s. We've measured it in other environments like cells in animals. We're now looking also at a type 1 animal model, which is not easy to get to, but we're trying to get deeper into that space. I tell you, just from our seat where we are, you look at competition, you look at hurdles, you look at the FDA, you look at all these things. If you look at type 1, there's not an approved agent really in type 1 in phase III. What does that mean? That means there's very little competition. The approval study of the last agents that got approved for stage two is 75 patients in the phase III, meaning the size of what you have to show, the benefits of what you have to show in type 1 are much different than the space over here in diabetes, where obviously we're lucky because we're not chronic. We fall out of these huge demands the FDA has in terms of safety because the target population is so big. In type 1, I feel if we have, if we can show C-peptide increase, which is the hallmark of benefit for a patient, that we can fairly quickly do that. Meaning if I have the right investigator with a few patients, take 10 patients - 20 patients, and I show you C-peptide increase, that would be game-changing. We're on that as well. It's not in our pipeline because we haven't secured the study yet, but that's one of the key goals of the company. Show this proof of concept. Okay. In terms of the funding picture, do you have the funds to, presumably you have the funds to get to the 650 readout? That's pretty soon. Do you have the funds for the two phase IIs at the end of next year, early 2027, the post-GLP-1 and the high HbA1c, low BMI people? Do you have the funds to reach that date? Yeah. We will get funding. We probably will have a public statement in our next quarter release where we will say funding will last, and we have said that into 2027. It's just specificity of, depends a little bit of how much spend do you have prior to 2027, and that changes the range, how far you get into 2027. It is into 2027. We have reduced the company, and just by the number, look at the number, 40 employees. We had over 100 at some point. We really laser-focus now on those two indications, type 2 diabetes, obesity. We don't do any more sort of platform research. All these things have stopped. We have unburdened the company from a lot of expenses. We're now down to what we think is a very good operational level where you can't really cut further if you want to do the things we're doing. You will see in our next quarter, it's one of the questions that you probably will have on, has the burn prediction stayed the same with the 40% we said in our last quarter? Yes, we haven't changed that guidance. You will see us come down dramatically on expenses, and we will work on that further. Just to show you how focused we are, every contract I'm after, I just want to know from the vendor, did I have a three-way bid? Am I at market with this price? Is this an old price? Can I do anything on this price? Can I get out of this agreement and get into a new agreement? I'm very focused from an operational perspective on ensuring I have market rates and I have competitive and negotiated market rates for every sizable contract. Sizable for me is actually at the $5,000 level and above. That's why I get interested because my investment of time, one phone call to the vendor or a quick negotiation with the finance team is all that's needed to check out, are we, and we've made policy around it. We're a steward of this money that we now have. We think it's very valuable, and obviously we're thankful for that we can get this opportunity. We're going to get to those milestones. That's our commitment to Wall Street. Okay. Okay. Excellent. We will certainly be following everything going on and watching for the next data card. It'll be an exciting journey. Lots coming. Thank you, both of you. I appreciate it. Thank you. Okay, thanks.