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Welcome, everyone, to Jeffery's 2026 Global Healthcare Conference. My name is Roger Song, covering Semicat Biotech. It is my pleasure to have the five-side chat with our company, Biomia Fusion, and then we have COO, Remsis, and then we have Steve, Chief Development Officer. Welcome, gentlemen. Thank you, Roger. Thank you. Awesome. Remsis. Why not you give two minutes or a couple minutes about Biomea Fusion at the high level, where you are, and then we're heading to, and then we can have a dialogue. Sure, of course. So first of all, thank you for inviting us. It's exciting to be here and exciting to being covered by you, Roger, and Cha-Cha, because you do really good work. Thank you. So the company is, we're focused on metabolic diseases. What does that mean? It means basically in indication terms diabetes and obesity. The company has strategically shifted probably three, four years ago into this greater market because we identified a protein that since 2005 has been more and more found to be crucial for the body's own mechanisms to adjust to a metabolic need, meaning your body is, when you're obese and you do not, most people who are obese do not get diabetes. Why? Because their body compensates in a way that we now understand better, and you upregulate prolactin, you downregulate this protein called menin. And when we looked at that and we saw the function and the improvements that occur as you downregulate men and not only in obesity but also in pregnancy, female pregnancy that occurs, has that as a function as well to not become diabetic during pregnancy. we saw that this protein men could be a very interesting target for drug development and so we've done a large study that found out who is our target patient population we finished the readout of that study last year we're now going into phase two studies in this target population it's called 211 212 insulin deficient patients are the most responding patients and those patients who are on the GLP-1. There's reasons for that. We can show you the background, and probably we'll talk about it here. And then we have also, as we looked at the space overall, and since we're biotech entrepreneurs and developers, we saw there is a need for not only in the obesity space drugs that are addressing the disease, but also keeping patients on drug, meaning in obesity, about 7 out of 10 patients fall off they are current GLP-1 based therapies and why is that because typically even if they have insurance coverage they feel uncomfortable right there is some some form of nausea some some form OF discomfort so can I create a drug a small molecule that is that is orfoglipron like meaning it has the qualities of orfaglipon which is a great drug but it just it is more acceptable it is more harmonized with the body that was the attempt we started that program about three years ago we're now in the clinic in phase one and we're basically for the next 12 months we have a lot of readouts coming the data on obesity the data in 211 the data in 212 and we now have had early successes in an all-comer study in type 1 as well so it's type 2 type 1 and obesity that we're focused on Awesome. Right. I think that's a good overview. Okay. And then I think we should probably focus a little bit more on the diabetes set first at Menon because that's part of the key mechanism here, and I know you have obesity, small molecule, which data will be even sooner, right, so we can talk about that a bit later. For Menon inhibitor, you know, we follow Menon Inhibitor space quite closely as well. I think you also initially doing the oncology. I think the first time I saw many inhibitor in diabetes is maybe two, three years ago at the ADA. So they have some, a couple of preclinical poster there. So it's very provocative, so I have to say, and then you're basically generating that beta cell. And then we do cover diabetes cell also pretty close, and then just looking for some new mechanism beyond whatever we are currently using in GLP-1 or insulin. So maybe my question is, well, I think you already aligned with the FDA for certain subpopulation of the type two, and then why did you make that decision to focus on those population? And then the more interesting question is seems you are the first company to developing drug or doing clinical trials for those population. What's the regulatory conversation there making you feel confident that, as you do the phase two, we'll talk about it, and then this will be our registrational subpopulation? Okay, so there's a lot that you sort of touched upon. Let me back roll just a little bit. So in diabetes, every agent we have today is a chronic agent. There is not one agent that is restoring any function. It's basically, we're trying to convince your body to let go of that sugar faster that is toxic to your system, in essence. And it very simplifies the problem, I agree. But at the end of the day, all treatments are chronic. Your beta cell function is depleting over time while you are on these drugs. And about a third, if not half, of the patients will end up on some form of insulin therapy as they go through their disease journey. So there is a need for new drugs, because half of the patients who are diabetic are above seven. That's the level where it's critical. That's when disease occurs, that's when you lose a limb. That's why we have 80% of patients who are diabetic, because they're uncontrolled, ending up dying from a diabetes-related disease, one. And another factor which people tend to forget is you lose 10 years of life when you have diabetes. That shows you there is a need for, please, something that is more restorative, then we're not addressing the problem, essentially. What we found is, and this starts in 2005, it's not our work, it is work that others have done. They have found this impactful protein that sits in the pancreas and the body is, it is a checkpoint, it basically controls a bodily function. And as I indicated earlier in obesity and in pregnancy, this protein is dysregulated or reduced in its function, and by that, people have seen since 2005 and 2007, and then in 2010, those are early research we saw, and everybody else in the industry has seen it as well, where people clearly show in your pancreas, which is there to produce insulin, that protein has a central function. If it were down-regulated, the body recovers or restores that function versus treatments today in diabetes that are more trying to sort of avoid the problem rather than address the problem. And so what we looked at early on was, okay, menin as a target has been identified for AML and other cancer targets, yes. Different function, different target, I mean very different, also the dosing is quite different. So then we said, okay, if we can safely get into the pancreas with our small molecule and can bind to the target effectively and target it, meaning can I take reduced menin in a way that the body is accepting my medicine, could I be potentially be used for diabetes? We've done cell experiments, we've done animal experiments, and we're now in humans. But I can safely, I can say that we are addressing the target quite safe. We understand the consequences of addressing the targets. We do not need to be dosing chronically, which is a key factor in diabetes because when you give our drug for 12 weeks, we can see this restaurational effect happening immediately after and we see you have benefits even a year down the road. So when we met with the FDA and showed them all our work, they said, that's interesting. Non-chronic, wow. Show me safety efficacy like we all have to do, but your endpoint is, and our primary endpoint is six months. Show me six months, meaning you're off drug three months, and then show me nine months as a secondary endpoint, and show me the core criteria we use in diabetes is A1C, which is a measurement of your blood sugar, right? So show me how you're affecting your blood sugar we can't we can beta cells there's a billion of them and they're the size of your fingernails so how am I going to judge that right but I can adjust the effect that we have on those cells by what they're do and what they are doing is they produce insulin and insulin reduces sugar so it's easy everybody agrees that that's a valid endpoint so they they gave us that also as an endpoint and they said show me in a pre-specified patient population which we're now doing in two studies, that you have this effect of reducing A1C over time without being on drug, and that is what we're not showing you with those two phase two studies. We've seen it in our newcomer study already, and we feel we have pretty much alignment on that. There's not a lot of discussion around the study design, the endpoint. It's fairly clear. The patient population, you asked about that as well, is identified by BMI, that's probably the biggest driver for finding an insulin deficient patient, he's typically not obese. Then you have insulin resistance, different form of diabetes. If you're insulin deficients, you're typically not obesity, you are like overweight or regularly weighted and you have, what we found is you have high A1C obviously because your insulin is not there. enrollment criteria, you're an adult because we're not in juveniles yet, and what else, you typically have had disease for a while, meaning we're trying to find a patient that is failing standard of care. We don't need to replace standard of cares. We have enough standard of caregivers. There's 60 approved agents in diabetes. They're all trying to do something. What we're saying is when you fail all those, we're trying to prevent you from going on insulin because that's when your real problem starts. That's where we fit in. So we said to the FDA, failing one to three agents is a third criteria for us. We do well when you failed, meaning we do actually better there. So those are the enrollment criteria we used for our main study that we call 211, which which is the insulin-deficient study. In another subset of patients, which we found the drug to be working really well, are the GLP-1 patients that are on a GLP1, but their sugar is not really controlled. So if you're treated with a GLT-1, typically you're obese. We found that what menin inhibition does to the pancreas as well is it upregulates receptors. By upregulating those receptors, we're not only enlarging the pool of beta cells, but you have more receptors. These receptors, when the GLP-1 is being used as a drug, are creating more communication between drug and target, and we've seen synergistic effects. We've seen benefits when you're on a GLP1 receptor agonist. And so we've looked at that population. There's great reduction in A1C, so again, A1c the endpoint. You're on a GLP-1, good, very clear, and your A1C is high. That's it, meaning fairly easy because that's the population we had in our all-commerce study. So also their endpoint is clear. Study design is clear, 60 patients each study, easy. I would say one study is faster to enroll, easier to enroll is the insulin-deficient population. There's abundant patients of those. With the GLP-1, people titrate, they go up, down, they change. It's not quite as easy to capture them at the right time because that profile isn't fully worked out. We have so many drugs now coming online that have so many benefits that people are not stable. We need them stable on the GLT-1 and having a high A1C. So we're fine-tuning that study, but we're going to enroll both studies, and we feel very comfortable that we have alignment with FDA. Okay. Thanks. I think that's pretty detailed and really helpful. A couple follow-up question. One is, maybe can you just confirm or give us some example, any other trial have ever looked at this diabetes subpopulation as the exploratory, maybe, but in terms of the or pivotal, any other has tried that? And then that's number one. Number two is, I understand this is phase two, right? so you get an alignment. And I agree, this inclusion criteria seems pretty straightforward to me. I think you can either identify, I see, I heard you said that GLP-1, maybe because of the enrollment criteria, you have to be unstable, and we know GLP 1, the dynamic, so it's pretty complex there, so maybe you need to fine tune that. But overall, it's a pretty straightforward in terms of the identification. But how you think about FDA will look at this data around phase two we can talk about the what you want to achieve there but have they ever indicated this could be our real pivotal our label population I think since we are the first addressing men and as a target in diabetes where we as well as they are what we're doing something new so when you do something new it's it's there's there a degree of hesitancy because we all don't know the first idea is you're not chronic right so now all the rules for diabetes are written for chronic agents so we already agreed with them that those rules do not apply meaning these 5,000 patient studies that are large because they're chronically dosed if I'm a one-time only drug I do not need to have evidence based trial results prior to going into you know a regulatory approval process because I'm just not as harmful to the patient as I could be with a chronic agent think about it the drug washes out in 24 hours so there's not real there's There's no real issue there if I dose you for 12 weeks with something that has shown in animals and in all our experiments to be fairly quote unquote benign, nothing's benign but it's in relation relative benign if you look at our safety profile. So answering your question, I believe we have, you asked an interesting question because you're asking is there somebody who had those enrollment criteria. There's nothing that has done non-chronic, so that's a new thing. Nobody has done Menon, that's new thing, doesn't mean we can't get there. I don't think the FDA is at all opposed, they're actually doing the opposite. They want non- chronic agents, if you look at how they treated teplizumab. Teplizomab is a drug that is non-cronic, it's given for stage two type one diabetes. If you really think about it, you're giving a drug for somebody who doesn't know he has the disease. they approved it so they're willing to do the unusual just to get solutions in that are are not run-of-the-mill meaning we have enough other drugs so we fit that criteria quite well we're restoring something where we're trying to regain health aspects that are valuable to the patient so I think we have alignment on the way we're addressing the target the the endpoints I feel were good study design is all good. However, I agree with you. If you look at clinical trials and you see how many studies are ongoing, what are their enrollment criteria? It's not unusual to have A1C as your enrollment criteria. Of course, you need to identify the disease. It's unusual to have BMI as an enrollment criteria, because in order for an obesity drug to be obesity-focused, you've got to be obese, which is BMI over 30. So to have a less than 32 BMI criteria or failing one or three prior drugs, it's not unusual. So I believe our criteria for the insulin-deficient patients is acceptable and you can find other studies that have done similar things. It's the GLP-1 failing or uncontrolled or still having high A1C while you're on a GLP1. It's a new class of drugs, right? And they're failing, meaning patients are actually having problems while on these drugs. and they're not controlling the A1C. So what do I do with that patient population? I would say there, I agree with you, we're chartering maybe new enrollment criteria, but we're in the study, the protocol has been accepted, we're working through it. I'm very confident that we're on track and in alignment with FDA at this stage. There's no reason for me to think otherwise. Yeah, okay, good, thanks. And then I like the TDO analogy here, so one-time treatment. Maybe just on the one-times treatment, two questions. One is on the FDA perspective or the traditional trial, do you expect it will be just 12-week treatment or whatever the treatment you decided eventually, and then you follow them for a certain time, and then that will be the pivotal trial. can this man be kind of redosed later, or if so, and then how much longer the follow-up you need? No reason not to redose. Just from all the work we have done, there is no problem, is there a need? And if you look at pregnancy, if a woman gets pregnant and breastfeeds, the breastfeeding adds less probability of getting type two diabetes later on in her life. If she breastfeeds two times, if she has children two times three times, four times, the probability of getting diabetes goes down. So there is a long term benefit of having had prolactin up regulated, menin down regulated and the benefits of that with a restoration of the pancreas producing more insulin through more beta cells we're doing the same thing yet with the drug so 12 weeks of treatment should and that's actually what we what we're we're testing for a year but we think the effect is lasting meaning i'm restoring your pool of beta cells just imagine that there's 40 million people in the u.s that run around with diabetes there's a hundred that have pre-diabetes 100 million people you take a pill for 12 weeks i can restore your your capacity to overcome this disease by yourself you're done now if you don't insult the body further if you do the right things to gain back the health can you keep that effect we don't know we think you can no reason for us to believe you can beta cells in your or my body live for decades they don't die so do I replicate those cells to live for decades, that's the theory, but we both don't know. So what I'm saying is that we're on a path where that is a potential outcome, and we're testing for that, but FDA requirements are show me a year. They're not saying show me five years. The year is, six months is the endpoint, primary, secondary, 12 months. We will follow those patients in this study. What we will do is we will roll them over in a new study so we can stay in touch with a patient and check their A1C and have a feedback loop to those patients. That for us is a way to see is there a need to restore their pool again? And if there will be a need in the future, we could potentially consider redosing them. I believe the FDA will say, look, here is your phase three, I understand, thank you for the data. Keep a tap on those patients and let us know what are the needs for redosing? If there is a need for redossing, how are you gonna address that? But it's a secondary question. It's not a question they're asking right now, and I don't think it's the question they would ask in a phase three. Okay, got it, that's good. And then now, another question is on the potential payer side, right, if it's get approval, you know, considering this can be a one-time treatment, but also with the potential to be redosing later. So how are you going to price this, and then also how payroll will think about this treatment, the overall cost? Yeah, so if you look at it from a patient's side, I would argue huge benefit because I'm not taking a drug all day long, I'm non-insulin, I don't have to check my sugar. There's a lot of benefits. one two oh what are the complications that are occurring from diabetes so neuropathy heart as i said earlier 80 of the patients die die of diabetes related complications so you have i mean you have limbs removed you have all these problems from toxifying your body through sugar so So, if I avoid that and I can show, yes, there is a health benefit that leads to less complications, these are all costs that we can potentially save the system. What we've done is we've an analysis through one of our consultants trying to understand if you're on insulin and I could prevent insulin by a year, what is the dollar value of that? It's about $30,000 plus just in costs that one could do a simple math on by finding what does it cost the system? How much can an insurance company benefit from us? So if we were to price it as a regular diabetes drug, it would be between $8,000 and $12,000. That's roughly where the price point is for years of drug. Once you fail the frontline cheap treatment, you go into a probably $10,000 to $12,000, maybe $8,000 to $11,000. The prices are coming down right now. Would I price myself there? It's not a question we're asking ourselves. We're not in the commercial phase yet. We'RE not in phase three. But if I were to compete at that price point and deliver a value that is lasting beyond the year, I'm already creating benefit so if the if the benefit lasts for five years it's a huge benefit maybe we price differently at that stage but just in in thinking in terms of abundance there's millions of patients and there's a big demand and there is no therapy that does what we do so i will find a price that is attractive for both sides um we as a company will and likely uh pharma will help us do that Okay, great. I think we are in a lot of conversation is the path forward, right? Because this is your, you are charging this unprecedented kind of territory here. And so maybe just back to the upcoming events. so this phase two for those two population are still on track to report a the second half and then that six months endpoint what you want to achieve there in terms of the Delta what's the clinical meaning for if you look at other studies that were approved in type 2 diabetes you have to hit sort of a 0.5 percent reduction in a1c so the scale starts to become meaningful above seven so if you're average of eight you get down to 75 that's a benefit if you get down below seven it's it's another endpoint people use how many patients can be below seven but that's very secondary the primary is how much are you reducing a1c and I believe if we hit the 05 hurdle we should get there placebo-adjusted we have seen between one five and one eight that's a lot i know i'm not projecting that in a larger phase two study we will hit those markers but if we were above zero five between zero five and one i would say we are we're doing great that's six months that's no that's a very that's 12 months our last readout six months you can see the curve in six months i would first i mean the first thing we have to achieve is completion of enrollment last patient in in both studies that's the marker from there we wait uh six months and at six months you got to be on track to get to those markers so if you just do linear and it's nothing's linear in this world but if you were to linearly look at it you if you want to hit zero seven let's say at 12 months you gotta be at zero three five at six right so looking at zero five is my marker at 12 months. I got to be somewhere on a curve to get to that marker. Once we're at six months primary readout, we will go to 12 months, that's secondary. And the secondary has to be 05 or above. Got it. And then the second half of the data readout is six months, not 12 months data. Well, first I got a head last patient. And if it's 31st of June, then it'll be the end of this year. We're working really hard are getting there important is that both studies are doing one a little better than the other but we will we will get somewhere in that ballpark yes okay got it all right so I think you know as we mentioned this ECOVA is the focus of the conversation but you do have a small molecule alpha based GLP-1 data will be still in 2q or that's a you know tell me a little bit more about that what's the expectations there so we have a quite a few we're gonna go into a DA and I'm not sure you will be there so we have lot of the new data will be coming what you want to achieve there why as a as another small molecule compound well we all start working maybe on the same problem as if you're in our industry and you are you can you know that we are trying to solve problems and what is exactly the problem we're trying to solve. The problem we're trying to solve is patients needing a help with obesity, and it's not necessarily for beauty reasons, but it's actually for health reasons. And the GLP-1 pathway your body uses to tell yourself, hey, I've eaten, I need some insulin. So you produce a hormone, GLP1, and the GLT-1, now we are using drugs that do the same thing to tell your body, hey you're done you have eaten let's go through the pathway of giving you the the idea of you you're you're full and that is a the backbone of the way we're addressing obesity today and we kind of agree as an industry it's pretty good it's working it is working however patients over time are not staying on their drugs they're switching drugs they they're titrating and they're dropping out they're unsatisfied. So if you are in a critical obese BMI size, you need to reduce because we know obesity is inflicted with cancer, with all these other diseases that come from obesity. So getting you out of that stage is important, but keeping you on drug is also important. So our goal was make a GLP-1 that is more tolerable. How do we do that? Peak to trough of orfaglipron, which we believe is a great leader in the oral space. The first problem was get rid of injection. Nobody wants an injection, so we created an oral. Second is, can you improve the oral? The oral orfoglipon in phase 3 now needs six months to titrate out. Nobody want to wait for six months. Obviously, they're cornering the market, but slow titration, why is it slow? Because of the impact it has on your system. They also want to keep patients on drug. Can I avoid the slow titration and titrate fast first? Can I improve tolerability for you so you can stay on drug and don't have all the side effects that prompt you to get off drug? That was the impetus to start this program. We're now in the clinic. We are in phase one. We re in the MAD cohorts, meaning we re in multiple ascending doses in target patients that are obese but otherwise healthy where we go from one week by week four week increments and we see what does our what do the various cohorts do the top cohort gets read out we are we're moving along in these mad cohorts quite quite well and we're going to give updates so awesome all righty i think the time's up yeah really appreciate the time here and then i really appreciate everyone watching or listening Yes, thank you. MR. Thank you.