Welcome, everyone, to Jeffrey's 2026 Global Healthcare Conference. My name is Roger Song, covering Simica 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.
Ramesh, why not you give two minutes or a couple minutes about Biomia 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 be covered by you, Roger, and Cha-Cha, because you do really good work. 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 their current GLP-1-based therapies. And why is that? Because typically, even if they have insurance coverage, they feel uncomfortable, right? There is some form of nausea, some form of discomfort. So can I create a drug, a small molecule that is orthoglipon-like, meaning it has the qualities of orthoglipon, which is a great drug, but it just 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 one as well. So it's type two, type one, and obesity that we're focused on.
Awesome. I think that's a good old video. And then I think we should probably focus a little bit more on the diabetes side first at Menin because that's probably 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 Menin inhibitor, you know, we follow Menin inhibitor space quite closely as well. I think you also initially are doing oncology. I think the first time I saw Menin inhibitor in diabetes is maybe two, three years ago. at the ADA, so they have a couple of pre-clinical 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 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 develop a drug or doing clinical trials for those population. What's the regulatory conversation there make you feel confident as you do the phase two, we'll talk about it, and then this will be our registrational subpopulation so there's a lot that you sort of touched
upon let me 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 we're and it's 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 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 than ... We're not addressing the problem, essentially. What we found is, and this starts in 2005, it's not our work, it's work that others have done. They have found this impactful protein that sits in the pancreas, and the body is, it's a checkpoint, it basically controls a bodily function. And as I indicated earlier in obesity and in pregnancy, that 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 downregulated, 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 potentially be used for diabetes? We've done cell experiments. We've done animal experiments. We're now in humans. And I can safely, I can say that we are addressing the target quite safe. We understand the consequences of addressing the target. 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 restorational 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't 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 judge the effect that we have on those cells by what they're do and what they're 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 the 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 now showing you with those two Phase II studies. We've seen it in our Orkhamer 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're 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 deficient, you're typically not obese. You're overweight or regularly weighted. And what we found is you You have high A1C, obviously, because your insulin is not there, another 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 care. We have enough standard of care. 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 fail, meaning we do actually better there. So those are the enrollment criteria we used for our main study that we call 211, 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 GLP-1, but their sugar is not really controlled. So if you're treated with a GLP-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 GLP-1 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. It's 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 GLP-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, really helpful. A couple follow-up questions. 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 registration or pivotal, any other mechanism 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 the enrollment criteria, you have to be unstable, and we know GLP-1, the dynamic, so it's pretty complex there, so maybe that's, you need to fine-tune that. But overall, it's pretty straightforward in terms of the identification. But how you think about FDA, we'll look at this data from phase two, we're going to talk about what you want to achieve there, but have they ever indicated this could be a real pivotal or label population?
I think since we are the first addressing menin as a target in diabetes, where we, as well as they, are, we're doing something new. So when you do something new, there's 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 agree 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 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 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 it's in relation relative benign if you look at our safety profile so um answering your question i believe we have um you asked an interesting question because you're you're asking is there somebody who had those enrollment criteria i there's nothing that has done non-chronic so that's a new thing. Nobody has done Menon. That's a new thing. Does it 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 tiplizumab, tiplizumab is a drug that is non-chronic. It's given for a 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 and they approved it so they're willing to do the unusual just to get solutions in that 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 endpoints I feel were good, study design is all good, however I agree with you, if you look at CLIN 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 not 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, you know, still having high A1C while you're on a GLP-1. 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.
Okay, good. Thanks. And then I like the TDO analogy here, so one-time treatment. Maybe just on the one-time 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 menin be kind of redosed later or if so and then how much longer the
the follow-up you need no reason not to read those just from all the work we've 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 2 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 upregulated, men and downregulated, 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're testing for a year, but we think the effect is lasting, meaning I'm restoring a pool of beta cells. Just imagine that. There's 40 million people in the U.S. that run around with diabetes. There's 100 that have pre-diabetes, 100 million people. You take a pill for 12 weeks, I can restore 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't. 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 end point. 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 the 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 redosing, 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 a question they would ask in a phase three.
Okay, got it, that's good. And then now another question 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 a payer will think about this treatment overall cost?
Dr. Yeah, so if you look at it from a patient side, I would argue huge benefit because I'm not taking a drug all day long, I'm not on insulin, I don't have to check my sugar. There's a lot of benefits. One. Two, 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 limbs removed, you have all these problems from toxifying your body through sugar. 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 done an analysis through one of our consultants It's trying to understand, if you're on insulin, and I could prevent insulin by a year, what is the dollar value of that? And it's about $30,000 plus, just in cost 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 stock, it would be between $8,000 and $12,000. dollars that's roughly where the price point is for years of of drug um once you fail you know the frontline cheap treatment you you you go into a probably ten to twelve thousand dollar maybe eight um to twelve thousand dollars 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 huge 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
pharma will help us do that okay great I think that we are in another 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 you still on track to report it in the second half? And then is that the six months endpoint, what do you want to achieve there in terms of the Delta? What's the clinical meaning for, you know?
If you look at other studies that were approved in type two diabetes, you have to hit sort of a 0.5% reduction in A1C. So the scale starts to become meaningful above seven. So if you're average of eight, you get down to seven, five. That's a benefit. If you get down below 7, it's another endpoint people use how many patients can be below 7, but that's very secondary. The primary is how much are you reducing A1C, and I believe if we hit the 0-5 hurdle, we should get there. Placebo-adjusted, we have seen between 1-5 and 1-8. That's a lot, I know. I'm not projecting that in a larger phase 2 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 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 got to be at zero three five at six months so looking at 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 zero five or above got it and then
the second half of the data readout is six months not a problem first I got a
head and if it's 31st of June then it'll be the end of this year we're working really hard on getting there important is that most 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 is the focus of the conversation but you do have a small molecule awful based GLP one data will be still in 2q or that's you know tell me a little bit more about that what's the expectation there so we have a quite a few we're gonna go into ADF, I'm not sure you will be there, so we have a lot of the new data will be coming. What do you want to achieve there? Why 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 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 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, GLP-1, and the GLP-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 idea of you're full. And that is 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'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 Orphaglipuron, which we believe is a great leader in the oral space. So 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 Orphaglipuron in phase three now needs six months to titrate up. Nobody wants 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're 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
gonna give updates soon awesome alrighty I think the time's up and yeah really appreciate the time here and then I really appreciate everyone watching and listening yes thank you