Hi, everyone. My name is Maury Raycroft, and I'm one of the Biotech Analysts at Jefferies. I'd like to welcome Benny Sorensen, the CEO of Hemab Therapeutics. Hemab just recently IPO'd. Thanks so much for joining us today. Yep. You are more than welcome, Maury. I'm glad I'm here. Thank you for the invitation. We're going to do fireside chat format. Maybe for those who are new to the story, if you can give a one-minute intro to the company. Sure. Hemab Therapeutics is pursuing a vision of reimagining the treatment of blood coagulation disorders. We are aiming to build a multiple product, exclusive coagulation franchise company. To kind of move that from pie in the sky to pie in the oven, we are off to a good start. Our first program, sutacimig, has completed phase I/II in Glanzmann's thrombasthenia and is ready to enter phase III pivotal second half of this year. sutacimig also have another phase II study ongoing in Factor VII deficiency, which will read out initial data in 2026, early 2027. We have a second clinical stage asset, HMB-002, running phase I/II first-in-man in patients with the most prevalent bleeding disorder in the world called von Willebrand disease. Here we have initial single ascending dose data and are projecting the first multiple ascending dose efficacy data coming out in 2026, early 2027. We're excited to start talking about HMB-003, which we will present data at ISTH here in July in Paris. Th ere's more behind it. Really, that's in a nutshell, the company. Yeah. It's a great overview, you mentioned sutacimig in Glanzmann syndrome first. Let's dive into that. Maybe just talk about the data you've reported to date, and you've got an upcoming presentation at ISTH. How much additional data can we expect there? Yeah. That's an easy question, by the way. All the data that is in the S-1 will be presented at ISTH, and there's no new data. Got it. In the S-1, and at ISTH, we will present the complete Part B multiple ascending dose data, and that includes also data from Part C, the open label extension. Just high- level, what have we learned so far, f rom an efficacy point of view, we see up to 87% reduction in the annualized treated bleed rate, which is a regulatory-endorsed primary endpoint, and we see that in our low-dose weekly dosing regime. Another very important efficacy outread that we are proud of is if you take the 40% of patients that actually are experiencing life-threatening bleed events within the last 12 months, in Part B, we saw a 100% reduction of those severe bleed events, and that is still way over 60% in the open label extension. We have done a protocol analysis where we did an analysis in all patients that had a bleed event in run-in. There we can see 92% of patients are experiencing a benefit of variable size. Orthogonal efficacy readouts that are really compelling. We have a really robust safety tolerability data package, positioning us strongly for entering phase III. That data package includes that we know that there is a risk of exaggerated pharmacology at high exposure, where there can be Grade 2 venous thrombotic events occurring. Important to kind of get that learning in phase I/II. We can mitigate that going into pivotal. I'm having flashbacks from developing HEMLIBRA, developing QFITLIA, developing Alhemo. I was involved in all of those developments. Unfortunately there, we learned about thrombotic events in phase III. That is not fun. Much prefer to kind of have that understanding now, and can do that important risk mitigation going in. Compelling efficacy data, a management safety tolerability profile. We feel very compelled for next step. Yeah. That's a great overview of the data. Maybe digging in a little bit there, so for the open label extension, are you saying how many patients are still in the open label extension? We still have a significant number of patients. I don't know the exact number, Maury, in there. What it is, as we also say in the S-1, what it's showing is we sustain efficacy. There's no new kind of safety tolerability events. There's no new ADA events. It is supportive of the totality of knowledge we have. Yeah. Based on your comments around safety, do you feel like you've gotten enough data at this point w here you're confident? Yeah. I guess that was the first lesson learned in our interactions with the regulatory authorities is that the data are sufficient to transition to pivotal. There, the open label extension data was important. There's no doubt. Okay. For the upcoming FDA discussions on your phase III trial design, plan for midyear, is the meeting scheduled, and what are the potential scenarios for endpoints, comparator arm, and minimum ATBR reduction? Good. Here, the real good news is that we have a Breakthrough Therapy designation. We are not on the hook for needing to schedule meetings all the time. It's pretty much a continuous ongoing dialogue. We have already had meetings and aligned on multiple variables. For instance, we are aligned on all primary and secondary endpoints, and those are the primary and secondary endpoints we already interrogated in the phase I/II. We are aligned on an open-label study design, just like we did in phase I/II. We are already aligned on the primary statistical analysis, which will be the negative binomial regression analysis that's used in all bleeding studies. That's also what we did in the phase I/II. Then we are aligned on the safety mitigation strategy to make sure we target an exposure level that keeps us away from risk of exaggerated pharmacology, and we got a lot of praise from regulators in the way that we are building mitigations in there, educating investigators to make sure they look carefully at what patients to enroll into the clinical trial. The two topics that we are still making sure we are aligned on will be whether we run a single-arm trial or whether we try our best to see if we can optimize that to a randomized control trial. It really adds very little additional risk to us, but it could generate a higher probability of getting the drug approved globally to go to an open-label randomized control trial. We'll keep tinkering on that a little bit, and then our clinical pharmacology and FDA's clinical pharmacology are collaborating, making sure we have the right dose regime aligned as well. Got it. Which already now is low dose weekly w hether it is that number or that number, they are very close to each other. It could be tweaked a little bit slightly. Yes, a little tweak, but it really won't change anything. Got it. Okay. For the single-arm study versus randomized controlled study, I guess what's your base case scenario there? Well, base case is that we do what's been done in the past which is a single-arm trial j ust like we did in the phase I/II. As you all know, right, the regulatory authorities here in the U.S. and around the world has been experiencing a little bit of a pendulum where single-arm trials have not necessarily been as favored as, and even an open-label randomized control trial. I think it is worth spending a little time to see whether we can find a way of getting that slight improvement in study strength. Yeah. Okay. Honestly, I will give the FDA a lot of praise for actually being honest and say, "Guys, we know that all the arguments for doing this, but there may be semantics that actually matters for the future. Okay. For size of study, if it's single arm versus randomized control. Nothing will change with the size. Nothing changes. Nope. Okay. Statistical analysis plan is the same. Same. Everything is same. Powering as well. Same everything. Yeah. Got it. Okay. For this study, well, you mentioned the safety mitigation education as well. I guess, how does that process work? Does it take a long time? Well, key lessons learned from phase I/II is exposure is the number one driver. Then underlying predisposition. You don't need to add in multiple kind of eligibility criterias for that. It's all about educating your investigators. With the events in hand, that education is taken serious. I think we've learned really important stuff. The mitigations we have in place have been regulatory endorsed. We're in a good spot. Got it. Also wondering for the phase III, is that going to include some sort of a run-in period? Definitely How are you going to handle? We definitely need a run-in to make sure we have prospectively collected data on the annualized treated bleed rate. That is irrespective of whether it's a single-arm trial or whether it's randomized. How long would that be, and how do you factor in like the types of patients? Run-in up to six months. Six months. Up to. Yeah. Yeah. What proportion of the phase III enrollment is going to come from U.S., E.U., or? Yeah. By the way, we are constantly doing feasibility. We have not provided external guidance yet on where we think the majority of patients will come from. There will be patients enrolled across all kind of global jurisdictions, U.S., Europe. It's very likely there also will be patients from Gulf States and Japan. Got it. Okay. Right now, not providing the guidance on what proportion comes from where. I think you're going to see that kind of population based distributed. That's my best guess. Okay. How many patients do you think you're going to need in this study? It's ultra rare disease. To get a sufficient safety database, 75-100 patient. If you put that into perspective that the phase II was 34. None of those numbers are scaring me at all. For the 34 patients, how long did it take you to enroll? Here's a fun fact I would tell everybody. It was slow in the single ascending dose, Maury. Like it has been in every single ascending dose trial I've ever done, even in health volunteers. We present the data from like 13 patients in the multiple ascending dose just to our investigators, just like an internal data update. Within four months, we enrolled another 20 patients. Boom. The second they kind of said, "There may be activity in this drug," they must have called every single patient they had. It's amazing. Yeah. It's kind of a good rate to think about if it's 100 patients. Yeah. I would say as a rule of thumb, the enrollment period there is going to be comparable to what you see in hemophilia trials. Yeah. Okay. Makes sense. Whether it's randomized or single arm, that really doesn't. Oh, it doesn't change anything in regards to that. Yeah. Okay. Any thoughts on how to, for the VTE risk factor, could there be exclusion criteria in the phase III and- Well, yes, I alluded to that, right? This is predominantly making sure we pick the right dose regime to avoid exposures that could lead to exaggerated pharmacology, and the rest is really educating investigators. You don't need to do a laundry list of exclusion criteria. We've talked a lot about this, where it seems like you guys have pretty good understanding of what caused the VTE. Yeah. In all of the three cases, it's a combination of exposure and then u nderlying predisposition. The cases had three or more underlying concurrent predispositions. Right. Okay. For the Factor VII Deficiency proof of concept data later this year or early 2027. How are we setting expectations there? After summer, we'll provide a little bit more detail on the number of patients. What I will say now, here we are fortunate that in Factor VII Deficiency there are just very obvious biomarkers like prothrombin time and factor VII levels. Yeah. If we reduce the prothrombin time and see increases in VII, we have a proof of concept. Right. Really don't need a hell of a lot of patients to conclude that. Yeah. After that, if we can see that, Maury, there is a clear path. Right. Yeah. For this setting, how do you think about just heterogeneity in bleeds here? Yeah. It's a smaller sample size. How should we think about that? Yeah. I don't know if it's that much smaller, right? As you know, we do natural history studies across all our indications. We have also done one in Factor VII Deficiency. The Factor VII Deficiency 360, I recall, have 100 patients in the natural history study, has already giving us really a thorough insight into lead bleed frequency. It is probably not going to be sufficient as a control, and we will supplement it with prospectively collected data as well like we do in Glanzmann. It's giving us a lot of guidance already. Got it. I guess for both Glanzmann and Factor VII with the natural history patients, you're probably keeping track of those patients to some extent, or what proportion of those patients could be eligible for your studies? Too early to say, to be honest t oo early to say. Understood. Wondering too, just theoretically, would FDA accept pooling Glanzmann and Factor VII data for a single BLA filing, or these require separate regulatory paths? There's going to be timing that's going to define that. I think we're going to finish in Glanzmann before we finish in VII. I think the advantage that you could potentially leverage is that regulators often allow you to combine safety data. That can then make your efficacy set slightly smaller. I Think that that's a possible scenario. Got it. Okay. Maybe let's talk about the market opportunity a little bit. How many Glanzmann and Factor VII deficient patients do you think are undiagnosed or undertreated because of a lack of prophy option? Yeah. Well, right now, we know that there is at least 10,000 diagnosed patients with Glanzmann and Factor VII deficiency across U.S., Europe, Gulf states, Japan, and a small set of rest of world that uses specialty drugs. You're asking me how many do I think are not diagnosed yet or not known. That will be based on a guess. I'm not sure I feel particularly comfortable with that guess right now. I don't think it's going to be like PNH, where when Alexion launched eculizumab for PNH, I think they said there is one in a million. Now fast-forward today, I think it's 10 in a million or something like that. I don't think it's going to be like that. Okay. There will definitely be a subset of patients that has been pushed out because they don't have access to prophy or has been miscategorized as bleeding disorder of unknown disorder, don't know what to do with you. What that number is yet, not quite sure. We are trying to kind of learn more in the community on what that may look like. It could be a significant number. Right. Yeah. Makes sense. Yeah, bottom line, seems like there's underdiagnosis. There's probably a lot of patients out there that aren't on the radar because there's nothing for them. Yes. Okay. What competitive dynamics do you see in hemophilia prophylaxis that are relevant to Glanzmann and von Willebrand disease? Yeah. I think lessons learned in hemophilia is if you look at the journey of treatment, it started with on-demand bleed management, and then conversion to prophy. Yeah. Then conversion to sub-Q prophy regimes. Today, 80%, 90% of all patients with severe hemophilia are on prophy, right? HEMLIBRA generates $5 billion a year by being a weekly sub-Q weight-based dosing regime vial and syringe. I think what we are trying to do is we want to skip the on-demand and go straight to the sub-Q prophy, right? It's a leapfrogging from treatments from the 1960s and '70s to 2027. Right. Yeah, I guess for, you mentioned HEMLIBRA, what else about HEMLIBRA is applicable to what you guys are doing? Sub-Q weekly. I think the price tag of Hemlibra is one that we use as a base case. Yeah. You could argue that that's maybe a bit of a conservative base case because Glanzmann's and Factor VII deficiency is a lot less prevalent. Maybe the unmet need is multifold higher than in hemophilia. Hey, we need some anchor point, and that's a good anchor point to start with. Yeah. Payers, I guess any perspective into payer behavior as it comes to HEMLIBRA that could be relevant? I don't know, man. Yeah, I seriously don't know. Good question. Yeah. Fair enough. Let's shift gears and talk about 002 for von Willebrand disease. You've shown some early safety data there, but you're going to have a more robust update expected later this year, early 2027. Yep. Where are you at with dosing, and what von Willebrand factor level increase do you need to achieve for clinically meaningful ABR reduction? Just the state of state, we have presented the data, and that is also in our S-1 prospect, is 20 and 50 milligrams of fixed-dose data. Already at 20 mg and 50 mg, we see favorable safety tolerability, and we are already there seeing a 1.5-fold increase in von Willebrand factor and Factor VIII, which is kind of our predefined success criteria. I don't think we really need much more than that. We will investigate more about the durability. At ISTH, we will present data on 20 mg, 50 mg, and 150 mg. I honestly consider that somewhat incremental, Maury, because it is just more PK and PD, and we already hit our 1.5-fold, so I am like, I don't expect there to be a lot more news in that data set. At that time point, we will also announce that we then transition to the multiple ascending dose. Got it. The multiple ascending dose data, and the early efficacy readout from that will come either at ASH or EAHAD, so December or February. Got it. Okay. For the three doses, 20 mg, 50 mg, and 150 mg? 150 mg. 20 mg, 50 mg, and 150 mg is coming at ISTH. Got it. Okay. How do you anticipate the mechanism is going to translate clinically versus protein S inhibition, which is one of your competitors? Yeah. That's a good question, by the way. Just a couple of general statements. I'm a huge fan of Star Therapeutics because they are also trying to innovate and generate a change for patients with bleeding disorders, and innovation benefits patients. I also think that what makes this relationship really friendly is we are pursuing two distinctly different mechanisms. Yeah. At HMB-002, we are aiming to investigate what happens if you increase levels of von Willebrand factor and factor VIII. They are investigating what happens if you inhibit protein S and thereby try to bypass von Willebrand factor and Factor VIII. I sincerely don't want to guess on one or the other. I think we are pursuing ours in a clear conviction that the simplicity and the intuitiveness of simply correcting the underlying pathophysiology is going to have a broad appeal to patients and physicians. Right. Yeah, it makes sense. From a mechanism standpoint and just with the heterogeneity in von Willebrand disease, it's like there's different subtypes of patients. Mechanisms could work differently based on those patient types. How do you think about that? We are going to work in all Type 1s and Type 2As, Type 2M and Type 2N, so HMB-002 is designed to work in about 98%-99% of all patients. It is unlikely to have a lot of monotherapy effect in Type 3, but when we talk to our physicians, they're kind of like, "Yeah, we are still going to use HMB-002, but we will use it in combination with concentrates. Instead of giving them concentrates two or three times a week, we may give them concentrate once or twice a month. Got it. Yeah. Of course, it will also extend the half-life of exogenously administered von Willebrand factor. Right. Which we recently published in our pre-clinical paper in "Blood Advances." There is a study done in non-human primates dosed with von Willebrand factor concentrate and HMB-002, and you can see it hugely increases the half-life. Got it. Is there more quantification on that, the concentrate reduction amount that would be needed? Oh, I don't know, man. I'm guilty of developing recombinant von Willebrand factor in my days at Baxter, and despite all of the resources we had available there, I don't think we found more than 250 patients with Type 3. Right. Yeah. They deserve improvement in their treatment, but the endeavor we are on is really to try to serve the thousands and thousands of Type 1s and Type 2s. Yeah. Makes sense. For Star's VGA039, they've shown phase I/II data where they use ABR with historical bleed event recall for 6- 12 months. Does this change the reliability of the results in your view, and how could those results change in a phase III study? Just as a general point of view, I'm not going to comment on their design choices with regards to how they have collected their data. I'm happy to share the way we are thinking. In the von Willebrand disease 360, which is our natural history study with about 600, there were 611 patients in there. About 60 of those patients provided the following data retrospectively, recall on bleeds, and then 60 of them started collectively collecting bleeds, and then we compared individually what is an individual's capacity to accurately estimate their annualized treated bleed rate Recall versus prospective. The more bleeds people have, the worse they are in providing an accurate estimate. It can be as much as a 70%, 80% difference in if you had 50 or more, you now have 70%, 80% less b y prospectively collecting. At Hemab, we have decided to do prospective run-in. We have more than 80 patients right now in a minimum of four months prospective run-in using our validated electronic bleed diary to collect baseline annualized treated bleed rates that we can use then to compare with individually when we start chronic treatment with HMB-002, and therefore, generate, in our opinion, hopefully a high-quality estimate on efficacy. Got it. Has FDA commented on whether they have a preference or their views on the measure? The FDA has commented. There's also the last couple of decades of clinical drug development in hemophilia, prospectively collected data is considered a high-quality estimate o f bleed rates. I guess going back to the question, do you think the STAR data could change in the phase III? I have no opinion about that at all. Yeah. Okay. I still wish them all the best because y eah, that's the best scenario for patients. Yeah. Okay. They're also going to have data at the ISTH meeting as well. Once you disclose your data later this year, early 2027, what are the measures that we will be able to cross compare across the studies? That is also really hard to estimate, Maury. I guess they are looking at annualized bleed rate of all bleeds. We are using annualized treated bleed rate, so hard to compare those two estimates. Yeah. Yeah, I think that's going to be really hard. Yeah. Okay. Commercially, if both products reach the market, how do you think about just differentiating commercially? Well, first and foremost, von Willebrand disease is about 5x more prevalent than hemophilia, where there are 30 approved products. Right. I'm sure that there'll be plenty of market opportunity for more than one product out there, maybe even more than two. I hope so for patients. I think the lesson learned for HEMLIBRA in hemophilia A is that the simplicity, the intuitiveness of administering a treatment that gives you factor VIII equivalent activity is one that I think will translate over to von Willebrand disease. Yeah. HMB-002, again, it is simple, it's intuitive. It just increases levels of von Willebrand factor and Factor VIII. I think that will have a strong appeal both to patients and to physicians. I think that that will be a key differentiator. I also think that it will matter with regards to efficacy data. Yeah. I think as a guiding principle at Hemab, we will first focus on efficacy, and we will add on convenience. Got it. Okay. That makes sense. My next question is just around the weekly sub Q. Could you go to less frequent dosing potentially? Oh, sure. I think the lesson learned from HEMLIBRA was the first pivotal trial was done with weekly, and then there was added on every other week, a monthly dosing regimen. Right. What you see patients and physicians are doing is kind of cycling until they find the dose regime that gives them the ideal efficacy. I think that is the mindset that we will also be pursuing next steps. Got it. Okay. Looking ahead, could you potentially design your phase III differently versus STAR's ongoing study? What's the anticipated timeline for your phase III start? That's going to be two answers I can't really provide. I think, just again, as a guiding principle for us, it will not be to design a study that is a copy-paste of something else. It will be to try to design a study that has the highest possible probability of generating a strong data set to enable global approval of the drug because that's what we really aim for. It is to maximize the value proposition of these medicines is for them not to just be used in the United States, but globally. Right. Okay, makes sense. More to come on that front. More to come on that. Yeah. By the way, here, let the data drive it. I think that what we learn from both our prospectively collected natural history from the intervention study will position Hemab really favorably to design the strongest possible pivotal trial. Right. I wanted to briefly ask on 003, are there any hints? Any hints. All of the abstracts go live at the end of June, and I promise there'll be a curtain raiser press release so that you'll get the go look for the abstract. If you want to be a spy, I'm sure you can find s ome titles already on some websites. Yeah, the real data will come when all the abstracts gets released. Okay. I guess anything more on what drove the prioritization decision? It's another extremely high unmet need subset. It's something that we've worked on for a long time. It has a lot of the Hemab characteristics in it. It's a validated technology, and we've already disclosed it's a fatty acid conjugated peptide, so it's kind of a GLP-1-like molecule applied in hemostasis. Got it. Okay. That's helpful. I think we're out of time. Maybe to close out, if you want to comment on your pro forma cash and runway assumptions and key catalyst and investors you're focused on? Yeah. Super proud of our IPO, which was $347 million raised. Combined with the cash in hand we had, we have a runway into 2029 on the current plans. Got it. Thanks so much for joining us today, Benny. Oh, thank you, Maury. Appreciate it. Almost there.