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 Hemop Therapeutics. Hemop just recently IPO'd. Thanks so much for joining us today.

You are more than welcome. Maury, I'm glad I'll be here. Thank you for the invitation.

And we're going to do fireside chat format. So maybe for those who are new to the story, if you can give a one-minute intro to the company. Sure.

So HEMAP Therapeutics is pursuing a vision of reimagining the treatment of blood coagulation disorders. We are aiming to build a multiple products exclusive coagulation franchise company. And 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, SUTASAMIC, has completed Phase I, II in Glansman's Rombistenia and is ready to enter Phase III pivotal second half of this year. SUTASAMIC also have another Phase II study ongoing, in fact, VII deficiency, which will read out initial data in 26, early 27. We have a second clinical stage asset, HMBOO2, running Phase I, II, first in man, in patients with the most prevalent bleeding disorder in the world called von Wilben's disease. Here we have initial single ascending dose data and are projecting the first multiple ascending dose efficacy data coming out in 26, early 27. And then we're excited to start talking about HMBOO3, which we will present data at ISGH here in July in Paris. And there's more behind it. So really, that's, in a nutshell, the company.

Yeah, it's a great overview. And you mentioned Stastomac and Glansman 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?

Yeah, that's an easy question, by the way. All the data that is in the S1 will be presented at ISTH. and there's no new data but in DS1 and at ISGH we will present the complete part B multiple ascending those data and that includes also data from part C the open label extension and you know just high level what have we learned so far from 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. And then we have done a protocol analysis where we did an analysis in all bleeding, all patients that had a bleed event and run in. And there we can see 92% of patients are experiencing a benefit of variable size. So orthogonal efficacy readouts that are really compelling. And then we have a really robust safety tolerability data package, positioning us strongly for entering phase three. That data package includes that we know that there is a risk of exaggerated pharmacology and high exposure where there can be grade two venous thrombotic events occurring. Important to kind of get that learning in phase one too so we can mitigate that going into Pivotal. And I'm having flashbacks from developing Himlibra, developing Q-FITLIA, developing all hemo. I was involved in all of those developments. And unfortunately there, we learned about thrombotic events in phase three. That is not fun. So I much prefer to kind of have that understanding now and can do that important risk mitigation going in. So compelling efficacy data, a management of tolerability profile, we feel very kind of 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, except number in there. And what it is, as we also say in DS1, what it's showing is we sustain efficacy. There's no new kind of safety tolerability events. There's no new ADA events. So it is supportive of the totality of knowledge we have.

Yeah, and based on your comments around safety, do you feel like you've got enough data at this point where you're confident?

Yeah, you know, and 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. And, you know, there the open label extension data was important. There's no doubt.

And so for the upcoming FDA discussions on your phase three trial design, plan for mid-year, is the meeting scheduled? And what are the potential scenarios for endpoints, comparator arm, and minimum ATPR reduction?

So here, the real good news is that we have a breakthrough therapy designation. So we are not on the hook for needing to kind of 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 1-2. We are aligned on an open-label study design, just like we did in phase 1-2. 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 1-2. And 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, you know, they look carefully at what patients to enroll into the clinical trial. The two subjects that are, 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 controlled trial so we will keep tinkering on that a little bit and then our ClinPharmacology and FDA's ClinPharmacology are collaborating making sure we have the right dose-dose regime aligned as well which already now is low dose weekly I just – whether it is that number or that number, they are very close to each other.

So it could be tweaked a little bit.

Yes, a little tweak, but it really won't change anything.

Got it. Okay. And so for the single-arm study versus randomized controlled study, I guess what's your base case scenario there?

Well, base case, you know, is that we do what's been done in the past, which is a single-arm trial, just like we did in the Phase 1-2. But as you all know, right, the regulatory authorities here in the United States and around the world has been experienced a little bit of a pendulum where single arm trials have not necessarily been as favored as an even an open label randomized control trial. So 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.

And 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, you know, there may be semantics that actually matters for the future.

And for size of study, if it's single arm versus random?

Nothing will change in the size.

Nothing changes. Okay. And so statistical analysis plan is the same? Everything is same. Powering as well? Okay. And then 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, you know, the key lessons learned from phase one, two is, you know, exposure is the number one driver and then underlying predisposition. And you don't need to add in multiple kind of eligibility criteria for that. It's all about educating your investigators. And with the events in hand, that education is taken serious. So 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. And also wondering for the phase three, is that going to include some sort of a run-in period? And how will you handle it?

We definitely need a run-in to make sure we have prospectively collected data on the annualized treated bleed rate. And 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 types of patients?

Run in up to six months.

Six months? Yeah. And what proportion of the phase three enrollment is going to come from? U.S., EU?

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.

But right now, not provided 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. Okay. And how many patients do you think you're going to need in the study? It's an ultra-rare disease.

You know, to get a sufficient safety database, 75 to 100 patients. And if you put that into perspective that the phase two 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 will tell everybody. It was slow in the single ascending dose, Maury. Like it has been in every single, single ascending dose trial I've ever done, even in health volunteers. um then we present the data from like 13 patients in the multiple ascending dose just to our investigators just like an internal data update and within four months we enrolled another 20 patients boom okay so the second they kind of said ah there may be activity in this drug they must have called every single patient they had yeah okay so that's kind of it's kind of a good rate to think about if it's 100 patients. I would say as a rule of thumb, the enrollment period there is going to be comparable to what you see in hemophilia trials.

Makes sense. And whether it's randomized or single-armed, that really doesn't...

It doesn't change anything in regards to that.

And any thoughts on how to, for the VT risk factor, Could there be exclusion criteria in the phase three?

As I alluded to that, right, this is predominantly making sure we pick the right dose-dose rating to avoid exposures that could lead to exaggerated pharmacology. And the rest is really educating investigators.

Yeah, yeah.

You don't need to do a larger list of exclusion criteria.

And we've talked a lot about this where it seems like you guys have a pretty good understanding of what caused the VTE. Yeah.

You know, in all of the three cases, it's a combination of exposure and then underlying predisposition. And, you know, the cases had more or, you know, three or more underlying concurrent predispositions.

Right. Okay. And for the factor seven deficiency proof of concept data later this year or early 27, 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, you know, here we are fortunate that in factor seven deficiency, there are just very obvious biomarkers like pro-frombin time and factor seven levels. If we reduce the pro-frombin time and see increases in seven, we have a proof of concept. Really don't need a hell of a lot of patients to conclude that. And after that, if we can see that, Maury, there is a clear path.

And for this setting, how do you think about just heterogeneity and bleeds here? It's a smaller sample size. How should we think about that?

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 7 deficiency. The Factor 7 deficiency of 360, I recall, have 100 patients in the natural history study, has already given us, you know, really 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 Glanzman. But it's giving us a lot of guidance already.

Got it. I guess for both Glanzman and Factor 7 with the natural history patients, you're probably keeping track of those patients to some extent. What proportion of those patients could be eligible for your studies?

Too early to say, to be honest. Too early to say.

Understood. And wondering, too, just theoretically, would FDA accept pooling Glanzman and Factor 7 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 Glanceman before we finish in 7. I think the advantage that you could potentially leverage is that regulators often allow you to combine safety data, and that can then make your efficacy set slightly smaller. So I think that that's a possible scenario.

Got it. Okay. And maybe let's talk about the market opportunity a little bit. So how many Glanzman and Factor 7 deficient patients do you think are undiagnosed or undertreated because of a lack of pro-fee option?

Right now, we know that there is at least 10,000 diagnosed patients with Glantzman's, in fact, seven deficiency across U.S., Europe, Gulf States, Japan, and a small set of rest of the 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, and 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, you know, when Alexion launched Iglesias for PNH, I think they said there is one in a million. And then 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. But there will definitely be a subset of patients that has, you know, been pushed out because they don't have access to prophy or has been miscategorized as bleeding disorder, of unknown disorder. I 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.

Makes sense. So bottom line, it 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. And so, yeah. And what competitive dynamics do you see in hemophilia prophylaxis that are relevant to glansman 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 and then conversion to sub-Q prophy regimens. 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 violent syringe. I think what we're trying to do is we want to skip the on-demand and go straight to the sub-Q prophy, right? It's leapfrogging from, you know, treatments from the 1960s and 70s to 2027.

Right. Yeah, and I guess for, you mentioned Hemlibra.

What else about Hemlibra is applicable to what you guys are doing? subq weekly you know uh i think the the price tag of hemlibra is one that we use as a base case yeah and you could argue that that's maybe a bit of a conservative base case because uh you know glanceman's in fact seven deficiency is a lot less prevalent uh and maybe the unmet need is multifold higher than in hemophilia but hey i mean some anchor point and that's a good anchor point to start with yeah and 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 um fair enough and uh so let's shift gears and talk about o2 for von willebrand disease um so you've shown some early safety data there but you're going to have a more robust update expected later this year early 27 yep um where are you at with dosing and what uh von willebrand factor level increase do you need to achieve for clinically meaningful reduction so just the state of state right we have presented the data and that's also in our s1 prospect is uh 20 and 50 milligrams the fixed dose data uh already at 20 and 50 milligrams we uh we see favorable safety tolerability and we are already there seeing a 1.5 fold increase in more open factor and factor eight, which is kind of our predefined success criteria. Don't think we really need much more than that. We'll kind of investigate more about the durability. At ISGH, we will present data on 20, 50, and 150 milligram. I honestly consider that somewhat incremental, Maury, because it's just more PK and PD, and we already hit our 1.5 fold. So I'm like, you know, that's not, I don't expect there to be a lot more news in that data set. But at that time point, we will also announce that we've then transitioned to the multiple ascending dose.

Got it.

And the multiple ascending dose data and the early efficacy readout from that will come either at ASH or EAHED, so December or February.

Got it. And so for the three doses, 2050 and 150? 150, yeah.

2050 and 150 milligrams is coming at the ICH.

Got it. Okay. And how do you anticipate the mechanism is going to translate clinically versus protein acid inhibition? Which one of your competitors?

Ah, yeah, that's a good question, by the way. You know, just a couple of general statements, right? I'm a huge fan of staff 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, you know, what makes this relationship really friendly is we are pursuing two distinctly different mechanisms. At HMBOO2, we are aiming to investigate what happens if you increase levels of enrollment factor and factor VIII, and they are investigating what happens if you inhibit protein S and thereby try to bypass enrollment 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. And 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 HMBOO2 is designed to work in about 98% to 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're still going to use HMBOO2, 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.

Because, of course, it will also extend the half-life of exogenously administered monrobin factor. Which we recently published in our preclinical paper in Blood Advances. There's a study done in non-human primates dosed with monrobin factor concentrate and HMVOO2. And you can see it hugely increases the half-life.

Got it. And so is there more quantification on that, the concentrate reduction amount that would be needed?

Oh, I don't know, man. And I'm guilty of developing recombinant monrobin 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. They deserve, you know, 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. um and uh for stars vga 039 uh they've shown phase 1 2 data where they use abr with historical bleed event recall for 6 to 12 months does this change the reliability of the results in your view and how could those results change in a phase 3 study i'm sorry as a just as a general point of view i'm not going to comment on you know their design choices with regards to how they have collected their data.

But I'm happy to kind of share the way we are thinking. In the von Robben's disease 360, which is our natural history study with about 600, there are 611 patients in there. About 60 of those patients provided the following data. Retrospectively recall on bleeds and then 60 of them then started collectively collecting bleeds and then we compared individually what is an individual's capacity to accurately estimate their annualized treated bleed rate um recall versus perspective uh the more bleeds people have the worse they are in in kind of providing an accurate estimate it can be as uh as much as a 70 80 percent difference uh in you know if you had 50 or more you now have 70 80 percent less by prospectively collecting. As a result of that, you know, at HEMAP, we have decided to do prospective run-in. So we have more than 80 patients right now in a minimum four-month prospective run-in using our validated electronic bleed diary to collect baseline analyzed treated bleed rates that we can use then to compare with individually when we start chronic treatment with HMBO2 and therefore, you know, generate, in our opinion, hopefully a high-quality estimate on a phagus.

Got it. And has FDA commented on whether they have a preference or their views on the measure?

The FDA has commented, and, you know, there's also the last couple of decades of clinical drug development in hemophilia, right, prospectively collected data is considered a high-quality estimate of bleed rates.

And so I guess going back to the question, Do you think the STAR data could change in the phase three?

I have no opinion about that at all. I still wish them all the best because that's the best scenario for patients.

And they're also going to have data at the ISTH meeting as well.

Once you disclose your data later this year, early 27, what are the measures that we will be able to cross-compare across the studies? you know that is also really hard to kind of estimate maury i guess uh they are looking at uh annualized bleed rate of you know all bleeds we are using annualized treated bleed rate so hard to compare those two estimates um yeah yeah i think that's going to be really hard yeah okay uh and commercially um uh if both products reach the market uh how do you think about just differentiating commercially? Well, first and foremost, right, the von Routemann's disease is about five times 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, you know, Hemlibra and 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 Rolben's disease, where HNPOO2, again, it is simple, it's intuitive. It just increases levels of von Rolben factor and factor VIII. I think that will have a strong appeal both to patients and to physicians. So I think that that will be a key differentiator. I also think that it will matter you know um with regards to efficacy data yeah uh and i think at as a as a guiding principle at hemab we will kind of you know first focus on efficacy and we will add on convenience got it okay that makes sense kind of my next question is just around the weekly subq um could you go to less frequent dosing potentially oh sure um now i think the a lesson learned from him libra was right we we uh the first pivotal trial was done with weekly and then there was added on every other week and a monthly dosing regime. And what you see patients and physicians are doing is kind of cycling until they kind of find the dose-dose regime that gives them the ideal efficacy. And I think that is the mindset that we will also be pursuing next steps.

Got it. Okay. And looking ahead, could you potentially design your phase three differently versus STARS, ongoing study, and what's the anticipated timeline for your phase three, sir?

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. So more to come on that. More to come on that.

Yeah. And by the way, here, let the data drive it.

Yeah.

And I think that what we learned from our, from our, both our prospectively collected natural history from the intervention study will position HIMAP really favorably to design the strongest possible pivotal trial.

I wanted to briefly ask on OO3, are there any hints?

Any hints? All of the abstracts go live at the end of June, and I promise there will be a curtain race of 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 some titles already on some websites, but But, yeah, the real data will come when all the abstracts get released.

Okay. I guess anything more on what drove the prioritization decision?

It's another extremely high on met-need subsets. It's something that we've worked on for a long time. It has a lot of the heat map 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. So 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 I had investors.

Super, 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.