Greetings, and welcome to today's Insight Conference Call and Webcast. At this time, all participants are in your listen-only mode. A question and answer session will follow the formal presentation. You may be placed into question queue at any time by pressing star 1, and we ask you to please ask one question and then return to the queue. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Alexis Smith, Vice President, Head of Investor Relations. Alexis, please go ahead.
Good morning, everyone, and thank you for joining us today. The press release and presentation for today's call can be found on the Investors page of our website. Today, I'm joined by Bill Muri, Chief Executive Officer, Pablo Cagnoni, President and Global Head of R&D, and Dave Gardner, Chief Strategy Officer, who will offer prepared remarks. Suki Apatye, Chief Financial Officer, and Stephen Stein, Chief Medical Officer, will join us for the Q&A portion of today's call. Before we begin, I would like to point out that we will be making forward-looking statements which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors in our SEC filings for additional details. With that, I'll hand it over to Bill.
Good morning, and thank you for joining us. Today, we're announcing Insight's acquisition of Star Therapeutics' Vega program, centered on VGA 039, a first-in-class Phase III asset in von Willebrand disease that we believe can become an important new growth driver for Insight. I'll briefly cover why this deal makes sense strategically and financially, and then Pablo will walk through the data and development path, and Dave will discuss the market opportunity and commercial framework. We conducted extensive due diligence on this asset across scientific, translational, clinical safety, regulatory, and commercial dimensions, and came away with a high level of conviction in both the strength of the data and the attractiveness of the opportunity. BGAO 39 checks all the boxes we look for in a business development opportunity. It's squarely within our core, hematology. The science, the disease, and the R&D and commercial operating models are all areas where insight has real expertise. Second, VGA 039 is supported by a high-quality, consistent data package with three layers of validation, mechanistic validation through target engagement, translational validation through restoration of thrombin generation, and clinical validation with strong early human efficacy and safety data. Third, the development path is clear and manageable, with alignment already in place with regulators who granted VGAO 39 breakthrough designation for the treatment of von Willebrand disease earlier this year. And importantly, it has the potential to be highly accretive to sales and growth post-29, with approximately $1 billion or more in net sales potential. Taken together, we believe this structured transaction is strategically aligned, financially meaningful, and consistent with our framework for capital allocation and value creation. The acquisition fits directly into our broader strategy, transitioning insight beyond a single cornerstone product. We're constructing a portfolio of multiple growth drivers rather than making one oversized bet, and VGA fits this strategy well. It strengthens our pipeline and represents a smart use of capital with an attractive upside and manageable risk profile. On a product level, as you'll hear from Pablo and Dave, VGA039 is designed to restore normal thrombin generation and reduce bleeding by modulating protein S activity. Current treatments for Von Willebrand disease are burdensome, inconvenient, and often fail to adequately control bleeding. If successful, VGA039 has the potential to become the standard of care for a sizable, underserved patient population, and to be for von Willebrand disease what hemlibra has been
for hemophilia A. With that, let me turn it over to Pablo. Thank you, Bill. Good morning, everyone. Our interest in this opportunity begins with a significant medical need and a novel first-in-class therapeutic approach that we believe could address key limitations of existing therapies. Well, Willebrand disease is the most common inherited bleeding disorder, affecting 135,000 diagnosed patients in the U.S. and many more worldwide. The disease is highly heterogeneous, encompassing multiple subtypes and a broad spectrum of clinical severity. As a result, patients can experience a wide range of bleeding complications, with the most common clinical manifestations including gastrointestinal bleeding other mucosal bleeds and heavy menstrual bleeding many of those bleeds can be managed outside the hospital setting however recurrent or severe episodes especially gi bleeding and in rare cases critical organ bleeding can be clinically significant and are the leading causes of emergency visits and hospitalizations. Patients with more severe disease can also experience hemophilia-like bleeds, including joint. The underlying cause of von Willebrand disease is a deficiency or dysfunction of von Willebrand factor, or VWF, a key protein involved in normal blood clotting or hemostasis. VWF plays a dual role in hemostasis by helping platelets adhere to sites of vascular or injury, and by stabilizing cloning factor VIII. When VWF is absent, reduced, or dysfunctional, both bladeless function and coagulation can be impaired, resulting in prolonged, recurrent, or spontaneous bleeding. Diagnosis includes bleeding history and specialized testing that measures the amount and function of one-wheeleron factor, with the latter determining the C subtype. In the United States, an estimated 35,000 patients have clinically significant disease burden and receive care at specialized hemophilia treatment centers, or HTCs. Current management includes on-demand treatment for acute bleeds and prophylaxis, which is based primarily on von Willebrand factor replacement. While prophylaxis can be effective, it requires frequent infusions and breakthrough bleeding is still common. Despite guidelines' support, prophylaxis remains underutilized, primarily due to the honorous nature of the schedule of infusions. These limitations underscore the need for novel prophylactic therapies that can provide effective bleed prevention while reducing treatment burden. That brings us to VGA039, an antiprotein S monoclonal antibody designed to modulate endogenous anticoagulant activity and support more effective hemostasis. Protein S serves as a cofactor for two key anticoagulant pathways, TFPI-alpha, which regulates the initiation phase of coagulation, and activated protein C, or APC, which regulates the propagation phase by inactivating factors 5A and 8A. By modulating protein S cofactor activity for both pathways, VGA-039 is designed to normalize thrombin generation in a controlled manner. The goal is to improve clot formation and stability without replacing von Willebrand factor and without driving excessive systemic coagulation. This mechanism is particularly compelling in von Willebrand disease, where the bleeding phenotype is heterogeneous. By enhancing thrombin generation downstream, independently of the underlying von Willebrand factor defect, VGA 039 has the potential to provide broad prophylactic coverage across from Willebrand disease subtypes and bleed types. VGA-C039 has been evaluated in four clinical studies, including Vivid 3, a Phase 1-2 multi-dose safety and efficacy study in adults and adolescents. In the trial, patients receive a monthly subcutaneous dose of VGA-C039 over a 17-week treatment period with the option to continue into Vivid 5, an open-label extension trial. Enrolled patients had a history of serious and or frequent bleeding episodes, including mucosal bleeds, GI bleeding, and hemophilia-like joint and muscle bleeds. Pre-study historical annual bleed rates, or ABRs, range from 0 to 431, reflecting the heterogeneity of the population. Most patients had a baseline ABR of greater than or equal to 12, which is consistent with high bleed population we are evaluating in Phase III. In this study, VGA039 demonstrated a substantial medial annualized bleed rate reduction of 81% across all participants, including those with no prior IV prophylaxis and switch patients. The depth of the response was also significant. Two-thirds of patients with a non-zero baseline achieved at least a 75% reduction, with one-quarter of them achieving zero qualifying ABR during the multi-dose treatment period. Notably, activity was observed across all von Willowbrunn disease subtypes and bleeding manifestations, consistent with the hypothesis that enhancing thrombin generation downstream of the underlying VWF defect may provide benefit across the heterogeneous VWD population. In precedent clinical trials with other investigational therapies across bleeding disorders, including VWD, ABI reductions from early studies like Vivid 3 were highly concordant with registrational study results. The safety and tolerability profile to date is also encouraging. VGA 039 was well tolerated in Vivid 3 with no withdrawals on therapy and no thromboembolic events reported. Taken together, this data supports the potential of VGA 039 as a novel, once-monthly subcutaneous prophylactic therapy for patients with von Willebrand disease and were the basis for FDA-granting breakthrough therapy designation. We have regulatory alignment on the registrational program for VGA 039. The Phase III study is designed as an open-label, intrapatient comparison study with a six-month observational baseline period, followed by 12 months of active prophylaxis. Patients will receive monthly subcutaneous VGA 039 using a weight-banded flat dosing. The primary endpoint is improvement in total AVR, including both treated and untreated bleeds, comparing each patient's active treatment period against that patient's own observational baseline. The study is expected to enroll approximately 60 patients, and is on track to deliver top-line data in early 2029, supporting a potential launch shortly thereafter. As Bill mentioned, our conviction is supported by the convergence of mechanism, pharmacodynamic evidence, early clinical activity, and a phase 3 design aligned with both the biology of the disease and the needs of the patient population. I will now turn it over to Dave, who will discuss the commercial opportunity for VGA-C039 and why
this asset is a strategic fit for Insight. Dave? Thanks, Pablo. PGA039 checks all the boxes when we think about our business development strategy at Insight. It is highly adjacent to our core hematology franchise, leveraging existing commercial and R&D capabilities. It has established human proof of concept. It is in phase three with the potential to launch in the PERI LOE timeframe for Jackify. And the commercial opportunity is needle moving in magnitude for
insight with blockbuster potential. But most importantly, this represents a novel step change
for patients who have yet to experience the exciting innovation that has been brought to other bleeding disorders. Let me start with the last point, which is how impactful VGA039 could be for von Willebrand disease patients from a practical perspective. Today, the prophylaxis options available for von Willebrand are primarily IV factor replacement therapies. These products can reduce bleeding, but they require frequent infusions, often two to three times per week. This burden is a major reason prophylaxis remains underutilized, even among patients with severe and frequent bleeds where benefit risk favors bleed prevention. VGA039 has the potential to change that paradigm. On the left of the slide, you can see that the current prophylaxis model requires frequent IV infusions with replacement therapy. Patients have to make a choice. Deal with frequent infusions or treat acute bleeds as they happen. In many cases, patients will need both. On the right side is the proposed VGA 039 regimen, a once-monthly subcutaneous injection. This difference matters. In hemophilia, we've seen that effective subcutaneous prophylaxis can transform treatment patterns and patient expectations. We believe a similar dynamic could be in play in the high unmet needs segment of VWD. Our commercial focus for VGA039 is not on the entire diagnosed population of 135,000 in the U.S., but rather a focused, defined population within von Willebrand disease who experience severe or frequent bleeding. As Pablo mentioned earlier, today roughly 35,000 patients are treated in HTCs and other specialty settings. At least 7,000 to 10,000 of them have severe or frequent bleeding and are eligible for prophylaxis today. This is our initial target market. Due to the limitations of the current options, only around 2,000 of them are on prophylaxis or prophylaxis-like regimens today. Our target population is not the average von Willebrand disease patient. It is a high burden segment characterized by recurrent GI bleeding, clinically significant mucosal bleeding, joint or muscle bleeds, and other patterns. In severe von Willebrand disease, annual bleeding rates can be very high, in some cases reaching 30 or more events per year. From a market development standpoint, we believe VGA 039 will do two things. First, it will convert patients currently receiving IV prophylaxis to a less burdensome monthly subcutaneous option. Second, it will expand the prophylaxis-eligible treated population by making prophylaxis more practical for patients and physicians who today may avoid regular IV therapy because of administrative burden. We have seen in hemophilia A that when prophylaxis becomes more practical, adoption can become the norm, with rates approaching 90% versus only 25% in severe or recurrent von Willebrand disease today. There is a real opportunity to close the gap between those who need prophylaxis and those who are receiving it. Our pricing assumptions are anchored to existing prophylactic regimens and supported by the severity of disease in this target population. Severe von Willebrand disease is associated with meaningful healthcare utilization, including iron replacement, transfusions, emergency visits, hospitalizations, and ambulatory care, which supports the health economic rationale for more effective and convenient prophylaxis. Finally, Insight is well-positioned to launch VGA 039 successfully, given our deep hematology expertise and established commercial infrastructure. In short, VGA039 gives us a late-stage hematology opportunity with a differentiated mechanism, a practical monthly subcutaneous profile, and the potential to meaningfully improve care for a clearly defined high-need von Willebrand population. Taken together, we believe these attributes support both the potential to establish a new standard of care and a significant blockbuster peak sales opportunity. Back to Bill.
Thanks, Dave. Ultimately, this transaction reflects how we think about business development insight. We're focused on opportunities that can create asymmetric outcomes, where the upside materially outweighs the downside. We've structured the deal with a combination of upfront consideration of $1.25 billion and up to $750 million in sales milestones, which aligns economics with value creation. It preserves balance sheet flexibility and supports the potential for a strong return on invested capital. Just as importantly, we do not view this as incremental innovation. Based on the data generated to date, we believe this asset has the potential to establish a new standard of care. Opportunities like that are rare, and they create a fundamentally different value proposition than assets that simply offer modest improvements over existing therapies. Before we move to Q&A, I want to recognize the work of Star Therapeutics. They have built a differentiated program in an area of real need, and we are excited to carry that work forward with their team. Our focus now is on ensuring smooth integration and executing the Phase 3 study. With that, operator, please open the line for questions.
Certainly. We'll now be conducting a question and answer session. If you'd like to be placed in the question queue, please press star 1 on your telephone keypad. If you'd like to remove yourself from the queue, please press star 2. A confirmation tone will indicate your line is in the question queue, and we ask you to please ask one question, then return to the queue. Our first question is coming from Salveen Richter from Goldman Sachs. Your line is now live.
Hi, this is Lydia. I'm for Salveen. Thanks so much for taking our question. Could you just speak to strategically the timing of the deal and then also any risks related to the VGA039's mechanism, particularly around thrombo-amelic events? Thanks so much.
Related to the timing of the deal, I don't think we tie BD to a calendar. um we have you know two sources of developing our product line internal r&d and then external bd and we looked at this opportunity it was highly differentiated the timing was right in terms of what we're solving for post 29 we have a phase three uh ready asset and we looked at the risk-adjusted returns on this, and we were ready to act. I think that this is probably as close to a textbook example of the type of deal that makes sense for a company like Insight. And we also still have balance sheet flexibility if we see other deals. And we're patient right now. If we see something that makes sense, we'll do it. If not, we'll wait. Thank you.
So let me take the second part of the question. We believe the risk here is very low. Let me tell you why. Number one, we reviewed more than 60 patients' worth of data, and we reviewed all the data from the open-level expansion study. There were no relevant treatment emerging adverse events of thrombosis. Furthermore, we saw no evidence of clinically relevant D-dimer elevations in any of these patients. And we think that's for a couple of really important reasons. Number one, the dosing of EGA-039 and the dosing strategy that the DART team put in place was a PD-driven, pharmacodynamic-driven dose selection. By measuring the amount of thrombin generation, we know that if the exposures to 039, the concentrations are between 25 and 100 microamps per ml, there is normalization of thrombin generation. And that is the key word here, is normalization of thrombin generation without overshooting thrombin generation. By doing that, we think the risk of clinically relevant thrombotic events are very, very low, and we were comfortable as we reviewed all the data that I
described. Next question is coming from Edson DeGer from Barclay. Your line is now live.
Great. Thanks for taking the question. Congratulations, Dale. Just a couple of – just one question really on the blockbuster potential for GA039, particularly around pricing. I think about once-monthly prophylactic products like Tuxero for heterotory and geodema. Is that a right way to look at that from a pricing standpoint? And any color you can provide on how you can get to the $1 billion peak potential? That'd be great.
Thanks for the question. I'll turn it over to Dave.
Sure. Thanks for the question. So if you look at not only VWD prophylaxis regimens, but prophylaxis across bleeding diseases, you come up with price points in the $500,000 all the way to upwards of a million dollars a year. I would say that we're not banking on the upper end of that, but I would think about a net price point in that kind of $500,000 per year range is how to think about it. Yeah. What I would just add,
answer is think about what david talked about during his prepared remarks if you have a hemophilia a like segment of von willebrand's meaning severe frequent bleeders and we looked at claims data we looked at the literature we surveyed a very high percentage of the hemophilia treatment centers in the united states you have seven to ten thousand people if you use annual cost of therapy of five hundred thousand the lower end of the range you're looking at a market between $3.5 and $5 billion. That doesn't assume that you achieve, for example, what has been achieved in the hemo-VAA market where prophylaxis has garnered 90% of the population. So there's a credible path here to a product that can move the needle at Insight and generate north of a billion dollars.
Thank you. Our next question today is coming from Derek Archilla from Wells Fargo. Your line is online.
Morning, this is Jake Monford, Derek. Thanks for taking our question. So just from your diligence process, how are you thinking about this approach targeting protein S compared to others aimed at stabilizing VWF?
This is a completely different mechanism. The mechanism of modulating protein S, which is such a key element in the coagulation cascade, we think is highly differentiated and uniquely suited for the most severe forms of von Willebrand disease. Now, because it normalizes thrombin generation, regardless of quality factor levels, potentially it could work across other indications. But we believe it's uniquely suited for the group of patients that are more in need of better prophylaxis, and that's type 3 and a lot of type 2 bone-wheeler and disease patients. I think other approaches that have been recently advanced are very different because they're more focused on stabilizing and elevating existing levels of bone-wheeler and factor, which would not solve the problem of patients with type 3 and many type 2 von Willebrand disease. So as we looked at this, we think the highly differentiated nature, the fact that it's likely to address, and it does in the work that we reviewed, the needs of the most severe patients with VWD, we thought that was a very differentiated approach.
Our next question today is coming from Ashwurma from UBS. Your line is now live.
Great. Yeah, thanks for taking your questions and congrats on the deal. Maybe just in terms of like the phase three focus here, is this on the high breeders with no prior IV prophylaxis? And I see that like in this data, it shows that you've also generated 75 to 100% lead reduction in patients who switched from prior prophylaxis treatment. So is that a market segment that you want to follow up at a later point of time, just help us understand, like, what are the different pieces of the market and how you want to pursue them? Thanks.
That's most definitely a group of patients we will address as well. We have very early data, and some of those patients already from the MAD study that we reviewed. They're not included in the current pivotal trial, but will be absolutely a focus of a future pivotal trial. It's a very important group of the population and we intend to address their need. Thanks for the question.
Our next question today is coming from Evan Siegerman from BMO Capital Markets for Line
Is Now Live. Hi, guys. Thank you so much for taking my question. So, Bill, in the past, a multiplier and how you think about the world in terms of, you know, to acquire, you know, aside from indication, you know, aside from expansion beyond just VWD and kind of other bleeding indications. How else could this be a multiplier? And what else might you be looking for in a next asset beyond this company? Thank you. Well, I think as it relates to VGA039 being
a multiplier, you know, I think, you know, Insight's at a size right now where if we have a credible path to $1 or $2 billion, that is a real needle mover. I mean, we're not a giant diversified company where you need $2.5 to $5 billion in peak sales potential for a product to be highly material. And we're going to get a lot of leverage out of this business because we have all of the infrastructure we need in R&D and commercially. And as I said, I think this is about as close to a textbook type deal that we could do. It really checks all the boxes. As it relates to other things that we're going to do, you know, you know our three areas, Evan. We have hematology, oncology, and immunology. And I don't think it's going to be the case that we replace Jackify with one big swing. I think often those types of deals, whether it's a large company or a small company, can often destroy value. And, you know, we're not trying to meet a deal quota. We're not trying to count the number of deals we're doing. We're looking for things like this, which I think are differentiated. It's got an acceptable risk-reward profile, and it's right in our core. And if we see those things in those areas, we'll act. And if we don't, we're going to be patient.
Next question. Today is coming from Michael Schmidt from Guggenheim Partners. Your line is now live.
Hey, guys. This is Rosie. Congrats on the deal. So on the patient population, you've called out roughly 5,000 to 8,000 patients who have recurrent bleeds but aren't currently on prophylaxis. What do we know about why those patients are on treatment today, and what kind of market share do you expect CGA039 to capture in that subgroup specifically? I guess if I may add another question, just how do you think about the relative size of the U.S. versus XPS opportunity here?
Thanks for the question. I'll turn it over to Dave.
Yeah, thanks for the question. So in terms of penetrating the population who have severe frequent bleeding but are not currently on a prophylactic or prophylaxis-like regimen, I think that's the gist of the first question. When we surveyed physicians and spoke to dozens of KOLs about this, the indication is that it's multiples of that initial 2,000. So if you ask physicians, they would say it might get up to four to five X. So when we define the population in the way that we did of severe current frequent bleeders, we expect high penetration in that subset. I think that all you need to do really is take that 2000 and double it to have a really, really meaningful one to $2 billion opportunity for us. The physicians are telling us it would be more like 4 to 5x. So I think we're in relatively good shape there. In terms of how to think about the U.S. versus ex-U.S., we've modeled the ex-U.S. as a relative minority in the total peak sales opportunity. If you look at other examples such as Hemlibra and other bleeding diseases, the ex-U.S. can be a very, very meaningful portion of the total sales. So I think If anything, we might be being conservative on the ex-U.S. front, but we absolutely anticipate this being a global launch.
And, Rosie, I would just add, if you think about how you segmented the market, there's 2,000 people taking prophy, which is with replacement therapy, and it's multiple times a week. VGA 039 gets approved. There's a high likelihood that the majority of those 2,000 patients could be put on VGA 039. right there starts at roughly a billion dollars. And then there's the expansion of the prophy market. And as Dave said in his prepared remark, it's only 25,000 of that severe frequent bleeding, 25% of that frequent severe bleeding subset. In hemophilia A, different disease, more serious, it's 90%. If we get prophy utilization up to 45% of that overall segment, you're talking about 3,000 to 4,500 patients, and so that is going to be a sizable opportunity for us. Thank you.
Today is coming from Jessica Fyre from JPMorgan. Your line is now live.
Hey, guys. Thanks for taking my questions. Maybe following up on kind of the theme of a couple of the other ones, so of the 7,000 I think 10,000 U.S. patients eligible for prophylaxis today, would all of those patients who are not currently on infusions meet the enrollment criteria for the Vivid 6 Phase 3 trial, or can you tell us kind of what proportion would? And then recognizing the differentiated dosing frequency here, what's the primary comparator or benchmark you're going to hold your Phase 3 data up against when it reads out? Thank you.
So let me take the first part of the question, and then I think Dave and Bill may want to comment. So the eligibility, as I mentioned, is ABR of 12 or greater. So patients are going to be followed for six months. They have to capture the bleeding episodes. If the ABR is 12 or greater, that's what they need to move to the prophylaxis phase of the study. Each patient is his or her own control here, Jess. There's no comparison with other approaches, since there's nothing similar to this. Obviously, if on Willebrand disease patients, they are managed with conventional prophylaxis, which is basically factor replacement therapy. And as Dave reviewed, this is very onerous for patients. The rates of reduction that we've seen were over 80% of ABR reduction in the clinical data that we've reviewed, even in the open-label expansion. And a lot of the patients, as I mentioned in my prepared remarks, had ABRs. so basically zero once they were switched to VGA039. So that profile that I just described and the statistical design are fully aligned with FDA, so we're comfortable with the sign of the study, and we're very comfortable based on the review of the open label extension data that we had. Dave, you want to add?
So, yeah, I think it's a good question, Jess. In order to isolate the treatment effect and measure the magnitude of bleed reduction, you're right not all seven to ten thousand would qualify for the phase three protocol to state that clearly in terms of who we would compare to there's as you know a handful of approved agents in vwd we know that they all have impressive bleeding reductions we think those are one relevant benchmark the visit the feedback we get is that because these are relatively small studies and estimates can move around with just individual patients that it's key to show that you reduce bleeding by more than 50%. It's key to hit the primary endpoint by the way it's designed with the agency. And after that, you know, we think the profile will win. Great. Thanks, Dave.
Thanks, Jess. Thank you. Our next question today is coming from Eric Schmidt from Cantor Pestero.
Your line is now live. Hi, good morning, everyone. This is Imogen on for Eric. Congratulations on the deal. I guess a question on recruitment, so the timelines here, given the relatively small spies of the study and a fairly small number of sites open, do you see potential to accelerate
the early 29 timeline now that it's in Insight's hands? Thank you for the question. A couple of comments on that. The first part is we need to remind you the design of the study. So when a patient is enrolled, they first have to be followed for six months in order to capture the ABR. Then they get started on therapy. The treatment is a year in order to be able to assess the ABR reduction in those patients. So immediately from when the last patient's enrolled, you have an 18-month period that you have to wait. The STAR team has done a fantastic job implementing the study. We reviewed the screening logs and enrollment and the site opening schedule. obviously we bring to bear a larger organization with a much larger footprint, and we'll do everything we can to accelerate the enrollment in the trial. And there might be ways to do that. We'll provide further guidance as we transfer all the obligations to INSIGHT, but we'll obviously try to accelerate the enrollment of the study. But I just want to remind everyone, there's that 18-month period that patients had to be followed for six months for the basal ABR, and then one urotherapy to capture the reduction in bleeds. Thanks for the question, Imogen.
Thank you. Our next question today is coming from Matt Phipps from William Blair. Your line is now
live. Good morning, Gene. Thanks for taking my call. Congrats on this deal. I think it fits nicely. Just wanted to quickly ask, I know the trial excludes patients with very low levels of factor VIII. How many patients might have that exclusion criteria? And then just confirming that the same weight-banded dosing is going to be used in the Phase II trial that was shown the PK of in the ASH presentation? Thank you.
Matt, thanks for the question. Yeah, the answer to the weight-banded dosing is yes. The same dosing that we use in order to trial that was implemented in order to trial and that we're using the open level extension will be used in the Phase III trial. There's three doses, 225, 300, and 450, depending on the weight of the patient.
On the factor VIII levels, Matt, just to clarify, we want to make sure patients don't have high factor VIII levels, so we're limiting to patients needing to be at the lower limit of normal. If you look at the population, we did extensive work on this, the patients who fall into the category of severe frequent bleeders that we have defined as our target patient population, virtually all of them are going to have low factor VIII levels.
Thanks, Matt.
Thank you. Our next question today is coming from Jay Olson from Oppenheimer. Your line is now live.
Oh, hey, guys. Congrats on the deal, and thanks for taking the question. Just to follow up on Bill's earlier comment, what's the level of interest you're seeing amongst patients and prescribers to move away from factor-based prophylaxis and switch to a more convenient and potentially more effective, safe or option for prophylaxis like O39? And then also, if you could please comment on your appetite for moving into adjacent bleeding disorders like hemophilia.
Go ahead, Dave. Thanks, Jay. So the physician interest is incredibly high in this. I'd say it starts with a discussion around how patients on IV prophylaxis would prefer a simple monthly subcutaneous option. But very quickly, it goes to how much this can expand the population. I think a lot of patients really consider going on prophylaxis but opt against it because of the onerous profile. Most of the physicians we spoke to commented that patients, including those in the Vivid 3 program who had opted out of getting IV prophylaxis, didn't actually realize how bad their disease was until they had experienced some relief. So I think we'll just, if we produce the product profile that we're looking for, the interest in this will be incredibly high, both in the current population on prophylaxis and beyond it.
Bobby, you want to take the second question?
I'll be happy to. Thanks for the question, Jay. So theoretically, let me take a step back. So VGH039 increases thrombin generation regardless of clotting factor levels. So mechanistically, there's no reason why it could not work in other bleeding disorders as well. The STAR team, and we agree with their approach, addressed von Willemburg disease first because there is a bigger need, as we've been discussing during the call, particularly in patients with severe von Willemburg disease, for better, more effective prophylaxis. So that approach is something we fully agree with, and we're going to drive this forward as fast as possible. They have presented, the STAR team, preclinical data in other bleeding disorders, and we'll have conversations internally and then with key opinion leaders about initiating potential trials in other potential bleeding disorders. But mechanistically, VGA-039 should work regardless of the bleeding disorders we're talking about Because what it does is it normalizes thrombin generation regardless of clotting factor levels. Thanks for the question, Jay.
Our next question today is coming from Judah Fromer from Morgan Stanley. Your line is now live.
Thanks for taking the questions. Congrats on the deal.
Maybe just first, can you give us a little more detail on overlap in call sites for your Hemonc sales force and kind of hematologists treating these bleeding disorders?
And then just assuming this will be a chronically dosed antibody, any evidence of any drug antibodies or neutralizing antibodies that you've seen thus far?
Thanks for the question, Judah. As it relates to the market or the target audience, you're talking about roughly 150 hemophilia treatment centers. In fact, the program here is going to look very similar in size and shape to what we're already doing at bone marrow transplant centers all across the country, where there's roughly the same number. And so we have a pretty good sense of what it will take to commercialize this product.
Let me take the second part of the question. We have not seen any evidence of ADAs in the ongoing open-level extension trial, or any of the trials, for that matter.
Thank you. Our next question today is coming from Kripa DeVaraconda from Truish. Her line is now live.
Thank you for taking my question, and congratulations on the deal. So from the data that you've seen so far, do you have a good sense of what the average duration of treatment could be, especially when we think about the real-world use of the drug? And what's your level of confidence that this could be a chronic therapy, and how does that play into your estimate of the peak opportunity?
Great. Dave will start off, and then Pablo will add.
Thanks, Kripa. So between Vivid 3 and the open-label extension, we have not seen any evidence that patients won't take this chronically. And so we have yet to give you an estimate on duration of therapy, and that's good news because virtually everyone is ongoing, and we don't see any signs of any reasons for discontinuation.
let me complete that i i i don't see why a patient with severe von Willebrand disease that has abrs over 12 which is enrollment criteria for this study and some of these patients have 30 40 50 an abr 30 40 50 and that is receiving a once a month subcutaneous injection that is well-tolerated and has no major side effects that we know at this point, why would that stop at any point in time? So, I think what we're looking at here is a chronic ongoing therapy, particularly for the patients with more severe bone marrow disease.
Great. Thanks for the question.
Thank you. Our final question today is coming from Salim Syed from Azuho Security. Your line is now live.
Great. Thanks for the question, guys. Congrats on the deal. Just one from us. Given that this is as an open-label study, how are you guys handling the data internally? Is this something that you plan to sort of look at as you go and you'll have knowledge to that, or is there some sort of blinded protocol even for you guys, even though it's open-label? And related to that, if you wanted to change the protocol to build in a room, if you saw good data, is that something that you could do?
Thanks for the question, Pablo. Yes, thank you for the question. So the way we will handle, as you described, an open-label study is the same way we handle other open-label studies, whether they're randomized or not. And there is a team within the company that basically monitors the study, but we are blinded to the ongoing results of the study. So this is treated with a level of regulatory rigor that it has to for a pivotal trial. So the answer is we will not have access, obviously, to the data as the study is ongoing. When it comes to modifications to the protocol, I think it's a little bit too early to comment on that. We will obviously transfer all the obligations to inside. The process basically starts today to do that. And then we'll make decisions, as you usually do in any pivotal trial where there's any need for interim analysis. Now, very importantly, we have full alignment with FDA here in the design of the study, and so we would take any change. We would be very cautious about making any changes to the ongoing study or the statistical analysis plan because of agreements we have with FDA.
Great. Thank you for the question.
Thank you. We've reached the end of our question and answer session. And, ladies and gentlemen, that does conclude today's teleconference webcast. You may disconnect your lines at this time and have a wonderful day. We thank you for your participation today.