All right, let's go ahead and get started, guys. Next up, really happy to have the team from Viridian Therapeutics. It's been a great year, great couple of years. Preparing for a really big 2026, actually.
Lost, in terms of the proptosis. So there's three elements that we measure in those studies: proptosis response, which is the bulging of the eyes, a reduction of that bulging; diplopia, which is double vision, you want to respond to, or resolution there; and then clinical activity score, which is essentially a proxy for pain, inflammation, and how the patient feels about their inflammation. And we did very, very well across all three of those endpoints. We submitted our Breakthrough Therapy Designation for the program after the data came out.
And we emphasized in our application how quickly we were able to get a treatment effect, which is a rapid treatment effect that occurred after just three weeks, after just one infusion. It's the majority of patients achieved that, and that was statistically significant, obviously. That was one element of our application. We also had our diplopia or double vision response in the chronic population, which had not really been seen before by the previously approved product. That was a great element. Finally, we have a different infusion treatment regimen. We treat over the course of roughly three months versus the currently approved product, which is at six months. We have five infusions. We put in 70% less drug, a lot of really positive attributes to our drug.
And we're really looking forward to the next steps in the regulatory process with that. With shortly following that, and we have our top line data for our active and chronic populations using our subcutaneous program coming up in Q1 and Q2, respectively, in the active and the chronic. We, that is the same antibody as the IV, the only difference being the half-life extension that's been engineered into the antibody for subcu delivery that's been formulated to fit into an auto injector, small volume auto injector pen, one that's commercially validated and used in multiple already approved products. It's very easy for self-administration at home. So we think that's a very exciting prospect for patients in terms of getting them additional access.
So the IV program plus the subcu program entering into a, what is already a $2 billion market in the U.S. alone, we think we can expand in that market. We think we can grab share. What is critical about this, this market is a new start. So it's not, we're not trying to switch anybody off of the currently approved product. We just, we offer a different treatment option, at every point of the physician conversation with their, with their patient when they come in post-diagnosis. So really exciting setup. The data's been great, from our perspective. We think, we have good alignment with FDA, as we move forward in the process. We are looking at geographic expansion. We, we have guided that we will file the MAA, the marketing authorization in Europe in Q1 of this coming year.
The TEPEZZA, which is already approved in the U.S., is approved in Europe. They're working through pricing. We get the benefit from that. We'll get a look at what kind of pricing they get, and we'll go from there, in terms of what kind of business we build in Europe. But we have the time to do that given the timing of the regulatory filing. Japan, we just announced a deal earlier this summer, where we partnered in Japan, in that market. TEPEZZA's already gotten a great price, so we can follow in their footsteps there too. So the setup is really nice, from a commercial perspective, and we are executing across the board on that program. So the other part of our portfolio is anti-FcRn, another validated target.
We like validated targets, validated mechanisms with big markets, where we can come in with differentiated profiles and hopefully offer improvements for patients or better treatment options for patients. So that is the strategy. And although thyroid eye disease is a really good example of that, just given the differentiation that we've been able to try to engineer into the program, FcRn is also a good example of that, because we think we can. We have two different programs there. Our 006 program is an Fc fragment. It's a similar concept to Vyvgart, which is obviously, I think, considered the gold standard still. And we like the fragment approach. We're finishing up our first in human study there. We'll have more direction to provide on that program later.
We are also filing an IND for our 008 program, which is a half-life extended approach, which is obviously has great possibility in the FCRN world, given how fast it clears and how frequently the dosing occurs for those patients. So we're really looking forward to seeing the healthy volunteer data from that study in the second half of the year as well. So we have a lot going on, a lot of really positive momentum execution across the board. And we like the strategy and how we can take advantage of some of these big markets.
Awesome. All right, maybe we can just go temporally. So to start on 003 subcu side.
Yep.
The REVEAL-1 study in the first quarter.
Mm-hmm.
Maybe just, it's probably helpful to recap. What is the patient population that you're enrolling in this REVEAL-1 study? How's that different from THRIVE, THRIVE-2? And then I guess next question, what's your expectations on placebo or on proptosis response from an efficacy perspective?
Yeah, maybe I'll have Shan answer that one.
Yeah, sure. So from a the REVEAL-1 study obviously is in active patients, top line data expected Q1. REVEAL-2 is in chronic patients. We've designed both of these two studies very similarly to how we design the THRIVE and THRIVE-2 studies for the veligrotug program. And in particular for active TED, it's capturing those patients who are in that initial phase of their onset of symptoms for thyroid eye disease. Our inclusion criteria is patients within 15 months of that initial onset of TED symptoms. On the chronic side, we are again enrolling a very broad and the broadest and most representative population of chronic patients. And this is through the inclusion of patients with Clinical Activity Score from that entire spectrum of zero to seven. Again, a reminder, Clinical Activity Score measures the pain, the inflammation, the redness, swelling that these patients feel.
These are the symptoms that really prompt them to, for patients who are chronically with TED, they, for better or worse, have come to generally live with whatever level of proptosis they've stabilized back into. But the reactivation of that disease, with the swelling and the inflammation, is what prompts them to be reminded of when they first got the disease in the first place and is motivating for patients to go back and seek treatment with their physicians. So that's why we think it's important to have included this population in both the THRIVE-2 for IV side, but then also replicating that inclusion criteria for REVEAL-2 on the subcu side as well.
We think both of these studies are set up very nicely and are de-risked from a standpoint of the molecule for 003 subcu, which is designed to be half-life extended, but otherwise the CDRs, the variable domain of the antibody, is identical to the veligrotug IV molecule, which means that what we were able to do is show what the PK exposures are, based on modeling for the two doses that we're testing, Q4 weekly and Q8 weekly in the pivotal trials, and both of these exposure levels were matching or even exceeding the exposures that we saw from IV at the time that we did this comparison back in the 2023 timeframe.
So we, the bottom line is we are looking at PK exposures that we believe are in the range of activity because we had already seen the same levels of exposure being clinically active in a phase two trial, which again, we're referencing back to the 2023 timeframe for veligrotug. All of that is a really nice setup and comes around to, Gavin, your question about, what do we think, sort of the bar for success here is. The goal that we see here is for a physician to look at the top line data for subcu 003 and say, this matches their expectations for the level of efficacy that IGF-1R has come to set in the marketplace, and that efficacy still references back to TEPEZZA 'cause that's what they have the most experience with right now.
We look at the bar for success being what the proptosis levels were achieved by TEPEZZA in the registration trials that they conducted. That is a range of about 50%-70% on a placebo-adjusted basis for proptosis. We think if 003 can achieve proptosis, which we believe it is de-risked to be able to do anywhere in that range, we have met the bar for efficacy from a proptosis standpoint for these physicians and patients. Of course, the profile for 003 is exceedingly convenient. We designed it and we expect to launch it in an auto injector that's been commercially de-risked. It will be at home self-administration and so that a patient would not need to live anywhere near an infusion center or even need to go to the infusion center to get their treatment.
Awesome. All right. So when you reference 50%-70% placebo-adjusted proptosis response, what are your expectations on what the placebo arm will do? And I guess some of the context is there have been other trials in this space that have shown a higher placebo response. I'm not sure if there's any explanations you have for why those were different from your THRIVE-1 and THRIVE-2 studies.
Yeah, let me. I'll just jump in. I can point out that we've run the two largest studies ever conducted in thyroid eye disease, so THRIVE-1 and THRIVE-2 were the two largest to date. REVEAL-1 and REVEAL-2 are even larger. We have paid particular attention to that with respect to, you know, there's always concerns about placebo drift, but we have demonstrated in those two studies that we have some protocol design features that we are, that obviously, you know, we think are very helpful with respect to that, so we're trying to, we're very vigorous about it. There's a lot of, you know, discussions with the PIs. There's a lot of overlap with our PIs from THRIVE and THRIVE-2 into REVEAL-1 and REVEAL-2. We have our same clinical operations team. We have our same CRO, so there's a lot of consistency in terms of operationally across those studies.
That gives us the confidence that I think you're referring to.
Sorry, I just don't know what I'm supposed to do. Sorry.
All right, perfect. That makes a lot of sense, and do you have an expectation on what the placebo arm will do from a proptosis response rate perspective?
We haven't come out and set expectations for that. Obviously, we wanna see the data itself, but given the experience that we've had with THRIVE and THRIVE-2, where, it wasn't just the primary endpoint, but all along the time course, the placebo rates were very consistently low, and the treatment rates were very consistently high or that rapid onset of treatment effect that we talked about earlier. So we feel really good going into the REVEAL-1 and REVEAL-2 studies from a placebo standpoint.
Yeah, if you go back and look at our data, you can see the curves on both the treatment arm and the placebo arm are very consistent across the endpoints and the time points, which in our view shows, you know, the skill of our operational team.
Yeah. Awesome. All right. On the, on the safety side of things, I know there has historically been investor focus on the hearing events, right? You actually came out and put out very low events in THRIVE and THRIVE-2. So I guess we're thinking about the subcutaneous studies, specifically REVEAL-1 first. What should our expectations be there, right? It's a longer study, so should we see a higher rate of hearing events or there's a subcu dynamic where the exposure is a little bit lower from a Cmax perspective? What are you guys thinking there?
Yeah, this goes back to the PK exposures and the PK parameters that I was referencing earlier. So on the efficacy side, we think Cmin drives efficacy for antagonistic antibodies, and we've shown that Q4 weekly, Q8 weekly, those Cmins are achieving or exceeding levels of the IV from that phase II study. But then on the safety side, whether it's Cmax or overall exposures, both of these PK parameters are lower for the subcu than the IV, which is, we think, actually a good thing from a safety standpoint because it means that there's an upside potential here for safety to look even better with the subcu. A reminder though, that the safety profile for IGF-1Rs is now quite well known. It is very well known. It's expected. Physicians know how to manage it.
The majority of these are mild and transient, meaning they almost all go away after patients come off of IGF-1R treatment, and so we don't think we need a win on safety. In other words, to be better on safety, to have a compelling commercial profile for the subcu drug, but there is that potential for an upside there on safety.
I would just point out in the moderate to severe population, there's quite an urgency to treat, depending on where you fall on that continuum. I mean, the proptosis, the diplopia. I mean, imagine this is primarily a patient population of women in their forties and fifties. They have active lives. They have families. They have jobs. All the things that you would expect. It is a very debilitating disease. It's disfiguring, and so there's a real big patient impact here, and so with that safety profile as being well known and managed, and then having that combined with that urgency to treat, it's a, you know, that's what makes us so excited about being able to offer this as a treatment option for patients.
Yeah, that's great. Actually, on, on that point, as we're thinking about the veligrotug launch next year, what are your expectations for how quickly this launch is going to go?
Well, we haven't really guided on that, obviously yet. I think there's a lot of excitement, you know, that we had very big studies, as I mentioned. We had a lot of participation. There's a lot of anticipation coming in, with respect to a different treatment option. But we haven't provided any specific guidance with respect to launch. I mean, there's certain things that we're gonna look for. You know, we're building a company here, so we wanna make sure that we do it right. We also have subcu coming in right behind it. So we've gotta be really good at what we do. And so, you know, we've got a great team in place and we're looking forward to that. But we'll have more to say about that as we get closer.
Yeah, that makes sense. Maybe in the last little bit of time, we can just kind of wrap up with financing milestones as we look ahead to next year.
Yeah. So Shan and her team just ran a great deal this summer in Japan with one of the best Japan deals with respect to upfront, milestones and royalties, a fantastic deal for us. That was in the summer. We announced in October that we did a royalty deal, which was great 'cause that's a non-dilutive approach that brought in the necessary capital. We then topped that off with an equity raise, because we felt that an additional equity raise would help us be able to guide to everyone that we are now expect to get to profitability and break even, which is a really powerful thing for us to be able to say. That obviously includes our revenue assumptions, but it also includes our FcRn development as well.
The last number we put out with respect to cash was just shy of $900 million. We're well positioned to execute across a really exciting portfolio.
Awesome. With that, I think we'll wrap it up there. But Steve, Shan, thanks so much for joining.
Thank you, Gavin.
Thank you.