Good morning, everyone. Thanks for joining us here at the Leerink Partners Global Healthcare Conference. My name's Tom Smith. I'm one of the senior biotech analysts here at Leerink. It's my pleasure to welcome our next company to the stage, Viridian Therapeutics. Really happy to be joined up here by the President and CEO, Steve Mahoney, and Chief Business Officer, Shan Wu. Thank you both for joining us.
Thanks for having us.
Yeah, thanks, Tom.
Steve, 2024 was a huge year for the company. You guys had multiple positive phase 3 readouts for your lead program. Now 2025, I think, is a big year of execution for you guys, progressing towards your potential first BLA filing. Why don't you just kick us off maybe with some introductory comments for those in the audience who might be less familiar with the Viridian story and tell us what you've been up to at Viridian?
OK. Yeah, as Tom referenced, we had, first, thank you for inviting us. We will probably be making forward-looking statements that carry risks and uncertainties, and we refer you to our SEC filings going forward. With that said, we did have our two phase 3 readouts in roughly the fourth quarter of last year for our active THRIVE study and the chronic THRIVE-2 study. Those results were better than expected, I think, with respect to our across all the endpoints and all the time points. Very consistent, very robust. These were the two largest phase 3 studies in TED ever conducted. The results were fantastic and a really positive step forward for patients due to some of the differentiation that we were able to show versus the currently available product that's available for patients today.
By that, I mean we showed a very rapid onset of action. To back up, the main endpoints here are proptosis responder rate, which is essentially the bulging of the eyes and reduction of the bulging of the eyes; diplopia, which is double vision. We're looking to have responders, but we're also looking for complete resolution in the trial. Then Clinical Activity Score, which is essentially a proxy for pain, redness, inflammation of the eye. Across all those endpoints, as I mentioned, we had very consistent, very robust results, positive results across all the time points. Very nice, clean curves across all the time points. It was very encouraging to see that.
In terms of some of the differentiation that we saw, the key points were we saw diplopia resolution that was very encouraging because this is what patients are mostly concerned about: double vision, their ability to work, drive, read, et cetera. This is primarily women in their 40s and 50s. You want to see that type of resolution that we saw in our study and, again, differentiated profile. We also saw rapid onset of action. We were seeing statistically significant proptosis response after one infusion. As you can imagine, from a patient perspective, the faster you can get relief, the better. The other areas we saw, we were very much in line with the current available therapy. That was all super encouraging. We saw those differentiations on the efficacy side, both in the active and the chronic study.
On the safety side, we had a very generally well-tolerated profile, which we expected given that this is IGF-1R inhibition and it's a known, clinically validated, and commercially validated target. The one key area of interest on the AEs has always been hearing impairment, which is a composite term. In our studies, and in general with IGF-1R, we've seen that it is generally mild in nature. A lot of times it's tinnitus or autophony, which is an echoing in the ear, which resolves on its own and is mild in nature. In our studies, we had very, very low dropout rates, which speaks to the overall safety profile. That was also super encouraging because that risk-benefit is squarely in place. That was the phase 3 studies. Those turned out to be great. Now we're moving towards BLA for that study.
We are on track as guided and as planned for a second-half BLA filing this year. That is very encouraging. We also started, as you referenced, we also started two other phase 3 studies in our subcutaneous program. That was all the IV program. We have a subcutaneous program that is also in phase 3. We call those studies REVEAL and REVEAL-2 in the active and the chronic population. We are advancing those. We are enrolling those studies now. Everything is on track. As said, we will have our top-line data from those studies in the first half of 2026, coming up relatively soon, as it is already March. The subQ program is essentially based on the IV program.
It's the same antibody with the same binding domain and CDRs, the only difference being a half-life extension technology that we've shown in our healthy volunteer study to increase the half-life of the antibody by four to five times, which is a great result because that could result in more convenient dosing for patients while still preserving the efficacy and the safety, or actually maybe even potentially improving on the safety. We do look to preserve the efficacy of the IV based on the antibody itself. That's the thyroid eye disease franchise. We also have an FcRn franchise, which we have now. We are in the clinic, and we will have our first data set in Q3 of this year in healthy volunteers.
We want to see what you would ordinarily expect to see out of FcRn, IgG suppression, albumin sparing, and we'll get a sense of dosing. That is kind of where we are on the portfolio. There is a lot going on. To your point, we've executed extremely well over the past year, and we continue to do so.
That's great. OK, let's start with the lead IV, IGF-1R, veligrotug. We had the top-line data. You kind of walked through the highlights of it: more rapid onset of action, lower rates of hearing impairment, more convenient dosing administration, shorter dosing interval. I guess of those attributes and the market research that you've done to date, what do you think is going to be the main driver of uptake for veli relative to you alluded to the one available therapy to date, Tepezza? What's the one kind of major driving differentiating factor for you that's going to drive that commercial uptake?
Yeah, I mean, these are cross-trial comparisons, so you have to draw your own conclusions here. Yes, we saw rapid onset of action. In terms of priorities, I think it has to start with efficacy. These are moderate to severe patients. They have severe bulging of the eyes, as I mentioned, double vision. They're in pain. As I also mentioned, these are women in their 40s and 50s. They have families and jobs and lives that they have to tend to every day. The quality of life impact of this disease is pretty bad. We are looking to alleviate that. We are looking to do that quickly. We did show a differentiated rapid onset of action, statistically significant in the chronic population after just one infusion. Fantastic to see.
The diplopia, as I mentioned, is such a significant impact on their lives. Having not only the response, but the complete resolution that we saw in our data for both studies was a huge differentiator. They just simply do not have that data from the currently available one. That is really impressive to the physicians that we speak with. Obviously, safety is there because that risk-benefit profile, when you make a decision with the patient and the physician, have that conversation, that is a really important component. The key to this from a commercial standpoint that is really important for everyone to understand is that when we bring this profile, this IV profile, if we can talk about subQ separately, but when we bring the IV profile to the market, this is a new start market.
We try to emphasize this to everyone so people understand. We will not need to ask anybody to switch off any existing therapy. The currently available product is a fixed course. Even if you've been treated in the past and your symptoms come back, you're essentially a new patient. Every newly diagnosed patient is a new patient. Every chronic patient that has a flare, because this is autoimmune disease, you will see flares as with any other autoimmune disease. When they come into the physician's office, when it's our IV and their IV, there will be a choice to make. We have a differentiated clinical profile based on the things that I mentioned. We also do it with fewer infusions, faster infusion time, and 70% less drug.
We think that might be the contributing factor to our safety profile that we think looks better. When that patient makes that decision at that moment in time, commercially, we expect that that's a potential revenue shift right there. That new start market dynamic is really important for our commercial prospects.
Yeah, that makes sense to me. Sticking with THRIVE 1, your primary endpoint here was at 15 weeks.
Yes.
Data looked really good versus Tepezza at 24 weeks. I know you continue to collect follow-up data. I guess how important is the durability data? Maybe can you comment on what level of visibility you have into it and what you've seen to date with some of the longer-term THRIVE-1 data?
Shan answered that one.
Yeah, it's a great question. Thanks, Tom. With regards to durability, we are following patients in THRIVE and THRIVE-2 out to a total of 52 weeks, so 37 weeks past that 15-week top-line data readout. When you look at Tepezza, based on the Tepezza experience, the majority of these patients maintain their response after they stop treatment with Tepezza. There can be a recurrence of the autoimmune symptoms of thyroid eye disease because it is an autoimmune disease. When we talk to physicians and we ask them, well, when does that occur? When do patients, if they recur, when would that typically come back? It can vary, but it's generally months, if not years, after they've come off of treatment. What that tells us is the drug, first of all, is long gone out of the body of the patients.
The recurrence is probably more driven by the biology of this disease being an autoimmune disease. Coming back to veligrotug, we would expect the durability of veligrotug to be similar to Tepezza in the follow-up period and beyond because, again, this is not something that's based on the drug still being in the body. The drug is long gone. Yes, durability is something that we think will be a consideration for patients and physicians, but we're not expecting things to be different here for veligrotug. In terms of visibility, the studies are still ongoing. We're not taking a look at the data in terms of every visit that is in the follow-up period because every time you do that, there's a stats hit to the integrity of the study. We're maintaining the blindness of the study.
This might be data that we put straight into the BLA. It might be something more appropriate for a medical congress. Let us get to the end of the follow-up periods, and we'll figure out kind of abstract timing submissions for medical congresses and in conjunction with that BLA submission as well. More to come on that.
Got it. OK, we'll stay tuned on that. I want to talk about the THRIVE-2 study. This is your chronic TED study, a little bit different design than what Horizon did with Tepezza. You guys enrolled a much broader patient population, much more inclusive, I think, and probably representative of real-world chronic or low disease activity TED. I think very important that you actually have these data to be submitted with the first BLA. Maybe you just talk through, I guess, your expectations with respect to labeling and how you think that may or may not be differentiated versus how Tepezza is labeled and therefore kind of reimbursed today.
Yeah, sure. I'll start, but Shan can jump in. I think that's a critical difference is that we expect to have our chronic data in our label, and Tepezza does not have their chronic data in their label. That's a function of the fact that they ran two active population studies for their registrational studies. They did not have the chronic data, and they got pushback from payers, presumably, which is why they ran their chronic study. They did not start that until 18 months after they got approval for thyroid eye disease in general and their indication. To your question, they also ran their chronic study in a low Clinical Activity Score population.
On the scale of 0 to 7, their patient population that they studied was on the 0 or 1, which by definition means that these are patients who are not complaining about their pain. They're not experiencing the redness because they're in the lower end of that scale. Now, we looked at that differently and said we should run a more representative study because we know for a fact, and our study demonstrated this, that chronic patients do have higher levels of pain than 0 or 1. We saw quite a few of that in our chronic study as well. We wanted to have a more fulsome data set to bring to payers and have those conversations. Obviously, we do all that. We're doing payer work well in advance of launch. We're testing these profiles with payers, and we have been.
We feel really good about how that's positioned. I think if you think about the practical implications of that commercially, because they do not have it in their label, their reps cannot be talking to physicians about chronic data, and their MSLs have to come in with published papers about a post-approval study. I think we have an advantage there in terms of the ability of being able to put all the data out in front of physicians. That is really encouraging. I think also our data is more representative, so we can actually talk about the entire chronic population. That will help us with patients. That will help us with physicians, and it will certainly help us with payers.
Yeah, that makes sense. I want to talk about the BLA filing, and you're targeting the second half of the year. I know you also have an ongoing phase three STRIVE study that is more of like a safety exposure study. I think you said fully enrolled in December. I guess first, can we expect to see any data from STRIVE potentially presented this year? I know part of the purpose of running that study is to generate the exposures needed for the BLA, but you've said that's also not gating. Could you also talk about kind of what the gating factors are to filing the BLA?
Yeah, the timing of the BLA is driven almost exclusively by the THRIVE-2, the chronic study follow-up period. We present the top-line data in December, but we have the follow-up period that needs to play out. We just simply need to get to that point, collect that data, clean it, lock that database, and then that data will be dropped into the BLA filing. Obviously, we're doing all the work on the BLA filing now so that we're ready to drop that data in when ready. That's really what drives the timeline. What was the other first question?
With respect to STRIVE.
Oh, STRIVE. Yeah, STRIVE we actually completed in early January, just to clarify. We completed that study in early January. That's never really been on the critical path for us. The function of STRIVE is simply to fill out that safety database. We need a certain number of patients to have been exposed to the drug for a certain amount of time. STRIVE allows us to supplement the treatment studies to complete the safety database. The primary purpose, the endpoints are all safety-driven. What we really just need to do is take that safety data and put it in the BLA as well.
Got it. Do you think we may get some visibility? I understand it's totally a safety study, but just in terms of also it's another data set that can help us kind of confirm the hearing impairment rates that we saw from THRIVE, THRIVE-2.
Yeah, I mean, I think primarily that's, again, to add to the BLA. Yeah, we have multiple opportunities to look at how we can get that data out there, but we haven't landed that plane just yet.
Understood. OK, let's talk about, I guess, the commercial environment. We get a lot of questions from investors. It feels like sentiment, I guess, around the overall commercial dynamics has come down quite a bit, I think. The Tepezza sales trajectory has kind of stalled out here between $1.5 billion-$2 billion. Can you just talk about, I guess, your impression of some of those market dynamics and what could be, I guess, preventing broader uptake of Tepezza or that lack of re-acceleration of growth? How do you guys plan to address that?
Yeah, again, I'll start and Shan, jump in. First and foremost, you're talking about roughly a $2 billion market, right? I think there was concern last year that the competitive landscape was crowded and that if it stayed at a $2 billion market, you were going to divide it amongst a number of players. It's important to note that the competitive landscape has gotten a lot clearer in the past several months with respect to some of the other mechanisms that have, or some of the other approaches that, quite frankly, don't look as competitive as initially thought to be or expected to be. That's all really good. I think that clears out the competitive landscape. More importantly, we think what Tepezza's penetration of the market still has a long way to go.
We enrolled over 400 patients in our clinical trials last year, not all in the U.S., so not all off the top line of Tepezza revenues. Other studies were being conducted too, which also impacted their revenues. I do not know if their revenues are reflective of even the market that they are reaching. Again, we think there is further penetration. They have acknowledged on their earnings calls that they have a single-digit penetration of the market. We believe that. We think that when you look at the treatment paradigm for Tepezza, it is pretty onerous. It is six months of people's lives. It is eight infusions. You have to go every three weeks to get an infusion. Not everybody lives near an infusion center. That can add up and can be dissuasive for people to try to take that approach.
Again, we think we can make that easier for folks, particularly in the IV, and then obviously subQ would be entirely different. We think we can grow the market, not only in the U.S., but they just got approved in Japan, so they're blazing that path for us, which is great. They got a really good price in Japan, which is encouraging. We are waiting to see how they do in Europe. They filed last year. There is ex-U.S. growth to be had as well. Anything that I?
On the chronic side, they have talked about still making their way through getting reimbursement with payers for chronic patients. I do think that is a barrier that they have had even after having generated that chronic data. That is something that we'll start to see hopefully more penetration into. It doesn't seem like they have enough penetration into that broader, larger chronic population just yet.
Yeah, at the last earnings call, or maybe it's the earnings call before that, they said that they were north of 50% commercial insurance coverage in the U.S. As you can tell, that's a handicap that they have to overcome. I think they're doing that. I think they're putting in that work, which is only to our benefit. The more they clear the way, the better for us.
Right. Yeah, let's talk about the subQ program. Maybe you could build on some of those commercial comments. How do you expect low volume subQ to potentially open up the market? Maybe you could talk about the dosing that you're exploring, convenient, relatively infrequent low volume subQ in the REVEAL programs and how you think that'll change the market dynamics.
Yeah, so we intend to launch subQ in an auto injector. It's already a commercially available auto injector. It's the same one that Dupixent uses. It's an Ypsomed auto injector pen. We've already formulated the drug into 2 mLs, which no one else has been able to do. Tepezza's a 20 mg per kg volume. That is a really hard volume to concentrate down to 2 mLs. We've already done ours. We're going to start with a huge advantage of coming out with an auto injector pen at launch is our plan. Just very intuitively, if you don't live near an infusion center and now you have the option of having an auto injector pen delivered to your door, and you mentioned the dosing regimens, we want to see how that data plays out. We're exploring Q4 weekly and Q8 weekly.
I'll have Shan explain how that matches back to the IV. At a very basic level, through specialty pharmacy distribution, we'll deliver the pen to your door. We do think that over time, when the market matures, that subQ should take 70%+ of this market. From a competitive standpoint, we're really kind of standalone in terms of the profile that we have. We think commercially that's going to be a really good setup. Our IV launch will help set up the infrastructure. IV is going to stick around. IV will have a role in this even when the market matures. The IV launch that we will do next year, that will help build the infrastructure. We could plug subQ into that machinery.
We expect that to accelerate the subQ launch even better than what we're going to see with IV, which we also expect to be an accelerated launch.
Yeah.
Do you want to talk about dosing regimens?
Yeah, on the study design, we are looking at two active doses every four weeks or every eight weeks for patients. Both of these would be fantastic regimens. We think potential best in class. This is a low volume auto injector, as Steve said. We believe both of these dosing regimens to be de-risked as well based on what we've seen with veligrotug IV, which has the same binding domain, same CDRs as 003. When we confirmed the PK and PD profile of 003 back when we ran the healthy volunteer study, when we did PK modeling based off of that, we were really pleasantly surprised that Q4 weekly exposure levels were approximately that of 10 mg per kg IV. Q8 weekly, even more pleasantly surprised that those exposure levels were approximately that of 3 mg per kg IV.
Three mg per kg IV being something that we had tested in a phase two study in TED patients showed just as robust of clinical responses across proptosis, CAS, and diplopia. The 003 REVEAL-1 and 2 study designs give us a unique opportunity to test really convenient dosing regimens for patients that they can self-administer at home. That Q8 weekly arm, because of the lower overall exposures, can we actually preserve the efficacy of IGF-1R, which we believe we can, while lowering overall exposures for potentially even better safety profile.
That makes sense. With respect to REVEAL timing, you guys enrolled the THRIVE studies. The execution was stellar there. It really did not seem that you ran into any enrollment issues, as we have seen with some of the competitors in the space. I know you are leveraging a lot of that infrastructure to enroll REVEAL. I guess first, you just comment on how enrollment is going in REVEAL. Is it a similar cadence as THRIVE? When we think about expectations for top-line data in the first half of 2026, how should we think about sort of that efficacy bar for success there? We are looking at a 24-week endpoint here, but how are we stacking up versus veligrotug 15, Tepezza 24? Do we have to be equivalent, or is there some margin for error there? Because we do have a low volume SubQ more convenient offering.
First, thank you for asking about execution, because I love execution more than anything. I mean, I love my family, but I love execution. And we do deliver. We are intensely focused on execution. Thank you for acknowledging that. We did enroll those studies ahead of time. We over-enrolled. None of the competitors, all of the competitors had delays in their enrollment. As I said, we enrolled over 400 patients last year. Yeah, we have a great system. We have a great team. We are applying all of that to REVEAL, the REVEAL studies. We have the same infrastructure, largely the same. There is some variability, but it is largely the same. We have the same CRO. We have the same clin ops team internally. The machine was built last year, and now it is humming. We do expect everything is on track with REVEAL.
We have aggressive timelines, but we're on track. In terms of setting expectations for those readouts in REVEAL, as Shan mentioned, because it's essentially the same antibody with the same binding domain and CDRs, we expect it to behave in a very similar fashion. We are trying to approximate those exposure levels to create the same levels of results that we saw from THRIVE and THRIVE-2. It is relatively straightforward, at least as much as you can say that in clinical trials. The execution's there. The rationale for the biology is there, and the dosing regimen is there. We feel like we have de-risked it substantially with THRIVE and THRIVE-2 results. The antibody, again, does what it's supposed to do. We saw great results. We'd like to replicate those if we can.
Great. Just in the last minute, I do want to touch on the FcRn.
Yes.
Because you're going to have the first in human data in Q3.
Right.
Yeah, help us think about how you're framing expectations for the first in human data, sort of what the product profile looks like, what you're expecting relative to, say, Vyvgart or Tepezza.
Yeah, I mean, the nice thing about, so Vyvgart is clearly the gold standard. Everything is referenced against it. Everything gets compared against it from an efficacy and safety profile. There seems to be something special about the fragment approach. We recognize that, which is why we are taking a similar approach. We believe we are the only other Fc fragment in clinical development. All the full-length antibodies, I think we're still trying to sort out exactly where those are going to land. Clearly, the hypothesis of deeper suppression of IgG translating into better clinical outcomes. Again, I think we just need to see that play out. That being said, our 006 program, which will have the healthy volunteer data in this year, Q3, that will answer a lot of questions. The translatability from primates to healthy volunteers to diseased patients has been pretty clean.
There is a clear path for us to follow. If we can be in a similar type of profile to Vyvgart in terms of ranges of all those things, those parameters that we talked about, that would be a great place to land. Because again, we're the only other Fc fragment in clinical development that we know of. It is a great start. We have our half-life extended version, which we're still in our primate studies. That is a really exciting possibility. That would be a game changer in FcRn just due to the frequency in which FcRns have to be dosed currently and the inconvenience that can cause for patients. We'd really love to be able to improve that. We're in the primate studies. We'll see how that goes. We'll have more to say on that later this year.
Yep, we'll stay tuned for the non-human primate on 008 and the first in human for 006.
Also an IND for VRDN-008 by the end of this year as well.
Right. Great. All right. We'll stay tuned for those clinical updates. Thank you, Steve and Shan, for joining us and for the insights. We'll stay tuned.
Yeah, appreciate it.
Thank you, Tom.
Thank you.