Viridian Therapeutics, Inc. (VRDN) Earnings Call Transcript & Summary

Welcome to the Viridian Therapeutics conference call to report top line results from THRIVE-2, our Phase III clinical trial in patients with chronic thyroid eye disease. [Operator Instructions] As a reminder, this conference call is being recorded. I will now hand the call over to Ms. Louisa Stone, Manager and Investor Relations of Viridian. Please go ahead.

Thank you, and welcome, everyone, to our conference call to report top line results from THRIVE-2, our Phase III clinical trial in patients with chronic TED. The press release detailing these results is available on the Investors page of our corporate website at www.viridiantherapeutics.com. With me today are Steve Mahoney, our President and CEO; and Shan Wu, our Chief Business Officer. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements regarding our financial outlook in addition to regulatory product development and commercialization plans and research activities. These statements are subject to risks and uncertainties that could cause actual results to materially differ from those forecasted. A description of these risks can be found in our most recent Form 10-Q and 10-K on file with the SEC. With that, I'll turn the call over to Steve Mahoney, our President and CEO.

Great. Thank you, Louisa, and good morning, everyone. We are thrilled to be back talking about veligrotug. As you know, we have already presented highly compelling Phase III data from our THRIVE study in the active TED population. Today, we have the pleasure of presenting top line results from our THRIVE-2 clinical trial, which is the largest Phase III clinical trial conducted to date in the broadest set of chronic patients. In fact, it is the largest clinical trial ever run in thyroid eye disease. A quick reminder that in September, we disclosed data from THRIVE in active TED, where we showed that veli achieved all primary and secondary endpoints with a high level of statistical significance. We showed a rapid onset of treatment effect and drug was generally well tolerated after 5 infusions. Veli also has a significantly shorter infusion time in course of therapy than the currently available IGF-1R. Fast forward to today and the story for veli is now even stronger. Now that we have successfully delivered 2 Phase III clinical trials for veli, you will see we have created a compelling and differentiated profile on efficacy, safety and convenience. With this profile, we believe veli can become the new standard of care in TED. Before I get going, I would like to extend a thank you to the TED community, the patients, investigators, partners, and of course, our own internal Viridian team who have moved mountains this whole year to deliver the great data that we have for veli. All right. Now let's get to the THRIVE-2 data. Slide 4. Veli THRIVE-2 data was better than we expected. Veli met all the primary and secondary endpoints in THRIVE-2, showing robust responses on all of the measures of proptosis, diplopia and clinical activity score or CAS, with a high degree of statistical significance. These strong responses were consistent across all endpoints and time points with treatment effects being observed as early as 3 weeks after just one infusion of veli. We are thrilled to show the first demonstration of statistically significant diplopia response and diplopia resolution in patients with chronic TED. This effect was consistent regardless of their baseline CAS. Veli was generally well tolerated with a safety profile consistent with all previous veli studies, including THRIVE. 94% of veli-treated patients completed their course of treatment, and we observed a low 9.6% placebo-adjusted rate of hearing impairment. We are really excited about the results from the largest Phase III clinical trial conducted to date in thyroid eye disease. Moving to the next slide. We'll have a quick look at the THRIVE-2 study design. We designed THRIVE-2 to enable access for the broadest possible chronic TED population. The study enrolled a total of 188 chronic TED patients with roughly 40% of enrollment coming from the United States. We randomized 2:1 to receive veli or placebo. Patients received 5 doses of veli or placebo every 3 weeks for a total treatment period of just 12 weeks, almost half of that of the currently available approved therapy. The primary efficacy endpoint is proptosis responder rate with key secondary endpoints relating to CAS and diplopia, also known as double vision. Now for a quick look at the baseline characteristics, we were very pleased to see these were well balanced across the veli and placebo arms. And as with the case with THRIVE, and as expected for the TED patient population, the majority of patients enrolled in the study were female and the average age of the participants was approximately 50 years old. The average time from the onset of symptoms in THRIVE-2 was almost 6 years in the veli arm. Now let's turn to the data. I am thrilled to announce the positive top line efficacy results from THRIVE-2. I'll speak to a few of the highlights here, and then we'll show more detailed data over the next several slides. On the primary efficacy endpoint of proptosis responder rate, patients in the active treatment arm achieved a 56% response rate compared with 8% on placebo, for a placebo-adjusted rate of 48%. This is a significant and clinically meaningful response in a patient population that has been historically difficult to treat. It is important to note that the proptosis response was consistent regardless of patients' baseline CAS. That is not all. I am really pleased to share with you that THRIVE-2 is the first study ever to demonstrate diplopia response and resolution in a global Phase III clinical trial of chronic TED patients and that these results were highly statistically significant. Of the patients who had diplopia at baseline, 56% showed an improvement in diplopia after treatment with veli, seen here in the diplopia responder rate. And 32% of veli patients achieved complete resolution of their double vision at 15 weeks. This effect on diplopia was again consistent regardless of a patient's baseline CAS just as it was for proptosis. Finally, on CAS, amongst the patients with higher CAS at baseline, 54% achieved reduction of CAS to 0 or 1, meaning that they had no or minimal disease activity at 15 weeks, with a mean reduction in CAS of 2.9 points. As a reminder, CAS is a 7-point composite scale of disease activity, including pain, redness and swelling. These results exceeded our expectations. As a reminder, this is the only global Phase III clinical trial to demonstrate a benefit across all of these endpoints in chronic TED patients. Now let's look at these data across time points. Starting with proptosis. As we showed earlier, 56% of patients receiving veli demonstrated a proptosis response at week 15 compared with 8% of patients on placebo. We were pleased to see the clear separation of the veli and placebo curves across all time points in the study, which were all statistically significant. Veli showed a robust response in 25% of patients at 3 weeks after just 1 infusion. And these improvements continued for the full course of treatment. On the right, the mean proptosis change from baseline was also consistent with the deepening of the proptosis reduction observed in the study with a mean reduction of over 2.3 millimeters at week 15. Now let's turn to diplopia. Diplopia, or double vision, as you can imagine, can be severely debilitating for patients and their quality of life. When patients have diplopia, they may have trouble with their day-to-day activities, such as driving or reading, which can negatively and significantly impact their ability to work or take care of their family or even live independently. Physicians and patients tell us diplopia is one of the hardest parts about living with this disease. We saw rapid activity from veli on diplopia response with 47% of patients showing improvement at 6 weeks after just 2 infusions. This was a statistically significant result. Diplopia response is measured by at least a 1 point reduction on the Gorman scale for the -- for patients, improvement by just 1 point can be extremely meaningful. It may even allow them to avoid surgery. On the right, we also saw rapid activity from veli on diplopia complete resolution with 31% of patients showing a complete resolution of diplopia at 6 weeks, again, after just 2 infusions. This is what's also a statistic significant result. This is obviously incredibly exciting to see veli have this level of impact on diplopia in patients with chronic TED who, on average, in the THRIVE-2 study been living with TED for almost 6 years. There has been a lot of skepticism as to whether it would be even possible to address diplopia in chronic TED as teprotumumab failed to demonstrate an effect on diplopia in their chronic Phase IV clinical trial. THRIVE-2 is the first pivotal Phase III study that demonstrate that there is hope for chronic TED patients with double vision and we look forward to including these data in our BLA submission for potential inclusion in veli's labeling. Because physicians are particularly interested in our MRI data, we are excited to point out that our proptosis results in THRIVE-2 were consistent regardless of whether it was measured by imaging or by Hertel exophthalmometry, just like we showed in THRIVE. Moving over to safety. Veli was generally well tolerated. The vast majority of adverse events were mild in 94% of patients treated with veli completed their treatment course. Now looking at the safety table, we have a favorable safety profile that is consistent with what we observed in THRIVE. These adverse events are consistent with the known and manageable profile of IGF-1Rs and the vast majority of them were mild in nature. With respect to hearing impairment, as a reminder, tepro's chronic Phase IV study showed an absolute hearing impairment rate of 22% and a placebo-adjusted rate of 12%. As you can see in THRIVE-2, we had only a 12.8% absolute rate of hearing impairment, which placebo adjusted to 9.6%. We are really pleased with this same profile. To summarize THRIVE-2, we ran the largest and broadest Phase III trial conducted in TED patients -- chronic TED patients to date. THRIVE-2 has delivered compelling results by achieving all primary and secondary endpoints with high levels of statistical significance. The THRIVE-2 data also shows that veli can rapidly and consistently reduce patient symptoms. We observed this across all endpoints and all time points. We think veli's differentiated clinical profile in THRIVE-2 just changed the game for chronic TED patients. All right. Now let's describe what we believe to be the totality of the data from THRIVE and THRIVE-2 and what that means to TED patients. This is no longer simply about shorter infusion times in course of therapy. We now believe that we have a differentiated profile based on the efficacy and safety data that we've seen from THRIVE and THRIVE-2. We will include data from both active and chronic TED patients in our BLA submission to support labeling. Across both THRIVE and THRIVE-2, we saw robust and consistent clinical responses for all the disease relevant end points of proptosis, CAS and diplopia, regardless of whether a patient has the active or chronic form of the disease. Veli is the first product candidate to demonstrate statistically significant diplopia response and resolution in a global Phase III clinical trial of chronic TED patients. Physicians have been skeptical that this result was possible. Veli has also consistently demonstrated a rapid treatment effect in active and chronic TED, and veli has been well tolerated and has a favorable safety profile. With this differentiated profile, we believe veli could transform the standard of care in TED and we are more excited than ever to advance veli toward BLA in the second half of next year with an expected launch in 2026. We look forward to submitting the BLA and taking this next step towards bringing this important therapy to TED patients. And if approved, we will give patients a new choice. We expect veli's differentiated profile would drive rapid commercial adoption in this new start market. Unlike markets where new entrant has to switch patients off of existing therapy to gain market share every quarter, every year, a completely new set of TED patients will make a decision as to which available therapy is best for them. We believe the choice is obvious. We expect to be in a position to execute and rapidly launch veli. TED is a large market. The currently marketed IGF-1R is annualizing approximately $2 billion in sales, even with a limited penetration of the 190,000 moderate-to-severe TED patients in the United States. With its differentiated profile, we believe veli, if approved, has the opportunity to become the leading product by market share and to further penetrate the addressable patient population. As evidenced by the rapid enrollment we had in veli's clinical trials, strong patient demand is there. We enrolled over 360 TED patients in 2024 alone. The TED market is well defined and with a concentrated call point of about 2,000 core prescribers, many of whom participated in THRIVE and THRIVE-2. Tepro was launched by Horizon with less than 100 sales reps and still delivered over $800 million in net revenues in its first year on the market. In fact, as a reminder, it sold $166 million in its first whole quarter during the height of the pandemic. With the large TED market focused commercial footprint and our ongoing building of a world-class and experienced commercial team, we believe Viridian is well positioned. In a new start market and with veli's differentiated profile, we believe the successful and rapid launch of veli is possible. So the THRIVE-2 data today reads through to our potentially transformative subcutaneous VRDN-003 program that shares the same binding domain as veli. Patient dosing continues in our Phase II -- in our 2 Phase III clinical trials of VRDN-003, known as REVEAL-1 and REVEAL-2. These trials leverage the clinical operations machine that we have built through THRIVE and THRIVE-2. We are on track to deliver top line data in the first half of 2026 for both trials and submit a BLA by year-end 2026, approximately 1 year after veli's BLA submission. With these 2 products, we expect to build the best-in-TED franchise. Finally, on this slide, you can see we have multiple meaningful catalysts across our TED FcRn portfolios. Let me take a moment to walk through these before we open for Q&A. For veli, we are driving toward our anticipated BLA submission in the second half of '25, supported by the strong data we now have in hand from THRIVE and THRIVE-2, with the potential for a U.S. commercial launch in 2026, if approved. We also expect this data package to support a marketing authorization application in Europe. For subcutaneous 003, both of the REVEAL clinical trials are actively dosing patients. We hope to reproduce veli's remarkable results in a low-volume, infrequent self-administered subcutaneous injection. We anticipate top line data from both of the REVEAL clinical trials in the first half of 2026, which we anticipate will enable a BLA submission that same year. Moving to our FcRn portfolio. First, we are on track to file an IND later this month for 006, the only other known Fc fragment targeting FcRn in development, for which we have already demonstrated compelling IgG lowering in nonhuman primates with no effect on albumin levels or LDL. We expect to disclose data from the healthy volunteer clinical study for 006, including IgG reduction in the second half of 2025. Lastly, we recently reported single dose nonhuman primate data for 008, our bispecific half-life extended FcRn inhibitor. These data confirmed 008's extended half-life versus efgart. We are very excited about 008's potential to deliver a best-in-class profile for what we believe is a large commercial opportunity across many autoimmune diseases. We plan to submit an IND for 008 by year-end 2025. We're excited for the opportunity to drive continued value creation for our shareholders, and we look forward to future disclosures across this portfolio. It has been my pleasure to share top line -- our exciting top line data from THRIVE-2 with you all today. This would not be possible without the entire TED community. And I would want to thank patients and their caregivers, our investigators and their research teams for their contributions to the success of this program. I would also like to thank the Viridian employees for all of their hard work and their dedication to bringing these better treatment options to patients. And with that, I will turn the floor over to the operator for questions.

[Operator Instructions] Your first question comes from the line of Laura Chico from Wedbush Securities.

Congratulations on the data. This looks fantastic. I guess one on efficacy, one on safety. First on efficacy, one thing that's come up quite a bit with the KOL checks, has been on diplopia and kind of the burden that puts on patients. Wondering, Steve, could you talk a little bit more about the complete response improvements. It looks like that benefit is starting pretty early. And just maybe a little more context around what that means for folks. And then on safety, it does look like there was a treatment-related SAE. Just a little bit more color on that, if you could.

Great. Thanks, Laura. Yes, look, diplopia is a -- obviously a very debilitating disease, as you can imagine. It is -- it impacts, as I mentioned on the call, it impacts every aspect of life for people because of their double vision impacting their ability to read, right, drive, work, take care of their families. As a reminder, this is -- this primarily impacts women in their 40s and 50s who have lives, they have their jobs. Look, we're really excited about this diplopia. This is -- we are going to have the first data set available for diplopia showing an actual difference in diplopia response and resolution. Just as a reminder, 32% of the veli patients in the study had complete resolution of their diplopia at 15 weeks, 18% placebo-adjusted TEPEZZA can't do the cross-trial comparisons for you. But as to point out the data set that you didn't see any difference between treatment and placebo. So we're -- we, clearly veli has a profound effect on resolving diplopia for chronic patients. And we saw the same thing in THRIVE in the acute patient population. And again, we're the only one to have shown this type of response and resolution in a Phase III. And don't forget, what we've done here is we've run the largest Phase III study ever run in TED chronic patients. This is the broadest population of chronic patients. As I mentioned on the call, a time from onset of symptoms is 6 years, again, by comparison of just the baseline characteristics, at least the tepro study was almost a year less than that. So this is a broad representative population of chronic patients. So to see these diplopia results and to have that only data set that we will bring to the BLA submission, that's a really great place to be on the -- with respect to diplopia and as I said it's really important for patients. With respect to the SAE, Shan do you want to take that question?

Sure. Happy to. And maybe before getting to the specific question, it would be helpful to start at the top that the safety that we saw throughout THRIVE-2 is really similar to THRIVE, if not better. Almost everything was slightly better than THRIVE, and we had a lower incidence of overall AEs in the study. These reported AEs are all, for the most part, known and expected for the class. The vast majority were mild, as we said, and all are considered manageable if you talk with physicians, especially with the profound efficacy that we just showed. And as I mentioned, 94% of the veli treated patients completed the full course of treatment. We had one SAE that was deemed to be related in the veli arm and also one SAE deemed to be related in the placebo arm. And so that was a pretty interesting result, in particular, on the veli arm, just a bit more color on there. It was a episode of vertigo but it actually resolved after 2 days, and the patient came back and continued to complete all courses, the AE emerged after the third infusion. They came back and completed infusion 4 and 5. And so it's a really great result and out of the largest study in TED to have that is a really thrilling place for us to be.

Your next question comes from the line of Alex Thompson from Stifel.

Congrats as well on the data. A couple for us. I think you mentioned that you saw efficacy regardless of baseline CAS score. I was wondering if you could provide a little color on what you're seeing in the context of different disease durations as well on efficacy endpoints. And then on some of the adverse events and other safety questions here. Can you talk a little bit more about some of the hearing impairment adverse event that you saw whether there was any resolution at this point? And then for discontinuations, any color on what drove discontinuations here.

Yes. I can start with the first one. This is Shan again, on the -- you're absolutely right, and we were thrilled to see that the proptosis and diplopia responses here were regardless of baseline CAS. You'll recall that we enrolled patients with the entire spectrum of CAS as 0 or 1. So this is the most representative in the broadest TED population, chronic TED population that's in contrast to tepro, which only limited themselves to a subpopulation of CAS 0 and 1. So we were thrilled to see these results. Was there a second part to that question?

Yes. Yes. Did you see any differences with disease duration and the efficacy endpoints?

Got it. So Obviously, this is top line data and durability beyond the 15 weeks will be something that we'll assess and be able to present later. What we saw in THRIVE, we -- what we said there was a preliminary look at week 24 data, really showed a maintenance of the durability and given all of the consistency here in THRIVE, THRIVE-2 all of the efficacy, across all time points, all efficacy endpoints, regardless of baseline CAS, we feel really confident about the efficacy here across all of those measures for veli and that includes durability.

Yes, Alex, I think that's a really important point to underscore. Just look at the robustness and the consistency of the robustness across all the end points and all the time points, the antibody is behaving as it should. And it's really created -- I mean, again, to do that in the context of this largest study and broadest patient population for chronic and to see that consistency regardless of your underlying baseline CAS, this is the good consistency is what we wanted to see. Do you want to do -- so on your hearing impairment, Alex, what was your question?

Any more details you can provide on the types of hearing adverse events you saw?

Yes. Maybe I can take that one as well. The vast majority of these were tinnitus just like it was in THRIVE and all of these were mild, except one, which was moderate. And we saw hearing impairment in the placebo arm as well as you saw in the safety table.

Your next question comes from the line of Gregory Renza from RBC Capital Markets.

Steve and team, congratulations on the really nice data. Steve, maybe just 2 for me, just real quick. I appreciate all the color on the safety and tolerability. Maybe just to close the loop, certainly, with the September THRIVE data, there were discussions just around the infusion-related reaction, the potential imbalance with that study. I believe we're not seeing any today. I just wanted to confirm and just have you touch on maybe what that means and the implications there if there is an absence of infusion-related reactions for this THRIVE-2? And then secondly, while, of course, the veli's BLA submission and focus for the second half of 2025 as you touched on. Just wanted you to comment a bit about what you're prioritizing as part of the package and the efforts to really get that over the goal line and meet that goal? And maybe related to that, if you could just give us an update on the STRIVE safety database and the trial you're running there towards that BLA? Thanks so much and congratulations again.

Great. Yes. Thanks for the question, Greg. Yes, so on the infusion-related reactions, simply, we just saw lower rates. It's just that simple. In fact, if you look at the AE table, the majority of those also were just lower rates than what we saw in -- even in THRIVE. And THRIVE was already, in our view, a great safety profile. So yes, we're just really happy about the infusion reactions being much lower in this case. So that's a really great result. With respect to the BLA submission, yes, as we've been pretty consistent, the timeline is dictated by the follow-up period. So this is just top line release, as you know. So we're moving through the follow-up periods on these patients, and we're -- and we'll be ready to go with the BLA submission in the second half of this year as guided. And what's important in the BLA filing again, which is a great advantage for us, we think, is we'll have the active population and the chronic population in the BLA submission for possible -- hopefully, for inclusion in the labeling that we'll get and that -- to have that on day 1 is certainly great. That will help with physicians, that will help also with payers. So really looking forward to having that complete data set. STRIVE, you asked about STRIVE as well. As usual, we are -- as usual this year, we are well ahead and STRIVE is enrolling very, very nicely. And we will -- that is not on the critical path for BLA in any event, we've been pretty consistent about that. The follow-up period for THRIVE-2 is what dictates the timing. So all systems go on track.

Your next question comes from the line of Michael Yee from Jefferies.

Congrats on the great data. We had 2 questions. One was how you think about comparing and contrasting cross trial to TEPEZZA, which has a different enrollment criteria, lower CAS scores. I think you reiterated your effects were consistent across all of the CAS scores. So I just wanted to see how you think about that and whether you think your patients are sicker or whatnot? So maybe compare and contrast that a little bit as people often will. And then secondly, on the filing, can you just clarify the timing of the gating step for the filing is the follow-up you said for STRIVE-2? How does -- for THRIVE-2, how does STRIVE play into that in any way?

Yes. Yes, I'll take the second question first, Mike. Yes, the timeline is dictated by the follow-up period for THRIVE-2. STRIVE is well within that. And so it's more driven by THRIVE-2. So that's pretty straightforward. On the question with respect to -- you asked about the TEPEZZA in the comparisons. Look, let me just reiterate super quickly here. We think we've got a highly differentiated profile now. As I said, the story has changed. Given the fact that we just ran the largest and the broadest population of chronic TED, the fact that we saw all these strong rapid responses in all the categories, you mentioned CAS but we also saw it in proptosis and diplopia resolution and improvement, which obviously had never been shown before. And then to your point, Mike, this was -- we saw all of this, regardless of the patient's underlying CAS score. And we saw statistically significant responses in proptosis and diplopia as early as 3 weeks and 6 weeks, respectively. So you're seeing that rapid onset of action that is really powerful and consistent with what we saw in THRIVE as well. Don't forget the diplopia responses that we saw in THRIVE. The totality of the diplopia data is amazing. So that's differentiation in themself. And then if you want to go through it step by step, you look at our proptosis response 48% placebo adjusted after 5 infusions. So at week 15, it's across our comparison, so you've got to draw your conclusions but the data set from TEPEZZA was their best result was 37% at 24 weeks, and [indiscernible] was even at 17% at week 18. So that's, in our view, a pretty good delta for us. Again, as I mentioned, we've stat sig on proptosis response as early as 3 weeks. And we think that rapid onset actually differentiates and again, very consistent with what we saw in THRIVE. On diplopia, we had 32% of the veli patients had complete resolution of diplopia at 15 weeks, 18% placebo-adjusted. TEPEZZA, again, cross-trial comparison just pointing out to data set, TEPEZZA saw no difference in their treatment and placebo arms. So we feel that veli has a profound effect on resolving diplopia for chronic patients. And we're the only program to be able to show that in data. So that's pretty powerful from our perspective. And then on CAS, you -- we noted that over 50% of the patients that were evaluable with cast scores showed a response. So over 50% showed a response in a reduction to 0 or 1 at 15 weeks. So again, this is all regardless of their underlying CAS scores for the other elements here. So just differentiated profile, Mike, to your question about how we stack up, and we feel really good about the consistency we see here.

So sorry to clarify on the first question. It's 6 months follow-up from THRIVE-2 is the key one there.

Yes, it's 37 weeks post last dose is the follow-up period. Remember, we finished enrollment in July for this study. So -- and then it depends on last -- patient last visit and then we'll go from there. But we're -- we've been pretty consistent on our guidance and everything is on track.

Your next question comes from the line of Thomas Smith from Leerink Partners.

Let me add my congrats on the stellar data. Just want to follow up on THRIVE and some of the longer-term data you're generating from THRIVE. Can you just comment on whether you've plans to present any of these data before the second half '25 BLA submission? Just trying to get a sense of whether you'll have visibility into the durability data here before the submission. And then second on 003. Can you just talk a little bit about how you're thinking about read-through from these results to the 003 program? And given the consistency of the results and the speed of enrollment at THRIVE, can you comment on how much overlap there is with the clinical sites and investigators between the 001 THRIVE and the 003 REVEAL programs?

Thank you, Tom, for all those questions. So you asked about THRIVE durability. Look, we're -- as you know, this is top line, right? So as we mentioned when we did the THRIVE in September, we did say that our preliminary data was very encouraging, and we have great confidence in that. We still have great confidence in that. So that looks great. Obviously, durability -- or your question around durability for THRIVE-2, obviously, we're still at top line. So not really anything to do there. And then we'll look at medical congresses going forward for that level of detail. That's medical congress territory. With respect to -- I'll take the 003 read-through. Quite simply there, it's the same binding domain as the veli antibody. And we're matching exposures from the IV and that's the intention is to match those exposures and get similar responses for 003. And so again, that study -- those studies, both of them are actively dosing patients now, and we expect to move that quickly. And then your question on STRIVE, STRIVE as I said, we are in really good shape on STRIVE and it is not a -- on the critical path for BLA.

Got it. That's super helpful. And can you just comment on how much overlap there is at the clinical sites and investigators between THRIVE, THRIVE-2 and the REVEAL programs for 003?

Yes. Quite a bit of overlap, Tom, actually -- yes, sorry, didn't complete that answer for you. Yes, quite a bit of site overlap between all those studies. What's great about that, too, is it's the same CRO. It's the same clinical operations team here at Viridian. And as I mentioned, we've enrolled over 350 patients in 2024 alone. So we've got a pretty good system and a good machinery that we've built, and we're just plugging into that.

Your next question comes from the line of Gavin Clark-Gartner from Evercore ISI.

Congrats on the great data. I just wanted one quick clarification on the hearing side, how many cases of hearing reduction were seen on either arm of the trial? And what was the severity of these events?

Thanks for the question, Gavin. I think we're starting to get into a bit of kind of medical meeting presentation territory but happy to provide a bit more color there. As we mentioned, the majority of these cases were tinnitus and all but one was -- all were mild, except one. We did see some events of -- that were representative of hearing reduction in both arms. So there were 7 events in the veli arm and one in the placebo arm, a reminder that this trial had 125 patients in the veli arm. So I think these were really fantastic results, as I mentioned previously in response to another question, all of these were mild with the exception of one.

Great. And just to clarify, the one case that was not mild, did the patient have any other baseline characteristics or other factors that may explain that event?

It's interesting you asked that. Actually, that patient has some confounding background. The patient had an inner ear infection leading into the study. So we think that could be compounding.

And we have time for one final question. And your final question comes from the line of Julian Harrison from BTIG.

Congrats on another impressive data set. I'm curious what your expectation is for labeling around hearing reverse events, correct me if I'm wrong but I'm pretty sure you have not seen any confirmed cases of permanent hearing loss with veli, assuming that holds true through BLA submission next year, is your expectation you should receive a differentiated label with respect to permanent hearing loss?

Yes. I mean I think the same answer that Shan just gave with respect to that. I think we -- obviously, this is just top line, right? So resolution and all that kind of stuff, that's all part of follow-up. But we haven't seen anything along those lines, Julian, as to what you're asking. So I think we feel really good going into BLA because as again, -- we're seeing -- these are the largest -- THRIVE and THRIVE-2 are the 2 largest studies ever run in Phase III. The numbers are big. We saw really low rates for all this hearing impairment. In fact, as we said, THRIVE-2 actually has even lower rates for -- across the AE table than what we saw at THRIVE. So that's all great. And again, I think we'll have more to follow up on. But right now, it all looks good, particularly with the issue you just brought up.

I'll add to that, that for the most part, and this is a manageable profile as well, that hearing impairment, the vast majority of these are mild and almost all of them resolved after treatment. And that's been the experience with IGF-1Rs in general. So we wouldn't expect that to be any different here.

Yes, all mild, except for that one. That's it. In a big study.

And then a follow-up, if I may. The placebo rates, if we were to just maybe compare this to TEPEZZA a little bit. I understand the entry criteria are very different. Does that maybe explain why the placebo rates look lower across trials?

Are you referring to the placebo response in -- on the efficacy side or on the safety side?

Efficacy.

Yes. Look, I think on the placebo, that's very consistent with what we saw in THRIVE. And importantly, we have our MRI data or imaging data that validates that placebo response. So that correlation there gives us a lot of confidence that what we're seeing is right and the consistency across the board underscores that as well.

And that concludes our question-and-answer session. I will now turn the call back over to Steve Mahoney, President and CEO of Viridian Therapeutics for closing remarks.

Yes. Great. Thank you. Yes, we're really excited about the data that we've seen. It's just that simple. We've got a differentiated profile now. The story -- as I mentioned, the story has changed. And we are -- we've just run the largest and broadest representative population of chronic patients. We saw the robustness and the consistency across all the endpoints and the time points. And importantly, this is a new start market. So we have an opportunity and every time a patient comes in the -- into a physician's office, we have an opportunity to show this data and/or have the physician explain this data. And we think that choice is going to be obvious at that moment in time. So thanks, everyone, for attending today, and we look forward to speaking in the future.

This concludes today's conference call. Thank you for your participation. You may now disconnect.