Viridian Therapeutics, Inc. ($VRDN)

Good morning, ladies and gentlemen, and welcome to the Viridian Therapeutics conference call to review top line results from the REVEAL-1 Phase III clinical trial in active thyroid eye disease. [Operator Instructions] As a reminder, this conference call is being recorded. I will now hand the call over to Greg Rossino, Senior Director of Investor Relations at Viridian. Please go ahead.

Thank you, Kate, and good morning, everyone. Thank you for joining us on our conference call to discuss the top line results from REVEAL-1, our Phase III clinical trial of Elegrobart in patients with active thyroid eye disease. You can access the press release and the slides for today's call on the Investors page of our corporate website at viridiantherapeutics.com. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those forecasted. A description of these risks can be found in the forward-looking statement disclaimer in the press release and slides issued this morning as well as Form 10-K on file with the SEC. On today's call are Steve Mahoney, our President and Chief Executive Officer; Radhika Tripuraneni, our Chief Medical Officer; Shan Wu, our Chief Business Officer; and Tony Casciano, our Chief Commercial Officer. Following prepared remarks, we will open the call for questions. With that, I'm pleased to turn the call over to Steve.

Thanks, Greg. Good morning, everyone, and thank you for joining us today. We are excited to share top line results from REVEAL-1, our Phase III pivotal study evaluating Elegrobart or ELE in patients with active thyroid eye disease. REVEAL-1 met its primary endpoint, demonstrated clinically meaningful activity across multiple key endpoints and ELE was generally well tolerated. Before we get going, I'd like to thank the TED community, the patients, investigators, partners and research staff and everyone else who contributed to this trial. We're excited to continue to advance the field and treatment of TED. Over the past several years, TED treatment has evolved from steroids or invasive surgery to the first approved IV IGF-1R therapy and now to potentially veligrotug, Viridian's next-generation IV program, which is under FDA priority review with a PDUFA target action date of June 30. While meaningful progress has been made, there remains a clear need to make treatment easier for TED patients. Based on the REVEAL-1 data, we believe ELE has the potential to be the first-ever subcutaneous auto-injector, enabling patients to self-administer at home while delivering clinically meaningful outcomes for their proptosis or bulging of the eyes and diplopia or double vision. In other words, ELE has the potential to meaningfully impact how patients look, how they function and how they feel. We can do this in a convenient profile in as few as 3 doses that could expand the TED market that is already annualizing at approximately $2 billion today despite being served by a single IV therapy. We anticipate submitting our BLA for ELE in Q1 2027, and we are excited to potentially bring a transformative and differentiated treatment solution to patients. Before I hand it over to Radhika, I'd like to walk through the REVEAL -- she's going to walk through the REVEAL-1 top line data. I want to just point out a few key takeaways. First, we're pleased to announce that REVEAL-1 met the trial's primary endpoint. In the Q4 weekly dosing arm, we observed a highly statistically significant treatment effect on proptosis responder rate at week 24 as measured by exophthalmometry. Proptosis responder rates were 54% with Q4 weekly dosing at 63% with Q8 weekly dosing compared to an 18% rate seen in our placebo arm. Second, on diplopia or double vision, 51% in the Q4 weekly arm had complete resolution of their diplopia at week 24 compared to just 16% of placebo patients. These are meaningful outcomes for patients as proptosis and diplopia are the endpoints that most directly impact appearance, function and quality of life. Third, ELE had rapid onset of proptosis response in both treatment arms and in the Q4 weekly arm. Also, rapid onset of diplopia response and complete resolution with clear separation from placebo after a single dose. Finally, with respect to safety, ELE was generally well tolerated. We observed low rates of hearing impairment. All reported events across both Q4 and Q8 arms were tinnitus with no associated reductions in hearing. We believe this profile from the largest Phase III pivotal clinical trial conducted to date in active TED positions ELE as a highly effective subcutaneous auto-injector that patients can self-administer at home in as few as 3 doses. So with that, I will turn the call over to Radhika to walk through an overview of the study design and the results.

Thank you, Steve, and good morning, everyone. I'm excited to be able to share the REVEAL-1 study results with you this morning. Let's start with an overview of the study design. The study enrolled a total of 132 patients with active TED randomized 1:1:1 across 2 active ELE treatment arms, Q4 weekly and Q8 weekly and a placebo arm. In each treatment arm, patients received a loading dose of 2 injections or 600 milligrams, followed by 5 single injection doses in the Q4 weekly arm. In the Q8 weekly arm, patients received 2 single injection doses or matching placebo. The primary efficacy endpoint was proptosis responder rate or PRR at week 24 in the Q4 weekly arm as measured by exophthalmometry. Key secondary endpoints included clinical activity score or CAS and diplopia response and complete resolution and the corresponding endpoints for the Q8 weekly arm. Following the primary endpoint analysis, patients are being followed through week 52. Slide 7 reviews the study disposition of REVEAL-1. The vast majority of patients completed treatment in all arms of the study. Baseline characteristics were generally well balanced across the 2 ELE arms and the placebo arm. As expected for the TED patient population, the majority of patients enrolled in the study were female, and the average age of patients was approximately 50 years of age. Baseline values for proptosis, CAS and diplopia were generally in line with our expectations and precedent studies in this active TED patient population. Now let's turn to the results. In this slide, we see data across the efficacy endpoints in the Q4 and Q8 weekly treatment arms compared to placebo. As a reminder, the FDA and EMA requested different primary endpoints for the 2 different geographies. REVEAL-1 met its primary endpoint. Q4 weekly ELE had a 54 proptosis responder rate as measured by exophthalmometer versus 18% in the placebo arm, which was a highly statistically significant result. REVEAL-1 also met the EU primary endpoint. Q4 weekly ELE had an overall responder rate of 51% versus 16% in the placebo arm, which was also a highly statistical significant result. On to the key secondary endpoints. ELE Q4 weekly arm also showed a highly statistical significant mean change from baseline in proptosis. Key secondary endpoints were analyzed using fixed hierarchical testing where the Q4 weekly endpoints were tested first and the Q8 weekly endpoints were tested after. The next endpoint in the hierarchy after mean change from baseline in proptosis was CAS reduction to 0 or 1 in the Q4 weekly arm. We observed an unexpected and large placebo response, and this endpoint did not achieve statistical significance. When we look at diplopia, which we know is a debilitating symptom for many TED patients, 51% of patients treated with Q4 weekly ELE achieved complete resolution of their diplopia compared to only 16% of placebo patients with a low p-value as reflected on the slide. Similarly, 71% of patients experienced a diplopia response compared with only 32% of placebo patients. In the Q8 weekly arm, ELE showed a 63% proptosis responder rate by exophthalmometer, again, with a very low p-value. We are particularly pleased to see this kind of proptosis response with only 3 doses. Q8 weekly arm also showed a compelling 2.5 millimeter mean reduction in proptosis from baseline, once again with a low p-value. We also measure proptosis by MRI, which was reviewed by 2 independent mass central readers and confirmed a clinically meaningful benefit on proptosis. Due to the location of CAS 0 or 1 early in our testing hierarchy, the subsequent prespecified endpoints are deemed nominally significant, which means that these endpoints show clinically meaningful and significant treatment effects as evident by the low p-values throughout the slide. Overall, we believe this is the strongest subcutaneous clinical data seen to date in TED. Based on this data and the robust proptosis reduction seen with the Q8 weekly regimen in just 3 doses and the compelling diplopia resolution with the Q4 weekly regimen that rivals IV therapies but can be delivered in an at-home auto-injector, we plan to submit for approval of both the Q4 and Q8 weekly dosing regimens. With that, let's see how these results looked across time points. When you look at the proptosis responder rate or PRR for both Q4 and Q8 weekly arms, you can see 30% of the patients already achieved a proptosis response at week 4 after just a single dose of ELE. This early separation was sustained and deepened across all subsequent time points through week 24. On the next slide, we see the mean change in proptosis from baseline for Q4 and Q8 weekly arms. Separation from placebo was observed at week 4 after a single dose of ELE. Again, the treatment effect deepened over time. Next, as we did in THRIVE and THRIVE-2, we looked at MRI measured proptosis responder rate and mean change in proptosis over time as reviewed by 2 independent massed central readers. Both endpoints as measured by MRI showed robust responses consistent with exophthalmometer. Both the Q4 and Q8 weekly arms achieved meaningful levels of proptosis response and mean change in proptosis from baseline, while very little treatment effect was seen in the placebo arm. This provides independent confirmation of the significant and clinically meaningful effect of ELE on proptosis. On the next slide, we see the diplopia results over time with Q4 weekly ELE regimen. Again, as we see early separation on both diplopia response and diplopia complete resolution as early as week 4 after just one dose of ELE. This effect deepens over time with 52%. That means 1 of 2 patients achieving complete resolution of their diplopia by week 24. Now let's shift over to safety. ELE was generally well tolerated across both treatment arms. The vast majority of adverse events were mild. We saw 2 discontinuations due to adverse events, one in the Q4 weekly arm and one in the placebo arm. We see a well-tolerated safety profile consistent with the class. The rates of hearing impairment were low. We observed an 11.3 and a 2.3 placebo-adjusted rate in the Q4 and Q8 weekly arms, respectively. None of these events led to interruptions in dosing or discontinuations. All of the observed events across both treatment arms were tinnitus and none were associated with reductions in hearing. In fact, the sole events of hyperacusis occurred in the placebo arm. All injection site reactions were grade 1, except for one grade 2 erythema. None of the ISRs led to interruptions in dosing or discontinuations. The majority occurred early in treatment course. As a reminder, this study used a vial and syringe to administer ELE. We are completing our auto-injector bridging study and expect to launch with a low-volume auto-injector. We are thrilled to see these results from REVEAL-1 and to share them today. In summary, the study met its primary endpoint with high statistical significance for both the FDA and EMA. Both Q4 and Q8 weekly ELE achieved clinically meaningful rates of proptosis response. The effect was rapid, showing significant reductions in proptosis as early as week 4 after just one dose of ELE. Q4 weekly ELE further showed rapid, significant and clinically meaningful diplopia responses with more than half of the patients achieving a complete resolution of their diplopia, all with a well-tolerated safety profile. As we mentioned, based on this data, we plan to submit both of these regimens for approval. Looking forward to REVEAL-2, our Phase III clinical trial evaluating Q4 weekly and Q8 weekly ELE in patients with chronic TED. REVEAL-2 will be our fourth pivotal trial for the treatment of TED and our largest to date. We look forward to presenting results from REVEAL-2, which is on track for top line data in the second quarter of 2026. We expect to submit a BLA for ELE in the first quarter of 2027. And with that, I'll turn it back to Steve.

Thank you, Radhika, for walking us through these exciting results. While today's call focused on ELE, it's important to remember that IV Veligrotug or Veli has an upcoming PDUFA target date on June 30. Veli showed a rapid onset of proptosis treatment effect, statistically significant impact on diplopia, including in patients with chronic TED, and it achieved it with only a 12-week course of therapy and 70% less drug. Veli received breakthrough therapy designation from the FDA in 2025, and its BLA is currently under priority review with the FDA. As we approach the upcoming PDUFA date, we have built a fully operational commercial and medical affairs organization, including field sales, field medical, market access and patient services. These teams have all been actively engaged with key stakeholders in the field in support of a strong Veli launch. In particular, our med affairs team has been actively engaged with the scientific community ever since the THRIVE readout to educate physicians on Veli's profile and to raise awareness of both Veli and Viridian ahead of our anticipated launch. With a potential approval decision just 3 months away, we are ready to launch Veli as the first product in our TED portfolio. Looking ahead to the future of TED, we are excited to have both Veli and ELE in our portfolio. Today, the TED market has one approved IV therapy. Despite low penetration by this therapy in the market, it still annualizes to approximately $2 billion in revenue. We believe Veli will be a highly compelling IV product. It has a strong clinical profile and a significantly shorter treatment course that appeals to many patients and physicians, positioning Veli to become the go-to IV treatment in TED. The ELE data presented today, including a robust proptosis response seen with the Q8 regimen in just 3 doses as well as the compelling diplopia resolution with the Q4 regimen that rivals IV therapies and can be delivered now in a -- as an at-home auto-injector. That positions ELE to be potentially expanding the TED market meaningfully beyond IV-treated patients. Between Veli, Q4 and Q8 ELE, we believe we have a solution for TED patients regardless of the severity of their disease or the presence or absence of diplopia. And with that, I'd like to once again thank our appreciation to the patients, their advocates, our investigators and research staff and everyone who made this REVEAL-1 clinical trial possible and a success. So with that, we'll open up the call for questions.

[Operator Instructions] Your first question comes from the line of Thomas Smith with Leerink Partners.

Congrats on the data. From a regulatory perspective, can you talk about the prespecified analysis plan and whether or not there's any risk to approvability for the Q8-week regimen because of the stat hierarchy? And then same question with respect to getting some of these other key secondary endpoints included in the label such as the diplopia resolution that looked really good. Just wondering if there's any risk to getting that included in the label.

Thanks, Tom. Yes, I appreciate the question. We are very confident that we can move these forward. First and foremost, the REVEAL-1 did meet its primary endpoint. So by that definition, it's a successful study. And so when we look at -- and we plan to submit, just to be clear, we plan to submit the BLA as we've guided for both doses in Q1 2027 because we believe each arm is compelling and could be appropriate, quite frankly, for different patient populations. Q4 looks great from the standpoint of reaching a proptosis responder rate that's highly stat sig. Q8 looks maybe even better on proptosis responder rate and maybe has a -- when you look at the safety, although the overall safety profile is very good and very -- as expected, Q8 looks even a little bit better. So both would be compelling for patients. So we think we can move those forward. I would also focus on the diplopia response and resolution that we saw in the Q4 weekly arm, which is really encouraging, where -- and so when we look at these different profiles and moving them forward based on hitting the primary endpoint, we think this is approvable. On the -- and I'll have Shan maybe address the stats plan that you asked about.

Yes. Thanks, Steve. Happy to do that. Based on the highly statistically significant primary endpoints and so not just proptosis responder rate, which is the endpoint that the FDA really focuses on, they believe that to be the most important endpoint for thyroid eye disease, but we also met highly statistically significant on the overall responder rate, which is the European endpoint. So I think this unequivocally supports the positive study and completely supports the approvability of ELE. On the stats plan, you're probably referring to the secondary endpoints. And here, what we showed was actually there for the majority of these endpoints consistently having very clinically meaningful and significant effects on these endpoints as you saw with all of the p-values that -- low p-values that Radhika presented. As she mentioned, CAS 0, 1 was located early in the stat hierarchy and with the large unexpected placebo response and not meeting that from a p-value standpoint, we do refer to the rest of the endpoints as being nominally significant. But just looking at the effect size, even looking at Q8 weekly proptosis responder rate, again, this is the response that the FDA really cares about the meaningfulness of that endpoint and the effect size that we saw is tremendous. And so we feel really good about the ability of these endpoints to make it into the label. We, of course, will seek inclusion of these endpoints in the label, and there are actually many precedents of drugs who've been able to do so ahead of us.

Your next question comes from the line of Michael Yee with UBS Financial.

We had -- thinking about the results today, it seems like you had maybe slightly higher placebo rates and perhaps slightly lower treatment arm rates, although it hit statistical significance. And is therefore, part of a registrational package. Can you just remind me how you think about the results as it relates to the chronic study coming up? And traditionally, results can come down a bit in chronic, which is a bit more difficult to treat heterogeneous population. So how do you see the results today playing in the results in Q2 and thinking about the powering and some of the scenarios that may evolve from that versus what others have shown?

Yes. Thanks, Mike. Okay. Yes, I think certainly, everyone can see that the placebo rate that you referred to is higher than our prior experience across multiple endpoints. And while the treatment effect of ELE is highly significant and clinically meaningful, we do acknowledge that the treatment effect is less than what we saw in PRISM. Now with respect to how that reads through, but let me just remind you that -- it's highly statistically significant. It's clinically meaningful on the proptosis. And what we see is that ELE delivers the majority of the IV IGF-1R efficacy. But now we can do that in a convenient subcu auto-injector that we can deliver to people's homes. So we think that, that is a potential to expand the market here. And particularly, as Shan was just answering the prior question, when you think about the diplopia response that we saw, the high rates of complete resolution and diplopia resolution and response that we saw in the Q4 weekly arm, the proptosis response we saw in the Q8 weekly arm. So that is -- and the p-values that Shan was referring to, that is all pretty important. So with respect to REVEAL-2, we do expect to move forward, as we mentioned, with both arms. And we -- the REVEAL-2 study is larger. It's a larger study. We have planned and powered it for that purpose. We know the chronic population. And so we feel good about the REVEAL-2 based on what we see today. It doesn't change how we think about REVEAL-2.

And on REVEAL-2, maybe just another comment on that. Here, the point that chronic patients are different than active patients. I'll say that we've always planned for that. We have always planned for chronic patients to be harder to treat. We took that into account for REVEAL-2. Remember that the REVEAL-1 endpoints here are highly statistically significant. So the treatment effect is robust. We have very, very low p-values. We powered REVEAL-2 sufficiently as well as a larger study. We enrolled over 200 patients there. And also in REVEAL-1, I think the results here give us a lot of confidence that the drug is reaching the levels of exposure that we have predicted in our modeling going into the study. So that also translates over to REVEAL-2 as well. So in general, we feel really good about REVEAL-2. And then remember also that the CAS endpoints are not relevant for the chronic patient population.

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

I wanted to think through the upcoming TEPEZZA subcu data. Maybe first, you could just remind us what the product presentation for that subcu is. And I guess not seeing a dose response here to me indicates I can't biologically think of a reason that they could do better on efficacy. So I'd be curious from your perspective, if you think you're maybe getting some more mild patients into this trial. And I'm not sure if that's a temporal thing with kind of the TED population or maybe kind of a fact of using a subcutaneous form that can get some more mild patients. But I would just, in general, be curious what your thoughts are for that upcoming trial.

Thanks, Gavin. Yes, so I'll take the subcu TEPEZZA question. Based on what we -- what has been disclosed publicly, their approach looks like it involves a wearable subcu infusion pump. So it's something that's attached to the abdomen. It seems from what we understand is dosed every 2 weeks. It's not extended, dosed every 2 weeks up to 24 weeks. So just by contrast, ELE is designed as a low-volume auto-injector, as you know. And so we like -- the half-life extension gives us the ability to dose that infrequently. And we just think that's tested well in commercial research for the profile. On the other question, I'll turn that over to Shan for -- to answer.

Yes. Maybe to address the dose response first. I think that's right on the proptosis part of it. And what we saw, again, as I mentioned in response to the last question, observed PKs in this study were pretty much as we were predicting, including the Cmin. And then IGF-1 levels across both dosing arms were also at that maximum what we have seen before, 4x from baseline. And so this is really consistent with our belief that the receptor target of IGF-1R is fully saturated in both of these dosing arms. So sort of no matter how you look at it from a proptosis standpoint, whether it's Hertel, MRI, the results have overlapping confidence intervals and error bars. And so we really do think that we're getting to a pretty similar level of response in both of these arms as well as both of these arms performing extremely well on the total effect size.

The last part of your question, Gavin, I think, was related to whether or not we believe we have more milder patients in our study. That's not the case. When you take a look at the baseline characteristics of the REVEAL study and even compare them to THRIVE, you can see a pretty consistent element across the patient population, both in terms of the key clinical characteristics. So this is very much a consistent moderate to severe patient population.

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

I guess I was curious if you could walk through kind of the path for getting the subcu auto-injector ready for filing next year.

Sure. Yes. Thanks for the question, Alex. The auto-injector is something that's been in our plans. We've worked into the development plan already as well. So in addition to the pivotal studies that we are running, including the BL1 data that we showed today, we are also running an auto-injector study, which will enable us to submit the BLA together with the auto-injector data, which would enable, we believe, an approval and launch with ELE in the auto-injector. This is a commercially validated auto-injector. Our CMC tech ops team is all over in terms of getting this auto-injector ready and manufacturing and the device development is always on a parallel path to the pivotal study, so not always, but you want it to be on a parallel path. So it's not rate limiting for the development of the drug. And that's exactly what we plan for here.

Your next question comes from the line of Joseph Thome with TD Cowen.

You indicated filing both regimens and that these different options might be better for certain types of patients. I guess, can you kind of walk us through, do you see discrete patient subsets that might be more applicable for Veli versus ELE Q4 week and Q8 week? And maybe relatedly, what proportion of thyroid eye disease patients just aren't seeking treatment right now? And how do you think that could change with the subcu option?

Absolutely. Great question. So maybe just a reminder, this is a $2 billion market currently annualizing. We see single-digit penetration. We believe one of the keys to expanding this market is providing more accessible treatment options to patients. The goal here was to find a way to safely deliver IGF-1R therapy in the convenience of the home for these 10 patients. So we feel like we've done that based on the results of REVEAL-1. We've done so in as few as 3 doses. When you look at Q4 in particular, having the ability to offer patients a diplopia resolution in the comfort of their own home, we think is very compelling and very powerful. So we see this as a good day for patients. It's a great day for physicians as well, where we can offer not 1, but potentially 2 new convenient safe options in the comfort of a patient's home.

Your next question comes from the line of Laura Chico with Wedbush.

I just wanted to follow up on some earlier commentary from Shan. Could you talk a little bit about strategies that were administered enacted during the study to ensure doses were administered at a proper interval? And I know this was conducted using the file syringe, but I guess any issues related to adherence or issues with self-administration?

Yes. Thanks, Laura. This is Radhika. I think, first, we feel very confident in how we conducted the study. We've done a significant amount of training and consistency and similar to what we did with THRIVE with regards to oversight. We follow the standard process with regards to ensuring that the drug was administered. And I just want to clarify, I thought I heard you say self-administer. The patient is not administering the drug at the clinic site in the course of the study. The physician and the site draws up the drug and is being administered. So it's still in the course of the clinical trial, a physician. So we're confident that the drug is being administered as per the patient was randomized.

Your next question comes from the line of Gregory Renza with Truist Securities.

Let me add my congrats on the results today. Steve, I know you commented on your resource position being sufficient through profitability. Just wondering if you could walk us through maybe some of the inputs that inform that when it comes to the revenues as well as the investments and some of the milestones that are in the mix throughout this runway.

Yes. Thanks, Greg. So yes, no impact on our guidance with respect to profitability. The components there is our current cash and our anticipated near-term milestones that we have and future of ELE and ELE revenues, obviously, as those get approved. So we still believe that our -- we are sufficient to fund our plans through profitability. So that has not changed.

Your next question comes from the line of Rami Katkhuda with LifeSci Capital.

I guess with regards to the hearing-related AEs associated with LE, they were a little higher than what was observed in THRIVE 1, especially in the Q4 arm. Can you touch on the severity in more detail and when they typically occurred?

Yes. Thanks for the question. So just as a reminder, all of the events that happened were generally mild in nature with regards to the hearing impairment events and all of the events in the Q4 and Q8 arm in the study were tinnitus. None of these events were associated with any detected changes in hearing function. And that one case of hyperacusis that I mentioned earlier, it was in that placebo arm. So in general, this is a really good clinical profile to have, not only in the Q4, but also in the Q8 arm. I think your question was sort of also referring to the THRIVE rate. The THRIVE rate is also a little bit of a different number for the patient population. So that end is a little bit larger. So there's an element that you should consider with regards to that.

Your next question comes from the line of Douglas Tsao with H.C. Wainwright.

This is Doug Tsao. I was just curious, did you take blood samples to ensure PK matched the modeling that you had done going into the REVEAL studies?

Doug, thanks for the question. This is Shan. Great question. And short answer is yes. Absolutely, we sampled PK throughout the study. And as we -- as I mentioned earlier, we really did achieve the exposures that we were aiming for and that we have predicted based on modeling for Q4 and Q8. So observed values overlaid almost entirely on the predictive value. So from an intended exposure standpoint, I think the drug performed great.

Your next question comes from the line of Lachlan Hanbury-Brown with William Blair.

I guess, first, just wondering if the statistical analysis plan for REVEAL-2 is finalized or if you're thinking about making any changes to that after these results? And maybe second, curious how you think about sort of pricing in the commercialization of both doses. I understand you probably don't have a price yet, but assuming that they're going to be the same presentation, just sort of half as many doses. How do you think about pricing the product for both regimens being approved?

With respect to REVEAL-2, again, we saw a really great effect size here, and that was highly statistically significant. So we feel really good going into REVEAL-2 and the fact that, that is also a larger study, which we had planned for. So we're really confident in the results that we saw today and really think that it will read through nicely to REVEAL-2.

And just a reminder, CAS 0 and 1 is not part of the hierarchy.

Yes, I just address the pricing question real quick. So early to talk about what the pricing strategy is, obviously, or how we'll price ELE. What we can say is we're really excited by the results, and we're really excited about the options that these present to physicians and patients. We feel very confident that payers will see the value that is intrinsic with delivering safely IGF-1R therapy to a patient's home, whether that's Q8 or Q4. We think there's a lot of optionality here for us when it comes to pricing, and we're excited to kind of work through that.

Your next question comes from the line of Rich Law with Goldman Sachs.

Congrats on the success of the trial. I want to gauge deeper into commercial use between the Q4W and the Q8W doses. Do you think the results are reliable enough to explain the differences in proptosis and the appropriate response rate between these 2 doses to have a different use case? And also, like launching both doses, there are commercial complications. Is there any -- like what results in the chronic study would change your view that you would only commercialize one dose?

Yes. So maybe I'll start with the last question first. We're confident in the REVEAL-2 study. I don't think that there's results that would change our thinking on ELE from a commercial perspective at this point based on what we're expecting. From a use case perspective, yes, you could see a difference, right? So I would say both had clinically meaningful responses, right, when it comes to proptosis. So yes, I would say, numerically, one looks different than the other. But I would argue that patients and physicians would find both clinically meaningful, especially when you think about the possibility of providing this to the comfort of a patient's home in a simple-to-use low-volume auto-injector. I think of particular interest when you look at the Q4 arm is the majority of patients seeing a complete resolution of diplopia. That's a very powerful option to offer patients, a complete resolution of diplopia and the comfort of their own home. So you could see potential choices and options when a physician is taking care of a TED patient based on their symptomatology. Having more choices, we think everybody wins when you have more choices for patients in this market.

Your next question comes from the line of Derek Archila with Wells Fargo.

This is Jacob on for Derek. So given the data today, how do you think the market splits out between the IV and subcu IGF-1 class? And then related to that, are there certain subgroups of patients that ELE was effective in or you'd expect to see greater adoption in?

Yes. I'll take the first question. So again, very excited about the profile, very excited about the potential to offer 2 options with ELE to patients with TED. We believe that providing IGF-1R therapy safely to a patient's home is the key to unlocking this market. We think this gives us the potential to not only take significant share from the active population, but we do also believe that this has the potential to significantly expand this market. So we remain excited about the commercial prospects.

Your next question comes from the line of Jason Butler with Citizens.

Could you just give us some thoughts on the long-term follow-up data that we'll get from REVEAL-1 and in particular, the efficacy expectations?

Yes. We're just at top line right now. So we have more work -- I mean, we literally just got this top line. So we have more work to do on follow-up, but it's just like the THRIVE and THRIVE-2 studies that we ran. We have -- the study ends at 52 weeks. So we'll have more data during the course as the study finishes up.

Your next question comes from the line of Andy Chen with Wolfe Research.

This is Brandon on for Andy. Does the new database change how you view the eventual revenue split between IV and subcu? If you could detail any internal assumptions that you're thinking maybe half-half, 70-30? Curious to know your thoughts on that.

Yes, good question. Just to reiterate, based on the strength of the data and based on the potential profile of delivering IGF-1R therapy safely to a patient's home, whether it's in Q4 weekly or in as little as 3 doses, we think this profile, we think ELE has the potential to not only convert share in the active population and then obviously, assuming a positive REVEAL-2 data readout as well, expanding into chronic, we think it can convert active and expand this market in a significant way. So we remain excited about this profile for sure.

Your next question comes from the line of Serge Belanger with Needham & Co.

First one, regarding the proptosis responder rate, can you just talk about the differences between when it's measured via Hertel and the MRI? Are these typically the differences we see between both of these methods? And then secondly, regarding the market, it's kind of been stalled at $2 billion for the last few years. What do you think is the key to moving that upwards in the future?

So I'll start with the clinical and Tony will complete with the commercial question. So I think when you're talking about Hertel versus MRI, so sort of 2 things are happening in the course of the study. What happens is the patient shows up into the clinic, the physician uses the appropriate device, and it's done in the manner as noted in the protocol with regards to the instrument, how frequent and how it's documented. And that sort of is a standard process that's done in the course of clinical care and ultimately in the course of following our protocol for both REVEAL and ultimately for REVEAL-2 as well. The question about MRI and how that's done, the local site does the actual scan and they're following a protocol with regards to the quality and the conduct of that scan of how it should look like. And that scan is then uploaded and then provided to a central reader that's also looking at it in a blinded fashion by 2 central individuals. That data is reviewed and entered separately into the database. So those are 2 separate elements. I think when you're thinking about Hertel and MRI, I think we're here at Viridian kind of at the cutting edge of TED research, and there really are no other Phase III studies that have conducted simultaneous Hertel and MRI measurements. So we have a really great opportunity to kind of advance the field as we look at both of these endpoints as measured -- or this endpoint is measured by both of these modalities. But the reality is that the consistency of the clinical effect that we see in both the Q4 and the Q8 arm really gives us comfort in the clinical outcome measurements that we shared with you today.

Yes. And then I'll take the question on market. So yes, the market has been relatively flat annualizing out to $2 billion a year. We view this not as a market problem. We view this as an existing profile problem. And while TEPEZZA is a great drug, it's helped a lot of people, it is burdensome, logistically challenging to get completion of therapy. Just as a reminder, 60 to 90 minutes, each infusion, over 8 infusions can take 5 to 6 months to complete therapy. We know from our research that roughly 30% of patients that are offered TEPEZZA refuse it. One of the primary reasons they state is because of that burden of the therapy. So this is part why we're so excited to improve that experience for patients getting an infusion with Veli, and we take it a whole another level with ELE. Now with 2 potential options, right? Not just delivering it safely at home, but being able to do that in as little as 3 doses, we think, is very compelling and has the ability to open this market up.

Your next question comes from the line of Lisa Walter with RBC Capital Markets.

Congrats on the news. Just wondering on your regulatory strategy, would you consider filing a BLA based on this data alone, especially considering the FDA is now encouraging a single trial filing? Any color here would be helpful.

Thanks for the question, Lisa. This is obviously really great data and the efficacy here that we have seen across all of the endpoints, not just the primary endpoints is significant. And as I mentioned before, the FDA really does care about proptosis responder rate as the endpoint that they care the most about with regards to thyroid eye disease and the safety looked really great as well. So we like the prospects of what we see, and then we look forward to confirming that with REVEAL-2, and we have guided to submitting a BLA in the first half -- sorry, the first quarter of 2027.

Your next question comes from the line of Faisal Khurshid with Jefferies.

I think you were sort of asked this, but I just wanted to reiterate the point. With respect to REVEAL-2, is your expectation that the relative trend in terms of the comparison of subcu ELE compared to the IV options, like I think you described it as like capturing like a portion or more than half of the benefit of the IV options. Like would you expect that same relative benefit to carry over to REVEAL-2? And if so, how do you think about the competitiveness of a profile like that in the chronic TED population.

So just to make sure we understood your question, I think you're talking about what does -- what would -- maybe, could you repeat that question maybe? I'm not sure I understood it.

Yes, yes, 2 parts to the question. First part, for REVEAL-2, would you expect the same like relative comparison to the IV options as REVEAL-1, where the subcu is directionally lower efficacy than the IVs? And then if you expect that, how do you think about potential uptake in chronic TED?

Well, look, I mean, I think what we saw here in REVEAL-1 is pretty robust proptosis responses. The chronic population is a bit different as we saw with THRIVE and THRIVE-2, but we've designed the REVEAL-2 study with that patient population in mind, certainly. So it's a larger study. It's well powered for that patient population. We don't have -- just to repeat, we don't have the CAS 0, 1 reduction in the hierarchy. It's just not part of it because we have 0, 1 patients enrolled in that study. So that's just not how it works. That was always the case. So yes, we feel -- I mean, just to reiterate, we do feel good about the REVEAL-2. I think the expectation level for REVEAL-2 is if we hit stat sig on that study, we have 2 well-controlled positive studies to move forward with from a regulatory path.

I will now turn the call back to Steve Mahoney for closing remarks.

I just want to say thank you to everybody for joining the call. We -- I think the key takeaways from this study is that we saw good proptosis response, highly statistically significant proptosis response. We think the ELE program captures the vast majority of the IV efficacy. There are -- with Q4 and Q8 representing proptosis response to anti diplopia response and resolution in Q4, proptosis response in Q8. We think this is a great suite of solutions that we can offer to patients and physicians. So thanks for listening today, and we'll -- I'm sure we'll be talking to several of you on the other side. So thank you.

Ladies and gentlemen, that concludes today's call. You can now disconnect. Thank you, and have a great day.