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-2 Phase III clinical trial in chronic 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, Franz, and good morning, everyone. Thank you for joining us on our conference call to discuss the top line results from REVEAL-2, our Phase III clinical trial of Elegrobart in patients with chronic thyroid eye disease. You can access the press release and 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 certain 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 positive top line results from REVEAL-2, our Phase III pivotal clinical trial evaluating Elegrobart or ELE in patients with chronic thyroid eye disease. I would like to first thank the TED community, the patients, the caregivers, investigators and research staff and everyone else who contributed to this trial. Before reviewing the REVEAL-2 results, it's helpful to remember how TED disease management has evolved. It has historically been focused on steroids and surgery, then move to the first approved IV IGF-1R therapy, which has established a large $2 billion market today despite only single-digit penetration. Now Viridian is advancing a new wave of therapies. Veligrotug IV, which was granted both breakthrough therapy designation and priority review by the FDA is on track for a PDUFA target date of June 30. And now our plan is to launch ELE as the first subcutaneous auto-injector for both active and chronic TED with the potential for as few as 3 doses. Viridian is proud to advance these innovative TED treatments for patients so that they may benefit, whether in the clinic or at home, regardless of their disease severity. We are changing the paradigm of how and where the disease is treated. REVEAL-2 is the second of 2 pivotal clinical trials for ELE. You will remember that our REVEAL-1 clinical trial in active TED achieved great outcomes for patients with both the Q4 weekly and Q8 weekly dosing regimens. Trial met its primary endpoint with high statistical significance showed a rapid onset of treatment effect and achieved meaningful outcomes on multiple secondary endpoints and ELE was generally well tolerated. As you will see shortly, we are very excited to present the positive REVEAL-2 results today. We believe the data today positions ELE to be the treatment of choice for the chronic TED population if approved, with the potential to meaningfully expand the number of these patients receiving IGF-1R therapy. Based on these results, we continue to progress towards the BLA submission in Q1 2027. With that, let's get to the data, and I'll turn it over to Radhika.

Thank you, Steve. I would like to start by walking through a couple of key takeaways from REVEAL-2. First, we are pleased to announce that REVEAL-2 met the trial's primary endpoint with a highly statistically significant treatment effect that showed IV-like proptosis in both the Q4 weekly and Q8 weekly treatment arms. REVEAL-2 also achieved meaningful benefits on diplopia or double vision in the Q4 treatment arm. You can see that 61% of Q4 patients achieved a diplopia response and 44% achieved complete resolution of their diplopia. With respect to safety, ELE was generally well tolerated and consistent with REVEAL-1, including low rates of hearing impairment. ELE is now the first and only subcutaneous program to demonstrate positive data in a pivotal Phase III clinical trial for chronic TED. Now let's get into the REVEAL-2 study design. The study enrolled patients with chronic TED. A reminder that we designed this trial to capture the broadest possible chronic TED population by including patients with any clinical activity score or CAS at baseline. The patients were randomized across 3 arms comprising a Q4 weekly ELE, a Q8 weekly ELE and a placebo arm. In each treatment arm, patients receiving a low dose of 2 injections or 600 milligrams followed by 5 single injection doses in the Q4 arm. In the Q8 arm, patients received 2 single injection doses or matching placebo. The primary efficacy endpoint was proptosis responder rate in the Q4 arm at week 24. Key secondary endpoints included proptosis responder rate in the Q8 arm, proptosis mean change from baseline, diplopia response and diplopia complete resolution in both the Q4 and Q8 arms. Slide 8 reviews the study disposition of REVEAL-2. with 204 enrolled patients, REVEAL-2 is the largest pivotal clinical trial ever run in TED, and I'll note that 91% of ELE treated patients completed treatment. 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 the patients was just over 50. Baseline values for proptosis, CAF and diplopia were generally in line with our expectations and precedent clinical trials in this chronic TED patient population. As I mentioned, we enrolled patients with any CAS, and we saw a balanced distribution of baseline CAS scores across the 3 arms of the study. Now let's turn to the results. This slide summarizes the results across the primary and all key secondary efficacy endpoints for the treatment arms compared to placebo. The REVEAL-2 met the primary FDA endpoint of proptosis responder rate in the Q4 arm, Q4 weekly ELE achieved a 50% proptosis responder rate versus 15% in the placebo arm, which was a highly statistically significant result. Similarly, in the Q8 arm, we saw a highly statistically significant result of 54% proptosis responder rate. We are particularly pleased to see this kind of proptosis responder rate with only 3 doses which we view as highly impactful in potentially driving uptake in chronic patients. We also achieved statistical significant results on proptosis mean change from baseline with a 1.88 and a 2.08 millimeter reduction in the Q4 and Q8 arms, respectively, versus a 0.52 reduction in the placebo arm. With these proptosis results, we believe we delivered on the promise of providing IV-like clinical efficacy with a simple subcutaneous dosing regimen that we plan to launch in an auto-injector. Let's now look at diplopia, which we know is also debilitating symptom for patients that significantly affects everyday life. As shown here, Q4 weekly ELE resulted in 61% of chronic patients achieving a diplopia response versus 38% of placebo patients, which was statistically significant. 4% of patients on Q4 ELE achieved complete resolution of diplopia, another meaningful outcome. This is the first and only subcutaneous therapy to have demonstrated impact on diplopia for the chronic TED population. As a reminder, the FDA and EMA requested different primary endpoints. REVEAL-2 also met the EU primary endpoint of overall responder rate with high statistical significance. We believe REVEAL-2 2 reinforces ELE as having the potential to deliver meaningful benefit to TED patients in as few as 3 doses. For chronic test specifically, these data could, for the first time, really help motivate a historically understating population and get them off the sidelines and onto a treatment that could improve their lives. These data for Q4 and Q8 ELE confirm our plans to seek regulatory approval for both dosing regimens. With that, let's see how these results look across time points. When you look at the proptosis responder rate for Q4 and Q8 arms, we observed a separation from placebo at or week 4, which continues to deepen across subsequent endpoints through week 24. Moving to the mean change in proptosis for Q4 and Q8 arms. Separation from placebo was observed at week 4 after just a single dose ELE in both treatment arms. Again, this treatment effect deepened over time through the end of the treatment period. On Slide 13, we show the diplopia outcomes for the Q4 weekly arm and the improvements over time, resulting in 61% of patients achieving a diplopia response and 44% of patients achieving complete resolution at week 24. Again, this is the first demonstration of meaningful effect on diplopia with the subcutaneous IGF-1R and chronic TED. On this slide, we show key proptosis and diplopia results in the subpopulation of patients who had low clinical activity scores at baseline. This is the same CAS inclusion criteria used for teprotumumab in its Phase IV clinical trial for chronic TED. All proptosis and diplopia results were meaningful across both dosing arms and generally consistent with the REVEAL-2 results overall. For proptosis, you can see the P values are well below the threshold for statistical significance even in the subpopulation. There is another great -- this is another great outcome, and this shows ELE's potential to be an efficacious solution for all chronic patients regardless of CAS baseline, and reinforces our plans for the ELE profile to unlock this population with potentially as few as 3 doses in a simple and convenient auto-injector. Now let's shift over to safety. ELE was generally well tolerated across both treatment arms and the vast majority of adverse events were mild. On to the safety table, we see a well-tolerated profile with 8 categories consistent with the class. With respect to AEs of interest, the rates of hearing impairment were low with 4.1% and 8.8 placebo adjusted rate in the Q4 and Q8 treatment arms, respectively. For those patients who experience hearing impairment, the majority reported tinnitus. The majority of injection site reactions were grade 1 with more occurring in the placebo arm than in the treatment arm. None of the ISRs led to interruptions in dosing or discontinuations. We are thrilled to see these results from REVEAL-2 and to share them today. In summary, the study met its primary endpoint with high statistical significance. Both Q4 and Q8 ELE achieved statistical significant proptosis response demonstrating IV-like clinical efficacy. REVEAL-2 was also the first demonstration of meaningful effect on diplopia with a subcutaneous approach in chronic TED, which we expect will be highly compelling for patients to initiate therapy. And with that, I'll turn it back to Steve.

Thank you, Radhika, for walking us through this exciting REVEAL-2 results set. These data validate and extend the positive results we saw in REVEAL-1 in active TED, making these 2 pivotal clinical trials the first and only positive subcutaneous data in both active and chronic TED. With REVEAL-1 and REVEAL-2, we believe ELE has the potential to deliver a simple, effective and well-tolerated treatment active and chronic TED patients, and we look forward to pursuing our BLA, which we expect to submit in Q1 2027. We plan to launch ELE in a simple one-step auto-injector with each dose delivered in just seconds, which a patient can self-administer at home in as few as 3 doses. With this profile, we expect ELE to be the most convenient option for TED, if approved, positioning it to be the treatment of choice for TED. We know only a fraction of the TED population is treated today with many patients and physicians discouraged by the burden of the only available product, which is an IV regimen comprising of 8 infusions, 60 to 90 minutes each that takes almost 6 months to complete a course of therapy. We expect that IGF-1R efficacy, coupled with the convenience of ELE will attract new active and chronic patients to seek treatment, fundamentally reshaping the treatment paradigm in TED in driving growth of the $2 billion TED market beyond today's single-digit penetration by a single product. We are extremely excited about the prospects for ELE. Looking ahead to the future of TED, with Veli IV,Q4 ELE and Q8 ELE, we believe now we have a TED portfolio that can provide a potential treatment solution for all TED patients. We believe Veli will be a highly compelling IV product. It has a strong clinical profile and a significantly short treatment course that will appeal to many physicians and patients. With the PDUFA target date next month, we have built a fully operational, commercial and medical affairs organization in our ready to launch Veli as the first product in our TED portfolio. With today's REVEAL-2 chronic TED data for ELE validating and building upon REVEAL-1, we believe ELE has the potential to transform the treatment paradigm for active and chronic tat. We believe the ELE profile will renovate strongly in today's IV market and serve as a key to unlocking future market growth, meeting patients where they are with the efficacy, safety and convenience that they need. Viridian is proud to advance these innovative TED treatments for patients so that they may benefit, whether in the clinic or at home regardless of their disease activity or severity. We're changing the paradigm of how and where this disease is gated. And with that, I'd like to once again express our appreciation to the patients, their advocates, our investigators and research staff and everyone who made this REVEAL-2 clinical trial possible and a success. So now we'll open the call for questions. Thank you.

[Operator Instructions] All right. And your first question comes from Faisal Khurshid from Jefferies.

So now that you have all 4 of your positive Phase III readouts between IV veligrotug and subcu Elegrobart. Could you just walk us through essentially how you see the pieces fitting together with your overall go-to-market strategy and also how you see this relative to the competitive landscape, including the recent competitor update?

Great. Thanks, Faisal. It's a great question. So I think we should start with we're really happy with the REVEAL-2 data. To reiterate, this is the first and only Phase III subcu data showing IV-like proptosis improvement in chronic TED patients along with compelling improvements in diplopia. This is the efficacy that we expected to see from ELE and we achieved it in as few as 3 doses. So that's exciting. With respect to the REVEAL-1 study that you referenced, let me remind you that REVEAL-1 was positive study. The study met its primary endpoint with high statistical significance and had meaningful improvements on multiple secondary endpoints where we showed compelling benefit not only on proptosis, but also diplopia with a really strong safety profile. So take those together, we have a clear regulatory path. We have a positive REVEAL-1 study and a positive REVEAL-2 study. And our plan now is to do all of that with the simplicity and the convenience of an at-home one-step auto-injector, where we can do that in as few as 3 doses, and where each dose only takes a matter of seconds to deliver. So we believe that, that altogether, we believe ELE is really well positioned to capture significant share not only of the existing market or the current market but as well as expand the market from here by motivating new patients to start therapy as we referenced on the call.

Yes. Maybe I'll take the first part of that question, I believe it was about the go-to-market approach across the now 3 options, certainly Veli with the PDUFA right around the corner next month, followed by 2 options with ELE Q4, Q8. We couldn't be more excited about the commercial setup for Viridian. As a reminder, this is a $2 billion market today with one approved competitor. We believe Veli has a very competitive profile, we look to differentiate on 3 primary attributes: first, speed of onset, which we clearly demonstrated and saw in both THRIVE and THRIVE-2, with a rapid onset of effect. Two, in the treatment duration, so we believe not just fast onset of effects, but quicker completion of therapy with finishing therapy was 12 weeks versus 21 weeks with a branded competitor. And then lastly, the clear benefit that we witnessed with Veli in the chronic patient population, in particular, intopia resolution, which we know is one of the most bothersome symptoms with had patients today. So we feel very excited about Veli to compete and win in the existing $2 billion market. We think this is a very good setup for us head-to-head Veli versus TEPEZZA. And then to have the benefit of ELE Q4, Q8, right behind it. leveraging the same infrastructure that we will build for Veli is a very nice setup for us filled with commercial synergies. We view the best ELE launch as a solid Veli launch. As noted, we are fully staffed and fully prepared to hit the ground running ahead of that PDUFA date and look forward to competing against Amgen and TEPEZZA in the market in the near weeks to come.

And your next question comes from Thomas Smith from Leerink Partners.

This is Nash [indiscernible] on for Thomas Smith. Congrats on the data. We have a few questions. So first, you highlighted proptosis and the diplopia outcomes in the low-cost subgroup. Can you provide more color on how Elegrobart performing in the higher CAS group and the time effect was consistent across productivity? And second, on safety, you noted low rate subcu impairment and that the majority of events alternatives. Were there any other cell-related adverse events observed such as type of accuses, and can you comment on severity, reversibility and whether any cases otitis object paying last? And lastly, assuming Elegrobart is approved for those Q4-week and Q8 dosing. Have you envisioned routing your 2 residents commercially? And how come do you view Elegrobart profile versus other potential acute options including TEPEZZA body infusion?

Thanks for the questions there. I will take the first one on the low CAS versus higher CAS and then pass it on to my colleagues. We were really excited to see the consistency of proptosis as well as diplopia results regardless of baseline CAS. So we showed the low CAS subgroup on the slides that Radhika walked through, which had the same inclusion criteria, by the way, as the TEPEZZA product Phase IV study. And there, we show that Q4 week and Q8 week proptosis and proptosis results really looks like the full study and maybe even a little bit better. With that consistency, you can infer that the higher CAS subgroups were also generally consistent with the overall REVEAL-2 study in general. So we're really pleased to be able to offer this level of efficacy, which, again, a reminder is IV-like with a very convenient dose regimen, and in particular, for the low CAS population, we think this is the profile. We believe this is the profile that will really motivate these patients with lower CAS that come off of the sign lines and seek treatment. Radhika, I'll pass it to you on safety.

Yes, thanks. So we're really happy with the clinical profile and the safety profile that we observed here in the study. As I mentioned on the call, we saw very low rates of hearing impairment. That was a 4.1% and 8.8% placebo adjusted in the Q4 and the Q8 weekly arms. Overall, the studies are very consistent between both REVEAL-1 and REVEAL-2. In the REVEAL 2 study, the majority of the patients with hearing impairment for tinnitus. And so that's something that we are not surprised to see. We did have 2 participants in each ELE arm who also reported mild hypothesis, which is just a reduction in hearing. These patients did complete their treatment, had noticing interruptions, and really what's important is that none of those patients had any detectable changes in hearing at the end of their treatment period. Additionally, we actually have some resolution of these events already noted. We did also see a case of a station tube disorder in both the Q4 and the Q8 arm. Both of those were mild. Ultimately, this profile is very consistent with regards to the results you'd expect with an IGF-1R class, and we feel these results to be quite favorable in terms of what it provides to the patients and ultimately for the physicians should they choose to prescribe it.

Yes. Maybe I'll take the question if there's a question there about the 2 dosing regimens together and all and how we view them fitting commercially. So first and foremost, we're really excited about being able to offer the value of an IGF1R home simply in safe plan as little as 3 doses, thrilled by the fact that both profiles look extremely strong. We believe there is value in providing choice to physicians and patients, and we're happy to do that with both the Q4 and Q8 weekly dosing regimens. . We would view Q8 as the go-to regimen for most patients based on early feedback with the potential to move to Q4 weekly if the patient has a heavy diplopia burden. I think the data is pretty clear, both for REVEAL-1 or REVEAL-2. It fits the nice natural positioning and this is what we're hearing in our early discussions with KOLs. Maybe I'll pass it to Steve to talk about the -- how may compete with the on-body device with TEPEZZA.

Yes, thanks. I think that's an important point to address. So I appreciate the question. Well, I think, first of all, we just -- I think we just have to acknowledge that we are the only subcutaneous. The TEPEZZA subcu is not really a subcu. It's an infusion pump. Today, all we have is that there's a TEPEZZA IV available today, there's a TEPEZZA that's an on-body infusion or an OBI that's in development. But in the case of the on-body infusion, the drug is infused in that case, using a wearable device every 2 weeks for a total of 12 infusions over a 24-week period. So we estimate that the device likely infuses about 8 to 10 mls per infusion. And there's only one commercially available device that can do that type of volume. The device measures 4 inches long. It's 2 inches wide. It's battery powered. It's attached to your abdomen for the duration of the infusion. And with these types of volumes, we expect each infusion to take up to 30 minutes. There are very few commercial precedence for a successful on-body infusion device. In fact, the last OBI, Amgen tried to commercialize the Repatha OBI they took it off the market in favor of an auto-injector because the overwhelming majority of patients were being prescribed the auto-injector as a more patient-friendly format. So I say that because I just -- I hope it's clear to folks that we -- the ELE is a completely different profile. We plan to launch using a commercially validated simple, convenient one-step auto-injector, delivering a full dose in seconds that allows the patients to complete a full course of treatment and as few as 3 doses. In fact, we use the same injector pen as is used with DUPIXENT. So we just believe that this is a far more compelling and convenient profile for TED patients that today -- we saw in today's results, which really importantly, we saw IV-like efficacy on proptosis, plus the benefit on diplopia for these TED patients. So as Tony just alluded to, between Veli IV, Q4 weekly ELE, Q8 weekly ELE, we feel really confident about our ability to compete against TEPEZZA IV and then certainly against the TEPEZZA on-body infusion device.

That's very helpful. And congrats again on the data guys.

Next question comes from Laura Chico from Wedbush.

Just 2 quick ones for me. First, on I'm not sure if Radhika can explain a little bit. I think I missed it. But with respect to the 3 discontinuations on the ELE arms, when did those occur in the study? Was that earlier in administration? Or I guess, just kind of timing wise, when did that happen? And then, Steve, you've made a lot of comments about the kind of competitive setup versus teprotumumab OBI versus ELE, and I think that the last slide certainly kind of brings on the point on the frequency of injections. I just want to make sure I'm understanding -- in terms of market expansion, the concept of building out the TED market or expanding utilization. Is it the convenience factor ELE that brings chronic head patients off the sidelines? Or does this have more to do with the data from REVEAL-2? Just wondering you kind of distill that a little bit more. .

Sure. I'll start first with the safety question. So I think when you look at the discontinuation rate, first of all, ELE was really well tolerated. And ultimately, as it presented or I think I shared on the previous slide, 91% of the ELE treated patients actually completed a treatment period. So the completion rate was generally consistent across both the Q4 and the Q8 arm. The AEs that ultimately led to discontinuation. There was a Grade 2 hyperglycemia in Q4, and there was a Grade 1 tinnitus in Q8 and a Grade 3 muscle spasm, which is a footprint and also in the Q8 arm. These AEs were, I think, generally somewhere in the middle course of therapy for most of them. There are events that generally are seemed to be manageable by the physicians, but I think circumstances for the patient suggested the discontinuation.

So Laura, I got your question on the competition. I'm going to turn that over to Tony. I think we can -- but I think just overall, certainly, it's driven by the data that we saw today on the efficacy and the safety side. And then the convenience is that added upside, but I'll just turn it over to Tony.

Yes, it's a great question. I think the short answer is both convenience and the strength of data. I think that those 2 together create a profile that we believe can unlock this market. We think the key to unlocking the market is to safely and simply deliver an IGF-1R home. We've done that in 2 consecutive trials and as well as 8 doses, and we think that's extremely compelling. So at a more granular level, how do we think that this profile expands the market. And we're calling this at a doubling. We believe this market can at least double at maturity, and we get there in a couple of different ways. So the first of which I think we said before, our market research continues to be back that as many as 3% of patients that are offered TEPEZZA to date decline therapy, one of the top reasons they state often is the burden in logistics involved in an accused product like the TEPEZZA just not willing to set up for that. So we do believe that with a profile like ELE, many of those patients who say no today, that will say, yes, with the availability of the profile like ELE in the marketplace. Another reason we believe this market will grow another way it will, is we do believe that this profile, based on our market research will be more attractive to more physicians. So we think a key to unlocking some of these patients that are on the sidelines today, particularly in the chronic population by activating more physicians who are currently seeing them. This is general ophthalmology but also endocrinology. Here is a place where we agree with Amgen's [indiscernible] of creating new prescribers in this area. It's a strategy they've been deploying for a couple of years now. So we agree there's an opportunity to activate more prescribers, and that will activate more patients. We disagree on the profile required to unlock those patients. We believe a profile like ELE again, that can be delivered safely and simply to a patient's home, changes the willingness of a position to initiate IGF-1R therapy with patients that need it. The third one, when you do that, when you activate more physicians, you inherently will address more patients in addition to lowering the bar and sliding patients selection more to the moderate and mild side of moderate to severe. We know with a profile like ELE from a market research that physicians start to view the patients differently and tend to offer an IGF-1R to more mild patients. And that's just not in chronic, that's across the board. So a fourth way that this market grows, which is a bit agnostic to TED and agnostic to Veli and ELE. It has to do with just the increased promotional effort. Again, this $2billion market today is constituted of roughly 2,000 core prescribers. There's about 125 Amgen reps today promoting an IGF-1R. We'll add close to 100 reps roughly doubling the size and doubling the promotion effort behind an IGF-1R. And we believe it's reasonable to assume that, that in and of itself will also expand the market. So 4 ways, we think it's double, at least double, and of which, again, with the 3 options that we just discussed the Veli, ELE Q4 ELE Q8. We believe we have an answer for most of those patients.

And your next question comes from Rami Katkhuda from LifeSci.

I want to pass along my congratulations. I guess in both REVEAL-1 and 2, proptosis benefit looks better with Q8 week dosing, while the plug improvements were greater than the Q4 arm. Do you believe these trends are due to variability of the disease? Or do you have any additional hypothesis as to why that's the case? And then maybe from a commercial perspective, do you know what percentage of the chronic head market is currently being penetrated by TEPEZZA? And will you have to make a bigger push into endocrinologist offices to better capture the chronic TED population end of the day.

Thanks for the question, Rami. I'll go ahead and take this first one. I think that we were just really pleased to see the consistency with REVEAL-1 in terms of these results, as you mentioned, Q4 and Q8 both showed really great proptosis reduction. We see these as being in line with each other -- in terms of there not being a dose response here necessarily on proptosis, that's consistent with the underlying PK/PD as well. So once again, just like in REVEAL-1, we saw PK levels as predicted pretty much similarly to our modeling there and that also matched REVEAL-1 and then on that PD biomarker IGF-1 levels, we also saw in both Q4 and Q8 on that same 4 to 6x increase from baseline of IGF-1, which we've come to expect for a full antagonism -- for antagonist for IGF-1 receptor. So all of this is consistent with our belief that the receptor is fully saturated even at that Q8 dose. And so taken all together, it's not surprising that the clinical outcomes on proptosis would be similar for Q4 and Q8. Now we do see a difference in diplopia. This is now the second large pivotal study where we consistently see that Q4 diplopia response and performing better than Q8. I think it just, in general, puts us in a really great position to be able to offer both regimens. As to your question for why this might be the -- ultimately, proptosis and diplopia are different. They have different potentially underlying biological drivers for that. And diplopia is more than just the bulging eyes and consistently across our data. It looks like diplopia is potentially a bit harder to treat. But kind of the main takeaway here is, as we look at both Q4 and Q8, it puts us in a really great position to offer both dosing regimens. We expect that many patients will have an excellent experience with the Q8 regimen with the proptosis response that they would see in just 3 doses, again, in a simple auto-injector. And then for subsets of patients, as Tony mentioned earlier, those with diplopia burden, the Q4 weekly arm would be a regimen that will really benefit them as well.

Yes. I'll take the 2 questions. So one on chronic penetration, it's low single digit. So of the 7,000 patients annually that are initiated on TEPEZZA that make up a $2 billion market today, roughly 80% of those are active. So the balance coming from chronic and then the resulting penetration is extremely low. There was a question there about Elegrobart and we believe that endocrinology will play a bigger role kind of post product like ELE. We -- but the short answer is yes. This is an area, as I mentioned, where endo has been pushing hard over the past year or 2 to promote TEPEZZA and create drivers. They've been limited by their profile. But I think they're spot on with the opportunity there. Why Endo? A lot of these patients, the chronic patients in particular, who are being seen long term for their underlying grade disease are being seen by endocrinologists. So we think that's a more direct path for some of these patients, and we think that the ELE profile will be more conducive I'm going nonprescribed IGF-1R. From a synergy perspective, I think it's important to note, one of the reasons why we love this set up so much is at launch, we'll have some level of effort on infusion centers in support of ELE. As we introduce ELE into market, if approved, we're able to reallocate some of that effort away from infusion centers and towards endocrinology. So again, another nice strong synergy between the 2 products that sets up nicely for Viridian.

Your next question comes from Michael Yee from UBS.

We had 2 questions. Obviously, with the launch of IV coming, how do you think about payer access in the first 6 or 12 months in the context that Amgen seemed to have pretty good access and a strong launch. I wanted to think about how we should expect or how we should think about the cadence of the launch given second to market but a better profile. And then also, obviously, they may have had pent-up demand or just a bolus. So maybe compare and congress that how you think we should think about the first couple of quarters of the launch around the corner. Second question is, obviously, you reported EPS. So there's lots of other pipeline going on to you. And I just want to ask a question on FcRn since I think you announced that there would be some update to the lead program in terms of the development and maybe that's because you're waiting for the longer-acting data that is reading out later this year. So how should we think about the longer-acting data and what you'll put out and presuming that might be the better program to take forward. How do you think about that?

Yes. So I'll take the question on payer access, great question. Start off by saying I agree with your comment about our profile. Second, from a payer access perspective, I think it's about what you'd expect in most cases with a second the market biologic. So we would anticipate roughly 6 months to get to critical mass on coverage. I do think it's important to point out, we have been in market engaging with payers, utilizing the pie presentation that affords us the ability before approval to talk to not just payers but also formulary decision makers at a fusion centers. So we've done a lot of work already to prepare the market for our entry whenever that approval comes. Post approval, while we're waiting for coverage to expand, and we'll be actively working to do that as fast as humanly possible. I do think it's important to point out that the product is still accessible to medical exception. This is an area where there's an expectation that there'll be PAs require to access this product. This is not something that's new to these offices that are writing TEPEZZA today. They are set up for it. They understand that they'll need to potentially have discussions with the payers in a couple of rounds of a PA that's not new. That's not something that would be unique to Veli. So a long way of saying we've done everything we can to accelerate. Payers will still take the time that they take to review. We have to wait for the P&Cs to meet, but we're ready to jump on those opportunities as they present and would expect critical mass around the 6-month mark.

And I'll take the second question on FcRn and what we'll be looking for later this year. So we have 2 molecules there, VRDN-006 which is an Fc fragment, which we believe is the only other fragment that is in development besides the approved product. So that is a potentially exciting profile for that program. There, we saw in healthy volunteer studies, actually what we would have expected to want to see IgG reductions in line with the class of albumin LDL, generally well tolerated. And so we will share this year the next steps for that program. So the development plan and how we're thinking about the 0 to 6 development path. And then our second program, VRDN-008, which we really believe has the potential to be best-in-class. This is our half-life extended FcRn inhibitor. This molecule we submitted an IND at the end of last year as planned, and that has been cleared with the FDA and we've actually been enrolling patients in the Phase I healthy volunteer study and that data is on track for second half of this year. We will be looking to confirm that half-life extension, IgG levels, sparing of albumin and LDL, which by the way, we saw all of that in nonhuman primates in the preclinical setting, the half-life here was 3x that of efgartigimod when it was performed in a head-to-head study. And then more importantly, that led to a more sustained IgG reduction. So we think the potential for this molecule is pretty tremendous with that half-life extension. And as you may know, the data from nonhuman primates in the FcRn space has historically been very translatable to humans. So we're excited about having that data second half.

And your next question comes from Joseph Thome from TD Cowen.

Congratulations on update. I think earlier, it was mentioned that your survey work points to about 30% of patients declining TEPEZZA maybe due to the administration burden. I guess, are these more active patients or chronic patients that are declining? And maybe how often are chronic patients actually coming in to seeing physicians either for underlying grades or or something else, just trying to understand a little bit more how hard it's going to be to maybe access the segment or easy? And then just a housekeeping question. Where are you with the development of the at-home auto-injector, I guess, what needs to be done with that? And is that going to go in the initial BLA submission.

Thanks, Joe. I'll start with that last question in terms the development of the auto-injector. So we ran the pivotal studies with auto and syringe, which is a very typical way to do this so that the autoinjector development, device development is not on critical path. We do have an unparallel auto-injector study that has completed enrollment and completed enrollment very, very quickly. So that is very much on track. We do plan to submit that in time for BLA and with the goal to launch in an auto-injector. But again, this is all very typical device development time lines and to have pivotal studies in addition to a parallel auto-injector device study.

I believe there's a question in there about the 30% decline, and that's different across active and chronic. And then a follow-up question on where we would need to go to access chronic patients. I think those were the 2 questions. So the first of which, patient rejection is very unique for the patient. It depends on their view of the burden of their symptoms. They probably less to do with if they have active or chronic disease and more to do with how burdens some of their symptoms are up against the challenge of the therapy that they've been offered at that point. So regardless, we believe introducing more convenient options like first Veli and then eventually ELE, whether that's a Q4 or Q8 dosing regimen is an opportunity to improve that expense rate from an access in the chronic population. So these patients are being seen long term on a regular basis by endocrinologists for their underlying Graves disease. So this is not a situation where we need to advertise the patients that have the dose a specialist. It's why we believe targeting endos with the products and profile like ELE will give us access, we'll activate physicians and actually activate more mild patients in the process.

Your next question comes from Gregory Renza from Truist Securities.

It's [ Anish ] on for Greg. Congrats on the data. Maybe just one on the low cash subgroup analysis, given that the patients have samples here to your comp to the tepro Phase IV data, how do you plan to leverage these data with regulators, docs and payers, obviously, understanding the differences between IV and subcu. Just want to get a sense of how you're thinking about tapping and these patients that we've been talking about that are otherwise sidelined. Thanks so much.

Yes. Thanks for the question. Yes, we're really excited about this data. In terms of regulators, I think this fits squarely into the consistency that we see with the overall REVEAL-2 study, which, again, is consistent with REVEAL-1. And so we've said a couple of times on this call that we will have 2 positive Phase III studies to submit a BLA in the first quarter of 2027. This low CAS data is a subpopulation. It is something that we believe we will be able to use in the commercial setting because of the consistency with the overall anticipated label for ELE. So -- and as we mentioned, this is a critical part of the chronic patient population that will really unlock give these patients off to the sidelines and onto therapy.

Yes. And just commercially, I think we're really excited to share this data with both payers, physicians and patients. I think there's a natural skepticism when you look at temptations with that low of activity score that there's a benefit to be had. With an IV let alone being able to offer that in home. So we do think that this will be very compelling data to all stakeholders. We're excited by it, and we believe that this will be a really exciting data set to bring forward into the market. .

And your next question comes from Douglas Tsao from H.C. Wainwright.

I'm just curious, when we look at the data, obviously, the Q4 seems to have an advantage in the diplopia response. If we look at the Q8, the data looked very compelling across all metrics in the low CAS group. And so I'm just curious, do you plan on sort of trying to actively segment the market in any way across dose regimen? Or do you think that perhaps these are sort of not necessarily sort of full subgroups and that you're going to sort of lead to the option for clinicians to sort of sort out themselves?

Yes, excellent question. So we are really excited about being able to offer a choice to physician and patients within the ELE profile. Not something that we would push or pull towards. I think we think it naturally sets itself up as mentioned before, that the Q8 would be to go to regimen for most patients, if the patient happens to have heavy diplopia burden, Q4 might be a better choice. But we would leave that entirely up to the physician in a patient. We think that's a choice that physicians would welcome, and perhaps another attribute that we can differentiate on the attribute of choice where they have just from a choice today.

And maybe as a follow-up, when we think about patients starting on the Q4, you think about sort of a sort of access standpoint and maybe pricing standpoint, just enabling patients if they're not necessarily getting the response they're looking for to maybe sort of switch up towards a sort of Q4 regimen, sort of midstream rather than sort of completing treatment and then coming back.

Yes. So I think there's a payer access question in there, which I'm happy to address. So obviously, it's early to be disclosing our payer or pricing strategy. But what I would like to acknowledge is just the really good work that Horizon and Amgen have done to establish the value of IGF-1R for TED patients. As we sit here today, over 85% of covered lives, there's a policy in place for them for both active and chronic that's considering a WACC price or list price for an average patient on TEPEZZA of up over $500,000. So a really nice job. It created a lot of room for us to navigate. When we talk to payers, what they tell us on a consistent basis is that if Veli and also ELE is priced at parity to a typical patient for TEPEZZA, but they would anticipate getting parity access, which we'd be really happy with. So one more point on ELE in particular. So as noted, we believe that the Q8 regimen will be the go-to regimen. We would approach pricing conversations with a Q8 regimen as a full course therapy.

Your next question comes from Alex Thompson from Stifel.

I guess maybe as you think about kind of the rest of the data to be done at for the later part of the next -- the rest of this year, how should we anticipate 52-week data updates relative to what we see for the veligrotug and what other data generation is there prior to BLA submission?

Yes. Thanks for the question, Alex. These studies are obviously top line data, and we are following patients for an additional 28 weeks to that full 52-week period. This is the -- we do anticipate needing to complete that 52-week period for both studies to submit for BLA. In terms of additional data updates, I think everything has been so consistent so far between all of the different studies, REVEAL-1, REVEAL-2, that we'll just see. But in terms of the additional data coming in from the trials, I think the expectation is that it would be consistent with what we have seen so far.

Your next question comes from Rich Law from Goldman Sachs.

Congrats on exciting data for REVEAL-2. So we heard that from some clinicians that they prefer using corticosteroids for the low CAS chronic patients. So I know you didn't study the corticosteroids here, but how do you think ELE's data here would compare to corticosteroids as you could ultimately compete with those in a chronic setting. And then the second question is that you mentioned previously that your price value ELE as a total treatment courses on capacity price point. What is the strategy for ELE's Q4W relative to Q8W? With Q4W will be proportionally priced to Q4W based on the number of injections?

I can take those. So the first question on how we believe ELE would compare to steroids, Obviously, there's no head-to-head confection against steroid. I would offer up, I think, where you're seeing steroids being an option for your kind of low CAS chronic patients today was before this data. Again, going back to the point that the only choice right now would be steroid surgery or 8 infusions lapping up to 6 months, 6 to 90 minutes out of whack, right, for a patient that's been living with the disease for a bit. I think it's a lot to ask them to sign up for TEPEZZA. I think all of that changes based on the strength of these data, if approved, with ELE in the market, being able to deliver an ID-1 patient so am safely and simply and a little doses. I think it changes the calculus for patients and for physicians and that patient subgroup. From a pricing perspective yes, maybe I'll just cut to the quick. I think we view Q8 as a workhorse for ELE. We think that will be the primary choice as noted, payers view this class on a course of therapy basis. So they will base the Veli price 5 infusions versus TEPEZZA 8 infusions and we're making pricing decisions. We think they do the same when it comes to ELE, and we would have those negotiations discussions based on a Q8 regimen.

Your next question comes from Lachlan Hanbury-Brown from William Blair.

Congrats on the data. I guess maybe a quick one just on the background of patients in the study, what prior therapies have had? I assume obviously not a prior IGF-1, but maybe were there any differences or how representative whether prior therapies between steroids, rituximab or other off-label things to the broader chronic population today? And maybe second, Tony, you talked about sort of the reallocation once launches from IV centers to endocrinologists and maybe general apologists. Just wondering, is the roughly 100 reps enough for you to sort of fully cover both with that reallocation? Or would you be looking to maybe add incrementally to make sure that you can adequately address the expanded prescriber base that you're looking to target with ELE?

Yes, I'll take the second one first. Yes. So the short answer is yes. So we've built this sales force with ELE in mind, and believe that, that transfer of efforts away from infusion centers to the endocrinology and general ophthalmology that's sufficient. Again, I would remind folks that there's 125-ish reps today with Amgen, and they are covering all 2,000 core prescribers and also general ophthalmology and endocrinology, that's based on the concentrated footprint in this space. That's endo-included. So we believe we can cover it with the roughly 100.

And then addressing, I think, the first question with regards to the patient population. The only really main exclusion criteria with regards to what patients couldn't have had really IGF-1R therapy. So these are basically treatment-naive patients with regards to IGF-1R class approaches, but they may have had other medications like such as steroids for instance.

Your next question comes from Derek Archila Archila from Wells Fargo.

A bit about the low penetration of TEPEZZA in the beginning of the call and then a doubling of the TED market with ELE. Could you break us a little further for us? [Technical Difficulty]

And your next question comes from Andy Chen from Wolfe Research.

This is Brandon on for Andy. When we come to 3Q earnings in November, what should we expect to hear about metrics on the IV launch regarding patient forms or other metrics? And how are you defining patient starts form? Is that going to be after patients already clear prior auth with infusion centers? Or is that going to be before clearing prior auth?

Yes. I'll take that question and then I think maybe we'll go back to Derek think you got cut off there. Yes. So what we'll be judging success early days for the launch of Veli. One, obviously, will be just getting out, reaching physicians, sharing the data once approved with the approved label materials. So obviously, we'll keep an eye on how quickly we're able to educate physicians. Again, this is a very concentrated call point roughly 2,000 core prescribers, so we can do that rather quickly. Second, we will be watching very closely for our patient enrollment forms. We look at them every which way you can imagine. So at enrollment all the way through the process, all the way to completion of therapy, haven't disclosed yet what we'll be sharing, but we'll give a good view on how we're viewing the strength and success of the launch through a couple of those metrics. The other metric that I would that came up before that we obviously were watching and keeping a close eye on and reporting on will be just our level of payer coverage and how fast we're able to obtain that.

Operator, we've got Derek, I think you got cut off with why to back on, please?

And your next question comes from Derek Archila from Wells Fargo.

Can you hear me okay?

Yes, we can hear you now, Derek. Sorry about -- I don't know how you got cut off of time.

Okay. No worries. This is Jacob on for Derek. Congrats on the data. So you mentioned a bit about the low penetration rate of TEPEZZA at the beginning and then a doubling of the market with ELE. I was wondering if you could just bring this out a little further to us and talk a bit about your expansion projections in chronic TED based on this data. And then similarly, what you think these projections look like an active TED? .

Yes, great question. So actually the double comes across the board, active and chronic. Obviously, chronic is the most underserved today with a lack of options that they find compelling. Starting from a relatively small -- relatively smaller base as cited with the penetration rates of over 80% of current using from active. But we think that the profile of Veli will be attractive across active and chronic. -- to be quite honest with you. So -- and again, for the reasons stated, we believe that we improved the rejection rate, we add prescribers. We flag. We enable more mild patients into the IGF-1R discussion and then just the increase in promotional effort, roughly doubling the size of promotional power behind the IGF-1R, we think also increases the size of the market.

Thanks, and congrats again.

At this time, I would now like to turn the call back over to Steve Mahoney for the closing remarks. Please go ahead.

Yes. Great. Thank you. So really happy with the data. As you can tell, we're really happy about the profile of ELE in the Q4, Q8 adding that to Veli with the IV launch expected soon. So we look really forward to being able to serve the 10 patients with this suite of products. So thank you, everyone, for listening today, and we appreciate your attention. Thanks.

Ladies and gentlemen, that concludes our conference for today. Thank you all for joining. All participants may now disconnect. Thank you.