Good morning, ladies and gentlemen, 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. At this time, participants are in a listen-only mode. Later, we will conduct a question and answer session, instructions will be given at that time. As a reminder, this conference call is being recorded. I will now hand the call over to Greg Rossano, Senior Director of Investor Relations at Viridian. Please go ahead.
Thank you, Franz. 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, 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 Ellay 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 moved 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 thirtieth.
Now, our plan is to launch Ellay 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 Ellay. You will remember that our REVEAL-1 clinical trial on active TED achieved great outcomes for patients with both the Q 4 weekly and Q 8 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. Ellay 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 Ellay 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 a 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, Ellay was generally well-tolerated and consistent with REVEAL-1, including low rates of hearing impairment. Ellay is now the first and only subcutaneous program to demonstrate positive data in a pivotal phase III clinical trial for chronic TED. 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 three arms comprising a Q4 weekly Ellay, a Q8 weekly Ellay, and a placebo arm. In each treatment arm, patients receiving a low dose of two injections or 600 milligrams followed by five single injection doses in the Q4 arm. In the Q8 weekly arm, patients received two 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 LE-treated patients completed treatment. Baseline characteristics were generally well-balanced across the 2 LE 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, CAS, 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 LE 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 statistically 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 have 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 a debilitating symptom for patients that significantly affects everyday life. As shown here, Q4 weekly LE resulted in 61 of chronic patients achieving a diplopia response versus 38% of placebo patients, which was statistical significance. 44% of patients on Q4 LE 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 reinforces LE as having the potential to deliver meaningful benefit to TED patients in as few as 3 doses. For chronic TED specifically, these data could, for the first time, really help motivate a historically underserved patient population and get them off the sidelines and onto a treatment that could improve their lives. These data for Q4 and Q8 LE confirm our plans to seek regulatory approval for both dosing regimens. With that, let's see how these results looked across time points. When you look at the proptosis responder rates for Q4 and Q8 arms, we observed a separation from placebo after week 4, which continued to deepen across subsequent time points 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 of LE 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 in 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 this subpopulation. This is another great outcome, and this shows LE's potential to be an efficacious solution for all chronic patients, regardless of CAS baseline, and reinforces our plans for the LE 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. LE was generally well-tolerated across both treatment arms, and the vast majority of adverse events were mild. Onto the safety table. We see a well-tolerated profile with AE 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 rates in the Q4 and Q8 treatment arms, respectively.
For those patients who experienced 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 elegrobart achieved statistical significant proptosis response demonstrating IV-like clinical efficacy. REVEAL-2 was also the first demonstration of meaningful benefit on diplopia with the subcutaneous approach in chronic TED, which we expect will be highly compelling for patients to initiate therapy. With that, I'll turn it back to Steve.
Thank you, Radhika, for walking us through this exciting REVEAL-II result set. These data validate and extend the positive results we saw in REVEAL-I in active TED, making these two pivotal clinical trials the first and only positive subcutaneous data in both active and chronic TED. With the REVEAL-I and REVEAL-II, we believe Ellay has the potential to deliver a simple, effective, and well-tolerated treatment for 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 Ellay 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 three doses.
With this profile, we expect elegrobart 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 eight infusions, 60-90 minutes each. That takes almost six months to complete a course of therapy. We expect that IGF-1R efficacy coupled with the convenience of elegrobart will attract new and active and chronic patients to seek treatment, fundamentally reshaping the treatment paradigm in TED and 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 elegrobart.
Looking ahead to the future of TED with veli IV, Q4 elegrobart, and Q8 elegrobart, 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 shorter 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 and are ready to launch veli as the first product in our TED portfolio. With today's REVEAL-2 chronic TED data for elegrobart validating and building upon REVEAL-1, we believe elegrobart has the potential to transform the treatment paradigm for active and chronic TED.
We believe the Ellay profile will resonate 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 treated. 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. Now we'll open the call for questions. Thank you.
Thank you. We will now begin the question-and-answer session. If you would like to ask a question, please press star 1 on your telephone keypad to join the queue. If you would like to withdraw your question, simply press star 1 again. If you are called upon to ask your question and are listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question. Just a reminder, we ask you to please maintain your line open when asking your question. As of now, I would like to have a few seconds to compile the Q&A roster. Thank you. All right. Your first question comes from Faisal Khurshid from Jefferies. Please go ahead.
Hey, guys. Thank you so much for taking the question. Now that you have all four 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? Thank you.
Great. Thanks, Faisal. It's a great question. I think we should start with, we're really happy with the REVEAL-2 data. You know, just to reiterate, this is the first and only phase III subQ 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. That's exciting. With respect to the REVEAL 1 study that you referenced, let me remind you that REVEAL 1 was a 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. Taking those together, we have a clear regulatory path. We have a positive REVEAL 1 study and a positive REVEAL 2 study.
Our plan now is to do all of that with the simplicity and the convenience of a at-home, 1-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. We believe 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, which I believe was about the go-to-market approach across the now three options. Certainly Veli, with the PDUFA right around the corner next month, followed by two options with elegrobart 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 three primary attributes. First, speed of onset, which we clearly demonstrated and saw in both THRIVE and THRIVE-2, with a rapid onset of effect. 2, in the treatment duration.
We believe not just fast onset of effect, but quicker completion of therapy, with finishing therapy in as little as 12 weeks, versus 21 weeks, with a branded competitor. Lastly, the clear benefit that we witnessed with veli in the chronic patient population, in particular in diplopia resolution, which we know is one of the most bothersome symptoms with TED patients today. We feel very excited about our ability 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.
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. I look forward to competing against Amgen and TEPEZZA in the market in the near weeks to come. Yeah.
Excellent. Thank you.
Your next question comes from Thomas Smith from Leerink Partners. Please go ahead.
Hi, this is Natt Sarunsuk on for Tom Smith. Congrats on the data. We have a few questions. First, you highlighted proptosis and diplopia outcomes in the low CAS subgroup. Can you provide more color on how oleglobart performed in the higher CAS subgroup? The treatment effect was consistent across baseline sensitivity. Second, on safety, you noted low rates of hearing impairment and that the majority of events were tinnitus. Were there any other hearing-related adverse events observed, such as hyperacusis? Can you comment on severity, reversibility, and whether any cases were associated with objective hearing loss? Lastly, assuming oleglobart is approved for both Q4 week and Q8 week dosing, how do you envision positioning the two regimens commercially? How competitive do you view oleglobart's SQ profile with the other potential SQ options, including TEPEZZA on 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. 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's chronic phase IV study. There we show that Q4 week and Q8 week proptosis diplopia results really looked 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.
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. 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 to come off of the sidelines and seek treatment. Radhika, I'll pass it to you on safety.
Yeah, thanks. We're really happy with the clinical profile and 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 an 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 those patients with hearing impairment were tinnitus.
That's something that we are not surprised to see. We did have 2 participants in each LE arm who also reported mild hypoacusis, which is just a reduction in hearing. These patients did complete their treatment, had no dosing 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 had some resolution of these events already noted. We did also see a case of a eustachian 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 IGFR class, and we feel these results to be quite favorable in terms of what it provides to the patients and ultimately for the physician should they choose to prescribe it.
Maybe I'll take the question. I think there was a question in there about the 2 dosing regimens together in elegrobart and how we view them fitting commercially. First and foremost, we're really excited about being able to offer, you know, the value of an IGF-1R at home, simply and safely, and 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 regimens 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's pretty clear, both REVEAL-1 and REVEAL-2. It fits a 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 how elegrobart may compete with the on body device with TEPEZZA.
Thanks. I think that's an important point to address, so appreciate the question. Well, I think first of all, we just have to acknowledge that we are the only subcutaneous. The TEPEZZA subQ is not really a subQ, it's an infusion pump. Today all we have is 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 8-10 mL per infusion.
There's only 1 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. With these types of volumes, we expect each infusion to take up to 30 minutes. There are very few commercial precedents 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. I say that because I hope it's clear to folks that the LE is a completely different profile.
You know, we plan to launch using a commercially validated, simple, convenient, one-step auto-injector, delivering a full dose in seconds, that allows a patient to complete a full course of treatment in as few as 3 doses. In fact, we use the same auto-injector pen as is used with Dupixent. We just believe that this is a far more compelling and convenient profile for TED patients, that today, you know, we saw in today's results, which really importantly, we saw IV-like efficacy on proptosis, plus the benefit on diplopia, for these chronic TED patients.
As Tony just alluded to, between veli IV, Q4 weekly LE, Q8 weekly LE, we feel really confident about our ability to compete against the TEPEZZA IV, and then certainly against the TEPEZZA on body infusion device.
That's very helpful. Thank you. Congrats again on the, on the data, guys.
Your next question comes from Laura Chico from Wedbush. Please go ahead.
Thanks very much for taking the question. Just two quick ones for me. First, on safety, I'm not sure if Radhika can expand a little bit. I think I missed it. With respect to the 3 discontinuations on the LE 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? Steve, you've made a lot of comments about the kind of competitive setup versus teprotumumab OBI versus LE, I think that the last slide certainly kind of brings home the point on the frequency of injections. I just wanna 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 on LE that brings chronic TED patients off the sidelines, or does this have more to do with the data from REVEAL-2? I'm just wondering if you can kind of distill that a little bit more. Thank you.
Sure. I'll start first with the safety question. I think when you look at the discontinuation rate, first of all, LE was really well-tolerated, and ultimately, as I presented, or I think I shared on a previous slide, 91% of the LE-treated patients actually completed the treatment period. The completion rate was generally consistent across both the Q4 and the Q8 arms. 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 was a foot cramp, also in the Q8 arm. These AEs were, you know, I think generally noted somewhere in the middle of course of therapy for most of them. They're events that generally are deemed to be manageable by the physicians, but I think circumstances for the patient suggested the discontinuation.
Laura , I got your question on the competition. I'm going to turn that over to Tony Casciano. I think we can be at, but I think just overall, yeah, certainly it's driven by the data that we saw today on the efficacy and the safety side. Then the convenience is that added upside, but I'll just turn that over to Tony Casciano.
Yeah, it's a great question. I think the short answer is both convenience and the strength of data. I think that those two 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 to a patient's home. We've done that in 2 consecutive trials and as little as 8 doses. We think that's extremely compelling. At a more granular level, how do we think that this profile expands the market? We're calling this at a doubling. We believe this market can at least double at maturity. We get there in a couple of different ways. The first of which I think we said before, our market research continues to read back that as many as 30% of patients that are offered TEPEZZA today decline therapy.
One of the top reasons they state often is the burden and logistics involved in an infused product like TEPEZZA. They're just not willing to sign up for that. We do believe that with a profile like veli, many of those patients who say no today will say yes with the availability of a profile like veli 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. We think a key to unlocking some of these patients that are on the sidelines today, particularly in the chronic population, is by activating more physicians who are currently seeing them. This is general ophthalmology, but also endocrinology. Here's a place where we agree with Amgen's the opportunity of creating new prescribers in this area.
It's a strategy they've been employing for a couple of years now. 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 veli, again, that can be delivered safely and simply to a patient's home, changes the willingness of a physician to initiate IGF-1R therapy with patients that need it. The third way, when you do that, when you activate more physicians, you inherently will address more patients in addition to lowering the bar and sliding patient selection more to the moderate and mild side of moderate to severe. We know with a profile like veli from a market research that physicians start to view the patients differently and tend to offer an IGF-1R to more mild patients. That's just not in chronic, that's across the board.
A fourth way that this market grows, which is a bit agnostic to TED and agnostic to veli and veli, it has to do with just the increased promotional effort. Again, this $2 billion 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 promotional effort behind an IGF-1R. We believe it's reasonable to assume that that in and of itself will also expand the market. Four ways we think this doubles, at least doubles. Of which, again, with the three options that we just discussed of veli, Q4, LAQ8, we believe we have an answer for most of those patients.
Thanks very much.
Your next question comes from Rami Katkhuda from LifeSci. Please go ahead.
Hi, James. Wanted to pass along my congratulations and thanks for taking my questions as well. I guess in both REVEAL-1 and REVEAL-2, proptosis benefit looks better with Q8 week dosing, while diplopia improvements were greater in the Q4 week arm. Do you believe these trends are due to variability of the disease or do you have any additional hypotheses as to why that's the case? Maybe from a commercial perspective, do you know what % of the chronic TED 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 at the end of the day?
Thanks for the questions, 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 PKPD as well. Once again, just like in REVEAL-1, we saw PK levels as predicted pretty much similarly to our modeling there. That also matched REVEAL-1. On that PD biomarker, IGF-1 levels, we also saw in both Q4 and Q8 arms that same 4 to 6x increase from baseline of IGF-1, which we've come to expect for a full antagonism, full antagonist for IGF-1 receptor. All of this is consistent with our belief that the receptor is fully saturated, even at that Q8 dose.
Taken all together, it's not surprising that the clinical outcomes on proptosis would be similar for Q4 and Q8. We do see a difference in diplopia. This is now the second large pivotal study where we consistently see that Q4 diplopia response in performing better than Q8. I think it just in general, you know, puts us in a really great position to be able to offer both regimens. You know, ultimately proptosis and diplopia are different. They have different, potentially underlying biological drivers for that. Diplopia is more than just the bulging of the eyes and, you know, consistently across our data it looks like diplopia is potentially a bit harder to treat.
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 a excellent experience with the Q8 regimen, with the proptosis response that they would see in just 3 doses, again, in a simple auto-injector. For subsets of patients, as Tony mentioned earlier, those with diplopia burden, the Q4 weekly arm would be a regimen that would really benefit them as well.
Yeah. I'll take the 2 questions. 1 on chronic penetration. It's low single digit. 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 from chronic, and the resulting penetration is extremely low. There was a question in there about endos and do we believe that endocrinology will play a bigger role kind of post a product like elegrobart. We believe the short answer is yes. This is an area, as mentioned, where Amgen has been pushing hard over the past year or 2 to both promote TEPEZZA and create prescribers. They've been limited by their profile, I think they're spot on with the opportunity there.
Why endo? You know, a lot of these patients, the chronic patients in particular, who are being seen long-term for their underlying Graves' disease are being seen by the endocrinologist. So we think that's a more direct path for some of these patients, and we think that the Ellay profile will be more conducive to an endo wanting to prescribe an IGFR. From a synergy perspective, I think it's important to note one of the reasons why we love this setup so much is at launch we'll have some level of effort on infusion centers in support of Veli. As we introduce Ellay into the market, if approved, we're able to reallocate some of that effort away from infusion centers and towards endocrinology. Again, another nice strong synergy between the two products that sets up nicely for Viridian.
Makes a lot of sense. Thank you.
Your next question comes from Michael Yee from UBS. Please go ahead.
Thank you. Good morning. 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? Wanted to think about how we should expect or how we should think about the cadence of the launch given 2nd to market, but a better profile. Also obviously they may have had pent-up demand or just a bolus. Maybe compare and contrast that and how you think we should think about the first couple quarters of a launch around the corner. 2nd question is, obviously, you reported EPS, you know, there's lots of other pipeline going on too.
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 'cause you're waiting for the longer acting data that is re-reading out later this year. 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? Thanks.
Yes, 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 to market biologic. You know, we would anticipate, you know, roughly 6 months to get to critical mass on coverage. You know, 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 infusion centers. 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, you know, 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 through medical exception. This is an area where, you know, there's an expectation that there'll be PAs required to access this product. This is not something that's new to these offices that are running TEPEZZA today. They are set up for it. They understand that they'll need to, you know, potentially have discussions with the payers and a couple rounds of a PA. That's not new. That's not something that would be unique to Veli. A long way of saying, you know, we've done everything we can to accelerate.
Payers will still take the time that they take to review. We have to wait for their P&Ts to meet. We're ready to jump on those opportunities as they present and would expect critical mass around the six-month mark.
I'll take the second question on FcRns and what we will be looking for later this year. We have 2 molecules there, VRDN-006, which is a Fc fragment, which we believe is the only other fragment that is in development besides the approved product. That is a potentially exciting profile for that program. There we saw in healthy volunteer studies exactly what we would have expected to want to see. You know, IgG reductions in line with the class, sparing of albumin, LDL, generally well-tolerated. We will share this year the nextsteps for that program. The development plan and how we're thinking about the 006 development path.
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're actually been enrolling patients in the phase I healthy volunteer study. 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, LDL, which by the way, we saw all of that in non-human primates in the preclinical setting. The half-life here was 3 times that of efgartigimod when it was performed in a head-to-head study. More importantly, that led to a more sustained IgG reduction.
We think the potential for this molecule is pretty tremendous with that half-life extension. As you may know, the data from non-human primates in the FcRn space has historically been very translatable to humans. We're excited about having that data second half.
Very good. Thank you.
Your next question comes from Joseph Schwartz from TD Cowen. Please go ahead.
Hi there. Good morning. Congratulations on the update. Thank you for taking my question. 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? Maybe how often are chronic patients actually coming in to seeing physicians either for underlying Graves' or something else? Just trying to understand a little bit more how hard it's gonna be to maybe access this segment or easy. 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 gonna go in the initial BLA submission? Thank you.
Thanks, Joe. I'll start with that last question, in terms of the development of the auto-injectors. We ran the pivotal studies with vial and syringe, which is a very typical way to do this so that the auto-injector development, device development is not on critical path. We do have a in parallel auto-injector study that has completed enrollment very, very quickly. That is very much on track. We do plan to submit that in time for BLA, and with the goal to launch in a auto-injector. Again, this is all very typical device development timelines and to have pivotal studies in addition to a in parallel auto-injector device study.
Yeah. I believe there's a question in there about the 30% decline and if that's, you know, different across active and chronic. Then a follow-up question on where we would need to go to access chronic patients. I think those were the two questions. The first of which, you know, patient rejection it's very unique to the patient. It depends on, you know, their view of the burden of their symptoms. I think probably less to do with if they have active or chronic disease and more to do with how burdensome their symptoms are up against, you know, the challenge of the therapy that they've been offered at that point.
Regardless, we believe introducing more convenient options like first veli and then eventually, veli, whether that's a Q4 or Q8 dosing regimen, is an opportunity to improve that acceptance rate. From an accessing the chronic population. You know, these patients are being seen long-term on a regular basis by endocrinologists for their underlying Graves' disease. This is not a situation where we need to, you know, advertise to patients to have them go see a specialist. It's why we believe targeting endos with a product and profile like veli will give us access, will activate physicians, and actually activate more mild patients in the process.
Great. Thank you.
Your next question comes from Gregory Renza from Truist Securities. Please go ahead.
Hi, guys. It's Anish on for Greg. Congrats on the data. Thanks for taking our question. Maybe just one on the low subgroup analysis. Given that the patient subgroup samples here comp to the TEPEZZA phase IV data, how do you plan to leverage these data with regulators, docs, and payers? Obviously, understanding the differences between IV and sub Q. Just wanna get a sense of how you're thinking about tapping into these patients that, you know, we've been talking about that are otherwise sidelined. Thanks so much.
Yeah. Thanks for the question. Yeah. 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. 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 subgroup 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 veli.
As we mentioned, this is a critical part of the chronic patient population that will really unlock getting these patients off of the sidelines and onto therapy.
Yeah. Then just commercially, I think, you know, 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 TED patients with that low of a activity score, that there's a benefit to be had, with an IV, let alone, you know, being able to offer that in-home. 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, you know, a really exciting data set to bring forward into the market.
Thanks, guys.
Your next question comes from Douglas Tsao from H.C. Wainwright. Please go ahead.
Hi, good morning. Thanks for taking the questions. I guess 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. I'm just curious, do you plan on sort of trying to actively segment the market in any way across dose regimen? Do you think that perhaps, you know, these are, you know, sort of not necessarily, you know, sort of full subgroups and that you're gonna sort of leave it to the option for clinicians to sort of sort out themselves? Thank you.
Excellent question. We are really excited about being able to offer a choice to physician and patients within the veli profile. Not something that we would push or pull towards. We think it naturally sets itself up as mentioned before, that the Q8 would be the go-to regimen for most patients. If the patient happens to have, you know, a heavy diplopia burden, Q4 might be a better choice. We would leave that entirely up to the physician and the patient. We think that's a choice that physicians would welcome. You know, perhaps another attribute that we can differentiate on the attribute of choice, where they have just one choice today.
Maybe as a follow-up, when we think about patients starting on the Q4, what do you think about a sort of access standpoint, 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, you know, rather than sort of completing treatment and then, you know, coming back? Thank you.
Yeah. I think there's a, you know, payer access question in there, which I'm happy to address. Obviously it's early to be disclosing our, you know, payer or pricing strategy. 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, you know, considering a WAC price or list price for an average patient on TEPEZZA of over $500,000. A really nice job. They've created a lot of room for us to navigate.
When we talk to payers, what they tell us on a consistent basis, you know, if, veli, and also Ellie, is priced at parity to a typical patient for TEPEZZA, that they would anticipate giving parity access, which we'd be really happy with. One more point on Ellie in particular. 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 of therapy.
Great. Thank you very much.
Your next question comes from Alex Thompson from Stifel. Please go ahead.
Hey, great. Thanks for taking our question. I guess maybe as we think about kind of the rest of the data to be generated for elegrobart over the next, you know, the rest of this year, how should we anticipate 52-week data updates relative to what we've seen for veligrotug? What other data generation is there prior to BLA submission? Thanks.
Thanks for the question, Alex. These studies are obviously top line data, and we are following patients for a additional 28 weeks to that full 52-week period. 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. In terms of the additional data coming in from the trials, you know, I think the expectation is that it would be consistent with what we have seen so far.
Great. Thank you.
Your next question comes from Paul Choi from Goldman Sachs. Please go ahead.
Oh, hey guys. Congrats on the exciting data for REVEAL-2. We heard that from some clinicians that they prefer using corticosteroids for the low CAS chronic patients. I know you didn't study the corticosteroids here, but how do you think veli's data here would compare to corticosteroids as you could ultimately compete with those in a chronic setting? The second question is that, you know, you mentioned previously that you'll price value or veli as a total treatment course around TEPEZZA's price point. What is that strategy for veli's Q4W relative to Q8W? Will Q8W be proportionally priced to Q4W based on the number of injections? Thanks.
Yes, I can take those. The first question on how we believe veli would compare to steroids. Obviously, there's no head-to-head comparison against steroids. I would offer up, I think, where you're seeing steroids being an option for your, you know, kind of low cast chronic patients today was before this data. Again, going back to the point, their only choice right now would be steroid surgery or eight infusions lasting up to six months, 60 to 90 minutes out of whack, right? For a patient that's been living with a 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 veli in the market, being able to deliver an IGF-1R to a patient so safely and simply in as little as 3 doses, I think changes the calculus for patients and for physicians in that patient subgroup. From a pricing perspective, maybe I'll just cut to the quick. I think we view Q8 as the workhorse for veli. We think that'll be the primary choice. As noted, payers view this class on a course of therapy basis. They will base the veli price, 5 infusions versus TEPEZZA's 8 infusions when making pricing decisions. We think they do the same when it comes to veli, and we would have those negotiations and discussions based on a Q8 regimen.
Great. Thank you.
Your next question comes from Lachlan Hanbury-Brown from William Blair. Please go ahead.
Hey, guys. Thanks for the questions and congrats on the data. I guess maybe a quick one just on the background of patients in the study. You know, what prior therapies they had. I assume obviously not a prior IGF-1R, but maybe, you know, were there any differences or how representative were the prior therapies between steroids, rituximab, other off-label things to the broader chronic population today? Maybe second, Tony, you talked about sort of the reallocation once veli launches from IV centers to endocrinologists and maybe general ophthalmologists. 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 veli?
Yeah, I'll take the second one first. Yeah. The short answer is yes. We built this sales force with veli in mind, and believe that that transfer of effort 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. We believe we can cover it with the roughly 100.
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 is really IGF-1R therapy. You know, these are basically treatment-naive patients with regards to IGF-1R class approaches. They may have had other medications like such as steroids, for instance.
Oh, thanks.
Your next question comes from Derek Archila from Wells.
A bit about the low penetration of TEPEZZA in the beginning of the call and then a doubling of the TED market with veli. Could you break this a little further for us?
Yes. Hello, your next question comes from Andy Chen from Wolfe Research. Please go ahead.
Hey, this is Brandon for Andy. Thanks for taking the question. 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? How are you defining patient starts form? Is that gonna be after a patient's already clear prior auth with infusion centers, or is that gonna be before clearing prior auth? Thank you.
Yes. I'll take that question. I think maybe we'll go back to Derek. I think he got cut off there. Yes. 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 labeling 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 I think 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. At enrollment all the way through the process, all the way to, you know, 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 cite that came up before, that we'll obviously be watching, keeping close eye on, and reporting on, will be just our level of payer coverage and how fast we're able to attain that.
Thank you.
Operator, let's get Derek. I think he got cut off. Let's let him back on, please.
Sure. Your next question comes from Derek Archila from Wells Fargo. Please go ahead.
Hey, can you guys hear me okay?
Yeah, we can hear you now, Derek. Sorry about I don't know how you got cut off last time.
Okay. No worries. This is Jacob on for Derek. Thanks for taking our question, and congrats on the data. You mentioned a bit about the low penetration rate of Tepezza at the beginning and then a doubling of the market with veli. I was wondering if you could just break this out a little further for us and talk a bit about your expansion projections in chronic TED based on this data. Similarly, what you think these projections look like in active TED?
Yeah, great question. We actually see a double-digit across the board, actives and chronic. Obviously chronic is the most underserved today with a lack of options that they find compelling. Starting from a relative, you know, small, relatively smaller base, as cited with the penetration rates of over 80% of current use coming from actives. We think that the profile of Ellay will be attractive across, actives and chronic, to be quite honest with you. Again, for the reasons stated, we believe that we improve the rejection rate, we add prescribers, we slide, we enable more mild patients into the IGF-1R discussion.
Just the increase in promotional effort, roughly doubling the size of promotional power behind an IGF-1R, we think also increases the size of the market.
Great. Thanks. To Brett again.
There are no more questions at this time. I would now like to turn the call back over to Steve Mahoney for the closing remarks. Please go ahead.
Yeah, great. Thank you. Really happy with the data. As you can tell, we're really happy about the profile of Ellay in the Q4, Q8, adding that to veli with the IV launch expected soon. We look really forward to being able to serve the TED patients with this suite of products. Thank you everyone for listening today, 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.