Viridian Therapeutics Inc Aktie

All right. Good afternoon. Let's kick off our next session. It is my pleasure to host Viridian Therapeutics. And with me, we have Steve Mahoney and Shan Wu, CEO and CBO of the company. So a lot to talk about, very, very exciting year. Very. But before we go do it, I'm going to kick it off to Steve and Shan for opening remarks.

Yes. Thanks, Rich. Thanks for having us. We appreciate it. We are on the verge of commercial approval. We are -- have a PDUFA date of June 30. So very short time period until we are -- we expect to be on the market.

All of our regulatory interactions have been consistent and positive and give us a lot of confidence going into that PDUFA date. We are right on track with everything. So that's exciting. We can talk about launch dynamics and that type of thing in more detail as we go. We obviously also had our top line readout from our subcutaneous studies, REVEAL-1 and REVEAL-2, both highly positive studies, both proptosis response and diplopia.

We are advancing our Q 4- and our Q 8-weekly dosing regimens with a BLA submission targeted for Q1 of '27. So also exciting because we think that's a potential -- has a lot of potential in the TED market going forward.

We also have a TSHR program that we have guided to an IND in Q4 of this year. So that's exciting, too, because that gives us applicability both in thyroid eye disease, but also in Graves' population, which is exciting and complementary to the portfolio.

And then finally, we have our FcRn portfolio is continuing to move forward. We have -- we have finished our first-in-human for our 006 program, which looked just like it should in terms of IgG suppression and albumin-sparing that looked great.

And now we're waiting on the results from the first-in-human we're working through our first-in-human study on the 008 program, which is a half-life extended approach for FcRn. So a very exciting portfolio turning into a commercial company, but a lot of great stuff in the pipeline.

Got it. So the PDUFA is coming June -- any time, right? June 30? With the PDUFA date. I mean I think we've seen it where some of these PDUFA moving ahead of time. So with that, I don't know if I'm -- yes. Can you give us an update on the launch prep? Are you guys just ready to go? You just pushed the button and sales force is all trained up. Like where are you with that process?

Yes. We are all ready to go across the board. So we have -- the sales team has been on board for -- they came in, in certain waves, but all the hiring has been done. They're trained on -- we know the label is somewhat predictable. So we've been able to train them. They're obviously not -- they're not out there talking to physicians about anything yet. But they are -- they do have the ability to at least have -- make an introduction and have a nonproduct-specific conversation.

So that stuff is all good. We've had our medical affairs team is out in the field for quite some time, which is great because they're able to talk about the data from the clinical trials. And we have our patient support services, which is also built and ready to go. Supply chain is ready to go, market access.

So in all of our systems, our internal G&A support for launch, everything is ready to go. So we are operationally launch ready. We've actually been launch ready for a few weeks now. So we are all ready to go. We can accept patient enrollment forms the day after we get approved. So we're ready to go.

Okay. More questions on that topic later. But the FcRn, I think you mentioned that we'll see updates on the FcRn for 006 and 008. What data will you be presenting? And also, are you going to be presenting the actual indication that you want to develop into? And then also how would you differentiate from...

Yes, I can take that one. So we have 2 programs with FcRn and 006, which is an Fc fragment, and we really like the Fc fragment. We think there may be something special about a fragment that the full-length antibody so far have not been fully able to replicate the safety and efficacy of the currently available fragment and 006 would be the other one that is in development.

We've communicated that Phase I studies from -- in healthy volunteers, the data looked as expected. So IGF-1R IgG suppressions in line with the FcRn class sparing of LDL and albumin well tolerated. So very clean profile across the board. So that's exciting for that program.

And then 008, which has the half-life extension that we've talked about. It's the difficult to engineer half-life extension into an FcRn molecule, but we've been able to do it. And that is in ongoing healthy volunteer studies right now, Phase I, and we expect data second half of this year. And with that, we will plan to look at and disclose and share the healthy volunteers data with regards to IgG suppression.

We want to see that in line again with prior studies and what we have seen in nonhuman primates, which historically have been very translatable to humans. We'll want to see tolerability and in particular, with regards to LDL and albumin to see that being spared, which again, we saw in primates, so looking to confirm that.

And then importantly, looking to confirm the half-life extension, which, again, head-to-head versus efgart in the primate studies, we saw longer half-life, 3x the half-life as well as more sustained IgG suppression. So that will be very exciting data from a healthy volunteer standpoint to confirm that in humans, which will allow us to really extend the dosing interval between doses of FcRn, which we think could be a game changer for patients.

Both of these programs, we've designed to be subcutaneous and patient self-administered, which is still an unmet need for patients in FcRn. And so we believe that we will be able to move the field forward with either one of these profiles.

Right. I see. Okay. And then you will be disclosing the indication and then sort of the development plan for those indications.

Yes, that's right. So for each of these programs, we do plan to update everyone on how we're thinking about next steps in development indication strategy, correct.

Fantastic. Okay. And you guys recently raised $300 million to equity and convertible senior note. And I remember you guys mentioned that you guys already have enough capital to kind of sufficiently take the company to cash flow positive.

So was that just to pay down, I think, the Hercules Capital credit facility? Is there anything beyond that? Is there any consideration to pay off the DRI financing deal as well? Like what's -- anything there?

No. Well, so what we did is, yes, we were able to pay down the Hercules facility, lower our cost of capital as a result of doing that. So that was a smart corporate governance for us to be able to do that. We also talked about the fact that we have this TSHR program that I referenced in the introductory.

And we are also looking at ways of possibly retreating in the Veli program, in the ELE program. All of the commercial activities, all the commercial launch for both Veli and ELE were already covered. We thought it was a good idea to take advantage of the convertible market terms. Very favorable market. We thought that was a good idea.

And then we did a small equity component to it as well. But yes, we are -- yes, we were guiding towards profitability before that deal, and we're obviously more comfortable and more comfortable territory given additional capital. But again, we've got a lot of really good investments to make here across the portfolio. So we look forward to that.

Can you share like the sales force that you guys have already ready to go? How many are there? Are they structured like dedicated by specialty like are they all target different doctors? Or are they more like some are for endo, some are for ophthalmologists and some are for surgeons? Like how are you guys thinking that?

It's more geographically laid out for the sales force. Sales force is a little under 100. And then on top of that, obviously, we have medical affairs team, which is a crucial part of kind of rare disease commercial efforts as well with respect to being able to go through all the clinical data in detail with folks.

And then we have the patient support services on top of that. So we have a concentrated call point here where there's really 2,000 core prescribers that we need to reach. They are identified in the claims analysis. We know who they are with respect to -- this is the group that writes primarily all of the -- or essentially writes all of the TEPEZZA prescriptions.

So we -- that is our target audience. And so we are rightsized for that because, as you know, TEPEZZA is a $2 billion steady-state product right now, and we think adding our voice to that, adding particularly our profile of Veli into that prescribing habits is -- that's the target. So that's -- the sales force is set up to do that.

I see. Okay. And then so when I turn on TV, I see a lot of TEPEZZA commercial, right? They're everywhere. And so from a resource perspective, Amgen is obviously putting a lot of resources in there. Sound like they probably have more sales reps than what you guys -- what the number that you guys quoted. Just given all that, are you concerned about just not matching the resources?

Would you consider like from a DTC perspective, will you consider matching to what Amgen is doing? Or are you -- or is there like other more innovative type of channel that you can go and not have to spend the same type of money toward those campaigns?

Yes. So a couple of points. First and foremost, their sales force is not that much bigger than ours. it's incrementally bigger at most. So we are correctly sized, particularly relative to them. In terms of direct-to-consumer advertising, I don't think you'll see a lot of us do it. We can do a lot of that on social media.

Obviously, there's a lot of easier ways to do that from a capital allocation standpoint. But I think more importantly, we applaud the direct-to-consumer that they're doing. It's good for patient education, physician education that they've been doing for a while, payer education they've been doing for a while.

We get to take advantage of all that. All that legwork that they do is channeling those patients to the physicians that we're going to be calling on. And I think the physician reaction to having another treatment option available to them is really exciting.

This is the first time with -- if once we get approved, we'll be able to offer the only other treatment option that's been available. And physician -- we think there's a lot of physician excitement about that. We think there's a lot of patient excitement about that. So from a resource standpoint, that's all channeling to the places where we're going to be.

I see.

And remember that this is a new start market. So patients are not -- we're not looking to switch patients off of any treatment that they are on and doing well on because everything is fixed dose.

The currently approved treatment is fixed dose. Veli IV will be fixed dose. It's a shorter course of treatment actually from a fixed dose standpoint. And so we expect those patients in terms of raising awareness and channeling those patients to physicians to be a potential new start patient for Veli as well.

We feel really good about the clinical profile and soon to be -- we anticipate commercial profile for Veli, given the data that we generate in both THRIVE and THRIVE-2, in particular, the points of differentiation that we've talked about before that form the basis for our applications for breakthrough therapy designation as well as priority review, first of all, rapid onset of treatment effect on the active side. Chances are a patient who starts therapy will have already had a proptosis response after just infusion after 3 weeks.

And then secondly, diplopia improvement and resolution for these patients, in particular, on the chronic side, which Veli is the first drug -- drug candidate, I should say, to have shown that level of diplopia benefit and statistically significant in chronic patients.

And we offer all of that with a shorter duration of treatment in just 12 weeks that a patient will complete the entire full course of treatment. And then each infusion is only 30 to 45 minutes long.

And remember that this is a market that's primarily made up of women in their 40s and 50s. It's an autoimmune disease. These are people with very busy lives with families and jobs and just the active -- activities of daily life in that age group. And so the ability to bring, as Shan just referenced, a shorter treatment period of just 5 infusions, shorter infusion times, just on a logistics basis of the clinical profile is what it is with the differentiation that we think that Shan just referenced, but then simply just ease of the treatment.

Okay. Got it. So the PDUFA is coming, we're going to see your label coming out very soon. How do you think it's going to be -- how do you think it's going to differentiate against TEPEZZA's label? I mean I think a lot of -- Shan, I think you highlighted a lot of things there that some of these advantages that we saw from the THRIVE trial. Do you think like how would those be reflected in the label relative to how TEPEZZA show? And also, obviously, I think the chronic data, right? They don't have chronic data in the label, you will. But what are some of the other key differentiation, especially those points that you mentioned?

Yes. Those points that I mentioned in terms of rapid onset of treatment effect, diplopia response and complete resolution all in a shorter course of treatment, those are the key data points from THRIVE and THRIVE-2, our 2 pivotal studies.

So we would anticipate having that data in our label in both active and chronic TED, in which case, we would be the first drug approved for thyroid eye disease with both active and chronic data in our label.

So that's a major differentiation point for the label. Remember that when TEPEZZA was first approved, the indication was broad. It was for not just restricted to active TED, which was the basis for their registrational trials, but inclusive of all TED patients. And so we do think the FDA views this population as a continuum of disease and does not necessarily differentiate between active and chronic TED.

And so we expect to also have a broad indication. But the labeling, again, this is where Horizon has done a very good work in getting a clean label on both the efficacy as well as safety data that's in there, and we get the benefit from that, but replacing the data with the data that we generated from THRIVE and THRIVE-2, which we think are very compelling.

I see. Okay. And then -- so I know part of the launch prep, you guys go in -- I mean, every company do a lot of these qualitative and quantitative market research with payer prescribers and patients. What are the findings there in terms of like how many of them actually recognize that differentiation that people actually recognize it and would be -- would see that as an advantage for them to...

I think what's more important when it comes to the payers is the feedback that we've gotten is we've been in communication with the payers for quite some time, including the preapproval information exchanges that you can do now.

I think what's really critical and important is that now that TEPEZZA has 85% of commercial insurance plan coverage for -- in the U.S., which has taken a bit of time, but it's a great setup for us to walk into.

And so our interactions with payers have been essentially their communication to us is you can get parity coverage at a parity pricing. So they recognize the value of IGF-1R. I mean, particularly when you look at the competitive landscape from 1.5 years ago where you had -- or 2 years ago where you had IL-6, which didn't quite pan out.

They failed one of their studies, IL-11, obviously, that didn't go forward either and then FcRn as well, right? So when the payers fully recognize the value of IGF-1R. And so when they look at our profile, the feedback has been coverage, which is a great place to be 85% of coverage is to step into. That will take a bit of time just because -- every plan has its own kind of time lines that we have to deal with, but it's a great spot.

But so you don't think that they're going to use preferred or exclusive contracting. Do you believe in your research, most of them are saying that, look, parity access would be something that...

Yes. That's the feedback.

We're not going to try to get you guys at each other.

No, we haven't seen that.

Interesting. Okay. So when do you -- so and again, going back to the market research with the prescribers, some prescribers are very comfortable they've been using TEPEZZA for years, right? They're very comfortable whether they know inside out in some way.

There's a new product coming out, they don't really have experience with it. How many -- I mean, like for those doctors, do you -- I mean, how long do you think it takes for them to kind of get used to it? And how many prescribers are in that camp? Was more or less just want to stick to what they know and not very adventurous to try something new. How many are in that camp versus how many are more open to like, look, I saw the data from your THRIVE trial looks very encouraging. I want to start trying.

Yes. The latter is the overwhelming response that we've gotten. It has been very consistent that there's a lot of excitement around the availability of a treatment option and a willingness to try that. I mean, for all the reasons that we talked about with the rapid onset, the diplopia data and the treatment regimen.

Those are exciting prospects for the first time since -- in the last 6 years. So there's a lot of willingness to try. And now our job is to make sure that we make those experiences as good as possible for both, obviously, for the patient, first and foremost, but the physician as well. And I think that will go a long way.

We also enrolled high-volume TEPEZZA prescribers in our clinical trials. So many of these physicians already have experience with ELE and actually, in fact, probably have had experience with ELE since there was good overlap in trial sites for both of the 2 programs.

And of course, as we mentioned, our medical affairs team has been out there talking with these 2,000 core prescribers so that they are well educated on first aware of Veli as a potential option and also well educated on the data that we've generated from THRIVE and THRIVE-2.

And it's helpful that it's the same mechanism. It's IGF-1R. We are a full antagonist. And so that for physicians, understanding that it is the same mechanism is also very helpful.

I see. Okay. Let's talk about the chronic patients a little bit here. TEPEZZA has been struggling with these patients, single-digit penetration. What's the potential of Veli in that chronic TED setting? Is it just because you have 3 less infusion and suddenly that opens up, like how should we think about that chronic setting? Is it more -- or should we have to wait for the subcutaneous for ELE to come up in order to be better penetrate that population?

I would say that our strategy out of the box, as we described, those 2,000 core prescribers is more of a conversion of their prescribing habits. And currently, they prescribe probably on an 80-20 basis active versus chronic.

We do think that the profile has the potential -- the Veli profile and IV has the potential because it can possibly make the logistics side of it easier that might bring some people off the sidelines from a chronic perspective.

But in the short term, our strategy is to convert those current prescribing habits and so we can grab share. Reminder, this is a $2 billion market with a single product. So the ability to come in, have an option, grab some of that market share in those prescribing habits, that's the main priority in the early days.

We'll see how -- we do think it's going to be attractive to chronic patients. And then obviously, when we come with the subcu, that really unlocks that chronic population because the urgency to treat, depending on where they are, and there's -- it's such a continuum of or spectrum of patient experience on the moderate to severe, where they fall on that index. And we do think that the subcu would be instrumental to unlocking a lot of those chronic patients.

Yes. So I mean, given that these chronic patients have like a very highly variable disease and likely less severe in terms of symptoms and inflammation. I mean, how are they being treated now if they're not using TEPEZZA? And also, what proportion of them truly need an IGF-1R?

Yes. So we ran the 2 largest studies that have ever been run in chronic patients. And these are patients that, by definition, to get into the studies, had more than 3 millimeters above normal proptosis. We had a very high percentage in the -- both THRIVE-2 and THRIVE and REVEAL-2 with the chronic studies where they had diplopia as well.

And so these -- the symptomology, because there's a lot of variability in that chronic population, we did enroll patients in our chronic studies that had both proptosis and diplopia, and they had low clinical activity scores or they had high clinical activity scores. So -- and that's basically a proxy for pain and inflammation.

So there's a lot of variability. And we think that the chronic population has not particularly gravitated towards the currently available therapy, primarily, in our view, from our research because of the profile.

It's -- I mean, if you think about it, it's -- if you've been living with the disease and you're being asked to go for 6 months of infusions, that can be a lot, particularly, again, as I mentioned, this is women in their 40s and 50s with very active lives.

And so our whole approach here, both with IV and with subcu is to try to make things easier. And we do believe that, that's going to resonate with that patient population and expand the market there. But we think that's primarily a profile issue...

We enroll both of those chronic studies very quickly. So THRIVE-2 on the IV side as well as REVEAL-2 on the subcu side. And the majority of the REVEAL-2 study came from the U.S., 56%. And that's with a commercially available therapy that's here in the U.S.

So that is a good signal for the motivation that these patients have to seek treatment and their willingness to come on to treatment to have their -- the symptoms of their thyroid eye disease be addressed. We think that they're just being underserved right now by what is currently available.

I see. Okay. Let's move on to ELE. We don't have a lot of time left. So there's a lot to talk about it there, too. So you guys presented the Phase III results for the REVEAL-1 in active and REVEAL-2 in the chronic study. REVEAL-1 fell short of your own expectation that within TEPEZZA's proptosis response. But REVEAL-2 showed IV-like results that fell between TEPEZZA and Veli's proptosis response. How do you sort of reconcile the difference between these 2 studies?

Yes. Look, I think as a reminder, REVEAL-1 was highly static on the primary endpoint, the proptosis reduction for Q 4. We saw very clinically meaningful responses in diplopia in the Q 4 arm. And then the Q 8-weekly arm is an option for patients where we saw really good proptosis responses. That was in the active study.

And so we -- then we saw that reinforced to your point, on REVEAL-2, highly stats seeing on proptosis response for Q 4, but we also saw very good response on diplopia. And so the Q 4-weekly option, and our intention is to move forward with both of these treatment options, Q 4 and Q 8, Q 4 looks very promising proptosis and diplopia.

Q 8-weekly promising for people with -- where diplopia may not be their main complaint, but proptosis is. And just if you think about getting -- this is IGF-1R in an auto-injector pen. So everyone knows that IGF-1R is the mechanism that actually is the most effective in this disease population.

And so the ability to put IGF-1R in an auto-injector pen that's very simple. It's at home, patient administered at home, that is going to be very meaningful for this patient population because if you think about where we fit, we've got IV. We get an IV that we just talked about for all the reasons that, that's a very attractive profile. Q 4-weekly for proptosis and diplopia patients and Q 8-weekly for proptosis.

So we have an answer. We believe we have an answer for any patient that walks in with moderate-to-severe TED. We can address it across. And so those studies reinforce both of those profiles.

I see. Got it. So even though ELE's inhibition the IGF-1R saturated and you guys showed similar PK/PD profiles. Why do you think that the REVEAL-1 and 2 results were lower, right?

Yes. So just right. So we had the PK/PD, both looked like they were supposed to in terms of on the PK side, what we saw there plus the IGF-1 levels that we would see from the PD side.

So the drug did what we expected it to do. We may have seen some clinical variability in REVEAL-1. But then REVEAL-2, as you pointed out, brought that as expected, brought that you like efficacy.

So I think that kind of reinforces the profile. You may have seen some variability in REVEAL-1. But at the end of the day, we've tested these profiles with physicians and the response has been overwhelmingly, okay, that looks like IGF-1R in an auto-injector pen.

That's a great profile for us. I think that's the bottom line. It's very simple. Everyone knows that IGF-1R is the right mechanism. And now we're -- we expect to be able to pen in an auto-injector.

Okay. Got it. So when you think about the patients that are suitable for ELE versus Veli, how do you think about that setting, right? You have these products come out in the active setting and the chronic setting, how do you think -- how do patients choose between...

Yes. I mean a little bit to repeat myself, I guess. But on the IV side, we think there's an IV appropriate patient population, no doubt. As you go up the index and severity and that urgency to treat, they're very well -- we expect forever, we expect there to be patients that will be appropriate for IV, whether that's because their physician wants them in a controlled setting like an infusion center or the patient wants to be in a controlled like a sight-threatening patient, you would want to put them on IV.

And we have -- that's what we have Veli for that kind of severe. And we think it's obviously done very well with the moderate end of that spectrum as well. So we think that's a great option. When subcu is available, we do expect that the patients that are non-IV that Q 4-weekly has that impact on proptosis and diplopia and then the Q 8-weekly is really geared towards the proptosis. Again, we cover that spectrum of patients, and we have an answer for anybody who walks in.

I see. Okay. So I always look at chronic and the active patients as 2 very different and distinct populations in some way. Is there -- and therefore, because of that, you need different products that cater towards their needs. Do you -- I mean, do you share this view that these are sort of 2 kind of distinct patients? And then also, if that's the case, then what product attribute do you believe that are more suitable for active and chronic patients?

Yes. We -- the way we look at it is there's certainly the active population, again, along that spectrum that I described for moderate to severe. But there's also that same moderate-to-severe spectrum in chronic.

You'll have patients that have lived with the disease, but they're not necessarily complaining about the pain and the inflammation that goes with it. They may have settled into their proptosis. Diplopia is a little harder to settle into, but there is some element of that. So we call them kind of like a chronic stable population, which is really where TEPEZZA was studied in that population. But then there's a chronic flaring population is what we call it.

So these are people -- as I said, we had people to get into our studies. Again, the largest studies ever run in these chronic to get into our studies, you had to have above normal proptosis and a large percentage had diplopia as well.

So there are patients in that chronic that, again, to Shan's point, they enrolled that study quickly. They're the biggest studies ever run. And so it speaks to the market demand that's still out there for these patients. But yes, there is a distinction, there's a lot of chronic patients. It's very underpenetrated, which is the opportunity in front of us with both Veli and then obviously ELE subcu.

Right. Got it. And then I do want to ask you this question. So besides the OBI from Amgen, they have another IGF-1R subcu asset in development called AMG 732. So this is -- I believe this is another legacy product from Horizon's acquisition. I think it's in Phase I/II development and it's a new molecular entity. So designed for subcu, not like TEPEZZA OBI, which is really just more like TEPEZZA, we formulated for subcutaneous.

So given that this asset and then TEPEZZA OBI is not being developed for chronic TED. And my guess is that this one could be. How do you -- have you heard much about this asset and your thoughts about it so far?

Yes. Let's start with the OBI for a second. The OBI is 4 inches long, 2 inches thick. It's got gears, batteries. You have to insert the cartridge into yourself. You have to wear it on your abdomen for up to 30 minutes. It's an infusion. It's not a subcu. It's an infusion pump that you wear on your stomach.

You have to do it every 2 weeks for 24 weeks. So not really clear where that fits into the competitive profile. Compare that to the auto-injector pen that we have, which is the same pen that DUPIXENT's use very patient-friendly. A lot of people are familiar with it.

So we don't think that's really -- we don't really see that as a competitive profile in this. It's just not sure where it fits. With respect to the Amgen 732, yes, we're aware of it, but it's several years behind. We don't know exactly what it is. We think it's IGF-1R, but we don't know exactly how it's set up. They haven't talked a lot about it, but it's -- they just got started with Phase II, so they're years behind.

Right. Fantastic. So we're out of time. Thank you so much. It's been a pleasure hosting you guys, as always. I'll turn it to you guys for any final remarks.

No. Look, we're about to be commercial. We've got a great profile, very highly supported by the Phase III data. We've got a great commercial team, very familiar with buy-and-bill dynamics. And we are -- so we're ready to go operationally and just and regulatory interactions have been great. And then we're looking forward to advancing ELEs with BLA in Q1 '27. And then the FcRn portfolio is coming too along with TSHR.

Look forward to it. All right.

Thanks, Rich.

Thanks.

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 and 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 weekly 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, 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 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 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 millimeter 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. 44% 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 reinforces ELE 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 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 after week 4, which continues 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 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 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 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 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 rate 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 ELE achieved statistical significant proptosis response demonstrating IV-like clinical efficacy. REVEAL-2 was also the first demonstration of meaningful benefit 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 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 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 TED. 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. Just 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 taking 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 in as little as 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, in diplopia resolution, which we know is one of the most bothersome symptoms with TED patients today.

So 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. 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 Nat Charoensook, 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 performed in the higher CAS subgroup and the treatment effect was consistent across baseline sensitivity?

And second, on safety, you noted low rates of impairment and that the majority of events were tinnitus. Were there any other healing-related adverse events observed such as hypoacusis? And can you comment on severity, reversibility and whether any cases were associated with objective hearing loss?

And lastly, assuming elegrobart is approved for both Q 4-week and Q 8-week dosing, how do you envision positioning the 2 regimens commercially? And how competitive do you view elegrobart subcu profile versus other potential subcu 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. 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 showed that Q4 week and Q8 week proptosis and 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. 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 to come off of the sidelines and seek treatment. And 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 those patients with hearing impairment were 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 hypoacusis, 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 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 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 now and how we view them fitting commercially. So first and foremost, we're really excited about being able to offer the value of an IGF-1R home simply and safely in 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 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 ELE 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, 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 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.

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 in 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 chronic 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. Congrats again on the data, guys.

Next question comes from Laura Chico from Wedbush.

Just 2 quick ones for me. First, on safety. 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 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 on ELE that brings chronic head patients off the sidelines? Or does this have more to do with the data from REVEAL-2? Just wondering if you can 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 I presented or I think I shared on the previous slide, 91% of the ELE treated patients actually completed the 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 foot cramp, 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 deemed 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 begin. 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 to a patient's 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 30% 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. They're just not willing to sign 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 a 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 [Technical Difficulty] 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 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 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 promotional 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 the double, at least doubles, 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 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 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 endocrinologists' offices to better capture the chronic TED population at the 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 arms, 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 of the 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 in there about endos and we believe that endocrinology will play a bigger role kind of post product like ELE. We believe -- the short answer is, yes. This is an area, as I mentioned, where Amgen has been pushing hard over the past year or 2 to promote TEPEZZA and create prescribes. 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 Graves' disease are being seen by the 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 to an endo wanting to prescribe an 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 the 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 contrast 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, sparing of albumin and 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 006 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 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 of the development of the auto-injector. So we ran the pivotal studies with vial 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 a parallel 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 to have pivotal studies in addition to a parallel auto-injector device study.

And then 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. 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 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 that acceptance rate and 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 to have them go see a specialist. It's why we believe targeting endos with a product and profile like ELE will give us access, will 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 CAS subgroup analysis. Given that the patients have samples here 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 in to 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 TED patients 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 and the 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, that 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 we generated for the later part of the next -- rest of this year, how should we anticipate 52-week data updates relative to what we've seen for 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 of ELE as a total treatment course on TEPEZZA's price point. What is the strategy for ELE's Q4W relative to Q8W? Would Q4 -- sorry, would Q8W 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 steroids. 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 lasting up to 6 months, 60 to 90 minutes out of WACC. But 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 IGF-1R to patient's home safely and simply in as little as 3 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 stop with 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's 8 infusions when making pricing decisions. We think they do the same when it comes to ELE, and we would have those negotiations and 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 they had? I assume obviously not a prior IGF-1, but maybe were there any differences or how representative were the 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 ELE 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 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 is 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 from Wells Fargo.

[Technical Difficulty] 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. I 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. I 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 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 he got cut off. Just let him 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 last 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.

There are no questions at this time. 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 TED 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.

Good morning, ladies and gentlemen, and welcome to the Viridian Therapeutics conference call to review top line results from the REVEAL-1 Phase III clinical trial in active thyroid eye disease. [Operator Instructions] As a reminder, this conference call is being recorded.

I will now hand the call over to Greg Rossino, Senior Director of Investor Relations at Viridian. Please go ahead.

Thank you, Kate, and good morning, everyone. Thank you for joining us on our conference call to discuss the top line results from REVEAL-1, our Phase III clinical trial of Elegrobart in patients with active thyroid eye disease. You can access the press release and the slides for today's call on the Investors page of our corporate website at viridiantherapeutics.com.

Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those forecasted. A description of these risks can be found in the forward-looking statement disclaimer in the press release and slides issued this morning as well as Form 10-K on file with the SEC.

On today's call are Steve Mahoney, our President and Chief Executive Officer; Radhika Tripuraneni, our Chief Medical Officer; Shan Wu, our Chief Business Officer; and Tony Casciano, our Chief Commercial Officer. Following prepared remarks, we will open the call for questions.

With that, I'm pleased to turn the call over to Steve.

Thanks, Greg. Good morning, everyone, and thank you for joining us today. We are excited to share top line results from REVEAL-1, our Phase III pivotal study evaluating Elegrobart or ELE in patients with active thyroid eye disease. REVEAL-1 met its primary endpoint, demonstrated clinically meaningful activity across multiple key endpoints and ELE was generally well tolerated.

Before we get going, I'd like to thank the TED community, the patients, investigators, partners and research staff and everyone else who contributed to this trial. We're excited to continue to advance the field and treatment of TED. Over the past several years, TED treatment has evolved from steroids or invasive surgery to the first approved IV IGF-1R therapy and now to potentially veligrotug, Viridian's next-generation IV program, which is under FDA priority review with a PDUFA target action date of June 30. While meaningful progress has been made, there remains a clear need to make treatment easier for TED patients.

Based on the REVEAL-1 data, we believe ELE has the potential to be the first-ever subcutaneous auto-injector, enabling patients to self-administer at home while delivering clinically meaningful outcomes for their proptosis or bulging of the eyes and diplopia or double vision. In other words, ELE has the potential to meaningfully impact how patients look, how they function and how they feel.

We can do this in a convenient profile in as few as 3 doses that could expand the TED market that is already annualizing at approximately $2 billion today despite being served by a single IV therapy. We anticipate submitting our BLA for ELE in Q1 2027, and we are excited to potentially bring a transformative and differentiated treatment solution to patients.

Before I hand it over to Radhika, I'd like to walk through the REVEAL -- she's going to walk through the REVEAL-1 top line data. I want to just point out a few key takeaways. First, we're pleased to announce that REVEAL-1 met the trial's primary endpoint. In the Q4 weekly dosing arm, we observed a highly statistically significant treatment effect on proptosis responder rate at week 24 as measured by exophthalmometry. Proptosis responder rates were 54% with Q4 weekly dosing at 63% with Q8 weekly dosing compared to an 18% rate seen in our placebo arm.

Second, on diplopia or double vision, 51% in the Q4 weekly arm had complete resolution of their diplopia at week 24 compared to just 16% of placebo patients. These are meaningful outcomes for patients as proptosis and diplopia are the endpoints that most directly impact appearance, function and quality of life.

Third, ELE had rapid onset of proptosis response in both treatment arms and in the Q4 weekly arm. Also, rapid onset of diplopia response and complete resolution with clear separation from placebo after a single dose. Finally, with respect to safety, ELE was generally well tolerated. We observed low rates of hearing impairment. All reported events across both Q4 and Q8 arms were tinnitus with no associated reductions in hearing.

We believe this profile from the largest Phase III pivotal clinical trial conducted to date in active TED positions ELE as a highly effective subcutaneous auto-injector that patients can self-administer at home in as few as 3 doses.

So with that, I will turn the call over to Radhika to walk through an overview of the study design and the results.

Thank you, Steve, and good morning, everyone. I'm excited to be able to share the REVEAL-1 study results with you this morning.

Let's start with an overview of the study design. The study enrolled a total of 132 patients with active TED randomized 1:1:1 across 2 active ELE treatment arms, Q4 weekly and Q8 weekly and a placebo arm. In each treatment arm, patients received a loading dose of 2 injections or 600 milligrams, followed by 5 single injection doses in the Q4 weekly arm. In the Q8 weekly arm, patients received 2 single injection doses or matching placebo.

The primary efficacy endpoint was proptosis responder rate or PRR at week 24 in the Q4 weekly arm as measured by exophthalmometry. Key secondary endpoints included clinical activity score or CAS and diplopia response and complete resolution and the corresponding endpoints for the Q8 weekly arm. Following the primary endpoint analysis, patients are being followed through week 52.

Slide 7 reviews the study disposition of REVEAL-1. The vast majority of patients completed treatment in all arms of the study. Baseline characteristics were generally well balanced across the 2 ELE arms and the placebo arm. As expected for the TED patient population, the majority of patients enrolled in the study were female, and the average age of patients was approximately 50 years of age. Baseline values for proptosis, CAS and diplopia were generally in line with our expectations and precedent studies in this active TED patient population.

Now let's turn to the results. In this slide, we see data across the efficacy endpoints in the Q4 and Q8 weekly treatment arms compared to placebo. As a reminder, the FDA and EMA requested different primary endpoints for the 2 different geographies. REVEAL-1 met its primary endpoint. Q4 weekly ELE had a 54 proptosis responder rate as measured by exophthalmometer versus 18% in the placebo arm, which was a highly statistically significant result. REVEAL-1 also met the EU primary endpoint. Q4 weekly ELE had an overall responder rate of 51% versus 16% in the placebo arm, which was also a highly statistical significant result.

On to the key secondary endpoints. ELE Q4 weekly arm also showed a highly statistical significant mean change from baseline in proptosis. Key secondary endpoints were analyzed using fixed hierarchical testing where the Q4 weekly endpoints were tested first and the Q8 weekly endpoints were tested after. The next endpoint in the hierarchy after mean change from baseline in proptosis was CAS reduction to 0 or 1 in the Q4 weekly arm. We observed an unexpected and large placebo response, and this endpoint did not achieve statistical significance.

When we look at diplopia, which we know is a debilitating symptom for many TED patients, 51% of patients treated with Q4 weekly ELE achieved complete resolution of their diplopia compared to only 16% of placebo patients with a low p-value as reflected on the slide. Similarly, 71% of patients experienced a diplopia response compared with only 32% of placebo patients. In the Q8 weekly arm, ELE showed a 63% proptosis responder rate by exophthalmometer, again, with a very low p-value.

We are particularly pleased to see this kind of proptosis response with only 3 doses. Q8 weekly arm also showed a compelling 2.5 millimeter mean reduction in proptosis from baseline, once again with a low p-value. We also measure proptosis by MRI, which was reviewed by 2 independent mass central readers and confirmed a clinically meaningful benefit on proptosis. Due to the location of CAS 0 or 1 early in our testing hierarchy, the subsequent prespecified endpoints are deemed nominally significant, which means that these endpoints show clinically meaningful and significant treatment effects as evident by the low p-values throughout the slide.

Overall, we believe this is the strongest subcutaneous clinical data seen to date in TED. Based on this data and the robust proptosis reduction seen with the Q8 weekly regimen in just 3 doses and the compelling diplopia resolution with the Q4 weekly regimen that rivals IV therapies but can be delivered in an at-home auto-injector, we plan to submit for approval of both the Q4 and Q8 weekly dosing regimens.

With that, let's see how these results looked across time points. When you look at the proptosis responder rate or PRR for both Q4 and Q8 weekly arms, you can see 30% of the patients already achieved a proptosis response at week 4 after just a single dose of ELE. This early separation was sustained and deepened across all subsequent time points through week 24.

On the next slide, we see the mean change in proptosis from baseline for Q4 and Q8 weekly arms. Separation from placebo was observed at week 4 after a single dose of ELE. Again, the treatment effect deepened over time. Next, as we did in THRIVE and THRIVE-2, we looked at MRI measured proptosis responder rate and mean change in proptosis over time as reviewed by 2 independent massed central readers. Both endpoints as measured by MRI showed robust responses consistent with exophthalmometer. Both the Q4 and Q8 weekly arms achieved meaningful levels of proptosis response and mean change in proptosis from baseline, while very little treatment effect was seen in the placebo arm. This provides independent confirmation of the significant and clinically meaningful effect of ELE on proptosis.

On the next slide, we see the diplopia results over time with Q4 weekly ELE regimen. Again, as we see early separation on both diplopia response and diplopia complete resolution as early as week 4 after just one dose of ELE. This effect deepens over time with 52%. That means 1 of 2 patients achieving complete resolution of their diplopia by week 24.

Now let's shift over to safety. ELE was generally well tolerated across both treatment arms. The vast majority of adverse events were mild. We saw 2 discontinuations due to adverse events, one in the Q4 weekly arm and one in the placebo arm. We see a well-tolerated safety profile consistent with the class. The rates of hearing impairment were low. We observed an 11.3 and a 2.3 placebo-adjusted rate in the Q4 and Q8 weekly arms, respectively. None of these events led to interruptions in dosing or discontinuations.

All of the observed events across both treatment arms were tinnitus and none were associated with reductions in hearing. In fact, the sole events of hyperacusis occurred in the placebo arm. All injection site reactions were grade 1, except for one grade 2 erythema. None of the ISRs led to interruptions in dosing or discontinuations. The majority occurred early in treatment course.

As a reminder, this study used a vial and syringe to administer ELE. We are completing our auto-injector bridging study and expect to launch with a low-volume auto-injector. We are thrilled to see these results from REVEAL-1 and to share them today. In summary, the study met its primary endpoint with high statistical significance for both the FDA and EMA. Both Q4 and Q8 weekly ELE achieved clinically meaningful rates of proptosis response. The effect was rapid, showing significant reductions in proptosis as early as week 4 after just one dose of ELE.

Q4 weekly ELE further showed rapid, significant and clinically meaningful diplopia responses with more than half of the patients achieving a complete resolution of their diplopia, all with a well-tolerated safety profile. As we mentioned, based on this data, we plan to submit both of these regimens for approval.

Looking forward to REVEAL-2, our Phase III clinical trial evaluating Q4 weekly and Q8 weekly ELE in patients with chronic TED. REVEAL-2 will be our fourth pivotal trial for the treatment of TED and our largest to date. We look forward to presenting results from REVEAL-2, which is on track for top line data in the second quarter of 2026. We expect to submit a BLA for ELE in the first quarter of 2027.

And with that, I'll turn it back to Steve.

Thank you, Radhika, for walking us through these exciting results. While today's call focused on ELE, it's important to remember that IV Veligrotug or Veli has an upcoming PDUFA target date on June 30. Veli showed a rapid onset of proptosis treatment effect, statistically significant impact on diplopia, including in patients with chronic TED, and it achieved it with only a 12-week course of therapy and 70% less drug. Veli received breakthrough therapy designation from the FDA in 2025, and its BLA is currently under priority review with the FDA.

As we approach the upcoming PDUFA date, we have built a fully operational commercial and medical affairs organization, including field sales, field medical, market access and patient services. These teams have all been actively engaged with key stakeholders in the field in support of a strong Veli launch. In particular, our med affairs team has been actively engaged with the scientific community ever since the THRIVE readout to educate physicians on Veli's profile and to raise awareness of both Veli and Viridian ahead of our anticipated launch. With a potential approval decision just 3 months away, we are ready to launch Veli as the first product in our TED portfolio.

Looking ahead to the future of TED, we are excited to have both Veli and ELE in our portfolio. Today, the TED market has one approved IV therapy. Despite low penetration by this therapy in the market, it still annualizes to approximately $2 billion in revenue. We believe Veli will be a highly compelling IV product. It has a strong clinical profile and a significantly shorter treatment course that appeals to many patients and physicians, positioning Veli to become the go-to IV treatment in TED.

The ELE data presented today, including a robust proptosis response seen with the Q8 regimen in just 3 doses as well as the compelling diplopia resolution with the Q4 regimen that rivals IV therapies and can be delivered now in a -- as an at-home auto-injector. That positions ELE to be potentially expanding the TED market meaningfully beyond IV-treated patients. Between Veli, Q4 and Q8 ELE, we believe we have a solution for TED patients regardless of the severity of their disease or the presence or absence of diplopia.

And with that, I'd like to once again thank our appreciation to the patients, their advocates, our investigators and research staff and everyone who made this REVEAL-1 clinical trial possible and a success. So with that, we'll open up the call for questions.

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

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

Thanks, Tom. Yes, I appreciate the question. We are very confident that we can move these forward. First and foremost, the REVEAL-1 did meet its primary endpoint. So by that definition, it's a successful study. And so when we look at -- and we plan to submit, just to be clear, we plan to submit the BLA as we've guided for both doses in Q1 2027 because we believe each arm is compelling and could be appropriate, quite frankly, for different patient populations.

Q4 looks great from the standpoint of reaching a proptosis responder rate that's highly stat sig. Q8 looks maybe even better on proptosis responder rate and maybe has a -- when you look at the safety, although the overall safety profile is very good and very -- as expected, Q8 looks even a little bit better. So both would be compelling for patients. So we think we can move those forward.

I would also focus on the diplopia response and resolution that we saw in the Q4 weekly arm, which is really encouraging, where -- and so when we look at these different profiles and moving them forward based on hitting the primary endpoint, we think this is approvable. On the -- and I'll have Shan maybe address the stats plan that you asked about.

Yes. Thanks, Steve. Happy to do that. Based on the highly statistically significant primary endpoints and so not just proptosis responder rate, which is the endpoint that the FDA really focuses on, they believe that to be the most important endpoint for thyroid eye disease, but we also met highly statistically significant on the overall responder rate, which is the European endpoint. So I think this unequivocally supports the positive study and completely supports the approvability of ELE.

On the stats plan, you're probably referring to the secondary endpoints. And here, what we showed was actually there for the majority of these endpoints consistently having very clinically meaningful and significant effects on these endpoints as you saw with all of the p-values that -- low p-values that Radhika presented.

As she mentioned, CAS 0, 1 was located early in the stat hierarchy and with the large unexpected placebo response and not meeting that from a p-value standpoint, we do refer to the rest of the endpoints as being nominally significant. But just looking at the effect size, even looking at Q8 weekly proptosis responder rate, again, this is the response that the FDA really cares about the meaningfulness of that endpoint and the effect size that we saw is tremendous. And so we feel really good about the ability of these endpoints to make it into the label. We, of course, will seek inclusion of these endpoints in the label, and there are actually many precedents of drugs who've been able to do so ahead of us.

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

We had -- thinking about the results today, it seems like you had maybe slightly higher placebo rates and perhaps slightly lower treatment arm rates, although it hit statistical significance. And is therefore, part of a registrational package. Can you just remind me how you think about the results as it relates to the chronic study coming up?

And traditionally, results can come down a bit in chronic, which is a bit more difficult to treat heterogeneous population. So how do you see the results today playing in the results in Q2 and thinking about the powering and some of the scenarios that may evolve from that versus what others have shown?

Yes. Thanks, Mike. Okay. Yes, I think certainly, everyone can see that the placebo rate that you referred to is higher than our prior experience across multiple endpoints. And while the treatment effect of ELE is highly significant and clinically meaningful, we do acknowledge that the treatment effect is less than what we saw in PRISM.

Now with respect to how that reads through, but let me just remind you that -- it's highly statistically significant. It's clinically meaningful on the proptosis. And what we see is that ELE delivers the majority of the IV IGF-1R efficacy. But now we can do that in a convenient subcu auto-injector that we can deliver to people's homes. So we think that, that is a potential to expand the market here.

And particularly, as Shan was just answering the prior question, when you think about the diplopia response that we saw, the high rates of complete resolution and diplopia resolution and response that we saw in the Q4 weekly arm, the proptosis response we saw in the Q8 weekly arm. So that is -- and the p-values that Shan was referring to, that is all pretty important.

So with respect to REVEAL-2, we do expect to move forward, as we mentioned, with both arms. And we -- the REVEAL-2 study is larger. It's a larger study. We have planned and powered it for that purpose. We know the chronic population. And so we feel good about the REVEAL-2 based on what we see today. It doesn't change how we think about REVEAL-2.

And on REVEAL-2, maybe just another comment on that. Here, the point that chronic patients are different than active patients. I'll say that we've always planned for that. We have always planned for chronic patients to be harder to treat. We took that into account for REVEAL-2. Remember that the REVEAL-1 endpoints here are highly statistically significant. So the treatment effect is robust. We have very, very low p-values.

We powered REVEAL-2 sufficiently as well as a larger study. We enrolled over 200 patients there. And also in REVEAL-1, I think the results here give us a lot of confidence that the drug is reaching the levels of exposure that we have predicted in our modeling going into the study. So that also translates over to REVEAL-2 as well. So in general, we feel really good about REVEAL-2. And then remember also that the CAS endpoints are not relevant for the chronic patient population.

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

I wanted to think through the upcoming TEPEZZA subcu data. Maybe first, you could just remind us what the product presentation for that subcu is. And I guess not seeing a dose response here to me indicates I can't biologically think of a reason that they could do better on efficacy. So I'd be curious from your perspective, if you think you're maybe getting some more mild patients into this trial.

And I'm not sure if that's a temporal thing with kind of the TED population or maybe kind of a fact of using a subcutaneous form that can get some more mild patients. But I would just, in general, be curious what your thoughts are for that upcoming trial.

Thanks, Gavin. Yes, so I'll take the subcu TEPEZZA question. Based on what we -- what has been disclosed publicly, their approach looks like it involves a wearable subcu infusion pump. So it's something that's attached to the abdomen. It seems from what we understand is dosed every 2 weeks. It's not extended, dosed every 2 weeks up to 24 weeks.

So just by contrast, ELE is designed as a low-volume auto-injector, as you know. And so we like -- the half-life extension gives us the ability to dose that infrequently. And we just think that's tested well in commercial research for the profile. On the other question, I'll turn that over to Shan for -- to answer.

Yes. Maybe to address the dose response first. I think that's right on the proptosis part of it. And what we saw, again, as I mentioned in response to the last question, observed PKs in this study were pretty much as we were predicting, including the Cmin. And then IGF-1 levels across both dosing arms were also at that maximum what we have seen before, 4x from baseline. And so this is really consistent with our belief that the receptor target of IGF-1R is fully saturated in both of these dosing arms.

So sort of no matter how you look at it from a proptosis standpoint, whether it's Hertel, MRI, the results have overlapping confidence intervals and error bars. And so we really do think that we're getting to a pretty similar level of response in both of these arms as well as both of these arms performing extremely well on the total effect size.

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

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

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

Sure. Yes. Thanks for the question, Alex. The auto-injector is something that's been in our plans. We've worked into the development plan already as well. So in addition to the pivotal studies that we are running, including the BL1 data that we showed today, we are also running an auto-injector study, which will enable us to submit the BLA together with the auto-injector data, which would enable, we believe, an approval and launch with ELE in the auto-injector. This is a commercially validated auto-injector.

Our CMC tech ops team is all over in terms of getting this auto-injector ready and manufacturing and the device development is always on a parallel path to the pivotal study, so not always, but you want it to be on a parallel path. So it's not rate limiting for the development of the drug. And that's exactly what we plan for here.

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

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

Absolutely. Great question. So maybe just a reminder, this is a $2 billion market currently annualizing. We see single-digit penetration. We believe one of the keys to expanding this market is providing more accessible treatment options to patients. The goal here was to find a way to safely deliver IGF-1R therapy in the convenience of the home for these 10 patients. So we feel like we've done that based on the results of REVEAL-1.

We've done so in as few as 3 doses. When you look at Q4 in particular, having the ability to offer patients a diplopia resolution in the comfort of their own home, we think is very compelling and very powerful. So we see this as a good day for patients. It's a great day for physicians as well, where we can offer not 1, but potentially 2 new convenient safe options in the comfort of a patient's home.

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

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

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

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

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

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

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

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

Yes. Thanks for the question. So just as a reminder, all of the events that happened were generally mild in nature with regards to the hearing impairment events and all of the events in the Q4 and Q8 arm in the study were tinnitus. None of these events were associated with any detected changes in hearing function. And that one case of hyperacusis that I mentioned earlier, it was in that placebo arm. So in general, this is a really good clinical profile to have, not only in the Q4, but also in the Q8 arm.

I think your question was sort of also referring to the THRIVE rate. The THRIVE rate is also a little bit of a different number for the patient population. So that end is a little bit larger. So there's an element that you should consider with regards to that.

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

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

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

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

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

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

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

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

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

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

Yes. So maybe I'll start with the last question first. We're confident in the REVEAL-2 study. I don't think that there's results that would change our thinking on ELE from a commercial perspective at this point based on what we're expecting.

From a use case perspective, yes, you could see a difference, right? So I would say both had clinically meaningful responses, right, when it comes to proptosis. So yes, I would say, numerically, one looks different than the other. But I would argue that patients and physicians would find both clinically meaningful, especially when you think about the possibility of providing this to the comfort of a patient's home in a simple-to-use low-volume auto-injector.

I think of particular interest when you look at the Q4 arm is the majority of patients seeing a complete resolution of diplopia. That's a very powerful option to offer patients, a complete resolution of diplopia and the comfort of their own home. So you could see potential choices and options when a physician is taking care of a TED patient based on their symptomatology. Having more choices, we think everybody wins when you have more choices for patients in this market.

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

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

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

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

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

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

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

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

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

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

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

So I'll start with the clinical and Tony will complete with the commercial question. So I think when you're talking about Hertel versus MRI, so sort of 2 things are happening in the course of the study. What happens is the patient shows up into the clinic, the physician uses the appropriate device, and it's done in the manner as noted in the protocol with regards to the instrument, how frequent and how it's documented. And that sort of is a standard process that's done in the course of clinical care and ultimately in the course of following our protocol for both REVEAL and ultimately for REVEAL-2 as well.

The question about MRI and how that's done, the local site does the actual scan and they're following a protocol with regards to the quality and the conduct of that scan of how it should look like. And that scan is then uploaded and then provided to a central reader that's also looking at it in a blinded fashion by 2 central individuals. That data is reviewed and entered separately into the database. So those are 2 separate elements.

I think when you're thinking about Hertel and MRI, I think we're here at Viridian kind of at the cutting edge of TED research, and there really are no other Phase III studies that have conducted simultaneous Hertel and MRI measurements. So we have a really great opportunity to kind of advance the field as we look at both of these endpoints as measured -- or this endpoint is measured by both of these modalities. But the reality is that the consistency of the clinical effect that we see in both the Q4 and the Q8 arm really gives us comfort in the clinical outcome measurements that we shared with you today.

Yes. And then I'll take the question on market. So yes, the market has been relatively flat annualizing out to $2 billion a year. We view this not as a market problem. We view this as an existing profile problem. And while TEPEZZA is a great drug, it's helped a lot of people, it is burdensome, logistically challenging to get completion of therapy.

Just as a reminder, 60 to 90 minutes, each infusion, over 8 infusions can take 5 to 6 months to complete therapy. We know from our research that roughly 30% of patients that are offered TEPEZZA refuse it. One of the primary reasons they state is because of that burden of the therapy. So this is part why we're so excited to improve that experience for patients getting an infusion with Veli, and we take it a whole another level with ELE. Now with 2 potential options, right? Not just delivering it safely at home, but being able to do that in as little as 3 doses, we think, is very compelling and has the ability to open this market up.

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

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

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

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

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

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

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

Well, look, I mean, I think what we saw here in REVEAL-1 is pretty robust proptosis responses. The chronic population is a bit different as we saw with THRIVE and THRIVE-2, but we've designed the REVEAL-2 study with that patient population in mind, certainly. So it's a larger study. It's well powered for that patient population. We don't have -- just to repeat, we don't have the CAS 0, 1 reduction in the hierarchy. It's just not part of it because we have 0, 1 patients enrolled in that study. So that's just not how it works. That was always the case.

So yes, we feel -- I mean, just to reiterate, we do feel good about the REVEAL-2. I think the expectation level for REVEAL-2 is if we hit stat sig on that study, we have 2 well-controlled positive studies to move forward with from a regulatory path.

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

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

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

All right. Good morning. Welcome -- so for the next session, we have Steve Mahoney and Shan Wu from Viridian. Welcome to your second Goldman Sachs conference. And before we get started, I'm going to turn it to you guys for any opening remarks.

Okay. Well, great. Rich, thank you for having us here today. We may be making forward-looking statements during the course of the presentation. So please refer to our SEC filings for the risk factors.

We are advancing the portfolio on -- across the board, everything is on track, everything is moving well. We -- as you know, we finished our Phase III studies. Well, we had our top line data readouts for our Phase III studies in active and chronic patient populations last year. Data was overwhelmingly positive across all the endpoints, all the time points.

So very encouraging Phase III data. We're now marching towards BLA filing in the second half of this year. We're just waiting for the THRIVE-2 chronic study follow-up period data to come in, and then we'll be able to do that. So everything is on track there.

We just recently announced our long-term follow-up data for the ACTIVE study, which looked very promising, answered the question as to whether we would be -- see a durability of response. We thought that was pretty clear from that data, which was great.

And we also announced recently our Breakthrough Therapy Designation, which obviously was quite validating from the FDA to get that designation, which essentially says that they feel that we have the potential to substantially improve against the standard -- current standard of care. So that would be -- that's obviously great. It also increases our -- potentially our odds for priority review, which pull in the launch timing.

So IV program moving along great. And then we're also enrolling our subcu program in our Phase III studies there, REVEAL-1 and REVEAL-2, that is also all on track. It will have first line -- top line readout in the first half of next year. So the TED portfolio is moving right along and doing well.

We also have an FcRn portfolio. We've got healthy volunteer data coming out in Q3 this year. That will help us determine IgG suppression, albumin sparing and we'll get an insight into some dosing. And we think that our development of the Fc fragment, the only other company out there developing the Fc fragment besides VYVGART, and we're pretty excited about that.

And we also have our half-life extended version of FcRns, which could be a potential game changer, but we're filing an IND on that at the end of this year as well. So we'll get first-in-human data next year. So portfolio is moving well, well capitalized and we're in good shape.

Fantastic. Obviously, this is a very important year, a lot of execution going on. Maybe just a little bit about what we should expect to see? I know you mentioned you guys are looking to file the BLA for veli. Are we going to see -- are you guys going to show any of the 52-week safety data? Or is that something that you would show to investors? And also, how is the REVEAL-1 and 2 study going for 003? Is that on track to have data coming next year?

Yes. So answering the last question first, yes, 003 is on track. Just a reminder, the subcu antibody and the IV antibody are essentially the same antibodies, the only difference being the half-life extension technology in the subcu.

So we do expect that the subcu will behave similarly to the IV antibody because it's the same binding domain, same CDRs, so it will block the receptor in the same way. We saw -- in the healthy volunteers, we saw very comparable PK/PD data, which is what we wanted to see, and that gave us confidence to go right into Phase III on the back of that health volunteer data.

BLA filing is on track, like I said, second half of this year, and we're waiting for the THRIVE-2 chronic data to finish the follow-up period, and then we'll drop that into the BLA and then we'll be ready to go.

And will you show the 52-week follow-up safety...

So we showed the 52-week follow-up safety data for the ACTIVE study. We had that -- we included that when we did the durability response on proptosis. The safety profile looked great. Vast majority of any AEs reported that were all mild anyway, they all resolved -- the vast majority of them resolved. So the safety profile and the follow-up period look good, again, as expected.

Right. Okay. Fantastic. So obviously, there's a lot of -- you guys are expecting to file the BLA and then -- and right after that, you would have to prepare for the commercial launch? And how is that part of the preparation going?

Yes, we've had a senior commercial team in place for quite a while, as you should, when you expect to launch. So we've got a Chief Commercial Officer and marketing, sales operations, supply chain, market access importantly. So we've got the team in place, and we've built out our launch plans.

If we do get priority review because Breakthrough Therapy Designation can often lead to priority review, it's the same review criteria, we'll have to request that once we file the BLA but we think it increases our odds certainly, that breakthrough therapy can increase your odds for priority review. And if we got that, and we were -- so we're planning as if we're getting that. So we're going to be ready no matter what happens to launch. And we've got a very experienced team to be able to do that.

Fantastic. And obviously, you guys have been monitoring TEPEZZA sales. That's a very important metric to investors, to the market and obviously, to you guys as well. And when you look at that sales, it's been declining a little bit in 1Q '25. What do you think is driving that decline? And how do you think of the overall condition of the market in terms of is it going to continue to trend that way? Or is it going to -- you see a more stability of the...

Well, I think, first and foremost, let's acknowledge that we're still talking about a $2 billion market, right, roughly. So we think that with our IV profile, which we just showed in our Phase III, both in active and chronic, and the differentiation, again, cross-trial comparisons, but the Breakthrough Therapy Designation kind of supports this, is our data looks really good.

And we think that, particularly with diplopia, complete resolution, diplopia response, rapid onset of treatment effect and the durability of response and the safety profile, don't forget, we had lower hearing impairment rates. That's a key area of interest for folks on the safety side. We have lower rates despite the fact that we were looking for it versus when TEPEZZA ran their trials, they weren't really looking for it because it wasn't known.

So that all, in our view, offers a differentiated profile. Again, cross-trial comparisons, but again, breakthrough therapy supports this. We think that profile being introduced into the market with more treatment options available to patients with 5 infusions versus TEPEZZA's 8 infusions, 10 mg per kg versus 20 mg per kg, 70% less drug going in and getting this clinical outcome, we think that's going to open the door for more patients and encourage them to come in and get access to this drug.

So we think regardless of what TEPEZZA's performance is, we think the market is certainly healthy. Look at our clinical trial enrollment, we enrolled over 400 patients in trials last year. There are other trials out enrolling for thyroid eye disease patients as well, but that's pretty healthy demand coming from the market side, and over half of those came out of the U.S., by the way.

So we think the patients are certainly there and we think a different profile with more treatment options for patients will drive. And then obviously, when subcu comes in, we expect subcu to be available a year after IV, we think that will even drive further penetration because now we can mail an auto-injector to your house and you're not -- you don't have to go to an infusion center.

But we do think, just to be clear, IV will stick around. There are physicians [Audio Gap] patients in a controlled setting and there are patients who want to be in a controlled setting of an IV infusion center.

Fantastic. So when you watch TV, you see a lot of DTCs on TED from Amgen. So there's a lot of awareness going on. And then I think Amgen has mentioned that they've been getting good traction with the ocular specialists and they're looking to expand to ophthalmologists and endocrinologists but that seems to be a little more challenging to do.

How are you guys thinking about sort of the commercial in terms of what you need to do to build awareness? Do you feel -- are you looking at the three sort of class of physicians that you would want to target? Are these the same type of physicians? And also, how do you think about the awareness that's being created? Do you have to come out and sort of match the same sort of like awareness DTC campaigns?

Yes. First, I think everything that they're doing is, benefits us. They're educating patients, disease awareness, they're educating physicians on IGF-1R inhibition and they're educating payers. So we benefit from all that because, again, we come in with the same mechanism, same target. So our conversations are certainly a lot easier, particularly when you -- when we have the profile that we have.

I think we should start there. That's all to our benefit. We actually -- we think that broadening the approach like they've done with respect to more general ophthalmology and endocrinology, those will be -- that's more of a -- in our view, more of a referral network to the neuro ophthalmology and the oculoplastics who are the primary prescribers of -- for TED.

Because even in an endocrinology world, you have patients who present initially with presumably with Graves but as soon as the eye manifestation shows up, they want to consult with ophthalmology. And so that's where we think there's 2,000 core prescribers in the U.S., which is a -- certainly a manageable number for a company like us and a company like Horizon originally. The infrastructure we need to build to reach the core prescribers is certainly manageable.

Okay. Great. And then Amgen has also been saying that the U.S. -- that the total addressable market size is about 100,000 patients, of which 80% of those are chronic. However, they continue to say that they only have a low single-digit penetration into that market with TEPEZZA. Why do you think chronic is so difficult? It's been quite some time now since they did their Phase IV study. And how is Viridian better positioned to address the chronic patients?

Yes. First, I think we think the market is actually bigger than 100,000. You can see in our deck, we talk about it more like 190,000, closer to 200,000 patients with moderate to severe. We agree that the large proportion of those are going to be in more chronic.

But that means there's still also an incident population of roughly 20,000 new patients coming into that pool every year. And that is based on a number of different research. But if -- with their single-digit penetration that you referred to, we agree with that. We think that, that number is small.

Now their ability to penetrate into chronic, it's hard to say, except for the fact that we think that there was more response that you could achieve in the chronic and I think our data is differentiated on that, again, it's cross-trial comparison, so you have to put the caveats on that. But our chronic data is really compelling.

I mean if you look at our diplopia response, diplopia is double vision. If you look at our diplopia response and our diplopia complete resolution, so your double vision going away, that our numbers were really impressive. So we think that's going to drive better penetration to the chronic population.

Again, our safety profile helps with that analysis as well. The physicians we've talked to have been very excited about our chronic data. So we think that we can drive better penetration on that basis.

I see. And then looking at your data, do you believe that the same treatment regimen is needed for chronic compared to the active patients because their inflammation is less severe? I mean I'm wondering if a shorter or a lower cost sort of treatment regimen is more suitable to help encourage use and help penetrate the market a little bit better and maybe with the payer reimbursement.

Well, in fact, I think if you look at our chronic study, to get into the study, you have to have 3 millimeters of proptosis above normal. So by definition, these are proptotic patients walking in the door. They also -- we also ran, which is different than how TEPEZZA designed its studies, we -- clinical activity score is on a scale of 0 to 7.

TEPEZZA studies were limited to patients with 0 or 1. And these are -- clinical activity score is a proxy for pain and inflammation, redness, like gradiness that people feel in their eyes. By limiting it to 0 or 1 like TEPEZZA did, by definition, those are people who are not necessarily complaining about their pain.

When we ran our study, we had patients with 0 or 1, but we also had a number of patients with higher CAS scores than that, which indicates -- clear indication that the chronic market has proptosis, has pain, has redness and diplopia. I mean we had a large portion of our patients in the chronic study had diplopia at baseline. So these are people that are certainly symptomatic. And that's why we designed the study that we did to make sure that we got the most representative population for chronic.

Now we can have our chronic data in our label -- just as a reminder, TEPEZZA's does not have chronic data in its label. It's got a broad indication statement but not the data. And so we're going to have that on day 1. We are -- the payers are fully aware of what IGF-1R inhibition can do now on the backs of TEPEZZA. And so we just think we're in a better position to drive that penetration into the population.

Great. And then in May, you guys announced that you guys received a breakthrough designation from the FDA. How beneficial do you think this is to maybe -- I mean, there's a big benefit to the regulatory path, obviously, in terms of how the market is going to be perceiving by getting that feedback from your KOLs, clinicians, being more on their radar and how -- maybe tell me a little bit about the awareness of that? And then what is the path for the breakthrough designation for -- to the priority review? Like what do you have to do to get to that priority review?

Yes. Well, I think, first and foremost, breakthrough therapy is a recognition by FDA that this is a serious condition, right? I think that's certainly true. And then what it does for us in terms of the benefits for us is, obviously, there's a more formalized, clear communication channel with FDA, although we were having great alignment in communication with FDA in any event. So that is one component of breakthrough.

The other component, which you referred to, is the increasing your odds for priority review. They are distinct designations, but they're based roughly on the same criteria. So you can't ask for priority review until you file. We will -- when we file, we will put that request in, and again, we think it has increased the chances of us getting priority review, which would be fantastic if we could pull in our launch timing.

And again, as I've mentioned in the beginning, what breakthrough therapy is, is a mechanism by which FDA actually compares your data to the standard of care. And for them to come out and say, we grant you breakthrough designation, that is essentially indicating based on the definition of breakthrough that we represent a potential substantial improvement over currently available therapies. So a great place for us to land with our alignment with FDA.

Fantastic. And you guys show -- earlier, you mentioned about this, that the positive long-term durability study for data for the Phase III THRIVE study. And I think there, you showed about 70% of patients were able to maintain the proptosis response at week 15 all the way through week 52.

How do you -- how does this compare to the long-term data for TEPEZZA? And also, do you believe there's a meaningful differentiation from a longer-term durability perspective compared to TEPEZZA?

Shan?

Yes, I can take that one. So as you mentioned, we showed really strong durability of response for patients at week 15 who had a response, 70% of those maintained their response at week 52, which was really good to see. The number that is in the TEPEZZA label is 53%. And so not making any cross-trial comparisons, but we feel really good and confident about the number that we have reported on at week 52.

Ultimately, at the end of the day, the question that was still remaining out there was whether veli with a 70% less drug, 5 infusions or fewer infusions than TEPEZZA, whether the strong responses that we saw at week 15 would continue. And I think we answered that with this data. And I think that's durability numbers that we would expect to be in our label, which again, is a very strong position for us at launch.

Great. And then how do you think about the patients who did not -- were not able to maintain their proptosis response to 52 weeks? Any implication there for potentially a weak treatment?

Yes, it's -- so just a reminder that the vast majority of patients did maintain their response. So we're talking about a minority of patients and this being an autoimmune disease that can have ups and downs and reactivation of the disease as some of our KOLs referred to it. So it's not unexpected to have some patients who don't maintain that response.

We think retreatment is absolutely an opportunity and based on real-world data today, we do know of some patients that are getting retreated with the currently available IGF-1R. And the good news is they seem to respond again in KOL support retreatment. So that's something that we will be exploring and looking at as a potential.

Okay. Fantastic. And in terms of veli's durability in the chronic patients for the THRIVE-2, will you be showing that data as well when that becomes available? And also, how are you guys looking at the expectation for that? Are you going to benchmark to that 70% in the active patients? And is there any risk that the durability for chronic may not be as robust compared to the active?

I think if you look at all the data we've put out to date, it's completely consistent across endpoints, time points, durability time points, safety side, again, breakthrough therapy kind of a validation of all of that. So the antibody has answered every question all along the way.

So whether we put -- we don't have the THRIVE-2 data follow-up period yet. We don't have all that data yet. But we -- it is the last piece of the BLA. So we will be scrambling to get that into the BLA, so we can file as quickly as possible. So what -- our plans for whether we put that out or not, I don't know if we need to. It will be in the BLA anyway and maybe we'll have it in the medical congress at some point.

But I think we've answered the question on durability of response, whether the drug could actually do it or not given the amount of drug that we're putting in. But we'll have the data eventually and we'll get it out at medical congress or it will just be in the BLA.

Fantastic. And then obviously, I think for safety, I think this is important to mention that you guys have a lower -- placebo-adjusted hearing effects are lower compared to TEPEZZA. How important is that?

I mean we talked about -- I mean, for the longest time, you guys talked about having 5 dose instead of 8 would be a major differentiation. And having that sort of that slightly better, lower hearing effects. How important do you think is that to the clinicians when they're looking -- deciding between treatment options?

Yes. We do think it will be helpful as a part of the overall package of efficacy and safety that we're delivering. And of course, the fewer infusions and shorter infusions that comes from veli. It's a benefit risk conversation that physicians will have with patients. When we first showed the data to some of our KOL advisers back when we reported on the Phase III data, one of the things that they talked about was it makes the conversation that they have with the patients much easier.

Now that the available therapy has been on the market for 5 years, patients know this can be a side effect and they go on Google, they go on online forms and they go in and ask their physician questions about hearing impairment as a potential AE. And so that is a conversation that many physicians are having with the patients.

And so the fact that we can give them, the physicians, a chance to have an easier conversation, I think, is definitely helpful for our overall profile. A reminder that the overall hearing impairment, we're not really talking about reductions in hearing function. The vast majority of these are mild events like tinnitus, which is a ringing of the ears or hearing some echoing of one's voice, and almost all of it resolves when the patients come off of therapy as we also corroborated with our week 52 data.

So this is a manageable risk profile for physicians. They're very comfortable managing hearing impairment as a umbrella set of potential AEs, but anything that we can do to make it easier for them to have that benefit risk conversation with the patient would be better.

Great. And then I know we talked about the U.S. commercial prep and how that's ongoing. How do you think about Europe? Is the plan to also file the regulatory submission for EU sometime in 2026? Or -- and how are you thinking about commercializing veli in Europe?

Yes. So we're trying to keep all our options open ex U.S. certainly. We think from an epidemiology standpoint, Europe is certainly a viable market. We'll be curious to see how pricing works. Obviously, that's a key component to any European launch or commercial opportunity. But we did guide that we would have our MAA filing in the first half of '26. So we're going to get the BLA in.

We designed the Phase III studies in -- with Europe in mind as well. Meaning we have an end point in there that the European regulators want to see, which is the overall response rate, which essentially is just your proptosis response and your clinical activity score combined. So we had that in our study to begin with, knowing that, that's what Europe would look for.

So we'll be ready to go. We just need to switch from BLA into MAA once we get in and then -- and of course, we're just watching how Europe develops in the meantime, and we're just keeping our optionality open. We don't have to spend any money from that optionality, which is always great.

And then other parts of the world, the normal markets like Japan, we're looking at what we're going to do there as well. So we have all our options open. And just a reminder, TEPEZZA has been on the market now for 5 years, and they're just finally going into Japan and Europe. Horizon was focused on the U.S. So we could skip the waiting period there and get those ex U.S. revenues going as well.

So I know it's maybe still a little too early to talk about pricing, but how are you guys approaching that? Obviously, you have a competitor that already have a price out there. Are you guys looking mostly -- you have a differentiated drug, and that looks better in many dimensions. And how are you guys looking at the pricing? Is it going to be mostly parity? What's your approach to thinking about that?

Yes. Well, first, it is too early to talk about pricing. But yes, we're looking at all of that. Obviously, we spent a lot of time with our market research and are talking to payers. We know what the current price is for TEPEZZA and we are looking -- I think all we could say really at this point is we would probably price on a per course of therapy like they do. But other than that, more to come later.

I see. And also the payer coverage. I think one thing when we look across all the payers is that they all limit TEPEZZA's use to once per lifetime. There are some retreatment possible for that. Maybe comment about how do you see the payers looking at another drug in this market? What's important to them? And do you think they would loosen up at some point at that once per lifetime for veli? And what do you need to do to show there?

Yes. I mean I think they'll do that in response to data, as always. I think in terms of making progress with payers, TEPEZZA is already doing that. They were -- on the chronic setting, they got pushed back from payers because they did not have any chronic data at launch. They ran a chronic study 18 months after approval, generated that data, it was available in 2023.

Like I said, they had a limited trial design with respect to particularly clinical activity score 0 or 1 but they've made progress. In their last call, they indicated that they had jumped from 55% commercial insurance coverage up to 85%, which is all good for us.

Just as a reminder, this is all good for us. They're clearing the way for us to come in and have a differentiated profile that we think will be more palatable to payers anyway. So this is all good lead work that they're doing for us. And we think based on our market research and based on our talking to payers, we think we're going to be in a good spot.

Okay. So the VRDN-003, the subcutaneous formulation, you have two ongoing Phase III studies, data is coming out next year. How are you thinking about what's the expectation for that in terms of what do you need to achieve? Are you benchmarking to veli -- to veli's Phase III study? Is that sort of the goal for 003?

Yes. So we have both of those two ongoing studies, as you mentioned. We think 003 is a derisked approach given the data that we've generated with veli. Back when we designed the REVEAL-1, REVEAL-2 studies and the decision to take a Q4 weekly and Q8 weekly active dosing arms into that study, that was all based on being able to achieve similar exposures of veli at 10 mg per kg and 3 mg per kg IV, respectively.

And that was -- both of those dosing arms show really great efficacy back in the Phase II trial, which of course is now 10 mg per kg IV, we've seen spectacular data from THRIVE and THRIVE-2. So we think the efficacy and safety for 003 is derisked coming out of what we've seen for veli, both from an efficacy standpoint.

And then to the extent that lower overall exposures, even Q4 weekly with a subcu smoothing out Cmax but in particular, with Q8 weekly being more at the exposure levels of 3 mg per kg, to the extent these lower exposures can lead to an even better safety profile while preserving the efficacy of IGF-1R is a really exciting place to be for the 003 studies.

On exact expectation setting for those two studies, we haven't gone -- come out and set that yet. But we do believe that everything we've generated with veli IV and because the two molecules share CDRs, have the same pharmacology, we would expect to behave similarly, interact with the target in the same way at the same exposure levels, we feel really good about the REVEAL-1 and REVEAL-2 studies.

Got it. So you haven't set expectations, but when -- how should the market look at this? Is it -- does it have to be as good as veli or if it comes slightly below that for efficacy? Is there still value in that?

Yes. I think the way that we look at it is providing more options for patients, a subcu option, whether it's Q4 or Q8, both of those would be best-in-class regimen for subcutaneous. There's nothing out there that we know of that is that infrequent and as auto-injector that will be mailed to a patient's home.

And at the end of the day, either one of those two options would be great for patients and we give them a range of options, including IV veligrotug as something that they can choose from.

Great. And then looking at both the Q4W and Q8W dosing regimen. Is the plan to take both to commercial? How are you guys going to decide between both of these going forward?

Yes, we'll definitely need to look at the data before making that decision of how we take things forward. But again, as we said, either one of these would be fantastic regimens for patients and it comes down to what the safety and efficacy data shows from the trials, and we'll make decisions accordingly based on that.

Okay. Great. And then for 003, are you guys still committed to launching it with an auto injector? And then how is that portion of the development going for 003?

Yes, it's going really well. Everything is on track as we guided to a top line data first half of next year with a BLA submission anticipated by the end of the year. That BLA submission would be with an auto-injector. So all of that has been worked into the time lines for BLA.

Fantastic. One last question before I turn it to you guys for closing remarks. Anything in the competitive landscape that you guys are still tracking for in TED? Obviously, I think there's a lot of competitors that released data over the past year and a lot of them have been disappointing. And is there anything else that you guys are tracking, anything else that you think could be worth looking more into?

No, it's a good question. I mean, I think that was one of the big overarching questions last year is what about the competitive landscape. The competitive landscape is really cleaned up really nicely in our favor. As you mentioned, there's been a number of companies that have had data that didn't look all that compelling versus what we've been able to offer.

And again, when we look at -- it's a cross-trial comparison. When we look at our different profiles in a new start market, I mean, that's the key here. We're not asking anybody to switch. When it's just us and TEPEZZA, we think we -- we're not asking people to switch off TEPEZZA to try us. These are -- everyone comes in the door and we get -- they'll have options with respect to our drug versus TEPEZZA. And we think we're in a good position there.

But the rest of the competitive landscape, I think there's either a recognition that the other attempts at IGF-1R inhibition were not that compelling. And then the other mechanisms are not particularly on target. You have broad anti-inflammatories, you have broad IgG suppression. We just don't think that that's on target for the cell signaling that's taking place for moderate to severe patients with TED. So the competitive landscape is cleaned up quite nicely for us.

Well, Steve, Shan, it's been a pleasure hosting you for a second time at the Goldman Sachs conference. Thanks so much for attending. And I'm going to turn it to you for any final concluding remarks.

Yes, sure. Look, bottom line, we have derisked programs, validated mechanisms, clinically validated, commercially validated mechanisms, which is our approach. We like to try to make things better and easier for patients versus what the first entrant, and so all of that is on track.

We're executing across the portfolio, and we just continue to march along and keep derisking these programs even further and everything is on track for -- we're going to be a commercial company next year. I think that's a pretty exciting prospect.

And we're continuing to advance our FcRn portfolio as well, which very much fits into that derisked and exciting development path for a derisked market.

Great. Thank you.

Great. Thanks, Rich.