All right, good morning. Welcome. For the next session, we have Steve Mahoney and Shan Wu from Viridian. Welcome to your second Goldman Sachs conference. Before we get started, I'm going to turn it to you guys for the opening remarks.
Okay, 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 across the board. Everything's on track. Everything's moving well. As you know, we finished our phase three studies. We had our top-line data readouts for our phase three studies in active and chronic patient populations last year. Data was overwhelmingly positive across all the endpoints, all the time points. Very encouraging phase three 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 we'll be able to do that. Everything's 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 see a durability of response. We thought that was pretty clear from that data, which was great. 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 current standard of care. That is obviously great. It also increases potentially our odds for priority review, which will pull in the launch timing. IV program moving along, great. We are also enrolling our sub-Q program in our phase three 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.
The TED portfolio is moving right along and doing well. We also have an FCRN portfolio. We've got healthy volunteer data coming out Q3 this year that will help us determine IgG suppression, albumin sparing, and we'll get an insight into some dosing. 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. 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. We'll get first-in-human data next year. The 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 veligrotug. 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? Also, how's the Reveal 1 and 2 study going for VRDN-003? Is that on track to have data coming next year still?
Yeah. To answer the last question first, yes, 003 is on track. Just a reminder, the sub-Q antibody and the IV antibody are essentially the same antibodies, the only difference being the half-life extension technology in the sub-Q. We do expect that the sub-Q will behave similarly to the IV antibody because it's the same binding domain, same CDRs. It'll block the receptor 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 three on the backs of that healthy 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.
Would you show the 52-week follow-up?
We showed the 52-week follow-up safety data for the active study. We included that when we did the durability response on proptosis. Safety profile looked great. Vast majority of any AEs reported were all mild anyway. They all resolved. The vast majority of them resolved. The safety profile and the follow-up period looked good, again, as expected.
Right. Okay. Fantastic. Obviously, there's a lot of—you guys expecting to file the BLA, and then right after that, you would have to prepare for the commercial launch. How is that part of the preparation going?
Yeah, we've had a senior commercial team in place for quite a while, as you should when we expect to launch. So we've got a Chief Commercial Officer, 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. If we got that and we were—so we're planning as if we're getting that. We're going to be ready no matter what happens to launch. We've got a very experienced team to be able to do that.
Fantastic. 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. When you look at that sales, it's been declining a little bit in 1Q 2025. 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 do you see more stability?
I think first and foremost, let's acknowledge that we're still talking about a $2 billion market, right, roughly. We think that with our IV profile, which we just showed in our phase three, both in active and chronic, in the differentiation, again, cross-trial comparisons, but the breakthrough therapy designation kind of supports this, is our data looks really good. 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 the key area of interest for folks on the safety side. We had 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. 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 five infusions versus Tepezza's eight 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. We think regardless of what Tepezza's performance is, we think the market's 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. That's pretty healthy demand coming from the market side. Over half of those came out of the U.S., by the way.
We think the patients are certainly there, and we think a different profile with more treatment options for patients will drive. Obviously, when sub-Q comes in, we expect sub-Q 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 do not have to go to an infusion center. We do think, just to be clear, IV will stick around. There are physicians in a controlled setting, and there are patients who want to be in a controlled setting of an IV infusion center.
Fantastic. When you watch TV, you see a lot of CTC on TED from Horizon Therapeutics. There is a lot of awareness going on. I think Horizon Therapeutics 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? Are you looking at the three sort of classes of physicians that you would want to target? Are these the same type of physicians?
Yeah.
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 awareness DTC campaigns?
Yeah. First, I think everything that they're doing benefits us. They're educating patients, disease awareness. They're educating physicians on IGF-1R inhibition, and they're educating payers. We benefit from all that because, again, we come in and we have the same mechanism, same target. Our conversations are certainly a lot easier, particularly when we have the profile that we have. I think we should start there. That's all to our benefit. We think that broadening the approach like they've done with respect to more general ophthalmology and endocrinology, 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 for TED because even in an endocrinology world, you have patients who present initially with presumably with the Graves, but as soon as the eye manifestation shows up, they want to consult with ophthalmology.
That's where we think there's 2,000 core prescribers in the US, which is 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. Epamountgen has also been saying that the US, 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 for Tepezza. Why do you think chronic is so difficult? It's been quite some time now since they did their phase four study. How is Viridian better positioned to address the chronic patients?
Yeah. First, I think we think the market's actually bigger than 100,000. You can see in our deck, we talk about 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 more chronic, but that means there's still also an incident population of roughly 20,000 new patients coming into that pool every year. That is based on a number of different research. With their single-digit penetration that you referred to, we agree with that. We think that number is small. Now, their ability to penetrate into chronic is hard to say except for the fact that we think that there was more response that you could achieve in the chronic. I think our data is differentiated on that. Again, it's cross-trial comparison, so you have to put the caveats on that.
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, our numbers were really impressive. 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. 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 bit better and maybe with a payer reimbursement.
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. By definition, these are proptotic patients walking in the door. We also ran, which was different than how Tepezza designed its studies, clinical activity scores on a scale of 0 to 7. Tepezza studies were limited to patients with 0 or 1. Clinical activity score is a proxy for pain and inflammation, redness, that grittiness 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. These are people that are certainly symptomatic. That is 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 does not have chronic data in its label. It has a broad indication statement, but not the data. We are going to have that on day one. The payers are fully aware of what IGF-1R inhibition can do now on the backs of Tepezza.
We just think we're in a better position to drive that penetration into the chronic population.
Great. In May, you guys announced that you guys received a breakthrough therapy designation from the FDA. How beneficial do you think this is to maybe, I mean, there's a benefit to the regulatory path, obviously, in terms of how the market's going to be perceiving veligrotug. By getting that feedback from your KOLs, clinicians being more on their radar, and maybe tell me a little bit about the awareness of that. What is the path for the breakthrough therapy designation to the priority review? What do you have to do to get to that priority review?
Yeah. 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. 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 and communication with FDA in any event. 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. You can't ask for priority review until you file. When we file, we will put that request in. 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.
As I mentioned in the beginning, what breakthrough therapy is, is a mechanism by which FDA actually compares your data to the standard of care. For them to come out and say, "We grant you a designation," that is essentially indicating based on the definition of breakthrough that we represent a potential substantial improvement over currently available therapies. A great place for us to land with our alignment with FDA.
Fantastic. You guys show, I think earlier you mentioned about this, that the positive long-term durability study for data for the phase three THRIVE study. I think there you showed about 70% of patients were able to maintain their proptosis response at week 15 all the way through week 52. How does this compare to the long-term data for Tepezza? Also, do you believe there's a meaningful differentiation from a longer-term durability perspective compared to Tepezza?
Yeah, I can take that one. 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%. 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 veligrotug, with the 70% less drug, five infusions, so fewer infusions than Tepezza, whether the strong responses that we saw at week 15 would continue. I think we answered that with this data.
I think it's durability numbers that we would expect to be in our label, which again is a very strong position for us at launch.
Great. How do you think about the patient who were not able to maintain their proptosis response to 52 weeks? Any implication there for potentially a retreatment?
Yeah. Just a reminder that the vast majority of patients did maintain their response. 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 refer to it. It's not unexpected to have some patients who don't maintain that response. We think retreatment is absolutely an opportunity. Based on real-world data today, we do know of some patients that are getting retreated with the currently available IGF-1R. The good news is they seem to respond again and KOLs support retreatment. That's something that we will be exploring and looking at as a potential.
Okay. Fantastic. In terms of Veligrotug's durability in the chronic patients for the THRIVE-2, will you be showing that data as well when that becomes available? Also, how are you guys looking at the expectation for that? Are you going to benchmark to that 70% in the active patients? Is there any risk that the durability for the 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. The antibody has answered every question all along the way. We don't have the THRIVE-2 data follow-up period yet. We don't have all that data yet. It is the last piece of the BLA. We will be scrambling to get that into the BLA so we can file as quickly as possible. Our plans for whether we put that out or not, I don't know if we need to. It'll be in the BLA anyway. Maybe we'll have it in a medical congress at some point.
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. We'll have the data eventually, and we'll get it out in medical congress, or it'll just be in the BLA.
Fantastic. Obviously, I think for safety, I think this is important to mention that you guys have a lower placebo-adjusted hearing effects, lower compared to Tepezza. How important is that? I mean, we talked about, I mean, for the longest time, you guys talked about having five doses instead of eight 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?
Yeah. We do think it will be helpful as a part of the overall package of efficacy and safety that we're delivering. Of course, the fewer infusions and shorter infusions that come from Veligrotug. It's a benefit-risk conversation that physicians will have with patients. When we first showed the data to some of our KOL advisors back when we reported on the phase three 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 five years, patients know this can be a side effect, and they go on Google, they go on online forums, and they go in and ask their physician questions about hearing impairment as a potential AE. That is a conversation that many physicians are having with the patients.
The fact that we can give the physicians a chance to have an easier conversation, I think it's 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. Almost all of it resolves when the patient comes off of therapy, as we also corroborated with our week 52 data. This is a manageable risk profile for physicians. They're very comfortable managing hearing impairment as an umbrella set of potential AEs. Anything that we can do to make it easier for them to have that benefit-risk conversation with the patient would be better.
Great. I know we talked about the US 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? How will you think about commercializing veligrotug in Europe?
Yeah. 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. We did guide that we would have our MAA filing in the first half of 2026. We're going to get the BLA in. We designed the phase three studies with Europe in mind as well, meaning we have an endpoint 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. We had that in our study to begin with, knowing that that's what Europe would look for. We'll be ready to go.
We just need to switch from BLA into MAA once we get in. Of course, we're just watching how Europe develops in the meantime. We'll just keep our optionality open. We don't have to spend any money for that optionality, which is always great. Other parts of the world, the normal markets like Japan, we're looking at what we're going to do there as well. We have all our options open. Just a reminder, Tepezza has been on the market now for five years, and they're just finally going into Japan and Europe. Horizon was focused on the US. We could skip the waiting period there and get those ex-US revenues going as well.
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 has a price out there. Are you guys looking mostly, you have a differentiated drug, and that looks better in many dimensions? How are you guys looking at the pricing? Is it going to be mostly parity or what's your approach to thinking about that?
Yeah. First, it is too early to talk about pricing, but yes. We're looking at all of that. Obviously, we've spent a lot of time with our market research and talking to payers. We know what the current price is for Tepezza. I think all we can say really at this point is we would probably price per course of therapy like they do. Other than that, more to come later.
I see. Also, the payer coverage. I think one thing when we look across all the payers is that they all limit Tepezza use to once per lifetime. There is some retreatment possible for that. Maybe comment about how you see the payers looking at another drug in this market. What's important to them? Do you think they would loosen up at some point that once per lifetime for veligrotug? What do you need to do to show there?
Yeah. 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. On the chronic setting, they got pushback 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, zero or one. 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 would be more palatable to payers anyway.
This is all good lead work that they're doing for us. 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 three studies, data's coming out next year. How are you thinking about what the expectation for that in terms of what do you need to achieve? Are you benchmarking to Veligrotug, to Veligrotug's phase three study? Is that sort of the goal for 003?
Yeah. So we have both of those two ongoing studies, as you mentioned. We think 003 is a de-risked approach given the data that we've generated with veligrotug. 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 veligrotug at 10 mg per kg and 3 mg per kg IV, respectively. And both of those dosing arms show really great efficacy back in a phase two trial, which of course now 10 mg per kg IV, we've seen spectacular data from Thrive and Thrive 2.
We think the efficacy and safety for 003 is de-risked coming out of what we've seen for Veligrotug, both from an efficacy standpoint and then to the extent that lower overall exposures, even Q4 weekly with a sub-Q 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-1Rs is a really exciting place to be for the 003 studies. On exact expectation setting for those two studies, we haven't come out and set that yet. We do believe that everything we've generated with Veligrotug 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, Reveal 2 studies.
Got it. So you haven't set expectations, but how should the market look at this? Does it have to be as good as Veligrotug, or if it comes slightly below that for efficacy, is there still value in that?
Yeah. I think the way that we look at it is providing more options for patients. A sub-Q option, whether it's Q4 or Q8, both of those would be best-in-class regimens for subcutaneous. There's nothing out there that we know of that is that infrequent and is auto-injector that would be mailed to a patient's home. At the end of the day, either one of those two options would be great for patients. We give them a range of options, including IV, veligrotug as something that they can choose from.
Great. Looking at both the Q4W and the Q8W dosing regimen, is the plan to take both to commercial? How are you guys going to decide between both of these going forward?
Yeah. We'll definitely need to look at the data before making that decision of how we take things forward. Again, as we said, either one of these would be fantastic regimens for patients. It comes down to what the safety and efficacy data shows from the trials. We'll make decisions accordingly based on that.
Okay. Great. For 003, are you guys committed to launching it with an auto-injector? How's that portion of the development going for 003?
Yeah. It's going really well. Everything is on track. As we guided to 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. All of that has been worked into the timelines 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. A lot of them have been disappointed. 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's 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. I mean, when we look at, it's a cross-trial comparison, but 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're not asking people to switch off Tepezza to try us. Everyone comes in the door and they'll have options with respect to our drug versus Tepezza. We think we're in a good position there.
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. 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. The competitive landscape is cleaned up quite nicely for us.
Steve, Shan, it's been a pleasure hosting you for a second time at the Goldman Sachs conference. Thank you so much for attending. I'm going to turn it to you for any final concluding remarks.
Yeah, sure. Look, bottom line, we have de-risked 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. All of that is on track. We're executing across the portfolio. We just continue to march along and keep de-risking these programs even further. Everything's on track for we're going to be a commercial company next year. I think that's a pretty exciting prospect.
We're continuing to advance our FCRN portfolio as well, which very much fits into that de-risked and exciting development path for a de-risked market.
Great. Thank you.
Great. Thanks so much.