Viridian Therapeutics, Inc. (VRDN) Earnings Call Transcript & Summary

Hello, and welcome to the Viridian Therapeutics Conference Call to report top line results from THRIVE, our Phase III Clinical Trial in Patients with Active Thyroid Eye Disease. [Operator Instructions] As a reminder, this conference call is being recorded. I will now hand the call over to Ms. Louisa Stone, Manager of Investor Relations at Viridian. Please go ahead.

Thank you, and welcome, everyone, to our conference call to report top line results from THRIVE, our Phase III Clinical Trial in Patients with Active TED. The press release detailing these results is available on the Investors page of our corporate website at www.viridiantherapetics.com. Joining me on the call this morning are Steve Mahoney, our President and CEO; and Shan Wu, our Chief Business Officer. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements regarding our financial outlook in addition to regulatory, product development and commercialization plans and research activities. These statements are subject to risks and uncertainties that could cause actual results to materially differ from those forecasted. A description of these risks can be found on our most recent Form 10-Q and 10-K on file with the SEC. I would now like to turn the call over to Steve Mahoney, our President and CEO.

Thank you, Louisa, and good morning, everyone. We are thrilled today to present the top line results from THRIVE, our Phase III clinical trial in patients with active thyroid eye disease or TED. Before we get going, I would like to extend a thank you to the TED community, the patients, investigators, partners and research staff and everyone else who made this trial and these results possible. It is worth remembering that just a few years ago, before 2020, the only treatment options available to TED were steroids or invasive surgery. For a disease where patients with moderate-to-severe TED are living with debilitating symptoms of proptosis, pain and double vision. With the approval of teprotumumab in 2020, TED patients had a targeted therapy available to them for the first time. However, teprotumumab's high treatment burden of 8 intravenous infusions given almost over 6 months every 3 weeks can present a significant barrier for patients to start therapy. Viridian has designed next-generation molecules and sought to quickly advance differentiated options for patients. And we are tremendously excited today to present exciting positive results from our first pivotal Phase III trial of veligrotug, which we have previously referred to as VRDN-001. Throughout the rest of this presentation, I will refer to veligrotug as veli. Veli is an antibody that inhibits the same target as teprotumumab, IGF-1R, a validated target known to drive TED pathology. Veli is administered at 10 mg per kg for only 5 infusions. And as you will see today, it showed positive compelling and consistent responses in THRIVE, the largest placebo-controlled Phase III study conducted to date in active TED. In addition to veli, we are also developing VRDN-003, our potential best-in-class subcutaneous program, which shares the same binding domain as veli and has been enhanced with a half-life extension technology. 003 is designed to be a low-volume infrequent subcutaneous injection that patients can self-administer at home. We initiated our 2 Phase III -- pivotal Phase III clinical trials for 003, REVEAL-1 and REVEAL 2, in August this year. Now let's get to the THRIVE data. We are thrilled to report that veli met all the primary and secondary endpoints in THRIVE at 15 weeks, including measures of proptosis, clinical activity score or CAS and diplopia, with a high degree of statistical significance. We saw a rapid onset of treatment effect with responses in as few as 3 weeks on all disease endpoints after just 1 infusion of veli. Veli was well tolerated with no treatment-related serious adverse events and 96% of veli treated patients completed all doses of treatment. The potential for hearing impairment is a known side effect of IGF-1R class, and we were pleased to observe that just a 5.5% placebo-adjusted rate of hearing impairment. None of these hearing impairments resulted in any dose interruptions or discontinuations. With this rapid, compelling and consistent clinical response and favorable safety profile, we believe veli, if approved, has the potential to be a differentiated and meaningful option for patients with TED. We believe these results provide strong support for 003, which we will discuss later in the presentation. And now let's jump into THRIVE. Moving to the next slide. Here's a quick look at the THRIVE study design. The study enrolled a total of 113 active TED patients with roughly half enrolled in each of the United States and Europe, randomized 2:1 to receive veli or placebo. Patients received 5 doses of veli or placebo every 3 weeks for a total treatment period of just 12 weeks. The primary efficacy endpoint was proptosis responder rate, or PRR, measured by Hertel Exophthalmometry at week 15. Key secondary endpoints included measurements of CAS, diplopia or also known as double vision. Patient efficacy and safety follow-up continues in the study through week 52, and now let's turn to the results. Starting with baseline characteristics. We were pleased to see these were well balanced across the veli and placebo arms. As expected for the TED population, the majority of patients enrolled in the study were female and the average age of participants was approximately 50 years old. Baseline values for proptosis, CAS and diplopia were in line with our expectations and the precedent studies in this patient population, including about 2/3 of the patients with diplopia at baseline. Our baseline characteristics were also similar between patients enrolled from the U.S. and Europe. Turning to the next slide. I'm thrilled to announce the impressive efficacy results from THRIVE's top line. This study demonstrated a high level of statistical significance with a p-value of less than 0.0001 across all endpoints in the primary and all secondaries as well at 15 weeks. I'll speak to a few of the highlights here and then I'll show you some more detailed data over the next few slides. On the primary efficacy endpoint of proptosis responder rate, patients in the active treatment arm reached a 70% response rate compared with a 5% on placebo, confirming the robust activity of veli. We were pleased to see robust, statistically significant results across all secondary endpoints measuring symptoms that we know are highly meaningful to patients living with TED. To highlight a few, over 60% of patients receiving veli achieved a CAS score of 0 or 1 in just 15 weeks. As a reminder, this represents no or minimal disease activity, and more than half of the patients treated with veli, who had diplopia at baseline, achieved complete resolution of their double vision. This is an outstanding result. Now we'd like to turn to show you these data across time points, highlighting the consistently rapid and deep responses we saw with veli across endpoints. We'll start with proptosis. As we just reviewed, 70% of patients receiving veli demonstrated a proptosis response at week 15 compared with 5% of patients on placebo. We were also pleased to see the clear separation of the veli and placebo curves across all time points in the study, including more than half of the patients achieving a response at 3 weeks following just 1 infusion of veli. These improvements continued for the full course of 5 infusions. On the right, the mean proptosis change from baseline was also consistent with the rapid and deepening patient responses observed in the study with a mean reduction of nearly 3 millimeters at week 15, a result that is clinically meaningful for patients. Now let's turn to diplopia and CAS. We know that diplopia or double vision is a symptom that is debilitating for patients and can significantly impact our activities of daily living and quality of life. Patients with double vision may have trouble with day-to-day tasks such as driving or reading. In THRIVE, we saw over half or 54% of patients receiving veli achieve a complete resolution of their diplopia from baseline to week 15, with a placebo-adjusted complete resolution rate of over 40%. We believe this is a remarkable result. Now on to CAS. As a reminder, CAS is a 7-point composite scale of disease activity, including pain, redness and swelling. A CAS score of 0 or 1 represents the elimination or near elimination of the symptoms of TED, 64% of patients receiving veli in THRIVE achieved a CAS score of 0 or 1 in just 15 weeks, with a placebo-adjusted rate of over 45%. Again, we believe these are great results for patients across all endpoints. The proptosis results we presented today were measured using Hertel Exophthalmometry, which is the most commonly used method for measuring proptosis. In THRIVE, in addition to Hertel, we also, for the first time in a randomized controlled study, developed and systematically employed a methodology to also assess proptosis via imaging. As you can see, these data are remarkably consistent across the 2 measurement tools and therefore, provide additional support for the significant impact of veli in proptosis. We look forward to sharing further data on our imaging results. Moving on to safety. Veli was generally well tolerated with a safety profile that we are very pleased with. The vast majority of adverse events were mild, and there were no treatment-related serious adverse events. In addition, 96% of patients treated with veli completed all 5 doses, which was fantastic to see and above our expectations. Looking at the safety table, we observed an adverse event profile consistent with previous veligrotug studies. Importantly, we saw a low 5.5% placebo-adjusted rate of hearing impairment, which was better than we expected. Further, none of these hearing events led to dose interruptions or discontinuations and all patients completed their full course of treatment. Across all adverse events, the vast majority were mild and only 1 patient discontinued for a related treatment emergent adverse event, which was also mild. Overall, this data gives us confidence in the safety profile of veli, and we are very pleased with these results. In summary, we are exceedingly proud of these results from THRIVE. We achieved all primary and secondary endpoints with high levels of statistical significance. We saw strong treatment effects as early as 3 weeks and a favorable safety profile. These results demonstrate veli has the potential to present a highly compelling product profile for patients. We look forward to bringing this important therapy to patients as the first commercial product in our TED franchise, if approved. We believe the THRIVE data presented today also provides strong support for 003, which has the potential best-in-class profile as our next-generation subcutaneously delivered IGF-1R inhibitor. Now let's talk about THRIVE-2. We are on track to deliver top line results from our second Phase III clinical trial THRIVE-2. At the end of this year, in patients with chronic TED, we completed enrollment for THRIVE-2 in July, exceeding the enrollment target with the approximately 40% of patients enrolled from the U.S. With 188 patients enrolled in THRIVE-2, this is the largest randomized placebo-controlled study in TED to date. The strong results from THRIVE reinforce our confidence in THRIVE-2, and we look forward to sharing the top line data from that study at the end of the year. Our excitement for the THRIVE data today goes well beyond veli to our potentially transformative subcutaneous 003 program. 003 shares the same binding domain as veli and therefore has the same activity against IGF-1R. It only differs from veli in its half-life extension technology, and then to our knowledge, is the only half-life extended IGF-1R antibody. This shared pharmacology along with the veli exposure that showed clinical responses in earlier studies guided our selection of every 4-week and every 8-week dosing regimens. The THRIVE results we are reporting today validate the choice of these regimens and reinforce our confidence in the potential of 003. We initiated Phase III studies REVEAL-1 and REVEAL-2 in August this year, and we are on track to deliver top line data in the first half of 2026. On this next slide, you can see the clear differentiation in the dosing paradigms between our TED franchise and the current standard of care, which was a major advance for patients that were historically receiving surgery and steroids. We believe that our differentiated profiles for veli and 003 can become preferred treatments for TED patients, if approved. Let's start with veli. With a 10 mg per kg dose versus 20 mg per kg, 5 infusions versus -- instead of 10 -- or instead of 8, excuse me, and shorter infusion time per dose, patients received approximately 70% less drug and spend 70% less time in an infusion chair than the current standard of care. With veli, patients complete all infusions in just 3 months. With the strong THRIVE data that we showed today, which includes demonstration of the onset of clinically meaningful effects at just 3 weeks after just 1 infusion, we believe veli will present a compelling and differentiated treatment profile for patients. Moving on to 003. We believe its profile as an infrequent self-administered subcutaneous injection that patients can take at home every 4 or 8 weeks has the potential to both improve the patient experience and make our TED treatments available to more patients. Moving on to the market opportunity, we believe both potential products in our TED franchise have the profile to penetrate the TED market and do it quickly, given the unique market dynamics that I'll describe in a bit more detail. Unlike markets where a second entrant has test to switch patients off their existing therapy, every year, a completely new set of patients will make a decision as to which available therapy is best for them. For a second-to-market drug with a differentiated profile like veli, this is an opportunity to drive rapid uptake. The current marketed IV IGF-1R is now annualizing over $1.9 billion in sales with regulatory filings ex U.S. that are anticipated to further grow the market. If veli is approved, its launch could lay the foundation for the potential launch of our subcutaneous 003 program, which we expect would expand the reach of the IGF-1R therapeutic class. We anticipate 003 could potentially launch only 1 year after veli, if approved. Finally, on this slide, following today's exciting THRIVE results, you can see that we have multiple meaningful catalysts across each of our 2 TED and FcRn assets beginning later this year. Let me take a moment to walk through these before we open up for Q&A. On TED, veli's second Phase III trial, THRIVE-2, will have top line data in chronic patients at the end of this year. Together, THRIVE and THRIVE-2 would form the core clinical package to support a potential BLA submission in the second half of 2025 with the potential for a U.S. launch in 2026. We also expect this data package to support a potentially -- a potential market authorization application in Europe. For 003, we anticipate top line data from both the 003 subcu REVEAL clinical trials in the first half of 2026, which we anticipate will enable BLA submission that same year. Before we wrap up, I'm going to quickly touch on several milestones in our FcRn portfolio. First, we are on track to file an IND by year-end for 006, the only other known Fc fragment in development. for which we have already demonstrated compelling IgG lowering in nonhuman primates with no effect on albumin or LDL levels. We expect to release data from the healthy volunteer clinical study including IgG reduction in 2025. Finally, later this year, we will also present nonhuman primate data from VRDN-008, 008 is a bispecific FcRn inhibitor containing a domain that binds albumin and is designed to extend the half-life and meaningfully improve the pharmacology of this validated mechanism. We will share more details on the program later this year, and we are very excited about its potential to deliver a best-in-class profile in what we believe is a large commercial opportunity across many autoimmune diseases. We anticipate submitting an IND for 008 at the end of 2025, in line with other next-generation FcRn programs in the field. We're excited for the opportunity to drive continued value creation for Viridian shareholders, and we look forward to future disclosures across the portfolio. It has been my pleasure to share the exciting top line data from THRIVE with you all today. This would not be possible without the entire TED community. I would like to thank the patients and their caregivers, our investigators and their research teams for their contributions to the success of THRIVE. I would also like to thank all of Viridian employees for their hard work and dedication to bringing better treatment options to patients. And with that, I will turn the floor over to the operator for questions.

[Operator Instructions] Our first question comes from Michael Yee from Jefferies.

Congrats on a great result. We have 2 questions. One was on efficacy and just thinking about the results that you've put out today. How you think that, that positions you on the subcu, which I know you are completing, I know that the subcu has both a monthly and a once every 2 months. I'm trying to recall, but I think that those design was based on bridging the 2 different doses you have shown previously. So today's results, I presume, would fall within that expectation that both of those arms could work. So could you just walk through maybe your view on how that handicaps or increases the probability of success, that would be great. And then just a quick question on safety. You have a bunch of different things listed on the AE table, but I wanted to know specifically whether any hearing loss cases. And then also how you think about muscle spasms and any of those other numbers on that chart.

Yes. Great, thanks Mike. Let's talk about the -- your first question on subcu. So first and foremost, no changes as to the design of REVEAL-1 or REVEAL-2 as a result of these data. These data are fantastic. This only reinforces our confidence in the exposure levels that we expect to have in the REVEAL studies for subcu. Just a reminder, 001 and 003 or veli and the 003 program, share the same binding domain in the antibody, and the subcu program 003 simply has a half-life extension technology associated with it. Their preclinical activity was very similar, pretty much the same. So seeing this data from the veli study, we believe it's enormously derisking for 003 on both efficacy and safety. The data we just showed is going to enable the dosing regimens that you're referring to with respect to Q4 weekly and Q8 weekly. We see, as you can imagine, we see tremendous market potential for the subcutaneous with the self-administered auto-injector that we can deliver to people's homes. And we're looking forward to moving that forward. I just provided the timing on that. We look forward to the top line data readout in the first half of 2026. I'll point out just in terms of timelines, we are using the same infrastructure that we just did a great job executing on THRIVE and THRIVE-2. We exceeded enrollment targets in both studies. We did those studies on time, if not faster than expected. And we're using that same infrastructure to enroll the subcu study, which initiated in August. So we initiated both REVEAL-1 and REVEAL 2 in August. So those were on time. So we're excited there. I hope that answers that question. On safety, you asked about hearing loss. Just a reminder, like let's just take a quick step back on safety overall. This is the largest study run in TED to date. I think the overall safety profile for 001 is well tolerated. It's in line with IGF-1R, as you would expect, not drawing any clinical trial comparisons, you have to reach your own conclusions. I'm not going to make conclusions for you. But the reported AEs, and I'm going to get to your specific question, but the reported AEs are known. They're expected for this class. They're almost all mild and all considered manageable especially with the profound efficacy balanced by the profound efficacy of IGF-1R inhibition. And we had no SAEs related to the drug. You saw the discontinuation rate was extremely low, 96% of patients treated completed all 5 of their infusions. So we feel really good about that, with that as a backdrop. Now to your question, we had 2 related treatment emerging events representing reductions in hearing. One was mild and one was moderate. But in both cases, I'll just reiterate, in both cases, there was no interruptions to dosing. There was no modifications to dosing schedule, and all of those patients completed their dosing. And so that's a decision that's made by the patient, but it's also made by the physician. So that's a really -- I think that's pretty telling as to how that worked out in terms of the hearing. Again, I'll just remind you of the really low and better-than-expected low placebo adjusted rate here.

I'll just add to that. This is Shan speaking. I'll just add to that, that the rest of those were tinnitus essentially.

The next question comes from Rich Law from Goldman Sachs.

Congrats on the results from me as well. So given how much better it show compared to your expectation, how do you think the clinical profile compares with TEPEZZA now in the commercial setting? And will you raise your expectations for THRIVE-2 to show a similar and potentially clinical differentiation against TEPEZZA in the chronic TED patient as well? And I have a second question that I'll save for later.

Okay. Great. Thanks, Rich. So you're asking for how we expect to commercialize the veli program in terms of our clinical profile versus the standard of care, which is currently TEPEZZA. Well, clearly, you can see that at a very basic level, we are 5 infusions. And again, I'm just describing the profile. We're 5 infusions at 10 mg per kg versus 8 infusions at 20 mg per kg. And you can see that the consistency of the response across all of our endpoints shows you that on proptosis response, on CAS score, on diplopia resolution, you can see the data that we put out today, that is a super compelling clinical profile. Now you take that same profile and you're in a new start market, and this is a critical component of the commercial market. In a new start market, we are not trying to switch patients off any existing therapy or chronic therapy. A new -- every patient is a new patient, they come in the door and they want to understand what are their options. When our clinical profile is there available and theirs is as well, and the choice is, do I do 5 infusions or 8? Or do I do 10 mg per kg and 20 mg per kg? In 2/3 less overall drug with a faster infusion time, I think, we think that the patients are going to -- with the similar outcomes as what we're seeing here, again, not a cross-trial comparison, you've got to draw that conclusion for yourself. But when you see those profiles lined up against each other, we think we're going to win that conversation every time. That is the type of thing where you're going to choose -- we believe patients will choose that lighter IV burden. So I think that's how we expect the profiles to match up. With respect to the THRIVE-2. THRIVE-2, obviously, this is a derisking event in our view with respect to the results for THRIVE-2. Again, I think we just want to be competitive with the current standard of care. These results, if you look at our -- across the board, again, I'll just emphasize the consistency of clinical benefit across all our time points and the end points. So we -- again, we just think that these results only increase our confidence in the outcomes for THRIVE-2.

Okay. Got it. And then my second question is that, when you look at the placebo effects, this seems -- it seems much lower than those reported by TEPEZZA. Was there anything that you implemented that help control the high placebo effects or variability? And also, when you look at the time curve, the placebo response looked consistent around like 11% to 13% for the proptosis response, but -- and then dropped to like 5% at week 15. Is that just [indiscernible] noise or any thoughts there?

Thanks, Rich. This is Shan. I can take that question. So starting with the placebo response, we were really pleased to see that as we said before, the noise of the Hertel Exophthalmometer can be magnified by small numbers. And remember that our Phase II studies had a placebo arm that was quite small, of only 5 patients. And we've been saying all along that we powered THRIVE to really effectively account for that noise, and you can see that we indeed did that here. And really THRIVE is the largest controlled trial that's ever been conducted in thyroid eye disease. And so we're really pleased to see this. And the big reason was to reduce the variability of Hertel and we think we've accomplished that goal. And then on your second question regarding -- I believe there was a second question on the time course with regards to the range across the time course between treatment arm and placebo, I think we're just exceedingly pleased to see the consistency. As you saw from the presentation, we -- over majority of patients responded on proptosis after just 1 infusion, that was remarkable to see, and that result was carried through for the entirety of that 15-week time point and really it's just super consistent across all of those time points.

Our next question comes from Gregory Renza from RBC Capital Markets.

Steve and Shan, congrats on the updates and the results today. Steve and Shan, you've commented on the consistency of the trial results. I'm just curious if you could comment a bit on the contributions of the U.S. and the ex U.S. sites and any consistency or lack thereof that you've seen with respect to the patient performance? And then I have some follow-ups.

Sure, Greg. Yes. So as a reminder, we enrolled for THRIVE, half the study was enrolled in the United States and almost half in Europe. There were some patients in Australia. So really good distribution and in terms of baseline characteristics, very consistent across the board.

And as we've all observed, just trial demand when it comes to signing patients, can you just give us an update on the safety database that you're generating, what you need, how that is tracking and how these results can perhaps potentiate that moving forward?

So yes, we're -- we have reiterated that we're on track for our BLA filing. Obviously, our safety database fits within the BLA filing. So everything is on track. Nothing to -- yes, we're -- everything is moving forward and we feel really good about our enrollment curves actually across all of our studies.

Great. Great. And then last question for me. I know you commented on the diplopia. Just curious if you could help put that in context, just the clinical meaningfulness of that, how that really translates into a patient benefit? And as you think about differentiation with the on-market products, how that and the other secondary endpoints can really set you apart? Thanks again and congrats on the data.

Yes. Thank you for that question. Well, you can imagine, diplopia or double vision can be enormously debilitating for patients. In fact, physicians will tell us that the proptosis or the aesthetically, how people look, and then the diplopia are the 2 biggest concerns for patients. So you can imagine what double vision can do to your quality of life in terms of your ability to read, write, drive, go to work. And you can see how that can cascade from there in terms of not wanting to leave your house. And so that can be really difficult for patients. So these results, to look at a 54% achievement of diplopia resolution at 15 weeks, that is fantastic. That's a great result. And as I noted in my comments in the slides, and just again, as a reference to the TEPEZZA outcome, they had a combined placebo adjusted rate of 25% versus our 43%, 42%. So that is a significant step forward, and I think that's going to be -- it's really going to resonate with physicians and patients. I think I would just emphasize again, Greg, based on your question on differentiation, there's a lot of consistency here across all these end points. These are the endpoints that matter to patients, as I mentioned, proptosis and diplopia, but we had very good results on CAS, which is a proxy for pain and inflammation, irritation. That's a really good proptosis -- a very good response there on CAS. So we feel really positive across all of these endpoints. And again, I'll just reemphasize on the time points. You saw that rapid onset of action or relief with 53% of patients getting a proptosis response after just 1 infusion. That is incredible and exceeded our expectations. So we're really happy with all of these outcomes.

Our next question comes from Laura Chico from Wedbush Securities.

I have one on the onset of activity. So I think you mentioned that most patients are receiving or achieving the response after a single infusion. I'm wondering if you can talk a little bit about this type of kinetics in context with 003. How should we be thinking about the potential for onset of activity in the REVEAL study?

Well, like we said, the same binding domain, the only difference between the antibodies for veli and the subcu antibody is the half-life extension. As I mentioned in the slides, we saw a lot of -- the preclinical activity was essentially the same. So we expect to see that act in a similar fashion. With respect to the onset of activity, I think we'll have to wait and see, but I think our expectations, what we're trying to do is match exposures, right? I mean that's the whole name of the game for subcu versus IV. And that will be -- so we'll see what happens, but we think that's -- we expect to see similar.

Okay. And then I guess just with respect to the ex U.S. filing strategy, I believe there was a separate primary endpoint for Europe, but I think it was also achieved here. Just wondering if you can opine a little bit on the timelines there or additional ex U.S. submissions?

Yes. So we're planning to pursue Europe as well. We believe that the data package that we're putting together in THRIVE and THRIVE-2, with the safety database, will all be sufficient for Europe. And our expectation is to submit in Europe as quickly as possible after the U.S. BLA.

Got it. Okay. Last one, just on the safety. I don't think I heard any clarification or additional color on the injection site reactions. Any characterization there you could share?

Are you referring to the infusion -- are you referring to the...

Sorry, the infusion-related reactions.

Okay. Yes. Sure. Yes. So infusion-related reactions are, as I mentioned in the slides, these are known and expected for the IGF-1Rs and the antibodies in general. So none of these infusion reactions were severe. And infusion reactions are widely managed in everyday practice at infusion centers or even at home infusion. And so just -- and as I mentioned also, we saw no interruptions in dosing. No discontinuations due to infusion reactions, no modifications of their dosing schedules. And so that was really good. And then I'll point out that the vast majority of these infusion reactions occurred in the first or second infusion.

Perfect. Congratulations, guys.

Our next question comes from Thomas Smith from Leerink Partners.

Let me add my congrats on the data. First on efficacy, I know the focus here is on the 15-week primary endpoint. I was just wondering if there are any early insights into the durability response beyond that time point or any visibility into when we could learn more on durability? Maybe if you could just remind us or elaborate on your expectations for durability relative to what TEPEZZA has shown with their 24-week regimen?

Yes. So obviously, this is a top line data release. So we -- this is still an ongoing study. Everything we've shown today, we told all these profound effect on all the endpoints as expected for an anti-IGF-1R antibody, and there's no reason to expect any differences regarding the maintenance of response through week 24. In fact, we have a small subset of patients out to week 24. That data is early and preliminary, but it confirms this for us that we see that responses are maintained. Again, early data, but encouraging and we'll present this data at the appropriate time.

Got it. That makes sense. And then if I could just ask a follow-up. I mean, the focus here is obviously on TED. But I was wondering if you could just elaborate on what we can expect from the FcRn franchise updates over the next 12 months as we start to look forward to some of the news flow coming out of those compounds?

Yes. Sure. So we have -- as I noted in the presentation, we have several things coming. We have our 006 program. IND is still on track to be filed at the end of this year, which is great. So we're making great progress there. And then we'll run a healthy volunteer study and get data that will help us with dosing on that next year, which we also mentioned. And then the 008, the half-life extended approach, we are -- we'll have nonhuman primate data for that later this year as well.

Got it. Congrats again on the data.

Our next question comes from Alex Thompson from Stifel.

I want to add my congrats as well. Two for me. I guess for THRIVE-2, you've talked about derisking this readout. I wonder if you could talk a little bit more about the sort of similarities and differences in this population versus a more active population and sort of the context for what you think the bar for success would be for THRIVE-2? And then more broadly, looking ahead, I guess, could you talk a little bit more about your broader vision for a franchise here with an IV product coming in first and then in a subcu product coming later, and how you're thinking about broadly competing and expanding the market?

Yes. Great. Okay. So on THRIVE-2, we -- first and foremost, we find that this data is really helpful, and we believe it derisks THRIVE-2, and that is based on the consistency of the clinical benefits across all the endpoints that I've talked about with respect to proptosis and diplopia and CAS. So that THRIVE data really shows us what this antibody can do. THRIVE is just, as a reminder, THRIVE is currently the largest study ever run. And THRIVE-2, when it completes, will be even larger. We have 188 patients in that study. So we're well powered for the chronic population. And looking at these numbers that we saw across these end points, we just think that this just increases our confidence in THRIVE-2. And we look forward to giving you those results at the end of this year. In terms of bar for success in THRIVE-2, we're just -- we want to be competitive. And so let's just see where we land, but we think this is a derisking event for that. With respect to competition in the market, IV and subcu, we think IV is going to stick around. IV is going to be a part of the market even when it's mature. There's plenty of examples out there in the world where that's the case. And so we expect that, obviously, subcu will drive a big portion of the market. We have talked about before that possibly a 70-30 split in a mature market, 70% subcu, 30% IV, but these are sizable markets. The current market for IV is annualizing at $1.9 billion in sales. And we think we're going to grab some of that plus we'll be able to expand the market. The biggest part for expansion of the market is the -- making the subcu program available to patients who may not live next to or near an infusion center or just don't have the same type of access to infusion centers than other people do. And when we launch, our expectation is to launch with an auto-injector that we can deliver to people's houses, and they can self-administer at home. So we think increasing that availability for patients will significantly expand the market from there. And obviously, we talked about expansion to market. We just talked a little bit about Europe and we know that there's been filings in Japan. We intend to do that as well. So a lot of potential for expanding the market here.

Our next question comes from Rami Katkhuda from LifeSci Capital.

Congrats on the data. Two quick ones from me. First, I just wanted to confirm that you're using kind of the same definitions and methodology of measuring hearing related AEs as Horizon did? And then secondly...

Yes, 100%.

Okay. Awesome. And then rates of AEs with tepro increased from optic to the Phase IV study in chronic TED patients. Is this likely going to be the case in THRIVE-2? Or have investigators just become more aware of these associated AEs with the IGF-1R class as a whole?

Do you mind repeating? So let me answer your first question, but I'm going to ask you to repeat the second question because I wasn't quite following the question. Your first question was on, did we use the same methodology as tepro in terms of reporting AEs and hearing impairment in particular. And the answer to that question is 100%, yes. We used the exact same methodology. So would you mind repeating your second question? It was a little hard to follow.

Yes, of course. So basically, with tepro from the Phase III optic study to the Phase IV chronic TED patient study, you saw an increase of AEs across the board. I guess, is this likely going to be the case for THRIVE-2? Or have investigators just become more aware of kind of the AEs associated with the IGF-1R class?

Okay. So I think I understand now. So yes, when the original tepro studies were run, it was not well understood at all that hearing impairment was -- could be associated with IGF-1R inhibition. And so when they ran those studies, there was no one really paying attention to that hearing impairment. Their first study there, those registrational sites, 0% placebo response, 10% absolute. And then when they ran the chronic study, the hearing impairment AEs went from -- went up to 22% on the absolute basis and 10% on the placebo response. And therefore, you had a placebo adjusted of 10% in the registration and 12% on the chronic. So you're referring to the evolution of understanding. Now we're running these studies several years later. And we actually ran the most comprehensive -- we ran not only the biggest study in TED so far, but also the most comprehensive with respect to hearing assessment. And so -- and we're still seeing this really low rate of 5.5% placebo adjusted. That is, as I said earlier, that's an outstanding outcome for us. But I think that's a -- you referenced the evolution on the tepro side, but do we expect to see this in THRIVE-2? I don't know. I mean I think this is a pretty comprehensive set of data. So we feel really confident about what to expect. This, again, this is a derisking in our view of the THRIVE-2.

Got it. Congrats again.

Our next question comes from Julian Harrison from BTIG.

Congratulations on these data. I'm curious about your outlook for 003, its competitive positioning as an auto injector in the subcu landscape. Maybe with some comparison to other subcu options that could become available later this decade. Also wondering if the THRIVE data today reinforce maybe an expectation that you have an investing category subcu option?

Yes, so just to kind of reiterate here, the veli or the 001 program and the 003 program have the same -- it's the same binding domains. The antibody is the only difference with the subcu, it's the half-life extension. So a lot of similar -- expected similar activity there. In terms of the competition, to your question, as to what it looks like, they haven't commented on exactly what it looks like. We don't -- we don't have real information or guidance from them as to exactly what their subcu offering looks like. We do know that with the 20 mg per kg dose, you are talking about a pretty -- that's a large volume to concentrate into, for a subcu offering as opposed to ours where we've already formulated down to a 2 ml formulation that we can fit into an auto-injector pen. And as I said, we expect to launch with an auto-injector. And you can imagine how much -- how easy that can be for patients when it's delivered to your house and you can self-administer at home. So we think that's a highly competitive profile. Without knowing exactly what else is coming, it just doesn't appear that -- we firmly believe that we'll be potentially best-in-class because we have all the advantages that I just laid out.

Next question comes from Jason Butler from Citizens JMP.

Let me add my congrats on the results. Wondering, Steve, if you could just give some high-level thoughts about the scale of the commercial infrastructure that you intend to launch 001 with? And then just again, any high-level thoughts on the kind of medical affairs work that you'll be doing over the next year or so to, for example, build awareness with physicians and payers?

Yes. Great. So I'll take the second question first. Yes, I mean, we really, really look forward to getting all this data out there so people can understand it. I think there's been a lot of anticipation in the physician community. And certainly, the patient community to look for more options. And I think what we're describing today is a fantastic option for patients and physicians as well. Your first question on scale of commercial infrastructure. That's the great thing about this. This is a defined call point. It requires -- it does not require a large infrastructure. In fact, we can do this. If you look at Horizon's, this is easily one that a small company can do. Horizon's initial sales force was roughly 130 sales reps and they had a spectacular launch. So we certainly can fit into that without too much of a commercial build required. We will be maniacally focused on patient services in order to make sure that we get patients enough access as best as possible. So yes, and then the European infrastructure, we expect to be even smaller because it's more Center of Excellence focused. So not a big commercial build required to get the revenues that we expect.

Our next question comes from Kalpit Patel from B. Riley Securities.

Maybe one for the hearing impairment, the 5.5% placebo-adjusted rate, do you expect that rate to deviate over time as you follow patients for a longer period? Or do you expect that to remain consistent whenever you report additional data? You did mention earlier on the call that you did see some data at 24 weeks, so just curious on this specific AE.

You know what, Kalpit, I guess I'll take that because, look, this is a top line result, top line data readout. I think that level of detail in terms of tracking those patients, we still don't have the full data set. So why don't we kind of -- we'll get into that level of detail at an appropriate time when we have more data to discuss and we'll do that at a medical meeting or something.

Okay. Got it. And then what's -- just curious what's driving the hearing impairment in that placebo group? I think TEPEZZA study, if I recall correctly, had 0%. So just curious what's happening in the placebo group.

Well, they had 0% in the first study, that was not exactly representative of what they saw later. In one of the earlier questions that someone asked, we discussed the evolution, in the chronic study, the absolute rate jumped up to 22%, the placebo rate jumped up 10%. So -- and then I think there's been publications out there showing real-world evidence that takes it even higher. But yes, I don't think the -- looking at that 0% placebo rate is all that informative.

Got it. Okay. And then for the efficacy metrics, the mean change in proptosis and the diplopia complete resolution rate, it seems like there is sort of a slope there at the end from 12 to 15 weeks. Do you think patients would continue to benefit more if they had received additional infusions given that slope? Or do you think we're maxing out there at 15 weeks?

Well, I think that's probably another one. Let's see what the data set. I mean, as I mentioned to someone on an earlier question about resolution, we expect to maintain these responses based on some of the early data that we've seen. But again, that's early and we'll see how that plays out. But our expectation is to be able to maintain these responses out to week 24. And that, I mean, that makes sense to us. So we'll have to see, again, we'll have more data to come.

Got it. Congrats the data.

Our next question comes from Gavin Clark-Gartner from Evercore ISI.

Congrats on the results. I just wanted to circle back specifically to the hearing loss cases. So I believe you noted there were 2 events, 1 mild and 1 moderate. I just wanted to confirm, were those both on the veli arm? And what did you see for hearing loss for the placebo arm?

So on the -- yes, so just to reiterate, thanks for the question, Gavin. So we had, as I mentioned, we had 2 related treatment-emergent events that had reductions in hearing associated with them. One was mild, one was moderate. And again, just to hammer home this point, it had no impact on dosing, no interruptions, no modification in schedule, no discontinuation. So they completed the treatment course.

I'll add to that, that, Gavin, that was in the veli arm. And just a reminder of the size of that one was 75 patients, so 2 out of 75 is 2.5%, which is a remarkable rate. And as we mentioned earlier, the rest of it were essentially tinnitus, including with the placebo arm. We also did see a grade 2 hearing impairment in the placebo arm. And so you can see that this is an expected and known symptom in these patients.

And just to be clear, the grade 2 hearing impairment on the placebo arm, was that a hearing loss case?

It was tinnitus.

Okay. That helps. And secondly, a totally separate topic. We've heard that TEPEZZA's first subcutaneous approach is an on-body injection. So just assuming that is true and is an on-body injection, could you just comment on an auto-injector versus on-body, the commercial dynamics and potential adoption with those 2 different approaches?

Yes. Well, I mean, I think so assuming that's true, assuming that's true, there's obviously an advantage to -- there's -- it's just more involved, an on-body is more involved. I think the infusion time, it's more of an infusion pump that you wear and it has a slower infusion time over the course. There, we expect that the profile you're referring to is not half-life extended. And as I mentioned earlier, the volume that -- converting that 20 mg per kg dose into something that it is competitive with an auto-injector, it seems like an uphill battle. And as I mentioned, we've already formulated to fit our 2 ml into a 2 ml auto-injector pen and we can deliver that to your house so you can self-administer at home, and that is a really, really competitive advantage in our view. It's just easier to manage. Can we just have -- I think we're getting close to time, so maybe 2 or 3 more questions?

Noted on that. Our next question comes from Derek Archila from Wells Fargo.

Congrats on the data. Just a follow-up on the 2 hearing events. I guess, did this require any type of intervention? And also what infusion did they occur at? And then just the second question, I guess, now that we've seen the profile of veli, you've talked a lot about subcu expanding the market, but do you think that a shorter course IV might also expand the market? How many patients are deterred by TEPEZZA study based on the AE profile and also the 8 infusions?

Yes. So just to take the first question, there was no -- well, as I mentioned, there was no discontinuation or no interruption to their dosing. In terms of what physicians did as a result of that, that's a whole another level of detail we'll have to get into. That's not really in front of me for our top line data release. But I think just reiterating once again, no impact on dosing schedule and those patients completed their infusions. So that's that. And then in your question about timing. Again, we'll have all that. That's probably more appropriate for a medical meeting. We'll have that at some point. This is just intended to get the information out at the top line. Shorter course IV, are you -- your question is referring to us as a shorter course IV with our 5 infusions versus 8?

Correct. Yes. I mean does that have the opportunity to also expand the market?

Yes, we think so. I mean, I think the current tepro profile is relatively burdensome. And this is a, again, just talking about just sheer profile, not doing any cost comparison here, but just sheer profile, we're a lighter IV burden, 2/3 less drug, 70% less time in the infusion chair. So from an overall burden perspective, we think our profile matches up very well.

Our next question comes from Andy Chen from Wolfe Research.

This is Emma on for Andy. Congrats on the data. Can you please talk qualitatively about how you would approach pricing in this market when competing against Amgen. Do you have per dose price parity or price parity on the whole regimen or some sort of discounting strategy?

Honestly, I think it's just too early to get into pricing conversations. We're fully aware, we've got a really experienced commercial team. So we have a good idea as to what the market dynamics are there. Again, we think we have a really competitive profile with the lighter IV burden and new start market is incredibly important to the story. But in terms of specific pricing guidance, we haven't come out with that yet.

Our next question comes from Douglas Tsao from H.C. Wainwright.

Congrats on the data. I'm just curious how you think you will be able to sort of enter the market between both the active and sort of chronic phases of TED? And how has the market evolved recently? It's been sort of a little hard to tell, just given sort of fits and starts that we've seen with TEPEZZA in the marketplace as you've seen a shift in balance between the number of types of patients being treated. And where do you expect to see greater success in the early going with VRDN-001?

Yes. Again, I think the key there is the new start market, not converting people from chronic therapies or trying to get them to switch. They come in and they ask what's available to them. And we think as we've discussed, we think we stack up very nicely with the lighter IV burden similar outcomes to 15 weeks versus 24. And so obviously, the rapid onset of action that we talked about. So we think that's a great start for market penetration dynamics. In terms of how treat -- patients have been treated over time, I think that's -- definitely, we see Amgen making progress in the chronic population, which is encouraging. They've had year-over-year revenue growth, which is important to see. We like to see that trajectory in terms of the market size. And so we think we'll get traction to your question, we'll get traction in that new start market.

Well, I guess I was sort of more curious about just between the chronic and active TED phases of the market and how it's evolved just with Amgen/Horizon getting that on the label and sort of where they're starting to enjoy traction?

Yes. I mean they had it on the label. They had a TED label at -- when they got approved. The problem is they didn't have -- they hadn't generated the chronic data. They ran that chronic study about 18 months later after approval. And so they've been generating that data to have those conversations with payers and make sure that they -- so they're trying to deliver those data sets to payers and continue to grow access, and which is only to our benefit. Those conversations, we get to take advantage and leverage when we get on the market.

Our next question comes from Serge Belanger from Needham & Company.

This is John on for Serge today. Congrats on the data. First, on discontinuations. There are obviously very few, which is a great sign. But amongst the few that you did see, were there any similarities or trends between why those patients did discontinue? And then quickly, is there any inclination as to kind of whether patients would have greater benefit from additional infusions, whether you go beyond 5? And is this something you've explored? And could it be a potential option for patients when you eventually go to market?

Yes. So I think that the answer to both those questions, Serge, is no. We didn't really see any similarities in discontinuations. Reminder, this is a really big study, the largest ever run, a lot of patients. We only had, as I said in the script, we only had 1 patient that discontinued related to drug, and that was mild. That was a grade 1. So yes, no real similarities on the discontinuations for just, again, only one discontinued on the treatment arm. With respect to patients getting benefit beyond 5, just to be clear, I just -- I think the -- that's -- we need to see the complete data set, right? This is the top line data, and we're not expecting to see -- we're not expecting to need additional doses. You can see the consistency in the clinical benefits. And as I mentioned earlier, we expect to maintain those responses. There's no reason not to expect to maintain those responses. So we feel really good about the 5 infusion arm, that is -- we landed right where we were hoping and across the board on all these end points, as I've said several times now.

That is now the end of our Q&A session. I'd now like to hand back over to Steve for final remarks.

Well, thank you, operator, and thank you, everyone, for joining the call. This is an exciting day for us here at Viridian. These are fantastic results. We are very, very happy. And just as a reminder, we've got a whole portfolio here on the TED side, but also the FcRn. We're moving fast on -- as I mentioned, we've got 006 IND at the end of this year. There's that, as we've talked about before, that's a drug that's very much like efgart, which is a massive and really attractive drug. So with that safety and efficacy profile, that's really, really difficult to match. So we are really looking forward to that program as well. I just want to remind people that we have this portfolio. So we are off to the races here at Viridian and thank you for joining the call today.

Thank you so much for attending today's call. Have a wonderful day. You may now disconnect.