VRDN

Steve Mahoney provided an overview of Viridian's strategy, pipeline, and recent progress. The THRIVE Phase III trial for 001 IV in active TED completed enrollment in March with 113 patients (exceeding the 90-patient target) and is expected to share top-line results in September 2024. THRIVE 2, the Phase III trial for chronic TED, is ongoing and on track for top-line data by year-end. The company anticipates filing a BLA for the 001 program in the second half of 2025. The subcutaneous 003 program completed a positive Type C meeting with the FDA and is on track for a midyear pivotal program. The FcRn portfolio is progressing with plans to file an IND for 006 by the end of 2024 and share 008 nonhuman primate data in the second half of 2024. The company ended the quarter with $613 million in cash, cash equivalents, and short-term investments, maintaining a cash runway into the second half of 2026.

Thrive Phase III trial top-line results expected in September 2024. THRIVE 2 Phase III trial top-line data expected by year-end. Anticipated BLA filing for 001 program in H2 2025. Subcutaneous 003 pivotal program on track for midyear. Aim to file IND for 006 by end of 2024. 008 nonhuman primate data expected in H2 2024. Cash runway into H2 2026 maintained.

Forward-looking statements are subject to risks and uncertainties outlined in the company's most recent Form 10-Q and 10-K. Uncertainties include clinical trial outcomes, regulatory approvals, and market acceptance of products.

Q: Congrats on the progress here. First, with respect to the THRIVE data that's coming in September, I'm wondering if you can kind of help us frame what success looks like on the efficacy side? But then also, with respect to reduced drug exposure, how would you think this might impact the rate of hearing impairment events that you might see in THRIVE? And then secondarily, just related to STRIVE, I'm wondering if you could talk a little bit more about the inclusion of the active control arm?

A: Yes, sure. Thanks, Laura, for the question. In terms of what is good look like for THRIVE efficacy, as we've stated previously, we think a profile that looks like TEPEZZA, is similar to TEPEZZA, would be a really good place for us to land. So, with respect to hearing, yes, certainly, I think what we're looking for in the same vein on efficacy for safety, getting a similar profile on the safety because the safety profile for TEPEZZA is good. It's benign. And you referenced hearing in particular. To the extent the lower exposures improve upon that, that would be great. To the extent it's Cmax driven. We obviously have a lower Cmax just by virtue of the volume that we deliver versus TEPEZZA. So that could possibly be helpful. We'll have to see. But I think in terms of what good looks like, we'd love to see some more profile. With respect to your question on STRIVE -- yes, I mean, look, this STRIVE is simply to complete the safety database, which is just normal blocking and tackling for a BLA submission. So nothing there unusual. On the active control arm, it's just -- you've got to run a well-controlled study. And so we have the option of an active control arm of 3 mg per kg. It randomized as 3:1. So the numbers will be heavily weighted towards the 10 mg per kg. Again, it's all for the safety side of it. So I hope that answers the question.

Q: I guess I want to drill in a little bit more on safety in particular. I guess when you look back at the TEPEZZA safety profile from the Phase IIIs versus the more recent chronic TED study, like -- do you feel like the chronic TE Dstudy might represent a better -- if you ran a study today with more focused hearing measuring if that's more of a par for safety? Or how are you thinking about like what TEPEZZA safety actually looks like today versus when those Phase IIIs were started? And then for the top line for 001 in Phase III, do you expect to be able to share any data beyond 15 weeks as part of that, either for safety or efficacy?

A: Well, I can take the second one first, Alex. No, top line is top line. So it will be a readout at the 15-week endpoint. With respect to your question on what would -- it sounds like you're asking what is TEPEZZA post the clinical trials and what that real-world experience is. Yes, that is all part of it, like we're trying to understand that as well. I mean, I know [indiscernible] is trying to understand that, the physician community, the patient community, they're all trying to understand that. And maybe Tom too, do you want to just explain how we're approaching our reporting of AEs in the same way that TEPEZZA did?

Q: Hello? Okay. Great. I guess we can hear you. So two questions. First was on the ongoing THRIVE study. Can you talk a little bit about how you can control for the hearing impairment and hearing loss events. I know that if you actually go look back at some of the TEPEZZA post-marketing studies that there is some commentary and analysis around how patients have some of this hearing loss already and there's factors already going on with some of these TED patients in the background. And so just trying to think about how you can screen and protect for that and think about that as you go through your Phase III. And then on the subcu plans for Phase III, I think you said that you met with the FDA and you're planning to start Phase III. Can you just talk a little bit about how that meeting went? And I know there were some uncertainties about going directly into Phase III. So just talk a little bit about your confidence there or anything else that you need to do in order to start the Phase III for subcu?

A: Yes. Great. Thanks, Mike. Let me take the second one first, and then I'll ask Tom Ciulla to weigh in on the baseline hearing question that you had first. So with respect to the 003 program we did have a positive meeting. We have not received the minutes yet. So -- but we had a positive meeting, and we are reiterating our guidance that we are going to start a pivotal program midyear this year. So -- we will provide a lot more detail once we get -- once we get on the other side of minutes, but before we start the study. So more to come. But to answer your question, positive meeting, we feel good about our -- reiterating our guidance on starting that pivotal program. So we're pretty excited there. With respect to the THRIVE and the baseline hearing, I'll ask Tom Ciulla to jump in there, please.

Q: Just had two. First, on the Type C meeting for 003, does the FDA want to see any dose-ranging work in TED patients as part of that pivotal? Or do you believe you can start dosing immediately in like a blinded pivotal portion of the trial?

A: Yes. So thanks, Gavin. Like I said, give us a little bit more time. We'd like to see the minutes, but just take comfort from the fact that we are -- we feel positive coming out of that meeting and that we are starting our pivotal program, which is what we've been -- what we were guiding to previously, but we've now had that meeting. So we feel good about where we're going. But give us a little bit more time, and we'll be able to break down those details for you. But that's kind of where we are, and we feel good.

Q: Sounds good. We'll await more details. And are you able to provide any details on how the THRIVE baseline characteristics compared to TEPEZZA's Phase III?

A: Yes. That's another one, Gavin. I mean, it's a great question. I totally appreciate it. It's just that we're just not there yet. We don't have all that information for baseline THRIVE. There's -- we just completed enrollment. And so it's going to take us a bit to just get all that together. So more to come on that one as well.

Q: Congrats on all the progress. You touched on the significant ex U.S. market opportunity in TED. I guess are you planning to file for approval of 001 in the U.S. and Europe in parallel once all the data is in hand? And how large the opportunity could that ultimately represent?

A: Yes. I think the epidemiology in Europe is very similar. So we know that to be the case, similar to the U.S., that is. With respect to our ex U.S. plans, again, that's something we'll probably talk a bit more about later. We are -- as you can imagine, we are absolutely thinking about all that and the best approaches in these different geographies, even beyond Europe. So that's all in the works. And we'll have more to say at a later time.

Q: This is Adam on for Derek. I guess just a couple of questions on the time line really. So given THRIVE is still reading out like mid 2024-ish and THRIVE 2 reading out end of the year, what factors are driving a second half '25 BLA submission in TED? And is this related to the STRIVE study then? And in that sense, is an interim cut would that be sufficient from STRIVE for BLA submission? Or does the whole STRIVE trial need to be completed to support the BLA submission?

A: Great. Thanks, Adam. I appreciate that question. Yes. So -- what's driving the time line is -- remember, so we've talked about THRIVE 2, that's a top line readout at the end of the year. So by definition, it's not the completed study, right? So we have to let that -- we have a follow-up period. There's a total of the 52-week follow-up period, but only 37 weeks post the last dose. So there's a follow-up period that is -- have to be taken into account. And it's primarily THRIVE 2 to that's driving the time line. It really doesn't -- we're not expecting STRIVE to have an impact there. IN fact, STRIVE should fit squarely within that time line. And so we feel that, that's probably the driver. And we don't need all of STRIVE. What you see there is that on the ct.gov, you see 212 patients. That's the maximum number that we'll need. We can do a data cut as soon as we reach the requisite number for the safety database. And there's a little -- there are moving parts that go with that in terms of you can have dropout rates in your THRIVE and THRIVE 2. So we kind of over -- we overengineer or over-setup the STRIVE study, but we can do a data cut when we hit that threshold. And again, all of this is really typical. You have to have a safety database that accompanies our BLA submission. So it all kind of is normal blocking and tackling from our perspective. But just kind of take into account that, that THRIVE is just a top line readout. So there's more to do after a top line readout, which drives the second half '25 filing.

Q: Steve. Congrats on the progress. Maybe, Steve, for you and perhaps Tom, just wanted to get your latest views on the competition for patients and clinical trials. Certainly, as your trials are heating up and appreciate all the progress you have made. There are others out there as well. Tepro with the subcutaneous. What's the latest on driving demand? And what levers are you pulling to really accelerate the enrollment as well as the trial execution.

A: Yes. So I'll turn this over to Tom in a second. But yes, I think if you could see that we enrolled -- not only did we enroll THRIVE on time, we exceeded enrollment. We had really strong patient demand to drive that all within the month March. I think that's a -- I think that should be a clear sign to the world that there are lots of patients out there with TED that want to access IGF-1 arc therapy. So that's a really good sign for us. Don't forget also that we had roughly half of the patients were enrolled in the U.S. I know that was a question mark for people. I think we've definitively answered that the U.S. is very -- we've got the opportunity within the U.S. and then the other half in Europe, where the -- as I mentioned, the epidemiology is the same. So that might be just a general answer, Tom. Ciulla, do you want to talk about how competition for trials is shaking up?

Q: I understand FcRn is kind of in the background this year, but I'm wondering if there's maybe an IGF-1R to FCR in sequence in TED, that could be worthwhile the study in the future? Or are you mainly interested in FcRn opportunities beyond TED at this point?

A: Yes, it's the latter, Julian. Yes, we would -- we just don't think -- for TED patients, we firmly believe that IGF-1R is the key to that disease or the heart of that disease. That's where the cell signaling is taking place. You've got to hit that receptor in order to disrupt that. And so FcRns, the IL-6s, the other modalities are not -- or other mechanisms, we don't feel are on target for moderate to severe TED patients. So for us, the IGF-1R is the key to TED. So FcRn, we'll take that in different places as we alluded to in the deck.

Q: So with TEPEZZA sales trending down slightly, can you give us some perspective on why you think the new start market there appears to be somewhat stagnant and how you see this as a potential opportunity for you?

A: Yes. I mean I think it's hard for us to comment on Amgen sales. I think they are -- they did report on their call last week, they did report year-over-year growth, which is the first time they've done that since the announcement of the merger. So we see that as a really good sign. Amgen was also really confident on their call that they believe that the market continues to be underpenetrated, which we agree with, and they believe that it's going to continue to grow. Growth areas -- don't forget the growth areas also include the other geographies, the introduction of subcu. And so they've now -- they've filed in Japan and Europe, which is good as they're continuing to kind of blaze that trail for us. And don't forget, even in the backdrop of all this, they did close to $1.8 billion or close to $2 billion in sales in 2023 in the backdrop of all this as a first entrant. So again, we feel that there's plenty of room to run in TED, not only in the U.S. but elsewhere as well. And then we think subcu -- particularly our subcu, which we think is potentially going to be best-in-class, where we can have patients that can access it just by delivery at home, and they can self-administer at home. We think that's a game changer for TED patients. And I think the physician community agrees with us on that. So yes, we're not particularly worried about IGF-1R being the right place for TED patients. And I think Amgen is going to prove that as well.

Q: That's super helpful. And I guess, could you give us some perspective on when we might expect to see initial FdRn data with the IND coming the end of the year, maybe second half to mid-year 2025?

A: Yes. In our deck, you can see that we've got some healthy volunteer data that's pegged to the second half of '25 for that 006 program. It's a little ways out, so we'll look to see if we can pull that time line in. But we feel we're on track for that IND and then we'll get the healthy volunteer study going. And so we'll get some data there. I think -- don't forget the 008 nonhuman primate data that has -- in other FcRns that has proven to be pretty translatable. So we're pretty excited to see that. We saw great humanized mice data for 008, but obviously, that's mice data. We want to see the NHPs. We'll get that in the second half of this year. So we think that's actually a relatively important thing for us to get. So we're looking forward to FcRn moving forward. We've got a lot to do there.