VRDN - NASDAQ

Welcome to the Viridian Therapeutics First Quarter 2024 Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to hand the call over to Ms. Louisa Stone, Manager of Investor Relations at Viridian. Please go ahead.

Thank you, and welcome, everyone, to our First Quarter 2024 Earnings Conference Call. The press release reporting our financial results and corporate updates is available on the Investors page of our corporate website at www.veridiantherapeutics.com. Joining me on the call this morning are Steve Mahoney, our President and CEO; Tom Ciulla, our Chief Medical Officer; 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 in 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.

Thanks, Louisa, and welcome, everyone, to our first quarter earnings call. I'll start by giving a brief overview of Viridian, and then we'll get into more detail about our programs and recent progress. For those of you who are new to the Viridian story, our strategy is to identify market opportunities where there's a clear unmet need and where there is potential for us to develop differentiated products. We then aim to engineer the best possible therapeutics and then move rapidly to advance our programs to patients. Turning to Slide 4. Slide 4 shows our pipeline, which includes both a thyroid eye disease or TED portfolio as well as an FcRn targeting autoimmune portfolio. We have several exciting updates to provide across our pipeline today, which we'll get into next. We're really excited to highlight for you today the significant progress that we've made across the business so far this year. Beginning with our 001 IV program, we are pleased to announce that THRIVE, our Phase III trial evaluating 001 in patients with active TED, completed enrollment in March. In fact, not only did Thrive reach the target enrollment of 90 patients in mid-March, but we exceeded enrollment for a total of 113 patients due to strong patient demand at our clinical trial sites. We expect to share top line results for THRIVE in September 2024. THRIVE 2, our Phase III trial initiating 001 IV in patients with chronic TED continues enrolling and is on track for top line data at the end of this year. Lastly, for 001, we are announcing that we anticipate filing a BLA for the 001 program in the second half of 2025. For our subcutaneous 003 program, which we believe has substantial to be best in class, we recently completed a positive Type C meeting with the FDA, and we are moving forward with our preparations for our pivotal program in line with our previous guidance. We will provide additional updates for 003 program before we start that pivotal program, which remains on track for midyear. We are also progressing our FcRn portfolio as planned. We are aiming to file an IND for 006 by the end of this year, and we plan to share 008 nonhuman primate data in the second half of 2024. Lastly, we ended the quarter with $613 million in cash, cash equivalents and short-term investments, and we maintain our cash runway into the second half of 2026, also as previously guided. Now I'd like to turn to our TED portfolio and talk more about the programs and our progress in a bit more detail. As a reminder, TED is an autoimmune condition characterized by inflammation and damage to the tissues around and behind the eyes. This leads to symptoms, including proptosis or bulging of the eyes, redness, swelling, double vision and retraction in the eyelid. In severe cases, TED can be sight-threatening. With those symptoms as a backdrop, there is already a large market opportunity in TED that comes with global growth potential and an expansion that can come with better options for patients. There is an estimated 190,000 people in the U.S. alone who are living with moderate to severe TED. These patients are only served by one marketed IGF-1R IV therapy currently, which generated approximately $1.8 billion in sales in just the U.S. alone in 2023. This approved therapy requires 8 infusion every 3 weeks, which can be a significant burden for patients. We see opportunity for us to provide differentiated options for TED patients with both our IV and subcu programs. Because TED is an autoimmune disease characterized by flaring symptoms, patients with moderate-to-severe symptoms struggle with quality of life issues that make it hard for them to drive, work and even sleep. Because it is a flare-based disease, it is considered a new start market, which means that it doesn't matter when a patient was diagnosed because you need to treat the flare or the onset of those symptoms. This new start market also means that all patients experience symptoms -- will have the opportunity to choose for available treatment options with no chronic treatment to displace. Once a flare is treated, patients do not remain on an anti-IGF-1R therapy. So when a subsequent flare arises, physicians will have the opportunity to choose from available treatment options, including potential new options to manage these flares in their patients. This is a great position for our IV and subcu programs in TED because we believe that we are developing potential best-in-class therapies in a drug class that is shown to be highly effective in inhibiting IGF-1R and in treating TED. Turning to the specifics of our product candidates. Viridian is developing two anti-IGF-1R antibodies for TED. 001, which is delivered intravenously and 003, which is delivered subcutaneously with the potential for self-administration. As you can see here, 003 and 001 have the same binding domain, and we expect them to bind IGF-1R similarly. They differ because 003 is engineered to have an extended half-life, which we have shown to be 40 to 50 days in healthy long tiers, which is 4x to 5x that of 001, its parent molecule. With 001, we hope to have a fast-to-market differentiated IV therapy for patients with fewer doses and a shorter infusion time than the current standard of care. With 003, we hope to have -- we hope to develop a convenient, less frequent, low-volume therapy that patients can self-administer at home. Let's review the 001 program, our progress, and what makes us excited about the Phase III readout that we expect in September. On Slide 11, this is a reminder that we've already shown robust clinical activity with 001 after JSTI infusions in a Phase II clinical trial in active TED. This robust activity is across all key areas of the disease, proptosis or the bulging of the eyes, clinical activity score and diplopia or double vision. We have added data from the TEPE

[Operator Instructions] The first question comes from the line of Laura Chico with Wedbush.

Congrats on the progress here. I guess I have two questions for you. 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?

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 TEPE

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

I guess I want to drill in a little bit more on safety in particular. I guess when you look back at the TEPE

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 TEPE

Sure. So Alex, as you know, the field is evolving, as alluded to, there's updated guidance from the FDA, which led to a label change for Tepro, as you know, and in current clinical practice, physicians are assessing patients hearing at baseline during and after treatment. So we are recording adverse events using MedDRA terms. And as you know, this is just a standard way of recording patient-reported changes in their health, including hearing. This is a standard for any clinical trial, including TEPE

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

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 TEPE

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.

Thanks, Michael. So as we said in the previous answer, adverse events in the study is reported via the MedDRA terms versus the standard methodology for reporting patient changes in their health including hearing, and this was done in the TEPE

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

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?

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.

Sounds good. We'll await more details. And are you able to provide any details on how the THRIVE baseline characteristics compared to TEPE

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.

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

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?

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.

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

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?

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.

Got you. That makes sense. And I guess, can you provide any numbers then on what that threshold is? And then just kind of following up on the STRIVE study too, is this a safety database you expect to leverage then with any potential regulatory path for VRDN-003?

Yes. So 003, as we've talked about previously, is a different molecular entity. So it will have its own path. So the answer to that question is no. On the first question, the threshold is -- the threshold, again, like I said, 212 is the max number. We're not -- we'll see where we end up. The total number is 300, but that includes THRIVE and THRIVE 2 active patients on 10 mg per kg. So we're not anticipating needing the entire STRIVE study. And again, most importantly, STRIVE is not expected to drive the time line for BLA submission. It's more the THRIVE 2.

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

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.

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?

Sure. Thanks for your question, Gregory. I'm out in the field a lot talking to investigators and KOLs, both in the U.S. and ex U.S. And I can tell you there's a lot of excitement about our entire portfolio and as you know, our Phase II trial showed really promising results, and that's driven a lot of interest, hence, the over-enrollment that Steve referenced. Also, I can tell you that with respect to STRIVE, we have an active control. There is no placebo, and we think that's going to drive enrollment there. So I think overall, just lots of positivity around our TED portfolio and our trials. I really can't comment on competitors, but what I can say is just lots of excitement and enthusiasm around our portfolio.

Your next question comes from the line of Julian Harrison with BTIG.

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?

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.

Your next question comes from the line of Trevor Allred with Oppenheimer.

So with TEPE

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.

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?

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.

At this time, we have reached the conclusion of the question-and-answer session. I would now like to turn the call back to Viridian's President and CEO, Steve Mahoney for closing remarks.

Great. Thank you, operator, and thanks, everyone, for joining the call this morning. We've made a lot of progress, and we are executing. We're delivering on what we've said, and that's important. We know that's important to you as well. So thank you for your participation today, and we look forward to talking to you in the future.