Welcome to the Viridian Therapeutics First Quarter 2024 Conference Call. 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. 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 as well as regulatory, product development, 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 potential 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 the 003 program before we start that pivotal program, which remains on track for midyear. We are also progressing our FcRn portfolio as planned. We aim 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 are 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 infusions every 3 weeks, which can be a significant burden for patients. We see an opportunity 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 experiencing symptoms will have the opportunity to choose from 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 an excellent 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 has 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 volunteers, 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 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 TEPEZZA clinical trials after two doses on this slide to show the data side by side. While cross-trial comparisons are difficult, we are encouraged by the clinical responses observed after just two doses of 001. On Slide 12, you can see that 001 was well tolerated in active TED patients with no serious adverse events, no infusion reactions, and no discontinuations. Similarly, active TED patients with chronic TED after just two infusions, 001 meaningfully reduced disease burden across each disease point as well. On Slide 14, 001 was also well tolerated in chronic TED patients. Based on this Phase II data, we believe that the clinical regimen of 001, with fewer infusions, shorter infusion time, and lower cumulative drug exposure, has the potential to be a better choice for moderate to severe patients with TED. Now turning to our Phase III trial for 001. I would like to take a moment to thank all of the patients and clinical trial site teams who have participated in our THRIVE trial. We are not done yet, and our achievements so far would not be possible without them. As we announced today, we completed enrollment for THRIVE in March with 113 patients, which exceeded our enrollment target of 90 patients due to strong demand and interest at our clinical sites. About half of THRIVE's patients were from the U.S., and the other half came from Europe. We expect to provide top-line results for this study in September of this year. THRIVE 2, our second pivotal study in TED, is ongoing and on track for top-line readout at the end of this year. In addition to THRIVE and THRIVE 2, we recently initiated STRIVE, which is a planned safety study. STRIVE is a study of 001 in TED patients to complete the sufficient safety database for BLA submission alongside the patient numbers from THRIVE and THRIVE 2. In conclusion with 001, we are developing a potentially differentiated IV therapy for patients with fewer doses and shorter infusion time than the current standard of care while inhibiting the same IGF-1R target, which has been shown clinically and commercially to be effective in treating TED. We are very excited about bringing forward 001 as a potential option for patients, which could mean significantly less drug for patients, fewer visits than the infusion center, lower volumes, and less infusion share time. Our next program, subcutaneous 003, will take this differentiation even further with the possibility of lower frequency subcutaneous administrations and potential for at-home self-administration using auto-injectors. We know from market examples that a later entrant subcu therapy can convert meaningful portions of an existing IV market, and we've included two of those examples here. In each of the cases on this slide, subcutaneous offerings grew the overall market size of the class, in addition to quickly commanding a significant share of the IV markets. And keep in mind that these subcu examples have the same or more frequent dosing than their IV counterparts. This would not be the case with 003, which is designed to have potentially a best-in-class dosing profile. Also, it is important to point out in both examples that neither of these are in new start markets. Again, the TED market is a new start market where we need to treat flaring disease or onset of symptoms as opposed to trying to convert patients from a long-term chronic therapy. With 003, we hope to provide patients with an anti-IGF-1R therapy that is a better option with respect to less overall drug exposure and more convenience. On Slide 19, we show the complete data set from our Phase I healthy volunteer study of 003 to assess PK and PD. The update here is the inclusion of the last cohort, Cohort 5, where participants received two doses above 28 days apart. The data confirms the differentiated PK and PD for 003 seen in the first 4 cohorts with an extended half-life of 40 to 50 days and sustained increased levels of the PD biomarker IGF-1. On Slide 20, you can see that the subcutaneous 003 was well tolerated in the Phase I study, including in the latest Cohort 5 with no serious adverse events or discontinuations related to treatment, and observed adverse events were generally Grade 1 and mild. As we shared previously, our pharmacokinetic modeling for 003 predicts that three potential dosing regimens are available to us: 003 every 8 weeks, every 4 weeks, and every 2 weeks, could achieve or exceed the exposure levels of 001 that we saw in the active and chronic studies that were correlated to robust clinical activity from our Phase II clinical trials in TED. This gives us a lot of optionality as we move towards our pivotal studies for 003 and importantly, gives us the potential to develop for patients a best-in-class low-volume subcu delivery option. We are pleased to announce today that we have completed our Type C meeting with the FDA, and we are on track to initiate pivotal clinical trials for the 003 program. We will share more details on the pivotal trial design before we start those studies. Now turning to our FcRn portfolio. On Slide 24, in addition to TED and consistent with our development strategy, we are developing an exciting portfolio of potential best-in-class FcRn inhibitors to address the unmet needs of patients living with autoantibody-mediated autoimmune diseases. FcRn inhibitors represent a large market opportunity. The first FcRn inhibitor, Efgart or Vyvgart, is approved for myasthenia gravis and is in registration for CIDP and it’s already annualizing over $1 billion in annual sales. Myasthenia gravis alone is a large market with projected sales of over $4 billion annually by 2028. In addition to myasthenia gravis, as you can see from the slide, there are additional sizable autoimmune indications that would meaningfully add to the FcRn opportunity. Our FcRn franchise includes two assets, 006 and 008. With 006, we are excited to have the only other FcRn targeting Fc fragment in development other than efgartigimod. Argenx has shown that its Fc fragment achieved substantial efficacy while sparing an effect on albumin or LDL and shows better tolerability than the full-length antibodies. We are on track to submit an IND for 006 by the end of this year and look forward to sharing more about the program in the future. Next, on the right, is 008, our protein engineering efforts identified a molecule derived from Fc fragments that both extended the half-life and generated meaningfully deeper IgG reductions in animal models. We believe 008 is a potential best-in-class extended half-life molecule targeting FcRn with the potential to more durably suppress IgG. We are on track to provide 008 nonhuman primate data in the second half of this year, as guided, and we are excited to bring forward this portfolio of next-generation FcRns to potentially offer patients a more convenient dosing profile compared to current weekly IV or subcu infusions. In addition, by aiming to improve the duration and depth of IgG suppression with 008, we hope to offer a best-in-class option for patients. Our team is executing. We have made excellent progress across the company in the first quarter of the year, and we look forward to continuing that momentum through the rest of the year to deliver on our multiple upcoming catalysts. As I mentioned previously, we plan to report THRIVE top line in September and THRIVE 2's top line is on track for the end of the year. The FcRn programs are also proceeding as expected. It has been my pleasure today to provide these exciting updates across our portfolio, and in particular, for 001 and 003, reflecting the work that we've completed during this quarter. This progress and our recent achievements reflect our team's ability to execute, and we are well positioned to continue the work and deliver on our exciting upcoming catalysts. Last but not least, we remain well capitalized, ending the quarter with $613 million, and the runway is into the second half of 2026. So with that, I'll ask the operator to open the call for questions.

The first question comes from 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 would success look like for THRIVE efficacy, as we've stated previously, we think a profile that looks like TEPEZZA, similar to TEPEZZA, would be a really good place for us to land. So, with respect to hearing, certainly, we are looking for 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, this STRIVE is simply to complete the safety database, which is just normal blocking and tackling for a BLA submission. So nothing unusual there. The active control arm consists of an active control of 3 mg per kg, randomized as 3:1, meaning 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.

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

I would like to explore the safety aspect further. When comparing the safety profile of TEPEZZA from the Phase III trials to the recent chronic TED study, do you think the chronic TED study provides a clearer understanding of safety, especially if a study were conducted now with a more targeted approach to hearing? How do you perceive the current safety profile of TEPEZZA in relation to when the Phase III trials began? Additionally, for the top line results of study 001 in Phase III, will you be able to share any data beyond the 15-week mark regarding safety or efficacy?

I can address the second question first, Alex. The top line results will be available at the 15-week endpoint. Regarding your inquiry about TEPEZZA after the clinical trials and its real-world experience, that is certainly something we are exploring. The physician and patient communities are also trying to gain a better understanding of it. Tom, would you like to explain how we plan to report adverse events similarly to how we did with TEPEZZA?

Sure. So Alex, as you know, the field is evolving. There's updated guidance from the FDA, which led to a label change for Tepezza, as you know. 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 TEPEZZA's pivotal trials. We're also assessing audiometry as is done in clinical practice at baseline in prespecified points. So we're essentially doing what's done currently in the evolving clinical practice.

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 back to some of the TEPEZZA post-marketing studies, 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?

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, but we had a positive meeting and we are reiterating our guidance that we are going to start a pivotal program midyear this year. We will provide a lot more detail once we get on the other side of the minutes, but before we start the study. So more to come. But to answer your question, positive meeting, we feel good about 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 are reported via the MedDRA terms versus the standard methodology for reporting patient changes in their health, including hearing, and this was done in the TEPEZZA trials. As I mentioned, we're also using audiometry for monitoring, and that's consistent with the current clinical practice and FDA guidance. We do have an exclusion criterion for hearing loss at baseline, which you can see that exclusion reported on clinicaltrials.gov.

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 feel positive coming out of that meeting and that we are starting our pivotal program, which is what we've been guiding to previously. But we've now had that meeting, and 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 TEPEZZA's Phase III?

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. We've 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 an opportunity could that ultimately represent?

Yes, I believe the epidemiology in Europe is quite similar to that in the U.S. Regarding our plans outside the U.S., we will discuss that in more detail soon. As you can imagine, we are fully focused on identifying the best strategies in various regions, not just in Europe. We are working on this, and we will share more information at a later date.

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 timeline 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 sufficient from STRIVE for BLA submission? Or does the whole STRIVE trial need to be completed to support the BLA submission?

Thanks, Adam, for the question. What's influencing our timeline is primarily THRIVE 2, which will have its initial results by the end of the year. This does not mean the study is complete, as we have a follow-up period to consider. The total follow-up duration is 52 weeks, but we will only have 37 weeks of data following the last dose. It's mainly THRIVE 2 that is shaping this timeline, and we don't anticipate STRIVE will affect it. In reality, STRIVE aligns well within our schedule. We don't require the entirety of STRIVE to proceed; the current updates show we've enrolled 212 patients, which is the maximum needed. We can analyze the data once we hit the required number for the safety database. There are some variables at play, such as potential dropout rates in THRIVE and THRIVE 2. We designed STRIVE with a bit of extra capacity, but we can conduct our data analysis when the necessary threshold is met. This is standard practice as we need a safety database for our BLA submission. Keep in mind that THRIVE serves as just a preliminary readout, and further work is required after that, which informs our filing in the second half of 2025.

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. As we've discussed before, 003 is a distinct molecular entity, so it will follow its own pathway. Therefore, the answer to your question is no. Regarding the threshold, as I mentioned, 212 is the maximum number we are considering, but we will see where we ultimately land. The total number is 300, which includes active patients from THRIVE and THRIVE 2 on 10 mg per kg. We do not expect to need the entire STRIVE study, and most importantly, STRIVE is not anticipated to influence the timeline for the BLA submission. It is primarily the THRIVE 2 study that will be relevant.

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 I 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 and trial execution?

Yes. I will hand it over to Tom shortly. However, I want to highlight that we not only enrolled THRIVE on schedule, but we also surpassed our enrollment goals. There was significant patient demand that drove this within March. This clearly indicates that there are many patients with TED eager to access IGF-1R therapy, which is encouraging for us. It's important to note that about half of the enrolled patients were from the U.S., addressing any doubts regarding its potential. We have clearly demonstrated that the U.S. represents a substantial opportunity, while the other half of the patients were from Europe, where the epidemiology is similar. Tom Ciulla, would you like to discuss how the competition for trials is evolving?

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. 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 that there is lots of excitement and enthusiasm around our portfolio.

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

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

Yes, it's the latter, Julian. We firmly believe that IGF-1R is central to treating TED patients. The cell signaling occurs at that receptor, and it's essential to target it to disrupt the disease. We do not consider FcRns, IL-6s, or other mechanisms to be appropriate for moderate to severe TED patients. For us, IGF-1R is crucial for TED. We plan to explore FcRn in other areas as mentioned in the presentation.

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

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?

Yes, it's difficult for us to comment on Amgen's sales. However, they reported year-over-year growth during their call last week, which is significant since it's the first time they've achieved this since the merger announcement. This is a very positive indicator. Amgen expressed strong confidence that the market remains underpenetrated, a sentiment we share, and they anticipate continued growth. It's important to note that growth opportunities also extend to other regions and the introduction of subcutaneous treatments. They have now filed in Japan and Europe, which is encouraging as they pave the way for us. Additionally, despite the challenges, they achieved nearly $1.8 billion to $2 billion in sales in 2023 as the first entrant, which underscores the potential for growth in TED, not just in the U.S. but globally. We believe our subcutaneous option, in particular, has the potential to be best-in-class, enabling patients to receive it at home and administer it themselves. This could be a significant advancement for TED patients, and we believe the physician community shares this perspective.

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

Yes. In our presentation, you can see that we have some promising volunteer data scheduled for the second half of 2025 for the 006 program. It's still a bit in the future, so we will try to accelerate that timeline. However, we believe we are on track for that IND, and then we will initiate the healthy volunteer study to gather some data. Additionally, the 008 nonhuman primate data has shown to be quite translatable, which we are really excited about. We observed excellent data from humanized mice for 008, but of course, we need to look at the NHP results. We expect to have that data in the second half of this year. We consider this data to be quite important for us, so we are looking forward to advancing FcRn. We have a lot of work ahead of us.

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.

This concludes today's conference call. You may disconnect your lines. Thank you for participating.