Viridian Therapeutics, Inc. ($VRDN)

All right. Good afternoon. Let's kick off our next session. It is my pleasure to host Viridian Therapeutics. And with me, we have Steve Mahoney and Shan Wu, CEO and CBO of the company. So a lot to talk about, very, very exciting year. Very. But before we go do it, I'm going to kick it off to Steve and Shan for opening remarks.

Yes. Thanks, Rich. Thanks for having us. We appreciate it. We are on the verge of commercial approval. We are -- have a PDUFA date of June 30. So very short time period until we are -- we expect to be on the market. All of our regulatory interactions have been consistent and positive and give us a lot of confidence going into that PDUFA date. We are right on track with everything. So that's exciting. We can talk about launch dynamics and that type of thing in more detail as we go. We obviously also had our top line readout from our subcutaneous studies, REVEAL-1 and REVEAL-2, both highly positive studies, both proptosis response and diplopia. We are advancing our Q 4- and our Q 8-weekly dosing regimens with a BLA submission targeted for Q1 of '27. So also exciting because we think that's a potential -- has a lot of potential in the TED market going forward. We also have a TSHR program that we have guided to an IND in Q4 of this year. So that's exciting, too, because that gives us applicability both in thyroid eye disease, but also in Graves' population, which is exciting and complementary to the portfolio. And then finally, we have our FcRn portfolio is continuing to move forward. We have -- we have finished our first-in-human for our 006 program, which looked just like it should in terms of IgG suppression and albumin-sparing that looked great. And now we're waiting on the results from the first-in-human we're working through our first-in-human study on the 008 program, which is a half-life extended approach for FcRn. So a very exciting portfolio turning into a commercial company, but a lot of great stuff in the pipeline.

Got it. So the PDUFA is coming June -- any time, right? June 30? With the PDUFA date. I mean I think we've seen it where some of these PDUFA moving ahead of time. So with that, I don't know if I'm -- yes. Can you give us an update on the launch prep? Are you guys just ready to go? You just pushed the button and sales force is all trained up. Like where are you with that process?

Yes. We are all ready to go across the board. So we have -- the sales team has been on board for -- they came in, in certain waves, but all the hiring has been done. They're trained on -- we know the label is somewhat predictable. So we've been able to train them. They're obviously not -- they're not out there talking to physicians about anything yet. But they are -- they do have the ability to at least have -- make an introduction and have a nonproduct-specific conversation. So that stuff is all good. We've had our medical affairs team is out in the field for quite some time, which is great because they're able to talk about the data from the clinical trials. And we have our patient support services, which is also built and ready to go. Supply chain is ready to go, market access. So in all of our systems, our internal G&A support for launch, everything is ready to go. So we are operationally launch ready. We've actually been launch ready for a few weeks now. So we are all ready to go. We can accept patient enrollment forms the day after we get approved. So we're ready to go.

Okay. More questions on that topic later. But the FcRn, I think you mentioned that we'll see updates on the FcRn for 006 and 008. What data will you be presenting? And also, are you going to be presenting the actual indication that you want to develop into? And then also how would you differentiate from...

Yes, I can take that one. So we have 2 programs with FcRn and 006, which is an Fc fragment, and we really like the Fc fragment. We think there may be something special about a fragment that the full-length antibody so far have not been fully able to replicate the safety and efficacy of the currently available fragment and 006 would be the other one that is in development. We've communicated that Phase I studies from -- in healthy volunteers, the data looked as expected. So IGF-1R IgG suppressions in line with the FcRn class sparing of LDL and albumin well tolerated. So very clean profile across the board. So that's exciting for that program. And then 008, which has the half-life extension that we've talked about. It's the difficult to engineer half-life extension into an FcRn molecule, but we've been able to do it. And that is in ongoing healthy volunteer studies right now, Phase I, and we expect data second half of this year. And with that, we will plan to look at and disclose and share the healthy volunteers data with regards to IgG suppression. We want to see that in line again with prior studies and what we have seen in nonhuman primates, which historically have been very translatable to humans. We'll want to see tolerability and in particular, with regards to LDL and albumin to see that being spared, which again, we saw in primates, so looking to confirm that. And then importantly, looking to confirm the half-life extension, which, again, head-to-head versus efgart in the primate studies, we saw longer half-life, 3x the half-life as well as more sustained IgG suppression. So that will be very exciting data from a healthy volunteer standpoint to confirm that in humans, which will allow us to really extend the dosing interval between doses of FcRn, which we think could be a game changer for patients. Both of these programs, we've designed to be subcutaneous and patient self-administered, which is still an unmet need for patients in FcRn. And so we believe that we will be able to move the field forward with either one of these profiles.

Right. I see. Okay. And then you will be disclosing the indication and then sort of the development plan for those indications.

Yes, that's right. So for each of these programs, we do plan to update everyone on how we're thinking about next steps in development indication strategy, correct.

Fantastic. Okay. And you guys recently raised $300 million to equity and convertible senior note. And I remember you guys mentioned that you guys already have enough capital to kind of sufficiently take the company to cash flow positive. So was that just to pay down, I think, the Hercules Capital credit facility? Is there anything beyond that? Is there any consideration to pay off the DRI financing deal as well? Like what's -- anything there?

No. Well, so what we did is, yes, we were able to pay down the Hercules facility, lower our cost of capital as a result of doing that. So that was a smart corporate governance for us to be able to do that. We also talked about the fact that we have this TSHR program that I referenced in the introductory. And we are also looking at ways of possibly retreating in the Veli program, in the ELE program. All of the commercial activities, all the commercial launch for both Veli and ELE were already covered. We thought it was a good idea to take advantage of the convertible market terms. Very favorable market. We thought that was a good idea. And then we did a small equity component to it as well. But yes, we are -- yes, we were guiding towards profitability before that deal, and we're obviously more comfortable and more comfortable territory given additional capital. But again, we've got a lot of really good investments to make here across the portfolio. So we look forward to that.

Can you share like the sales force that you guys have already ready to go? How many are there? Are they structured like dedicated by specialty like are they all target different doctors? Or are they more like some are for endo, some are for ophthalmologists and some are for surgeons? Like how are you guys thinking that?

It's more geographically laid out for the sales force. Sales force is a little under 100. And then on top of that, obviously, we have medical affairs team, which is a crucial part of kind of rare disease commercial efforts as well with respect to being able to go through all the clinical data in detail with folks. And then we have the patient support services on top of that. So we have a concentrated call point here where there's really 2,000 core prescribers that we need to reach. They are identified in the claims analysis. We know who they are with respect to -- this is the group that writes primarily all of the -- or essentially writes all of the TEPEZZA prescriptions. So we -- that is our target audience. And so we are rightsized for that because, as you know, TEPEZZA is a $2 billion steady-state product right now, and we think adding our voice to that, adding particularly our profile of Veli into that prescribing habits is -- that's the target. So that's -- the sales force is set up to do that.

I see. Okay. And then so when I turn on TV, I see a lot of TEPEZZA commercial, right? They're everywhere. And so from a resource perspective, Amgen is obviously putting a lot of resources in there. Sound like they probably have more sales reps than what you guys -- what the number that you guys quoted. Just given all that, are you concerned about just not matching the resources? Would you consider like from a DTC perspective, will you consider matching to what Amgen is doing? Or are you -- or is there like other more innovative type of channel that you can go and not have to spend the same type of money toward those campaigns?

Yes. So a couple of points. First and foremost, their sales force is not that much bigger than ours. it's incrementally bigger at most. So we are correctly sized, particularly relative to them. In terms of direct-to-consumer advertising, I don't think you'll see a lot of us do it. We can do a lot of that on social media. Obviously, there's a lot of easier ways to do that from a capital allocation standpoint. But I think more importantly, we applaud the direct-to-consumer that they're doing. It's good for patient education, physician education that they've been doing for a while, payer education they've been doing for a while. We get to take advantage of all that. All that legwork that they do is channeling those patients to the physicians that we're going to be calling on. And I think the physician reaction to having another treatment option available to them is really exciting. This is the first time with -- if once we get approved, we'll be able to offer the only other treatment option that's been available. And physician -- we think there's a lot of physician excitement about that. We think there's a lot of patient excitement about that. So from a resource standpoint, that's all channeling to the places where we're going to be.

I see.

And remember that this is a new start market. So patients are not -- we're not looking to switch patients off of any treatment that they are on and doing well on because everything is fixed dose. The currently approved treatment is fixed dose. Veli IV will be fixed dose. It's a shorter course of treatment actually from a fixed dose standpoint. And so we expect those patients in terms of raising awareness and channeling those patients to physicians to be a potential new start patient for Veli as well. We feel really good about the clinical profile and soon to be -- we anticipate commercial profile for Veli, given the data that we generate in both THRIVE and THRIVE-2, in particular, the points of differentiation that we've talked about before that form the basis for our applications for breakthrough therapy designation as well as priority review, first of all, rapid onset of treatment effect on the active side. Chances are a patient who starts therapy will have already had a proptosis response after just infusion after 3 weeks. And then secondly, diplopia improvement and resolution for these patients, in particular, on the chronic side, which Veli is the first drug -- drug candidate, I should say, to have shown that level of diplopia benefit and statistically significant in chronic patients. And we offer all of that with a shorter duration of treatment in just 12 weeks that a patient will complete the entire full course of treatment. And then each infusion is only 30 to 45 minutes long.

And remember that this is a market that's primarily made up of women in their 40s and 50s. It's an autoimmune disease. These are people with very busy lives with families and jobs and just the active -- activities of daily life in that age group. And so the ability to bring, as Shan just referenced, a shorter treatment period of just 5 infusions, shorter infusion times, just on a logistics basis of the clinical profile is what it is with the differentiation that we think that Shan just referenced, but then simply just ease of the treatment.

Okay. Got it. So the PDUFA is coming, we're going to see your label coming out very soon. How do you think it's going to be -- how do you think it's going to differentiate against TEPEZZA's label? I mean I think a lot of -- Shan, I think you highlighted a lot of things there that some of these advantages that we saw from the THRIVE trial. Do you think like how would those be reflected in the label relative to how TEPEZZA show? And also, obviously, I think the chronic data, right? They don't have chronic data in the label, you will. But what are some of the other key differentiation, especially those points that you mentioned?

Yes. Those points that I mentioned in terms of rapid onset of treatment effect, diplopia response and complete resolution all in a shorter course of treatment, those are the key data points from THRIVE and THRIVE-2, our 2 pivotal studies. So we would anticipate having that data in our label in both active and chronic TED, in which case, we would be the first drug approved for thyroid eye disease with both active and chronic data in our label. So that's a major differentiation point for the label. Remember that when TEPEZZA was first approved, the indication was broad. It was for not just restricted to active TED, which was the basis for their registrational trials, but inclusive of all TED patients. And so we do think the FDA views this population as a continuum of disease and does not necessarily differentiate between active and chronic TED. And so we expect to also have a broad indication. But the labeling, again, this is where Horizon has done a very good work in getting a clean label on both the efficacy as well as safety data that's in there, and we get the benefit from that, but replacing the data with the data that we generated from THRIVE and THRIVE-2, which we think are very compelling.

I see. Okay. And then -- so I know part of the launch prep, you guys go in -- I mean, every company do a lot of these qualitative and quantitative market research with payer prescribers and patients. What are the findings there in terms of like how many of them actually recognize that differentiation that people actually recognize it and would be -- would see that as an advantage for them to...

I think what's more important when it comes to the payers is the feedback that we've gotten is we've been in communication with the payers for quite some time, including the preapproval information exchanges that you can do now. I think what's really critical and important is that now that TEPEZZA has 85% of commercial insurance plan coverage for -- in the U.S., which has taken a bit of time, but it's a great setup for us to walk into. And so our interactions with payers have been essentially their communication to us is you can get parity coverage at a parity pricing. So they recognize the value of IGF-1R. I mean, particularly when you look at the competitive landscape from 1.5 years ago where you had -- or 2 years ago where you had IL-6, which didn't quite pan out. They failed one of their studies, IL-11, obviously, that didn't go forward either and then FcRn as well, right? So when the payers fully recognize the value of IGF-1R. And so when they look at our profile, the feedback has been coverage, which is a great place to be 85% of coverage is to step into. That will take a bit of time just because -- every plan has its own kind of time lines that we have to deal with, but it's a great spot.

But so you don't think that they're going to use preferred or exclusive contracting. Do you believe in your research, most of them are saying that, look, parity access would be something that...

Yes. That's the feedback.

We're not going to try to get you guys at each other.

No, we haven't seen that.

Interesting. Okay. So when do you -- so and again, going back to the market research with the prescribers, some prescribers are very comfortable they've been using TEPEZZA for years, right? They're very comfortable whether they know inside out in some way. There's a new product coming out, they don't really have experience with it. How many -- I mean, like for those doctors, do you -- I mean, how long do you think it takes for them to kind of get used to it? And how many prescribers are in that camp? Was more or less just want to stick to what they know and not very adventurous to try something new. How many are in that camp versus how many are more open to like, look, I saw the data from your THRIVE trial looks very encouraging. I want to start trying.

Yes. The latter is the overwhelming response that we've gotten. It has been very consistent that there's a lot of excitement around the availability of a treatment option and a willingness to try that. I mean, for all the reasons that we talked about with the rapid onset, the diplopia data and the treatment regimen. Those are exciting prospects for the first time since -- in the last 6 years. So there's a lot of willingness to try. And now our job is to make sure that we make those experiences as good as possible for both, obviously, for the patient, first and foremost, but the physician as well. And I think that will go a long way.

We also enrolled high-volume TEPEZZA prescribers in our clinical trials. So many of these physicians already have experience with ELE and actually, in fact, probably have had experience with ELE since there was good overlap in trial sites for both of the 2 programs. And of course, as we mentioned, our medical affairs team has been out there talking with these 2,000 core prescribers so that they are well educated on first aware of Veli as a potential option and also well educated on the data that we've generated from THRIVE and THRIVE-2. And it's helpful that it's the same mechanism. It's IGF-1R. We are a full antagonist. And so that for physicians, understanding that it is the same mechanism is also very helpful.

I see. Okay. Let's talk about the chronic patients a little bit here. TEPEZZA has been struggling with these patients, single-digit penetration. What's the potential of Veli in that chronic TED setting? Is it just because you have 3 less infusion and suddenly that opens up, like how should we think about that chronic setting? Is it more -- or should we have to wait for the subcutaneous for ELE to come up in order to be better penetrate that population?

I would say that our strategy out of the box, as we described, those 2,000 core prescribers is more of a conversion of their prescribing habits. And currently, they prescribe probably on an 80-20 basis active versus chronic. We do think that the profile has the potential -- the Veli profile and IV has the potential because it can possibly make the logistics side of it easier that might bring some people off the sidelines from a chronic perspective. But in the short term, our strategy is to convert those current prescribing habits and so we can grab share. Reminder, this is a $2 billion market with a single product. So the ability to come in, have an option, grab some of that market share in those prescribing habits, that's the main priority in the early days. We'll see how -- we do think it's going to be attractive to chronic patients. And then obviously, when we come with the subcu, that really unlocks that chronic population because the urgency to treat, depending on where they are, and there's -- it's such a continuum of or spectrum of patient experience on the moderate to severe, where they fall on that index. And we do think that the subcu would be instrumental to unlocking a lot of those chronic patients.

Yes. So I mean, given that these chronic patients have like a very highly variable disease and likely less severe in terms of symptoms and inflammation. I mean, how are they being treated now if they're not using TEPEZZA? And also, what proportion of them truly need an IGF-1R?

Yes. So we ran the 2 largest studies that have ever been run in chronic patients. And these are patients that, by definition, to get into the studies, had more than 3 millimeters above normal proptosis. We had a very high percentage in the -- both THRIVE-2 and THRIVE and REVEAL-2 with the chronic studies where they had diplopia as well. And so these -- the symptomology, because there's a lot of variability in that chronic population, we did enroll patients in our chronic studies that had both proptosis and diplopia, and they had low clinical activity scores or they had high clinical activity scores. So -- and that's basically a proxy for pain and inflammation. So there's a lot of variability. And we think that the chronic population has not particularly gravitated towards the currently available therapy, primarily, in our view, from our research because of the profile. It's -- I mean, if you think about it, it's -- if you've been living with the disease and you're being asked to go for 6 months of infusions, that can be a lot, particularly, again, as I mentioned, this is women in their 40s and 50s with very active lives. And so our whole approach here, both with IV and with subcu is to try to make things easier. And we do believe that, that's going to resonate with that patient population and expand the market there. But we think that's primarily a profile issue...

We enroll both of those chronic studies very quickly. So THRIVE-2 on the IV side as well as REVEAL-2 on the subcu side. And the majority of the REVEAL-2 study came from the U.S., 56%. And that's with a commercially available therapy that's here in the U.S. So that is a good signal for the motivation that these patients have to seek treatment and their willingness to come on to treatment to have their -- the symptoms of their thyroid eye disease be addressed. We think that they're just being underserved right now by what is currently available.

I see. Okay. Let's move on to ELE. We don't have a lot of time left. So there's a lot to talk about it there, too. So you guys presented the Phase III results for the REVEAL-1 in active and REVEAL-2 in the chronic study. REVEAL-1 fell short of your own expectation that within TEPEZZA's proptosis response. But REVEAL-2 showed IV-like results that fell between TEPEZZA and Veli's proptosis response. How do you sort of reconcile the difference between these 2 studies?

Yes. Look, I think as a reminder, REVEAL-1 was highly static on the primary endpoint, the proptosis reduction for Q 4. We saw very clinically meaningful responses in diplopia in the Q 4 arm. And then the Q 8-weekly arm is an option for patients where we saw really good proptosis responses. That was in the active study. And so we -- then we saw that reinforced to your point, on REVEAL-2, highly stats seeing on proptosis response for Q 4, but we also saw very good response on diplopia. And so the Q 4-weekly option, and our intention is to move forward with both of these treatment options, Q 4 and Q 8, Q 4 looks very promising proptosis and diplopia. Q 8-weekly promising for people with -- where diplopia may not be their main complaint, but proptosis is. And just if you think about getting -- this is IGF-1R in an auto-injector pen. So everyone knows that IGF-1R is the mechanism that actually is the most effective in this disease population. And so the ability to put IGF-1R in an auto-injector pen that's very simple. It's at home, patient administered at home, that is going to be very meaningful for this patient population because if you think about where we fit, we've got IV. We get an IV that we just talked about for all the reasons that, that's a very attractive profile. Q 4-weekly for proptosis and diplopia patients and Q 8-weekly for proptosis. So we have an answer. We believe we have an answer for any patient that walks in with moderate-to-severe TED. We can address it across. And so those studies reinforce both of those profiles.

I see. Got it. So even though ELE's inhibition the IGF-1R saturated and you guys showed similar PK/PD profiles. Why do you think that the REVEAL-1 and 2 results were lower, right?

Yes. So just right. So we had the PK/PD, both looked like they were supposed to in terms of on the PK side, what we saw there plus the IGF-1 levels that we would see from the PD side. So the drug did what we expected it to do. We may have seen some clinical variability in REVEAL-1. But then REVEAL-2, as you pointed out, brought that as expected, brought that you like efficacy. So I think that kind of reinforces the profile. You may have seen some variability in REVEAL-1. But at the end of the day, we've tested these profiles with physicians and the response has been overwhelmingly, okay, that looks like IGF-1R in an auto-injector pen. That's a great profile for us. I think that's the bottom line. It's very simple. Everyone knows that IGF-1R is the right mechanism. And now we're -- we expect to be able to pen in an auto-injector.

Okay. Got it. So when you think about the patients that are suitable for ELE versus Veli, how do you think about that setting, right? You have these products come out in the active setting and the chronic setting, how do you think -- how do patients choose between...

Yes. I mean a little bit to repeat myself, I guess. But on the IV side, we think there's an IV appropriate patient population, no doubt. As you go up the index and severity and that urgency to treat, they're very well -- we expect forever, we expect there to be patients that will be appropriate for IV, whether that's because their physician wants them in a controlled setting like an infusion center or the patient wants to be in a controlled like a sight-threatening patient, you would want to put them on IV. And we have -- that's what we have Veli for that kind of severe. And we think it's obviously done very well with the moderate end of that spectrum as well. So we think that's a great option. When subcu is available, we do expect that the patients that are non-IV that Q 4-weekly has that impact on proptosis and diplopia and then the Q 8-weekly is really geared towards the proptosis. Again, we cover that spectrum of patients, and we have an answer for anybody who walks in.

I see. Okay. So I always look at chronic and the active patients as 2 very different and distinct populations in some way. Is there -- and therefore, because of that, you need different products that cater towards their needs. Do you -- I mean, do you share this view that these are sort of 2 kind of distinct patients? And then also, if that's the case, then what product attribute do you believe that are more suitable for active and chronic patients?

Yes. We -- the way we look at it is there's certainly the active population, again, along that spectrum that I described for moderate to severe. But there's also that same moderate-to-severe spectrum in chronic. You'll have patients that have lived with the disease, but they're not necessarily complaining about the pain and the inflammation that goes with it. They may have settled into their proptosis. Diplopia is a little harder to settle into, but there is some element of that. So we call them kind of like a chronic stable population, which is really where TEPEZZA was studied in that population. But then there's a chronic flaring population is what we call it. So these are people -- as I said, we had people to get into our studies. Again, the largest studies ever run in these chronic to get into our studies, you had to have above normal proptosis and a large percentage had diplopia as well. So there are patients in that chronic that, again, to Shan's point, they enrolled that study quickly. They're the biggest studies ever run. And so it speaks to the market demand that's still out there for these patients. But yes, there is a distinction, there's a lot of chronic patients. It's very underpenetrated, which is the opportunity in front of us with both Veli and then obviously ELE subcu.

Right. Got it. And then I do want to ask you this question. So besides the OBI from Amgen, they have another IGF-1R subcu asset in development called AMG 732. So this is -- I believe this is another legacy product from Horizon's acquisition. I think it's in Phase I/II development and it's a new molecular entity. So designed for subcu, not like TEPEZZA OBI, which is really just more like TEPEZZA, we formulated for subcutaneous. So given that this asset and then TEPEZZA OBI is not being developed for chronic TED. And my guess is that this one could be. How do you -- have you heard much about this asset and your thoughts about it so far?

Yes. Let's start with the OBI for a second. The OBI is 4 inches long, 2 inches thick. It's got gears, batteries. You have to insert the cartridge into yourself. You have to wear it on your abdomen for up to 30 minutes. It's an infusion. It's not a subcu. It's an infusion pump that you wear on your stomach. You have to do it every 2 weeks for 24 weeks. So not really clear where that fits into the competitive profile. Compare that to the auto-injector pen that we have, which is the same pen that DUPIXENT's use very patient-friendly. A lot of people are familiar with it. So we don't think that's really -- we don't really see that as a competitive profile in this. It's just not sure where it fits. With respect to the Amgen 732, yes, we're aware of it, but it's several years behind. We don't know exactly what it is. We think it's IGF-1R, but we don't know exactly how it's set up. They haven't talked a lot about it, but it's -- they just got started with Phase II, so they're years behind.

Right. Fantastic. So we're out of time. Thank you so much. It's been a pleasure hosting you guys, as always. I'll turn it to you guys for any final remarks.

No. Look, we're about to be commercial. We've got a great profile, very highly supported by the Phase III data. We've got a great commercial team, very familiar with buy-and-bill dynamics. And we are -- so we're ready to go operationally and just and regulatory interactions have been great. And then we're looking forward to advancing ELEs with BLA in Q1 '27. And then the FcRn portfolio is coming too along with TSHR.

Look forward to it. All right.

Thanks, Rich.

Thanks.