You can always move some of the chairs too to make it a little more... Awesome. All righty, I think we'll go ahead and get started. Hi, everyone. Thank you for joining us in the room and online, for day three of TD Cowen's 46th Annual Healthcare Conference. I'm Joseph Thome, one of the senior biotech analysts here on the team at TD Cowen. It is my pleasure to have with me today the team from Viridian Therapeutics. We have CEO Stephen Mahoney, we have CBO Shan Wu, and we have CCO Tony Casciano at the end.
Maybe before we dive into the individual programs, it would be great to just kinda hit the high level of, you know, the progress in 2025 and maybe what investors should be looking at in 2026, then we'll kinda, you know, dive deeper in the programs.
Sure. Great. Thanks, Joe. A lot of progress in 2025 sets us up right now. As I'm sure people are aware, we are, we have guided to the REVEAL-1 and readout for our SubQ program for Thyroid Eye Disease that will occur in Q1 of this year. I know, I realize we are in Q1, we are still on track, we're just talking some time this month. A lot of the work that we did in 2025 in terms of enrolling those studies and getting them ready, finishing the dosing of those patients and getting to our week 24 time point, our endpoint, we are all on track for that. That is a lot of progress that was made on that.
We also have REVEAL-2, which is the other subcutaneous program that also enrolled last year and that will read out in Q2 of this year. A lot of that 2025 has now translated into some very significant phase III readouts that could be transformative for Viridian. Obviously, I mean, I bring those up because they're kind of in the nearest term, but we are also preparing for a commercial launch with our veli program, which is the IV approach with TED, Thyroid Eye Disease, and we've got Breakthrough Therapy designation on that program. We got priority review and we have a PDUFA date established for June 30th of this year. A lot of commercial launch prep, and we're really excited about that.
The organization's done an amazing job to get us ready. We're looking forward to that. We are working, continuing to work with FDA to make our progress towards that PDUFA date. Everything is on track there as well. From a portfolio standpoint, we have our FcRn programs. We have two FcRn programs. One is VRDN-006, which is an Fc fragment approach, where we have finished up our first human study there. We've indicated that the IgG suppression levels and the albumin-sparing component of that drug in the first in human studies looked great. We will guide on our clinical development plans associated with that program later this year.
We also have our VRDN-008 program, which is a half-life extended approach, which as many of you know, the frequency of dosing in the FcRn world does give us an opportunity to improve upon that. We're in our first in human study there. Filed the IND at the end of last year, and we're moving forward, and we will have data for that program in the second half. We also announced a program in early January for TSHR, which I think is highly complementary to our efforts in TED and has a potential in the Graves' population as well. Lot of things moving. We're, we're in great shape, and operationally, everything is on track. We feel good.
Great. Maybe we'll start with veli first before we dive into the SubQ. Obviously we saw the very positive phase III studies that led to the submission, and the administration kinda benefit over standard of care. Tepezza's pretty clear. What do you think are the main points of the clinical data package, either on the efficacy or safety part, that you think are gonna ring, I guess, the most true and impactful for physicians, hopefully when this comes to market?
Well, maybe I can start, and then I'll have Tony, jump in. I think just to go back to the fact that we got the Breakthrough Therapy designation, last spring, late spring. The basis of that application was the fact that we observed in our phase III clinical trials, for veligrotug or veli, we observed, a rapid onset of treatment effect. We saw over a majority of patients receiving, experiencing a poptosis response after just one infusion, so at the three-week time point. That is different than, existing datasets. That's really important, as you can imagine, to patients and to their physicians.
The other component that we saw in the data was the fact that we saw diplopia or double vision response and actually resolution. That was really compelling. Quite frankly, I think it was better than what we even expected. It is a new data that really hasn't been out there in terms of for patients who are experiencing diplopia. That was a really big component for us to see in our data. Lastly, the third element of that Breakthrough Therapy designation application from us highlighted the treatment paradigm differences with respect to the fact that we do five infusions at 10 mg / kg. It's 30 to 40 minute infusion time.
Just factually, the existing competitor has eight infusions of 20 mg/ kg, and it's 60-90 minute infusion time. You can just see the just basic differences there. We submitted that. FDA does not necessarily tell you if one or all three of those elements guided their decision to grant us Breakthrough Therapy designation. What we do know is that that is the only time that the FDA, other than a Priority Review time period, does a cross-trial comparison. They do the cross-trial comparison, not us. They do it. To get Breakthrough Therapy designation where they're suggesting that it represents a potentially substantial improvement over standard of care, that is really big to us, obviously, and that's really important.
Long story short, that translated into priority review as well because the standard is very similar. That's what allowed us to get a PDUFA date of June 13th. Really moving forward. That is the definition that is the differentiation that has come out through the regulatory process. Maybe Tony, you could speak to how we see that playing out commercially.
Really nice job of touching on the primary points of differentiation that we're excited about. There's a lot to be excited about. I think rather than add too much to what Steve said, maybe just add some underlying context as to why we think those are meaningful points of differentiation in the market. The typical TED patient is a working-age female, 40-50-year-old female, active life, active job, really robust life that they're living and want to get back to. The difference in dosing, you know, is more than just five infusions versus eight infusions. It's 12 weeks versus 21 weeks. Right? That's compelling. That is very appealing to both patients and physicians, considering the patient type that we're talking about.
In addition to that, when TED hits these patients, when it first sets in, it can be super scary. All right? We hear from patients all the time that tell us about, you know, they wake up in the morning, and one of the first things they do is they feel their face to see how much worse the eye bulging has become. Then they may or may not look in the mirror as they get ready in the morning because they're afraid of how disfiguring it is. It's disfiguring, and that can happen fast, and it's super scary for these patients. The second point is it's not just disfiguring, it's disabling.
With double vision or diplopia, we hear these stories all the time, heartbreaking stories of women that have to give up their livelihood. We had a patient in not too long ago that told us she had to stop her job as a pharmacist 'cause she was afraid of making a medication error. These are heartbreaking stories. The key to me and the key to us as we're thinking about how we can help patients more with veli is not just getting them back to their lives faster, off of therapy faster, completion of therapy faster, but that speed of onset that Steve talked about is critical, right? This disease sets in, it happens fast, it's scary. You want resolution fast, and you wanna get back to your life even faster.
We think with veli, we've developed, you know, a product that not only is more simple to use, but faster, as well than what is typically seen in practice. Yeah.
Great. Obviously, the priority review and the Breakthrough Therapy designation bode well. You know, changes at the FDA are obviously high on investor minds. I feel like we have to ask, I guess, can you talk a little bit about the consistency of the FDA interactions that you've had maybe over the past year between the old FDA and the new FDA, and I guess anything that you can comment on sort of the current review, how those interactions have gone?
I think the short answer and the easy answer is, we feel very fortunate that the ophthalmology division is fully intact. It was not impacted by the changes that were ongoing starting last year. So for us, there's that, as you referenced it, there is this consistency of communication and the feedback. The conversations we've been having over the past two years with the FDA is with the same group that's been there and continues to be there. We like that consistency. The feedback has been very productive and very helpful. In fact, you know, Don't forget, we filed our BLA, submitted, I should say, sorry, we submitted our BLA during the government shutdown.
Quite frankly, FDA was very helpful in that respect. We are lucky that we have a division and a leadership team, a review team, all of that which has been consistent. We're just in good shape from that standpoint.
Maybe what do you hear, on Tepezza in the real world? I guess given the administration burden and sort of the timeline that you mentioned, obviously, Tony, are patients going back and receiving all of their treatments for Tepezza? Is there an opportunity, I guess, in the real-world setting for veli to kinda differentiate there with the reduced administration burden? You know, is there some efficacy that's left on the table just because of poor patient compliance with all of the infusions?
Based on our read of the market, most patients are finishing therapy. Our claims analysis suggests on average there's seven doses given for a typical patient, and that includes, you know, patients that have one infusion and stop for a variety of reasons. We think most are making it to the full course of therapy. Regardless of if they make it the full course of therapy or not, back to the original points of differentiation for us, whether you're talking about a partial course of therapy or a full course of therapy, there's lots of reasons to be excited based on the attributes through our clinical trials.
Yeah. This has been a debate, I guess, for years, but obviously as you're getting closer to the clinic, how large is the Thyroid Eye Disease market?
Yeah.
What proportion do you think would actually pursue treatment therapy first with an IV, and then maybe we'll circle back later with the SubQ option?
Yeah, sure. You know, our read on the market is there's roughly 500,000 TED patients living in the U.S. today. There's just under 200,000 that are moderate to severe, and roughly 150,000 that are under the care of a physician for their Thyroid Eye Disease. We do believe it's, you know, there's a huge opportunity left on the table to help more patients. Based on our read of the claims data, there's roughly 7,000 patients each year that are treated with Tepezza. You can do the rough math. It's not too hard to figure out that's low single-digit penetration to the overall opportunity. And we think there's a lot more patients that we can help.
One of the things we think is limiting penetration is, as you say, the burden of eight infusions, which we've already discussed. Again, I think we addressed some of that, and we lowered the bar to treatment by lowering the burden of treatment somewhat, with veli. With the introduction of elegrobart , when you're talking about it's simple to use at home, whether it's Q4-weekly or Q8 -weekly, a simple to use pen, in the privacy of your own home, we think you start to introduce not just additional patient types that are more willing to sign up for IGF-1, but different physician types as well, who are willing to prescribe a product like an Autopen, that aren't willing or comfortable to prescribe an infused product today.
The third point where we think we start to, you know, really look at expanding the market, on top of the 7,000 patients that are treated with an IGF-1 today with a SubQ, is we do know from research that a fair amount of patients that are offered Tepezza refuse Tepezza. One of the reasons they cite, one of the primary reasons they cite is the burden of the actual therapy. Again, we think we can eat into some of that rejection rate as well, yes, with veli, and then certainly with a more convenient product like elegrobart.
Then with veli's hopeful approval, can you talk a little bit about your sales force approach?
Yep.
You know, how much has Amgen kind of led the horse to water, I guess, here, and you can kinda just do what they do? Relatedly, what expenses should we be thinking about in terms of how expensive it will be to build this horse up?
Yeah, great questions. You raise a really good point. We are very grateful to Horizon and Amgen for building what is a $2 billion market spread across 2,000 core prescribers as well. Why that's an important number, 2,000 core prescribers, we believe we can address this market with just under 100 sales representatives. That will be your primary expense driver from a launch perspective. We won't guide to specifics on what the total expense is, but you can kind of work off of just under 100 sales representatives. Important to note, Horizon built this $2 billion market before being sold to Amgen. They did so with 50 reps at launch. They grew to 80 reps shortly thereafter.
Our best estimate on Amgen's current sales force size is just over 120. Why is it larger? Why is it 120? They are also, one of their growth strategies is focused on adding new prescribers. They're focused on not just the oculoplastics and neuro-ophthalmologists that do the bulk of the prescribing, those same 2,000 core prescribers that we talked about, but also adding endocrinologists, general ophthalmologists. Again, we are very supportive in those efforts. Every prescriber that they create, we will target at launch. Our launch strategy is a very simple one. You could write it on a dinner napkin. Anyone that is prescribing Tepezza will get a visit from a Viridian sales rep. We think, again, we can do that with less than 100.
How do we think about the chronic opportunity here? Obviously, Tepezza had a little bit of a roundabout way. They ran the phase IV. They had the low disease activity patients, and obviously-
Yep.
your phase III, enrolled a broader patient population. I guess.
Yeah.
How differentiated do you think that's gonna be, and is this just a harder market to penetrate and see adoption in? How do you think about that?
Yeah. Again, we think the chronic population in totality has a lower sense of urgency to treat than the active population, right? They've been living the disease for a while. They've become accustomed to living with those symptoms. There's one exception to that. When you look at the overall chronic population, we split that into a couple different groups. There's one group, which is the chronic stable. We think there's a relatively low urgency to treat with those patients. That's where the Tepezza data is today.
Mm-hmm.
from their phase IV trial. These are your, you know, high proptosis, low CAS or low clinical activity score patients, relatively stable. The other cohort that we think we have a disproportionate opportunity in is what we call the chronic flaring. These are patients that have had the disease for quite some time, but they're reactivating. We believe roughly 40% of patients, once they enter chronic, will reactivate or flare at least a couple times. We will have a disproportionate advantage by having that chronic data in our label at launch, is what we presume. We'll be able to target both those patients and with physicians, have those conversations based on the data, which, as Steve pointed out, was robust.
The last point I'll make on the chronic population, again, one of the most disabling parts of this disease is, the double vision, diplopia. The phase IV trial, with Tepezza failed to show a difference versus placebo in diplopia resolution. We had some robust numbers that we demonstrated in THRIVE-2. Again, we would expect that to be in the label. Yeah.
You've also mentioned the filing strategy ex U.S. I guess, how do you view the opportunity in the U.S. Versus ex U.S. For veli and I guess maybe, you know, even the platform at large? Is there a difference in how those patients are identified and treated versus in the U.S.?
Yeah. Let's start with the similarities. The market is roughly the same size as the U.S. The unmet need is, I would argue, bigger because there is no Tepezza on the market in the EU5 at this point in time. There's a situation where we get to faster follow. There'll be less time unopposed on the market for Tepezza if and when we decide to launch in Europe. Of course, we have filed. You saw that we're on track from a both from a filing perspective and from a preparation perspective. The big key unknown for us is what will pricing be in Europe, right?
We progress and keep those plans intact and assume that we will be going into Europe because we think there is a unmet need in a large number of patients. Of course, the key wild card is what pricing will be obtained. We get to see that again here too. We get to let Amgen do the most of the work there to build a value proposition within those countries and with those health authorities. We can then decide what makes the most sense from a go-to-market perspective based on that. Same is true with MFM. We have a little bit of time before we have to assign a price. We'll see what pricing Tepezza gets. We'll react accordingly.
I'm rooting for them again here too, and have confidence that they'll be able to secure some positive pricing in Europe. Yep.
Obviously, we did the deal in Japan. Shan and her team did the deal in Japan. I don't know if you wanna speak to that.
XUS, XEU, there are also additional opportunities as well, and, you know, Japan, Tepezza has launched there with a premium pricing, has been doing quite well based on their reads and calls. We're excited about that. We were able to do a very nice Japanese deal last summer with Kissei Pharmaceutical that across upfront milestones as well as royalties by any of those metrics, one of the top Japan deals in reads in history. I think that speaks to the attractiveness of the profile here that we were able to have many partners, potential partners at the table, to run a very competitive process and get to the numbers that we were able to do.
Great. Maybe we'll jump over to VRDN-003 or elegrobart. Obviously, the data are coming this month. Can you kind of walk us through how you got to the dosing scheme that you're studying in the phase III studies? How much does your experience with veli do you think de-risk the outcome, hopefully, of this trial?
Yeah. We're really excited about the upcoming trial readouts, because of that de-risking that you mentioned, Joe. From a maybe a starting point, the two molecules, from a binding domain, the CDRs, the variable domain of the antibody, they are identical. We have engineered half-life extension into the LE SubQ molecule, to give us that extended dosing potential. It is a new molecular entity. It's not identical sequence, but very much shared pharmacology. The way that we think about it, from the dosing regimens, Q4-weekly and Q8- weekly, we base these two on the PK exposures that we would be able to get to for LE. These PK exposures for both of these dosing regimens are in the range of what has been shown to be very clinically active from veli.
At the time when we did the phase I healthy volunteer study to confirm the PK and PD of the SubQ molecule, we had phase II data with the IV molecule at 3 mg/ kg , 10 mg/ kg , and 20 mg/ kg. Obviously, we took the 10 mg/ kg forward, but we had those two other doses to compare to. When we modeled the PK of LE SubQ, we saw that Q4-weekly from a Cmin standpoint was able to achieve the Cmins of that 10 mg/ kg IV dose from that phase II, which is a really great place to be. As a general rule for antagonistic antibodies, the field believes it's Cmin that drives potential efficacy. From a efficacy standpoint, we think Q4-weekly is very de-risked now that we have also THRIVE and THRIVE-2 data.
The intriguing part was Q8 -weekly actually showed Cmins to achieve and even exceed that of the 3 mg/kg IV dose. Again, because that looked really clinically active despite small patient numbers in that phase II, we never got a chance to explore that lower exposure with the IV 'cause we wanted to move quickly and get something to market as quickly as possible for veli, but we uniquely get to explore that with the Q8 dosing arm for the SubQ trial in REVEAL-1, REVEAL-2. To the extent that these exposure levels are still above target saturation, which is suggested by the clinical activity that we saw that we are, we could see a maintenance of efficacy at these Q8 lower exposures and perhaps an even better safety profile.
We think both of these are de-risked. Q4-weekly really protects the study. We only need one of these to hit for the studies to be successful and for us to be able to go on to submit the BLA. The Q8- weekly is a really intriguing arm because of that lower exposure exploration that we're able to do.
The company has laid out sort of a 50%-70% placebo-adjusted proptosis responder rate. The difference between kind of hitting the top and the end of that, is it mostly on kind of variation in placebo response from what you've seen in historical studies? Kinda what do you think is gonna drive that? We have seen a little bit of a graveyard at other SubQ opportunities. Obviously, these are different mechanisms. If LE works, it's gonna be, you know, great for Viridian. I guess any learnings from those studies that you think would apply, or are those just different mechanisms that didn't end up panning out?
Well, first I'd start with the fact that the 50 to 70 is established by Tepezza. That's study 1 and study 2 in their label, these are not numbers that, you know, that we came up with. These are numbers that are established by the data. And that's a placebo-adjusted basis, right? Your question is to, you know, how are we trying to control for placebo effect? We have a number of different ways that we try to do that. You are right that other trials have seen placebo arms that have been problematic for them. If you look at our THRIVE and THRIVE-2, we had very good control over the placebo arm.
From the standpoint of operationally, what we try to do is, we are very strict on the protocol. We have a lot of monitoring oversight, we try to be very specific on the study. For us, we have a lot of overlap with the clinical trial sites from THRIVE and THRIVE-2 for our REVEAL-1 and REVEAL-2 studies. We have a lot of the principal investigators have the experience that they had with veli. We have the same clinical operations team internally, which is critically important. I think that's I think we have one of the best clin ops teams in the industry. That's really important.
We have the same CRO. There's a lot of consistency across the board operationally. Do you tend to sometimes see placebo drift when it comes to a known mechanism and yeah, sure? That could potentially happen. I think we feel really good about how we operationally approached the study.
Great. How important is a signal on diplopia in this trial as well? Then, Shan, you mentioned the potential benefits that we could see on the AE profile. What do you think the bar is for some of these hearing AEs that we've seen, that seem to be kind of, you know, target and in class specific?
On the hearing part and just AE profile in general, at this juncture with Tepezza now having been on the market for six years and plenty of experience, the AE profile is known, it's expected. When we talk to physicians, they tell us they are very comfortable managing these potential AEs. For the most part, they're mild, and almost all go away once patients come off of therapy. For, you know, veli, we saw a very consistent profile to that. And for elegrobart, the SubQ, we would look for something similar as well. No surprises.
Not that we're expecting any, but really have the drug be driven by meeting that efficacy bar and then be something that physicians can prescribe once they are at home for patients to auto-inject and self-administer at home. On a diplopia standpoint, we'll see. You know, given the veli data, we feel really excited to see what the potential CAS could show on diplopia. As Tony mentioned, this is one of the areas that patients care about a lot. Because of that shared pharmacology, again, we're excited to see what we can show with elegrobart, and I think we've designed a trial in a way to be able to see that potential difference in diplopia.
Great. Maybe with the remainder time, we'll try to throw in the rest of the pipeline here. Maybe just a broad question on between VRDN-006 and VRDN-008, your FcRn programs, I guess, how are you thinking about? Are certain indications may be more applicable for one versus the other? Once you see data from VRDN-008, will you decide to advance one or the other? I guess just broadly, without obviously getting into specifics, I know that are gonna come later this year, how are you thinking about development there?
Yeah. Look, as I mentioned in the beginning, we like the way the VRDN-006 profile is shaped up and with respect to IgG suppression levels that are, you know, meet the industry expectations there. We also saw the albumin sparing, right? When it comes to FcRn, those are key components. We feel good there. We have guided to the fact that we will disclose our plans on VRDN-006 later this year. It is a competitive field.
Mm-hmm.
There's a lot of movement within the field going on already today. We do want to try to play that a bit close to our vest. As I mentioned on the VRDN-008 program, the half-life extended approach, we are in the clinic, and we are waiting for that data will show up in the second half of this year. That'll tell us what, you know, we like to let the data tell us what to do, right? We've got to figure out what that looks like, and then come up with a plan as to whether that where that applies, where's the most appropriate use of that. We like the low cost optionality that this brings. We don't have to spend a lot of money to find these answers.
We'll have more to say in the, in the second half.
For TSHR, how did you get excited about this mechanism? Obviously, unveiled that program earlier this year. Anything you can share on why this was the right next target and when we can see more data, either preclinical or otherwise?
Yeah. I think TSHR made a lot of sense to us strategically. This was a molecule that we developed internally, so we've been working on it for a while, and then unveiled it earlier this year in January. As you think about the mechanism of action for TED, TSHR, it's the TSH receptor and the IGF-1 receptor, and that receptor complex in the orbital fibroblasts behind the eye that really drive the fibroblast proliferation, tissue expansion, muscle expansion, fat expansion that leads to the pathophysiology of TED. It is, we believe, one of the on target mechanisms in addition to IGF-1R, and the two mechanisms could complement each other. It will be a great place to be, you know, fast-forward a few years for Viridian to provide all the potential treatment options for thyroid eye disease.
We've engineered this molecule to be half-life extended. We think it has the potential to be best in class, with infrequent dosing to really maximize patient convenience. TSHR also is on target for Graves' disease. It gives us a very natural pivot point to expand beyond TED, in addition to our FcRn portfolio. It made a lot of strategic sense for us to be continue to invest in TED and also invest in a mechanism that helps us to expand beyond TED as a company.
Can you talk about the interplay, maybe just quickly between those two indications, because some think that obviously, if you can have a therapeutic that treats Graves, maybe you will also be treating any sort of downstream TED that would pop up. I guess, do we know that? Is that clear? Is that not clear? What are your thoughts kind of on that?
Yeah, sure. I can take that one. I think it's important to remember the companies that are currently investigating products within Graves' disease. They're focused primarily on refractory patients.
Mm-hmm.
It's a small subset of the overall Graves population. Depends on, you know, who you listen to and who you look to, but 10%-20% of the overall population. Just from a pure modeling perspective, you think about, again, the under-penetration in TED today, and what would need to happen in that small refractory population from a penetration perspective of a new product, payer reimbursement kind of included. For that to materially impact the opportunity in TED, is not likely.
Mm-hmm.
as we model it, we view it as a de minimis risk, the overall opportunity in TED, just based on the basic kind of math.
Math.
Yeah. Yeah.
Just don't forget, the Graves' population that is under control, not the refractory population is under control with a generic-.
Mm-hmm.
antithyroid, right?
Yep.
That payer dynamic comes into play there as you start to think about that.
Great. Awesome. Well, with that, we're at time. Best of luck for exciting.