Equity research analyst here at RBC, and we're pleased to be joined by Viridian Therapeutics. Joining us from the company, CEO Steve Mahoney, and CBO Shan Wu. Guys, it's great to see you. Thanks for being here.
Yeah, thanks for having us, Greg.
Great to be here.
Great. A lot going on with Viridian. Certainly, a great deal has evolved as well over the last several months as you made progress on your programs and certainly advancing the company forward. Maybe, Steve, just having you provide an overview and just an intro to the company, the lead asset, 001, and your subQ and FcRn programs.
Great. Yeah. Thanks, Greg, and thanks, everyone, for coming this morning. So Viridian has a portfolio that's comprised of a thyroid eye disease franchise where we have an IV program and a subcutaneous program, and then we have an FcRn portfolio as well. The FcRn portfolio is at an earlier stage, but so on the TED program, which is thyroid eye disease, or TED, we have the IV program, which we announced last week. We will have our top-line readout for the active form of the disease in September of this year, which is on track with our prior guidance. And then our...
We have a top-line readout for the chronic form of the disease, another phase III readout at the end of this year, also on track with our guidance, our prior guidance. So, for the thyroid eye disease programs, as many of you know, there is an approved product, Tepezza, which is on the market. It has the same target, IGF-1R. And so we are, our phase III programs also target IGF-1R, and our subQ program as well. So what we're looking for is opportunities to differentiate from the first generation, and we have - there's a number of ways for us to do that, so we're excited about that portfolio. We're making great progress on the execution.
On the FcRn, we have the first program, which we'll file an IND for, again, on track, as we talked about, in our release last week. We'll have an IND that we intend to file for a program called VRDN-006, which is an Fc fragment, very much like efgartigimod. And then we have a VRDN-008 program, which is a bispecific, half-life extended version of anti-FcRn, which could be a potential game changer, given the fact that, since FcRn is clear so quickly, if we can maintain IgG suppression for longer periods of time, that, as I said, would be a potential game changer for patients just in terms of convenience, with sustained IgG suppression. So that's our portfolio, and again, everything from an execution standpoint, everything is on track, and we're moving along.
That, that's great, and certainly, execution is really the name of the game-
That's right
... for Viridian right now. With respect to 001, the trials going on, maybe just talk a bit, Steve and Shan, just on the landscape of clinical trials and performing those in TED. So I want to touch on the landscape in the market, but for now, when we think about just developmentally, how Viridian is navigating that with getting those patients, enrolling them, having them fulfill the trial obligations.
Yeah, great, and that's a timely question because last week in our earnings release, we did announce that we had completed enrollment in our THRIVE study, and THRIVE is for the active form of the disease. Not only did we complete enrollment, but we exceeded it. And geographically, I think this is important because there are a lot of folks out there saying, "Oh, you won't be able to enroll in the US in the face of Tepezza." That's not what happened. We enrolled half the study in the US, half in Europe, and again, we exceeded enrollment target. The target was 90, and we enrolled 113 patients in that study.
That's significant because I think that's a clear signal of the remaining demand in the market, even in the face of Tepezza, in the US, because remember, Tepezza is only approved in the US. So there's a lot of room to grow there. There's clearly a lot of demand. And so the underlying part of your question is, you know, are you experiencing problems enrolling your trials? We have not seen that. And we are... Again, we reiterated our guidance on the top-line readout for THRIVE-2, which is the chronic, again, indicating that we are--we're not seeing those problems, which is a good thing.
And to that, we know that Viridian is accumulating a safety database as well. It's certainly important for the full filing package. You had an announcement last week on the STRIVE trial as well.
Yeah.
Just talk a little bit about some of those nuances to help inform the audience about the active comparator-
Sure
... about the trial size and what your expectations and goals are for the trial.
Yeah. Every BLA has a safety database. So what we're doing is just typical. It's been planned for over a year. So nothing new has happened to require us to do a safety database. That is just normal blocking and tackling, so very typical. In terms of enrollment of that study, and again, just to the cadence of it, you wouldn't do your safety study before you do your efficacy studies. I mean, that's just normal as well. So we came out, and we've started that study, and we're starting that study, so we're not expecting that to be problematic from an enrollment standpoint. There is no placebo in that study. It's all comers.
And so that should enroll relatively quickly, and it, and it fits within the timelines that we've already guided to, and we did indicate that we would be filing. We expect to file a BLA in the second half of 2025, and the, and the safety database will be part of that, just like any other BLA submission.
Great, great. As you mentioned, with enrollment in THRIVE as the recent update, the top line coming in September, and then you've talked about Tepezza's performance as setting the bar for proptosis responder rate, it was 56% in active TED at week six. But just beyond that, how should we be thinking about bars of success for CAS score, for diplopia? Basically, the performing as good as or the potential for performing even better. How do you break down the potential comparisons, which are inevitable?
Yeah, I mean, I think, I think a successful outcome for us is a similar outcome to Tepezza.
Mm-hmm.
Right? We think that our five doses versus their eight doses is going to produce a similar profile on both safety and efficacy. So certainly, I think that's kind of the bottom line answer. We'll have more to say as the data comes in. I mean, obviously, the data is blinded and that type of thing right now, so we can't speak to that. But yeah, I think and that's across all those endpoints that you referenced. Proptosis is the primary, the CAS score, which is clinical activity score, that measures pain, mostly pain, but it's like redness and inflammation that they try to measure. And then finally, diplopia, which is your double vision.
And that's actually a really important point to make, is that these symptoms, proptosis or bulging of the eyes, pain, inflammation, diplopia, double vision, really prevents these folks from, in the moderate to severe category, in particular, from being able to read, being able to drive, being able to work, massive quality of life impact and leads to depression. So that is... It's really important that we get the treatment effect size that we can match the treatment effect size of Tepezza, because that's the benefit risk profile there is very clearly in favor of IGF-1R.
Mm-hmm.
You know, in the backdrop of all this, you know, Tepezza is doing close to $2 billion in sales in the U.S. alone, and their penetration rate is still relatively low. So it's really exciting market to be in. We're really excited to be coming along as the next generation and improving upon the first generation. So we're well situated.
And certainly, on the safety and tolerability study, when you speak of the risk-benefit profile for the class, auditory impairment comes up. We know label updates for Tepezza over the past year now. How do you put that into context with respect to VRDN-001 to help address some of those questions that arise?
Yeah, again, the benefit risk profile is still very much intact, for IGF-1R. Again, the treatment effect size is critical. The safety profile is largely benign and resolves on its own without intervention. I think that's an important point for people to keep in mind. You know, from the KOLs and the physicians that we speak to, you know, this is manageable, and they're growing in more confidence with being able to manage it, and we expect to be in the same similar profile, and we expect to be able to help them do that.
Certainly the THRIVE-2 in chronic TED, TED readout, maybe just to talk a bit about how that's progressing as well, maybe the translatability from the THRIVE study, that we could sort of think about, just given the differences in patient baseline characteristics. Oh, Shan, answer that question?
Sure. Yeah, I'd be happy to. So in terms of the THRIVE-2 study, as Steve mentioned, that is all on track. The trial is ongoing, with top line readout expected by the end of the year. In terms of translatability, we think a successful profile for THRIVE would be very translatable to THRIVE-2. The patients, even though they've been diagnosed quite a while ago, still have the same symptoms, and it's the flaring of the symptoms, proptosis, CAS, and diplopia, that brings those chronic patients back to see their doctor to be treated again for the flaring symptoms. So that's a great place to be for 001 . And of course, in our phase II studies, we saw robust clinical activity for both active and chronic patients.
Great. Great. And then just turning to that, the market landscape, you're watching Tepezza closely. We are as well. What's your view on the utilization, on the payer landscape, its landscape and the criteria for reimbursement, and namely just the market challenges that have been inherent with essentially a new product or Tepezza? How can 001 sort of fit in and be positioned there?
Yeah, I mean, I think we are. As I mentioned, we are well-positioned being coming in behind Tepezza. They've done a lot of the work that we would need to be doing with respect to educating the medical community, educating the patient community, and to your question, educating the payer community. And we are if you, if you remember, Tepezza did not run a study in the phase in the chronic form of the disease, so they hadn't generated the data necessary to go have those conversations with payers. We, as we mentioned, our THRIVE-2 study is in the chronic population, so we will have that data at the beginning when we go to engage with payers. It's a little early to get into pricing and reimbursement for us.
Mm-hmm.
But it's, you know, suffice it to say that it's great to have Amgen out there doing that education, showing the impact of IGF-1R, and, you know, we look to take advantage of that, when we get onto the market.
Great. Great. And maybe just turn to the broader portfolio, call it life cycle, call it diversifying, but with 003 and a subcutaneous option set expectations for those selections there and just the key elements for guiding that decision as you set up the next trial?
Yeah, again, another timely question, Greg. So in our earnings release last week, we referenced a positive Type C meeting with FDA with respect to our subQ program. We haven't seen the minutes yet, but it was a positive meeting. We are reiterating our guidance that we are going into a pivotal study for the subQ program in the middle of this year or mid this year. So that's really positive. With respect to dose selection, dosing regimens, we wanna get the minutes, and before we start that study, we'll come out, and we'll explain which dosing regimens we're gonna include in the trial design. As you...
Just as a reminder, when we did a subQ bake off, where we had the results in December, where we had multiple subQ programs that we ran through PK/PD to try to determine which one was gonna be best. We were very thankful, and as we were hoping, the 003 program emerged the winner because 003 has the same binding domain as 001, and we've already seen clinical response with 001. So the same binding domain, the only difference being a YTE mutation that gives extended half-life to the subQ molecule. So that was a really exciting outcome for us. And what enables us to do for the subQ program, and again, Tepezza never did a dose ranging.
They took an old oncology drug dose, 20 mg per kg and dropped it into thyroid eye disease. We are the first company to be able to really explore the therapeutic index. So because we have subQ exposures that can match IV exposures, for instance, three mg per kg IV, we can match the Cmin on that on an every eight weeks basis, as shown by our PK models that we announced back in December. So imagine how convenient that is. That's a loading dose and two injections, and you're done with your treatment out to 24 weeks. So that's a great spot to be in. We can also match exposures between three and 10 on once every four weeks injection.
And then we also referenced once every two weeks, which is a Dupixent-like schedule. And so we can match that exposure as well. So we have options, and I think that's what's really important. And we will come out before we start that study, and we'll give some more clarity as to exactly which active arms we're gonna take forward.
Do you have a base case or what you would consider a win? You mentioned the Dupixent-like twice-weekly dosing. It seems like that's the best case at this time, or all of them picking your children, which one should we be thinking about as a going-in position?
Yeah, I think we just need a little bit more time on that. Let's see what the minutes say, and then let's, we'll come out, and we'll announce the trial design.
Okay. And then just for the spirit of practicality, just remind us of the auto-injector pen device approach, how that's a potential at this point in time, differentiator from competitors like Amgen and even others that are out there exploring subQ.
Yeah. So we announced a deal with Ypsomed last fall. Ypsomed has several approved products in its auto-injector pen. So that's pretty standard in terms of we're not trying to reinvent the wheel there, which is great. Obviously, we've also announced that we have a formulation that allows us to put two mL into an auto-injector pen. And that's a critical differentiation from Tepezza. With 20 mg per kg, their ability to concentrate down to those levels, that's they're not gonna be able to do that. So they're gonna have to take a different approach with respect to their subQ. So that's a massive differentiation for us, and potentially best in class, or potentially best in disease.
When you think about patients being able to access an auto-injector pen that gets delivered to your house, it's low volume, it's infrequent injections, and you can self-administer at home. So we think that's a game changer for thyroid eye disease in the competitive landscape.
I'll add to that, that with 003, in the data that we shared back in December, we saw an incredible half-life extension as well, which the other IGF-1Rs in the market or in development don't have. So that really allows us to fit into a 2 mL auto-injector and enable patients to have a really convenient, infrequent dosing regimen that we think is gonna be the a key differentiator for us as well, to make us potential best in class.
Yeah, that's right. We're the only half-life extension, so that's an important point. Thank you.
That's, that's great. That's great. Well, maybe in the closing time we have, maybe flipping to the FcRn portfolio, what do you want investors to be most focused on from this emerging portfolio, Steve, in the next... Granted, as you acknowledged, things are early, but we're talking about them.
Sure.
Where should our focus be?
So we're, you know, as I mentioned, our 006 program, an Fc fragment, very much like efgartigimod. Efgartigimod has shown amazing safety and efficacy. So we believe we are the only other Fc fragment in development. So that's pretty exciting. I mean, that's a great place to be. We, as I mentioned, we will file an IND in that program and get into the clinic next year, is our expectation, so that's great. That's all moving along on track. And then when we talk about FcRn, it would be like, you know, not to overuse the phrase, but another game changer for FcRn, if we can have a half-life extended version that not only achieves those IgG-...
that you wanna see, but also maintain those for an extended period of time, that really provides a lot more convenience to patients. So that, you know, having that game changer in the portfolio in both, not only with 003 and the thyroid eye disease franchise, but also 008 in the FcRn, that it, that's, that's part of the strategy, and we'd like to see that unfolded, but it's, it's looking good. We'll, we'll feel good about that. And that non-human primate data in the second half of the year for 008, an important, because I think FcRns have shown that, that the NHP model is translatable to the clinic. So that's been a relatively important catalyst for us to see.
All right. Great, great. Just in the last moment, I wanna see if there are any questions from the audience in the room. Okay. Well, maybe I'll just close it up by just asking Steve, just on your resource positioning, certainly having the ability to be, I think, well-stocked, executing on your plan. Maybe just talk a bit about how that's being deployed, how it's spread across the programs, and where it's taking you.
Yeah, our capital allocation, kind of rough, you know, just, is allocated to the programs that I referred to. You know, we have, we have our phase IIIs, that obviously are fully funded. They're reading out. We have our subQ program, funded, and the FcRn portfolio. That was one of the reasons we did the raise in January, was to make sure that we could advance the FcRn portfolio along as well. So from a capital allocation standpoint, you know, we're, we're being careful. Obviously, we wanna spend money in the right places. And, you know, we all of this capital allocation generates the catalyst that we talk to. phase III readouts, for IV and subQ, IND, NHP studies, all these catalysts are funded, and that's a great place for us to be.
We're well capitalized. We guided last week, where we've got over $600 million in cash. So we're in a good spot right now, but we wanna be smart. I mean, they, you know, FcRn, FcRn, we're not gonna go in 10 different directions there. We gotta be really smart about how we allocate, because, you know, we're mindful of those development costs.
Great! Well, I think that's a great place to leave it.
Okay.
Steve, Shan, great, great to see you guys, and congrats on the progress, and look forward to tracking.
All right.
Great.
Thank you.
Thanks, guys.