Great. Thank you. Good afternoon. Welcome to another great session here at the Jefferies London Healthcare Conference. I'm Michael Yee, analyst for Viridian. Up here on the stage, we have a number of members of management. I know that the President, the new President and CEO, Steve Mahoney, would love to give some opening comments and a brief overview about Viridian. Also on stage with us, we have Shan Wu, the Chief Business Officer, as well as Peter Harwin. So, without further ado, I'll bring Steve on, and then we'll have some time as well for questions.
Great. Yeah. Thank you, Michael. Good afternoon, everybody. Thank you for joining. As Michael said, I'm just gonna give a very quick overview of the company, and we'll get right to the fireside chat. I will be making forward-looking statements today that contain risks and uncertainties. We refer you to our public filings with the SEC. We're excited to talk about Viridian today. We have what we consider to be a world-class portfolio of a thyroid eye disease franchise, as well as other autoimmune diseases that are addressable through FcRn inhibition. Before I get into strategy and pipeline, I wanna just highlight a few recent company announcements.
I joined as CEO just several weeks ago now, where I'm joining to build on the culture of operational excellence and also make sure that we have a robust relationship with our partners in the investor community. That's an important priority for us. I'm excited to be joining at this time. We have a lot of important next steps, in particular with our thyroid eye disease franchise, and we'll get into that in just a minute. We also closed on a $185 million PIPE financing, that puts us in a very strong cash position with close to $500 million. It will allow us to execute across our portfolio.
We are very fortunate in this market backdrop, and we very much appreciate the support and the confidence of our current and our new shareholders as a result of the PIPE. Of course, none of this would be possible without our patients who are participating in our clinical trials and our team back at Viridian, which is working really hard behind the scenes and relentlessly to try to bring these potentially best-in-class assets and medicines to patients. Viridian's strategy is to identify compelling market opportunities and find an ability to differentiate. We then design or engineer the best possible biologic for patients and then move as fast as we can into a position to solidify ourselves in the market.
This is evidenced by what we've done with the TED franchise, thyroid eye disease, and that approach is also what we'll be doing with the FcRn portfolio that we're gonna discuss in a minute. Here's a look at our pipeline. thyroid eye disease , we have our VRDN- 001 asset, which is a fast-to-market asset. It's already shown compelling clinical data. TED or thyroid eye disease is a significant market. Targeting IGF-1R gets to the heart of that disease, and IGF-1R is already generating close to $2 billion in annual sales in the U.S. alone.
We are currently enrolling two Phase III clinical trials for VRDN-001, both in our active and our chronic patient populations, and we are also developing several subcutaneous molecules, where we're going to identify a lead subcutaneous, subcutaneous candidate actually next month. We think that IGF-1R as a subcutaneous delivery could be the best therapy for patients in this disease area. At the bottom part of this slide, you see our recently announced FcRn portfolio. VRDN-006 is an Fc fragment approach, very much like efgartigimod. VRDN-008 is a bispecific that is novel and designed to be first-in-class, half-life extension, where you have IgG suppression and a persistence of that effect. So let's dive in a bit more on the thyroid eye disease franchise. VRDN-001, as I said, is a fast-to-market asset, already shown compelling clinical data.
Using IGF-1R inhibition has already been clinically and commercially validated mechanism of action. It's the only one approved for TED patients and has shown clinical efficacy through multiple randomized controlled studies. TED is also a significant market opportunity, and it's a unique one for a next-generation asset like ours. As I've mentioned, already doing close to $2 billion in annual sales in the U.S. alone. The European market is untapped. The unmet medical need and the epidemiology is roughly the same as the U.S. But even in the U.S. market, it's a largely, almost 100%, a new start market, which basically means that every year, every time a patient comes in the office, they have a choice to make as to which therapy they're going to choose for thyroid eye disease.
That is an exciting prospect for us because we match up well against Tepezza with respect to, we expect to have fewer infusions, five-dose schedule versus eight doses of Tepezza , and we have shorter infusion times. And when you compare VRDN-001 against Tepezza across clinical trials at the week six time point, VRDN-001 has compelling efficacy against all the relevant endpoints after just two doses. So that, those endpoints being proptosis as primary, CAS scores, and diplopia. So with that as a backdrop, we are charging forward in our Phase III studies. Again, we're enrolling both our active, the active form of the disease and the chronic form of the disease. And as I said, we are following up our IV portfolio, our IV program, with subcutaneous molecules, lead candidate to be announced next month.
Having an IGF-1R subcutaneously delivered with an extended half-life is, we believe, to be the best way to address this very difficult disease. So we envision patients being able to have infrequent dosing, self-administered, and they can do that at home. So that's also an exciting prospect for patients. I'm not gonna spend a lot of time on our newly announced FcRn portfolio today. We'll have a lot more to say in 2024. We recognize that we need to put some points on the board in our thyroid eye disease franchise, and that's where we are focused on that execution. For VRDN-006 , we have two approaches, VRDN-006 and VRDN-008 . We think both of these are important.
VRDN-006 is a Fc fragment, highly selective, highly effective, very much like the Argenx Fc fragment. When you look at the full-length monoclonal antibodies that are in the market, they've all had some relevant issues, whether they're albumin binding or whether they're intended to be independent of albumin. So we think the jury's still out on the full-length monoclonal antibodies as to whether that's going to be an approach that rivals the Fc fragment approach. VRDN-008 is a bispecific designed to be half-life extension. Again, as I mentioned earlier, IgG suppression and a persistence of that effect. And again, we'll have more and more to say about these programs as they progress, particularly in 2024.
Just to summarize, we are enrolling the THRIVE and the THRIVE-2 studies, active and the chronic forms of TED. We have a mid-year readout for the active form, the THRIVE study, and then we'll have an end-of-year readout in 2024 for the chronic study. Again, advancing the subQ programs, we'll have a lead candidate announced as of next month, and we'll have more to say there in terms of how we approach that. And then the FcRn portfolio is moving along as well. So we're focused on execution. We're also focused on making sure that we have good relationships with the investor community. So with that, I'll turn it back to Michael, and we'll get into the fireside chat.
Fantastic. Thank you so much. So maybe just, a good place to start would be either for, Steve, or Peter. Over the last 12 months or so, other than the fact that the biotech market has been challenging, I think there has been some perhaps misunderstanding of the various data sets that I've read out. Is your drug expected to be better than Tepezza ? How do you differentiate? How do you interpret the data? Do you... I guess, what is the messaging that we should take away from the data around how your drug compares to Tepezza , and how you are expecting, this product to stack up against Tepezza ?
Well, so I'll start, but just recognizing that that I'm two weeks into it. So, I'll have Peter provide a lot of color. I think it's first and foremost, we are not intending to come out and say that we expect to be superior to Tepezza . I think we do have some advantages that I referred to in terms of a shorter dose schedule, maybe five versus eight doses of Tepezza , shorter infusion times. We do like the data that we've seen so far in terms of those relevant endpoints with respect to proptosis in...
Again, comparing clinical trials at week six after two doses, but we like what we see proptosis-wise and diplopia, both of which are massive quality of life concerns for these patients, and then obviously the clinical activity scores as well. So I don't know if Peter, you wanna have some-
Yeah, sure. I'll just add a little bit. I mean, I think it's as simple as just reminding people of what data we have.
Okay.
And I think we're gonna do a lot better job of that under Steve's leadership, and we already added it back to the corporate deck. The most apples-to-apples comparison, comparing across trials with all the necessary caveats, is the week six time point, as Steve mentioned in the prepared remarks, in the active thyroid eye disease population.
Okay.
And there, the baseline characteristics are very similar. And not just that, it's not just about that, it's about in active TED, you get to see all the three hallmarks of the disease and what the drugs do on those, and that was CAS, proptosis, which is the primary endpoint, and also diplopia. And then within those, right, there's different looks. There's CAS reduction from baseline, there's CAS 0/1, and just to remind everyone, and it's in the corporate slides. We looked as good or better on every endpoint, sometimes clearly better, and again, we're not trying to set an expectation of superiority for hopefully obvious reasons. Sometimes I dream about it.
We'll see what happens, but I think a better regimen and for IV, I think clearly better, for what we're gonna bring forward on the subQ front as having the only half-life extended antibody in development for IGF-1R. I think that's a really exciting place to be. You know, happy to walk through the data.
Yeah, so I think that, with your point, and I think this has been unclear over the last year, is that the data supports your confidence that the Phase III results will be clearly very positive and at least as good as what Tepezza is showing. Because the data set so far, albeit early and small, are at least numerically better than Tepezza at all those three different endpoints. So there should be high confidence that it's going to be strong. Because the stock, the stock reacted one way, and people are like, "I don't know, is this drug working? It's-
I think there's a difference between an IR message mishap at mid-year-
Mm.
and the activity of the drug. And I'll just, I'll do a couple highlights. I promise I won't overdo it. But in the active cohorts, just to remind everyone, it's a little hard without the slide, but proptosis, if you just look at. So we have two Phase III trials in active TED from Tepezza . We have three cohorts at 3 mg/kg, 10 mg/kg, 20 mg/kg IV with VRDN-001. And when you look at that data, the proptosis by exophthalmometer was better by a few millimeters than Tepezza , again, comparing across trials. If you look at CAS, CAS 0/1, so complete elimination of symptoms, right? Signs and symptoms of the disease, or close to complete elimination, a really crucial endpoint. We were double to triple better.
It wasn't subtle, right? Again, comparing across trials, but it's certainly as good or worse. I feel very comfortable saying that. And then diplopia, complete resolution, which you know isn't an endpoint that's talked about all that much. But you know when you're just at a PI meeting, when you talk to physicians, this is one of the toughest symptoms for these patients. Diplopia improvement isn't enough. You wanna resolve it, and when you look at our cohorts comparing across two trials with Tepezza , absolute and placebo-adjusted. It was 20% more patients got to resolution at the week six time point.
Mm.
We gotta finish the Phase III studies, which are underway.
Yep.
Yeah, we're excited about it.
Okay, and so, you said putting points up on the board. I would say that execution and hitting milestones and timelines is critically important. You've embarked, and I guess you've started on the Phase III studies in both acute and I think on chronic as well. How much confidence and how much visibility do you have that you will be able to rapidly enroll the acute study? Because you do have to... I think the guidance is to report the data mid-2024.
That's right.
So if you can do some math out, you, you sort of need to enroll by spring of 2024, which is not that many months away. So how are you progressing on that study? You're finding patients, no issues there, feel very good about that, and then on chronic, same thing. How confident are you on execution?
Yeah, so I can take that. I think, first and foremost, when we came out with the announcement, particularly with the PIPE, less to do with me, more to do with the PIPE. But we reiterated timelines. This was the guidance. We felt comfortable saying we're gonna meet these milestones. I've gained additional confidence in the several weeks that I've been there.
Mm.
The infrastructure is well underway, the clinical trial infrastructure. It includes enrollment assistance vendors, patient assistance vendors, data management. We've got a good suite of products surrounding those trials for both THRIVE and THRIVE-2. You know, I come from Genzyme, I come from Synageva, Kiniksa, rare diseases, where these are the steps you need to take operationally to pull patients in, drive them to centers of excellence in Europe in particular, and then in the U.S. as well. So I think we're doing the right blocking and tackling to be able to do it. We feel good. We reiterated the timelines again on Monday when we did our earnings release. So,
Right.
... you know, we'll get there.
And, uh-
But the last-
Yeah, go ahead.
If I could just to add, and like chronic, of course, just started.
Yep.
Right? So, you know, we have much more visibility in active, but I'll just remind people, one, there's way more patients, and two, we just enrolled a few chronic cohorts earlier this year, and this is all publicly disclosed. But just to remind people, I mean, they enrolled rapidly, so-
Rapidly, okay.
We feel pretty good about that.
Okay, and, I'm actually not sure on this, I haven't checked, but or have you disclosed the geography? Is it generally a U.S. study? Is it U.S., Europe? And I actually don't know how that compared to Tepezza studies. And is that important, not important, does it matter?
I mean-
Okay.
... I don't think it's having sites in Europe is probably normal blocking and tackling. So yes, we have sites in Europe, we have sites in the U.S. Again, what we're trying to do is build the infrastructure with THRIVE, enroll chronic in the THRIVE-2, you know, very same clinical sites, principal investigators.
Right.
We've got a safety study run. So that infrastructure is being built in both regions.
So I can't remember perfectly, but I've just had a little bit more time than Steve's two weeks, but I'm pretty sure it was either roughly split across U.S. and E.U.-
Yep.
for the Tepezza studies, or at least there was a significant portion.
Mm-hmm.
I think you'll see something very similar here.
Okay.
Honestly, if you had to predict, right, you would say, "Well, this thing's gonna only enroll in the EU," and I think you're gonna see a nice proportion of both, just because-
Okay.
... Tepezza is available in the U.S.-
That's right.
... not available in the EU.
I'm just trying to think, is there a reason why that maybe there'd be more competition for patients here in the U.S. versus Europe, et cetera?
Uh, yeah.
I actually wonder how Hertel is measured in different regions, because that was something that had come up during the studies. That would be helpful-
The, the-
If you've looked at that at all.
Sure, sure. I mean, I know the Tepezza studies, they had a lot of enrollment in Europe.
Okay.
So it was U.S. and Europe. These PIs have already done, you know, these trials. They know how to use all the measurements, not just Hertel, but-
Yep.
... you know, all the other endpoints that we've mentioned. I feel very comfortable, at least from what we see today, that it's probably gonna be a similar breakdown.
Okay, yeah. In other words, no issues in terms of dynamics or in enrollment. These are all the major same sites, U.S. and Europe, where these major centers are. Hertel and the way it's measured and the primary endpoint, no concerns around that because that was also something that came up on the last disclosure, some confusion around Hertel versus MRI, yet Hertel is the primary endpoint and the regulatory endpoint, but there's a little bit of subjectivity and some noise around how that's measured.
Yeah.
I guess when you go to a much larger Phase III, you feel a lot of that will be smoothed out.
Yeah, I really believe so. I think the only other thing that I guess I could add is, you know, a lot of companies ahead of data, they'll tee up-
Mm.
... the data. They'll provide context, they'll have some KOLs on, maybe they'll provide some baseline criteria, right? Like, I could, this isn't, you know, guidance to do that, but I don't see why we wouldn't, right?
Okay. Yeah.
I think we'll let Steve and Shan-
We'll try to do that.
... kind of get their feet wet and make those decisions. But yeah, I think-
Okay.
... I think it's these are good questions, and I think we'll make sure-
Very good.
... they're answered correct.
This is all part of enthusiasm towards execution-
Absolutely.
... getting towards a pretty darn big event next year, which could be a huge value-creating event for Viridian, as you've embarked across this, and you have pivotal data next year. So I just wanted to remind, you know, we're excited about that because it's Phase III data, six months away from now, so-
No.
... that's important.
Yeah, we are, too. I mean, you know, Steve mentioned this earlier on putting some points on the board.
Yep.
You're not gonna hear us talk much about the FcRns. That is not because we're not excited. I mean, we are really excited, and we've been working on it for a while. But what we wanna do, after this change and make sure that people hear us loud and clear, is we know that you can put out the release with a $185 million raise, the support of the shareholder base-
Yep.
... and turn the tide from an investor sentiment perspective, but then you've gotta go put points on the board.
Yep, yep.
We just wanna do that first.
Yep.
... and then we'll talk about life after.
Yep. Gotta execute, gotta put up the data.
Absolutely.
That will be very validating for the team, and you'll start to get a lot more credit towards everything else. In the near term as well, while you're executing on that, obviously, the potential for a subQ administration will be a huge opportunity. Can you tell us about what you plan to report in the next month? I think you said next month around the subQ. There's a couple different candidates you're looking at, VRDN- 001, VRDN- 002, VRDN- 003. What is positive data, you know, for a Phase I, and what should we expect, and how do you feel around the potential for a subQ?
You got that, right?
No.
No, no, I'm just joking.
You made so much sense.
So it's this is something that I think is arguably the most exciting thing, but-
Mm.
... maybe we don't need to pick favorites. And I think that's a widely held view. We have the only half-life extended IGF-1R in development that we know of in biotech and pharma. We know how well these drugs work, incredibly well. The effect size is dramatic. It's not just dramatic, it's fast and dramatic. You really see this effect after, you know, one dose, two doses in a lot of patients. And I also think this is, this has been something that's confused people a little bit over the past bunch of months, and we're gonna provide a lot of clarity. One of the confusing points is some of the talk about VRDN- 001 subQ, which is our IV program.
Now, the talk about VRDN- 001 subQ has caused questions on, "Well, what's going on with the half-life extension? Do you guys care about the half-life extension?" We care immensely about the half-life extension. We think that is the most differentiated approach that you can take, and we're gonna talk about why that half-life extension is going to work, at what dose and regimen, and why, with clarity next month. What we talked about with VRDN- 001 is interesting, but that is standard life cycle management. When an IV drug gets approved, which hopefully we will with VRDN- 001, sometimes, you know, Argenx with efgartigimod, ocrelizumab, all, you know, there's a million examples now. They try to do a fast path to an sBLA with a little non-inferiority study-
Mm.
... by matching Cmin, AUC, and then getting that approval of a subQ version of their IV drug. We haven't provided guidance on that, but it's very rational and might be a speedy way to get to something that's probably more in the once-a-week range. What we're gonna talk about next month, and again, this is going to be—it's on us to make sure that this is crystal clear, is what we're taking forward, what type of profile that half-life extended molecule could put up and why? And Mike, I can keep going a little bit as to kind of the rationale.
Yeah, I mean, I think the idea of having a subQ version of something that's already in Phase III for IV is a plausible area that you could invest in.
Mm.
However, the idea that quite frankly, at the same time, VRDN-003 is a higher potency, full antagonist with a long half-life technology could make something, since it's pretty much all in the same Phase I, a much better program to invest in that would be very differentiating because that could be something like every two weeks or every month in a subQ.
Yeah.
I would think that having an AUC curve that looks like VRDN-001, but yet in a subQ with a loading dose, that should be pretty straightforward as you show us pictures of that.
Yeah. So of course, we haven't made our official selection yet, but I think it's no secret that VRDN-00 3 would be really exciting. And, and the reason why VRDN-00 3 is almost identical to VRDN-00 1, it just has half-life extension mutations.
Okay.
Not just in sequence, it's identical pharmacologically. So if you look at the potency, all the in vitro data, and we have NHP data, of course, we're just literally waiting for our healthy volunteer data from the CRO. Knowing all of that, you can leverage the efficacy data we have from VRDN-00 1 to speed up-
Right
... that best-in-class subQ program and not have to do your traditional Phase II to Phase III. We'll disclose exactly what we're doing, but, but the point is, what we know is 10 mg per kg IV VRDN- 001 at Cmin and, and AUC, that you get from those IV cohorts is extremely active. We know that all the way down to 3 mg per kg-
Mm-hmm.
... VRDN-001 IV at those, Cmin and-
Looks comparable.
... AUCs, those look comparable.
Yeah.
Arguably as active, and you kind of have to squint to say it's a little less active. If it is less active, it's very high on the dose-response curve. So we know that once we get the VRDN-00 3 data, it's not that binary. It's really just kind of a math equation. We're going to get subQ bioavailability, we're going to get PK, and we have all these simulations. We're going to plug in the final numbers, and we're going to make it crystal clear as to why-
And also potentially increases of the PD marker, IGF-1, which should also show you you're getting the same pharmacodynamic effect.
I think we've shown this-
Which another competitor may not have shown yet.
Exactly. Yeah.
Okay.
You already sold for me.
That one has data coming up at the end of Q1, so we will look for that as one of the other subQ competitors. But in any case, I know that you'll have an update on your program, next month. You're executing on the IV program. You've got a rejuvenated team here, and we look forward to a big 2024 together.
Great.
Very good.
Thanks so much.
Thank you.
Thank you, guys, very much.