Welcome, everyone. Thanks for joining us. This is Gavin Clark-Gartner with the Evercore ISI Biotech Research Team, and I'm really happy to be here with the Viridian Therapeutics team. So we have Steve Mahoney, who is the CEO, and we have Shan Wu, who's the Chief Business Officer, and we also have Peter Harwin, who is the managing member of Fairmount Funds and also on Viridian's board. Thanks for joining us.
Thank you.
Absolutely. Great place to start out. Steve, why don't you give us an overview? What's been happening at Viridian? Where things stand today?
Yeah, sure. Great. Thank you, Gavin. Thank you, everyone, for joining today. I'm just gonna try to do a quick run-through on the company overview, and then we'll get right to the fireside chat. I will be making, if you can tell him I gotta advance the slides. Which one's which?
3-4. Bear with us. We're just setting up the slides. There we go.
Sorry. Thanks. I didn't know which clicker it is. So we'll be making forward-looking statements. Please refer to our SEC filings. We are excited to talk about Viridian today. We're building what we believe to be a world-class portfolio in two key therapeutic areas: thyroid eye disease and as well as other autoimmune diseases addressable through FcRn inhibition. Before we get into our strategy and timelines and that type of thing, I just wanna highlight a few recent company announcements. First, I joined as CEO within the last 3-4 weeks with the goal of building on the culture of operational excellence at the company.
as well as make sure that we have a robust relationship with the investor community, and availability and transparency, and that's a really important priority for us. I'm really excited to be joining Viridian at this time. Just we have a lot of important next steps coming up, particularly with the thyroid eye disease or TED franchise. Lastly, we did recently announce, as part of the transition, we did a $185 million PIPE financing. It keeps us very well capitalized, with close to $500 million in cash, allows to execute across the portfolio, and, you know, we certainly acknowledge and appreciate our current and new shareholders that participated in that PIPE.
Then, obviously, we wouldn't be anywhere without the patients that agree to participate in our trials and the Viridian team that is working behind the scenes. So let's move to the Viridian strategy. What we try to do is identify compelling market opportunities where there's an ability to differentiate, and then we engineer and design the best biologic for patients that can then it allows us to move really rapidly into solidifying a position in the marketplace. We've done that so far with the thyroid eye disease franchise, and we're applying that same approach with FcRn. So here's, take a look at our pipeline. Again, world-class portfolio in thyroid eye disease and FcRn.
Thyroid eye disease is a large market with unmet need and room to grow. Targeting IGF-1R gets at the heart of thyroid eye disease, and it's already generating close to $2 billion in annual sales in the U.S. alone. The 001 program, as you see at the top, is our fast-to-market asset, and we've already shown highly compelling data, clinical data in that program. We're currently enrolling two phase 3s in the active and chronic form of the disease, and are advancing multiple subcutaneous programs that'll come in behind it. We're expecting to disclose our lead subcutaneous program in mid-December, so just in a few weeks. And that's all for the purpose of developing the best IGF-1R therapy available.
So we'll have more to say there. The FcRn portfolio at the bottom, 006, is a Fc fragment, very much like efgartigimod, and the 008 is a novel designed to be a novel first-in-class FcRn inhibitor that could achieve IgG suppression and maintain the persistence of that effect, so pretty exciting. So let's turn to why bringing a next-generation IGF-1R asset is an important development for patients. So, as I said, 001 is our fast-to-market asset. It's already shown clinical data that's highly compelling. It targets IGF-1R inhibition, which is a clinically and commercially validated mechanism of action that targets the heart of the disease that IGF-1R receptor complex. And as a reminder, IGF-1R is the only mechanism of action that's approved and has been through the randomized controlled studies.
The opportunity at thyroid eye disease is significant, and it's a unique one for a next-generation asset like what we have at Viridian. The U.S. market, as I mentioned, does close to $2 billion in annual sales on its own. The European market's untapped, unmet need, and the epidemiology is very similar to the U.S. So importantly, even when you look at the U.S. market, it's almost entirely a new start market, which means we're not trying to extract people from some chronic therapy. They actually... Every patient that comes in, even a chronic patient that's flaring, comes in and has a decision to make, so we can shift that entire revenue stream over to the better product profile that when patients have that choice at that time, and that's a really important development.
As I mentioned, the IV program is followed by the subcutaneous programs that we're looking at. We have that mid-December disclosure that we'll talk about. Viridian is the only biotech or pharma that is developing a potentially, you know, this best-in-class, half-life extended IGF-1R mAb. And that's, and subcutaneously delivered. So, we think that having a long-acting IGF subcutaneous delivered, self-administered at home, is the best option for patients, and so we're really excited about that prospect. So now we can take a closer look at our 001 data, which is IV, against Tepezza, which is the IGF-1R on the market currently. Again, getting at the heart of the disease, it's the only commercially validated mechanism of action, and there's significant market opportunity.
Next generation's gonna be important here, and next generation's important because we have unique attributes against Tepezza. We have fewer doses, 5 doses versus 8, shorter infusion times, 30 minutes versus 60-90 minutes. But it's actually gets really interesting when you do a cross-trial comparison here at the week 6 end time point, after just 2 doses. You can see the primary endpoint is proptosis, you can see on the, on the left, out in the middle column, essentially. Where across all doses, our 001 program had a 2.3 millimeter reduction in proptosis versus 1.9 for Tepezza.
In the 2 lower doses, interestingly enough, if you look at the 3 mg per kg and the 10 mg per kg, the activity, obviously, there's plenty of activity between 3 mgs and 10 mgs, and those scores are even better. When you look at the other relevant endpoints in TED, the Clinical Activity Score or diplopia, the story gets even better when you do this cross-trial comparison. So again, we believe we have the right target, we have the right market, and the ability to introduce a next generation asset, including a potentially best-in-class, half-life extended, subcutaneously delivered mAb. It's a great option for patients. We'll just touch quickly on FcRn. We'll have a lot more to say in 2024 as the program progresses.
As you can see, we have two approaches, both of which we think are important. 006, we have what we believe is as good as the argenx efgartigimod, the Fc fragment. It's highly effective, it's highly selective, and we're really excited about that. Argenx has shown that the Fc fragment is special. All the monoclonal antibodies, the full-length monoclonal antibodies, have had some sort of issue with respect to either albumin binding or even independent of albumin binding. So there's a lot more to see there in terms of... We're interested to see what that data looks like. But it seems going to be an uphill battle to rival the Fc fragment approach. And we think that's exciting, that Viridian could have the only other Fc fragment in the industry.
VRDN-008 is a bispecific, as I said, novel, extended half-life that could achieve the goal of IgG suppression and maintain the persistence of that effect. And again, we'll tell you more about the FcRn portfolio in 2024. Last slide, just to summarize, we're focused on execution. We have THRIVE, our THRIVE studies, which is the active and chronic form in the IV-VRDN-001 program. Those will read out mid-year and the end of next year. And we're also on track to disclose that subQ program, our lead subQ program, in mid-December this year. And we are advancing our FcRn portfolio. So with that, I'll turn it back to you, Gavin.
Yeah, great overview, and welcome on board, Stephen, S han.
Thank you.
Given that we're a couple of weeks out from the subcutaneous update, thought it'd be good to just level set on a few key points so everyone knows what to expect heading into this. The first question there is: In addition to some of the healthy volunteer clinical data, should we expect a comprehensive update on the registrational subQ path and strategy moving forward, or could that come at a later date?
Right. Yeah, so I think first and foremost, just principle-wise, we wanna make sure that we're really clear with what we have. And you know, we're still have our VRDN-003 healthy volunteer data that's still coming in. We had publicly disclosed that just chronologically, that was the cadence in which it was coming in. So we're still digesting that or still actually receiving data. So when we come out, we want to be crystal clear. We're hoping that that VRDN-003 lives up to what we're expecting. And we're gonna have to be really transparent about how we match to... Now, just as a reminder, VRDN-003 has the same binding domain as the VRDN-001. It just has the half-life extension technology embedded in it.
So a lot of same pharmacology. So it's really easy for us to match, and compare against the 001 exposure levels. And 001 exposure levels that correlated to activity and correlated to efficacy, we're gonna try to match those, and we'll show that. We'll show those PK curves, we'll show PD. And I think that's gonna be an opportunity for us. You know, we'll, we'll have full disclosure with respect to, IGF-1 levels, which I think are important PD marker. And, that just- it'll just give us an idea of where we can go and as to whether, whether 003 is gonna be the option available for us. I don't know, Peter, if you have anything you want to add?
Yeah, just on the path forward, so we're gonna take an accelerated path forward, which we've, which we've already publicly disclosed. You know, you're not gonna learn much, particularly if we're gonna go forward with 003 from a MAD study like we did with 001. You essentially can go back and connect the dots to the 001 efficacy, as Steve just said. Then we're gonna go talk to regulators and confirm the accelerated pathway, which you can only do, of course, once you have the data in-house. And then we'll disclose that after that.
We'll give you some sense of that at this update, but saying the specifics before we have that confirmation, of course, we don't want to do that.
That's fair enough. Excuse me. And then, is there the potential and maybe you don't want to answer this now, and wait a couple of weeks, and that's fine, but is there the potential that you may select more than one subcutaneous program, and what drives that decision?
Right. I think that's. We wanna be crystal clear, just to answer the question. We wanna be crystal clear that we know the value of a half-life extended mAb in this setting, subcutaneous. We know the value of that. And that's, you know, clearly the reason why we've been trying to develop it behind the scenes. Whether we end up with, you're referring to 001. I think we wanna be really focused on the half-life extension for this particular disclosure. It needs to be separated from the standpoint that 001 sub-Q is simply just a life cycle management decision to be made. It's not the, it's not the, it's not something that needs to be kind of coupled with 003.
So it's certainly an exciting option for us to have available, and I think that's the bottom line, is that we like having the flexibility that this could afford us. But we'll provide, as Peter said, we'll provide more detail on exactly what the strategy is at a later time, but we just like the optionality that comes with this.
Yeah, the way, the way we think about it is, we wanna stay laser focused, as Steve said, on what we think could be the best-in-class mAb, and we're the only company with a half-life extended mAb in all of biotech and pharma, and we wanna make sure that that message is clear. I think we'll give you, hopefully enough to educate you that 001, we can do that life cycle management if we want. So we're gonna absolutely give that clarity. The way we would decide would be how I think anyone would decide. Not, you know, having a best-in-class asset, critical. How about speed to market? I think once we have the confirmation as to how accelerated we could go with 003, that will probably drive that decision on 001, right?
So if 001 sub-Q as a life cycle management to 001 IV could be far more accelerated than that, then, well, that's, that's probably gonna drive some value. If 003 can catch up, well, that's probably a more interesting asset, just as, as a hypothetical. I think that's really how we're thinking about it.
I think that's very clear. Just to be clear on all the data that you're going to lay out, it's going to be for all three programs, all the cohorts, you'll give us safety, PK, and also the pharmacodynamics, specifically the serum IGF-1, you're gonna lay all of that out in detail, or could we see, you know, certain pieces of that data?
I think this is a really good opportunity for the company to provide a lot of detail. And we're gonna try to do that. I think you should expect to see data on 001, 002, 003 across the variety of domains that you brought up. Even if we select 003, you're gonna see data on 002. And that's what we plan to do. So, you're gonna see things like even PD and IGF-1 levels, which I know is probably a follow-up question.
Yeah, that, that is the follow-up question.
Yeah, you know, some of the competition has avoided showing that. We don't know why. We have no reason not to show that, and we'll certainly do so.
Sounds good. And maybe to frame expectations for the serum IGF-1 data, so correct me if I'm wrong here, but I believe 001 has shown a 4-6-fold increase from baseline in serum IGF-1. 002 is shown around a 3-fold increase. So presumably, that's kind of where we're laying things out in terms of where 003 could fall. Is our assumption that 003 should look a lot like 001? And then how do we interpret that?
I think it adds to the conviction and the choice, hopefully. You know, we have to see the data, but I think it's really important for two reasons. One, 001, as you said, has shown a more robust response than not just 002, but also Tepezza. It looks interesting. I think that's why people, or part of the reason why, there is interest on top of the clinical data that Steve walked through earlier. It's highly compelling, comparing across studies. I think we wanna see 003 in line with what we'd expect from 001.
I think it's also another, it's another way potentially to see how long does IGF-1 increase on 003 last versus 001, to get more conviction that, you know what, we really can extend this sub-Q schedule out to something like every four weeks uniquely. That's why it's important.
Yeah, that makes sense. And actually, we're just about at time, so rather than starting to dive into the IV program and the commercial side of things, I think we'll save that for a different venue, and look to hear the subcutaneous update in just a couple of weeks.
Great. Thanks, Gavin.
Thanks for having us.
Thanks for coming.
Yeah, thanks for having us.