We're gonna get going here with our next company presenter at the BofA Annual Healthcare Conference. I'm pleased to be introducing Viridian Therapeutics and Shan Wu, Chief Business Officer. My name is Jason Gerberry. I'm one of the BofA biotech analysts. Shan, thanks for joining us.
Thanks for having us. Thanks so much, Jason.
Yeah. So, maybe, I know you had some updates on your recent 1Q. Maybe if you can kind of relay the highlights and where you're at with, you know, your IGF-1 programs, and then we can get into more specific questions.
Yeah, definitely. You referenced our IGF-1R programs, which is part of our thyroid eye disease TED portfolio. We have two programs there, VRDN-001, which is our IV program that has a Phase III readout in active TED in September, which is really exciting. Then a chronic TED readout, THRIVE-2, at the end of this year in 2024.
Our latest updates there is we completed enrollment of the THRIVE active TED study in March and actually exceeded enrollment, which is a great indication for the patient demand that is in this space. Half of our patients were from the U.S., and half of our patients were from Europe as well. So that was great signal to see for the continued interest and demand from patients e ven though there's an approved therapy in this space.
Then for our 003 program, which is IGF-1 as well, our potential best in class, we have engineered that to have a longer half-life. W ith that, what we showed with healthy volunteers' data back in December is a half-life of 40 - 50 days, which, based on PK modeling, gives us a lot of options for potential dosing regimens.
Every eight weeks, every four weeks, even every two weeks, with that. A ll of those would be at exposure levels that have been shown to be clinically active with 001. J ust a reminder that 003 and 001 have the same binding domain, interact with the target in the same way.
There's a lot that we can predict about the 003 pharmacology based on what we have already seen with 001 in TED patients. So that, following a positive meeting with the FDA, we are reiterating that we're well on track for a start of a pivotal program mid-year.
Okay. So with the lead programs, can you remind me, is that the IV? Is that the subcut? I know that the value proposition has been sort of reducing the injection burden and a lot of the hassle that goes along with Tepezza, which is, I think, every three weeks for, like, half a year.
So maybe if you can just sort of frame how you see kind of your lead program addressing some of those unmet needs. From a safety standpoint, I don't know, is there any argument that could be made that maybe lower risks around some of the, I guess, SAE-- I shouldn't even say SAEs, but the auditory AE, that people have some concern about, like, that, that perhaps, you know, you may have a differential profile there?
Yeah, it's a great question. So with the 001 program, absolutely, the design there is to significantly be able to significantly reduce patient burden, the IV burden. We are looking at 10 mg per kg, five infusions in the Phase III studies, which is, you know, five infusions versus eight infusions which is the approved standard of care.
It's half the dose, which overall is about a third of the exposure that patients are getting over with Tepezza. 30-minute infusion times versus 60- to 90-minute infusion times. T he reason that this dosing differentiation is also really compelling is because of the market dynamics here with thyroid eye disease, which is a new start market.
What we mean by that is, regardless of when or yeah when a patient is diagnosed, whether they're newly diagnosed or they've had the disease for a long time but are flaring up again, that's what prompts a patient to go and seek treatment with their ophthalmologist, their physician. In that setting, the patients are coming on to be treated anew with a new course of treatment, which is a fixed dose of treatment.
So we're not taking patients off of chronic therapies, lifelong therapies. In that setting, where they have a choice between five versus eight infusions, that's a really great place to be for our 001 IV program. Then, of course, 003 would be the game changer that's designed to be a low-volume, 2-ml auto-injector, self-administered infrequently, that a patient would be able to take at home.
So you mentioned a chronic and an active study, and I think Amgen, on its most recent earnings call, sort of... Well, first of all, if you step back historically, like, Tepezza had a broad label that didn't make distinction between chronic and inactive, although I think maybe they got the chronic data added to their label subsequently.
So would both the chronic and active ultimately be part of the same filing for the same indication, or do you look at them as potentially—I imagine not—they're not two separate filings, but just want to clarify that point.
Yeah, it's a good clarification to make. We would be filing our BLA on the two well-controlled study, one in active, one in chronic. One of the things that, you're right, that Tepezza was approved with a broad label despite the registrational studies being in more of the active TED population.
That may have led to some market access payer challenges, and so the generation of data post approval in that chronic population is allowing them to make their way through payer access challenges as well. So we don't anticipate having that because we'll have both data in active and chronic patients at BLA filing and ultimately at launch.
Okay. So, I guess as we think about what you call the game-changing, the 003 profile, I guess then the main competitive interplay might be with FcRns potentially, or how do you see ongoing Phase III trials with FcRns as a competitive interplay?
I know, like, they'll probably say, "We can have a subQ, self-administered, no risk of auditory AE liability." On the flip side, you may say, we have, like, an established modality, right? That has traction that all the physicians are using and are more comfortable with. So maybe if you can kind of frame that dynamic.
Yeah, definitely. So the established mechanism, IGF-1R, is the proven mechanism, and it has proven to have a really remarkable treatment effect for the moderate to severe thyroid eye disease population. These patients are generally middle-aged, tend to be more women, and so they've got their lives to live.
T he moderate to severe symptoms that they get with TED are extremely debilitating. They can't read. They can't drive. They're losing their independence and quality of life, and we've heard just the other day that these patients can't sleep at night either because they literally can't close their eyelids, which are lid retracted.
S o the importance of treatment and quickly and to be able to get a treatment effect so they get relief from those symptoms is really remarkable. IGF-1R is the proven treatment, and it's also what is on target, really gets to the heart of thyroid eye disease. It's the IGF-1R receptor complex that over-signaling is leading to TED.
So some of these other mechanisms, FcRn, IL-6, now recently is IL-11, can they show the same effective, efficacy and, treatment effect? I think that remains a question. The Phase II data for FcRn didn't have as good of an effect as IGF-1R, and so the... We have to see. They're still early.
Yeah.
On the safety side, you wanted—you asked about that. I wanna make sure I address that as well. IGF-1R has a really good safety profile, even Tepezza. The hearing impairment are the large, for the most part, vast majority of it is reversible.
It's mild. Physicians now with four years of experience know how to manage it. T hen for our programs, both the IV and 003, we would be expecting exposures and dosing below what Tepezza has done. So, all great places and positions for us to be.
Yep. Okay. So, you know, obviously, I guess the focus will be in September, the Phase III. I believe you said that's the active TED trial. We've seen some data, obviously, from Tepezza. So is the goal really to just sort of show comparable effect size? Is there a reason to think that you may have a larger effect size treatment-wise, or is it really about differentiating on some of the other attributes that you highlighted?
Yeah, that's a great question as well. So we think a successful profile is one that shows similar efficacy, and if we look better, then that's even better. That would be upside. But with our five infusions versus their infusions, having a similar profile is a really compelling differentiation for patients, even in the IV setting, and that is in particular because of the new start market dynamic that's TED.
S o, I know that there was some scuttlebutt when Tepezza was approved, that the efficacy plateaued, maybe five or six weeks before the registrational endpoint. But the focus is on the last landmark, right? The 24-week to draw apples to apples comparisons to Tepezza, right, and then the durability of your treatment effect.
That's right. It would be our five infusions trial, of course, to their eight infusions. It would be a successful profile to see a similar efficacy between those.
Got it. Okay. J ust your general observations with the TED market, right? I mean, there's important validation from Amgen's investment in Horizon. But, you know, growth, I guess, has slowed since that time that Amgen has brought that on board and... But it's still staying steady at about a $2 billion market. I don't know. Do you feel that once chronic TED comes online for that product, that should be an even bigger market? Sort of what is your outlook for sort of the TED market in general?
Yeah. You reminded everyone of a really important point, that Tepezza is doing close to $2 billion in annual sales, so that's a large market already. Amgen is confident that they can continue to grow that market. They estimate their current penetration to be in the upper single digits, so there's plenty of room to grow here, even for a VRDN-001 drug, to be able to treat more patients with moderate to severe TED.
Then of course, our expectation with subQ, with the number of market analogs, is to not only be able to take share from IV, but to expand the overall market and the treated patients because of the broader access that patients would have with a convenient, low volume, infrequent, injection that they take at home, which is all a great place to be.
Ex-U.S. is another area for growth, and it's great to see that Amgen has now filed in both Europe and in Japan. Setting up for growth in those major ex-U.S. markets for thyroid eye disease. We know the patients are there. S o they'll be able to do the market development work, establishing the TED markets ahead of our 001 and 003 launches, educating physicians, patients, payers, which again is a great position for our portfolio.
I'm reminded of, you know, when I used to cover Horizon, there was some debate with the oculoplastic surgeons, the neuro-ophthalmologists, that they had a certain number of patients, but perhaps, you know, that had gotten fully penetrated. T hen I know that Horizon was talking about branching out through ophthalmologists, and maybe that's where some of the patients kind of either referral to those specialists was maybe getting slowed or...
So I guess I wonder, you know, another company and more marketing muscle in the space, how you open up that market? Because, I mean, you know, in a year's time, you're gonna be more of a commercial launch story, right? T hat's going to be one of the central debates, you know, can you grow and expand this market?
Yeah. Yeah, and in addition to that, the endocrinologists as well, who also help to manage these patients, many of whom have underlying Graves' disease. So, I think, again, in this area, Amgen is doing a lot of the lead work in expanding beyond the core prescriber base.
I think, in particular, for 003, that's a great profile with the subQ administration, without infusion centers and without visits to infusion centers to further be able to expand the prescriber base for IGF-1R treatments for TED.
Yeah. Have you done much work on that in terms of characterizing, you know, what proportion of the population just walks away and says, "That is too, too, too big of a or too long of a bridge to go across, to, to deal with the IV and the scheduling of that," and how an abbreviated or a self-administered, if you kind of can take that out of the equation, how that might open the market?
Yeah. It's important to remember, you know, we, we, Viridian is in Boston. We live in these large cities. There's a really large swath of the middle of the country where things are really far apart and patients live really far away from infusion centers.
Anecdotally, we have a PI in Denver who has a patient who is in Durango, six hours away, and she has chosen, despite having moderate to severe TED, to just live with her symptoms because that is a really heavy burden for everything else that she has going on, to be driving six hours to infusion centers or to participate in the Viridian trial. F or that patient, the PI would give her in a heartbeat, the subQ.
So absolutely, it's... There are a number of, as I mentioned, market analogs for this, for a accessible subQ at-home administration to reach a much wider swath of patients.
Okay. Well, we're up against time here, but thank you so much for joining us at the conference, and hopefully, you have a good remainder of your conference.
Thank you so much, Jason. It's great to be here.
Yeah. Thank you.