Viridian Therapeutics, Inc. (VRDN) Earnings Call Transcript & Summary

We're going to get going here with our next company presenter at the BofA Annual Health Care 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 SMID cap biotech analyst. And so Shan, thanks for joining us.

Thanks for having us. Thanks so much, Jason.

Yes. 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 your IGF-1R programs, and then we can get into more specific questions.

Definitely. So you referenced our IGF-1R program, which is part of our thyroid eye disease, TED portfolio. We have 2 programs there, VRDN-001, which is our IV program, that is -- has a Phase III readout in active TED in September, which is really exciting and then a chronic TED readout THRIVE-2 at the end of this year in 2024. What we -- 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 a great signal to see for the continued interest and demand from patients even though there is an approved therapy in this space. And then for our 003 program, which is a IGF-1R as well or potential best-in-class, we have engineered that to have a longer half-life. And with what we showed with healthy volunteers data back in December is a half-life of 40 to 50 days, which based on PK modeling, gives us a lot of options for potential dosing regimens, every 8 weeks, every 4 weeks, even every 2 weeks with that. And all of those would be at exposure levels that have been shown to be clinically active with 001. And just a reminder that 003 and 001 have the same binding domain, interact with the target in the same way, so there's a lot that we can predict about the 003 pharmacology based on what we have already seen with 001 and 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 midyear.

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 3 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. And 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 -- actually [ wouldn't ] say SAEs, but the auditory AE that people have some concern about, like that perhaps you may have a differential profile there?

Yes, 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, 5 infusions in the Phase III studies, which is 5 infusions versus 8 infusions, which is the approved standard of care. It's half the dose, which overall is about 1/3 of the exposure that patients are getting over with TEPEZZA, 30-minute infusion times versus 60- to 90-minute infusion times. And the reason that this dosing differentiation is also really compelling, it's 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 -- yes, 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 the patient to go and seek treatment with their ophthalmologists, 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 and in that setting where they have a choice between 5 versus 8 infusions, that's a really great place to be for our 001 IV program. And then, of course, 003 would be the game changer that's designed to be a low-volume 2 ml autoinjector, 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 active, although I think maybe they have 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 they're not 2 separate filings, but I just want to clarify that point.

Yes, it's a good clarification to make. We would be filing our BLA on the 2 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 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 subcu 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.

Yes, 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 and the 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. And so 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. And 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, 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 we have to see. They're still early. On the safety side, you want -- you asked about that. I want to 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 4 years of experience know how to manage it. And then 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.

Yes. Okay. So 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. 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 treatment-wise? Or is it really about differentiating on some of the other attributes that you highlighted?

Yes. 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 will be upside. But with our 5 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.