All right. Good afternoon. Let's kick off our next session. It is my pleasure to host Viridian Therapeutics. With me, we have Steve Mahoney and Shan Wu, CEO and CBO of the company. A lot to talk about. Very exciting year.
Very exciting.
Before we go through it, I'm going to kick it off to Steve and Shan for opening remarks.
Yeah. Thanks, Rich. Thanks for having us. We appreciate it. We are on the verge of commercial approval. We have a PDUFA date of June 30th, so a very short time period until we expect to be on the market. All of our regulatory interactions have been consistent and positive and give us a lot of confidence going into that PDUFA date. We are right on track with everything. That's exciting. We can talk about launch dynamics and that type of thing in more detail as we go. We obviously also had our top-line readout from our subcutaneous studies, REVEAL-1 and REVEAL-2, both highly positive studies, both of them proptosis response and diplopia. We are advancing our Q4 and our Q8 weekly dosing regimens with a BLA submission targeted for Q1 of 2027.
Also exciting, because we think that has a lot of potential in the TED market going forward. We also have a TSHR program that we have guided to an IND in Q4 of this year. That's exciting too, because that gives us applicability both in thyroid eye disease but also in Graves' population, which is exciting and complementary to the portfolio. Finally, we have our FcRn portfolio is continuing to move forward. We have finished our first-in-human for our 006 program, which looked just like it should in terms of IgG suppression and albumin sparing. That looked great. Now we're working through our first-in-human study on the 008 program, which is a half-life extended approach for FcRn. A very exciting portfolio, turning into a commercial company, but a lot of great stuff in the pipeline.
Got it. The PDUFA is coming.
June 30th.
anytime, right?
Yep. June 30th is the PDUFA date.
I think we've seen it where some of these PDUFA moving ahead of time, too.
Yeah, I don't know if I'm going super loud.
Yeah. Can you give us an update on the launch prep? Are you guys just ready to go? You just pushed the button and the sales force is all trained up. Where are you with that process?
We are all ready to go across the board. The sales team has been on board for, they came in in certain waves, but all the hiring's been done. We know that the label's somewhat predictable, we've been able to train them. They're not out there talking to physicians about anything yet.
They do have the ability to at least make an introduction and have a non-product specific conversation. That stuff is all good. Our medical affairs team has been out in the field for quite some time, which is great, because they're able to talk about the data from the clinical trials. We have our patient support services, which is also built and ready to go. Supply chain's ready to go, market access. In all of our systems, our internal G&A support for launch, everything is ready to go. We are operationally launch ready. We've actually been launch ready for a few weeks now, we are all ready to go. We can accept patient enrollment forms the day after we get approved.
Oh, wow. Okay.
We're ready to go.
Okay. More questions on that topic later. The FcRn, I think you mentioned that we'll see updates on the FcRn for VRDN-006 and VRDN-008. What data will you be presenting? Are you going to be presenting the actual indication that you want to develop into? How would you differentiate from [audio distortion]?
Yeah, I can take that one. We have two programs with FcRn, VRDN-006, which is an Fc fragment, and we really like the Fc fragment. We think there may be something special about a fragment that the full-length antibodies so far have not been fully able to replicate the safety and efficacy of the currently available fragment, and VRDN-006 would be the other one that is in development. We've communicated that phase I studies in healthy volunteers, the data looked as expected. IGF-1R, IgG suppression's in line with the FcRn class sparing of LDL and albumin, well-tolerated. Very clean profile across the board, so that's exciting for that program. VRDN-008, which has the half-life extension that we've talked about.
It's difficult to engineer half-life extension into an FcRn molecule, but we've been able to do it, and that is in ongoing healthy volunteer studies right now, phase I, and we expect data second half of this year. We will plan to look at and disclose and share the healthy volunteers' data with regards to IgG suppression. We want to see that in line again with prior studies and what we have seen in non-human primates, which historically had been very translatable to humans. We'll want to see tolerability and in particular with regards to LDL and albumin, to see that being spared, which again, we saw in primates. Looking to confirm that.
Importantly, looking to confirm the half-life extension, which again, head to head versus efgartigimod in the primate studies, we saw longer half-life, three times the half-life, as well as more sustained IgG suppression. That will be very exciting data from a healthy volunteer standpoint to confirm that in humans, which will allow us to really extend the dosing interval between doses of an FcRn, which we think could be a game changer for patients. Both of these programs we've designed to be subcutaneous and patient self-administered, which is still an unmet need for patients in FcRn. We believe that we will be able to move the field forward with either one of these profiles.
I see. Okay. You will be disclosing the indication and then sort of the development plan for those indications.
Yeah, that's right. For each of these programs, we do plan to update everyone on how we're thinking about next steps in development, indication strategy. Correct.
Fantastic. Okay. You guys recently raised $300 million equity and convertible senior note. I remember you guys mentioned that you guys already have enough capital to kind of sufficiently take the company to cash flow positive. Was that just to pay down, I think, the Hercules Capital credit facility? Is there anything beyond that? Is there any consideration to pay off the DRI Healthcare financing deal as well? Like, what's Anything there?
No. What we did is, yeah, we were able to pay down the Hercules facility, lower our cost of capital.
a result of doing that. That was smart corporate governance for us to be able to do that. We also talked about the fact that we have this TSHR program that I referenced in the introductory. We are also looking at ways of possibly retreating in the veli program, in the elegrobart program. All of the commercial activities, all the commercial launch for both veli and elegrobart were already covered. We thought it was a good idea to take advantage of the convertible market terms, this very favorable market. We thought that was a good idea. Then we did a small equity component to it as well.
Yes, we were guiding towards profitability before that deal, and we're obviously more comfortable in more comfortable territory given additional capital. Again, we've got a lot of really good investments to make here across the portfolio.
Yep
We look forward to that.
Can you share the sales force that you guys have already ready to go? How many are there? Are they structured, dedicated by specialty? Are they all targeting different doctors, or are they more like some are for endos, some are for ophthalmologists, and some are for surgeons? How are you guys thinking that?
It's more geographically laid out for the sales force. The sales force is a little under 100.
Yep.
On top of that, obviously we have medical affairs team, which is crucial part of rare disease commercial efforts as well.
go through all the clinical data in detail with folks. We have the patient support services on top of that. We have a concentrated call point here where there's really 2,000 core prescribers that we need to reach. They're identified in the claims analysis. We know who they are with respect to, this is the group that writes primarily all of the, or essentially writes all of the TEPEZZA prescriptions. That is our target audience, and so we are right-sized for that. As you know, TEPEZZA's a $2 billion steady-state product right now, and we think adding our voice to that, adding particularly our profile of veli into that prescribing habits is, that's the target. That's the sales force is set up to do that.
I see. Okay. When I turn on the TV, I see a lot of TEPEZZA commercials. Right? They're everywhere. From a resource perspective, Amgen's obviously putting a lot of resources in there. They probably have more sales rep than what you guys, what the number that you guys quoted. Just given all that, are you concerned about just not matching the resources? Would you consider, from a DTC perspective, will you consider matching to what Amgen's doing? Or is there other more innovative type of channel that you can go and not have to spend the same type of money toward those campaigns?
Yeah. A couple points. First and foremost, their Salesforce is not that much bigger than ours. It's incrementally bigger at most. We are correctly sized, particularly relative to them. In terms of direct-to-consumer advertising, I don't think you'll see a lot of us do. We can do a lot of that on social media. Obviously, there's a lot easier ways to do that, from a capital allocation standpoint. I think more importantly, we applaud the direct-to-consumer that they're doing. It's good for patient education. Physician education that they've been doing for a while, payer education they've been doing for a while. We get to take advantage of all that. All that legwork that they do is channeling those patients to the physicians that we're going to be calling on. I think the physician reaction to having another treatment option available to them is really exciting.
This is the first time, once we get approved, we'll be able to offer the only other treatment option that's been available until. We think there's a lot of physician excitement about that. We think there's a lot of patient excitement about that. From a resource standpoint, that's all channeling to the places where we're going to be.
I see.
Remember that this is a new start market, we're not looking to switch patients off of any treatment that they are on and doing well on because everything is fixed dose. The currently approved treatment is fixed dose. veli IV will be fixed dose. It's a shorter course of treatment, actually, from a fixed dose standpoint. We expect those patients, in terms of raising awareness and channeling those patients to physicians, to be a potential new start patient for Veli as well. We feel really good about the clinical profile and soon to be, we anticipate, commercial profile for Veli, given the data that we generate in both THRIVE and THRIVE-2. In particular, the points of differentiation that we've talked about before that form the basis for our applications for breakthrough therapy designation as well as priority review.
First of all, rapid onset of treatment effect on the active side. Chances are a patient who starts therapy will have already had a proptosis response after just one infusion after three weeks. Secondly, diplopia improvement and resolution for these patients, in particular on the chronic side, which Veli is the first drug candidate to have shown that level of diplopia benefit and statistically significant in chronic patients. We offer all of that with a shorter duration of treatment in just 12 weeks that a patient will complete the entire full course of treatment, and each infusion is only 30 to 45 minutes long.
Remember that this is a market that's primarily made up of women in their 40s and 50s. It's an autoimmune disease. These are people with very busy lives, with families and jobs and just the activities of daily life in that age group. The ability to bring, as Shan just referenced, a shorter treatment period of just five infusions, shorter infusion times, just on a logistics basis of the clinical profile is what it is with the differentiation that we think that Shan just referenced, the simply just the ease of the treatment.
Right. Okay, got it. The PDUFA's coming. We're going to see your label coming out very soon. How do you think it's going to differentiate against TEPEZZA's label? Shan, I think you highlighted a lot of things there that some of these advantages that we saw from the THRIVE trial. How would those be reflected in the label relative to how TEPEZZA show? Obviously, I think the chronic data. They don't have chronic data in the label. You will. What are some of the other key differentiation, especially those points that you mentioned?
Those points that I mentioned in terms of rapid onset of treatment effect, diplopia in response and complete resolution, all in a shorter course of treatment. Those are the key data points from THRIVE and THRIVE-2, our two pivotal studies. We would anticipate having that data in our label in both active and chronic TED, in which case we would be the first drug approved for thyroid eye disease with both active and chronic data in our label. That's a major differentiation point for the label. Remember that when TEPEZZA was first approved, the indication was broad. It was for not just restricted to active TED, which was the basis for their registrational trials, but inclusive of all TED patients.
We do think the FDA views this population as a continuum of disease and does not necessarily differentiate between active and chronic TED, and so we expect to also have a broad indication. The labeling, again, this is where Horizon has done a very good work in getting a clean label on both the efficacy as well as safety data that's in there, and we get to benefit from that, but replacing the data with the data that we generated from THRIVE and THRIVE-2, which we think are very compelling.
I see. Okay. I know part of the launch prep, you guys go and every company do a lot of these qualitative, quantitative market research with payer, prescribers, and patients. What are the findings there in terms of how many of them actually recognize that differentiation, that people actually recognize it and would see that as an advantage for them to use the drug?
I think what's more important when it comes to the payers is, the feedback that we've gotten and as we've been in communication with the payers for quite some time, including the pre-approval information exchanges that you can do now. I think what's really critical and important is that now that TEPEZZA has 85% of commercial insurance plan coverage for the U.S., which has taken a bit of time, but it's a great setup for us to walk into. Our interactions with payers have been, essentially, their communication to us is, "You can get parity coverage at a parity pricing." They recognize the value of IGF-1R. Particularly when you look at the competitive landscape from a year and a half ago, where you had, or two years ago, where you had IL-6, which didn't quite pan out. They failed one of their studies.
IL-11, obviously, that didn't go forward either. FcRn as well. When the payers fully recognize the value of IGF-1R, and so when they look at our profile, the feedback has been parity coverage, which is a great place to be. 85% of coverage is for us to step into. That'll take a bit of time, just because every plan has its own kind of timelines we have to deal with, but it's a great spot.
You don't think that they're going to use prefer or exclusive contracting? You believe in your research, most of them are saying that, "Look, parity access would be something that we're open to.
Yeah. That's the feedback.
We're not going to try to get you guys to outbid each other.
No, we haven't seen that.
Oh, interesting. Okay. Again, going back to the market research with the prescribers. Some prescribers are very comfortable. They've been using TEPEZZA for years. They're very comfortable with it. They know it inside out in some way. Here's a new product coming out. They don't really have that much experience with it. For those doctors, how long do you think it takes for them to kind of get used to it and how many prescribers are in that camp? Where it's more or less just want to stick to what they know and not very adventurous to try something new. How many are in that camp versus how many are more open to like, "Look, I saw the data from your THRIVE trial. Looked very encouraging. I want to start trying.
Yeah. The latter is the overwhelming response that we've gotten. It has been very consistent that there's a lot of excitement around the availability of a treatment option and a willingness to try that. For all the reasons that we talked about with the rapid onset, the diplopia data, and the treatment regimen. Those are exciting prospects for the first time since in the last six years. There's a lot of willingness to try. Now our job is to make sure that we make those experiences as good as possible for both, obviously, for the patient first and foremost, but the physician as well. I think that'll go a long way.
Right.
We also enrolled high volume TEPEZZA prescribers in our clinical trial. Many of these physicians already have experience with veli IV, and actually, in fact, probably have had experience with elegrobart since there was good overlap in trial sites for both of the two programs. Of course, as we've mentioned, our medical affairs team has been out there talking with these 2,000 core prescribers so that they are well-educated on, first aware of veli IV as a potential option, and also well-educated on the data that we've generated from THRIVE and THRIVE-2. It's helpful that it's the same mechanism. It's IGF-1R. We are a full antagonist. For physicians, understanding that it is the same mechanism is also very helpful.
I see. Okay. Let's talk about the chronic patients a little bit here. TEPEZZA has been struggling with these patients, single-digit penetration. What's the potential of veli IV in that chronic TED setting? Is it just because you have three less infusion and suddenly that opens up? How should we think about that chronic setting? Or should we have to wait for the subcutaneous or for elegrobart to come out in order to better penetrate that population?
I would say that our strategy out of the box, as we described those 2,000 core prescribers, is more of a conversion of their prescribing habits. Currently, they prescribe probably on an 80/20 basis, active versus chronic. We do think that the veli IV profile has potential because it can possibly make the logistics side of it easier. That might bring some people off the sidelines from a chronic perspective.
Yeah.
In the short term, our strategy is to convert those current prescribing habits, we can grab share. A reminder, this is a $2 billion market with a single product. The ability to come in, have an option, grab some of that market share in those prescribing habits, that's the main priority in the early days. We do think it's going to be attractive to chronic patients. Obviously, when we come with the SubQ, that really unlocks the chronic population because the urgency to treat, depending on where they are, and it's such a continuum or spectrum of patient experience on the moderate to severe, where they fall on that index. We do think that the SubQ would be instrumental to unlocking a lot of those chronic patients.
Right. Given that these chronic patients have very highly variable disease and likely less severe in terms of the symptoms and inflammation, how are they being treated now if they're not using TEPEZZA? Also, what proportion of them truly need an IGF-1R?
Yeah. We ran the two largest studies that have ever been run in chronic patients.
These were patients that, by definition, to get into the studies, had more than three millimeters above normal proptosis. We had a very high percentage in both THRIVE-2 and REVEAL-2 with the chronic studies where they had diplopia as well. The symptomology, because there's a lot of variability in that chronic population, we did enroll patients in our chronic studies that had both proptosis and diplopia. They had low clinical activity scores, or they had high clinical activity scores. That's basically a proxy for pain and inflammation. There's a lot of variability, and we think that the chronic population has not particularly gravitated towards the currently available therapy, primarily, in our view, from our research, because of the profile.
If you think about it, if you've been living with the disease and you're being asked to go for six months of infusions, that can be a lot. Particularly, again, as I mentioned, this is women in their 40s and 50s with very active lives. Our whole approach here, both with IV and with SubQ, is to try to make things easier. We do believe that that's going to resonate with that patient population and expand the market from there. We think that's primarily a profile issue.
We enrolled both of those chronic studies very quickly, so THRIVE-2 on the IV side as well as REVEAL-2 on the SubQ side. The majority of the REVEAL-2 study came from the U.S., 56%, and that's with a commercially available therapy that's here in the U.S. That is good signal for the motivation that these patients have to seek treatment and their willingness to come on to treatment to have the symptoms of their Thyroid Eye Disease be addressed. We think that they're just being underserved right now by what is currently available.
I see. Okay. Let's move on to Ellie. We don't have a lot of time left, so there's a lot to talk about there, too. You guys presented the phase III results for the REVEAL-1 in the active and REVEAL-2 in the chronic study. REVEAL-1 fell short of your own expectation that within TEPEZZA's proptosis response. REVEAL-2 showed IV-like results that fell between TEPEZZA and veligrotug proptosis response. How do you sort of reconcile the difference between these two studies?
Yeah, look, I think as a reminder, REVEAL-1 was highly stat sig on the primary endpoint.
Yeah
of proptosis reduction for Q4. We saw very clinically meaningful responses in diplopia in the Q4 arm. The Q8 weekly arm is an option for patients where we saw really good proptosis responses. That was in the active study. We saw that reinforced, to your point, on REVEAL-2. Highly stat sig on proptosis response for Q4, but we also saw very good response on diplopia. The Q4 weekly option, and our intention is to move forward with both of these treatment options, Q4 and Q8. Q4 looks very promising in proptosis and diplopia. Q8 weekly promising for people where diplopia may not be their main complaint, but proptosis is. Just if you think about getting This is IGF-1R in an auto-injector pen.
Everyone knows that IGF-1R is the mechanism that actually is the most effective in this disease population. The ability to put IGF-1R in an auto-injector pen that's very simple, it's at home, patient-administered at home, that is going to be very meaningful for this patient population because if you think about where we fit, we've got IV. We've got an IV that we just talked about for all the reasons that that's a very attractive profile. Q4 weekly for proptosis and diplopia patients, and Q8 weekly for proptosis. We have an answer. We believe we have an answer for any patient that walks in with moderate to severe TED. We can address it across it. Those studies reinforce both of those profiles.
I see. Yeah. Got it. Even though Ellie's inhibition for the IGF-1R saturated. Excuse me. You guys showed similar PK/PD profiles.
Why do you think that the REVEAL-1 and REVEAL-2 results were lower praise?
We had the PK/PD both looked like they were supposed to in terms of on the PK side of what we saw there, plus the IGF-1 levels that we would see from the PD side. The drug did what we expected it to do. We may have seen some clinical variability in REVEAL-1, but REVEAL-2, as you pointed out, as expected, brought that efficacy. I think that kind of reinforces the profile. You may have seen some variability in REVEAL-1, but at the end of the day, we've tested these profiles with physicians, and the response has been overwhelmingly, "Okay, that looks like IGF-1R in an auto-injector pen. That's a great profile for us." I think that's the bottom line. It's very simple. Everyone knows that IGF-1R is the right mechanism, and now we expect to be able to do that in an auto-injector.
Okay. Got it. When you think about the patients that are suitable for Ellie versus Veli, how do you think about that setting, right? You have two products come out in the active setting and the chronic setting. How do patients choose between them?
Yeah, a little bit to repeat myself, I guess, but on the IV side, we think there's an IV appropriate patient population, no doubt. As you go up the index in severity and that urgency to treat, forever, we expect there to be patients that will be appropriate for IV, whether that's because their physician wants them in a controlled setting like an infusion center, or the patient wants to be in a controlled setting. Like a sight-threatening patient, you would want to put them on IV. That's what we have Veli for, that kind of severe. We think it's obviously done very well with the moderate end of that spectrum as well, so we think that's a great option.
When subQ is available, we do expect that the patients that are non-IV, that Q4 weekly has that impact on proptosis and diplopia, and the Q8 weekly is really geared towards the proptosis. We cover that spectrum of patients, and we have an answer for anybody who walks in.
I see. Okay. I always look at chronic and the active patients as two very different and sort of distinct populations in some way. Therefore, because of that, you need different products that cater towards their needs. Do you share this view that these are sort of two kind of distinct patients? If that's the case, then what product attribute do you believe that are more suitable for active and chronic patients?
Yeah. The way we look at it is, there's certainly the active population, again, along that spectrum that I described from moderate to severe, there's also that same moderate to severe spectrum in chronic. You'll have patients that have lived with the disease, but they're not necessarily complaining about the pain and the inflammation that goes with it. They may have settled into their proptosis. diplopia is a little harder to settle into, but there is some element of that. We call them kind of like a chronic stable population, which is really where TEPEZZA was studied in that population. There's a chronic flaring population is what we call it. These are people, as I said, we had people to get into our studies. The largest studies ever run in chronic.
To get into our studies, you had to have above normal proptosis, and a large percentage had diplopia as well. There are patients in that chronic population that, again, to Shan Wu's point, they enrolled that study quickly. They're the biggest studies ever run. It speaks to the market demand that's still out there for these patients. Yes, there is a distinction. There's a lot of chronic patients.
It's very under-penetrated, which is the opportunity in front of us with both Veli and then obviously Ellie subQ.
Right. Got it. I do want to ask you this question. Besides the OBI from Amgen, they have another IGF-1R subQ asset in development called AMG 732. I believe this is another legacy product from Horizon's acquisition. I think it's in phase I to development. It's a new molecular entity. Signs for subQ, not like TEPEZZA OBI, which is really just more like TEPEZZA we formulated for subcutaneous. Given that this asset and then TEPEZZA OBI is not being developed for chronic TED, my guess is that this one could be. Have you heard much about this asset and your thoughts about it so far?
Yeah. Let's start with the OBI for a second. The OBI is four inches long, two inches thick. It's got gears, batteries. You have to insert the cartridge into yourself. You have to wear it under your abdomen for up to 30 minutes. It's an infusion. It's not a subQ. It's an infusion pump that you wear on your stomach. You have to do it every two weeks for 24 weeks. Not really clear where that fits into the competitive profile. Compare that to the auto-injector pen that we have, which is the same pen that DUPIXENT uses. Very patient-friendly. A lot of people are familiar with it. We don't really see that as a competitive profile in this. It's just not sure where it fits. With respect to the AMG 732, yeah, we're aware of it, but it's several years behind.
We don't know exactly what it is. We think it's IGF-1R. We don't know exactly how it's set up. They haven't talked a lot about it, they just got started with phase II, so they're years behind.
Right. Fantastic. We're out of time. Thank you so much. It's been a pleasure hosting you guys, as always. I'll turn it to you guys for any final remarks.
No, look, we're about to be commercial. We've got a great profile, very highly supported by the Phase III data. We've got a great commercial team, very familiar with buy and bill dynamics, so we're ready to go operationally. Regulatory interactions have been great. We're looking forward to advancing Ellie with BLA in Q1 2027. The SRM portfolio is coming, too, along with TSHR.
Awesome. Look forward to it.
All right. Thanks, Richard.
Thanks. Thanks, Steve, Shan .
Thanks.