All right, good morning, everybody. Welcome to the 2025 Jefferies Global Healthcare Conference. I'm really thrilled to kick off the morning with the team at Viridian. Up here on the platform, we have the CEO, Steve Mahoney, and the Chief Business Officer, Shan Wu. It's been exciting times for Viridian. You guys are super busy, obviously finishing up all of the phase III studies and filing to the FDA. Maybe I would just love to give the opportunity to Steve, maybe just to talk a little bit about, obviously, where you are with your lead program in TED, with IV, and then obviously execution on SUBQ, and talk a little bit about what's going on this year and the milestones and what we should be looking forward to that is important this year.
Yeah, great.
We do think that Breakthrough Therapy designation could improve our chances for getting that. That would be really exciting because we could get our launch going. Just a couple of things about the data from phase III, a couple of standouts. The main endpoints for the trials were proptosis response, which is bulging in the eyes. We want to reduce the bulging. Clinical Activity Score, which is a proxy for pain and inflammation. Then finally, diplopia or double vision. As you can imagine, from a patient perspective, proptosis and diplopia are the two biggest concerns. What do they look like and whether you have double vision? Double vision impacts, you can imagine, a number of things with respect to reading, writing, driving, working. These are primarily women in their 40s and 50s who are impacted by this disease. They have full lives of families and work.
To have those types of symptoms can be quite debilitating. We are very happy with the results because we showed very good improvement in not only responder to diplopia, but complete resolution of diplopia. Proptosis, we were very much in line with current standard of care, except that we were able to show a rapid treatment effect. In fact, after just one infusion, we were seeing a majority of patients achieve proptosis response, which is something people had not seen before. That was fantastic too. The data looks great. We are moving on. We did just recently put out there was one question that was overhanging, obviously, when you put out top-line data. What is the durability of that response? What is going to be the durability of that treatment effect?
We just put that data out several weeks ago, and that was 70% of people who had a response at week 15 were able to maintain that response at 40 weeks post-infusion or last infusion.
How does that compare to Amgen's TEPEZZA?
Yeah, so in their label, they have a 53% rate. Again, ours was 70%. Theirs is out to 72 weeks. So 51 weeks post-infusion, and ours is 40 weeks post-last infusion.
Okay. If you compare side-by-side cross-trial with all the caveats, but that's what we have to go on, you believe that your efficacy in various components of that are the same or in many cases better, particularly on diplopia.
That's an important part.
On safety, you believe that in both studies, you've shown lower rates of hearing impairment. That may have driven why you, well, I don't know, you tell us why the FDA gave you Breakthrough Therapy because that actually was quite a surprise. They were just trying to read into what you filed on, and was there something specific? Did they not communicate to that, or they just give you Breakthrough and they send you a letter? I'm just trying to think about what they saw there.
Yeah, that's right. They do not pinpoint exactly why they granted Breakthrough, but the request for Breakthrough was based on two key elements: the rapid onset of treatment effect. Again, we were seeing a majority response after just one infusion. The diplopia response and resolution, where our numbers, again, cross-trial comparison, but that is exactly what they do in Breakthrough. They looked at the diplopia resolution rates for TEPEZZA, which were essentially negligible. There was 3% placebo-adjusted, where we were closer to 20% placebo-adjusted for complete resolution of diplopia. That is a meaningful difference. We saw that in both. That was particularly true in the chronic population. We did see a 15-point delta in the active population as well. Really, really strong diplopia data. Again, they do not tell us what they based it on, but that was what the request was based on.
The safety.
Yeah, the safety is part of it. Hearing impairment is the AE of interest in this class. We did, as you pointed out, we have lower rates of hearing impairment than they did.
Okay. What is the gating step to filing this year? What needs to happen and how fast can you file, assuming you could get priority review, but we want to start by filing.
Right. We've been very consistent on our guidance. It has not changed over the past year. We need the chronic study follow-up period to complete before we can file. We are just waiting for that process to finish. We've already finished, as I mentioned, because we have our durability data. We already did finish the active study, the THRIVE study, and we were able to get that 52-week data out. We are still in the process of patients in the follow-up.
Do you need to have a pre-BLA meeting? What are the FDA interactions over the past six months and going forward? Do you have to have a pre-BLA meeting, et cetera? Obviously, there are changes at the FDA. I'm sure everybody knows Marty McCarry will be here later today, so maybe we'll ask him. In all seriousness, you have a group that you work with in that division. Obviously, we're just trying to figure out how the interactions are going and whether you feel like this should be pretty straightforward. I would agree that the Breakthrough Therapy thing was interesting. Seems to go a little bit missed, but I thought that was interesting, so.
Yeah, so we are in the ophthalmology division. We're under CDER. Our ophthalmology division appears to be completely intact. The leadership is there. Our review team is there. We, in fact, had, as part of the Breakthrough discussions, we actually had a face-to-face meeting down at FDA, which was great.
Who do you meet with there? Is that someone in the ophthalmology division or?
Yeah, ophthalmology division. Billy Boyd was in the room. He's the, I think he's considered the Director of that division now since Wiley Chambers left. The main point is that the ophthalmology division is intact. Our engagement with them has been great, and we feel we are aligned.
Right, because Wiley moved on, and so whoever has responsibilities, you did have a meeting with them.
Yes.
Okay, good. Okay. All right. There are two topics that we should also cover coming up. One is when you get that filed, you could have priority review. There will be presumably a PDUFA date in 2026. We look forward to that. Obviously, you're trying to finish up execution on the SUBQ. There are two parts there. One is to the extent that investors should be excited and valuing the commercial opportunity for IV, but then literally a year or so after that, here comes SUBQ. Maybe we take that in two steps. Where are you with SUBQ? What needs to happen? What do you expect out of those results? Those are important questions.
Yeah, no, and I think.
That's a whole step up over IV.
No, that's exactly right. I think you're setting it up the right way. In fact, with the fact that we will be a commercial company next year is our expectation. The data is very solid and in our alignment with FDA there. We do expect to be a commercial company. It's just a matter of when on IV. The SUBQ program is currently enrolling two phase III studies, active and chronic studies. That is all on track with our guidance, which is data in the first half of 2026. We expect to file a BLA at the end of 2026. We're about a year behind.
Yeah, in terms of completion of enrollment, where are you with those two studies and how's that going and all that kind of stuff?
Yeah, we are on track with everything. The study is exactly on track where we want to be, which is obviously a great sign. We will have that data in the first half of 2026.
Just to be clear, there's timing for the data in the first half of 2026, right? So top lining for completion of enrollment.
Yeah.
You can do the reverse math.
Yeah, you're going to have to do the reverse math.
You could be unguided, but okay. All right. Would you announce when you complete enrollment or that's an earnings call thing or?
Yeah, maybe.
Just thinking about milestones in the next few months.
Yeah, we would consider announcing that depending on what's going on, but yeah.
Are there two studies? Are they exactly duplicate or are there differences by regions or what?
They're staggered. They're both in the U.S. and Europe.
Okay. Staggered meaning that one will finish up later on.
Yeah, one will finish first.
All right. What do you expect out of those results? Do you think that the results should be essentially identical on all of the efficacy and safety endpoints cross-trial to your own IV? Do you believe that perhaps based on the administration as a SUBQ, that perhaps there could be better side effects because of hearing loss? There are different hypotheses as to how hearing loss comes about. Maybe with the SUBQ, you're blunting the CMAC, so maybe that's an interesting angle. I actually don't know. What do you think would happen with the efficacy and safety of the SUBQ data?
Right. So Shan's going to take this one.
Yeah, it's a really good question. I think it's worth taking a little bit of a step back and discussing a bit about why we're so excited about the SUBQ program. The VRDN-003 program, the antibody portion or the molecule, I should say, shares the same binding domain and CDRs and will interact with the target of IGF1R in the same way as the Veligrotug IV molecule. We've engineered the 003 molecule to have an extended half-life, which we confirmed earlier back in 2023. That data allowed us to take this straight into a set of phase III studies, and that was aligned with the FDA to test Q4 weekly and Q8 weekly dosing regimens for 003.
Once a month or once every two months?
That's right. Exactly. We think both of these would be exceedingly convenient for patients and would be a game changer from a dosing and administration aspect for patients. These would, we would anticipate, be self-administered autoinjector pens that would be mailed to the patient at home with at-home administration, which if you look at a number of analogs with SUBQ administration, it can significantly expand the number of patients that are actually treated because of that increased access without having to go to an infusion center.
Now, coming back to the shared pharmacology with our IV molecule with veligrotug, back when we put out that data in healthy volunteers confirming the half-life in 2023, we also did PK modeling showing that Q4 weekly and Q8 weekly, the exposures associated with 003 in both of those two regimens matched back to the exposures we saw with VELI IV in a phase II study that we had at the time. Q4 weekly was achieving CMIN levels and looked really great in terms of exposures of 10 mg per kg IV from that phase II study. Q8 weekly was showing that it achieved the CMINs of 3 mg per kg IV. Now, 10 mg per kg IV, obviously we just showed in THRIVE and THRIVE-2 really fantastic efficacy and safety data. We're really excited about the potential for the Q4 weekly arm.
Now the Q8 weekly, we were pleasantly surprised that it was able to, exposure-wise, match back to 3 mg per kg IV because that 3 mg per kg IV dose arm in the VELI study, small patient numbers, acknowledge that, but showed very, very great and robust clinical activity across all of those parameters of proptosis, CAS, and depression.
It's interesting because your, one question is 10 mg per kg is the dose you're using in IV. And it's interesting because 3 mg per kg IV did show similar efficacy as 10 mg. So from an FDA minimally effective dose concept, your phase IIIs didn't use 3 mg at all in any of the arms. Is that correct? They were 10 mg.
That's right.
Yeah. Now there's no real safety concerns. In fact, safety looks pretty good. There wouldn't really need, like other indications, they want you to find the lowest effective dose that's safe. There's no issue there. Three mgs did look basically the same. When you do your SUBQ, you're using a once a month that literally looks identical in exposure to the 10 mgs. Then a once every two months, which looks like the exposure of the lower IV dose, which also looks like the highest. You're covering both. Either one, they could look identical. One could look a little bit lower, but not clinically meaningfully different and give someone once every two months. How do you think about those scenarios? Obviously a win is they both look identical.
One win is one looks a little bit better than the other, but both could be approved. How do you think about those?
Yeah, we think both of those are de-risked and we'll make decisions on which dose to take for once we see the data. From both of those dosing regimens being de-risked standpoint and the fact that the Q8 weekly at a lower set of exposures could match the efficacy that we have seen or come to expect with IGF1Rs, but with the lower exposures lead to an even better safety profile. That's a really exciting potential for the REVEAL-1 and REVEAL-2 outcomes.
How do we look at that? Because they're obviously not going to be statistically compared to each other, but they would be, each arm would be compared to placebo. Now, if you go back to some of these nuances, which I don't have time to go into, you're more than well powered because I think the number of patients in there is like almost larger than the IV per arm. That shouldn't be a concern. You have more patients per arm each of those. You have more powering than the IV. If the once every month is identical to the IV, that's a huge win because now you have a once every month SUBQ. If the once every two months looks similar and beats placebo statistically significant, that's a huge win.
Yeah, these are all great profiles to have. At the end of the day, what we're really excited about for both of these is the fact of the self-administration. We can mail these to patients and they can self-administer at home, which will greatly expand the patient population that would be motivated to take an IGF1R.
I got to be honest, I don't actually know how I would characterize Wall Street's expectation. Wall Street's expectation is like, hey, if one of those arms win, presumably the monthly, you have a huge opportunity because you have a once a month SUBQ. If once every two months hits statistically significant, I certainly don't think Wall Street's really thinking about that. That would be huge, certainly where the valuation is. If both of them hit and they both look identical, would you just file both and try to get both in the label? Or that's an interesting question.
Yeah, we haven't gotten into those details yet. Let's see what the data shows. Either one of those dosing arms we think would be a game changer for patients.
I was going to say the same thing.
Certainly we got to have positive data. If the second one is also positive, the once every two months arm, I do not think anyone thinks that is even, that is even talked about. Let's say they are positive and the IV is getting approved and 2026 could be a huge setup because you could be an approved company and have this data in hand. People look at the TEPEZZA sales from Amgen, which I cover, and the sales are declining year- over- year. What do you believe based on your, we have our own checks too and we have heard different things, but what do you think is going on out there to explain the sales of the drug, which has a monopoly, TEPEZZA has a monopoly and the sales are declining year- over- year?
What do you think is the issue and why do you think Viridian would be able to change that?
I think first, kind of hard to comment on another company's execution and that type of thing. You know, if you look back at it, what Horizon originally ran, they did not run, when they were developing the drug, they ran active studies only. It was not until after approval where they seemingly got pushback from payers that there was no chronic data for payers to look to. They were not getting their reimbursement out of on day one. It took them several years. In fact, they did not even run a chronic study until 18 months after approval. That data got generated late in the game. On their last conference call, they said they made a big jump because all of last year they had a commercial insurance coverage of about 50%-55% in the U.S.
On the last call just a few weeks ago, they mentioned that they had broken through and gotten up to 85%. All of this is great for us because all they're educating, all the work that they do is great for us and great for patients most importantly, right? There is an education campaign for patients, there is an education campaign for physicians, all with respect to IGF1R, but there is also education of IGF1R for payers. These advancements that they're making with payers, particularly in the chronic population, are great for us because again, we have that data on day one. Our data looks, again, cross-trial comparison, but it looks favorable to us. The key for all of this is that this is a new start market, right?
For all of those groups I just mentioned, patients, physicians, payers, every time a patient comes in to see a physician because of their symptoms, the bulging of the eyes, the double vision, the pain, it's often described as having a grain of sand under your eyelid and you're just constantly trying to get it out. You can imagine how miserable that is. Someone comes in with symptoms, we don't have to get them to switch off of TEPEZZA.
We don't have to get them to switch off of anything because when they come in and they say, what are my options, my treatment options, and we're on the market and we can say, the physician can say, hey, look, I can get you again, cross-trial comparison, but it looks like a better clinical outcome, at least as good, if not better clinical outcome, but I can do it with five infusions versus eight. So ours is five, theirs is eight. 10 mg per kg versus their 20 mg per kg, 30-minute infusion time versus their 60-90-minute infusion time. All the things we talked about with the differences in the data. If we win that conversation right there, we can shift the revenue stream right then and there to veligrotug. That is a great market dynamic for us to walk into.
To your question about their sales in their record over the last several quarters, do not forget, TEPEZZA is a six-month regimen. I mean, that is six months of going to infusion centers. We are coming in and we are going to reduce that to three months. That is going to be really attractive, we think, to patients and physicians. Importantly, in the infusion centers, we will turn the chairs over.
By the way, most of these doctors that are prescribing, they do not have in-house infusion centers. Some people say the doctors have economic incentive to treat at their own facility because they want to keep the patient, see them once every three weeks.
Yeah, every three weeks, I recall.
Therefore they're making money and seeing the doctor or the patient every three weeks and they're getting paid to do the infusion. The infusion is not at their center. It's at some other center, which they have no economic ties to. Is that true?
Right. Yeah. In oncology, you'll have those types of economics where there's incentives for physicians to hold patients on a particular drug because they benefit from it financially in their own infusion center. Ophthalmology, they do not have their own infusion centers and they are primarily the prescribers, right? Even endocrinology, when they see the eye manifestation, will say, hey, you need to go see a neuro-ophthalmologist or an oculoplastic surgeon or even your ophthalmologist. The ophthalmology side of the world writes the prescription, but they send you down the street to an independent infusion center. Those market dynamics of keeping loyalty to a particular brand is not.
There's no economic there.
There's no economic benefit.
Yeah. Okay. So look, if we can get filed and get approved next year and then also the SUBQ data is coming next year, that's a huge setup. It's a big 2026 for you on that front. And that's ahead on TED.
Yeah, that's right. Exactly. I think key takeaways here, we're going to be a commercial company. We've got an opportunity in a new start market to grab meaningful share of patients. We think we're going to be more convenient. We think we've got better, we've got some differentiated data. SUBQ will plug in nicely to the IV infrastructure we're going to build this year.
Yeah. While that's happening, and yeah, I just want to emphasize because we were pleasantly at the Breakthrough Therapy thing that just happened and also the durability of it. All that was sort of just reported in the last couple of months.
Exactly. I think that was the key.
It's been a bit under, not as appreciated because there's so many other things going on macro-wise with the sector. Just wanted to say that that was interesting. Maybe in the last couple of minutes, again, I think not talked about a lot is you are pushing forward with an FcRn program. Maybe you could spend just the last couple of minutes perhaps teasing us with where you are with your FcRn. Now you kind of have like two different programs. One is a more straightforward one and then one could be a long-acting version. Can you just remind us where you are with those? Are you trying to do both or what is your strategy with FcRn?
Right. The first program is an Fc fragment, very much like Vyvgart. It's a similar approach. We believe, as far as we know, we are the only other Fc fragment in clinical development. Everything else is full-length antibodies or degraders or that type of thing. We like the fragment. Vyvgart, we believe, is still the gold standard from an efficacy and safety perspective. Obviously, these are big markets to operate in. The first two markets, MG and CIDP, are projected to be $9 billion-$10 billion over the next several years. According to some, there are another 75 indications that should be addressable by FcRn. These are large markets with lots of opportunities. We like the fact that we're the only other fragment because of the profile that Vyvgart's been able to create. That is our first program.
We have healthy volunteer data coming out Q3 this year. The reason healthy volunteer data is important in this world is because it confirms everything you really want to know. It confirms IgG suppression in, even though it's in healthies, it has been proven to be highly translatable to disease patients. So IgG suppression thresholds, we want to see that. We want to see how.
What level do we want to see? Because people cite different numbers. What do you want to see in healthy?
We want to hit that Vyvgart range of 60%-65%.
60%-65% reduction of antibodies.
Yeah. And that's just in the range of Vyvgart. If we can replicate that, that's a great sign. Obviously, you want to be albumin sparing, so you're not seeing those LDL spikes, which is what they saw with the tokamab. Finally, dose. We'll figure out some dosing information on this.
How will you differentiate with this one versus Vyvgart?
We have some ideas as to how that could play out. I think we want to see the data and then we'll come out with the data and say, here's where we can be differentiated.
Is it going to be faster onset, faster drops? Is it better dosing? Just like.
Yeah.
I'm not exactly sure.
Right. We're looking at.
Investors are not sure.
Yeah. We're looking at frequency. We're looking at dose levels. We're looking at route of administration. All those things be differentiated. But we do like the performance of the fragment. So that's the first program. And the second program is, as you mentioned, is a half-life extended version of that. It's an albumin binding domain that allows us for that half-life extension. It's very similar to Argenx in that case, I mean, we came out first, but Argenx does have a similar concept in development as well. And we're neck and neck on time.
Yeah. They have phase I data, first half 2026.
Right. We have an IND filing at the end of this year.
Okay. So you're not that far behind.
Yeah. Yeah.
Okay. Okay. Fantastic. Thank you guys very much. We've got some FcRn data coming later this year. I did not appreciate that. You obviously have a big 2026 with TED. I feel like it has been a bit of a tough biotech tape, but obviously this sets up quite well for some big events just around the corner.
Yeah. Yeah. Thanks for having us, Mike.
Thank you, guys. Thank you very much.