Sure enough. There we go. Great. Good afternoon. Thanks everyone for joining us. If folks from the last presentation could filter out, that would be fantastic as we kick off here. To everyone here for the presentation today, we're thrilled to have the Viridian team with us. We've got Scott Myers, and we really appreciate having everyone here at the conference. I'll go ahead and pass it over to him to make the most of the time, but thanks so much and welcome again.
Thank you, James. Pleasure to be here to share an overview of Viridian. Before I begin, of course, I'll be making some forward-looking statements. Please see our SEC filings for important disclosures. Viridian is developing best-in-class medicines for patients suffering from serious and rare diseases. We were founded in 2020. We're based in Waltham, Massachusetts, just outside Boston, with about 90 employees.
Our market cap, after some exciting news yesterday morning that I'll discuss in more detail, is now approaching $2 billion, with an initial focus on thyroid eye disease or TED. We're well-funded with cash at year-end of approximately $425 million. That funds us into the second half of 2025. Our core focus is to leverage our expertise in antibody discovery and engineering.
We look for first entrants that validate a novel mechanism of action, where we see a significant market opportunity and a serious disease with limited competition. If that first entrant leaves room for improvement, we'll identify and engineer what we think will be potential best-in-class antibodies and move them forward to patients as quickly as possible.
Our pipeline is led by both an intravenous effort in thyroid eye disease, VRDN-001, where I'll share some exciting data today. A subcutaneous effort. We have two different molecules, VRDN-002 and VRDN-003, both including half-life extension technology that we think can deliver a durable best-in-class entrant in thyroid eye disease. We do intend to grow beyond thyroid eye disease, beyond ophthalmology. We have preclinical programs in autoimmune and rare diseases, VRDN-004, 005, 006. We'll be excited to share more about these, at least one of these programs this year.
Thyroid eye disease, for those of you who are unfamiliar with this rare disease, is a debilitating autoimmune disease in which autoantibodies attack the insulin-like growth factor-one receptor, IGF-1R pathway. That leads to an expansion and inflammation of the tissue surrounding the eye. It's illustrated on the right-hand side of the slide here. It's a progressive disease with an acute or active stage, followed by a secondary chronic phase where the inflammation is less obvious.
The signs include the proptosis or bulging of the eyes, redness, swelling, double vision, and retraction of the lids. These are all characteristics of disease. In severe cases, it can be sight-threatening with optic nerve compression. It impacts more women than men at about a 5-to-1 ratio and is treated by several specialists, oculoplastic surgeons, neuro-ophthalmologists, comprehensive ophthalmologists, or endocrinologists. The symptoms of thyroid eye disease are quite distressing to patients.
They include dry eye, double vision or diplopia, light sensitivity, which is photophobia, decreased visual acuity, defects in the visual field, diminution of color vision, and again, in severe cases, optic neuropathy from compression of the optic nerve. While this is a rare disease, there are a large number of patients suffering from both the active and chronic form of the disease.
Over 20,000 active TED patients diagnosed each year in the U.S., so this is an incidence market. More than 75,000 patients with chronic thyroid eye disease in the U.S., and even larger patient populations in Europe and the U.K. This means there's a large commercial opportunity.
The first and only approved therapeutic is Tepezza, which is an intravenous course of therapy given over 8 infusions over about 6 months that within two years after launch, achieved an annualizing rate of $2 billion in revenue, almost entirely driven by active disease patients because that's where the only existing randomized controlled trial data exists.
The $2 billion market today, we see growing to $4 billion or more based on potential penetration into the chronic disease segment as well as ex-U.S. It's important to us that this is an incidence market. That means all patients are new starts. We don't need to convince patients to switch from Tepezza. We need to offer a compelling alternative when patients first become eligible for a biologic therapy. We're advancing 3 different antibodies in thyroid eye disease.
I'll first focus on our intravenous efforts, VRDN-001. Later on, in the presentation, I'll discuss VRDN-002 and 003, which we're developing as subcutaneous entrants. VRDN-001, like teprotumumab or Tepezza, is an IgG1 targeting the IGF-1R receptor. Where it differs is in how it binds and inactivates the receptor. Teprotumumab is a partial antagonist that leaves residual activity.
001 is a full antagonist. It more completely inactivates the receptor and leads to more robust biomarker responses, and as you'll see, we think the potential for better efficacy. Other than that, it performs like teprotumumab.
Very similar PK, half-life of 10-11 days, and we're dosing it every three weeks intravenously, same as teprotumumab. I'll review data from our proof of concept study in active TED patients. We had reported two cohorts worth of data studying 10 and 20 mgs per kg in August and November last year.
Just yesterday morning, reported data for a low dose, 3 mgs per kg. Active TED in this case means a Clinical Activity Score, which is a composite assessment of redness, pain, and swelling of 4 or higher out of a 7-point scale and symptoms onset within the last year.
The primary endpoint in TED development is proptosis, the bulging of eyes. We're measuring that both by the Hertel exophthalmometer. This is the most commonly used modality. It's been successfully used previously as a primary endpoint, and it's what we'll be using in our phase III program, the THRIVE program. We're also measuring proptosis with MRI imaging.
This is a more precise measurement that relies on central reading by two blinded reviewers, and it is both confirmatory in our smaller proof-of-concept cohorts, but also in our phase three study, will provide potentially differentiating findings to support our commercial launch. To give you an overview of how well VRDN-001 has performed, here we're presenting data on the top row, looking at all 21 patients together that have been dosed with VRDN-001 across the three, 10, and 20 mg per kg dose.
We do that because the evidence suggests that all three doses are saturating the response. Of course, we show the individual cohort data, the individual doses in the middle row, and the bottom we look at the Tepezza data at the same time point, the six-week endpoint after two infusions of drug.
What we see in terms of overall response, this is at least a 2-mm improvement in proptosis and a 2-point improvement in Clinical Activity Score. Two-thirds of VRDN-001 patients achieve this measure, less than half of Tepezza. Proptosis responder rate, which was the Tepezza phase primary endpoint as well as ours, 71% reached the hurdle of at least a 2-mm improvement from baseline proptosis compared to just over half in the Tepezza phase III The mean change in proptosis, underpinning that response rate, 2.3 mm, compared to less than 2 mm for Tepezza. Turning to Clinical Activity Score. Again, this composite assessment of inflammation, redness, pain, swelling. 62% of VRDN-001 treated patients achieved a CAS of zero or one, so a near...
A complete or near complete therapeutic response, nearly triple what's observed with Tepezza at this time point, and a doubling of the mean CAS change, more than 4-point reduction compared to a 2-point reduction in the Tepezza studies. Finally, diplopia, double vision, where here we report resolution, the complete freedom of double vision, which as you can imagine, is incredibly meaningful to patients. Over half of patients achieve this, closer to a third at within the Tepezza phase III study. Across the board, every single measurement, we're seeing favorable results that we think give us a great opportunity to launch a meaningful product. This is underscored, I think, when we look at a patient. Here's a case report from the 3 mg per kg cohort. This patient had proptosis of 29 mm at baseline.
CAS was seven out of seven. You can see the swelling, the redness. She's reported a lot of pain. 6 weeks later, proptosis was reduced by 5 mm, both by the Hertel exophthalmometer and by MRI. CAS was reduced by 6 points. Honestly, the picture tells you all you need to know. You can see just how dramatically two infusions and just weeks of therapy have transformed this patient. We're incredibly excited about the molecule we have on our hands and our plans moving forward. Just to review what we learned about VRDN-001. We see significant rapid improvements in the signs and symptoms of TED. Again, this is just two infusions at all three doses. Safety has been encouraging. No infusion reactions, no serious adverse events. We're seeing safety in line with Tepezza.
We've selected the 10 mg/kg dose, the middle dose, as our phase III dose going forward. We've now got 21 patients who've been treated with VRDN-001. We're now have an increasing number of patients, and we keep seeing the same finding, that we have a drug that's at least as good as Tepezza. The more we see this outperformance on multiple endpoints, the more we feel we may actually be able to deliver better efficacy.
The activity we observed at 3 mg/kg supports differentiation of the molecule. We're at a sixth of the dose of Tepezza. It also supports our efforts to develop a once-monthly convenient self-administered subcutaneous injection, which we think could be a game changer in this indication. We now have ongoing a proof-of-concept study in chronic thyroid eye disease, same design as the active cohorts that we've reported.
The only difference is that we're looking at patients with symptoms for more than one year and CAS out of any scale, so zero to seven. We'll have data from two cohorts later this half. Our phase III program has already commenced. We've reported first patient in the THRIVE study. This is a phase III study in active thyroid eye disease just last month.
We'll plan a second pivotal study in chronic thyroid eye disease to commence later this half. Both studies have three arms looking at placebo compared to the standard eight infusion course of treatment. That's the Tepezza regimen, as well as an accelerated five infusion course, which could allow patients to proceed to the completion of therapy within three months. The potential improvements that we have then are not just this shorter course of treatment.
It's a lower dose that enables shorter infusion times, 30 minutes compared to 60-90 minutes. Of course, based on the clinical data we've seen, we think we can deliver faster onset of symptom relief and improved efficacy. Let's turn then to VRDN-002 and VRDN-003. These are our half-life extended antibodies that we are developing as a low-volume, patient-friendly subcutaneous injection. VRDN-002 is a different molecule than VRDN-001. In fact, it more closely mimics the effects of teprotumumab. It binds to a similar epitope like teprotumumab that is a partial antagonist.
The key difference here is the incorporation of a validated half-life extension technology, Fc modification, which we've seen in healthy volunteers to quadruple the half-life, a half-life up to 43 days. The key benefit of that improved half-life is that we can reduce the dose, hence reduce the volume, hence get to in every other week or every four-week low volume subcutaneous injections.
Now, I've told you VRDN-001 is a standout in terms of its pharmacology, VRDN-002 in terms of its pharmacokinetics. Of course, we'd like to marry those benefits. We've done that in VRDN-003. This is identically the VRDN-001 molecule, except it includes the same Fc modifications as VRDN-002. We have the full antagonist features of VRDN-001, and we expect the PK to match or exceed what we observe with VRDN-002. Our plan is to advance both of these molecules.
We'll have clinical data later this year from both programs. We'll select one to advance into phase III, commencing early 2024. I won't go over the PK modeling in any detail on the slides. The red curves are the 3 mg per kg PK from IV VRDN-001. The blue on the left is VRDN-002. On the right, it's VRDN-003. What this shows us is that a 2-ml injection of 300 mg given every four weeks, but with a loading dose of two injections in the first setting. The two injections on day one, followed by a monthly single injection, exceeds the exposures of the 3 mg per kg 001. That means a monthly dose of 002 or 003 can give adequate exposure to deliver robust, meaningful efficacy to patients.
It is the half-life extension that we've incorporated in these molecules that the only IGF-1R antibodies in development with half-life extension that really sets these apart and puts us on a path to what we think could be a durable best-in-class entrant. The path forward for our subcutaneous efforts are to move OO2 into a proof-of-concept study.
We'll have data in the second half of this year from TED patients via the subq route. VRDN-OO3, we've accelerated from backup status to now a contender to be our subcutaneous entrant. We'll file an IND in the second quarter and have healthy volunteer data, and PK/PD that can leverage the VRDN-OO1 experience, so that by the end of the year, we can select whether VRDN-OO2 or OO3 is our choice to move into phase three and initiate phase three development for our subcutaneous program early 2024.
We're working on a pen device akin to the Dupixent profile shown here. A convenient self-administered device that maximizes settings of care, and hence both can be the favored choice for most patients, but also can help grow the market by expanding those settings of care. Our corporate priorities then, moving through the rest of this year and beyond. I talked about VRDN-001.
We have next up proof-of-concept data in chronic thyroid eye disease later this half. We've already started the THRIVE study, the active TED phase III program. We'll have top-line data in the middle of next year. The THRIVE-2 study in chronic thyroid eye disease will initiate later this half and have data by the end of 2024. In our subq programs, we just reviewed this. We're moving both 002 and 003 forward.
It's essentially a bake off to see with clinical data in hand for both molecules, which is our choice to move into phase three development early in 2024. Thinking ahead then, what does this mean for our long-term strategy? We aspire to build a fully integrated biopharma company. We will launch what we think can be a best-in-class intravenous therapy in the U.S. and beyond.
We will follow that with what we believe could be a durable best-in-class product with a self-administered subcutaneous injection, that pen device that I showed. We will replicate the excellence that we will develop in development and launch of these TED therapies in other autoimmune and rare diseases. We see a bright future for the company, and it's been a pleasure to share an overview with you today, and I'll be happy to answer any questions.
Thank you so much, John. For the question and answer portion, we're also gonna have Kristian Humer here, who's the chief financial and business officer, as well as, Todd James, Senior Vice President, Corporate Affairs and Investor Relations. While we're giving it a minute for questions to queue up, we've also got folks on the webcast watching as well. I'll go ahead and kick off with one.
You talked a lot about the potential for the subcutaneous administered dose and how that could expand the market. Could you give a little bit more on what the vision for that is, what the strategy is for that, post kind of deciding in the beginning of 2024?
We believe the market will segment. There are always gonna be some prescribers and some patients who prefer the intravenous route. That's in part why we think our best path is to develop VRDN-001 as quickly as we can. The advantage of a subcutaneous product, especially in a convenient self-administered pen device as we're working on, is not just that it's easier for patients.
It's a lot easier for prescribers as well, and for payers. Payers would rather not pay for trips to the infusion center. Prescribers, while the most intensive prescribers very quickly realized what this mechanism of action can deliver for patients and really transform their standard of care. That was really true in the neuro-ophthalmologists and some of the oculoplastic surgeons who see most of these patients.
When you think further out in the patient journey, as patients first encounter disease, they're often diagnosed by endocrinologists and comprehensive ophthalmologists who don't see as many of these cases. For them, trying to figure out how to work with a patient to get access to drug, to send them to an infusion center is well outside the norm in ophthalmology and endocrinology.
Being able to have a simple, convenient subcutaneous device that can be self-administered at home, we think can not just be a preferred choice for many patients and prescribers, but could help give more patients access to drug and thereby grow market.
Excellent. Another one following up on the subcutaneous. Obviously, you've spoken about the opportunity with an active thyroid eye disease there. Do you think there's any potential to explore the subcutaneous further on in the future, potentially for a chronic thyroid eye disease indication?
It's interesting. When Tepezza was approved, there was a single pivotal study and a single phase II, both in active thyroid eye disease, where symptoms have presented less than nine months ago, and CAS of four or higher.
The same CAS cutoff we're using in our active trials. Nonetheless, the label just is for thyroid eye disease, because the FDA at least does not recognize a distinction between active and chronic. It's a spectrum of disease. What's happened is that while the label is for TED, full stop, payers are really giving access to patients who match not the label, but the trial. We don't have any randomized controlled trial data yet. We're generating our own. There'll be other data coming out later this year from Tepezza.
We have seen numerous case reports, 50 or 60 case reports of patients with long-standing disease who have received Tepezza and have reported changes that very much mimic what's seen in active thyroid eye disease patients. Robust improvements in proptosis that don't seem to correlate with CAS or any other criterion.
There's a very large set of data suggesting this mechanism works as well in chronic thyroid eye disease as it does in active thyroid eye disease. We think we'll be able to show that with VRDN-001 via the intravenous route. Because that's an untapped part of the market, it represents a lot of the upside beyond the current $2 billion market. It will be a key part of our subcutaneous development plans as well.
Excellent. Thank you. I know you spent a lot of time in the presentation covering off on VRDN-001, 002, and 003. Is there anything further down in the pipeline? I know you guys have 004 through 006 as well.
Yeah. These are not IGF-1R, they are not thyroid eye disease. They are philosophically the same approach that we've taken to thyroid eye disease. There's a first entrant, proves the biology. We see a clear regulatory path and a market that currently is under competitive. More than that, we see an opportunity to engineer a product portfolio that we think could be best in class.
We're working to advance those, and we'll, as I said, we'll have at least one of those to disclose later this year. Because these aren't first in class entrants, because we don't bear the same level of technical risk, it allows us to invest early on in a franchise model, where just as in thyroid eye disease, from the beginning, we were working on an IV molecule and a separate sub-Q molecule.
We can take that same level of thinking because the technical risk is lower. That provides us more shots on goal, provides us some redundancy, and gives us a lot of opportunity to develop the best possible products for patient care.
Excellent. Thank you, John. Let me pause for a minute here and see if we've got any questions from the audience. Feel free to raise your hand, and we can have someone bring the microphone. Okay. Let me check real quick. I don't think we've got any from the webcast right now. One potentially that wasn't touched on as much is the European opportunity. How do you think about the opportunity above and beyond the U.S.?
Tepezza currently isn't approved in the EU or the U.K. Horizon had recently announced that they were going to look at development there. We've had two scientific advice meetings in Europe. The EMA will prefer a different primary endpoint, but otherwise the same studies will suffice. We have designed our phase III program to be globally enabling a registration, and can design our statistical analysis plans accordingly. While it's too early to go into the commercial details, we do see a meaningful opportunity in Europe and beyond.
That's excellent. Just pausing here a minute. I think if we've not gotten anything from the room, we can potentially wrap up. If you've got any closing remarks, Scott?
Sure. Well, again, thanks for having us here. Pleasure to be at the conference. In just two short years, we've built Viridian with, I think, an extraordinary opportunity. VRDN-001 has proven in early development to really be a stand-up molecule. I think we have something special on our hands.
Within the half-life extension antibodies, VRDN-002 and VRDN-003, we have a number of milestones that should create a lot of value. As we replicate this approach in further therapy areas, we think we can build a very promising, valuable company for the long run. We're just at the early innings here and excited to move forward.
Great. Thank you so much for joining us today. Thanks everyone for attending.