Greetings, and welcome to the Viridian Therapeutics fourth quarter and full year 2021 earnings call. At this time, all participants are in a listen-only mode. The question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the call over to John Jordan, Vice President of Investor Relations and Corporate Communications. Thank you. You may begin.
Thank you, Darryl. Good morning, everyone, and welcome to our fourth quarter and full year conference call. Today, after the market closed, we issued a press release providing our fourth quarter and full year financial results and business updates. A replay of today's call will be available on the investor relations section of our website one hour after the completion. After our prepared remarks, we will open the call for Q&A. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements about the company. These statements are subject to risks and uncertainties that could cause actual results to differ. Please note that these forward-looking statements reflect our opinions only as of today. Except as required by law, we specifically disclaim any obligation to update or revise these forward-looking statements in light of new information or future events.
Factors that could cause actual results or outcomes to differ materially from those expressed in or implied by such forward-looking statements are discussed in greater detail in our most recent filings on Form 10-K and our other periodic reports on Form 10-Q and 8-K filed with the SEC. I would now like to turn the call over to Jonathan Violin, President and CEO of Viridian.
Thanks, John, and good afternoon, everyone. Thanks for joining us for our fourth quarter and year-end 2021 conference call. I'm also joined today by Kristian Humer, our Chief Financial Officer and Chief Business Officer. I'll begin with a brief overview of the business, our recent milestones, as well as an overview of our pipeline, including progress we've made in advancing our lead candidates for thyroid eye disease, or TED. Then Kristian will review our fourth quarter and full year financial results. We'll then open the call for questions. We founded Viridian to advance new biologic treatments for patients suffering from serious diseases who are underserved by today's therapies. Our strategy is to employ a patient-centric model of innovation that leverages proven biology and validated technologies to reduce research and development risk.
We target therapeutic indications in which we believe our efforts could address gaps related to access, delivery, quality of life, efficacy, safety, or tolerability. We focus on product concepts that we can fulfill with our antibody discovery, engineering, and development expertise, either in-licensing or creating de novo antibodies we believe can provide best-in-class solutions for patients in need of more and better therapeutic options. 2021 was transformational for Viridian. In January, we were a newly public preclinical startup. Today, we have over 50 FTEs, two clinical-stage programs, an advancing and expanding discovery pipeline, and just under $200 million in cash to fund our activities into 2024. It's a testament to our team that we were able to rapidly complete IND-enabling activities for both VRDN-001 and VRDN-002 and initiate our first clinical trial in TED.
Key additions to our team in 2021 included our Chief Medical Officer, Barrett Katz, a neuro-ophthalmologist with deep experience in both clinical trials and patient care, including TED patients. Deepa Rajagopalan, our SVP of New Product and Portfolio Development, who brings significant expertise in strategy to commercial launch planning. Chief Financial Officer and Chief Business Officer, Kristian Humer, who has over two decades of financing and M&A experience in biopharma banking. They've joined the existing leadership team, including our Chief Scientist and Co-Founder, Vahe Bedian, and we've quickly recruited highly experienced teams and individuals to support our mission of rapidly and efficiently advancing new monoclonal antibodies to fill gaps in the treatment paradigm for TED and other serious diseases. I'd like to spend a few minutes reviewing our pipeline, focusing on our lead programs. TED is a new, large, and rapidly growing market that aligns with our strategy.
We see an opportunity to be the second entrant in this market, where we can advance patient care by providing differentiated product profiles that improve upon the currently approved treatment option. The only therapy approved by the FDA for TED is Tepezza, which is an intravenously administered monoclonal antibody that targets the IGF-1 receptor, or IGF-1R. The Tepezza clinical trial data provides strong validation linking the targeting of IGF-1R to clinical benefit in TED. However, clinical trials of Tepezza in TED reported to date employed a single dosing regimen, providing little guidance as to the optimal dosing required for efficacy. We believe there are multiple opportunities to develop novel IGF-1R-targeted therapeutics that improve on Tepezza's features, including dosing, schedule, route of administration, settings of care, and potentially safety and tolerability.
Our strategy is to advance market segmentation, providing an improved IV option for patients for whom the control and oversight of an IV infusion is preferred, and a convenient, self-administered, low-volume subcutaneous injection for patients who could benefit from this route of administration. We have two specific goals. First, to advance a higher affinity antibody with a less burdensome IV dosing paradigm, enabling a lower dose and/or fewer infusions to provide the efficacy of Tepezza in an improved product profile. Our second goal is to deliver a convenient, low-volume subcutaneous injection that enables treatment of TED patients in broader settings of care, allowing simple dosing either self-administered at home or in the prescribing physician's office. Our first goal in TED is addressed by our most advanced program, VRDN-001, a monoclonal antibody that blocks the IGF-1 receptor with subnanomolar potency, which we in-licensed from ImmunoGen.
This antibody was previously developed as AVE1642 and has been administered to over 100 oncology patients, providing a wealth of data that accelerated and de-risked our program. Data from preclinical studies and oncology trials suggest that 001 has the same mechanism of action as Tepezza and similar PK in humans. The key difference for 001 is its higher affinity. Both our own data and previously published data show that 001 has subnanomolar affinity and potency against IGF-1R. This may help reduce the dose required to deliver efficacy in TED patients. We see an opportunity to develop 001 as a differentiated IV product, addressing the need we've heard from TED stakeholders for a less burdensome dosing paradigm. In December, we announced dosing of the first subject in a phase I/II proof-of-concept clinical trial for VRDN-001. This trial is designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of 001.
The trial includes both healthy volunteers and randomized placebo-controlled cohorts of TED patients and will assess multiple measures of the signs and symptoms of TED, including proptosis, the bulging of the eye characteristic of TED. The study is designed to achieve several aims. First, to test if 001 can deliver efficacy comparable to Tepezza at doses similar to Tepezza to establish proof of concept that we have a highly active drug for treating TED. Secondly, after we've shown efficacy comparable to Tepezza, the study can enroll further cohorts to explore differentiating dosing paradigms, including low doses that may enable a low-volume subcutaneous injection as an alternative to IV infusion. The study remains on track with our previous guidance, and we expect to deliver top-line proof-of-concept clinical data in the second quarter. Let's discuss our expectations for that data.
To confirm that we can deliver efficacy comparable to Tepezza, we're initially using doses of 001 similar to Tepezza and assessing potential efficacy in two cohorts of TED patients. Each cohort will include eight patients, six receiving 001 and two receiving placebo. We want to see 001 deliver the same rapid improvement in TED symptoms as Tepezza, which would confirm that the preclinical and oncology data for 001 showing the same mechanism of action as Tepezza has translated to TED, and we'd know that we have a highly active drug we can advance quickly towards market. Our trial design includes two infusions on day zero and day 21, and then efficacy assessment at week six or day 42. That dosing interval matches the Tepezza course of treatment.
The first cohort will receive two infusions of 10 mg per kg of 001, and the second cohort will receive two infusions of 20 mg per kg. We're bracketing the Tepezza dose, which is 10 mg per kg on the first infusion and 20 mg per kg thereafter. Given the subnanomolar affinity and potency of 001 and biomarker data from oncology trials, we believe that both doses should be well above what's needed to saturate the receptor. We're assessing multiple efficacy endpoints and expect to have at least three for top-line data, proptosis, diplopia, and Clinical Activity Score. The primary efficacy measurement is proptosis at six weeks, which we'll report as the same two analyses as Tepezza, mean change from baseline, which will be our main focus, but also a responder analysis defined as a 2 mm or greater reduction from baseline.
Given the shared mechanism of action of 001 and Tepezza, we expect to see efficacy comparable to Tepezza. There are three Tepezza clinical data sets for us to consider. The phase II trial, the randomized portion of the phase III trial, and the open-label extension of the phase III trial in which placebo patients were crossed over to Tepezza. In those three data sets, the mean change from baseline in proptosis at week six ranged from approximately 1.7 mm to 1.9 mm, with a 95% confidence interval of approximately 1.4 to 2.3. The data will also be complemented by diplopia assessments and Clinical Activity Score, which, like proptosis, reproducibly showed benefit at six weeks in the three Tepezza data sets.
We'll also have top-line safety and tolerability data and would anticipate sharing full data, including PK, PD, and further measures of efficacy at a future medical meeting. Demonstrating that we have transformative efficacy similar to Tepezza would be significantly de-risking for Viridian and put us in a position to be second to market. The next goal will be to rapidly evaluate lower doses, potentially different dosing intervals, to understand how much we can differentiate 001 from Tepezza. As a reminder, this trial is designed to be flexible. The protocol allows for enrolling additional TED patient cohorts in which we can evaluate different doses, dose intervals, and number of infusions. If we see positive results in the proof of concept cohorts, we'll explore efficacy at a lower dose.
This is an opportunity to differentiate VRDN-001 from Tepezza by dose and also could support our ability to achieve a low-volume subcutaneous injection. In parallel, we're already preparing VRDN-001 for pivotal trials, including manufacturing material with commercial process. Pending positive proof-of-concept data, we anticipate advancing our program rapidly. We intend to sprint to market with a differentiated VRDN-001 product profile. We think lower dose, fewer infusions, and potentially different routes of administration would be a welcome advancement in treating TED. Let's now turn to VRDN-002, our next-generation IGF-1R targeted program. VRDN-002 is a humanized monoclonal antibody that incorporates half-life extension technology and was designed by our scientists to support administration of a convenient low-volume subcutaneous injection for the treatment of TED. This product presentation would maximize the settings of care, either at home by patients via self-administration or in the prescribing physician's office.
Data from preclinical and oncology studies showed us that across the IGF-1R class, while increasing target affinity may help lower dose, PK becomes limiting at low doses. If 002 half-life extension works as we expect, it should be very hard for any antibody lacking half-life extension to get to a more convenient subcutaneous product. At the end of January, we announced the FDA acceptance of our IND application for VRDN-002. We're currently proceeding with our first in human phase I clinical trial of VRDN-002, which is a single ascending dose study to explore safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenously administered VRDN-002 in healthy volunteers. We expect to announce data from this trial mid-year. The key outcome from this trial is to demonstrate how well the half-life extension technology improves PK, and these data will inform the feasibility of a low volume subQ product.
Should we see positive results, we expect to have everything we need, including our high concentration subcutaneous formulation of 150 mg/mL, to rapidly advance to a subcutaneous proof of concept trial in TED patients. With our VRDN-001 and VRDN-002 programs, we believe Viridian has an extremely compelling TED pipeline with two differentiated shots on goal, both with the ability to move quickly into registration-enabling studies. In addition to our efforts to create best-in-TED products in TED, we're also expanding our pipeline by applying our strategy of discovering and developing more convenient, better performing antibody products for indications in which proof of concept for the targeted mechanism of action already exists. VRDN-004 targets a proven mechanism of action in a rare disease, where we see opportunity to advance patient care and evolve the market with a new best-in-class entrant.
Our antibody discovery and engineering team has generated and optimized promising lead antibodies, and we're excited about this program. We'll disclose the target and indication when the time is right from a competitive perspective. VRDN-005 is a new discovery stage program, again, targeting an opportunity we've identified to advance a new best-in-class therapeutic. As part of this effort, we've licensed antibody libraries from Xencor, which we believe provide a high-quality starting point for our program. Like VRDN-004, we'll disclose the targets and indications for this program when we think the time is right, along with our broader pipeline strategy. For now, we're committed and focused on the importance and sizable opportunity we have with our TED programs. Operationally, we're very pleased at our progress over the last year.
We're executing on the strategy we laid out when we became a publicly traded company, and are grateful to our excellent and growing team, and also to our external partners, the contract research organizations, key opinion leaders, advisors, and of course, volunteers and patients in our clinical studies, all who help us advance our mission to provide new and better antibody therapeutics to patients who deserve new options. We look forward to another transformative year ahead for Viridian in 2022. I'll now turn the call over to Kristian, who will discuss our financial results for the fourth quarter and full year ending 2021. Kristian.
Thank you, Jonathan. Good afternoon, everyone. We entered 2022 in a strong financial position. This year, we look to advance multiple programs in TED while expanding our discovery pipeline. We closed out 2021 with approximately $197 million in cash equivalents, and short-term investments as of December 31st, 2021. Our current cash equivalents, and short-term investments will be sufficient to fund operations into 2024. Turning to expenses, which we also summarized in a press release issued after market today.
We reported research and development expenses of $22.4 million for the quarter ended December 31st, 2021, and $56.9 million for the year ended December 31st, 2021, compared with $15.3 million and $28.3 million for the comparable periods in 2020. The increase in research and development expenses was primarily driven by the advancement of our lead programs, including expenses related to manufacturing and IND-enabling studies. General and administrative expenses were $6.9 million for the quarter ended December 31st, 2021, and $25.8 million for the year ended December 31st, 2021, compared with $5.5 million and $13.3 million for the comparable periods in 2020.
The increase in G&A expenses last year was primarily due to increases in personnel-related costs, including severance, share-based compensation charges, and consulting expenses. Net loss was $28.9 million for the fourth quarter of 2021, and $79.4 million for the year ended December 31st, 2021, compared to $90.7 million and $110.7 million for the comparable periods last year. As of December 31st, 2021, Viridian had approximately 42.8 million shares of common stock outstanding on an as converted basis, which included 23.9 million shares of common stock outstanding and approximately 18.9 million shares of common stock issuable upon the conversion of shares of Series A and Series B preferred stock. With that, I'll ask the operator to open the call for questions.
Thank you. We will now be conducting a question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue.
You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please while we poll for your questions. Our first questions come from the line of Chris Howerton with Jefferies. Please proceed with your questions.
Great. Thank you so much for taking the questions, and appreciate all the progress. So I guess maybe for me, a few questions. One would be in the context of IV formulations, you know, what would be some of the differentiations that you think could be made in that setting for VRDN-001 relative to Tepezza? And for example, would less frequent IV infusions be important in that type of setting? The second question I would have would be, you know, is the VRDN-002 data from the midyear going to be gating in any way to opening up new cohorts for the phase II study with VRDN-001?
The final question, if I may, was just if you know, maybe without asking specifics, if there would be anything that would happen from competition, let's say from Horizon, that would accelerate your strategy to go towards VRDN-002 versus no longer trying to evaluate VRDN-001. Thank you.
Thanks, Chris. Thanks. With respect to the IV product and how that fits against a subQ product, we actually see, having done a lot of market research and commercial forecasting, our revenue can be maximized by having both an IV and a subQ. This is a big market. We believe it's going to segment. There are patients and prescribers who are going to prefer IV, although in the long run, we do think that low volume subQ would be the biggest category in the market. We see a lot of value in moving both of these programs forward. With respect to the IV product, there are a number of ways that this could be interesting.
Keep in mind that the great majority of the market right now is like acute patients treated by the IV route, right? This is a proven market now with I think room to grow as we segment it by bringing different products forward. With respect to IV, things like a lower dose fewer infusions can really reduce what we think of as the overall burden of care on patients, right? Each trip to an infusion center adds to the total cost of care. It's a hassle for patients. We also know that every infusion, particularly at a high dose, is adding a lot of drug burden, right? If we can get to lower doses, there's always the upside that maybe we'll start to see better and see tolerability.
We don't know. That's something that we're interested in. We'll collect data as we go. But, you know, less drug is always better. If we can do that, if we can have fewer infusions, we think there's room for a compelling IV entrant. With respect to your question of is VRDN-002 data somehow gating for what we're going to do with VRDN-001? No. We're gonna move VRDN-001 forward as quickly as we can, and don't need to see the VRDN-002 data, to make VRDN-001 decisions. The third question then, you know, would we accelerate VRDN and VRDN-002? The VRDN-002 program should be able to move forward quite quickly. Once we have those first human data, understanding how well the half-life extension technologies improve the PK.
Once we have that half-life, we'll be able to construct the dosing paradigms that we want to test in a subQ trial in TED patients. VRDN-002 can move forward quite quickly on its own. We're really excited about both of these programs.
Yeah. Maybe I set up a false choice there to some degree. Yeah. Okay. Okay. That's very clear. I appreciate it, Jonathan. Thanks for taking the questions.
Thank you. Our next question has come from the line of Thomas Smith with SVB Leerink. Please proceed with your questions.
Hey, guys. Good afternoon. Thanks for taking the questions and congrats on all the progress. Just on the upcoming VRDN-001 proof of concept data, can you just remind us regionally where you're enrolling the study? Can you provide any additional color on where you are in terms of enrolling the first two cohorts?
Yep. As you heard, we reiterated our guidance for data in the second quarter. The study is enrolling in North America, so the U.S. and Canada, where we're looking at a large number of sites, many of whom have experience in this space, that have enrolled in thyroid eye disease, some of the top sites, the Tepezza studies, and including obviously KOLs and investigators who know how to run these studies well and recruit patients. We've been very pleased, particularly as Barrett, our Chief Medical Officer, has been sharing our vision for both VRDN-001 and VRDN-002. We've seen a lot of enthusiasm for what we're trying to do here. I've been very pleased at how all that's going.
Okay. Maybe just to follow- up, on the competitive front, it sounds like Horizon's evaluating both Halozyme and non-Halozyme subQ formulations for Tepezza. How are you thinking about competitive timelines, I guess, competitive profiles? What are your current expectations in terms of when you think you'll get your subQ to market versus Horizon?
Yeah. Right. We've heard that Tepezza now is being formulated in high concentration. Let's think about what that might mean, right? Horizon's published data suggests they may need plasma concentrations that necessitate a 20 mg per kg dose. In an average-sized patient, that's 1.5 g for each dose. A good high concentration formulation would be about what we've been able to do, would be 150 mg per mL. That's 10 mL, right? We'll see what they're planning. We've heard some comments from them about kind of middle of this decade having BLA for a Halozyme-enabled subQ, which again, would be a large volume.
We have not given guidance yet for late-stage development, but as you've heard, we're designing both VRDN-001 and VRDN-002 programs to move very quickly and efficiently towards registration. Given the opportunity we think we have with these molecules with a higher affinity, with hopefully better PK, we think we can get to a low volume and have something pretty special on a compelling timeline.
Right. Okay. That makes sense. All right, guys. Thanks for taking the questions. Appreciate it.
Thanks, Tom.
Thank you. Our next questions come from the line of Monica Mirchandani with Evercore ISI. Please proceed with your questions.
Hey, this is JP Solomon on for Monica. Just on VRDN-001, what would be a win for you in terms of the proptosis response at 12 weeks, just since you're not dosing all the way till then?
The question on the 12-week follow-up, right? As we described, we're mimicking the timing of Tepezza dosing through week six, right? You dose on day zero, dose on day 21, and then measure efficacy at week six at day 42. We do have a six-week follow-up point at week 12, without continuing the dosing. We're just giving those first two infusions. To do cross-trial comparisons, we can really only look at week six. The follow-up for week 12 is an interesting question, and will start to inform the capacity that our drug has to lower dose or reduce infusion intervals. What's gonna happen between week six and week 12? Does efficacy quickly rebound? Does it plateau? Does it continue to improve? That's gonna be really informative for us.
It's really the week six data that will, through the cross-trial comparison, hopefully tell us, "Yep, we've got a highly active drug, immensely de-risking for the company and should put us in a really good place to move forward quickly.
Got it. Thank you so much.
Thank you. Our next questions come from the line of Rami Katkhuda with LifeSci Capital. Please proceed with your questions.
Hey, guys. Thanks for taking my questions. Two quick ones for me. First, is there any additional guidance that you can provide as to when in Q2 we can expect the data from the proof of concept study with zero zero one?
Sure. As you heard, we did reiterate second quarter as we've been saying for a while now. Look, it's not gonna be early in the second quarter. We just started the study in December. Everything's on track, we would expect data more like in the second half of the second quarter. That's. We're quite pleased with how progress is going.
Gotcha. Can you remind us if VRDN-001 and VRDN-002 kind of bind the same epitope of IGF-1R, and if there's any potential learnings from this proof of concept to VRDN-002 development?
Yeah. When we look at VRDN-001 and VRDN-002, the molecular pharmacology, the mechanism of action is highly conserved. Obviously the same target. They all share an epitope. They all cause, for example, similar amounts of receptor internalization. They similarly block receptor autophosphorylation. When we say similar mechanism of action, that's the preclinical data that we refer to. That gives us high confidence in VRDN-001 that it should deliver efficacy like Tepezza, but we need to prove that, right? That's why we're running the proof of concept cohorts for VRDN-001 the way we are, to very quickly answer that question, can we see strong, robust efficacy in the ballpark of Tepezza with VRDN-001? If that data is positive, I would argue that we've proven that the benefits of Tepezza are generalizable.
I think that should read through to some extent to 002. Now, 002 is a different molecule, so you know, we're not gonna argue anything from a regulatory perspective, but it would certainly increase our confidence.
Makes a lot of sense. Thanks, guys.
Thank you. Our next questions come from the line of Laura Chico with Wedbush. Please proceed with your questions.
Hey, good afternoon, guys. Thank you for making the time. I've got three for you. First, John, you mentioned the differentiation on the affinity between Tepezza and VRDN-001. I'm wondering, could you clarify how you think about the differences in half-life between VRDN-001 and Tepezza?
Sure. Well, if we look at non-human primates in oncology studies, the PK is very similar for VRDN-001 and Tepezza. That makes sense. They're both unmodified IgG1s. Our expectation would be that in TED patients, likewise, they'd have similar PK. The difference for VRDN-001 is both the higher affinity and how we're going to study it.
Okay, great. One follow-up then. I guess I wanted to ask on the potential to demonstrate any separation from Tepezza on the adverse event profile in this first proof of concept study. I guess, what duration of treatment would you need to see potentially to tease out differences on AEs? What areas would seem the most logical to see differentiation on? I guess there was a recent publication that detailed hearing dysfunction among VRDN patients in a case studies report. This was still demonstrating about 10% continuing to have hearing loss at a longer- term follow-up.
Right. Keep in mind that we're starting with small cohorts at Tepezza-like doses, and our baseline expectation would be similar levels of AEs. In fact, as we said, we're sort of bracketing the Tepezza dose, right? The ultimate goal of the program is to get to lower doses. If we see Tepezza, the similar frequency they use of Tepezza at 10 mg per kg, or even if they were a little higher at the 20 mg per kg dose, that's fine, right? The goal is not to be commercialized at those doses. The goal of these proof of concept cohorts is to, as quickly as we can, prove that we have a highly active drug on our hands.
From there, in the extension cohorts, we would be able to look at different doses, different dosing regimens, to see if there's an opportunity to have what we're describing as a less burdensome treatment paradigm, right? Lower dose, lower number of infusions, the kind of differences in adverse event profiles that we're interested in, that we're actually quite excited about, they're only gonna emerge over the long run. Baseline, we should expect similar rate of AEs with an upside over time. As we collect data, maybe we'll be able to see a lower rate or lower severity of AEs.
Okay, that's very helpful. Maybe last question for Kristian. How reflective of the forward spend are Q2 levels? I guess, should we presume these are reasonable run rates to build off of in 2022 in terms of R&D and SG&A spend? Or were there any kind of one-time costs in the Q2 numbers that we should consider as we're modeling forward estimates? Thanks.
No, these are reasonable rates to assume going forward. As I mentioned, the spend would get us into 2024.
Thanks, guys.
Thank you. Our next questions come from the line of Jason Butler with JMP Securities. Please proceed with your questions.
Hi, thanks for taking the question, and congrats on the progress. Just one on potential path to market for a subQ formulation of VRDN-001. Is there a potential for a parallel path here and both an IV and a subQ being included in the first BLA? Or is it more likely that if you advance a subQ VRDN-001, it would be, you know, subsequent filing? Thanks.
Yeah. Thanks, Jason. So we've not given any guidance like sort of later stage development. Honestly, we don't wanna tip our hand too soon. Between the high affinity of VRDN-001, and as we've said, you know, we see a lot of value in IV, there's an upside opportunity possibly for subQ. With VRDN-002, with half-life extension that we think should really differentiate the molecule's performance from everything else in the class right now, that's sort of the long- term win for subQ. Exactly how we build out our portfolio, we're pretty excited about what we're working on, and we'll set the stage in.
Great. How predictive were the preclinical PK data for Tepezza and for VRDN-001? I guess just how does that speak to your confidence in the ultimate PK profile you'll see for VRDN-002 based on the preclinical data you've already generated?
Yeah. Both VRDN-001 and really all the first generation IGF-1R antibodies had very typical half-lives for an IgG1 antibody. Nothing sort of stood out about them. We don't expect any strange findings. With VRDN-002, with half-life extension, there have been a number of examples now of these Fc modifications that increase antibody recycling, so they're dumped back into the bloodstream rather than destroyed. Very reproducibly, non-human primate PK has translated to better PK in humans. In fact, many of the precedent clinical programs showed a bigger increase in humans than they did in non-human primates. It's a highly validated technology. We've seen about a twofold improvement in half-life for VRDN-002 in non-human primates compared to VRDN-001 or VRDN.
We'd be looking to see that or better, as a differentiated profile in our first-in-human study.
Great. Thanks for taking the questions.
Thank you. Our next questions come from the line of Michael Higgins with Ladenburg Thalmann. Please proceed with your questions.
Thanks, guys, for taking the questions. Just to follow- up on your comments, I think in your prepared remarks, Jonathan, about the market research on the IV and subQ. It's intriguing that you're finding the value for the IV. If you could expand on that a bit. Is that related to reimbursement? Is that related to the setting of the patients? Curious. Thanks.
Thanks. Thanks, Michael. Hi. Look, I think this market is bigger than people realized a few years ago, and there are certainly other markets quite different in their own way, but that durably support different routes of administration. Think about the multiple sclerosis market, right? It's just not the case that markets turn over fully from one dosing route to another. IV obviously is growing quickly. It's going to be established treatment paradigm. While we do think that a low volume subQ is better, right, it's gonna be easier for patients. That the IV market is never going to go away, and it's big enough. We think that there are interesting things to do there, as well as bringing forward a little more subQ.
Interesting. Another question on the data we're looking for here in the back half of Q2. It sounds like we're getting six- and 12-week data from the first cohort. Just curious if you think we can get that 12-week data from the second cohort. Thanks.
Yeah. Don't know. That depends on timing and of course, what we want to hold back for a medical meeting. We just don't know yet. Obviously, we're focused on the six-week endpoint. That's where I think everyone will do cross-check comparisons to Tez, is this delivering Tez-like efficacy. And again, we'll have the proptosis measurements, but combining that with a Clinical Activity Score with the diplopia and double vision, we should have a very rich sense of how the drug is performing. That six-week endpoint for us is really the key. As we talked about a few minutes ago, the 12-week follow-up I think is really interesting in terms of informing us what might be possible as we go into the team.
That's helpful. Just one last one, if I could here. Looks like the back half of the year, you've got a lot of data that's come through and coming through. Just curious how, at this stage here in March, how much value you put on the additional cohorts from VRDN-002, since it's kind of a sequential or at least a delayed start from VRDN-001, of course. If you continue to wait or you just can simply pursue advancing VRDN-001. Thanks.
Sorry, the question is would we wait for VRDN-002 data to continue advancing VRDN-001? Is that your question?
Yeah, basically just wondering how far deep in the 002's cohorts do you go before deciding what to do with 001?
Yeah. As we talked about earlier, we think VRDN-001 has a lot of value. We want to quickly be the second entrant. We think we can do well with it. We'll be moving VRDN-001 forward, assuming we have positive data as quickly as we can in concentrations. That's not really dependent on VRDN-002. The healthy volunteer data for VRDN-002 really is going to help define how we develop VRDN-002, right? Once we have the half-life, we understand how well the half-life technology is working, then we can construct subQ dosing paradigms that make sense in patients, based on the data. We already have PK models. They're going to continue to evolve as we have clinical data.
We'll have everything else we need from a non-clinical CMC perspective to move into subQ proof of concept for VRDN-002. We really see VRDN-001 and VRDN-002 moving forward in parallel.
That's great. Super helpful. Thanks, Jonathan.
Thanks, Mike.
Thank you. There are no further questions at this time. I would now like to turn the call back over to Jonathan Violin for any closing comments.
Thank you. Thanks everyone for joining us today. As I hope you've heard, we are very excited about both the ongoing progress we're making across the pipeline and our upcoming milestones this year. We will look forward to updating you as our programs advance. With that, we'll close the call.
Thank you. This does conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.