Earnings Call Transcript - VRDN Q3 2022

Operator, Operator

Greetings and welcome to Viridian Therapeutics Third Quarter 2022 Earnings Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, John Jordan, Vice President of Investor Relations. Please, go ahead.

John Jordan, Vice President of Investor Relations

Thank you, Brock. Good morning, everyone, and welcome to the Viridian conference call to discuss the positive clinical data report earlier today for VRDN-001 in patients with Thyroid Eye Disease. Before we begin, I'd 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 10-Q and other reports on file with the SEC. I'm joined today by Dr. Jonathan Violin, President and CEO; Dr. Barrett Katz, our Chief Medical Officer; and Kristian Humer, our Chief Financial Officer and Chief Business Officer. I would now like to turn the call over to Jonathan.

Jonathan Violin, President and CEO

Thanks, John, and good morning, everyone. Thanks for joining us. Over the last quarter, Viridian continued to execute on all pillars of our strategy, designed to deliver the most complete portfolio of products for the treatment of Thyroid Eye Disease across the world. Thyroid Eye Disease, as you know, is currently a $2 billion market in just the United States and is expected to grow to over $4 billion globally, with just one product currently approved. We're advancing a portfolio of intravenous and subcutaneous programs towards this opportunity. For our IV VRDN-001 program, we're excited to share positive results from our second proof-of-concept cohort. Data we will review today for 20 mg per kg confirm the profile we initially presented for 10 mg per kg a few months ago. The data compares favorably to TEPEZZA on each key endpoint, including proptosis response rate, overall response, change in Clinical Activity Score, or CAS, proportion of patients achieving a CAS of 0 or 1 and resolution of diplopia. VRDN-001's safety profile continues to look very promising, with all adverse events being mild to moderate, no serious adverse events, no hearing impairment, no drug-related hyperglycemia and no infusion reactions reported in the 20 mg per kg cohort. I'm pleased to share that the 3 mg per kg cohorts for VRDN-001 is now fully enrolled, in fact overenrolled due to patient demand, and we plan to present top line data in early January 2023. I'm also excited to share that this month we initiated our first Phase 3 trial, the THRIVE trial in active Thyroid Eye Disease. Sites are now active and are screening patients. In the THRIVE program, we're evaluating two regimens of VRDN-001, the standard 8-infusion course and a shorter patient-friendly 5-dose regimen, which would be 43% shorter than the 8-infusion TEPEZZA regimen. Our confidence in the efficacy of the shorter 5-dose regimen is enhanced by new 12-week data from our 10 mg per kg cohort, showing that between week six and 12, with no further dosing, VRDN-001's activity is maintained. This supports our assessment that 5 infusions of VRDN-001 with a 12-week course will deliver the meaningful benefit patients need. In parallel to the VRDN-001 program, we also continue to make progress with our subcutaneous programs, where we aim to deliver a convenient low-volume auto-injector that patients can self-administer at home. We aim to be the first to market with this offering globally. Today we reported the final data for VRDN-002 from our healthy volunteer study, confirming that VRDN-002’s pharmacokinetics exceeded our expectations, with a half-life of up to 43 days, about four-fold better than TEPEZZA, VRDN-001 and all other IGF-1R antibodies in development. This is actually longer than the initially estimated 30 to 40-day half-life we reported a few months ago and positions VRDN-002 well for its upcoming subcutaneous proof-of-concept trial in Thyroid Eye Disease patients. Both VRDN-002 and our half-life extended version of VRDN-001, called VRDN-003, are on track and advancing quickly. We're poised to bring the first self-administered Thyroid Eye Disease therapy to patients in need of better options. We're also well-funded to execute on these plans, with cash to advance rapidly through multiple key milestones. We've ended the quarter with over $430 million in cash, providing a runway into the second half of 2025. Now let's discuss the data from the 20 mg per kg cohort in more detail. I'll hand the call over to Barrett Katz, Viridian's Chief Medical Officer.

Barrett Katz, Chief Medical Officer

Thank you, John. This cohort, like the 10 mg per kg cohort for which we announced data in August, enrolled eight patients, six randomized to receive two infusions of VRDN-001, three weeks apart, and two patients randomized to receive placebo. We measure safety, tolerability, and efficacy at baseline and at six weeks. Let's start with the baseline patient characteristics and epidemiology, which have been very similar across drug and placebo groups, across our trials and the TEPEZZA Phase 2 and Phase 3 trials, with similar levels of baseline proptosis, CAS scores and rates of diplopia. As you saw in our press release this morning, we are pleased to announce data from our 20 mg per kg cohort after the last patient's six-week visit last week, and the data further validates the efficacy of VRDN-001 and its rapid and clinically meaningful effects. I'd like to start with an overview of the data. We'll review the data from today's 20 mg per kg cohort as well as the data for all patients treated with VRDN-001 in the 10 mg and 20 mg per kg cohorts. I'm encouraged to see the reproducibility of our findings. VRDN-001 performs at least as well as TEPEZZA at the six-week time point, with robust and consistent results on every single measure, nearly doubling the overall response rate of TEPEZZA, our result being 75%, compared to 44% for TEPEZZA. We saw a 75% proptosis responder rate, defined as at least a two-millimeter change from baseline proptosis versus about 56% for TEPEZZA. We saw a larger mean change of proptosis from baseline. We observed almost three times the proportion of patients achieving a CAS of zero or 1, indicating a complete or near complete therapeutic effect and double the mean change from baseline CAS, 4.0 versus 2.1, similar in both cohorts. We saw more than double the rate of patients with complete resolution of their diplopia, which was 75% for us compared to 36% for TEPEZZA. These results speak for themselves. VRDN-001 is a highly active drug and compares favorably with TEPEZZA, the only approved drug. Let me review the data in detail. One of the key things we were seeking to learn from the 20 mg per kg cohort is, if the 10 mg per kg maximized activity, as we expected from the pharmacokinetic and pharmacodynamic data. And as we expected, the results are highly consistent between both cohorts. When we look at the individual patient proptosis responses, the magnitude of improvement is distributed similarly for the two doses. The majority of patients in each dose cohort had a proptosis response of at least a two-millimeter reduction from baseline. Further, we observed a similar trend for individual CAS responses. Every VRDN-001 treated patient had a CAS reduction of at least two points from baseline. Likewise, the IGF-1 increases, as noted in healthy volunteers, which we presented at the American Thyroid Association Annual Meeting last month, showed no difference between TED patients treated with 10 and 20 mg of VRDN-001. Overall, the clinical activity data and the IGF-1 data confirm that 10 mg per kg of VRDN-001 achieved maximum clinical activity. This data confirms our choice of 10 mg per kg as our go-forward dose for our Phase 3 THRIVE program, which is underway. Let's review the proptosis results. We've evaluated proptosis by both PI administered Hertel exophthalmometry and also by a more objective orbital MRI, which is read centrally and blinded by two independent masked readers. This is important because while the Hertel is robust and reliable for studies with large sample sizes, it is a manually applied and read device prone to variability as seen in the literature. In smaller studies, such as our proof-of-concept cohorts, it's useful to have a second independent and confirmatory measurement of proptosis, such as MRI scans, which have been used to assess Thyroid Eye Disease patients. We implemented a robust MRI analysis with centrally read blinded reviews. MRI readers were trained and screened for test-retest reliability. Images were read independently by two masked readers who used imaging software to measure the distance between the lateral orbital rim and the anterior definition of the eyeball. As of today, we have centrally read MRI data available for all four placebo patients and nine of twelve drug-treated patients. The results are highly instructive and exciting. Here on the left, we show individual patient changes in proptosis as measured by MRI, and you can see all four placebo patients had little change, with three of the four placebo patients showing slight increases in proptosis from baseline. Conversely, the majority of VRDN-001 treated patients had proptosis reductions of two to six millimeters. Each of these were also responders by exophthalmometry. We found that two placebo patients and one VRDN-001 patient were proptosis responders by exophthalmometry, but those responses were not confirmed by MRI. As shown in the middle panel, in the four placebo patients, proptosis as measured by centrally read MRI slightly worsened at week six, with an average increase of 0.3 millimeters. In marked contrast, in the nine drug-treated patients for whom we have MRI data, proptosis improved on average by a reduction of 2.75 millimeters from baseline. To provide context regarding the VRDN-001 proptosis response, when adjusted by excluding the responders not confirmed by MRI, we observed a 0.5-millimeter reduction in the placebo arm and a 2.05-millimeter reduction for VRDN-001, reinforcing the treatment benefit of VRDN-001 by two independent measures of proptosis, namely exophthalmometry and MRI. To further contextualize our findings, we can compare VRDN-001's mean change from baseline proptosis to the mean change seen in TEPEZZA Phase 2 and 3 trials, which was 1.8 and 1.9 millimeters, respectively, versus 2.04 millimeters for VRDN-001. Proptosis responder rate, defined as the percentage of patients with at least a two-millimeter change in baseline proptosis, was 75% for VRDN-001 versus 55% and 56% for TEPEZZA in their Phase 2 and 3 studies. Turning now to the Clinical Activity Score, or CAS, which is a composite scale assessing patient pain, redness, and swelling, we observed a 4.0-point improvement from baseline CAS following VRDN-001 treatment, which far exceeds the placebo response. It is noteworthy that given this rapid and sizeable change in mean CAS, many subjects experienced near-total reductions in inflammatory science and symptoms, defined as achieving a CAS of zero or one; 58% of VRDN-001 patients met this criterion while only one placebo patient did. In fact, two-thirds of drug-treated patients had a four-point or greater reduction in CAS, whereas no placebo patients did. Comparing the effects of VRDN-001 on CAS with the data seen for TEPEZZA, we find that the four-point mean change we observed for VRDN-001 compares favorably to TEPEZZA's reported effects. Furthermore, among subjects treated with VRDN-001, the percentage achieving complete or near-complete therapeutic response is 2.5 to threefold higher than that seen with TEPEZZA. We have shown compelling improvements in both proptosis and CAS. What about our overall response analysis? This more stringent efficacy assessment includes both proptosis improvement and the associated signs and symptoms most bothersome to patients. An overall responder is defined as someone achieving at least a 2-millimeter reduction from baseline proptosis and at least a two-point change in CAS. Notably, 75% of our subjects were overall responders—nine out of twelve patients demonstrated clinically meaningful improvements in proptosis, combined with at least a two-point reduction in CAS—while only one placebo subject achieved this combined response. Our overall responder rate favorably contrasts with Phase 2 and Phase 3 trials of TEPEZZA, which demonstrated overall responder rates of 46% and 44%, respectively. Lastly, regarding diplopia—the double vision often most distressing for TED patients—similar to the TEPEZZA trials, around two-thirds of patients had diplopia at baseline. For those that do, complete resolution represents the most important and stringent endpoint. Following VRDN-001 treatment, 75% of patients with baseline diplopia experienced full resolution of this symptom. Six of eight patients with baseline diplopia demonstrated complete resolution after approximately two infusions of VRDN-001, which is more than double the rate observed in either TEPEZZA Phase 2 or 3 trials. This highlights the compelling improvement we are achieving in proptosis, CAS, and diplopia, often with complete or near-complete resolution of the signs and symptoms associated with Thyroid Eye Disease. Now let's review safety and tolerability. There have been no reports of hearing loss, drug-related hyperglycemia, or infusion reactions in the 20 mg per kg cohort, and all adverse events were mild or moderate in severity. Some of the known on-target IGF-1R effects were observed as expected. We noted two cases of muscle spasm, both mild, which did not require intervention; in fact, one was deemed unrelated to the drug by the masked investigator. Overall, when we evaluate safety and tolerability across both cohorts, we remain optimistic about the encouraging profile and look forward to collecting additional safety data in our Phase 3 program. I will now turn the presentation over to Jon.

Jonathan Violin, President and CEO

Thank you, Barrett. As you heard, for every relevant measure, and particularly for the more stringent measures, we consistently observed signals that are at least as strong as we reported for TEPEZZA, and in many instances substantially higher. We now have a clear opportunity to differentiate VRDN-001 from TEPEZZA. We believe we can offer patients a shorter course of treatment, providing them with faster symptom relief, and possibly greater efficacy, alongside an attractive safety profile. Our Phase 3 program is designed to harness these opportunities. It consists of two pivotal efficacy studies: THRIVE in active Thyroid Eye Disease and THRIVE-2 in chronic Thyroid Eye Disease, which are expected to read out in the middle and end of 2024, respectively. In support of our global efforts, we recently completed a Type C meeting with the FDA, and two scientific advice meetings in the EU, in which we discussed our Phase 3 plans. Based on these interactions, our Phase 3 program is designed to deliver all the data necessary to support successful BLA and MAA filings in the US and EU, respectively. As Barrett mentioned, we're pleased to share that we've initiated the THRIVE study in active Thyroid Eye Disease patients, with sites actively screening patients. The THRIVE and THRIVE-2 trials will evaluate identical dosing regimens across a 24-week primary endpoint with three study arms: first, an eight-infusion regimen, matching the TEPEZZA regimen; second, a shorter five-infusion regimen that enables patients to complete their treatment course in just three months—43% faster than TEPEZZA; and finally, a placebo arm. To further enhance the treatment regimen, we are adopting a shorter 30-minute infusion time instead of the 60 to 90 minutes required for TEPEZZA. One of the reasons we believe a shorter course of treatment will be effective is that published data show little to no benefit from the last two infusions of TEPEZZA. Additionally, the efficacy of IGF-1R antagonists proves remarkably durable post-treatment. We now have our own data for VRDN-001 to support this durability, which we've noted from the 10 mg per kg cohort. We found that at 12 weeks, nine weeks following the last infusion of VRDN-001, efficacy remains largely unchanged. Patients who responded to VRDN-001 at week six maintained that response, with four out of five proptosis responders, four out of five overall responders, and four out of five patients achieving CAS reductions to 0 or 1. For diplopia resolution, all three patients with complete resolution at week six maintained that absence of double vision. Furthermore, the fourth patient with diplopia who had partially improved at week six continued to improve between weeks six and 12, achieving a complete diplopia response by that point. Overall, 100% of patients were free of double vision at week 12. When we examine the mean change in proptosis displayed on the slide, we notice similar maintenance of efficacy from week six to week 12. This durable response strongly suggests that a short three-month course of treatment will provide lasting efficacy to the 24-week endpoint and beyond. We're excited to have launched the VRDN-001 Phase 3 program and look forward to updating you on our progress. In summary, VRDN-001 continues to deliver significant improvements in the signs and symptoms of Thyroid Eye Disease. In both cohorts of TED patients, we've observed rapid and profound improvements across all key signs and symptoms of the disease. Based on this data, we're extremely excited about our Phase III program, which we initiated earlier this month. Separately, we've also initiated our proof-of-concept cohorts in chronic Thyroid Eye Disease, with initial data expected in the first half of next year, and we're on track to launch the THRIVE-2 Phase 3 trial in chronic Thyroid Eye Disease shortly thereafter, around mid-year next year. This positions us to read out both pivotal studies in 2024. We're also excited to share data in early January for our final acute Thyroid Eye Disease proof-of-concept cohort, evaluating 3 mg per kg, which has completed enrollment. Data from this cohort will further inform the feasibility of an every-four-week subcutaneous dosing paradigm for our subcutaneous programs, VRDN-002 and VRDN-003. These next-generation subcutaneous auto-injector programs are also advancing rapidly. We now have final pharmacokinetic data for VRDN-002, establishing a half-life of up to 43 days, better than the 30 to 40-day half-life we estimated at the interim analysis in August. This means that VRDN-002 achieves about four times the half-life of first-generation antibodies like teprotumumab. We are on track to obtain VRDN-002 subcutaneous proof-of-concept data in Thyroid Eye Disease patients, utilizing every two-week and every four-week dosing in the second half of next year. VRDN-003, which is VRDN-001 but incorporates the same half-life extension technology as VRDN-002, is also advancing quickly to IND in the second quarter of next year. Non-human primate data supports a half-life at least as good as VRDN-002. By the end of next year, we expect to have all the data necessary to select either VRDN-002 or VRDN-003 to move forward into pivotal studies and plan to initiate Phase 3 in early 2024. Together, our intravenous and subcutaneous programs will represent the most complete commercial offering for Thyroid Eye Disease patients. We will initially enter the IV market, projected to exceed $4 billion globally, with VRDN-001, followed shortly thereafter by our subcutaneous auto-injector product. We believe as a new entrant with a differentiated drug and a simpler dosing regimen, we will be highly competitive in this market. Each year, 20,000 to 25,000 new active Thyroid Eye Disease patients emerge in the US, and 35,000 to 40,000 in the EU will select a therapy, and we believe our products can be an attractive choice for many of them. In summary, we're thrilled with the new data we presented today, which confirms the profound treatment benefits of VRDN-001 for a growing number of Thyroid Eye Disease patients. These results heighten our confidence in our Phase 3 program, and we're pleased to have just started our Phase 3 THRIVE trial earlier this month. We are well-funded and moving swiftly to advance the most complete portfolio of Thyroid Eye Disease assets toward a market poised to exceed $4 billion, which is in urgent need of better therapies. Before we open the call for questions, Kristian will review our financials.

Kristian Humer, Chief Financial Officer and Chief Business Officer

Thank you, John, and good morning, everyone. I'd like to give a brief summary of our Q3 earnings. Cash, cash equivalents and short-term investments were $431 million as of September 30, 2022, compared with $197 million as of December 31, 2021. We believe that our current cash, cash equivalents, and short-term investments excluding our $75 million credit facility will be sufficient to fund our operations into the second half of 2025. As of September 30, 2022, Viridian had approximately 56.2 million shares of common stock outstanding on an as converted basis, which included 40.2 million shares of common stock outstanding on an aggregate of approximately 16 million shares of common stock issuable upon the conversion of 188,000 and 51,000 shares of Series A and Series B preferred stock respectively. Please refer to our earnings press release for a more detailed Q3 financial update. With that, we can open the call up for Q&A.

Operator, Operator

Thank you. Our first question today comes from Rami Katkhuda of LifeSci Capital. Please proceed with your question.

Rami Katkhuda, Analyst

Hey, guys, congrats on the updates, and thanks for taking my questions. A couple of quick ones for me. First, can you provide more color on the discrepancy in the percent of patients who achieve a CAS of zero or one between the 10 and 20 mg per kg cohorts?

Jonathan Violin, President and CEO

Sure. Thanks, Rami. Hi. So first of all, as you saw both cohorts had a percentage of patients achieving that CAS of zero or one higher than either of TEPEZZA's study. So in both cohorts, that looks great. But you're right, we had five of six patients in the first cohort and two of six in the second cohort, so there is a difference there. Now if you look at the baseline characteristics, you'll note that the baseline CAS in the 20 mg per kg cohort is a little higher than in the 10 mg per kg cohort or indeed the TEPEZZA cohort—the TEPEZZA Phase 2 and Phase 3 trials. So we think that explains why we're seeing very similar magnitude of CAS improvements—3.7 and 4.3 points in the two cohorts show up as what appears to be a bigger difference in the percentage of patients getting to a CAS of zero or one. In fact, if you look at the individual patient data, there are two patients of interest. One in the 20 mg per kg cohort had a 7-point score at baseline, had a 5-point improvement, a huge change in CAS; however, this only took the patient to a CAS of 2. So, while the improvement is substantial, it didn't meet the CAS criteria of 0 or 1. Likewise, the second patient started at 6, had a 4-point change, and ended up with a score of 2. So we're consistently seeing tremendous improvement in the Clinical Activity Score; it's just a slight difference in the baseline characteristics across the two cohorts.

Rami Katkhuda, Analyst

Got it. Makes sense. And then, can you touch upon if we've seen variability in proptosis change with the Hertel exophthalmometer in other studies?

Jonathan Violin, President and CEO

Sure. Yes. The TEPEZZA study, if you look at the New England Journal Phase 3 supplements from 2020, you can see the individual patient responses over time. If you examine the 12-week data, you can see that the average change with placebo is very close to 0, but the range is from plus 3 to minus 4.5. Now, that's fine when you've got a large sample size, and the study size was about 40 patients per arm, similar to our Phase 3. But when you have a smaller sample size, you will be more susceptible to that variability and it's not surprising. So this is a manual device applied to the patient's face by the investigator. The question is, how do we manage that in a smaller study? Thus, we are advocating for the use of an independent orthogonal and ideally more robust confirmatory measure. That's why we turned to MRI. As you heard, this is a centrally read process, where two blinded reviewers independently measure the data. So it's extremely rigorous, and most of the time, the MRI confirmed the exophthalmometry results. When occurrences arise where they do not match, which do you trust—the manual exophthalmometry, known for its variability, or the more rigorous MRI? We view the MRI as more accurate. This confirmation step has enabled us to thoroughly assess the performance of our drug in our smaller sample size. In our Phase 3 study, we expect to have a similar sample size to the TEPEZZA studies, so any variability associated with the exophthalmometer will tend to average out. It serves as a great endpoint for larger sample sizes, while MRI provides valuable insight in smaller studies. We will also incorporate MRI measurements moving forward, as it may yield differentiating data for us.

Rami Katkhuda, Analyst

Makes a lot of sense. Congrats again, guys.

Operator, Operator

The next question is from Gavin Clark-Gartner of Evercore ISI. Please proceed with your question.

Gavin Clark-Gartner , Analyst

Great. Thanks for taking my questions. So I had two. First, is there any scenario where you would consider adding a weekly dosing cohort for the subcutaneous Thyroid Eye Disease proof-of-concept trial, which, I guess, could be viewed as likely to end up?

Jonathan Violin, President and CEO

So based on what we know of the performance of VRDN-001 and the half-life we’ve observed for VRDN-002, we’re really confident in the every-other-week dosing paradigm. Really the question is, can we achieve less frequency than every other week? We'll learn more about that with the upcoming 3 mg per kg cohort. If that shows positive data, then we'll know that lower doses and lower exposures are necessary, allowing us to spread out the dosing paradigm. So, we are set on that every other week approach right now, and the question remains whether we can extend to every four weeks.

Gavin Clark-Gartner , Analyst

Yes. I got it. And then, on the commercial side, do you know roughly what percent of covered lives have site of care restrictions for TEPEZZA and require infusions to be given outside of the hospital outpatient setting?

Jonathan Violin, President and CEO

We actually don't have that information currently, as you can imagine, we're ramping up a significant amount of commercial work, given the very strong data we reported in August and again today. So you'll be hearing a lot more from us on the commercial front in the near future.

Gavin Clark-Gartner , Analyst

Sounds great. Thanks.

Operator, Operator

The next question is from Thomas Smith of SVB Securities. Please proceed with your question.

Thomas Smith, Analyst

Hey, guys. Good morning. Congrats on the data. And thanks for taking our questions. I guess, just first on the 20 mg per kg data for clarification. I know it's a small number of patients, but can you clarify what the mean proptosis reduction was in the placebo patients with this updated data set?

Jonathan Violin, President and CEO

So the mean proptosis, when we exclude the patients we couldn't confirm by MRI, was an improvement of 0.5 millimeter, very consistent with what was seen in the TEPEZZA studies.

Thomas Smith, Analyst

Okay. And then, thinking forward here to the 3 mg per kg data set, can you talk about your expectations for efficacy there? Are you expecting roughly equivalent efficacy based on what you've seen on the pharmacodynamic effect in healthy volunteers, or should we anticipate a moderation in efficacy with the lower dosage?

Jonathan Violin, President and CEO

Yes. The pharmacodynamic measurements—the increases in plasma IGF-1 we reported for healthy volunteers in August—suggest that there’s full receptor engagement systemically. While we can't draw a direct line between systemic target engagement and efficacy, it’s a strong hypothesis that we will see robust efficacy at 3 mg per kg. The important point is how that impacts us. We think the 10 mg per kg dose for VRDN-001 is the appropriate dose to pursue in Phase 3, balancing potential benefits and risks. Hence, we are moving that forward. The 10 mg per kg data will help guide our expectations for the subcutaneous product. Determining whether it will require every two weeks—which would be commercially compelling—or even longer will depend on the outcomes here.

Thomas Smith, Analyst

Okay. Got it. And then just maybe finally, when you had the 10 mg per kg top-line data, you provided some color on the safety and tolerability you were observing in the 20 mg cohort. I guess, what can you tell us about the ongoing 3 mg per kg cohort at this time? Any insights into safety or tolerability?

Jonathan Violin, President and CEO

We haven't reviewed any data from that cohort regarding safety or otherwise. The only information I can share is that no serious adverse events have been reported. That’s all we know thus far.

Thomas Smith, Analyst

Okay. Got it. Thanks guys. Appreciate you taking the questions and congrats on the data.

Jonathan Violin, President and CEO

Thanks, Tom.

Operator, Operator

The next question is from Laura Chico of Wedbush Securities. Please proceed with your question.

Laura Chico, Analyst

Hi. Good morning, guys. Thanks for taking my questions. I guess, I had one on safety and then one related to the Phase 3 study. So first, could you offer any additional clarification on the hyperglycemia event in the 20 mg per kg cohort? Was this exacerbated in response to treatment? How high did glucose levels increase? Apologies if I missed that earlier.

Jonathan Violin, President and CEO

Sure. I'll ask Barrett to comment on that.

Barrett Katz, Chief Medical Officer

Thanks, Laura. Because we aimed to study the same population as the Horizon study, we allowed for the enrollment of patients with known diabetes and known glucose intolerance. In this cohort, we actually enrolled a patient with known diabetes and less-than-ideal diabetes management. The patient presented with established hyperglycemia while on an oral agent for their condition. The hallmark of diabetes is glycemic variability and the patient during their time with us exhibited some variability in their glucose measures. The masked investigator was following this patient and determined that the variability observed was consistent with the underlying disease of diabetes and the expected fluctuations in glucose levels, which, as you know, are influenced by factors such as diet and meal timing. Consequently, the principal investigator determined that any change in this variability was indeed due to the underlying disease and not attributable to the drug.

Laura Chico, Analyst

That's super helpful. Thank you, Barrett. Maybe one follow-up question then. I think Jonathan you mentioned you completed the Type C meeting with the FDA around the Phase 3 design. I just wanted to confirm that no comparison to an active drug would be required. Regarding the current THRIVE design, with the arms for five cycles and eight cycles, would you anticipate that the potential for hearing impairment might diminish over a shorter infusion cycle?

Jonathan Violin, President and CEO

Correct, the dosing arms of the study that I described are moving forward as discussed with the agency: two active arms and one placebo arm. Regarding the potential for reduced hearing impairment with a shorter course of treatment, the answer is yes. One of the factors we are excited about is that a shorter treatment exposure could inherently limit the incidence of adverse events. However, we cannot definitively establish that. The adverse event profile we've observed thus far is extremely encouraging, and we look forward to amassing more safety data as we progress into Phase III.

Laura Chico, Analyst

Thanks very much, guys.

Operator, Operator

The next question is from Kalpit Patel of B. Riley Securities. Please proceed with your question.

Kalpit Patel, Analyst

Yes, hey. Good morning. Thanks for taking the questions. On Slide 7, I guess John, do you have any insights as to why the IGF-1 increases were lower for the 20 mg per kg cohort versus the 10? I noticed there's data for five patients instead of six. Was there anything specific about that one patient that was noteworthy?

Jonathan Violin, President and CEO

Great. Yes. We have data from five patients because the IGF-1 data takes a bit longer to come in. As you heard, the last patient's six-week visit was just last week. Therefore, we don't yet have the IGF-1 data for that last patient. Regarding the levels of IGF-1 across the two cohorts, we believe they are quite similar. Numerically, there are slightly lower levels observed, which we've encountered in the past. However, mechanistically, we find no basis to think there is any difference between these two cohorts. Once full receptor occupancy is achieved, the effects of the drug should be maximized, which is why we believe it's reasonable to consider these two doses equivalent. Hence, we are discussing data reporting from all twelve patients.

Kalpit Patel, Analyst

Okay. And then, I believe you guided to choose either 002 or 003 for Phase III development by early 2024. Given your timelines, I don't think you'll have any patient data for 003 by then. So, what gives you the confidence to select either of these candidates by early 2024?

Jonathan Violin, President and CEO

Thank you. Please keep in mind that VRDN-003 is essentially the same antibody as 001, just incorporated with the half-life extension technology. The variable domain is responsible for target engagement, while the half-life extending modifications reside in the Fc domain, the other end of the antibody, which means they do not impact the antibody's antigen-binding function, something we've already validated for VRDN-001. Consequently, VRDN-003 functions just like VRDN-001, with enhanced pharmacokinetics as evidenced by nonhuman primate data. We anticipate a pharmacokinetic profile for humans that is at least as favorable as VRDN-002's. The unique advantage here is that we can utilize exposure-response data from VRDN-001 to inform our Phase III dosing selection for VRDN-003. That’s why this comparison between 002 and 003 works so effectively. We expect to secure VRDN-002 proof-of-concept data along with its own PK/PD data and, simultaneously, healthy volunteer data for VRDN-003, facilitating a robust choice between the two crucially ahead of our pivotal studies, which we intend to initiate in early 2024.

Kalpit Patel, Analyst

Okay. Very helpful. Thanks for taking the question.

Operator, Operator

The next question is from Jason Butler of JMP Securities. Please proceed with your question.

Jason Butler, Analyst

Hi, thanks for taking the questions and let me add my congratulations on the data as well. I guess first, if you get to greater than every two weeks, e.g. every four weeks with 001, could you talk about the overarching product portfolio concerning 002 and 003, and how they would fit commercially?

Jonathan Violin, President and CEO

Certainly. We’re moving VRDN-001 forward as our intravenous product offering. The every two-week dosing as we observe now is established for 002 and 003. VRDN-001 might also be suitable as a subcutaneous option; we'll learn more about that with the 3 mg per kg cohort. Ultimately, we want to introduce the best product, and the half-life extension is progressing so positively that either 002 or 003 will become our subcutaneous offering. We will determine at the end of next year which molecule advances to pivotal studies. Thus, the portfolio we will bring forward consists of VRDN-001 for intravenous administration and either 002 or 003 for subcutaneous use. Since 002 and 003 are the only half-life extended antibodies in development, yielding an optimal profile for an IGF-1R antibody, we strongly believe that either will be distinguished as best-in-class and difficult to outperform.

Jason Butler, Analyst

Great. And can you talk about now with a larger sample size, the non-responders, is there anything notable about the baseline characteristics of those patients or any other insights that could guide your targeting of patients in the future?

Jonathan Violin, President and CEO

Honestly, the results have shown such consistency that we have not identified a true non-responder population. Even for patients who do not reach responder status for proptosis, they usually show considerable changes in CAS or diplopia. Therefore, we haven’t discerned any definitive non-responder group. The drug demonstrates efficacy across a wide range of patients.

Jason Butler, Analyst

Great. Thanks for taking the questions.

Jonathan Violin, President and CEO

Thanks, Jason.

Operator, Operator

There are no additional questions at this time. I would like to turn the call back to Jonathan Violin for closing remarks.

Jonathan Violin, President and CEO

Thank you. I'd like to extend my gratitude to the investigators, patients, and Viridian employees, who have contributed to our programs. Our data provides an incredibly strong foundation to advance our programs rapidly and purposefully to create valuable new therapeutics for thyroid eye disease. And with that, we'll close the call. Thanks for joining us.

Operator, Operator

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.