Welcome to the Viridian Therapeutics conference call. It is now my pleasure to introduce your host, Louisa Stone, Manager of Investor Relations at Viridian Therapeutics. Please go ahead. Thank you, Operator. Good afternoon, everyone, and welcome to the Viridian Therapeutics conference call to discuss the positive data from our phase II trial cohorts of VRDN-001 in patients with chronic TED, an amendment to our ongoing THRIVE phase III trial, and the latest progress in our subcutaneous program for the treatment of TED. A press release highlighting these updates and the presentation for today's call are available on the investors page of the corporate website at www.viridiantherapeutics.com. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements regarding our regulatory, product development, and commercialization plans and research activities. These statements are subject to risks and uncertainties that could cause actual results to materially differ from those forecasted. A description of these risks can be found in our most recent Forms 10-Q and 10-K on file with the SEC. Presenting on the call today are Scott Myers, our President and Chief Executive Officer, Dr. Barrett Katz, our Chief Medical Officer, Dr. Thomas Ciulla, our Chief Development Officer, and Dr. Kimberly Cockerham, an oculoplastic surgeon specializing in TED, as well as neuro-ophthalmology, orbital oncology, and oculofacial restoration at the SENTA Clinic in San Diego, California, and on faculty at the Stanford University School of Medicine. Dr. Cockerham is also an investigator in the VRDN-001 trial. Additional members of the Viridian leadership team joining the question and answer session at the end of today's presentation include Kristian Humer, our Chief Financial and Business Officer, and Todd James, Senior Vice President of Corporate Affairs and Investor Relations. I would now like to turn the call over to Scott Myers, President and CEO of Viridian. Thank you, Louisa. Good afternoon, everyone. We are excited to share the positive data from the two dose cohorts of VRDN-001 evaluated in our phase I and II trial for the treatment of patients with chronic thyroid eye disease or chronic TED. These important data establish proof of concept for Viridian in chronic TED and build upon the compelling data we previously reported in active TED during 2022 and earlier this year. In chronic TED, we are observing profound and consistent signs of clinical activity on endpoints measured after only two infusions of VRDN-001, three weeks apart and assessed at week six in both the 10 mg/kg and 3 mg/kg dose cohorts. Both doses were generally well-tolerated, with no serious adverse events reported. Following consistent feedback from stakeholders in the TED community, including key opinion leaders, our principal investigators, treating physicians and patients, as well as with the discussions we had with the FDA, we are amending our ongoing THRIVE phase III trial to include only the shorter 5-dose, 12-week treatment regimen along with a placebo arm, and we are removing the eight infusion arm from this phase III study. Primary and secondary endpoints will be assessed three weeks after the last dose at week 15. Our excitement of VRDN-001's differentiated mechanism as a full antagonist, coupled with its ability to generate clinically meaningful results as early as week six, gives us high confidence in attaining clinical success for this shortened treatment regimen. Excuse me. We believe it will potentially offer an attractive commercial profile that differentiates VRDN-001 in the market, both for patients and caregivers, from intravenous therapy for the treatment of TED. Following today's positive data in patients with chronic TED, our team is putting the finishing touches on the design of our second pivotal phase III trial, THRIVE-2, for chronic TED, which we plan to initiate this quarter and expect top-line results by the end of 2024. The low-dose datas support the continued development of a convenient, low-volume dosing profile for our subcutaneous injection candidates for the treatment of TED. Our team has made important progress in this endeavor and we remain on track to select our lead subq candidate in TED by year-end. We have completed important formulation work for all three subq candidates. We have filed the IND amendment for subcutaneous VRDN-001, as well as the initial IND for VRDN-003 with the FDA. Plan to initiate phase I trials for both candidates this quarter. Based on progress to date, the team continues to build on building a blockbuster franchise for the treatment of TED through the development of differentiated IGF-1R full antagonist IV and subq therapies. We believe our growing body of clinical data put us in a strong position to build and expand the markets for active and chronic TED therapies. Today, the TED market for IGF-1R antibodies has been limited to the U.S. We believe patients in regions outside of the U.S. can benefit from the access to these therapies. While we may choose to operate independently in certain ex-U.S. markets, in those regions in which we may not be able to maximize commercial opportunities, we will explore partnering with companies with the necessary infrastructure and experience to support our strategy. We believe a subcu product in TED has the potential not only to deliver valuable convenience to patients, but also offers the opportunity to expand the prescriber base inside the drug administration beyond the current concentration of subspecialist treaters to more ophthalmologists and endocrinologists. Having both IV and subcu products will allow us to work with caregivers and experts in TED to establish new treatment paradigms with the potential to provide longer-term benefit and value to patients with this vision-threatening disease. To execute our long-term vision in TED, we have focused on attracting and retaining experienced leaders to strengthen existing functions and to establish new areas necessary to drive our transition to a late-stage clinical development organization. We have established a corporate affairs team that includes patient advocacy and engagement under our Senior Vice President, Todd James. We have grown our clinical development and clinical operations organizations to execute on multiple global phase III trials, as well as the ongoing and planned development of our subq candidates. This work is occurring under the seasoned leadership of Dr. Barrett Katz, our Chief Medical Officer, and Dr. Tom Ciulla, our Chief Development Officer. We have established a medical affairs function led by Dr. Felix Geissler, which includes our first MSL and scientific communications team, both of which are focused on educating researchers and medical professionals throughout the TED community and raising awareness of Viridian's programs in TED. With our ongoing progress in subq administration, our Chief Product and Strategy Officer, Dr. Deepa Rajagopalan, has hired a small team of experienced professionals focused on our subq device product development efforts. Finally, in April, we hired Tony Casciano, Viridian's first Chief Commercial Officer. Tony and his new team are focused on pre-commercial activities, including research on marketplace dynamics, market access, and pricing. We will continue to grow as needed with a clear goal of balancing appropriate expansion with prudent allocation of our investors' capitals. Moving to the more detailed section of today's call, I will hand the presentation to our three presenters today, beginning with our esteemed guest presenter, Dr. Kimberly Cockerham, an internationally recognized thought leader in TED and an investigator in our VRDN-001 trials, and then moving to Dr. Barrett Katz, our Chief Medical Officer, and Dr. Tom Ciulla, our Chief Development Officer. I will now turn the call over to Dr. Cockerham to discuss her background and provide an overview of TED. Thank you so much, Scott, and good afternoon to everyone. Truly a pleasure to be joining on the call today to discuss the really exciting advances in thyroid eye disease therapeutics. Thyroid eye disease, also known as TED, has been my clinical interest and research passion for over two decades. As you can imagine, I'm thrilled at the enthusiasm for this space and the ability to offer my patients transformative interventions. A little bit about my background. I am a board-certified ophthalmologist with subspecialty training in neuro-ophthalmology, orbital disease, plastic reconstruction, and adult strabismus. In translation, that means I'm a subspecialist who takes care of all medical and surgical aspects of thyroid eye disease. I have seen approximately 300 TED patients a year for quite some time, first on active duty army at Walter Reed Army Medical Center, then within the VA system at UCSF, and then with adjunct faculty at Stanford for many years. I'm now in private practice in San Diego at the SENTA Clinic. Let's talk about the TED overview. This slide illustrates the underlying drivers of TED biology and how they impact the eye and the area behind the eye, called the orbit. IGF-1 is overexpressed on the orbital fibroblasts in thyroid eye disease and is co-located and co-acting with the TSH receptor. The signaling stimulates muscle and fat, and this results in expansion in addition to the inflammation. Next slide. Sorry, keep going on this slide. Sorry about that. Historically, thyroid eye disease has been described as a biphasic disease with an initial active phase that's characterized by inflammation. This results in pain, redness, swelling, eyelid retraction, proptosis, double vision, and blurred vision. The inflammation may resolve over months to years. For some, it will not improve without a therapeutic intervention. Once the inflammation recedes, the chronic phase of thyroid eye disease is characterized by a white eye, but with all the persistent symptoms and signs I just described, that alter significantly and interfere with the patient's quality of life. In both the active and chronic phases of the disease, proptosis, eyelid retraction, and eye deviations combine to create facial disfigurement. In severe cases, sneezing or coughing can result in the eye getting stuck in front of the eyelid, resulting in severe pain and anxiety. Optic nerve compression can occur at any phase of the disease and can cause complete blindness. Thyroid eye disease affects all ages and ethnicities, it affects women more than men at a ratio of approximately 5: 1. The typical thyroid eye disease patient is a woman in her thirties, forties, fifties, and the facial disfigurement deeply affects her psychosocial health, interfering with social interactions, relationships at home, and affecting her ability to drive, read, work on the computer, and be productive. Next slide, please. I touched on this in a previous slide, here you can see the different categories of the visual impairment. Almost all patients have dry eyes, as seen in of the slide left, and many patients go on to develop double vision, especially when they first wake up in the morning. There's like a blur image when they go to read their paper. In addition to diplopia and double vision, you can have photophobia or light sensitivity due to corneal breakdown and tear film alterations. They can get actually decreased vision in straight ahead, and/or visual fields in the periphery, visual field defects. They can have reduced color. Worst of all, an optic neuropathy can develop that is permanent and irreversible. Next slide, please. As I was previously describing, TED has had this historical view as a biphasic disease. We now understand that the transition varies from patient to patient. Some patients never have an inflammatory phase. Others have a very prolonged inflammatory phase that can last for decades. Patients who have been chronic for several years can even relapse or become inflamed again. Of therapeutic importance, the chronic patients, their quality of life remains impacted for years and even decades. Despite the improvement in the inflammation, they continue to have significant symptoms and signs. Prior to 2020, chronic thyroid eye disease patients endured decades-long persistence of bulging, double vision, pain, and dry eye symptoms that disrupted tasks of daily living. Next slide. What are the current treatments for thyroid eye disease? The current treatments vary depending on the patient. In some patients, and these are mainly patients that see general ophthalmologists or optometrists, patients have very mild, minimally symptomatic thyroid eye disease, and there's some supplementation with vitamin D and selenium recommended, artificial tears without preservatives, and they may be recommended a sleep mask and ointment if their eyelids don't close completely while sleeping. In contrast, the patients that are referred to me are, tend to be moderate to severe, where they are, the thyroid eye disease is interfering with their social interactions and tasks of daily living. In those cases, I discuss the following therapeutic options with my patients. The first three, intravenous steroids, orbital radiation, and off-label immunosuppressives, are items that we utilize in patients with active thyroid eye disease. Corticosteroids are widely used to combat inflammation. Topical are not helpful. Oral have a lot of side effects, IV works to relieve the redness and fluid accumulation. They're only helpful in active thyroid eye disease, where there's active inflammation. There is no clinically significant improvement in muscle size, fat volume, proptosis, or double vision. External beam radiation is controversial and typically used in conjunction with corticosteroids. Radiation is only helpful, again, in the active thyroid eye disease patient. Radiation, like steroids, does not restore the structure and function of the extraocular muscles, so it can't improve proptosis or double vision. Let's jump down to the bottom. Surgical management is reserved for chronic thyroid eye disease patients unless there's optic nerve compromise or corneal breakdown, which prompts urgent surgery. The surgical options are to remove bone to make more space for the enlarged muscles and fat. This bone removal is called orbital decompression. Unfortunately, this procedure can cause worsening of the double vision as the muscles fall into the hole that was created, and that creates permanent intractable double vision, not responsible, non-responsive to surgery. Strabismus surgery can improve double vision when looking straight ahead, but it doesn't restore structure or function. Finally, eyelid surgery can improve eyelid position and the ability to close. Going back to the off-label immunosuppressive agents, I really have not ever found these to be of any help, and they're also extremely difficult to get authorized due to the fact they are not FDA approved. Since the winter of 2020, intravenous IGF-1 has been my friend. This inhibitor just came on the market and has done amazing things for these patients. The FDA approved this TEPEZZA for all patients with thyroid eye disease. Unlike any of the therapies I've just discussed, this works independent of activity or duration of disease. Let me say that again. We currently have no other options on the market that work independent of the activity or duration of disease. It works in all forms of thyroid eye disease, whether it be active, chronic, or relapsed, all thyroid eye disease. Very impressive. As far as the other differences, unlike therapeutic options where we're, that just treat the inflammation, TEPEZZA enables tissue remodeling that restores the extraocular muscles and fat back to the normal pre-state, so it doesn't overcorrect. If you have a little bit of proptosis, it'll improve you a little bit and won't make you sink too far in. I'm not just clearing up the redness or breaking bones. I'm helping patients address the cause of their symptoms and signs. This intervention does not come without a cost. The treatment regimen is burdensome in and of itself, and the adverse events are well known, from hearing impairment to hyperglycemia and more. Next slide, please. The level and unmet need for thyroid eye disease patients remains very, very high. My colleagues in neuro-ophthalmology, oculoplastics, endocrinology, have been thrilled with the increased focus on the development of thyroid eye disease therapies over the past several years, as this is a rare disease or relatively rare disease, and it's been ignored for decades. At this point, I've been involved in the care of over 200 patients treated with the only FDA-approved therapeutic, yet there is substantial need to ease the treatment burden. In addition, the side effect profile, especially in at-risk populations such as elderly, those with preexisting hearing conditions, preexisting inflammatory bowel disease, or poorly controlled prediabetes or diabetes, have led some patients and their clinicians to choose to avoid this impactful therapeutic option. What would be ideal? Well, ideally, there would be a more convenient dosing regimen that will minimize the dose of the drug delivered, shorten the infusion duration, and decrease the frequency of delivery. This would potentially minimize the side effects, save on cost, and allow more patients to get authorized for this medication. Secondarily, it'd be very nice to have a similarly efficacious subcutaneous treatment option, which would dramatically reduce treatment burden for patients by allowing them to administer the treatment themselves in their home at approved dosing intervals. Finally, we really need to develop new treatment regimens that deliver longer benefit for patients. Thyroid eye disease is a chronic disease. Treatments or protocols with the potential to safely extend clinically meaningful improvements for duration of their lives would represent another important advance. With that, we'll turn back over to the presentation to Barrett to provide some background on VRDN-001 and the trial work done to date before I review today's data in the chronic thyroid eye disease studies. Barrett, you're up. Thank you, Kim, for sharing your perspective and background on TED. Good afternoon, everyone. I too am delighted to share in today's data announcement and for what it could mean for our patients and my colleagues in the field. I'm going to begin by providing some background on VRDN-001 and our proof of concept work before turning things back over to Kim to prevent and present the top-line data from our chronic TED cohort. VRDN-001 is a humanized antibody that targets the insulin-like growth factor one receptor, IGF-1R. It is differentiated by its binding and engagement with IGF-1R as a full antagonist. Preclinical studies have shown that VRDN-001 binds to a distinct epitope of the IGF-1R and binds longer than teprotumumab. VRDN-001 effects near complete inhibition of IGF-1 ligand binding to IGF-1R and blocks IGF-1R, both proximal and distally. We believe the impact of this binding activity is being seen in the clinic. VRDN-001 achieves a rapid onset of action in the first six weeks of treatment, driving significant clinical changes by a full target engagement in both low and high doses that we tested. This has the potential to provide important differentiation in the treatment of TED with a short course of therapy, five infusions over 12 weeks, compared with a 21-week, eight infusion regimen. We are also able to administer at a lower dose, 10 mg/kg, which when combined with our shorter course of therapy, could result in an optimized safety profile. With VRDN-001 30-minute infusion time, there is also the potential to shorten a patient's time and costs at the infusion center. With today's announcement, we've now established proof of concept in patients with both active and chronic TED. The key difference between our two trials' inclusion criteria was the clinical activity score, or CAS. In the active TED trial, participants had a CAS of four or higher, while in our chronic trial, any CAS, including zero, was acceptable for participation. Additionally, active TED was defined as having onset of signs and symptoms within the past 12 months, whereas chronic TED was characterized as having more than 12 months of signs and symptoms. Following the active TED data that was announced throughout 2022 and earlier this year, we've had the privilege to present our data to researchers and clinicians throughout the TED community at multiple medical congresses, including NANOS, the American Academy of Neurology, and ARVO, and at major meetings both here and across the world. Our data have been well received, and most recently, our VRDN-001 presentation in active TED was selected as the winner in the ENDO 2023 annual meeting in the presidential competition as Best Poster. Turning to our proof of concept trial design in chronic TED, the trial was quadruple masked and included two dose cohorts, 10 mg/kg and 3 mg/kg. Each randomized 3: 1 in favor of VRDN-001 versus placebo, with the aforementioned inclusion criteria. Target enrollment was eight patients in each cohort. The 3 mg cohort was over-enrolled, allowing all patients who had consented and were eligible to be randomized following screening to participate in the trial. In the 3 mg/kg dose cohort, seven patients were randomized to receive VRDN-001, and three patients were randomized to receive placebo. One patient randomized to receive VRDN-001 3 mg/kg discontinued the trial due to needing to leave the country for a family emergency prior to receiving their second dose of VRDN-001, leaving six patients treated with VRDN-001, 3 mg/kg evaluation for the week six clinical endpoint analyses. The pharmacokinetics we found were consistent for both doses throughout the study. As in our findings in the active TED cohort, we saw multifocal sustained increases in IGF-1 levels in the chronic patients, suggesting full target engagement for both 10 mg/kg and 3 mg/kg cohorts. I will now turn the presentation back over to Dr. Cockerham to present the patient's baseline characteristics and the top-line data from the trial. Kim? Thank you, Barrett. Before I jump into the data, I would like to review a few of the measures to help everyone better understand the process of evaluating a thyroid eye disease patient in the clinic and for the clinical trials. For proptosis, or eye bulging, the Hertel exophthalmometer is the gold standard. It's an office-based measuring device to quantitate proptosis, specifically how far the eyeball itself protrudes in front of the bones that form the box that holds the eye, known as the anterior orbit. It's measured by placing the Hertel on the orbital rims, as you can see demonstrated here. In contrast, the MRI determination of proptosis is an exploratory tool in thyroid eye disease clinical trials, but not yet a validated measure. The MRI is objective and more precise than Hertel and provides us with a second proptosis data point to confirm or reject the proptosis change measured by the exophthalmometer. Hertel is known for variability. MRI, in contrast, the MRI data allows us to measure and analyze activity within the orbital cavity, identifying potential treatment-related changes to orbital muscle and adipose tissue volumes. The evaluation of the symptoms of thyroid eye disease is performed by using the CAS score. Slide. Next. Another way to reevaluate signs and symptoms it is the CAS. This composite scoring ranges from zero to seven, quantifying redness, swelling, and pain based on the presence or absence of these seven signs and symptoms that are characteristic of thyroid eye disease. We add one point to the patient's CAS score for the presence of each of the following signs and symptoms. You can see the signs are listed as swelling of the eyelids, redness of the eyelids, conjunctival injection and chemosis, which is the gelatinous covering of the eyeball itself, inflammation of the caruncle or plica, that's a medial tissue closest to the nose. The symptoms, pain or pressure sensation in the area around the eye or behind the eye, and then pain with upward, downward, or lateral eye movement. It's important to note that the severity of CAS is not a predictor of overall severity of thyroid eye disease in any individual patient. For example, some patients with a score of zero can have devastating visual loss, constant disabling diplopia, or even severe proptosis with corneal exposure. In contrast, a patient with a higher CAS could have normal vision, no double vision, and minimal proptosis that doesn't impact the quality of life. We strive to reduce the CAS for patients, as lower CAS is clinically meaningful, but is not the best way to classify patients from a disease severity perspective when compared to proptosis. In truth, the CAS is not widely used by clinicians not involved in clinical research. The impact of thyroid eye disease on social interactions, work performance, tasks of daily living, such as driving and computer use, are much more clinically relevant and meaningful. That said, the CAS data is very strong and compelling for VRDN-001. Next slide. What were the baseline patient characteristics? On this slide, we'll go through each of these. I wanna highlight a few points. Beginning with the mean baseline proptosis. In the VRDN-001 treated groups, the mean baseline proptosis was in fact much lower than placebo in this trial and also lower than the level of proptosis seen in patients enrolled in the phase IV teprotumumab trial. It's important to remember that the baseline proptosis correlates to some extent with the patient's potential proptosis response to the drug, based on previous studies in this space. As I discussed earlier with the Hertel, a patient with more proptosis can have more room to improve to get back to their baseline, compared to a patient that has not so much proptosis at baseline. You wouldn't want them to have a big change because that would be an overcorrection. To see such dramatic results in this 10 mg/kg cohort is especially compelling. Basically, it's a tougher population to show improvement in the teprotumumab trial. Stated another way, VRDN-001 causes a restoration of muscles and fat volume towards baseline. When you reduce the size of the muscles, reduce the volume in the fat, you get improvement in proptosis, but less severe proptosis will return towards baseline with less change in the measured proptosis. With respect to the CAS, remembering that the inclusion criteria did not have specific requirements, the mean CAS scores ranged from 2.5- 4.0 points, compared to the teprotumumab phase IV clinical trial, where the inclusion criteria specifically was just two CAS scores, either a zero or a one. The duration of disease among our chronic patients was approximately 94 months. Very long. That's 7.8 years, which is significantly longer than the 5.4 years of disease among the patients enrolled in the phase IV teprotumumab trial. As a tenant of clinical medicine, the earlier in a history of a disease therapy is initiated, the better the clinical outcomes. Our population had their disease for much longer duration than that in the teprotumumab chronic study. A tougher population to see changes in. Enrollment consisted primarily of female patients with approximate age of 50, which is typical for the thyroid eye disease clinical trials and was seen in the teprotumumab chronic trial, too. Next slide. On this slide, we have a summary of the clinical activity measures evaluated at week six. On the summary table, you can see the data separated by each dose cohort. We can see 10 mg/kg and the 3 mg/kg, with a combined dose data for each of those clinical activity endpoints listed above. If you look at this for proptosis, 42% overall response, but for 10 mg/kg, it was 50%. The mean change in proptosis was a 1.6 mm if you pooled the data. For the 10 mg/kg group is 1.8 mm. For the mean change by MRI, it was -2 mm, and the 10 mg/kg was 1.5 mm. Those achieving a CAS of zero or one was 40% overall, but 50% in the patients receiving the 10 mg/kg. The CAS, the mean change was -2.3, but in the 10 mg/kg, it was -2.8. In all groups, the no patient had complete resolution of their diplopia after at the six-week mark after two infusions. Next slide. On this slide, we are taking a closer look at the proptosis response from baseline to week six. If you look at the chart on the left, we have a waterfall plot of individual proptosis change within dose cohorts. The response at week six ranged from 0 mm change up to 4 mm reduction for the 10 mg/kg treated patients, with a mean change of 1.6 mm across both cohorts. With only two infusions, a majority of the VRDN-001 patients achieved a reduction in proptosis at week six. Teprotumumab data at that same point, at week six, was 1.2. A nice reduction in proptosis that exceeded the proptosis reduction noted by teprotumumab at the same time point. The middle chart shows the individual proptosis change by MRI, and to the right is the mean proptosis change. A valuable, readable MRIs are available both at baseline and week six for all 5 placebo patients and for eight of the 12 VRDN-001 treated patients, or four of six from each dose cohort. Two patients from the 3 mg/kg cohort did not undergo a week six MRI, and two patients from the 10 mg/kg cohort have a week six MRIs that were not interpretable due to poor image quality, most typically, the patients moving during the MRI. When looking at the individual proptosis change by MRI, two placebo and one VRDN-001 treated patients who were responders by exophthalmometer were not confirmed by MRI analysis. You can see from the MRI data, VRDN-001 treated patients achieved a mean proptosis reduction of -2.0 mn, compared to a reduction of 0.2 mm in the placebo-treated group. Whether you're looking at the Hertel or the MRI, there was a significant reduction. As found in previous active TED cohorts, the ability to confirm or refute the exophthalmometry data with more precise MRI measures of proptosis is very valuable, given the small sample size in the proof of concept studies. Next slide. Let's look at the CAS details. Turning now to the chart on the left, shows the individual CAS changes for all VRDN-001 treated patients. The top axis shows the baseline CAS, the Y-axis shows change from baseline, and the X-axis and bar color identifies the dose cohort for each patient. As you can see, individual CAS changes ranged from zero to four-point reduction, which is achieved by three patients. The four patients with a change of zero were either zero at baseline or one, which provided little or no room for improvement with treatment. The chart on the right shows the mean change for CAS for patients with for patients with a baseline of greater than zero. Those ones you can see on the plot on the left that had zero are not included on the plot on the right. Placebo came in at - 1.2, whereas the VRDN-001 had a change of - 2.3 points of the CAS. Next slide. This next slide is my favorite slide. This slide shows a summary of the reported adverse events that were occurring in more than 10% in the chronic TED cohorts. You can see that five of the safety events listed were in the placebo cohort, and two were in the VRDN-001 treated patients. Mild back pain was reported by two patients, while two patients reported muscle spasms. The muscle spasms are not surprising with IGF-1 receptor antagonism, as they're a known class effect of this antibody. Leg cramps seem to resolve spontaneously without treatment, and there were no discontinuations due to safety. Importantly, no serious adverse effects. Notably, very much notably, especially to clinicians who have treated patients with teprotumumab, among the patients treated with VRDN-001, no hyperglycemia or hearing impairment events were reported. Let me say that again. In the treated patients, no hyperglycemia or hearing impairment events were reported. As many of you know, both of these adverse events have been recorded in other clinical studies in investigative therapies for thyroid eye disease and also for, seen with teprotumumab. Let's go to our final slide. To summarize the data and to provide my perspective, VRDN-001 resulted in clinical efficacy and demonstrated excellent safety when compared and when utilized in chronic thyroid eye disease subjects, with superior outcomes when compared to the HORIZON phase IV clinical trial when looking at these two cohorts with their six-week outcomes after two infusions. VRDN-001 reduced proptosis as measured both by Hertel and MRI measurements and improved CAS. The safety profile was excellent, with mild back pain and leg spasms noted and no hearing impairment or hyperglycemia adverse events and no infusion reactions. These results confirm that VRDN-001 should be effective in all thyroid eye disease, independent of severity or duration of disease. The safety profile of lowering the dosing and fewer infusions is promising for at-risk populations. I will now turn the call over to Dr. Tom Ciulla, Viridian's Chief Development Officer, to continue the presentation. Tom? Thank you, Kim. We are really excited about this new data in chronic TED for VRDN-001, so we really appreciate your joining us today to present these results and share your insights. I'm going to provide an update on our phase III trials and our recent progress and upcoming priorities for our subcutaneous candidates in development. As Scott mentioned earlier, we are amending the ongoing THRIVE phase III trial evaluating the safety and efficacy of VRDN-001. This slide shows the updated trial schema following the amendment. Previously, THRIVE included three arms: VRDN-001 eight- infusion regimen, VRDN-001 five- infusion regimen, and placebo. Patients were randomized 1: 1: 1 between the arms, and the primary and secondary endpoint evaluation was at week 24. As you can see on the slide, the updated THRIVE design has removed the eight- infusion regimen arm and now only has the VRDN-001 five- infusion arm and the placebo arm. Patients will be randomized 2: 1 in favor of the VRDN-001 arm. The primary endpoint evaluation will occur three weeks following the last infusion at week 15. We continue to expect top-line results in the middle of 2024. The THRIVE phase III trial amendment reflects our growing confidence in the clinical success of the five infusion treatment course of VRDN-001, our assessment of its potency, and key stakeholder feedback from the TED community. Based on the rapid onset of clinical activity prior to six weeks and the limited benefit that standard of care provides from the 18-24 weeks, we believe that our five infusion treatment regimen at a dose of 10 mg/kg has the potential to improve benefit risk for patients. This five- infusion regimen has potential to provide clinically meaningful improvements by week 12 and minimize any potential safety risks to which longer durations of therapy subject patients. Our team has spent a lot of time interacting with KOLs, principal investigators, and treating physicians. They have provided clear feedback that they view the five infusion treatment regimen as a significant improvement, and it also reflects where they believe intravenous treatment standard is already evolving to. Finally, for patients, a five infusion treatment standard could increase convenience and decrease costs by eliminating three trips to the infusion center. Following the chronic TED data today, our team is very close to finalizing the THRIVE-2 phase III trial design. Similar to THRIVE, it is a global quadruple-masked, placebo-controlled phase III trial. THRIVE-2 is evaluating the safety and efficacy of VRDN-001 in patients with chronic TED, as defined by proptosis of 3 mm or more for race and gender, 15 or more months since onset of signs and symptoms and any CAS. There will be two arms: VRDN-001, 10 mg/kg and placebo every three weeks. Additional details include, including target enrollment and randomization, will be provided closer to the start of the trial this quarter. We expect top-line results by the end of 2024. Moving now to our subcutaneous candidates. As a reminder, we have three subcutaneous candidates currently under development. We have VRDN-001, VRDN-003, and VRDN-002. All three candidates are humanized monoclonal antibodies that target the IGF-1R. VRDN-001 and VRDN-003 share the same binding domain and act as full antagonists of the target, while VRDN-002 acts as a partial antagonist to the IGF-1R. VRDN-003 and VRDN-002 share the same half-life extension technology, which provides the opportunity for more convenient dosing intervals every 2- 4 weeks, relative to VRDN-001, which would be weekly or every other week. Let's review our latest progress and upcoming priorities for our subcutaneous candidates. Earlier this year, we completed a formulation work for all three subcutaneous programs, allowing for a concentration of 150 mg/ mL, for administration of a 300 mg per 2 mL dose in subcutaneous clinical trials. In June, we filed with the FDA the initial IND for VRDN-003, and an IND amendment for subcutaneous VRDN-001. Following the submissions, we plan to initiate phase I trials of subcutaneous VRDN-003 and VRDN-001 in healthy volunteers in the third quarter of 2023, with initial data expected in the fourth quarter of 2023. We completed an enrollment of a phase I healthy volunteer trial of VRDN-002, single intravenous and single subcutaneous dose cohorts. Upcoming priorities also include initiation of a pen device supply agreement with an experienced drug delivery device manufacturer in the second half of 2023. Viridian expects to select its lead subcutaneous program by year-end 2023, and to advance the program into a pivotal phase II/III trial in the middle of 2024. I'll now turn the presentation over to Scott to close our presentation today, and then we look forward to taking your questions. Scott? Thank you, Tom. As you can see from the presentation this afternoon, you can understand why we are so thrilled by our data in the chronic TED, which established proof of concept and provide additional momentum for us as we drive our late-stage development toward potential approval. Our vision and goals are clear. We plan to launch with the best-in-class IGF-1R antagonist, followed by a convenient, self-administered that will have the potential to be the first and best-in-class subq pen device in TED. Our IV and subq programs are the foundation of our plan to create a blockbuster franchise in TED. Our long-term vision remains building a fully integrated biopharmaceutical company based on our success in TED. In addition to our work in TED, we have multiple preclinical programs and look to replicate our drug development and launch success in TED, in autoimmune and rare disease areas. We expect to unveil at least one of these preclinical programs later this year. With that, I'll now turn it over to the operator for questions. Operator? The floor is now open for your questions. To ask a question at this time, please press star one on your telephone keypad. If at any point you'd like to withdraw from the queue, please press star one again. You'll be provided the opportunity to ask one question and one further follow-up question. We'll now take a moment to compile our roster. Our first question comes from the line of Gavin Clark-Gartner from Evercore ISI. Please go ahead. Hey, thanks for taking the question. I had three, actually, all on the subq program. First, the INDs were just filed in June, and it seems like they're not cleared yet. I'm just wondering what the gating factor for filing those was. This is Scott, Barrett or Tom, would you like to handle that question? Sure. You know, we've completed work on our PK and PD for our IV program, and, you know, we currently have a lot of programs that are in process, and we're just going through the normal course of action of filing the IND for one and the amendment for the other. There's no, there's no particular issue with any of this. It's all proceeding as planned. Oh, got it. Hey, Gavin. Oh, yeah, go ahead. Sorry, this is Todd. They're just on the normal 30-day clock that we're waiting for clearance with the FDA, more to come on that. Yeah, that makes sense. Thanks. For the initiation of the pen device supply in the second half of this year, is that for the clinical use or the commercial use or both? Maybe just like any form, update on our formulations would be helpful. Yeah. We finished the Gavin, we finished the formulation works at 150 mg/ml, so we could show that we also had for the 300 2 ml pen. This would be for, certainly for the commercial put up, and then we'll be considering whether we can use that pen device early on, or we would use some sort of vial syringe in the early stage and then do a crossover to the final form factor. Okay, got it. For the subq healthy volunteer data in the fourth quarter, how many healthy volunteers will that be? Will that also include serum IGF-1? I don't believe we've disclosed how many healthy volunteers, but I do believe the PK and PD data will be included. ... I got it. Actually, sorry, my last one. I'm just wondering how you're thinking about endpoint for the subq program in a pivotal trial. I mean, you moved the IV dosing from eight to five doses only now, and you've kind of alluded to longer maintenance-style dosing for the subq before. I'm just wondering what the latest thoughts on that are. Thank you. Tom, would you like to take that question? Well, I think as you can see from our results today and from our active MAD study that we released throughout last year, that we hit on a whole variety of endpoints, including proptosis responder rate, mean change by exophthalmometry, mean change by MRI, CAS improvement, safety was excellent. You know, I think we have a lot of latitude and, you know, obviously we haven't thought in great detail about the endpoints for trial design and subq. So more to follow, but I think, you know, I think we've seen the potential efficacy with our assets, and I think we have a lot of potential to show efficacy with these endpoints. Just to add to what Tom suggested, we don't anticipate any new endpoints to be included in these studies. We take our direction from the tradition at the agency and the success of what's been shown beforehand. The question is in terms of timing, that will be worked out as we learn more about our compound and asset. Got it. Thanks for taking the questions. Our next question comes from the line of Michael Yee from Jefferies. Please go ahead. Hey, guys, thanks for the questions. First question was around thinking about the placebo response. I know that you cite the MRI data, which looks fantastic and clearly huge separation from drug. Can you just comment on thoughts around the placebo response when using [exophthalmometry]? I want to pronounce that right. The two folks that were excluded, how to think about that. My follow-up was for Dr. Cockerham, if she's still on there, how to think about trying to compare and contrast the chronic population and efficacy with TEPEZZA versus here, given the different CAS definitions, and how you would compare the two, given the two different patient populations? Thank you so much. Thank you, Michael, for the question. Tom, and maybe you want to follow up with Barrett, speak about the placebo, and then we'll have Kim address the different CAS scores. Sure. You know, with Hertel exophthalmometer, there's some inherent variability to this approach in measuring proptosis. Importantly, in this trial, was a very small sample size, that actually amplifies the variability. Although Hertel exophthalmometer is a standard device to measure proptosis by clinicians, and it's used as a primary endpoint in approval for TEPEZZA, for example, it's subject to inherent variability amplified by our small sample size. This is why we use the MRI to confirm, because it's a much more precise measurement. Our phase III trials will be strengthened by the larger patient numbers in both the active arms and the placebo arms, and we expect that variability to be diminished by this larger sample size. Again, we view MRI. Although we view it as an exploratory endpoint, it's a much more precise measure and allows us to really assess proof of concept. Makes sense. I think small numbers, but also just looking at the totality of the drug arm versus placebo arm, you clearly see pretty much everyone responds in the drug arm. I think that makes sense. Then maybe comparing and contrasting the efficacy given slightly different patient population definitions and, you know, for example, if you had just low CAS scores, what would you have seen with those patients more comparable to TEPEZZA study versus yours is a more all-comer, and we clearly see efficacy. How does the doctor think about those two populations? Thank you. I can take- Go ahead, Kim. Sure, I can take that. The thyroid eye disease is a continuum. Cutting it up into little pieces is not what I see in real world. Like the TEPEZZA has been effective in white chronic eyes, which would be 0-1 CAS, but it's also been effective in patients who have more of a persistent inflamed state with higher CAS scores despite years or decades of disease. The IGF-1 receptor has increased expression in all flavors of thyroid eye disease. Although we are comparing slightly different groups in that one had a longer duration, that would be the Viridian mark in Viridian study, and the other had a higher CAS, I think that there's no reason to think that this molecule will be different than TEPEZZA or less effective than TEPEZZA. If anything, things are pointing towards improved efficacy, lower dose, fewer infusions. Yeah, I agree with you. We're not comparing apples to apples, but if anything, we're comparing an easier apple to deal with in the TEPEZZA chronic study to the little bit more complex in our study. I'm just Barrett here. I just want to add something to what Kim has just shared. It's important to recognize that in HORIZON's phase IV study, there were two phrases for their inclusion criteria. The first phrase was a CAS of zero or one. There's an or there, and so there's a second phrase, and any patient who had stability of their diplopia and of their proptosis for a year was admitted with any CAS score. What I believe we're seeing is, in fact, there were patients in the HORIZON study that did have CAS scores greater than one. I believe our definition, what we chose to use for inclusion, exclusion criteria, is a much more real-world experience of what the clinician sees for chronic patients. Recall that in North America, clinicians have not been using CAS to analyze or categorize the disease state. That is something that is new and just people are learning about because of these trials. I believe what we've seen in our chronic definition is exactly what the clinician does in his or her office. Thank you. I totally agree. Yeah, I think that really the key is the CAS, whether it's the CAS or the Hertels, what it comes down to is when I'm talking to my patient is: Is this disruptive? Is there thyroid eye disease? Not when it's, when it happened or how red their eye is, but is it impacting their quality of life and their ability to be productive? That's what, you know, pushes me and other clinicians to decide to use TEPEZZA or another intervention. This CAS is very, it is not utilized clinically by almost anyone. It's just getting... It's the same with the Gorman score, the diplopia score. That's something that clinicians have not used prior to this, these clinical trials. Just to be clear again, Barrett here. Remember that if one carefully reads the advisory committee for the original HORIZON approval, it was clear from the agency's perspective, they don't differentiate chronic from active disease and strongly felt clinicians cannot differentiate chronic from active disease. That is why the initial label was so broad. In fact, with HORIZON's phase IV study, they reiterated that statement in the sense of reiterate the fact that they're saying chronic and active is but one disease. In the active, the inflammation is in the front of the eye. In the chronic state, it's behind the globe in the orbit. Great. Thank you, guys, on both of those questions. Appreciate it. Thanks, Michael. Our next question comes from the line of Derek Archila from Wells Fargo. Please go ahead. Hi, this is Adam on for Derek. Congratulations on the data. Very encouraging, and thank you for taking my questions today. Just a few from us. We were wondering, what is the rate of response you were seeing on proptosis? Can you put today's data in context relative to HORIZON's chronic data from, like, a baseline characteristics in efficacy standpoint? Just really quickly, also, how should we interpret the differences in dose response for proptosis, between the Hertel and MRI methods, particularly given, you were just highlighting that the MRI method is a more precise approach? Thank you. Tom, if you could take these on the rate of response. Sure. we had a, as you saw from the slide deck, we had a proptosis responder rate of 42%. That was at after only two infusions, and that was at six weeks. That compares favorably to what we saw with TEPEZZA after two infusions at six weeks. Theirs was 36%. Cross-trial comparisons, you know, really aren't valid, but numerically, ours is slightly ahead. I think that was your first question, and then you asked about baseline characteristics, and I think that's a really important point that we discussed in our prepared remarks. I just want to reemphasize that we had in our 10 mg/ kg cohort, the baseline proptosis measured 21.1 mm, and that compares to 24.4 mm in the phase IV chronic TEPEZZA trial. We were going up against a relative floor effect, and as Kim and Barrett mentioned in their prepared remarks, this created a higher hurdle for us. Furthermore, we had much more chronicity than was encountered in the TEPEZZA phase IV trial. For example, our mean number of months since the onset of TED symptoms and signs was 94 months versus their 63 months. That also creates a higher hurdle. Yet we had a result that was excellent. We had a improvement overall of 1.6 mm, which again, cross-trial comparisons aren't valid, that compares quite favorably than the 1.2 mm we saw after two infusions in the TEPEZZA trial. I think the baseline characteristics, you know, created a bit of a floor effect with respect to baseline proptosis and a higher hurdle with respect to chronicity, yet we had a really excellent response. Yeah, I just want to add to what Tom said. We actually began, by luck of the draw, with our cohort in the 10 mg/kg group. We had two strikes against us. Those patients had relatively low proptosis, and they had much longer disease. The fact that we saw the results we did suggests that it's especially compelling because we had a difficult group to see results in because of their level of proptosis and the longevity of their signs and symptoms. I think the final question was around dose response by exophthalmometry versus MRI. If you look at the values numerically, you know, one, they're not consistent with respect to dose response. They do show a consistent, impressive improvement, and I think the answer to that is that they're small sample sizes here. I think, you know, the MRI is important to us because it corroborates a measure that is somewhat variable, as I mentioned earlier. I, you know, I think both doses showed really compelling clinical effect after only two doses at six weeks. Furthermore, I think the lower dose, the 3 mg/ kg dose, gives us confidence that we have a path forward with a low volume subcutaneous injection. Great. Thank you. Maybe if I could just get one more in on the subq. Could you confirm, whoever you choose for the pen device partnership, will they have a validated product with, like, an existing drug that's already approved with that device? Yes. Yes, Adam, this is Scott. I can take that. Yes, it is. They have had marketed products before, so. Great. Perfect. Thank you, guys. Our next question comes from the line of Alex Thompson from Stifel. Please go ahead. Hey, thanks for taking my questions. Again, congrats on the data. I guess, two for me. I guess to follow up on the proptosis by exophthalmometry, I guess understandable that the N are small and there's variability, you know, by not disclosing it, should we assume that the reduction is at least the same as the low dose, around 1.5 mm mark? I guess, why not just disclose it? Then on the phase III trial, can you comment on how the enrollment is going and if the change from, you know, the two- dose cohorts to the single- dose cohort had anything to do with slower enrollment than expected? I think you reduced the overall end of the study now and the primary endpoint, the timeline has remained the same. Thanks. Tom, if you'd like to handle the first one, the proptosis exophthalmometry. Sure. You know, as I mentioned earlier, there's a lot of variability in here in the Hertel exophthalmometry. The sample size is exquisitely small, right? It's two in one cohort and three in the other. You know, it almost with such high variability and such small sample sizes, it's almost a meaningless value. What's really important here is the response by MRI. You know, as we disclosed in our slide deck today, the improvement by MRI was 2 mm in the treated subjects after only two infusions. By in the placebo group, there's essentially no change. There's a - 0.2. I think that, you know, that level of separation with a precise test like MRI, gives us lots of confidence that we're seeing a very potent biologic effect. Let me add something there, too. I totally agree with Tom. Proptosis is one metric of the disease. It is not the entirety of the disease. In fact, it's healthy to think of it as a proxy for the disease. You've got to look at the totality of the data here. These patients showed improvement in proptosis, improvement in CAS, and at some point in the future, we'll be sharing additional data as we get it, more analysis of it, of how they've changed in their quality of life and facial appearances. What we're seeing is significant changes in multiple metrics with just two infusions in a chronic cohort. This is Kim. If I could just add to that, as an investigator that's supposed to be masked, it's very obvious who's getting the drug. The patients are thrilled. They, within the, you know, the first infusion, after the first infusion, they're getting improvement. After the second, they're often, you know, no pain, dry eye symptoms are better. You know, they're just doing much, much better. So I want to really emphasize what Barrett just said, that this is to look just at proptosis in a very multifactorial disease like this, where quality of life is so impacted, it's just a little snapshot of the whole process. Yeah- [crosstalk] Go ahead, Tom. Alex, regarding your second question regarding THRIVE enrollment, we continue to believe that mid-2024 is the right guidance for top-line results. You know, we're in the process of implementing the amendment across IRB approval, FDA discussions, you know, necessary site interactions and training, and this will take a bit of time operationally. I'd like to just build on what Tom was saying. This change came out of a lot of out in the field work by the team that you're talking to today, as well as myself and our product development team, speaking to doctors that treat the patients, speaking to our PIs, speaking to key opinion leaders. When they would see the eight versus five, they thought, well, the five would be much more attractive for the patients. It's a faster time to do a crossover to placebo. It's faster infusion time at each session of the infusions, and it's just fewer infusions, so the patient wouldn't be burdened with the three extra trips to the infusion center. We also thought it also balanced the safety and and efficacy for these patients because we had heard that, during the pandemic, there wasn't as much TEP around, and people only got five infusions, and they did reasonably well. There was a lot that really informed our decision with this, but it had nothing to do with the safety, and it had nothing to do with enrollment. Great, thanks so much. Just to add to that, we wanted to remain flexible. We didn't want to be looking in the rearview mirror. We wanted to see where the market is moving, and we see that the market is moving to fewer infusions and a smaller dose and looking for subcutaneous administration. Our next question comes from the line of Thomas Smith from Leerink Partners. Please go ahead. Hey, guys. Good afternoon. Thanks for taking the questions, and congrats on the data. A couple questions on my end. I guess, first one, safety. You commented on the preliminary data as of the May 30th data cutoff. Just wondering if you could remind us of the duration of follow-up you're collecting for these patients, and if you could comment at all on whether there's been any incidents of hyperglycemia or hearing impairment after that May 30th date? Tom, would you take that question, please? Sure. you know, I don't think we're ready to disclose beyond the data cut that we did disclose because, you know, the data needs to be verified and cleaned and assessed. So far, the safety profile has been excellent. We've had no serious adverse events, no hearing impairment, and no hyperglycemic events. We're really pleased with the safety profile so far, as were we with the active TED cohorts in our multiple ascending dose studies. Okay, understood. Then, just a quick follow-up on the changes to the THRIVE program. Can you comment on what happens to patients who are initially randomized to the VRDN-001 infusion arm? How are these patients being treated with respect to the updated trial design and analysis plan? It's, Tom, would you like to answer that fair? Sure. A good question. you know, their data will be used in the safety, obviously. Any patients that have gone beyond five infusions would be censored. Any patients that have gone less than five infusions would be converted to the five infusion arm. Okay, that's helpful. Just one last question. I was wondering if you could expand on some of the comments about what logistically needs to happen to enable these study design changes. Do you have to go back and clear the IRB process at each institution and reconsent patients? Or sort of, I guess, just help frame how disruptive you think this may or may not be? Tom, maybe you can speak to we have sites in the central and then some individual, but that process is underway. As I alluded to, you know, as you're alluding to, these processes take time. We do have to file an amendment to the IND. We do have to, you know, file with the IRBs. You know, central IRB does create some economies of scale because many of the sites are under central, but there's also local IRBs. As you know, this is a global trial, we're also, you know, implementing these changes globally. All of these regulatory and ethics committee interactions do take time. As Scott said, not only do the ethics committees and regulatory interactions take time, we took great time and caution in discussing this with KOLs, with our investigators, and really with the TED treating community. There's a large amount of support for this, shorter course of infusions, as Scott just mentioned. Got it. That makes sense. Thanks for taking the questions, guys. Thank you. Our next question comes from the line of Gregory Renza from RBC Capital Markets. Please go ahead. Great. Thanks. Good evening, Scott and team. Congratulations on the news, thanks for taking my question. Two questions from me, Scott, primarily for Dr. Cockerham. First, just on the differentiation of VRDN-001. Perhaps Dr. Cockerham, just based on this early data and maybe your expectations for a target product profile, could you just help us quantify and maybe even characterize who would be candidates for the Viridian drug, but potentially not TEPEZZA, just based on your view on the data so far and the potential patient profile? Then just secondly, I know that you were encouraged by the safety profile. Just from a clinical standpoint, how would you explain the potential avoidance of hearing loss with the Viridian asset versus TEPEZZA, whether it's partial or full antagonism or otherwise? Thanks so much. Thank you. First off, during the last three years, I've seen approximately 1,000 patients. Of those 1,000 patients, only 200 were infused with TEPEZZA, so only 1/5. That was primarily because patients had one of two problems. They couldn't get an authorization, and because their insurance company wouldn't accept non-inclusion criteria of the clinical trial. Let's say the cap was off, or they had an optic neuropathy, or they just had the insurance company that was insisting they have rituximab or something silly. The other patients were elderly, frail, too old or too young, or with preexisting hearing loss, preexisting gastrointestinal issues to include inflammatory bowel disease symptoms, or had poorly controlled prediabetes or diabetes and concerns for hyperglycemia by their primary care endocrinologist. What I'm very heartened by is that this potentially is showing us efficacy that's thrilling the patients that are getting it, with a really excellent side effect profile. I think as part of the second question, the hearing was occurring, at least in my patient population and the published population, either after the third, fourth, or fifth infusion, and it was in patients getting the full dose, so 20 mg/kg. It happened more commonly in patients that had preexisting hearing issues, but it did happen de novo, which is scary. As far as the hyperglycemia, the hyperglycemia not only happened in patients who had prediabetes or diabetes. There were patients who had normal hemoglobin A1C, no history of diabetes, where they then had hyperglycemia issues. Patients have been hospitalized with really high blood sugars that make them sick. I'm very heartened to see this level of efficacy at these very small doses with only two infusions. That's why I think this is gonna really solve a problem because all those patients that I didn't treat are still out there in need of therapeutic intervention. That's great. Thanks so much for the color. Thanks. Our next question comes from the line of Kalpit Patel from B. Riley Securities. Please go ahead. Hey, good afternoon. This is [Andy Fleischer] on for Kalpit. Thank you for taking the questions. Can you help us understand what prompted the exclusion of the eight infusion regimen? It's understandable to differentiate with a five infusion regimen. Why not have the extra option on the table? I think Andy, I'll give you the headlines on that. When we looked at it, about to have the exposures at the eight and the five, if the five would've been better, it would obviously been the preferred choice of the treating physicians that we learned from talking to them. They didn't necessarily want a me-too tepro coming out. They wanted something that was differentiated. Because they saw the early onset of response and deep response, they suggested, as Tom mentioned, we did a lot of work. We just came up with that idea. We bounced it off the statisticians. We talked to more physicians and more KOLs, and that's how we arrived at that. It was not just an exclusion because we didn't want the data. Tom, can you add anything to that? No, not really. I think, I think five is much preferred. As Scott said, eight's a bit of a me-too. We have a lot of confidence, especially given the results we've seen in both the active and chronic MAD cohorts. We're very confident that five infusions will improve upon what we saw after only two infusions, which in of itself is quite impressive. I think it's a matter of, you know, the potential efficacy signals we're seeing and what the market wants, what patients want, and what our physicians want. [crosstalk] That makes sense. Andy, let me add one more thing. HORIZON's drug was a failed oncology drug 20 years ago, used for sarcoma. That, in the oncology research and the ecology trials, is where that eight infusion regimen came from. It never came from dose exploration. HORIZON did not do dose exploration. We did dose exploration in our MAD segments of our study, and we recognized that there was no legitimate reason to think that an eight infusion regimen was the correct regimen. That is why we used that, in a sense, as a fallback position and recognized that the five infusion arm is much more compelling, both to patients and to caregivers. That's helpful additional color. Then one follow-up for the KOL. You touched upon this a bit. Can you elaborate on whether patients with high baseline proptosis or high baseline CAS are more likely to achieve a proptosis response from your experience? It depends. There are some patients who don't respond to TEPEZZA. That said, most patients do, and there's not a consensus as to which patients do less well. Certainly, if it's a recent onset, the eye's red and swollen and they're proptotic, they may have significant change after just one infusion of TEPEZZA. When you get into the chronic patients with 10 to 20 years of quiet proptosis who've defied surgery, radiation, steroids, and nothing worked, I do couch my informed consent in those patients that, you know, likely they're not going to get as much improvement as I would expect in a patient that's much more recent onset with more inflammatory findings. Okay. That's helpful. Thank you for taking the questions. Oh, absolutely. Our next question comes from the line of Jason Butler from JMP Securities. Please go ahead. Hi. Thanks for taking the questions, and let me add my congrats on the data as well. I just have one for Dr. Cockerham. You made a comment before about a focus on extending duration of clinical responses. Just wondering if you could give us your thoughts on patients getting repeat courses of therapy over several year time frame to maintain benefit, and to what extent that's happening today with TEPEZZA? Thanks. Sure. Each patient is different. thyroid eye disease is a continuum. We have the patients that are inflamed, the patients that are quiet, the patients with big proptosis, the patients with just double vision. What I would love to see evolve over time is that we individualize the therapeutic regimen. That's what I'm doing currently with TEPEZZA. Not everybody gets eight infusions, and not everybody gets 20 mg/kg. If I have an older, frail patient, and I'm worried about side effects, I'm gonna alter the dose. I'm gonna alter how many they get. If patients start to have problems with any side effects, I'm gonna pause until that side effect resolves or significantly improves. What I'm hoping is that we start to do more individualized regimens. Some patients are gonna probably require, you know, two infusions and then maybe subcutaneous for six months and then try to taper off. I'm a neuro-ophthalmologist. I manage patients with giant cell arteritis. I have Actemra, monoclonal IL-6 antibody. I have the option of infusion or subq. At some point, I'm gonna try to start to taper the patient off and see whether their giant cell arteritis recurs. I very much see the way that I'm gonna treat the thyroid eye disease patients is very similar to how I treat giant cell arteritis or myasthenia gravis or any of these ones where there's options for therapeutic intervention, rather than sticking to, you know, one script for all. Just to add to what Kim suggested, the experience in ophthalmology is, first it's a regimen, and then clinicians treat the patient to some clinical endpoint. What we envision and suspect is that at some point in the future, in this arena, the therapy will go from induction maintenance. It may be, just as Kim suggested, a patient might need induction with IV medication and then maintenance with subcutaneous administration. That is our expectation of really where the market is going and should go. Always keeping an eye on the side effect profile, because obviously you don't want to trade the eyes for the ears or the eyes for the bowel. I think individualizing to optimize outcome but also prevent any side effects is super important, not only to clinicians, but patients and their families. Our final question comes from Laura Chico from Wedbush Securities. Please go ahead. Hey, thanks very much, guys, for fitting me in. I'm sorry to go back to this, I'm still stuck a little bit on the placebo proptosis response by Hertel. You know, if I'm looking at, I believe it's slide 25, there were two placebo participants that were responders by Hertel. I guess I'm trying to back into a number here, and I'm getting to something like a 1.6 mm reduction. Just, can you just simply maybe clarify what was the average placebo proptosis reduction by Hertel? Tom, would you like to take that question? Sure. You know, I'm not sure if I. Are we disclosing this? Is this something that we're? Yeah. Hey, hey, Laura. Let me speak here. The Hertel response for placebo by proptosis is well under what you just estimated. Again, similar to the approach that we took in active TED, given the small numbers, we see kind of no value in the placebo proptosis by exophthalmometer. The best way to think about placebo, based off of data that's in the public domain, is based off of the larger sample size in the teprotumumab then follow-up trials. Then following our larger phase III studies, that'll be the better way to think about placebo relative to our phase III data. Perfect. Okay, thank you very much for that. I guess I apologize if I missed this. With the amendment to phase III, the THRIVE study, how does that change the powering assumption now on the one arm? I guess, what are you powered for at week 15? Yeah. Yeah, thanks. We, the powering of that trial is well above 90%, Laura. Great. Okay, just last question here. I know that it's not gonna be required from a regulatory perspective, but was kind of discussed a little bit earlier. If you're moving to a five-dose regimen, how are you gonna be assessing durability of response? Just that would seem certainly more important from a payer perspective. Not curious how you're gonna be conducting longer-term follow-up, but how are you thinking about that? Thank you very much. Yeah. Tom, maybe you could review the endpoints and the follow-up on that. Sure. Could you repeat the question? Sure. Sorry. How are you guys looking at durability of response well past the study endpoint and how long those effects are maintained? You know, we're going to convert to this five infusion regimen versus placebo, randomizing a 2 to 1 fashion. The primary endpoint will be at 15 weeks. We're gonna follow those patients out for a total of 52 weeks, and we'll be evaluating durability along the way. Thanks very much, guys. I would now like to turn the call over to Scott Myers for closing remarks. Thank you, Operator. We are excited today to report more positive data from our TED trials of VRDN-001 and our phase III updates, and also really the progress our team's been making on our subq programs. I'd like to thank the investigators who have worked on our studies, the patients who have volunteered to help advance research in TED, our key opinion leaders and advisors that help us truly understand patient and market needs and help to inform our strategy, and finally, our Viridian employees, who work every day to innovate and develop important new therapies for patients. We hope everyone has a great summer. Before we sign off, I wanted to mention one housekeeping item related to our upcoming Q2 earnings report in August. Because we've provided such a comprehensive update today, we will announce Q2 earnings via press release only. We will resume a regular quarterly call in November for our Q3 earnings report. If you have any additional questions or areas of follow-up, please reach out to Todd James or Louisa Stone. Thank you again for joining us, and with that, we will close the call. Thank you, ladies and gentlemen. This does conclude today's call. Thank you for your participation. You may now disconnect.