Viridian Therapeutics, Inc.

Later, we will conduct a question and answer session and instructions will be given at that time. As a reminder, this conference call is being recorded. I would now like to hand the call over to Ms. Louisa Stone, Manager of Investor Relations at Viridian. Please go ahead.

Thank you and welcome everyone to our first quarter 2024 earnings conference call. The press release reporting our financial results and corporate updates is available on the investors' page of our corporate website at www.viridiantherapeutics.com. Joining me on the call this morning are Steve Mahoney, our President and CEO, Tom Shula, our Chief Medical Officer, and Sean Wu, our Chief Business Officer. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements regarding our financial outlook, in addition to 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 form 10Q and 10K on file with the SEC. I would now like to turn the call over to Steve Mahoney, our President and CEO.

Thanks, Louisa, and welcome everyone to our first quarter earnings call. I'll start by giving a brief overview of Viridian, and then we'll get into more detail about our programs and recent progress. For those of you who are new to the Viridian story, Our strategy is to identify market opportunities where there's a clear unmet need and where there is potential for us to develop differentiated products. We then aim to engineer the best possible therapeutics and then move rapidly to advance our programs to patients. Turning to slide four, slide four shows our pipeline, which includes both a thyroid eye disease or TED portfolio, as well as an FCRN targeting autoimmune portfolio. We have several exciting updates to provide across our pipeline today, which we'll get into next. We're really excited to highlight for you today the significant progress that we've made across the business so far this year. Beginning with our 001 IV program, we are pleased to announce that Thrive, our phase three trial evaluating 001 in patients with active TED, completed enrollment in March. In fact, not only did Thrive reach the target enrollment of 90 patients in mid-March, but we exceeded enrollment for a total of 113 patients due to strong patient demand at our clinical trial sites. We expect to share top line results for Thrive in September 2024. Thrive 2, our phase 3 trial initiating OO1 IV in patients with chronic TED, continues enrolling and is on track for top line data at the end of this year. Lastly, for 001, we are announcing that we anticipate filing a BLA for the 001 program in the second half of 2025. For our subcutaneous 003 program, which we believe has the potential to be best in class, We recently completed a positive type C meeting with the FDA, and we are moving forward with our preparations for our pivotal program in line with our previous guidance. We will provide additional updates for the 003 program before we start that pivotal program, which remains on track for mid-year. We are also progressing our FCRN portfolio as planned. We are aiming to file an IND for 006 by the end of this year, and we plan to share 008 non-human primate data in the second half of 2024. Lastly, we ended the quarter with $613 million in cash, cash equivalents, and short-term investments, and we maintain our cash runway into the second half of 2026, also as previously guided. Now I'd like to turn to our TED portfolio and talk more about the programs and our progress in a bit more detail. As a reminder, Ted is an autoimmune condition characterized by inflammation and damage to the tissues around and behind the eyes. This leads to symptoms including proptosis or bulging of the eyes, redness, swelling, double vision, and retraction to the eyelids. In severe cases, Ted can be sight-threatening. With those symptoms as a backdrop, there is already a large market opportunity in TED that comes with global growth potential and an expansion that can come with better options for patients. There is an estimated 190,000 people in the U.S. alone who are living with moderate to severe TED. These patients are only served by one marketed IGF-1R IV therapy currently, which generated approximately $1.8 billion in sales in just the U.S. alone in 2023. This approved therapy requires eight infusions every three weeks, which can be a significant burden for patients. We see opportunity for us to provide differentiated options for TED patients with both our IV and sub-Q programs. Because TED is an autoimmune disease characterized by flaring symptoms, patients with moderate to severe symptoms struggle with quality of life issues that make it hard for them to drive, work, and even sleep. Because it is a flare-based disease, it is considered a new start market, which means that it doesn't matter when a patient was diagnosed because you need to treat the flare or the onset of those symptoms. This new start market also means that all patients experiencing symptoms will have the opportunity to choose from available treatment options with no chronic treatment to displace. Once a flare is treated, patients do not remain on an anti-IGF-1R therapy. So when a subsequent flare arises, physicians will have the opportunity to choose from available treatment options, including potential new options to manage these flares in their patients. This is a great position for our IV and sub-Q programs in TED because we believe that we are developing potential best-in-class therapies in a drug class that is shown to be highly effective in inhibiting IGF-1R and in treating TED. Turning to the specifics of our product candidates, Viridian is developing two anti-IGF-1R antibodies for TED, 001, which is delivered intravenously, and OO3, which is delivered subcutaneously with the potential for self-administration. As you can see here, OO3 and OO1 have the same binding domain, and we expect them to bind IGF-1R similarly. They differ because OO3 is engineered to have an extended half-lens, which we have shown to be 40 to 50 days in healthy volunteers, which is four to five times that of OO1, its parent molecule. With O01, we hope to have a fast-to-market, differentiated IV therapy for patients with fewer doses and a shorter infusion time than the current standard of care. With O03, we hope to develop a convenient, less frequent, low-volume therapy that patients can self-administer at home. Let's review the O01 program, our progress, and what makes us excited about the Phase III readout that we expect in September. On slide 11, this is a reminder that we've already shown robust clinical activity with O1 after just two infusions in a phase two clinical trial in active TED. This robust activity is across all key areas of the disease, proptosis or the bulging of the eyes, clinical activity score, and diplopia or double vision. We have added data to the clinical trials after two doses on this slide to show the data side by side. While cross-trial comparisons are difficult, we are encouraged by the clinical responses observed after just two doses of OO1. On slide 12, you can see that OO1 was well-tolerated in active TED patients with no serious adverse events, no infusion reactions, and no discontinuations. Similarly to active TED, in patients with chronic TED, just after just two infusions, O01 meaningfully reduced disease burden across each disease point as well. On slide 14, O01 was also well tolerated in chronic TED patients. Based on this phase two data, we believe that the clinical regimen of O01 with fewer infusions, shorter infusion time, and lower cumulative drug exposure has the potential to be a better choice for moderate to severe patients with TED. Now turn to our phase three trials for 001. I would like to take a moment to thank all the patients and clinical trial site teams who have participated in our Thrive trial. We're not done yet, and our achievements so far would not be possible without them. As we announced today, we completed enrollment for Thrive in March with 113 patients, which exceeded our enrollment target of 90 patients due to strong demand and interest at our clinical sites. About half of Thrive's patients were from the US and the other half came from Europe. We expect to provide top line results for this study in September of this year. Thrive 2, our second pivotal study in TED, is ongoing and on track for top-line readout at the end of this year. In addition to Thrive and Thrive 2, we recently initiated Strive, which is a planned safety study. Strive is a study of O01 in TED patients to complete the sufficient safety database for BLA submission alongside the patient numbers from Thrive and Thrive 2. In conclusion with O01, we are developing a potentially differentiated IV therapy for patients with fewer doses and shorter infusion time than the current standard of care, while inhibiting the same IGF-1R target, which has been shown clinically and commercially to be effective in treating TET. We are very excited about bringing forward O01 as a potential option for patients, which could mean significantly less drug for patients, fewer visits to the infusion center, lower volumes, and less infusion share time. Our next program, subcutaneous 003, will take this differentiation even further with the possibility of lower frequency subcutaneous administrations and potential for at-home self-administration using autoinjectors. We know from market examples that a later entrant subcute therapy can convert meaningful portions of an existing IV market. We've included two of those examples here. In each of the cases on this slide, sub-Q offerings grew the overall market size of the class, in addition to quickly commanding a significant share of the IV markets. And keep in mind that these sub-Q examples have the same or more frequent dosing than their IV counterparts. This would not be the case with OO3, which is designed to have potentially a best-in-class dosing profile. Also, it is important to point out in both examples that neither of these are a new start market. Again, the TED market is a new start market where we need to treat flaring disease or onset of symptoms as opposed to trying to convert patients from a long-term chronic therapy. With OO3, we hope to provide patients with an anti-IGF-1 arc therapy that is a better option with respect to less overall drug exposure and more convenience. On slide 19, We show the complete data set from our phase one healthy volunteer study of OO3 to assess PK and PD. The update here is the inclusion of the last cohort, cohort five, where participants received two doses of OO3 28 days apart. The data confirms the differentiated PK and PD for OO3 seen in the first four cohorts with an extended half-life of 40 to 50 days and sustained increased levels of the PD biomarker IGF-1. On slide 20, you can see that the subcutaneous OO3 was well-tolerated in the phase 1 study, including in the latest cohort 5, with no serious adverse events or discontinuations related to treatment, and observed adverse events were generally grade 1 and mild. As we shared previously, our pharmacokinetic modeling for OO3 that showed that or predicts that three potential dosing regimens are available to us. 003 every eight weeks, every four weeks, and every two weeks could achieve or exceed the exposure levels of 001 that we saw in the active and chronic studies that were correlated to robust clinical activity for our Phase II clinical trials intent. This gives us a lot of optionality as we move towards our pivotal studies for 003. and importantly gives us the potential to develop for patients a best-in-class, low-volume, sub-Q delivery option. We are pleased to announce today that we have completed our Type C meeting with the FDA, and we are on track to initiate pivotal clinical trials for the OO3 program. We will share more details on the pivotal trial design before we start those studies. Now, turning to our FCRN portfolio, On slide 24, in addition to TED, and consistent with our development strategy, we are developing an exciting portfolio of potential best-in-class FCRN inhibitors to address the unmet needs of patients living with autoantibody-mediated autoimmune disease. FCRN inhibitors represent a large market opportunity. The first FCRN inhibitor, FGART or VivGART, is approved for myasthenia gravis and is in registration for CIPD. And it's already annualizing to over $1 billion in annual sales. Myasthenia gravis alone is a large market with projected sales of over $4 billion annually by 2028. In addition to myasthenia gravis, as you can see from the slide, there are additional sizable autoimmune indications that would meaningfully add to the FCRN opportunity. Our FCRN franchise includes two assets, OO6 and OO8. With OO6, we are excited to have the only other FCRN-targeting FC fragment in development, other than F-cartigamide. Argenix has shown that its FC fragment achieves substantial efficacy while sparing an effect on albumin or LDL, and shows better tolerability than the full-length antibodies. We're on track to submit an IND for OO6 by the end of this year and look forward to sharing more about the program in the future. Next on the right is OO8. Our protein engineering efforts identified a molecule derived from FC fragments that both extended the half-life and generated meaningfully deeper IgG reductions in animal models. We believe O08 is a potential best-in-class extended half-life molecule targeting FCRN with the potential to more durably suppress IgG. We are on track to provide O08 non-human primate data in the second half of this year as guided, and we are excited to bring forward this portfolio of next-generation FCRNs to potentially offer patients a more convenient dosing profile compared to current weekly IV or sub-Q infusions. In addition, by aiming to improve the duration and depth of IgG suppression with O08, we hope to offer a best-in-class option for patients.