Viridian Therapeutics Study update

Please go ahead. Thank you, Leah, and good morning, everyone.

Thank you for joining us to discuss Viridian's VRDN-008 phase I results and FcRn portfolio plans. You can access the press release and slides for today's call on the Investors page of our corporate website at viridiantherapeutics.com. Before we begin, I'd like to remind everyone that today's call and webcast will contain forward-looking statements, including statements about our portfolio plans. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those forecasted. A description of these risks can be found in the forward-looking statement disclaimer in the press release and slides issued today, as well as our SEC filings, including our Form 10-K, eight-K. With me today are Steve Mahoney, our President and Chief Executive Officer, Radhika Tripuraneni, our Chief Medical Officer, and Shan Wu, our Chief Business Officer.

With that, I'll turn the call over to Steve.

Thanks, Greg, and good morning, everyone. Thank you for joining us to discuss the VRDN-008 phase I results. We are really excited to announce that 008, our half-life extended FcRn inhibitor, when delivered subcutaneously, demonstrated what we view is a potential best-in-class FcRn profile. We believe subcutaneous 008 can deliver deep and sustained IgG reductions with an every eight-week dosing regimen, which represents a highly differentiated FcRn-targeted therapy for patients. Based on the strong 008 product profile, we plan to progress directly into pivotal development, initiating at least one registrational trial in 2027, starting with myasthenia gravis in mid-2027. Now, let's briefly revisit the 008 molecule and the target product profile.

VRDN-008 is licensed from Paragon Therapeutics and is a bifunctional molecule comprising an Fc fragment with an albumin-binding domain, designed to replicate the established efficacy and safety of Fc fragments while delivering sustained reduction of the pathogenic antibodies that drive autoimmune disease. Very proud to say that subcutaneous VRDN-008, with the data today, has exceeded our target product profile, demonstrating a half-life of 15 to 18 days, which is up to six times longer than those of first-generation Fc fragments. This led to deep and sustained IgG reductions through eight weeks after dosing in healthy volunteers, with 74% IgG reduction at peak, supporting a potential every eight-week dosing schedule. VRDN-008 also demonstrated a safety profile that spared albumin and LDL and was generally well tolerated, with no serious adverse events or dose-limiting toxicities. With that, I will turn it over to Radhika Tripuraneni to present the data in more detail.

Thank you, Steve. As mentioned, we are highly encouraged by this initial VRDN-008 clinical data. We are the first to show clinical PK and PD data for a half-life extended FcRn inhibitor, and we believe these results are best in class. In this phase I clinical trial, healthy volunteers were dosed with subcutaneous VRDN-008. The graphs here show PK and PD data after two doses, one administered at the start of the study and another one at week four. As you can see on the left, this data demonstrates a half-life for VRDN-008 of 15 to 18 days, which we believe is a highly distinct and differentiated PK profile for VRDN-008 relative to all other first-generation FcRn inhibitors. For reference, VYVGART, the current FcRn market leader, has a half-life of three to five days, as described on their label.

On the right, IgG reductions were rapid and sustained through eight weeks after dosing, achieving a peak reduction of 74%, which has historically translated to strong clinical performance for first-generation FcRn inhibitors. This profile exceeds expectations and unlocks for VRDN-008 to be dosed subcutaneously every eight weeks. As you know, the standard of care for FcRn inhibitors is weekly dosing. We believe VRDN-008's sustained response has the potential to transform FcRn treatment for patients by providing disease control with substantially greater dosing convenience. On to safety. VRDN-008 demonstrated a safety profile that spared albumin and LDL and was generally well tolerated. There were no serious adverse events or any dose-limiting toxicities observed in the trial, which is a great place to be. With these data in hand, we modeled the response of IgG reduction with every four-week and every eight-week subcutaneous dosing for VRDN-008.

When we designed VRDN-008, we set out to develop an FcRn inhibitor capable of Q4 weekly dosing. Our PK/PD data and modeling clearly demonstrate that we have surpassed that goal, enabling a potential Q8 weekly dosing regimen that sustains IgG reductions, exceeding our expectations. In fact, our model shows that every eight-week dosing of VRDN-008 surpasses the peak IgG reduction seen with first-generation Fc fragments. We are excited to advance the Q8 weekly subcutaneous VRDN-008 regimen into registrational studies, starting with MG. Let me now walk you through our registrational plans. We plan to initiate at least one registrational trial in 2027, starting with myasthenia gravis in mid-2027, assessing every four-week and every eight-week subcutaneous dosing versus placebo. The study will be randomized one-to-one-to-one with MG-ADL as the primary endpoint. MG is a natural first indication for VRDN-008.

As you know, FcRn inhibition is a well-established mechanism in MG, with a clear link between IgG reduction and clinical benefit, and we believe MG patients are in need of more convenient treatment options. We believe this validated mechanism, our strong 008 data, and our study design with two active dosing arms provide a path to move directly from phase I to a registrational trial, pending regulatory feedback. I will now turn it over to Shan to talk more about the 008 profile and the broader opportunity.

Thanks so much, Radhika. I would like to start by reiterating what we have here with 008. We engineered 008 to be a subcutaneous, half-life-extended FcRn inhibitor, and today, we showed that subcutaneous 008 can drive deep and sustained IgG reductions, supporting a potential best-in-class every eight-week dosing regimen. Now let us think about 008 in the context of the current FcRn treatment landscape. There are a number of FcRn inhibitors approved or in development, spanning different modalities and dosing frequencies, but each comes with trade-offs. Some therapies are dosed cyclically, which results in unpredictable treatment schedules for patients. Others require lengthy IV infusions or frequent dosing.

We believe there is a significant opportunity for a next-generation FcRn inhibitor like 008 that brings together the attributes that matter the most to patients: deep IgG reduction, sustained disease response, predictable and infrequent dosing, with easy subcutaneous self-administration, all of which are potentially enabled by what we believe to be the unique and exceptional PK/PD profile of 008. We have shown you our robust PK/PD profile and infrequent dosing schedule for 008. Now let us talk about how we plan to deliver it simply and subcutaneously. We are excited to announce that we are moving into pivotal development for 008 using the enFuse device, which uniquely provides a simple approach to every eight-week subcutaneous dosing. This is a next-generation device on the left of the page here. It is small, lightweight, and hands-free, designed for easy and discreet at-home self-administration with a single push of a button.

Importantly, enFuse is commercially validated and in use with multiple marketed products and in development with several others, including OCREVUS, a blockbuster market leader in MS. On the right, we have shown the large-volume auto-injector that is currently in development for VYVGART HYTRULO. For patients, we believe the choice would be clear. Compared to the large once-weekly auto-injector, we believe 008 administered every eight weeks with enFuse offers a superior patient experience. And we are in a great position, as we have held exclusive global rights to enFuse for FcRn-targeted therapies since January 2023. We believe 008 has the potential to fundamentally change what patients can expect from an FcRn inhibitor. As you can see on the slide, current commercially available options and those in development consist of IV infusions or weekly injections, which can be a significant treatment burden.

With 008, every eight-week dosing would translate to just seven simple subcu doses per year. This would greatly simplify and improve the treatment experience for patients compared to all of these other options, either commercially available or in development. As Radhika mentioned, we plan to initiate a registrational trial with 008 in MG in mid-2027. MG is a large and growing market, with FcRn inhibitors on track to generate over $7 billion in revenues this year, having grown 40% in the last 12 months, and projected to reach nearly $12 billion by 2030. We believe 008 has a highly differentiated profile with the potential to be the treatment of choice for MG patients, and we are excited to start our registrational study next year. MG is only the beginning.