Jade Biosciences, Inc. Common Stock Study update

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

We're excited by the continued progress that Jade Biosciences is making across our pipeline and the strong operational momentum behind our lead programs as we work towards our mission to bring life-changing, disease-modifying autoimmune therapies to patients. Today, we are pleased to provide a closer look at JADE301, the third program in our pipeline, which we recently unveiled. Moving to slide 2. I'd like to note that today's discussion will include forward-looking statements. These include statements about Jade's development plans, product candidates, and our cash runway. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements. For a full discussion of these risks and uncertainties, please review our filings with the U.S. Securities and Exchange Commission. Please also refer to our corporate website, jadebiosciences.com, for additional information and disclaimers.

On to slide 3. Before we begin the discussion on JADE301, I want to provide a brief overview of our pipeline. Our lead program is JADE101, a selective APRIL inhibitor that is currently in phase II development for the treatment of IgA nephropathy, or IgAN, a chronic autoimmune disease that leads to end-stage kidney disease for most patients. JADE101 is an ultra-high-affinity, half-life extended monoclonal antibody that has the potential for best-in-class efficacy and for convenient every 12-week maintenance dosing from a single subcutaneous injection. Following our positive interim phase I data readout earlier this year, we are more excited than ever about JADE101's profile to deliver value to patients and capture a significant share of the large IgAN commercial opportunity.

We expect to report interim phase II data for JADE101 in 2027 and anticipate initiation of our phase III registrational trial of JADE101 in the first half of 2027, pending FDA alignment. Next in our pipeline is JADE201, a half-life extended, afucosylated monoclonal antibody targeting BAFF-R, the B-cell activating factor receptor. We recently initiated a first-in-human study evaluating JADE201 in patients with rheumatoid arthritis, from which we anticipate interim data in 2027. That takes us to the focus of today's call, JADE301, our potentially best-in-class, half-life extended anti-interferon beta monoclonal antibody in development for dermatomyositis. On to slide 4. Earlier today, we announced that new preclinical data for JADE301 is being presented at this year's European Academy of Dermatology and Venereology Congress, or EADV. Dermatomyositis, or DM, is a rare, chronic, and debilitating autoimmune disease characterized by painful inflammatory skin disease and progressive muscle weakness.

Despite recent advances in treatment, it is a large and underserved opportunity with approximately 50,000 patients in the United States alone. As you will hear today, interferon beta is a key upstream driver of DM and is a clinically validated therapeutic target with selective inhibition demonstrating meaningful benefit across both skin and muscle disease. JADE301 was designed to optimize this mechanism with a goal of combining high-affinity binding, enhanced potency, and YTE-mediated half-life extension to support infrequent subcutaneous dosing. In preclinical studies, JADE301 demonstrated greater potency and an extended half-life in non-human primates versus a dazukibart comparator. Dazukibart is a first-generation interferon beta inhibitor currently in phase III development for DM. We believe these results support JADE301's potential as a best-in-class anti-interferon beta therapy. We expect to initiate a phase I healthy volunteer study in the fourth quarter of 2026, with initial data anticipated in the second half of 2027.

We have the privilege of being joined today by Dr. Rohit Aggarwal, a Professor of Medicine and the Medical Director of the Arthritis and Autoimmunity Center at the University of Pittsburgh, where he serves in the Division of Clinical Immunology and Rheumatology. As a treating physician and clinical investigator, Dr. Aggarwal will provide perspective on dermatomyositis, the patient and treatment burden, the evolving treatment paradigm, and the biological rationale for targeting interferon beta. Then Dr. Andrew King, Jade's President of R&D, will introduce JADE301's differentiated profile, walk through the preclinical data being presented at EADV, and provide an overview of our development plans for the candidate. Before I hand off the call to Dr. Aggarwal, allow me to first review the current and emerging DM treatment landscape on slide 5, which underscores our conviction in JADE301's potential best-in-disease profile based on its mechanism and intended subcutaneous administration.

To orient you to the data in the table, efficacy in DM is measured primarily through two endpoints due to the skin and muscle disease manifestations of DM. TIS, or total improvement score, is primarily a measure of improvement in muscle weakness and injury. CDASI, or Cutaneous Dermatomyositis Disease Area and Severity Index, is primarily a measure of skin severity. In the table, week 12 results of each therapy and the furthest reported data are included to provide additional context. Current standard of care in DM is quite burdensome for patients, relying heavily on steroids that can lead to significant side effects while leaving residual disease activity. Notably, when viewed through the lens of efficacy, safety, and convenience, each of the agents currently approved or in development carries a meaningful trade-off. IVIG, although approved for this indication, requires multi-day IV infusions and carries thrombosis and renal risks.

Brepocitinib, which was recently approved, represents an important advance. However, as a TYK2 JAK inhibitor, it comes with a black box safety warning of serious infection risk, increases in mortality, malignancy, MACE, and thrombosis. Additionally, we believe there is significant opportunity for further improvement in both skin and muscle outcomes. Anifrolumab, which is dosed weekly sub-Q, blocks the IFNAR receptor, inhibiting the interferon pathway more broadly, including both interferon alpha and beta, and potentially increasing the risk of viral infection and reactivation. Efgartigimod, which is also dosed weekly sub-Q and in a 5 mil formulation, works through FcRn antagonism and therefore may not address the underlying interferon beta-driven biology implicated both in skin and muscle disease.

Lastly, as you can see here, dazukibart, a selective interferon beta inhibitor, has shown robust muscle improvement and the strongest cutaneous benefit of the disease to date, which supports interferon beta as an upstream target. However, dazukibart has low subcutaneous bioavailability and therefore is delivered by IV infusion every four weeks. When you look across the field, no therapy today combines the attributes that matter most. Efficacy across both cutaneous and muscle components of the disease, a clean safety profile, and convenient administration to minimize treatment burden. By pairing selective interferon beta neutralization with subcutaneous dosing, our aim for JADE301 is best in disease clinical activity with a well-tolerated profile and a convenient dosing regimen. With that, I will now turn the call over to Dr. Aggarwal to tell us more about dermatomyositis and the underlying biological rationale for selectively targeting interferon beta.

Thank you, Tom, and good morning, everyone. Turning to slide 7. Dermatomyositis is a serious debilitating autoimmune disease that affects approximately 50,000 adults in U.S. It is a complex multi-system condition that is characterized by painful skin disease as well as progressive proximal muscle weakness that brings functional impairment. Unfortunately, up to 80% of patients do not achieve sustained remission in this disease area. Instead, they experience chronic painful disease with profound impact on their activities of daily living, underscoring the need for more effective treatment as well as better tolerated and durable treatment options. The burden on the patient is profound. Muscle disease can impair basic activities of daily living, such as walking, climbing stairs, bending, lifting, and so on. While painful skin disease and severe itch can disrupt their sleep and quality of life. DM, or dermatomyositis, can involve other organs, including lungs and cardiovascular system.

The treatment goal for patients with dermatomyositis is to reduce skin as well as muscle disease activity, preserve strength and daily function, and reduce the burden of chronic treatment. Turning to slide 8. As Tom outlined, approved therapies, including IVIG and more recently brepocitinib, have expanded treatment options for patients with dermatomyositis. From a physician perspective, however, the treatment decisions still require balancing efficacy, safety, steroid burden, as well as convenience. No single therapy is ideal for every patient, and treatment often needs to be individualized based on disease manifestation, organ involvement, as well as patient-specific factors. As a result, many of these patients continue to require corticosteroid and additional immunosuppressive drugs to manage their disease chronically. Despite these advances, residual disease burden is substantial. Many patients continue to experience ongoing symptoms, disease flare, and treatment-related burden, highlighting the need for additional therapeutic options for our patients.

Ultimately, physicians would welcome therapies capable of delivering durable control of both skin and muscle disease while minimizing safety concern, steroid exposure, as well as treatment burden. Turning to slide 9. One of the hallmark biological features of dermatomyositis is activation of type 1 interferon pathway in both skin and muscle tissue. Among the type 1 interferon, the evidence increasingly point towards interferon beta as a key driver of disease pathogenesis. As shown on the right side of the slide, interferon beta expression is markedly elevated in affected skin of dermatomyositis relative to healthy control, and serum interferon beta, but not interferon alpha, has been reported to correlate with severity of skin disease in dermatomyositis. This is important because it suggests that not all interferon signaling contributes equally to the disease.

Ideally, we would like to target the pathway which is most responsible for disease activity while preserving as much as possible the normal immune function of other pathways. We also know that interferon beta sits upstream of many inflammatory pathway implicated in driving skin and muscle injury in dermatomyositis, making it particularly attractive target for intervention. Taken together, selective neutralization of interferon beta offers the opportunity to interrupt a central driver of disease while preserving the remainder of interferon system, a distinction that may have implications both in efficacy and safety. Turning to slide 10. As Tom mentioned, dazukibart is a selective interferon beta monoclonal antibody currently being evaluated in phase III trial for dermatomyositis. From a clinical perspective, phase II data generated considerable interest because they offered the first opportunity to determine whether selective inhibition of interferon beta could meaningfully impact disease activity in patients with dermatomyositis.