Jade Biosciences (JBIO) FY 2026 earnings call transcript

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 Jade 301, the third program in our pipeline which we recently unveiled.

Moving to slide two. 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 three.

Before we begin the discussion on JADE 301, I want to provide a brief overview of our pipeline. Our lead program is JADE 101, a selective APRIL inhibitor that is currently in phase two development for the treatment of IgA nephropathy, or IGAN, a chronic autoimmune disease that leads to end-stage kidney disease for most patients. Jade 101 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 1 data readout earlier this year, we are more excited than ever about Jade 101'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 Jade 101 in 2027 and anticipate initiation of our Phase III registrational trial of Jade 101 in the first half of 2027, pending FDA alignment.

Next in our pipeline is Jade 201, a half-life-extended apucosolated monoclonal antibody targeting BATH-R, the B-cell activating factor receptor. We recently initiated a first-in-human study evaluating JAD-201 in patients with rheumatoid arthritis, from which we anticipate interim data in 2027. That takes us to the focus of today's call, JAD-301, our potentially best-in-class, half-life-extended, anti-interferon-beta monoclonal antibody in development for dermatomyositis. On to slide four. Earlier today, we announced that new preclinical data for J301 is being presented at this year's European Academy of Dermatology and Venereology Congress, or EATV. 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'll 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. J301 was designed to optimize this mechanism with a goal of combining high affinity binding, enhanced potency, YTE-mediated half-life extension to support infrequent subcutaneous dosing. In preclinical studies, JAD301 demonstrated greater potency and an extended half-life in nonhuman primates versus a Dazucaibart comparator. Dazucaibart is a first-generation interferon beta inhibitor currently in Phase III development for DM. We believe these results support JAD301'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 Agarwal, 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. Agarwal 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 J301's differentiated profile, walk through the preclinical data being presented at EADB, and provide an overview of our development plans for the candidate. But before I hand off the call to Dr. Agarwal, allow me to first review the current and emerging DM treatment landscape on slide five, which underscores our conviction in J301'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 tradeoff. IVIG, although approved for this indication, requires multi-day IV infusions and carries thrombosis and renal risks. Reposidinib, which was recently approved, represents an important advance. However, as a TIC2-JAC 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 dose weekly sub-Q, blocks the IPNAR receptor, inhibiting the interferon pathway more broadly, including both interferon alpha and beta, and potentially increasing the risk of viral infection and reactivation. F-cartigimod, which is also dose 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, Dazucaibart, 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, Dazucaibart has low subcutaneous bioavailability and therefore is delivered by IV infusion every four weeks. So 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 J301 is best in disease clinical activity with a well-tolerated profile and a convenient dosing regimen. With that, I'll now turn the call over to Dr. Agarwal 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's 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 dermaromyositis can involve other organs, including lungs and cardiovascular system. The treatment goal for patients with dermaromyositis 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, brepositinib have expanded treatment options for patients with dermaromyositis. But 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 dromeromyositis is activation of type 1 interferon pathway in both skin and muscle tissue. Among the type 1 interferon, the evidence increasingly points towards interferon beta as the key driver of disease pathogenesis. As shown on the right side of the slide, interferon beta expression is markedly elevated in affected skin of dromeromyositis related to healthy control. And serum interferon beta, but not interferon alpha, has been reported to correlate with severity of skin disease in dermaromyocytes.

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 pathways implicated in driving skin and muscle injury in dermaromyositis, making a 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 implication both in efficacy and safety.

Turning to slide 10, as Tom mentioned, Dezuki-Bad is a selective interferon-beta monoclonal antibody currently being evaluated in phase 3 trial for dermaromyositis. From a clinical perspective, a phase 2 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 dermaromyositis. In that study, patients treated with Dezuki Bart demonstrated substantial improvement in cutaneous disease activity as measured by C-dassy. In fact, 82% of the patients treated achieved at least 40% reduction in C-dassy, and the magnitude of improvement was notably greater than placebo across the dose groups.

You can see the resolution of skin disease shown in the images on this slide. Importantly, the benefits were not limited to skin. The study also showed improvement in tests or total improvement score, including patients with more prominent muscle involvement, and the therapy was generally well tolerated. As a clinician, we are always weighing efficacy against the realities of long-term treatment.

While these data validate the interferon beta as a therapeutic target, the treatment burden remains an important consideration when patients require an ongoing IV therapy. With that, I will turn it over to Dr. Andrew King, Jade's President of R&D, to discuss Jade 301 and the approach Jade has taken to build on this validated biology.

Thank you, Dr. Agahal. for joining us today and providing the clinical perspective on DM and the potential of selectively targeting interferon beta, a clinically validated therapeutic target in DM.

Moving to slide 12, the goal of JAD301 is to deliver the full disease-modifying benefit of interferon beta neutralization in DM with a convenient, infrequent, subcutaneous dosing schedule. Jad301 is a novel, fully human, neutralizing antibody, identified through a de novo discovery campaign, and was selected and engineered to deliver a differentiated, best-in-class profile.

In preclinical studies, Jad301 selectively bound interferon beta with higher affinity and greater functional potency than existing therapies. Jade 301 also incorporates clinically validated YTE FC engineering with the goal of driving half extension and supporting an infrequent dosing interval It was selected with molecular properties predictive of high subcutaneous bioavailability to address a major limitation of first-generation agent Dazukaibat, which has low subcutaneous bioavailability that requires high IV dosing to overcome. We believe the profile of Jade 301 has the potential to deliver the full disease-modifying efficacy associated with selective interferon beta inhibition in DM with a dosing profile that may meaningfully reduce treatment burden for patients.

With that, let's turn to the preclinical data presented at the EADV conference beginning on slide 13. To benchmark JAD301, we generated a Dazukaibar comparator from the publicly available antibody sequence and evaluated both molecules side by side in the same assays and under the same experimental conditions. Across these in vitro studies, we observed a consistent pattern. Jade 301 demonstrated higher binding affinity, greater functional potency, and more effective suppression of downstream interferon signaling. On the left side of this slide, J301 demonstrated approximately 2.5-fold higher binding affinity for interferon beta compared to Dazukai-Bat, with a KD of approximately 11 picomolar versus 28 picomolar. Jade 301 was also highly selective for interferon beta, with no detectable binding observed to any interferon alpha subtype or any other interferon family member protein.

The middle panel shows a cell-based assay measuring interferon beta-induced stat phosphorylation in a human immune cell line, in which JAD301 demonstrated potent and complete inhibition of interferon beta signaling with an approximately 2.5-fold greater potency than Dazukai-Bat.

Finally, in DM disease-relevant human dermal fibroblasts shown in the right panel, JAD301 potently and completely inhibited interferon beta induction of MX1, an interferon-responsive gene and a hallmark of the type 1 interferon response observed in the skin and muscle of DM patients. The IC50 of JAD301 was 11 picomolar compared to 91 picomolar for Dazukaibat, representing an approximately eightfold improvement in functional potency. These data demonstrate that JAD301 combines selective, high-affinity interferon beta binding with potent downstream interferon pathway inhibition across multiple experimental systems, supporting the potential of JAD301 to block the aberrant interferon beta signaling characteristic of DM pathogenesis. The data on slide 14 show a differentiated pharmacokinetic profile of Jade 301 in non-human primates, which has the potential to enable more patient-friendly dosing.

On the left side of the slide, following intravenous administration of a single 30 milligram per kilogram dose of Jade 301 in NHPs, The PK profile was characterized by slow linear clearance and an extended approximately 30-day half-life, threefold longer than the approximately 10-day half-life for Dazukai Bart in non-human primates. This result provides further evidence that half-life extension has been successfully incorporated into the Jade 301 molecule, supporting its ability to potentially provide prolonged systemic exposure and a best-in-class profile. On the right-hand side of the slide, following subcutaneous administration at 30 milligrams per kilogram, J301 demonstrated favorable pharmacokinetic properties with rapid absorption and an apparent elimination phase consistent with that observed following IV dosing, supporting the use of the subcure route in both non-clinical toxicology studies and planned clinical development.

Translational assessments further support the potential for high subcutaneous bioavailability of JAD301 in humans. The effective half-life extension observed with JAD301 in non-human primates, along with the predicted favorable subcutaneous bioavailability, supports the potential for a very differentiated dosing profile and reduced patient burden compared to Dazukaibar, which requires high IV doses administered by infusion every four weeks. On slide 15, we're highly encouraged by the promising preclinical profile of Jade 301 and look forward to advancing it into the clinic. This phase one first in human trial will be a placebo controlled single ascending dose study in 24 healthy volunteers across three dose cohorts. The objectives of the trial are to evaluate safety and tolerability of JAD301 and impacts on pharmacokinetics and immunogenicity across a range of exposures to support dose selection and future clinical development in dermatomyositis.

We expect interim data from this trial in the second half of 2027. With that, I'll now hand the call back to Tom.

Thanks, Andrew. Turning to slide 16. In summary, we want to leave you with three key takeaways. First, interferon beta is a clinically validated target intramatomyositis, which represents a large and underserved opportunity despite recent therapeutic advances.

Second, the preclinical data demonstrate that J301 combines the potential for enhanced potency, a half-life extended PK profile, and subcutaneous administration. Together, we believe these attributes support the potential for a differentiated product profile. And third, we are moving quickly into the clinic with phase one initiation expected in the fourth quarter of this year and interim data anticipated in the second half of 2027. With cash runway expected into the fourth quarter of 2028, Jade is well capitalized to pursue efficient and expeditious development of all three programs in our pipeline.

With that, I'll hand it back to the operator to open the line for questions.

Yeah, thanks, Patrick. Really appreciate the question. Ed, do you want to talk a little bit about the development pathway after Phase I?

Sure, yeah. So, I think the Phase I, as you point out, we want to understand, you know, the PK preliminary safety. I think at this point, probably a little too premature to comment on what the later stages are. I think the other interesting piece will be the Dasek-Hybarth Phase 3 readout, so I think that will help inform things as well.

Yeah, maybe just to add to that, yeah, out of the Phase 1, our goal really is to demonstrate that sub-Q profile. We think that's a huge advantage for patients over the IB administration of Dazukaibart. So that's going to be really the big win. We'll be able to then characterize what is the human half-life look like and make some dose predictions. The really nice thing, as Ed pointed out, is we'll learn a lot from Dazukaibart to really understand what are those sea trough concentrations that we need to hit to get that level of efficacy. And so, we'll be in a really good position to move the program forward quickly. So, we'll provide more guidance as that program emerges.

Thanks so much, Tyler. Yeah, Dr. Agarwal, why don't you talk a little bit about both patients and then we can hand it over to Andrew to talk about the expectations around the Phase I data.

Sure. So basically, each patient is very different. So, you know, there are different constellations of symptoms that everybody would report. But mostly, patients would report difficulties in activities of daily living, the things that you and me take for granted and we don't even think about for a second, getting up from a chair. It's incredibly difficult for our patients. They need help. They need to push through. Going up the stairs, sometimes it's impossible for my patients. They have to change where they're living because they just can't go up the stairs. So things, getting in and out of car, getting up from a toilet seat, all of those activities, lifting a gallon of milk that we think are, we don't even think, is difficult for our patients.

That's one thing they complain. The second thing they complain if they have rashes is not the cosmetic part of the rash. It's the painful quality of life altering part of the rash. It's painful, burning, itchy. That really drives them crazy. Not so much the cosmetic part. And the third most debilitating symptom that I hear is the lungs, where they have shortness of breath or cough, and as you know, many of myositis patients would have ILD. So those are the three most common manifestations, but it also depends what the patients currently have. Some patients may have more skin, some may have more muscles, some may have a mix of all. So every patient is a different story.

So maybe over to Andrew, yeah.

Yeah, thanks for the question, Tyler. The Phase I study will primarily be focused on pharmacokinetics for guidance on the dosing strategy moving forward. Unfortunately, interferon beta is negligible in its expression in healthy volunteers, so there's no direct way to get We will incorporate some exploratory ex vivo type PD assessments as a guide, but our primary dosing strategy is around matching the C-trough of Dazu Kaibat with a more potent molecule. As we highlighted, the binding affinity is approximately 2.5-fold higher with J301 relative to DASU, and the functional potency up to eight times higher than DASU-Kaibat.

So being able to match those C-troughs of DASU with a more potent molecule gives us high confidence. We'll deliver the full disease-modifying benefit of interferon-beton neutralization. One of the key considerations, as you mentioned in your question, is antibodies distribute at relatively low levels to the muscle, the important tiger organ of injury leading to the muscle weakness, Dr. Agaral described. Only about 1% of the systemic circulating concentration of monoclonal antibody does achieve localization within the muscle tissue itself. So this requires relatively high C-troughs then to target sufficient drug concentration in the skeletal muscle to provide that impact. So that's going to be an important part of the translational modeling in targeting a C-trough that provides IC99s over interferon beta in the muscle and skin.

Thanks, Akash. Yeah, really good question. Yeah, we've been looking at that Pfizer design quite closely, so I'll pass it to Ed. I going to go ahead and get started but just before I do yeah we think that there are some very key learnings from that Pfizer trial First of all it been a little slower to enroll we think probably because it IV so that probably not as easy And then also they are including both DM and PM patients so polymyositis which we understand has really added a lot of complexity to the trial in terms of recruitment So we think going into a pure DM population will really help just enhance that enrollment Ed, do you want to talk a little bit about how we're thinking about patient selection?

Yeah, sure. So, and again, I would just reiterate what Tom said. First and foremost, we will not be doing a basket study, or we're not envisioning doing a basket study. We will only be enrolling patients with DM. I think the lesson that we learned from the Pfizer Phase II is exactly what you pointed out. They had a much more significant population of skin only with a higher CDASI requirement, and they had fewer on the muscle side, I think only 18. We know that in DM, it's about 20 to 30% of patients have skin-only manifestations, so our view in terms of the inclusion criteria would be to ensure that the patients have both active skin and muscle disease, And then potentially study subpopulations where they have more skin exclusively active disease.

You know, in terms of the inclusion-exclusion criteria, I think similar to what you've seen across the brepacitinib studies, I think that's very representative in inclusion-exclusion. And we'll use that as a guide going forward.

So, I mean, we – Sorry, go ahead. It's probably a little bit early just to talk about the exact trial design, but obviously that's been a big advantage with what we've seen with PrepoSynidib, And then as well with FCAR 2G and M. So that's definitely something we'll look closely at.

Great. Thanks, Laura. Maybe just really quickly on the first question. No, we haven't disclosed the doses at this point. And then maybe I'll turn it over to Andrew to talk about the immunogenicity question. And then Dr. Agarwal, if you could talk about how you select which class of agents for which patients.

Yeah, thanks, Laura. So the immunogenicity profile in non-human primates has been fairly benign, although not especially especially predictive or translational to humans. By design, J301 is a fully human monoclonal antibody that was discovered in a de novo antibody discovery campaign in humanized mice. So that provides the greatest potential mitigation of immunogenicity by being fully human by design. We will be measuring ADA rates and the impact of PK in the Healthy Volunteers Study, but by design have attempted to reduce the risk of immunogenicity for the program.

Thanks, Andrew. And Dr. Agarwal, can you just comment on the question?

Sure. Yeah, I can speak to it. So basically the concept that what you question is rather than which one I would prescribe first is a more appropriate question because I do believe that almost all of these drugs that are in development will get used in the life of a patient of a dermatomyosidate because it's a chronic disease. And we have, just to give you an example, rheumatoid arthritis is 21 drugs approved.

It's only the fight is which one I would use first. But if I look at the history of my patients over 10 years, 20 years, chronic inflammatory autoimmune conditions, almost in most of my patients, I've used a bunch of them. Six, seven, eight agents have been used over the life. Because what happens is the one agent would work and then may eventually stop working or the body, you know, breaks through that and then they may get a flare and the next agent may be used. So I think more appropriate question, honestly, is which one I would use first and which of these mechanisms of infection I would use first. It also depends on, and specifically in dermaromyositis, we probably have two main mechanisms right now, but they are all both the JACTIC pathway, IVIG, and interferon pathway.

JACTIC pathway and interferon pathway are pretty much the same pathway, so simpler drugs such as oral would be preferred as a first agent over sub-Q, and sub-Q would be preferred over IV in the same mechanism of action. But when you talk about in a particular patient, it also depends on the risk profile of the patient. Let's say the patient has severe cardiovascular risk, then maybe one drug would be preferred over others. Patient may have pregnancy, you know, then one drug IVIG may be preferred over others. So there are many nuances when you talk about individual patient, which drug I would prefer first. But what I do believe in each disease states of myositis, such as dermatomyositis, we need multiple mechanisms of infection and multiple different drugs to really take care of the patient for the whole lifespan of the patient, which spans about 30, 40 years.

Great. Thanks, Mike. Really appreciate that. Andrew, do you want to take that first question on the DASU PKPD? And then actually maybe you can take the third one as well, which is the, what will we learn from DASU Kaibart that we can apply? And then I'm happy to talk about the indications.

Yeah, we have looked at all the publicly available PKPD modeling, including from the patents from Dazu Kaibat. Unfortunately, it's not a particularly biomarker-rich disease state. As I mentioned previously, there's low levels of circulating interferon beta, and it's difficult to get direct assessments of target engagement. Based on translational modeling, that 600 milligram dose does appear to be covering the IC99 in muscle, so providing a robust inhibition of interferon beta.

It is very important to have very tight interferon beta control because it's upstream in an amplification loop that drives further interferon beta production and tissue injury. With J301, our goal is to match the C-trough of Dazu Kaibart with, as you mentioned, a more potent inhibitor. And with the Half-Life extension incorporated and the potential for prolonged smooth systemic exposures, if there is additional efficacy left on the table, we feel like we're in a great position to capture that. Although a very differentiated dosing profile from Dazu Kaibat shifting from IV monthly dosing to sub-Q and frequent dosing, we think in itself represents a very significant differentiation, a reduction in patient burden, and an important innovation relative to Dazu Kaibat.

So that's the first question. Can you repeat the third question again? Sorry? I just recall you did ask about learning from the Dazukaibot clinical experience when we expect to see more information. We actually just saw a recent publication from the Dazukaibot And no new safety signals, so consistent with the initial clinical experience of a safe and well-tolerated mechanism.

The next major learning will come from the Phase 3 trial that's currently ongoing. It's for the clinicaltrials. gov to have a primary completion date in the middle of 2027. So that will provide significant further de-risking of the interferon beta mechanism in dermatomyositis. It also provides some potential insights in polymyositis, which also is being enrolled in that trial. And that could be an important guide for potential lifecycle management or indication expansion. But I'll turn it back to Tom to continue on the broader potential of 301 outside of DM.

Thanks, Andrew. And your line is breaking up a little bit. So maybe I'll just quickly repeat the DASU-Chybar Phase 3 data. I think the primary completion date is listed as July 2027, so that's when we'll learn a lot more about the results of that drug, which will help guide our development strategy. Yeah, in terms of indications, as Andrew mentioned, they're also looking at polymyositis, so we'll look closely at that data, understand what's the pathway there. But there are other indications as well that we're considering, things like cutaneous lupus and some other interferon beta-driven diseases that we want to evaluate. But really believe there's a large opportunity with dermatomyositis. We know there's 50,000 patients in the US alone.

And also recently with Reposidative being approved, we saw that they priced at $420,000 a year. So I think that's a very large and substantial commercial opportunity. With Jade's differentiated profile, we can capture a large portion of that opportunity. So I feel really excited by that. Thanks, Mike.

Yeah, thanks, Julian. Yeah, on the DASU chibrad efficacy, we felt really encouraged by the phase two data. We saw that highest level of activity on CDASI, so on the cutaneous component. So I really feel like that's going to be a big driver of uptake for the interferon beta class. And also very positive response on the total improvement score, which is a good barometer of the neuromuscular efficacy.

So do feel like that efficacy is very substantial with interferon beta. However, the study was small, so we'll have to look at really what the phase three looks like. And it's hard to say at this point, really, if we can improve upon that, just because that phase two study was fairly small. We need to look at what's occurring in the phase three. We're really encouraged by Jade's profile with two and a half fold greater potency and binding affinity. So feel like we do have a good opportunity to capture any efficacy that is available. In terms of PM yeah we look really closely at that data from Dazukaibart and if it offering benefit to patients in terms of disease activity with the safety profile that we anticipate then that definitely something that we would consider because having the differentiated sub dosing with J301 over Dazukaibart we think will be a really big advantage and really enable patients to will be coming from the line of Rami Kakuta of Lifeside Capital Your line is open.

Thanks, Rami. Yeah, those, I think, are great questions for Andrew. Do you want to look at interferon beta heterogeneity across patients and then also differentials in muscle and skin? Okay, I'm not hearing from Andrew. So, Ed, do you want to take that question?

Yeah, sure. So, I mean, I think with regards to the heterogeneity, as, you know, as was alluded to earlier, I think one of the things that we're aware of, particularly when it comes to monoclonal antibodies, is their penetration of the muscle tissue is going to be significantly less, maybe, Anywhere in the range of 1 to 4 percent of what you see systemically. Pfizer, in their phase 2, did skin biopsies, and they did look at the gene signature of interferon beta and showed a substantial reduction after treatment that was correlated with clinical response. I'm not aware of a significant amount of muscle biopsy data. They didn't conduct muscle biopsies, and it's not standardly done at this point in the disease.

So can't speak on the relative level of activity there. But it is in preclinical models has been evaluated as being a very high interferon beta disease. So I think the expectation is that you're probably having at least similar activity in the muscle as compared to the skin. And it's really more of by targeting that C-trough, making sure that we're getting a gradient that allows the monoclonal antibody to penetrate sufficiently to silence the local interferon beta activity.

Yeah, thanks, Matt. Appreciate the question. We think the goal here is just really getting to sub-Q dosing over Dazoo Kaibart will be really the largest differentiator in terms of patient convenience. So that's really the primary goal we're trying to establish through the phase one. We will have to look at what is the human half-life exposure levels, the subcutaneous bioavailability in the phase one to really be able to be more confident in terms of what that dose interval is. We do feel like with our profile, as you mentioned, more potent and longer half-life that at least we'll get to that Q4-week dosing that Dazu-Kybar has sub-Q, but potentially a little bit longer. But it's probably a little bit premature to really guide on what we anticipate the full dosing schedule to be.

The really nice element here, though, is we do know what the C-trough levels are for Dazukaibart. So we'll really be able to triangulate from the Dazukaibart C-trough levels to what we're seeing in our human exposure and half-life, to be able to really have a very good characterization of what that dose and dose interval will be for studies going forward. After the phase one, so hopefully to be able to move extremely quickly from that point forward.

Yeah, Ed, you've looked really closely at the DASU-Kybar trial. Can you comment on MMTA and creatinine?

Yeah, I mean, the trend was very positive. Our assumption that it is due to small numbers, that's why we're really excited about, you know, reading out with a larger phase three treatment in the middle of this coming year. So I think looking at MMT, as I said, the trend was very strong, so expected to be statistically significant with a larger treatment population.

Thanks, Arthur. Great to hear from you. Andrew, are you back on the line? Are you able to address, did you hear the question about MX1 and primary cells?

So, at this time, we've only measured MX1 in normal human dermal fibroblasts, as well as PBMCs from humans, as well as non-human primates. Mx1 is a downstream target gene of the interferon beta pathway and is a hallmark being upregulated both in the skin and the muscle in DM patients. However, at this time, we haven't directly assessed the impact of J301 in the setting of DM in those cell types, but it's a great question and something we're beginning to explore as to how to continue to build out translational confidence. in the interferon beta inhibition pathway in the setting of clinical DM.

Thanks, Andrew. And Dr. Agarwal, do you want to comment on kind of use of versus CTAG?

Right. So even mainly that we have to ask what are the regulators saying. So regulators so far, FDA has been very clear that they see dermatomyositis as a multi-system rheumatic disease, He's not a skin manifestation, not a skin disease. So basically, CEDAC would be great to have as a proof of concept, as a sub-secondary outcomes, as well as supportive evidence. But I think any study would have to demonstrate overall improvement with TIS as a primary endpoint. I don't think CEDAC would be the primary endpoint in any of the ongoing trials unless FDA changes their mind, mainly because CEDAC speaks only to the skin, whereas TIS. It speaks to muscles, but also include other organs, and that's the comprehensive nature is what the FDA is really looking for.

Did the disease overall get better, not only about the skin?

Thanks, Dr. Agarwal. And just to build on that a little bit as well, we do know that patients complain quite a bit, as Dr. Agarwal pointed out, about the pain associated with the skin manifestations. We know there's trouble sleeping in the majority of patients. We know actually 50% of patients are on opioids for their skin pain. And so we do believe that that impact on CDASI, which we haven't seen dramatic improvements with, with the current standard of care or some of the emerging therapies in development, that's where we think interferon beta can really differentiate substantially. So not only on better test improvements on that neuromuscular and other organ systems, but particularly around that CDASI and skin improvement.

Thanks, Tom.

Thanks. Maybe I'll take the second question first, Wayne, and thanks for the questions on cash runway, and then hand it over to Andrew to talk about how we're thinking about the data out of Phase 1 to guide development. Yeah, the current cash runway does get all three of our programs through into 2024, into Q4, 2028 across Jade 101. So it's a readout of the phase two trial in 2027, as well as initiating that phase three trial, continued development on 201. And then with 301, it is funding the phase one trial fully through the milestone of the data in 27, and then initiating a subsequent trial after that as well. So really, we feel like we're well financed through multiple catalysts and inflection points that will really create a lot of value for the company.

Andrew, do you want to talk about the biomarker in Phase I and how that's guiding our development?

Yeah, thanks, Tom. The primary focus in Phase I will really be on the pharmacokinetics of Jade 301 and matching the C-trough of Dazukaibat, which has provided that strong clinical efficacy in Phase II and the dose they've moved forward with in Phase III. Interferon beta expression in healthy volunteers is very low, so it's difficult to get a direct assessment of target engagement to understand the functional potency of Jade 301 in that early phase study.

However, we are trying to incorporate exploratory pharmacodynamic biomarker assessments that may provide some initial hint in the clinical setting of that improved potency relative to Dazukaibat. But ultimately, we're going to need to see patient data in DM, both on the cutaneous and muscle manifestations, to have a better picture of the comparative efficacy profile relative to Dazukaibat.

Thanks, Arseni. Andrew, do you want to take that one?

Yeah, we would expect the single ascending dose study in healthy volunteers to then set up and support future studies in DM patients. We have no plans to do a multiple ascending dose study in healthy volunteers. What we need to do is really align with regulators on the future development. This is a rare disease, and there could be approaches to develop J301 very efficiently. We are not currently in this indication, but what the phase two and subsequent phase three look like, it's a little premature to guide on that prior to interactions with regulators to understand expectations. But our goal is to advance the program as quickly as possible into DM patients as the next phase of development for J301.

Great. Thank you, operator. On behalf of the Jade Biosciences team, thank you for joining us today. A replay of this webcast will be available on our website. If you have further questions, feel free to reach out to our investor relations team at ir at jadebiosciences. com. Thank you.