Good morning, and welcome to the Jade Biosciences JADE301 Conference Call and Webcast. Please note that this call is being recorded and will be available for replay on jadebiosciences.com. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call for questions.
Now I'd like to turn the call over to Tom Frohlich, Chief Executive Officer of Jade Biosciences. 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 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 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 four. 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 five, 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 subcu, 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 subcu 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 seven. 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 eight. 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 nine. 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. In that study, patients treated with dazukibart demonstrated substantial improvement in cutaneous disease activity as measured by CDASI. In fact, 82% of the patients treated achieved at least 40% reduction in CDASI, 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 TIS 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 JADE301 and the approach Jade has taken to build on this validated biology.
Thank you, Dr. Aggarwal, 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 with JADE301 is to deliver the full disease-modifying benefit of interferon beta neutralization in DM with a convenient, infrequent subcutaneous dosing schedule. JADE301 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, JADE301 selectively bound interferon beta with higher affinity and greater functional potency than existing therapies. JADE301 also incorporates clinically validated YTE Fc engineering with the goal of driving half-life 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 dazukibart, which has low subcutaneous bioavailability that requires high IV dosing to overcome. We believe the profile of JADE301 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 JADE301, we generated a dazukibart 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. JADE301 demonstrated higher binding affinity, greater functional potency, and more effective suppression of downstream interferon signaling.
On the left side of this slide, JADE301 demonstrated approximately 2.5-fold higher binding affinity for interferon beta compared to dazukibart, with a KD of approximately 11 picomolar versus 28 picomolar. JADE301 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 JADE301 demonstrated potent and complete inhibition of interferon beta signaling with an approximately 2.5-fold greater potency than dazukibart. Finally, in DM disease-relevant human dermal fibroblasts shown in the right panel, JADE301 potently and completely inhibited interferon beta induction of MX-1, 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 JADE301 was 11 picomolar compared to 91 picomolar for dazukibart, representing an approximately eightfold improvement in functional potency. These data demonstrate that JADE301 combines selective high-affinity interferon beta binding with potent downstream interferon pathway inhibition across multiple experimental systems, supporting the potential of JADE301 to block the aberrant interferon beta signaling characteristic of DM pathogenesis. The data on slide 14 show a differentiated pharmacokinetic profile of JADE301 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 mg/kg dose of JADE301 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 dazukibart in non-human primates.
This result provides further evidence that half-life extension has been successfully incorporated into the JADE301 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 mg/kg , JADE301 demonstrated favorable pharmacokinetic properties with rapid absorption and an apparent elimination phase consistent with that observed following IV dosing, supporting the use of the subcu route in both non-clinical toxicology studies and planned clinical development. Translational assessments further support the potential for high subcutaneous bioavailability of JADE301 in humans. The effective half-life extension observed with JADE301 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 dazukibart, which requires high IV doses administered by infusion every four weeks.
On slide 15, we're highly encouraged by the promising preclinical profile of JADE301 and look forward to advancing it into the clinic. This phase I 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 JADE301 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 in dermatomyositis, which represents a large and underserved opportunity despite recent therapeutic advances. Second, the preclinical data demonstrate that JADE301 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. Third, we are moving quickly into the clinic, with phase I 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.
Certainly. Thank you. We will now begin the Q&A answer session. To ask a question, you must be dialed in by phone and press star one on your telephone keypad. Our first question will be coming from the line of Alex Thompson of Stifel. Your line is open.
Hey, this is Patrick on for Alex. Thanks for the update here. I guess, can you guys just walk us through maybe the path after the 2H 2027 interim. I guess, what do you need to see to go into DM patients, and is there a version of this readout that lets you maybe skip a small POC and go straight into a phase II-B, or is the POC certain here?
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. I think the phase I, as you point out, we want to understand the PK preliminary safety. I think at this point, probably a little too premature to comment on what the later stages of development look like. I think the other interesting piece will be the dazukibart phase III readout. I think that will help inform things as well.
Yeah. Maybe just to add to that. Yeah. Out of the phase I, our goal really is to demonstrate that subcu profile. We think that's a huge advantage for patients over the IV administration of dazukibart. That's going to be really the big win. We'll be able to then characterize what does 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 dazukibart to really understand what are those C trough concentrations that we need to hit, to get the level of efficacy. We'll be in a really good position to move the program forward quickly. We'll provide more guidance as that program data emerges.
Thank you.
Our next question will be coming from the line of Tyler Van Buren of TD Cowen. Your line's open, Tyler.
Hey, guys. Good morning. Thank you so much for the presentation. Dr. Aggarwal, if you're still on, it would be great to hear what your patients complain about most when it comes to symptoms when they present in the clinic. What symptoms are most bothersome? Obviously, you listed a bunch of them, but it'd be great to hear which ones they talk about the most. For the Jade team, maybe you could just on the phase I data at the end of next year, maybe you could elaborate on some of the biomarkers that you'll be able to show in this early study that could be reflective of efficacy and how we could compare that to the dazukibart data. Also maybe talk a little bit about the distribution into the muscle tissue, and how meaningful that could be.
Thanks so much, Tyler. Yeah, Dr. Aggarwal, why don't you talk a little bit about what[audio distortion].
Yeah.
Then we can hand it over to Andrew to talk about the expectations around the phase I data.
Sure. Basically, each patient is very different. There are different constellation 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 do not even think about for a second. Getting up from a chair is incredibly difficult for our patients. They need help. They need to push through. Going up the stairs sometimes is impossible for my patients. They have to change where they are living because they just cannot go up the stairs. Things, getting in and out of car, getting up from a toilet seat, all of those activities, lifting a gallon of milk that we do not even think, is difficult for our patients. That is one thing they complain.
The second thing they complain, if there are rashes, is not the cosmetic part of the rash. It is the painful quality of life altering part of the rash. It is painful, burning, itchy. That really drives them crazy, not so much the cosmetic part. 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 patient would have ILD. Those are the three main, most common manifestation, but it also depends what the patients currently have. Some patients may have more skin, some may have more muscle, some may have mix of all. Every patient is a different story.
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. There is no direct way to get pharmacodynamic target engagement measurements to help guide that dose selection. 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 dazukibart with a more potent molecule. As we highlighted, the binding affinity is approximately 2.5-fold higher with JADE301 relative to dazu, and the functional potency up to 8x higher than dazukibart. Being able to match those C troughs of dazu with a more potent molecule gives us high confidence we will deliver the full disease modifying benefit of interferon beta neutralization.
One of the key considerations, as you mentioned in your question, is antibodies distribute at relatively low levels to the muscle, the important target organ of injury, leading to the muscle weakness Dr. Aggarwal described. Only about 1% of the systemic circulating concentration of monoclonal antibody does achieve localization within the muscle tissue itself. This requires relatively high C troughs then to target sufficient drug concentration in the skeletal muscle to provide that impact. That is 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.
Our next question will be coming from the line of Akash Tewari of Jefferies. Your line is open, Akash.
Hey, thanks so much. Thanks so much. Just thinking about Pfizer's trial design and their development path and really what you could do differently, right. I feel like some of the art on these dermatomyositis trials is what do you do on amputation. Do you decide to do steroid tapering in phase II or not. I think one of the unique things about the Pfizer development plan is they split out muscle and skin affected patients, but they really didn't have that many patients with muscle weakness. So when you think about Pfizer's trial design relative to what you would want to do, what are some clear changes that you think you would make, in order to generate more meaningful data earlier or make a better clinical decision going into phase III?
Thanks, Akash. Yeah, really good question. Yeah, we've been looking at that Pfizer design quite closely, so I'll pass it to Ed. Just before I do, yeah, we think that there are some very key learnings from that Pfizer trial. First of all, it's been a little slower to enroll, we think probably because it's IV, so that's probably not as easy. 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. 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, 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%-30% of patients have skin-only manifestations. 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. In terms of the inclusion/exclusion criteria, I think similar to what you've seen across the brepocitinib studies, I think that's very representative inclusion/exclusion. We'll use that as a guide going forward.
Just to follow up on that. In terms of incorporating steroid tapering in phase II, it sounds like, yes, you will have steroid tapering in phase II?
[crosstalk]. It's probably just- Sorry. Go ahead 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 brepocitinib and then as well with eptacortilimab. That's definitely something we'll look closely at.
Thank you.
Our next question will be coming from the line of Laura Chico of Wedbush. Laura, your line is open.
Well, good morning. Thanks very much for taking the question. Just a couple housekeeping questions. First, apologies if I missed it, but from the phase I study design, have you disclosed those amounts that you're going to be evaluating for the subcu? Number two, what do you know about immunogenicity so far in the non-human primates, and will that be one other assessment you'll be sharing after the phase I? Then one for Dr. Aggarwal, just out of curiosity, with a couple of different mechanisms advancing, how do you envision physicians making selection choices on which therapies to use in DM patients? Thank you.
Great. Thanks, Laura. Maybe just really quickly on the first question, no, we haven't disclosed the doses at this point. Then maybe I'll turn it over to Andrew to talk about the immunogenicity question. Then Dr. Aggarwal, if you could talk about how you select which class of agents for which patients.
Yeah. Thanks, Laura. The immunogenicity profile in non-human primates has been fairly benign although not especially predictive or translational to humans. By design, JADE301 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 on PK in the healthy volunteer study but by design have attempted to reduce the risk of immunogenicity for the program.
Thanks, Andrew. And Dr. Aggarwal, can you just comment on selection?
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 dermatomyositis because it's a chronic disease, and we have. Just to give you an example, rheumatoid arthritis has 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 of chronic inflammatory autoimmune conditions, almost in most of my patients, I've used 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 breaks through that, and then they may get a flare, and the next agent may be used. I think more appropriate question, honestly, is which one I would use first, and which of these mechanisms action I would use first. It also depends on, and specifically in dermatomyositis, we probably have two main mechanisms right now, but they are all both the JAK/TYK pathway, IVIG, and interferon pathway. JAK/TYK pathway and interferon pathway are pretty much the same pathway. Simpler drugs, such as oral, would be preferred as a first agent over subcu, and subcu 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 other. Patient may have pregnancy, then one drug, IVIG, may be preferred over other. 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 mechanism of action and multiple different drugs to really take care of the patient for the whole lifespan of the patient, which spans about 30, 40 years.
Very helpful. Thank you.
[audio distortion]. Come from the line of Michael Yee of UBS. Michael, your line is open.
Hey, thanks. Good morning. A couple questions from our side. What do you know, or what has been published, or what do we know about dazu's PK/PD profile from the standpoint of saturating or covering the target such that your drug, which is more potent and may require less drug, will have room or opportunity to be higher efficacy than what Pfizer is doing in an IV formulation and probably giving a lot of drug. That's question one. Question two is, to what extent could you seek or look at other indications given the profile of your drug and given the opportunity to go elsewhere and have a broader development plan? Would that be something that could be interesting in phase II beyond just DM?
Last question is, given that Pfizer has taken a long time to enroll their study, and I note that there's changes on CT.gov for completion, is there anything that you think we would learn from them or from others that would help further de-risk your program? Thanks.
Great. Thanks, Mike. Really appreciate that. Andrew, do you want to take that first question on the dazu PK/PD? Then actually maybe you can take the third one as well, which is what will we learn from dazukibart that we can apply? Then I'm happy to talk about indications.
Yeah. We have looked at all the publicly available PK/PD modeling, including from the patents from dazukibart. 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 mg 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 JADE301, our goal is to match the C trough of dazukibart with, as you mentioned, a more potent inhibitor.
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 dazukibart, shifting from IV monthly dosing to subcu infrequent dosing, we think in itself represents a very significant differentiation, a reduction in patient burden, and an important innovation relative to dazukibart. That's the first question. Can you repeat the third question again? Sorry.
Yeah. The third question was around thinking about your mechanism or whether you could look at other indications beyond DM that could differentiate given the profile of your drug and go broader than just DM given the landscape.
I just recall, you did ask about learning from the dazukibart clinical experience when we expect to see more information. We actually just saw a recent publication. 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 III trial that is currently ongoing. It is listed on 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, and also provide some potential insights in polymyositis, which also is being enrolled in that trial. That could be an important guide for potential lifecycle management or indication expansion. [audio distortion]
I will turn it back to Tom to continue on the broader potential of JADE301 outside of DM.
Thanks, Andrew, your line is breaking up a little bit, so maybe I will just quickly repeat. The dazukibart phase III data, I think the primary completion date is listed as July 2027. That is when we will 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 are also looking at polymyositis. We will look closely at that data, understand what is the pathway there. There are other indications as well that we are considering, things like cutaneous lupus and some other interferon beta-driven diseases that we want to evaluate. But really believe there is a large opportunity with dermatomyositis. We know there is 50,000 patients in the U.S. alone.
Also recently with brepocitinib being approved, we saw that they priced at $420,000 a year. I think that is a very large and substantial commercial opportunity. With JADE's differentiated profile, we can capture a large portion of that opportunity. So feel really excited by that. Thanks, Mike.
Our next question will be coming from the line of Julian Harrison of BTIG. Your line is open.
Hi, thank you for hosting this event and for taking the questions. I have a related question on the topic of potentially best-in-class efficacy. I just noticed that positive dose response in the dazukibart phase II results. I am wondering how supportive is that observation in the potential of JADE301 having a best-in-class efficacy profile in addition to dosing? Sounds like you likely have a preferential drug at parity efficacy, but would love to get your thoughts on that upside scenario. Then I understand polymyositis is a little more heterogeneous than DM, but wanted to know if you see any optionality there for the interferon beta class, and if so, what would that pan-expansion likely look like? What do you maybe have to see from dazukibart phase III to get more supportive of that opportunity?
Yeah. Thanks, Julian. On the dazukibart efficacy, we felt really encouraged by the phase II data. We saw that highest level of activity on CDASI, so on the cutaneous component. Really feel like that is going to be a big driver of uptake for the interferon beta class. 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 will have to look at really what the phase III looks like. It is hard to say at this point, really, if we can improve upon that, just because that phase II study was fairly small. We need to look at what is occurring in the phase III. We are really encouraged by JADE's profile with 2.5-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 will look really closely at that data from dazukibart and if it is offering benefit to patients in terms of disease activity with the safety profile that we anticipate, then that is definitely something that we would consider because having the differentiated subcu dosing with JADE301 over dazukibart, we think will be a really big advantage and really enable patients to get that efficacy without the treatment burden. We will look at that very closely. Thanks, Julian.
Our next question will be coming from the line of Rami Katkhuda of LifeSci Capital. Your line is open.
Hey, guys. Thanks for taking my questions as well. I guess, how heterogeneous is interferon beta activity across DM patients? Could baseline interferon signatures or, I don't know, other biomarkers influence efficacy with the mechanism? Secondly, do you have a sense for the level of target coverage required in skin versus muscle? Could those compartments ultimately drive different dose requirements with this mechanism?
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? I'm not hearing from Andrew. So Ed, do you want to take that question?
Yeah, sure. So, I think with regards to the heterogeneity, 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%-4% of what you see systemically. Pfizer in their phase II 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.
Can't speak on the relative level of activity there. But it, in preclinical models, has been evaluated as being a very high interferon beta disease. I think the expectation is that you are probably having at least similar activity in the muscle as compared to the skin. It is really more of by targeting that C trough, making sure that we are getting a gradient that allows the monoclonal antibody to penetrate sufficiently to silence the local interferon beta activity.
Makes sense. Thank you very much.
Yeah. Our next question will be coming from the line of Matthew Phipps of William Blair. Matthew, your line is open.
Morning. Thanks for taking my question. Should the base case assumption be that acute 12-week subcu can be achieved given the 3x longer half-life? Or with Pfizer, given 600 mgs IV, should we assume that to maintain that kind of C trough with a dose that fits in an auto-injector subcu, it might need to be a little more frequently? Just curious what kind of base case assumptions you have going into this trial.
Yeah. Thanks, Matt. Appreciate the question. We think the goal here is just really getting to subcu dosing over dazukibart will be really the largest differentiator in terms of patient convenience. That's really the primary goal we're trying to establish through the phase I. We will have to look at what is the human half-life exposure levels, the subcutaneous bioavailability in the phase I 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 dazukibart has subcu, 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 dazukibart. We'll really be able to triangulate from the dazukibart 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 I. H opefully to be able to move extremely quickly from that point forward.
Thanks, Tom, and just a quick follow-up. Dazu in the phase II, it was non-significant increase in MMT8. Is that just a function of the small trial because it did show improvements in creatine kinase? Just curious how you think about the specific muscle benefit.
Yeah. Ed, you've looked really closely at the dazukibart trial. Can you comment on MMT8 and creatine?
Yeah, the trend was very positive. Our assumption that it is due to small numbers, that's why we're really excited about reading out with the larger phase III treatment in middle of this coming year. I think looking at MMT, as I said, the trend was very strong, so expected to be statistically significant with a larger treatment population.
Great. Thanks, guys.
Our next question will be coming from the line of Arthur He of H.C. Wainwright. Your line's open.
Hey, good morning, Tom and team. Thanks for hosting this. I have two questions, one for the Jade team. When I look at the poster, you guys evaluate the drug impact from the MX-1 expression. Just curious, have you guys looking that in the primary cell from the DM patient? The second question is for Dr. Aggarwal. If we are only looking at a DM patient, is that possible we just rely on the CDASI as the primary endpoint, or we still need the TIS including for the primary endpoint?
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 MX-1 and primary cells?
At this time, we've only measured MX-1 in normal human dermal fibroblasts as well as PBMCs from humans as well as non-human primates. MX-1 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 JADE301 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. Aggarwal, do you want to comment on kind of use of?
Sure.
Versus CDASI?
Yeah. Right, I can. Mainly that we have to ask what are the regulators saying. Regulators so far, FDA has been very clear that they see dermatomyositis as a multisystem rheumatic disease, not a skin manifestation, not a skin disease. Basically, CDASI would be great to have as a proof of concept, as a sub-secondary outcomes, as well as a supportive evidence. But I think any study would have to demonstrate overall improvement with TIS as a primary endpoint. I don't think CDASI would be the primary endpoint in any of the ongoing trial unless FDA changes their mind. Mainly because CDASI speaks only to the skin, whereas TIS speaks to muscle, 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. Aggarwal. Just to build on that a little bit as well. We do know that patients complain quite a bit, as Dr. Aggarwal 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. We do believe that that impact on CDASI, which we haven't seen dramatic improvements 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 TIS improvements on that neuromuscular and other organ systems, but particularly around that CDASI and skin improvement.
Thanks, Tom.
Yep.
Yeah. Our next question will come from the line of Kaveri Pohlman of Clear Street. Your line is open, Kaveri.
Hi, team. This is Wayne for Kaveri, and thanks for taking our questions. How much early biomarker data will be needed to determine whether JADE301's higher affinity can translate into superior efficacy versus similar drugs? Will the phase I SAD, MAD studies provide sufficient clarity, or will phase II data, will that be needed to establish the superiority? You mentioned the current cash runway is into 4Q 2028. How much development does the current cash position support, and are you considering partnering the asset after generating the POC data? Thank you.
Thanks. I will 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 are thinking about the data out of phase I to guide development. The current cash runway does get all three of our programs through into 2024 into, sorry, into Q4 2028, across JADE101. It is read out of the phase II trial in 2027, as well as initiating that phase III trial, continue development on 201. With 301, it is funding the phase I trial fully through the milestone of the data in 2027, and then initiating a subsequent trial after that as well. Really we feel like we are 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 is guiding our development?
Yeah. Thanks, Tom. The primary focus in phase I will really be on the pharmacokinetics of JADE301 and matching the C trough of dazukibart, which has provided that strong clinical efficacy in phase II and the dose they have moved forward with in phase III. Interferon beta expression in healthy volunteers is very low, so it is difficult to get a direct assessment of target engagement to understand the functional potency of JADE301 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 dazukibart.
Ultimately, we are 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 dazukibart.
Thank you. Very helpful. Thank you.
Our next question will be coming from Arseniy Shabashvili of Guggenheim Securities. Your line is open.
Good morning. This is Arseniy on for Vamil. Thanks for taking our question. I think you just alluded to this, but what would be the next steps after this planned phase I? Would it be a MAD study in healthy volunteers, or would you be going straight into patients?
Thanks, Arseniy. 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 JADE301 very efficiently in this indication. What the phase II and subsequent phase III look like, it's a little premature to guide on that prior to interactions with regulators to understand expectations. Our goal is to advance the program as quickly as possible into DM patients as the next phase of development for JADE301.
Thank you.
That concludes the question and answer period. I'll now turn the call back to CEO Tom Frohlich for closing remarks.
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@jadebiosciences.com. Thank you.
And this concludes today's conference call. All parties may now disconnect.