Good morning, everyone. Hope everyone's had a good conference week. Welcome to the 44th Annual J.P. Morgan Healthcare Conference. My name is Cliff Zhang, a member of the Healthcare Investment Banking team based out of New York. Our next presenting company is Jade Biosciences. And speaking on behalf of the company, I'm pleased to welcome CEO Tom Frohlich. Please give it up for Tom.
Thanks, Cliff. It's really a pleasure to be here. Thanks for hosting us at the conference. I'm really pleased to provide an overview of Jade on behalf of the team. Very exciting time for us as a company, so pleased to provide an overview. I will be making forward-looking statements, so if you have more requests for information, please contact or please read our SEC filings. So Jade Biosciences, we're a company that is really dedicated to developing best-in-class therapeutics for autoimmune disease. We were launched in the middle of 2024, really based on three assets that we have access to from a company that we've licensed from and have access to another one from Paragon Therapeutics.
Many of you are probably familiar with Paragon. They're a protein engineering company based out of Boston, have an excellent track record of developing very high-quality monoclonal antibodies, have a particular expertise in developing high affinity binding antibodies, but also in half-life extension technology. So really, the playbook for our three assets is to have best-in-class possibilities, to go after targets that have a high degree of clinical validation, but where we do believe we can improve upon that profile through that better binding through the entire dosing interval to potentially have better levels of clinical activity, but then, of course, to have a longer duration of action to provide less treatment burden for patients and a therapeutic that's much more convenient. So our lead program is JADE101 . It's an anti-APRIL, initially targeting IgA nephropathy, an extremely exciting area. I think it's developing into a much larger market opportunity than most people had previously recognized.
And we have a strong conviction that the selective anti-APRIL class is going to move to frontline and be foundational therapy. Now, within the selective anti-APRIL class, there are two agents that are further ahead of us that have provided that clinical validation. But we do believe there's a straight pathway for us to become the best in class and potentially the best in disease through that more complete inhibition of APRIL through the entire dosing period to provide that higher level of clinical activity, but of course, that longer dose interval as well to be the most convenient therapy on the market. That agent currently is in phase I. We completed enrollment last year, and we're currently monitoring the data. And we plan to have that data. We've guided last week that that data will be disclosed in the first half of this year.
Now, it is extremely important data for us, not only because it's the first data set for us as a company, but because in IgA nephropathy, it's a very biomarker-rich indication where we can see the biomarkers that are reduced in healthy volunteers are actually a direct read-through to the expected clinical activity in patients. W e will be able to pretty much fully characterize the drug through that healthy volunteer study, give us all the information we need to move extremely quickly into patient trials. And we did actually provide guidance last week that we do plan on dosing our first patient in the phase II around the middle of this year with data in 2027, so an extremely exciting program.
JADE201 is an anti-BAFF receptor, really along the lines of B-cell depleters, trying to overcome some of the challenges with agents like rituximab to provide more complete B-cell depletion and actually provide B-cell depletion as well in peripheral tissues to have higher levels of clinical activity. This agent is actually following in the footsteps of ianalumab, which is a program that's currently at Novartis in six different phase IIIs across a number of different autoimmune indications, so an agent with very broad potential, but looking to extend the half-life with that agent as well to be able to provide better receptor occupancy coverage through the dosing interval and provide better convenience for patients as well to be highly differentiated.
So that program is currently on track to get into a phase I first-in-human study in the second quarter of this year, aiming to have data on that in 2027 as well. We have a third program as well, which we have not disclosed the target yet for competitive reasons, but follows that similar format where there is a biological validation that's from a product that's further ahead in the clinic. And we aim to have that into the clinic in the first half of 2027. So an extremely exciting profile for us as a company. We have that backed by a very, very solid team. Me and actually Andrew King, who's our Head of R&D, who's going to come up here for Q&A. We both have a background at Chinook Therapeutics.
We were both early employees there and really there through the pipeline build right up to the acquisition by Novartis. We managed to recruit in what we think is kind of the best elements of that team, and we are driving these programs forward with a very highly capable, experienced team, but we're also backed by a strong financial foundation. We closed last year with $336 million, which is enough to fund operations across these three programs into the first half of 2028, so very exciting year ahead where we go from last year, 2024, starting the company, last year, building the foundations with a pipeline, with a team, the capital structure, and 2026 really looks to be a transitional year for us where we go to having clinical data and then multiple clinical programs as well.
So why are we so excited by JADE101 ? are four kind of key areas that we're really focusing on for our excitement. The first one is really around the potential market opportunity. As I mentioned, IgAN is probably slightly underappreciated in terms of its size. We believe it's a $10 billion-plus opportunity in the U.S. alone. Although recently we saw Otsuka get approval with sibeprenlimab in November of last year, and we actually were pleasantly surprised with Otsuka's pricing. They priced it at sort of the high end of the range of what we were anticipating. So actually, these market estimates are probably low. We've actually seen research analysts with multiples of that $10 billion numbers. So we think it's a very large, commercially attractive opportunity.
Within that opportunity, we think that the selective anti-APRIL class is going to move to frontline and be foundational therapy for all patients at risk of progression with IgAN. And that's really because they have this ability to reduce pathogenic IgA, which is that driving factor to be disease-modifying. They've demonstrated large reductions in proteinuria and stabilization of kidney function, doing that with a very safe tolerability profile. With JADE101 , though, we think we can be the best in class to use the qualities of our antibody to have superior potency and that long half-life to really provide the best clinical profile and have the best dosing interval that will be most convenient for these patients. And then, as I mentioned, there's a very efficient development pathway where we can see biomarkers in that healthy volunteer data that is hugely de-risking for the program because we can really see what the clinical profile will look like and also give us our dose and dose interval and allow us to move extremely quickly into patient trials.
I won't spend too much time on the market other than to say we do think it's a very large market. There's about 170,000 patients in the U.S., several hundred thousand in Europe, and several million in Asia. We do believe that 60%-75% of those patients do require treatment and are eligible for the selective anti-APRIL class. We choose that 60%-75% range because those are the percent of patients we believe are over half a gram of proteinuria a day. Those are the ones that are more at risk of disease progression. As you can see on the right-hand side of this chart, if you look at epidemiological studies of patients over time, those that are at high proteinuria levels per day do end up having rapid loss of kidney function.
It really is the goal of therapy to get patients as low as possible to minimize that long-term risk of progression. You can see those in the lowest quartile, below roughly 0.5 gram a day, are the ones that have the minimum chance of disease progression over time. The recent KDIGO guidelines really do spell that out in a lot more detail, the importance of this proteinuria target of less than 0.5 gram a day. There's three key elements there. One, they believe that any patient who is above 0.5 gram a day that is suspected of IgAN needs to get a biopsy to really be diagnosed. We believe that's going to expand the patient population. Anybody who's not below that target of 0.5 grams a day needs to have further therapy or more therapy added.
We think this really strict, aggressive proteinuria target is really going to highlight the need for highly effective therapies to come to the market. And it's going to be a key selection factor for physicians when they're deciding what therapy to initiate for their patients. The other element that we think is a good tailwind for the class is that the KDIGO guidelines have actually also recently really called out specifically with the availability of these new agents that IgAN needs to be treated like an autoimmune disease and that every patient needs to be on a therapy that has proven to reduce pathogenic IgA. So we think that's another big tailwind for that anti-APRIL class that will help support them move to frontline therapy.
The only two classes of agents that are in later stage development that have consistently shown these reductions in pathogenic IgA are really the selective anti-APRIL class or the dual APRIL BAFF. And we have a strong belief that the efficacy from those classes of agents is primarily driven by APRIL. And there's going to be a preference to select those drugs that are really selective anti-APRILs because BAFF is not contributing significantly to the efficacy of these agents. And we know that or we believe that because of the pathology of IgA nephropathy. If you look at the right-hand side of this slide, you can see that APRIL really is a plasma cell-mediated disease where the plasma cell is driving production of galactose-deficient IgA. Then that's recognized as foreign. There's an autoantibody. You get these immune complexes that form and then deposit on the kidney to create injury.
And we've seen that with broad B-cell depletion, which targets B cells outside the plasma cells, so things like Rituximab, there's actually no impact on IgA levels. There's no impact on proteinuria. And similarly, with specific BAFF neutralization with an agent called belimumab, which is a selective anti-BAFF inhibitor, it was tried in IgA nephropathy with actually no effect, did not reduce IgA or did not reduce proteinuria. So the flip side of that is anti-APRIL neutralizing agents have consistently shown reductions in proteinuria, shown reductions in pathogenic IgA, and in fact have even demonstrated early kidney function stabilization as well. So we strongly believe that the selective anti-APRIL therapies are going to emerge as the preferred class.
There's recent also phase III data that has looked at selective anti-APRIL, so sibeprenlimab on the left-hand side of this graph versus atacicept, which is a dual APRIL BAFF. You can really see that there's not a significant difference or there isn't a big additive effect of blocking BAFF. We believe in the presence of this data where you don't get additional clinical activity, but you have broader immunomodulation with the BAFF, that the preference is going to be for the selective anti-APRIL therapies. Why do we believe that there's room for us within the anti-APRIL therapies? We really believe there's a possibility to differentiate on two options, two areas.
One where I mentioned longer duration of action, so a better dosing interval. The second one is we don't believe the therapies currently in development are optimizing dosing. This is the phase II study from Otsuka's sibeprenlimab where they used IV body weight-adjusted dosing across three different dose levels. You can see that at the lower dose at the top here that they're not completely inhibiting APRIL. They're only actually getting complete inhibition of APRIL across the dosing interval at the top eight mg/kg dose. That was associated with higher levels of overall proteinuria reduction and actually getting more patients into that target zone of below 0.3 grams a day, so back into the clinical remission zone. But Otsuka actually switched from IV dosing to a flat SubQ in phase III, which is great for patients because it's much more convenience. Convenience is really going to drive uptake in this young patient population.
When they switched to their SubQ dose, they really chose a dose that's kind of approximating their middle dose, so around that four mg/kg dose. We believe that they're leaving some efficacy on the table that we can capture with our agent. What is JADE101 and why do we have a strong conviction we can capture that efficacy? It's designed from a de novo screening campaign, and it has ultra-high APRIL binding affinity. In fact, it's in the femtomolar range, which is 750-fold more potent than sibeprenlimab. It's also half-life extended, so it does have that extended pharmacology, which we believe will allow us to capture that full efficacy, but also have a long dosing interval for patients.
The NHP data really supports our thesis. You can see in the left-hand side here, looking at the PK curves in non-human primates of sibeprenlimab versus JADE101 . Sibeprenlimab's in the purple. You can see a typical PK clearance that you would expect with a monoclonal antibody. But with JADE101 having nearly four-fold longer NHP half-life, so 27 versus 7 days with sibeprenlimab, and that higher binding affinity really has much slower clearance and maintains higher plasma exposures for a much longer period of time.
On the right-hand side, that's associated with pharmacodynamics as well. We're very fortunate in IgA nephropathy that we have great PD markers, even in NHPs and healthy volunteers, so we can look at a drop in IgA, which is very closely correlated to galactose-deficient IgA drops, and you can see a typical clearance curve with sibeprenlimab where you get a very good drop initially, but then as the drug is cleared, you get a rapid rebound. But with JADE101 , you actually get deep and durable suppression of IgA over time, so we are in a phase I, as I mentioned. We are looking at typical endpoints like safety and tolerability.
We think tolerability is very important here. So we will be reporting out things like injection site reactions to make sure this is extremely convenient for patients and well tolerated. But as I mentioned, the key really is to look at the depth and duration of APRIL and the drop in IgA. And from that, we'll be able to really understand and fully characterize the drug and understand, are we hitting that profile of that top dose of sibeprenlimab IV that they can achieve with a single SubQ injection? And we've got conviction around that because Andrew and his team have created this translational framework to look at what effect did all the APRIL and BAFF antibodies have in healthy volunteers. And we can model that out and predict exactly what we anticipate seeing in patients and how that will impact proteinuria and hopefully kidney function stabilization as well.
As mentioned, this will give us all the information for the dose and dose interval to be able to move forward really quickly into patients. And this is just a chart showing that that work is very closely correlated, what you see in healthy volunteers in terms of IgA reduction to patients, that translational framework has held, and then also those IgA reductions, how they're associated with proteinuria, so giving us really that strong conviction of this healthy volunteer data. And finally, just this is a slide to kind of reinforce a little bit about the importance of convenience within this patient population. I don't think I've mentioned yet, but IgAN patients are typically diagnosed relatively young. They're diagnosed in their 20s and 30s. Typically, they're asymptomatic, and they also require decades and decades of treatment.
We think this profile that we're aiming for, which is kind of maximal efficacy available to the APRIL mechanism with infrequent dosing, we think Q8 week dosing is achievable, so roughly six injections a year. We believe that that will be really preferred by patients and give us the opportunity to gain significant share within this very relatively large indication. So I see I only have a couple of minutes left before the Q&A, so I'll go through JADE201 quite quickly. We are very excited by this mechanism. It's only actually a few quarters behind where we were with JADE101 , so it is coming along quite quickly. As I mentioned, this is an afucosylated anti-BAFF-R monoclonal antibody that's really designed to overcome some of the limitations with previous autoimmune targets.
Things like rituximab, so CD20 and CD19 do a relatively good job at getting B-cell depletion initially. But we know that deeper B-cell depletion is always associated with better clinical activity. And some of the limitations of things like rituximab is when you have rapid B-cell depletion, you actually end up getting an upregulation compensatory effect of increased BAFF because it's a pro-survival signal and it drives repopulation. So the aim with our agent is to have this dual mechanism of action where you can overcome that, where you do have the same enhanced effector function, so for that rapid B-cell depletion in circulation, but then you're also inhibiting that BAFF signaling by blocking the BAFF receptor and preventing that repopulation.
And that has a couple of benefits. One is you're preventing the repopulation in circulation, but also you're starving the B-cells that are in tissue that might be in areas where you don't have those effector function cells like NK cells to do that killing. So you can also potentially get tissue depletion, which is extremely important in a lot of indications. So we've designed JADE201 . As I mentioned before, we're following in the footsteps of ianalumab, which is at Novartis. So we've designed it to really retain similar pharmacology to ianalumab in terms of its ADCC activity and blocking that BAFF signaling, but overcoming the limitation by introducing a half-life mutation to provide that extended receptor occupancy and also allowing for better injection frequency. I won't run through all the data, but just to say we're getting good BAFF-R blocking and ADCC activity.
In NHP, we have shown very good B-cell depletion, and we are on track to initiate our first in-human study in the second quarter of this year. In the second quarter of this year, where we will be looking at safety tolerability, we are initiating this trial in Rheumatoid Arthritis patients. Think of that more like a healthy volunteer surrogate because with B-cell depleters, it's not ethical to go straight into healthy volunteers. In RA patients, you can recruit them fairly quickly. We'll be able to look at safety tolerability, look at PK, but also understand the dynamics of B-cell depletion, and also, we'll be able to get some glimmer of a signal on efficacy because we will be measuring swollen joints and tender joints to get a DAS28 score, but it's not really powered for efficacy, but we will get some signal there.
With rheumatoid arthritis, it's a great indication for this study, and we are potentially excited by the opportunity there in RA. About 15% of patients do end up on rituximab if they fail TNFs and IL-6s and JAKs, so there is a significant market opportunity there, but it's unlikely to rise to our lead indication. It is probably within our life cycle management strategy, but when we think about indications here, you can really think about any indication where rituximab is standard of care or has clinical activity, so we will be looking at a number of different areas and really trying to understand where we can provide the best benefit. There's two strategies here. One is really look at the areas where ianalumab is in later stage trials. As I mentioned, they're in six phase III trials.
So we will see more data on those over the next period of time while our trial reads out so we can really understand where can we rapidly differentiate from ianalumab. But there's also a number of indications where Novartis has not gone, probably for strategic or portfolio prioritization reasons where we could be a potential first in class, but a very large market opportunity for this BAFF-R program. So very excited. So
I'll close there just to say we're extremely excited with where we are in terms of our progress as a young company. I feel like last year we built that foundation with the team, the capital structure, got the pipeline mature to a level where we're extremely excited. And this next year is going to be an excellent opportunity for growth for us with this really crucial readout with the healthy volunteer study for JADE101 , where we will be able to characterize very fully the drug and give us the conviction to move forward really quickly, understand if we're having that profile where we're maximizing the clinical activity available to APRIL with a long duration of action, Q8 weeks or more if we get good data, and move forward into later stage trials.
So thank you very much. Looking forward to a big year of growth for Jade.
Thank you, Tom. So we'll now transition to the Q&A session. We're going to be joined by Chief Scientific Officer Dr. Andrew King. We've had a number of questions coming from the online audience, so we'll go through those and turn to the audience at the end if time permits. So these are questions regarding JADE101 . Can you please elaborate on the bar for success for the upcoming healthy volunteer readout? Andrew, you built that translational framework, so why don't you comment?
Yeah, although this is a healthy volunteer study, it is going to be a very detailed characterization of JADE101 and highly informative of the future development. What we're hoping to see for success is a favorable safety and tolerability profile consistent with what we've seen with the anti-APRIL mechanism of action. We would like to see a relatively minimal immunogenicity. That's going to become increasingly important given what we've seen from sibeprenlimab with 34% ADA positivity in their phase III study, having a significant impact on PK exposures.
But the real informative information from this study is the biomarker-rich response to the anti-APRIL mechanism. And our analysis has shown that the responses are highly consistent in healthy volunteers, as we'll see in IgAN patients. And ultimately, these biomarker responses are predictive of disease-modifying clinical activity. So what we hope to see is an extended PK profile that provides deep and durable deletion of APRIL, so a direct measure of target neutralization and the accompanying IgA response that we see with this anti-APRIL MOA, which is sustained for at least eight weeks, which will provide us confidence we can deliver the full disease-modifying efficacy of the anti-APRIL mechanism and do it with a convenient infrequent SubQ dosing schedule of no more often than every eight weeks.
Thank you. As a quick follow-up, can you maybe elaborate on the importance of the dosing interval in this patient population?
Yeah, we think this is really critical, and we're seeing convenience drive more and more of some of the choice drivers for clinicians and patients. As I mentioned, patients are typically diagnosed in their 20s or 30s, so they're young, they're healthy, they don't have comorbidities outside of their kidney disease. They're asymptomatic, which we know asymptomatic diseases are always tougher for compliance. So having something that's as convenient as possible is really important. And these are people that have probably busy jobs or taking care of kids and parents. So we think having something that's not that often to dose and you don't have to think about your disease is going to be really meaningful.
As Andrew mentioned, our target profile is Q8 week dosing, so six injections a year. We've done some small market research with clinicians to show the profiles of some of the competitors are Q weekly, some are Q4 weeks. And then we looked at Q8 weeks and potentially some longer dose intervals. And we found that really the big inflection point where you get significant share is when you go from that Q4 to that Q8 week dose. And we think that'll be a really meaningful choice driver to really get preferential share for JADE101 .
Thank you. Another quick question. So maybe how quickly do you think that Jade can move to the registrational study?
Yeah, as I mentioned, we feel like we can select the dose and the dose interval for JADE101 from this healthy volunteer data set that will report out in the first half of this year. We do plan to open label phase two study in the middle of this year to generate some open label data, providing further conviction around the profile of JADE101 to be able to report at medical conferences. But we don't think that phase II data is gating necessarily for the phase III. We've seen other sponsors go very efficiently into registration programs. And we think with the detailed characterization of the biomarker responses from the first-in-human study, we can have discussions with the FDA around what a registration program looks like in this evolving landscape of IgAN with multiple approvals now and plan to move as quickly as possible into that registration program.
Obviously, we're not first in class, so it's important for us to execute rapidly on this program to move it forward quickly.
Thank you. This is a question about the market opportunity. What did Jade learn from ASN data and the Otsuka label? And maybe also comment on pricing.
Yeah, I think I alluded to it in the presentation, but this is potentially going to be a much larger opportunity than a lot of people had appreciated. The epidemiological surveys that we look at show there's about 170,000 patients in the U.S. alone. Some other sources, I think Otsuka is quoting 205,000. So it's a sizable opportunity. And if you think that 60%-75% of those are treatment eligible above 0.5 gram proteinuria, that's a sizable population. There are two key things that came out of Otsuka's approval of sibeprenlimab in November. One was the pricing, like you mentioned. They priced at really the higher end of the range of anybody's anticipation. So we've seen published reports that they're pricing at $30,000 per vial.
It's 360,000-390,000 per year. I think most analyst models had about 200,000-250,000. So really upsizing the commercial potential there. So that's one piece of the market sizing. It's always price times volume. The other element that's driving this to be larger than we had anticipated is that every IgAN product that was historically approved always had a proteinuria cutoff to reserve the drugs for more severe patients that are at more risk of rapid disease progression. So the earlier drugs with accelerated approval had a cutoff. You had to be generally over 1.5 grams per day. That would come down to 1 gram a day, kind of similar to their inclusion criteria in their phase III upon full approval.
But what we saw with the Sibeprenlimab label was that they actually got quite a broad label with no proteinuria cutoff restriction. So we think really that opens up the eligible treatment population to really that full 60%-75% of patients that are at risk of progression above half a gram a day. So our initial kind of calculations of a $10 billion market opportunity, you take that math and that actually doesn't make much sense anymore. We actually looked at a report yesterday from Goldman Sachs that says, quoting, it's probably more like a $40 billion opportunity. So those are big numbers, but it is a significant opportunity where there's going to be multiple winners here, lots of room for multiple agents.
But we think with our profile of that highest clinical activity possible to the mechanism, plus the longest dose interval, the most convenient, we'll be able to take a sizable part of that market.
Thank you. This is the final question for JADE101 , and then we'll move to the rest of the pipeline. And this is a question about competitive dynamics. So clearly it's a large market, but there are a lot of players. What are the main ways that you think you can differentiate with JADE101 ?
Do you want to take that?
Yeah, as Tom mentioned during the presentation, we do think anti-APRILs are going to become frontline therapy for IgAN. And we want to deliver a best-in-class profile for the anti-APRIL mechanism of action. That's the combination of the full clinical benefit available to this MOA. We don't think any of the agents further advanced in development or approved are fully capturing the full magnitude of efficacy available. And we believe with JADE101 's ultra high binding affinity and half-life extension, we can more completely suppress APRIL throughout an extended dosing interval to deliver the best efficacy available. We've seen in sibeprenlimab's phase II study a nice dose response such that the best clinical activity, the greatest reductions in proteinuria, the highest rates of clinical remission were achieved with full APRIL suppression.
We hope to deliver that with our phase III profile and do it with a convenient infrequent SubQ dosing schedule. So no more than six injections per year for these young, otherwise healthy IgAN patients.
Thank you. These are questions now about JADE201 . We didn't really have much time. We quickly went through it. Can you walk us through the mechanism of action and how is it differentiated from other B-cell depleting agents?
Yeah, so it really does address some of the limitations of the first-generation B-cell depleting strategies. B-cell deplete is generally pretty effective at peripheral circulating B-cell depletion, but not as effective as tissue B-cell depletion. And tissue B-cells are probably the key source of auto reactivity and autoimmunity. And they're also what drives tissue injury through pro-inflammatory responses. The other limitation of conventional B-cell strategies is that in response to B-cell depletion, you get these large increases in BAFF that act to repopulate the B-cells, but are also thought to exacerbate auto reactivity and autoimmunity and can lead to relapses and flares on current B-cell depleting strategies. So this dual mechanism of action for a half-life extended APRIL-glycosylated anti-BAFF-R receptor monoclonal antibody addresses some of those limitations.
Firstly, it uses enhanced effector function through ADCC to kill B-cells through NK cells to get this deep peripheral circulating B-cell depletion of BAFF-R receptor positive B-cells. So that's immature, through plasma cells, B-cells involved in antigen presentation, autoantibody production, as well as pro-inflammatory responses. However, in the absence of sufficient effector cells like NK cells, and this becomes particularly important in tissues where NK cells are sparse and other B-cell depleters are not very effective at depleting those tissue B-cells, JADE201 binds the BAFF receptor and blocks pharmacological stimulation from that elevated BAFF. So it prevents this important pro-activation, pro-survival, pro-inflammatory signal to B-cells, ultimately resulting in tissue B-cell depletion through starvation of this important B-cell survival factor.
Novartis has reported with ianalumab really impressive tissue B-cell depletion in the clinical setting, an 84% decrease in salivary gland B-cells from Sjögren's disease patients with 24 weeks of treatment of ianalumab, clinically validating this important differentiated dual mechanism of action.
Thank you. We have a few minutes left, so we'll try to get through the rest here. Can you talk through the timelines of your phase I in rheumatoid arthritis, what success looks like, and what other indications you might go into?
If you want to talk through the phase one and I'll talk about the indications.
So on track to initiate a first-in-human in the second quarter of this year. That will be in rheumatoid arthritis patients, but really can be viewed as a surrogate for healthy volunteers for a B-cell depleter, an opportunity for us to generate safety tolerability data, but also very biomarker-rich PK/PD data, including the extended half-life of JADE201 , BAFF receptor occupancy, which we believe we will measure directly and is a driver of clinical efficacy with this mechanism of action, as well as detailed B-cell depletion and recovery through flow cytometry. We'll opportunistically capture exploratory efficacy measures of joint pain and swelling in a DAS28 score, although not really anchored around that given the study design and limited sample size for this first in-human study.
So success would look like a safety PK and PD profile that supports future development in a variety of different autoimmune diseases with an extended SubQ dosing interval.
Yeah, and as I mentioned in the presentation, in terms of indications, this is a really broad potential opportunity. Our estimates are there's 17 million patients in the U.S. with the indications where we could potentially go into representing a total $80 billion opportunity. So lots of opportunity, but we have to choose carefully as a smaller company where we allocate our capital. We do have a bit of a luxury of time while we wait for data from this RA study to really characterize the drug to be able to figure out where the best places are to differentiate. But during that time, we will see more information from ianalumab. As mentioned, they're in six different phase IIIs. They're in Sjögren's, in ITP, in SLE, lupus nephritis, warm AIHA , and systemic sclerosis.
We'll be able to see more data there and really understand where's the best place to differentiate, what kind of a trial can we run to really understand that in those indications. But then also we have a lot of other promising indications where rituximab is the standard of care. We can go directly head to head versus rituximab or think about potentially relapse refractory patients for a good opportunity. And we're evaluating those indications as well where Novartis hasn't gone, as we mentioned, for potentially strategic or pipeline prioritization reasons. And there's several very interesting indications there that we could go after as well for a first-in-class strategy too.
We have time for one more question. Can you give us any insights into the JADE-003 program?
No. W e aren't disclosing that. We have nominated the development candidate. It is for competitive reasons. We have seen when we disclose targets that you do get a lot of other agents pop up and chase. So we want to get closer to the clinic before we disclose that. We will disclose it at some point this year. But I can reiterate, it is following that same playbook. There is an asset that's further ahead that has shown good clinical validation of the target. But we do believe with our protein engineering, half-life extension technology, we can get a much better profile. So better coverage of the target through the dosing interval, better length of dosing for patients to make it much more convenient to reduce treatment burden.
What we are saying is it is a bit more of a discrete target in terms of the indication potential. So it's not like 201 that can be applied to multiple different autoimmune diseases. It's more 101-like where there's kind of a lead obvious indication to go into.
Thank you. That is all the time we have for today's session. Thank you all for coming to the talk and to the conference.