Jade Biosciences, Inc. (JBIO) September 2026 Conference Transcript

All right, hi everyone, thanks for joining us at the Wells Fargo Healthcare Conference. My name is Sadia Rahman, one of the biotech analysts here at Wells Fargo, and it's a pleasure to introduce Jade Biosciences for our next session. From Jade we have CEO Tom Froelich, President of R&D Andrew King, and CMO Edward Connor. So thanks for being here.

Before we get into Q&A, I'll hand it over to you for any opening remarks great thanks so much and thanks to you and the whole team for for hosting us it's been a really pretty get a chance to get back into the season after an amazing summer yeah really pleased to talk a little bit about about Jade or a fairly new company just started two years ago looking to develop best-in-class therapies across a number of different autoimmune diseases we have three assets that we've licensed in from Paragon which I'm sure many people are familiar with, a protein engineering company that really does discovery across a number of different monoclonal antibodies. Our lead program is Jade 101. It's an anti-April going after IGA nephropathy. Extremely exciting program. IGA nephropathy is an area of large unmet need. We believe it's around a 20 billion dollar market opportunity in the US alone and we believe that anti-April class is really going to become dominant and foundational therapy for patients at risk of disease progression. Jade 101 has a really good opportunity to become the best in disease molecule. We recently reported out some phase one data in June of this year showing very deep and profound reductions in IgA, the key pathogenic marker of potential disease progression. Approaching 70% the largest ever drops seen with a single dose in healthy volunteers with any any agent really showing that Jade 101 due to its potency can capture the maximal effective activity available to the mechanism also those reductions were sustained for up to 12 weeks really showing that we can have maintenance of the disease with a single injection just every three months so an extremely promising profile that we're really excited to move forward. We're currently in a phase two trial with Jade 101, reporting out that data next year in 2027, so moving quickly towards that key milestone for us as a company. But we're not waiting for that data set to advance a phase three study. We're actually working hard to initiate a phase three. We plan to dose our first patient in a phase three in the first half of 2027 and move very quickly towards a data readout there and commercialization, so we can try to capture as much of that large market as possible. We also have J201, which is just in a phase one study right now, that's an anti-BAF-R compound, that's a B-cell depleting agent that is applicable to a number of different autoimmune diseases, really anything where rituximab is standard of care, J201 has a chance to improve treatment there. We're following the footsteps of Ionalumab, which is an asset at Novartis that is currently in six different Phase 3s, reported out positive data in Sjogren's last year, as well as second-line ITP, and has a number of different readouts coming out over the next 12 months that will help inform our strategy there. But we're currently in a Phase 1 study in rheumatoid arthritis patients and planning to read out that data in 2027 as well. Our third program, which we just recently disclosed is Jade 301. It's an anti-interferon beta, and the lead indication there is for dermatomyositis, a very severe disease that affects both the muscle and the skin. And we're just gonna go into a phase one healthy volunteer study with that program. I'm looking forward to reading out some data on that one in 2027 as well. So very active build on the pipeline and the team. We have a great team that we've recruited. A number of us actually worked together at Chinook Therapeutics before. Andrew and I were both there essentially since the founding of that company. So we've managed to pull across a number of the best talent, so a lot of development capabilities. And we're well-funded as well. We've completed a few financings in the last year, which really funds our entire pipeline through to the fourth quarter in 2028, past all of those milestones that I talked about. So very exciting time for us as a company.

Yeah, definitely. So just wanted to dig into the phase one data that you presented a couple of months ago and Climb Bio, a competitor, also presented some phase one data, I believe, last week. So just, you know, talk about how the data sets compare between the two molecules. I mean, broadly, they look similar on baromarco-dynamic effects and kinetics. And they also are targeting a similar dosing interval and injection volume, I believe. So when you compare the data, you know, are there any differences that you would highlight in biomarker reductions? Any potential for meaningful differentiation between these molecules?

Yeah, it's a great question. We remain very confident that with Jade 101, we have the best profile, given those large levels of IgD reductions and the ability to sustain that for 12 weeks. Andrew, do you want to talk a little bit about the details and the differentiation there?

Yeah, so when we designed J101, our goal was to deliver the full disease-modifying efficacy of B-cell modulation in IGAN with a convenient infrequent dosing schedule. So we really wanted to optimize two specific parameters. One was to improve the potency over the first-generation agents, and the second was to half-life extend to be able to spread out that dosing interval. We feel like our phase one healthy volunteer data really demonstrated both of those attributes where we had an extended half-life relative to civiprenlimab by about 2.6 fold and demonstrated really remarkable in vivo IgA lowering potency, which reflects the high binding affinity to April that Jade 101 was selected for. And as a result, we see these rapid, large reductions in IgA, really reaching the biological max effect you can see with a single dose of a selective APRIL inhibitor. Our assessment of the CLIMB data suggests they've also effectively half-life extended their molecule, similar to Jade 101, but have done so with a compound that has lower binding affinity. So they really haven't been able to incorporate that improved potency, which we think is really critical to be able to drive early and rapid IGA reductions to maximum levels and do so consistently across the broader population, whereas with a lower binding affinity molecule, there is potential for less complete IGA suppression and more variability. And we think that's played out in the data. So as Tom mentioned, really confident about the profile of Jade 101 and excited to develop it as a best-in-class asset.

Is there anything in the phase one data that you would highlight that differentiates, you know, IGA reduction? You talked about maybe kinetics of IGA reduction?

Yeah, so I think it's both the depth, the duration, and the consistency of the IGA reduction at the 700 milligram dose of Jade 101, which is our planned induction dose taken forward into phase two and phase three, we saw rapid IGA reductions that reached 70% decrease from baseline and were sustained for 12 weeks following dose before recovery beyond that. And we saw highly consistent responses across the healthy volunteer participants included in the study with very small error bars. With Climb, they demonstrated IgA reductions that maxed out in the 55-ish percent range, including at their 320 milligram maintenance dose. Higher doses of Climb, either as two separate 320 milligram doses two weeks apart or a single 480 milligram dose, didn't appear to be able to break through that mid-50 percent flaw that they achieved. So more like those first-generation agents with cipiprenlimab that appeared to require repeat dosing over time in IGAM patients to approach the IgA reductions observed with Jade 101 with a single dose. We also saw higher variability in the response of IgA with CLIMB across all dose levels, which would be consistent potentially with the lower binding affinity, not being able to completely neutralize all biologically relevant APRIL present in the tissues, particularly the mucosal immune system, to drive local IgA production and mucosal immunity.

Got it. And based on the phase one data, you know, with Jade 101, it appears that Q8 weeks at the lower dose, the 350 mg, you know, provides more complete biomarker coverage for the duration of the dosing interval. How confident are you that the induction dose with 700 with Q12-week maintenance with the lower dose can, you know, provide the same control that you're looking for?

Yeah, really confident in the ability of the Q12-week maintenance to maintain those initial large IgA reductions that are produced by the induction dose. Our PKPD modeling suggests similar IgA reductions are maintained with either Q8 or Q12 week dosing, giving us further confidence that the Q8 week, the Q12 week maintenance interval provides the full disease modifying efficacy of IgA lowering for Jade 101. An important consideration here is that the maintenance dose is administered on top of the loading dose, so target-mediated drug disposition, which has been very impactful to the first-generation anti-April agents, is fully saturated at the time of that first maintenance dose. So it's really building a very strong PKPD foundation to then maintain with a low infrequent dose over time.

Got it. So compared to the first generation agents, like just talk about, elaborate on the PD findings from phase one and how they could translate into better efficacy, whether it's on proteinuria or something else.

Yeah, what we've seen with the first-generation agents across trials is that early IgA reduction just at eight weeks is highly predictive of the proteinuria reduction you ultimately see in IGAM patients at that nine-month time point with greater IgA reductions associated with greater proteinuria reduction. We also see with the first-generation agents that IgA reduction takes time to get to those peak levels with repeat dosing and is accompanied by deepening proteinuria reduction over time. So our goal with Jade 101, with this ultra-potent molecule and this loading dose, is to rapidly drive IgA down as quickly as possible to maximum levels to potentially bring that efficacy forward from what we've seen with the first generation agents. So the potential for larger reductions in proteinuria at that nine-month time point, which has been the initial focus on accelerated approval for the first generation agents. And importantly, that has the potential to be associated with achieving greater rates of targets of proteinuria thresholds in the KDGO guidelines. So more patients below 0.5 grams per day, more patients below 0.3 grams per day. So the potential to differentiate by this potent molecule and a loading dose strategy to bring the proteinuria reductions deeper and earlier, which is really what nephrologists treat to, because on a visit-to-visit basis, it's hard to track EGFR. And it's really an initial focus on reducing proteinuria, getting the disease into remission, and having high confidence of improved long-term kidney outcomes.

As far as the phase two readout, what would you like to see to conclude that there is differentiation? Is it, you know, and are we looking at a nine-month time point? Are we looking earlier? And would we get any, just talk about the timeline relative to for like the phase three initiation and whether there might be a selection of a single dosing interval versus both, or do you see value in proceeding with both dosing intervals? Sorry, I know that's a lot.

No, that's a good question though. Maybe I'll start with the phase two and then we can talk about the phase three plans. So yeah, we initiated that phase two in May of this year, so we are actively enrolling patients there. It is an open-label trial enrolling up to 30 patients, so 15 in a QA cohort and 15 in a Q12-week cohort following the dosing regimen that Andrew described with a 700 milligram low dose and starting those regimens at week four. We haven't predetermined what the data cut will be that we'll present next year, but we do want to make sure that we're presenting a meaningful data set with enough patients to be able to look at things like IGA reductions. Are we replicating in patients what we saw in healthy volunteers and then what level of proteinuria reduction are we getting? We'll probably follow something similar to a lot of the first-generation agents that showed kind of a handful of patients like 8 to 10 at sort of a 36 week time point because that has been the comparator but we'll provide more updates as we get them and then be able to disclose that next year. In terms of expectations like we really want to see just replicating what we're anticipating from from that healthy volunteer study which is like really good deep robust reductions in IGA and robust reductions in proteinuria. We're not going to wait for that data to to initiate the phase three. We are moving extremely quickly. We do have a lot of confidence and conviction out of that phase one data set that it did characterize that dose profile. We have the utmost confidence in that Q12 week dosing arm. And we believe that's gonna be the go forward dose that we go to commercialize. But we did design the phase three with those two dose arms to really enable us to go extremely quickly. There is an expectation with some global regulators that you do some dose range finding. So we do think having those two arms really enables us to move really quickly before we get a bigger, meaningful phase two data set to initiate that study. So we will carry that phase three forward with those two dose arms.

Got it. Good job covering all parts of that question. So, you know, recently we're seeing some of the EGFR readouts from the April BAF agents, and they're setting a pretty high bar for efficacy. What are your thoughts on the EGFR data that we're seeing and the apparent consistency between anti-April versus BATH-April agents? Do you think all of these agents reach some thresholds on April suppression where there is an EGFR ceiling at two years and could there be any differences that emerge if we follow patients longer?

Do you want to take that one?

Yeah, it has been truly remarkable to see the disease-modifying impact of these agents really stabilizing EGFR over extended periods of time, out through two years now in placebo-controlled Phase III trials and two-and-a-half years in open-label Phase II trials. EGFR stabilization is really the best you can hope to achieve in chronic kidney disease because the decrease in EGFR we observe at baseline is a result of a loss of nephron number, which can't be regenerated. So it's really stabilizing and maintaining the kidney function that we have. So that really is the bar to match in a phase three trial, and it would be very difficult to exceed that. But what we know long term, and this is not just over a two-year phase three clinical trial, but in the lifetime of an IGAM patient who's diagnosed typically in their 20s and 30s and requires therapy not for two years, but for decades, potentially lifelong, is that residual proteinuria is the greatest predictor of future progression. So although we don't think there's a large opportunity to differentiate on EGFR in a clinical trial setting, there is, as I mentioned earlier, the potential to demonstrate faster, a deeper proteinuria reduction, greater rates of those clinical remission type endpoints to give the nephrologist, give the patient the highest confidence that their long-term kidney outcomes through their lifetime, not just over the two years of a clinical trial, will be very promising.

And just digging a little deeper on the EGFR data, just curious what you make of the increases or slight increases in EGFR out to two years? You know, is that consistent with that initial resolution inflammation, you know, at that time point? And, like, normally I've heard that, you know, in the past when KOLs would talk about it, they would say normally we would expect a decline of, like, one ml per year in healthy individuals. So just curious what you think about that complete stabilization or even a slight increase.

Yeah, it is interesting that consistently across programs, we're seeing this small increase in EGFR relatively early after initiating an APRIL inhibitor. So it would be consistent with the potential resolution of some acute inflammation that's being driven by these immune complexes that are hemodynamically lowering EGFR. And you've resolved that and you've returned normal kidney function in the absence of that inflammatory response. because we are seeing numeric increases of EGFR above baseline that are sustained through that two-plus-year time point. So maybe that's the likely explanation. And the age-related decline that you would expect in these 40-plus-year-olds of one mil per minute per year is being hidden in that acute phase resolution.

Okay, makes sense. You've talked about BAF potentially adding some risk without adding efficacy in IGAN. Is there anything you're seeing in the biomarker data, particularly IgG depth and kinetics, that points to this potential liability for BATH?

Yeah, so what we've seen on the efficacy side is no additional clinical benefit from adding BATH inhibition. We're not seeing deeper IgA, GD-IGA reductions, deeper proteinuria, hematuria resolution, and as we've discussed, selective APRIL inhibition is sufficient for full EGFR stabilization. BAF inhibition does impact a broader set of B cells than APRIL inhibition, which selectively targets plasma cells, so it does introduce the potential for broader immunosuppression and infection risk. The safety data sets are still relatively immature over short periods of follow-up, following accelerated approval, But we have seen some hints in the phase 2 data and emerging phase 3 data of potentially numerically higher rates of upper respiratory tract infections, infections that last for a longer period of time than in placebo-treated patients. And for poivitacicept in particular, from phase 2, we have seen cases of hypogammaglobulinemia, which does increase the risk of immunosuppression. So it'll be interesting to watch these data sets mature over time without evidence so far of increased clinical benefit of adding BAF inhibition. What does the long-term safety profile look like with extended duration of treatment?

Yeah, and it's interesting that IgG seems to continue to decline slowly, even out past two years for BAF April or even anti-Aprils, right? just curious if you think those that you know with chronic dosing we could see increased cases of hypogam or or infections with these agents you know if there might be the need for like a dosing holiday and not you know long-term chronic dosing and you know is there anything you would watch for in like the like phase three presentations um for for example povi the two-year data

that could indicate uh these risks yeah we have limited long-term biomarker data uh for this class um to to review we've got the small open label zika kybar selective april inhibitor study out through two and a half years and it actually does seem like igg does stabilize at a maximum biological response of about 35% decrease from baseline, whereas you do continue to see some incremental decline in IgA and GDIGA1 over that period of time. So there does appear to be a flaw in IgG reduction that you get with selective APRIL inhibition. And as long as you select for patients that can tolerate that 35% or so IgG reduction before they achieve clinically significant hypogammaglobulinemia, it appears to be safe and well-tolerated long-term. We are particularly interested to see the povitacicept phase 3 data because of some of those early signals from phase 2. Here you're combining April inhibition, which gives you that 30-35% reduction in IgG with BAF inhibition, which in the case of Benlista, a selective BAF inhibitor does reduce IgG alone. So, it'll be interesting to see that combination effect with longer duration of treatment.

Yeah, and I think a lot of people are going to be watching for that data, but we also just hear anecdotally from clinicians and patients that, you know, if you're going to be hitting a broader compartment of the immune system, then you'd want to see some benefit in order to do that. So, we do think there's going to be a preference emerge over time for the selective anti-aparols because you are seeing all of the same benefits on efficacy with a more narrow targeting.

Got it. I wanted to switch to the pivotal trial plans with Jade 101. So obviously the treatment landscape is changing quickly, and again, multiple new approvals, including potentially a third B cell agent this year, and they're showing remarkable EGFR efficacy. So this could make placebo-controlled trials harder to do, particularly in the U.S. and China. So there could be new guidance on pivotal trials coming soon. What would you expect from that guidance, and would you expect that to come before you finalize your phase three plans?

Want to take that one in? Yeah, sure. So there was recently the National Kidney Foundation assembled a group of treating physicians, industry, and the FDA, and I think there was full acknowledgement that doing two-year placebo-controlled studies at this point, when you have agents coming on the market that are disease-modifying, these patients are inexorably losing kidney function that can't be recovered. so there's broad agreement that one year placebo control is sufficient and now I think combine that with the SIBI two-year EGFR data and you're seeing that the one-year estimate holding there is is sufficient so more where we think they are headed and this was reaffirmed at the recent GLOMCON conference in MAUI by the deputy director of that division was that one year endpoint is sufficient and that it would be expected to include both proteinuria and EGFR as well.

And that consortium did also evaluate do you need an active comparator or not in the studies and I think there was agreement unanimously that that just isn't feasible in a rare disease in a trial of this size so we think just a one-year trial as had described versus standard of care is it's going to be suitable for approval.

Interesting. And on the commercial opportunity, you know, we're seeing the early numbers from the cibapremumab launch. How does that validate the market for B-cell agents and IGAN? Do you expect that trajectory to continue or could, you know, uptake in the community settings require more time?

That's a great question. I think TBD a little bit, but we are very encouraged by the initial update of cibiprinlimab and it reflects what we're hearing from clinicians about the demand for these disease-modifying agents. They saw 2,000 patient starts in the first six months of this year and really have had increased their revenue guidance for the year, showing that like really strong demand. We do know that there's about 8,000 nephrologists in the U.S. about 10% of them are specialists working more at tertiary centers that really focus on primary glomerative nephropathies like like IGA nephropathy and those are the ones probably prescribing at the outset where they really are familiar with the class they understand the KDECO guidelines and the need to treat with these types of agents so those are probably that first wave that you're seeing through and to your point though there are a lot of community-based nephrologists that work more in dialysis centers and more with generalized kind of CKD that aren't up to speed on these types of agents and probably do need some market development and education and that might take some time but we are hearing feedback that as soon as people are kind of exposed to this class of medications that there's a high willingness to prescribe so we do think that there's a really big market potential for for this class of medications in fact enough to support multiple entrants and we are very encourage that there's an increased focus to really maximizing that clinical activity, and there's an increased awareness that you need to have something extremely convenient for patients. So we do think the profile of Jade 101 is really well positioned to capture a lot of that market.

And on that convenience, you know, there is some differentiation between the first three agents that have launched. What should we be watching to understand how important, you know, more convenient dosing is in this market to validate that Jade 101 could have an advantage even with a later entry?

Yeah, it's a good question. With the agents that are coming to market now, so Cibiprinlimab is dosed Q4, Etacicept, which was just recently approved, was once weekly, so we'll have to look at what is the share uptake versus those two. And then Vertex's product is gonna be once every four weeks, which should be approved later this year. So I think looking at the shared dynamics there will be informative. But we have done fairly extensive market research, including a conjoint analysis where we're looking at, you know, what variables of frequency is really driving uptake. And we do see that a strong choice driver for IGA nephropathy is that longer dose interval. So we're quite confident that a quarterly dose will command a lot of share in the marketplace. Yes.

Got it. All right. So switching to J301, which you unveiled the mechanism recently, it's a selective IFN beta and you plan to advance it for dermatomyositis. So IFN beta is elevated in DM, but I think alpha might also be elevated and anufrolumab blocks the shared receptor. So what led you to IFN beta rather than the broader interferon pathway? And is there evidence that blocking IFN beta alone can be efficacious?

Sure, yeah. I mean, in terms of the signature itself, I think it's very strongly skewed towards interferon beta. I'd have to understand what the alpha signature is because what we've seen, And I think the data validates that is that particularly in the gene signature analysis they did in their skin biopsies looks like it is primarily driven by interferon beta. I think the problem, of course, with interfering alpha as well is that on the viral immunology side, you run into increased risks not only of worsening viral infections, but also viral reactivation as well. So, you know, I think broadly speaking, is sort of, is that worth the additional potential safety liabilities when it appears to be predominantly interferon beta-driven?

Got it. And are you planning to advance this as a monotherapy? And, like, is there a broader applicability for this as monotherapy? Or would you consider combining it with Jade 101 or 201? one?

We see it's high value as a monotherapy. Again, if you look at, we're all familiar with brepacitinib data, but if you look numerically, both at CDASI, which is a measure of efficacy in the skin, dasycaibard is significantly better than what was seen in brepacitinib. And the TIS, her total improvement score is more based on the neuromuscular outcomes so breakfast and it did see improvements there I think about a 14.5 increase the DASIC hybrid study was underpowered but numerically they saw around 19.5 so again showing that on both sides of the equation whether it's skin or neuromuscular or they were outperforming it as well. So from that perspective, in our view, a monotherapy makes sense. We don't see the value add that would occur in applying an additional molecule.

Got it. And you're planning to present preclinical data at the end of the month or early next month. What could we see in that preclinical data at EADB to maybe help understand the potential of the mechanism?

Yeah, it's really a detailed characterization of the preclinical profile of Jade 301, so including binding affinity, potency, non-human primate, half-life, to really understand the differentiated profile relative to Dazukaibat, the Pfizer agent that, as Ed mentioned, has showed strong phase two proof of concept, but limited by high IV frequent dosing, providing a significant patient burden, the goal with Jade 101 is to deliver the full efficacy of the interferon beta mechanism with infrequent subcutaneous dosing profile.

Maybe in the last few minutes, I'll switch to 201. So you'll have phase one data in 2027. You know, what could did we learn from that data in RA patients on B cell depletion, BFAR occupancy, and how could it help prioritize indications? Or are we also looking at the Ionalumab data in additional readouts to help with that?

Yeah, I think that's a great point. So just a reminder to the audience, so J201 targets BAF receptor following in the footsteps of Ionalumab, which is a program that's at Novartis, currently in multiple phase threes, had positive Sjogren's data and ITP data. And we'll see readouts from systemic sclerosis, lupus, lupus nephritis. So all of those data sets will help inform our indication selection and prioritization. But we also see a number of other opportunities where Novartis likely didn't go for strategic or pipeline prioritization reasons where rituximab is standard of care. So there's some first in class indications we're exploring as well. But the first step is, as you mentioned, really getting that phase one rheumatoid arthritis data, where we'll be able to really understand the safety tolerability of J2O1, but look at some very important biomarkers that will help inform how differentiated are we from ionalumab, namely looking at B cell depletion dynamics and very importantly, receptor occupancy of BAF-R, because that will really help us understand, you know, what is the dose and the dose. interval that that will be carried forward for for for Jade 201 so we'll get that data next year and then we'll make more decisions on on which indications to go into once we understand the profile a little bit

better and just wanted to get your thoughts on I and Alabama data and show grins you know do you think that the limited like efficacy Delta there reflects more of the trial design and and you know trial conduct rather than and the true potential of the mechanism?

Yeah, it's an unfortunate result, I would say, because they, in Sjogren's, the average patient had an S-dye score at baseline of around 12. And with ionalumab treatment, they managed to get it down to six, which is actually quite a great improvement on S-dye. The unfortunate part was placebo had around a four and a half or 5% drop, so the delta versus placebo and the treatment effect was not large. it was a positive trial but just barely positive from a p-value standpoint but when we talk to clinicians, rheumatologists, they're really excited by that six-point improvement in SDIE and we know that the FDA gave them fast-track review so they'll get approved and we think they'll be really broad rapid uptake. We'll have to look closely at the way that trial was designed and the inclusion criteria for the patients to see you know how do we feel about advancing in an indication with with that type of a p-value but right now the way that we understand it is unlikely we would do something there alone as Jade potentially we could partner J 201 with someone who would want to invest in in Sjogren's but we see some other indications with kind of a clearer shot at demonstrating a significant result in a shorter time frame is probably being a priority for us at Jade.

Just last question, you talked about the current cash runway. How are you thinking about investing in Jade 101 and IGAN versus exploring combinations of these molecules that you have and, you know, investing in the individual assets?

Yeah, so we're well financed into Q4 of 2028 across all three programs, and that includes getting 101 into the Phase 3 and getting that program well underway, getting the Phase 2 data for JADE 101, JADE 201 getting the Phase 1 RA data, as well as a subsequent study with 201, and then JADE 301 passed a Phase 1 trial as well, so multiple catalysts. So we're lucky at this stage we don't have to think too much about prioritization one versus the other but you know obviously a big value driver for us is going to be Jade 101 in that phase three trial and really making sure we execute on that flawlessly but tons of room for for value creation ahead all right great well we're out of time but thank you so much for joining appreciate all the insights excellent thanks so much thank