I am Citi's U.S. healthcare strategist, filling in this morning. I am very glad to have the team of Jade Bio here with us. From the company, we have Tom Frohlich, CEO, Edward Conner, Chief Medical Officer, and Andrew King, who runs R&D. We'll go about 30, 35 minutes, and then Oh, there. We good? Okay. Well, there we go. We'll go about 30, 35 minutes, and if there are any questions at the end, feel free to certainly fire away. Tom, maybe start right at the top. For anyone in the room or listening who doesn't know Jade Bio well yet, how about a quick overview? What is the company, and what are you guys building? Yeah. Happy to, and first of all, thanks, Trevor, for hosting us and the entire Citi group. We're excited to be here. Jade Biosciences, we're a company focused on developing best-in-class therapeutics for autoimmune disease. We have three assets in our pipeline, all of which we've sourced from Paragon, which is a really high-quality protein engineering company based out of Boston, with a long track record of developing really high-quality antibodies that have half-life extension to really deliver the maximum efficacy available to any given target, with a really long duration of action that really minimizes treatment burden for patients. Our lead asset is JADE101. It's an anti-APRIL monoclonal antibody targeting IgA nephropathy as the lead indication. We think IgA nephropathy is an area of large unmet need, and potentially a very large market size, about a $20 billion opportunity in the U.S. alone. We're completely convinced that the anti-APRIL class is going to become the dominant class within IgA, and really becoming foundational therapy for patients, because it really does have the ability to have deep reductions in IgA, which is the pathogenic driver of the disease. It has deep reductions in proteinuria and can stabilize kidney function as measured by eGFR with very good tolerability. JADE101 has a very straight line at becoming the best-in-class anti-APRIL. We've recently reported some phase I data showing that in healthy volunteers, you get very large reductions in IgA, actually nearing 70%, which is the largest reductions seen to date with any agent. So we believe that will drive really meaningful proteinuria reductions for patients, and then lead to stabilization of eGFR. Also, in that data, we showed that that reduction in IgA could be sustained for 12 weeks, which we think will be extremely convenient for patients and minimize their treatment burden over time. So that program is very exciting for us. We're advancing it. It's currently in a phase II trial, with that data reading out next year in 2027. But we aren't waiting for that data to initiate a phase III. That data's not gating. We're very convinced by the characterization, the profile from that phase I data to enable us to activate that phase III. So we are aiming to get that trial initiated with the first patient dosed in the first half of 2027. So a very rapid pathway to getting to the market with JADE101. The second program we have is JADE201, which is an anti-BAFF receptor antibody, really following the footsteps of ianalumab, which is a product targeting the same target at Novartis, currently in six different phase III across a number of different autoimmune diseases. That's a B-cell depleting drug, so it has really activity or the potential for activity in any indication where rituximab is standard of care. So it has very broad utility. We currently are in a phase I rheumatoid arthritis trial with that medication. We'll be reading out that data in 2027 to really give us a characterization of that product. What's interesting there is ianalumab, what we're doing is we're solving the limitation that it has. It has a very short human half-life, just 10 days in humans. With JADE201, we're aiming to extend that half-life, which would allow us to be able to have more complete coverage of the receptor for the duration of the dosing interval, and then, of course, extend out that dosing interval as well to make a more convenient product for patients as well. So that program, we'll read out the data in 2027. On JADE301, our newly disclosed program, that's an anti-interferon beta targeting dermatomyositis, a very severe disease that has muscle weakness, muscle degradation, and then as well as painful and itchy skin lesions. Current treatment is very burdensome. It's treated by steroids and IVIG, which is very difficult for patients. There is an interesting pipeline coming along. brepocitinib, the JAK2 was just recently approved by Roivant, so really demonstrating the unmet need there, and they have very favorable pricing there. We believe we can deliver a better profile with interferon beta. There is a more advanced asset with Pfizer right now that showed very compelling phase II data with interferon beta in dermatomyositis, with a very robust improvement in TIS. That's the primary endpoint. Very importantly, also very good efficacy on the skin component of dermatomyositis, which historically with other medications has been very difficult to treat. We're going to improve upon dazukibart, which is the Pfizer interferon beta product. It has a very low bioavailability, so it needs to be delivered IV. We believe with our protein engineering that we can overcome that and deliver a much more convenient format for patients. So that program is scheduled to enter into the clinic in Q4 of this year, with a readout in 2027 as well. So big year coming up. That's all underpinned with a very strong team. As well, we're significantly financed. We closed the last quarter with $461 million, which will fund us through all of those programs through into Q4 2028. So very exciting time for us with a big year coming up in 2027. Great. Thanks for that very extensive overview. I guess I will just start with a competitive question, just because I would say it is the freshest thing on the tape. You had an earlier-stage competitor out last week with some phase I data for their long-acting anti-APRIL drug. The regimen that they are taking forward seems to be landing in a pretty similar place to yours on dosing interval. How do you read that data set, and does it change how you think about where JADE101 sits in the class? Yeah. We obviously looked at that data in detail and remained really excited about the best-in-class profile of JADE101. When we started out with the selection of a best-in-class anti-APRIL, we really focused on two properties that needed to be optimized relative to the first generation. One was half-life extension to be able to extend the dosing interval. IgAN is a disease that is diagnosed in 20 and 30-year-olds, and they require lifelong therapy. Reducing the patient burden and giving them freedom from their disease with a disease-modifying mechanism of action, we think represents a significant value for those patients. The second property where we saw limitations of the first-gen agents was on potency. There is a large amount of APRIL within the body that needs to be neutralized to drive rapid and deep and sustained IgA reductions, and the first-generation agents had relatively modest potency. JADE101 was selected with ultra-high binding affinity to APRIL. It is actually a femtomolar inhibitor to APRIL, with a KD about 750-fold lower than sibeprenlimab, the drug approved by Otsuka, and about 2,000-fold higher than Climb Bio. When we review the new data set from Climb, they look to have effectively half-life extended the agent similar to JADE101. But where we see the big advantage for JADE101 is the superior potency, resulting in faster, deeper, and more consistent IgA reductions that we think has the ability to deliver the best-in-class efficacy, the full efficacy available to B-cell modulation, with a convenient infrequent quarterly dosing profile. Strong competitor from Climb, but we are still really comfortable with the properties and profile of JADE101 and are excited to really focus on rapid development and advancement of that program. Great, thanks. You had mentioned the phase I interim results, and you presented those back in June. Maybe just take us back before that readout. What were you hoping to achieve with the data, and how does the data that you eventually generated actually compare to that going in? Yeah. So healthy volunteer data in IgAN, as you know, is very significant because you can measure IgA levels in healthy volunteers, and that's a direct read-through to what you anticipate seeing in patients, and it's a predictor of clinical activity. It's really de-risking for the program on the whole, as I mentioned in the intro, and allows us to move really quickly. Going into that, we wanted to have kind of comparable IgA reductions, as was seen with the first generation of anti-APRIL therapies, all of which achieved around 50%-55% reductions in IgA with a single dose. The other thing we want to do is have extended dosing on that. What we managed to achieve was nearly a 70% reduction in IgA, which is unprecedented and really hasn't been seen with any other agent with a single dose to date. That lasted for up to 12 weeks, which really does support that idea that we can have a Q12-week dosing interval. It was really exciting data for us, really de-risked the program, showed that we did achieve that best-in-class profile that Andrew described, and gives us confidence to move forward really, really quickly. Great. On the biomarkers, so historically, how well have they sort of carried across from healthy volunteers into actual patient studies? Yeah. It's really exciting that the IgA reductions observed in healthy volunteers have been highly consistent with those observed in IgAN patients, so it really does set up our program to move forward quickly in clinical development. What we've seen is that these early IgA reductions, whether they're in healthy volunteers or IgAN patients as early as 8 weeks, are highly predictive of the proteinuria reductions you see at week 36, which has typically been the primary endpoint of phase III IgAN trials to support accelerated approval. We do feel this data set's highly de-risking in terms of translating to that disease-modifying clinical benefit we've seen consistently with the anti-APRIL MOA and allows us to have confidence in our dose and dose interval selection to move the program forward as quickly as possible into pivotal trials. What is the feedback from nephrologists that has most shaped how you are developing JADE101? Is there something in there that you think maybe investors or even some of your competitors in this space are underappreciating at this point? Yeah. I think the ultimate goal for nephrologists and patients is to stabilize kidney function for a long time. These patients are typically diagnosed in their second or third decade of life, so they really do need lifelong treatment. If someone is diagnosed, let us say, at the age of 25, they have a 50% chance of losing their kidney functions over 10-12 years. This is something that is chronic that will need to be really administered for the entire life of the patient. That really long-term view is kind of resonating and coming back to us a lot. From that aspect, obviously convenience is going to be a big driver because if you are a young patient, maybe you are busy in your work, maybe you are starting a family, you are really going to want to not think about your disease as much as possible. Actually, this disease is largely asymptomatic, so that convenience is really going to be important to make sure that the patients are staying compliant, but also managing their disease. That is one element that is maybe a little bit underappreciated, that convenience is going to be a big choice driver for clinicians. The second one as well is we are seeing with the more advanced agents, the first generation of anti-APRILs, that we are seeing good eGFR stabilization in the clinical trials over a one or a two-year period. This is really, really encouraging because patients typically lose 5-6 mils per minute of eGFR function per year. Then stabilizing that back to kind of a normal kidney function is actually groundbreaking. The data was actually presented recently at a conference, and the nephrologists got up and applauded because they have not seen anything like this before. A lot of investors come back to us and say, "Well, you cannot do better than stabilization," which I think is a fair comment because we do not aim to do better than stabilization. I think what people underappreciate is it is over a short period of time. It is only one or two years that these agents are stabilizing in the studies, but patients need to think about 30, 40 years out. The best predictor of that long-term stabilization of kidney function is actually getting to very low levels of proteinuria. In fact, all the longitudinal studies say you need to get patients below 0.5 g a day of proteinuria to really minimize that long-term risk of disease progression. What we think is going to emerge in the differentiation of these products, it is not only having a good profile, but getting more patients down to below that target range of 0.5 g a day. That will be a key differentiator because that is what nephrologists are worried about for the long term for their patients. That is actually a big driver why the KDIGO guidelines just recently changed to say the target for all patients is to get them below that 0.5 g a day, in fact, down to below 0.3 g a day, which is back into that clinical remission range. We think coming out with JADE101 that has the most potent reduction in IgA, and potentially has the ability to get more patients into that range will be a big differentiator. Great. You mentioned eGFR. I guess maybe diving a little deeper into that, going after both BAFF and APRIL versus targeting just APRIL on its own, what do we know about the effect on that particular endpoint from the dual mechanism versus single mechanism? We have had a long-held conviction that selective APRIL inhibition is really the disease-modifying mechanism in IgAN because IgAN is a plasma cell-mediated disease, which is uniquely APRIL responsive, and it provides a targeted, and least immunosuppressive approach to IgAN patients. What we have seen in eGFR, only one phase III has read out, and that was the sibeprenlimab trial that Tom Frohlich referenced earlier, showing stabilization of eGFR with a selective APRIL inhibitor over a two-year period relative to the inevitable decline of about 10 mils over that two-year period in the placebo group. eGFR was actually numerically above baseline at the end of that two-year study in that patient population, so a really remarkable treatment benefit. The best pivotal trial evidence to suggest that selective APRIL inhibition alone is sufficient to provide that full eGFR stabilization benefit, which is the best we can hope for in IgAN because the loss of kidney function really represents loss of nephrons, which will not be regenerated with a therapy like this. In phase II studies, we have seen consistent stabilization of eGFR for various periods of time across selective APRIL inhibitors as well as dual APRIL/BAFF inhibitors. zigakibart from Novartis has open label phase II data out through 2.5 years, which looks remarkably similar to that of sibeprenlimab in phase III, full eGFR stabilization numerically above baseline out through that 2.5-year period in a high-risk IgAN patient population. We've also seen open label data from atacicept, a dual APRIL/BAFF inhibitor, showing a similar profile of eGFR stabilization through 2 years, and 1 year with povetacicept, the dual APRIL/BAFF inhibitor in phase II. It appears as though both agents, both mechanisms, selective APRIL or dual APRIL/BAFF, are both effective at stabilizing eGFR. But it really adds to our conviction that selective APRIL is the preferred strategy because it provides that full eGFR stabilization with the most targeted approach, the least broadly immunosuppressive way to provide that disease-modifying benefit to IgAN patients. Maybe just move on to the commercial market. The Otsuka launch, I think, continues to outperform, and probably beyond some of the loftiest expectations that some people had going in. When you look at that, and you position that against Vera, who is just launching Vertex, who are likely to have a launch in the coming months, how do you think about the commercial opportunity in front of you coming on what is likely to be, in a couple of years' time or a few years' time? Yeah, it's a great question. We remain convinced this is a very significant commercial opportunity. In the U.S., there's about 170,000 IgAN patients. 60% - 75% of those are above that half a gram a day threshold that we talked about, so they're at risk for progression and need more advanced therapies like a B-cell agent, which all the ones that you mentioned are B-cell agents. The KDIGO guidelines actually very explicitly say you need to treat all IgAN patients with an agent that depletes pathogenic IgA, so we think that class is going to become foundational and really be used extensively. We're very encouraged by the uptake of sibeprenlimab, and the big demand for these agents. We do think that they're moving into that frontline foundational position. But we think it's a big market. If you look at the 170,000 x 0.6 - 0.7 for the people above 0.5 g a day, and then multiply that by the price, which sibeprenlimab is priced at $390,000 a year, you very quickly get to very large numbers, so there's room for multiple entrants. We also think that the market is going to take a little while to fully develop. Right now, there's a segment of nephrologists that are very interested in IgAN and primary GN and spent a lot of time at the conferences reading the literature or in the studies, and those are the ones right now you're probably seeing putting all their patients on sibeprenlimab. But there's a big contingent of nephrologists that practice in the community. They're in dialysis centers treating generalized CKD, that will take some time to develop. And so that is why we are happy to have Otsuka and Vertex and Vera out there educating the market and creating that demand. I think it will give us a good market to launch into when JADE101 gets to market. Right. You have guided to the phase II data next year. When that does come, can you just walk us through what success looks like? I do not just mean that against the parameters of the study, but as you know, this is becoming a competitive field, and we are all going to make cross-trial comparisons to that. Maybe just define what success looks like, again, within the parameters of the study and in the competitive landscape. Yeah. The phase II study started back in May. It is a small open label trial in 30 IgAN patients at risk for progression, similar patient population to what will be studied in phase III. It is divided across two separate cohorts with two different dosing strategies. All patients will receive a 700 mg loading dose of JADE101. All will receive 350 mg beginning at week 4, and then one cohort of 15 will receive Q8-week maintenance dosing, and the other will receive Q12 maintenance dosing. It is a relatively small sample size, but we do expect to be able to deliver the disease-modifying benefit that other agents have shown. There are deep reductions in galactose-deficient IgA1, the pathogenic variant, resolution of hematuria, reductions in proteinuria, and the eGFR stabilization we have talked about already. That would be success for us, to be able to show that full disease-modifying benefit of APRIL inhibition with a Q12-week dosing interval. We think that would deliver a very meaningful benefit and value to the patient population. We have designed the study with this loading dose, so we would hope to see these rapid IgA reductions that we have seen in phase I healthy volunteers. Hopeful that may translate into improved proteinuria reductions earlier in the treatment landscape. We do want to be realistic with expectations of a 15-patient cohort, given the biologic variability in proteinuria, that we do not want to anchor too much around setting specific thresholds of expectations. But the full disease-modifying benefit of APRIL inhibition with 12 weekly maintenance dosing would be an incredible profile to take forward. Gotcha. You mentioned how you are moving forward in phase III without waiting for that to sort of read out. So, what can you say about the phase III design? When does it start? When can you have data at hand? Yeah. We have guided that we plan to start the phase III in the first half of 2027, so next year. We really focus on operationalizing that right now. The study in design will be similar to the phase II with those two dosing intervals, but placebo-controlled. There has been significant evolution on the phase III study design front. The FDA requested a consortium meeting with the National Kidney Foundation back in April, which consisted of regulators, KOLs in the IgAN space, sponsors, as well as a strong voice from IgAN patients, really focused on what do novel phase III study designs look like in this evolved setting of new therapies approved, particularly within the U.S., recognizing that it will be challenging to maintain the traditional 2-year placebo-controlled trials given the available therapies that patients have options for. What is been great to see with these data sets from the first-generation agents is that large and early separation in eGFR, you do not need 2 years of placebo control to see an eGFR benefit. The benefit you see at 1 year is predictive of the benefit you see at 2 years with this true stabilization, versus the 5 to 6 mil per minute decline on the placebo group. So we do anticipate a shorter duration of a placebo-controlled trial, likely a 12-month study with the key endpoints of proteinuria and eGFR, for full traditional approval. Originally, 9-month proteinuria was used to support accelerated approval with 2-year eGFR data confirmatory for full approval. So we think that phase III study design is going to be very efficient. There is a lot of excitement about APRIL inhibitors, particularly in the wake of the sibeprenlimab data a couple of months ago, showing true eGFR stabilization. Sibeprenlimab is not available globally, where these trials are conducted, so the only way to access a disease-modifying therapy like this is through clinical trials. So we do think there will be significant enthusiasm for that, particularly in the setting of only a 12-month placebo control period, where the study is randomized 2 to 1 active to placebo, and all participants are guaranteed a long-term open label extension with JADE101. So really excited about this evolution, and think there is a very efficient path to develop JADE101 through full approval. All right. Last question on JADE101. Then I want to move on to the rest of the pipeline. Just beyond IgA nephropathy, how are you thinking about where else JADE101 can go? Bearing in mind, you know, the commercial market in IgA is already turning out to be quite large. How could you differentiate beyond just that one indication? Yeah. This is something we're spending time thinking about. Obviously, IgA is a big opportunity, like you mentioned. What's really interesting about this profile is you knock down IgA robustly, as we've talked about. IgG is relatively spared, so stays pretty intact. Then you do also get large drops in IgM, sort of similar to what you see in IgA. We do think there's a couple of IgM-mediated diseases that are quite attractive. One in particular is multifocal motor neuropathy, which is an indication that is quite rare, but with this pricing, can support entry with JADE101. It's something argenx is going after with a complement inhibitor, but we believe we can go upstream and be disease modifying. There's a couple of others as well, like anti-MAG neuropathy that we're exploring. Those are things we're considering putting into a basket trial just to get a signal there and then see where would we go from there. That's something we're actively preparing. On the competitive front, we know sibeprenlimab is actually entering a number of different indications that we're watching very carefully. They've actually entered with sibeprenlimab, with their selective anti-APRIL, into a Sjögren's phase II study, that is anticipated to read out next year. We're going to watch that very carefully. If that does end up being positive, we think we can have a really good opportunity in that big indication. They've also announced they're going into FSGS minimal change disease and primary membranous nephropathy. Those are all potential areas that we can move into rapidly if there is a proof of concept. As you mentioned, large potential for JADE101. All right. Let's move on to JADE201. It's an anti-BAFF receptor antibody. Maybe just walk us through how it differentiates from, I know Novartis has a drug that's a comp here, and maybe some other anti-BAFF programs in development. Yeah. We are excited about the dual mechanism of action of JADE201. It is an afucosylated half-life extended anti-BAFF receptor monoclonal antibody. So really following in the footsteps of ianalumab from Novartis, which shares this dual MOA. It uses enhanced effector function mediated ADCC to rapidly and deeply deplete B cells. But also it has a second mechanism of action in that it binds the BAFF receptor and pharmacologically blocks it. So it blocks this really important pro-activation, pro-proliferation, pro-inflammatory, pro-survival signal in B cells. That is particularly important in the tissues where autoreactive and pathogenic B cells reside and are often not susceptible to ADCC-mediated depletion because of the sparse availability of effector cells like NK cells. So in that setting, we can block the BAFF receptor and provide deeper tissue depletion of these pathogenic B cells, and also block the compensatory increase in BAFF that drives B cell repopulation that happens with all B cell depleters. So really excited about getting at the source of pathogenic B cells with this MOA. Ianalumab has very strong pharmacologic characteristics. It is a strong binder with high affinity and a very potent B cell depleter. Its one limitation really is it has a short human half-life. And to maximize the benefit of that second mechanism of action, the sustained BAFF receptor blockade, to have the tissue benefit and blocking the repopulation signal, we have designed JADE201 with half-life extension mutations to be able to cover the receptor for extended periods of time, to provide better receptor occupancy, to potentially drive better clinical activity, and do so with a less frequent, convenient subcutaneous dosing profile. Great. Novartis' drug, it seems like it is going to be the first approved in Sjögren's. But I do not know if you mentioned this, but the efficacy there has been fairly modest, right? So, I guess just relating it back to how you feel about the mechanism of JADE201, so how can it meaningfully push on efficacy? Is it that half-life point? Is it something else with the deeper penetration in the tissue? Yeah. The data set in Sjögren's with ianalumab is really interesting. Some of what you mentioned with the smaller treatment effects versus placebo are probably representative of some of the challenges in Sjögren's specifically as a disease in terms of the heterogeneity of the disease population, the ability of ESSDAI, the primary endpoint, to reliably capture disease activity, and the very large placebo responses that are observed in that study. When you look at the baseline characteristics in that study, that ESSDAI was approximately 12 on average, and ianalumab reduced that to six. A 50% treatment effect is very large and a very impressive reduction in disease activity. The problem is the placebo went down by 4.5 - 5, such that the treatment benefit, while statistically significant, wasn't as large as we had hoped. They do demonstrate very deep circulating B-cell depletion in that study. They also demonstrated in a repeat salivary gland biopsy 84% decrease in B-cell intensity. So really demonstrating effective activity within the disease tissue. Anything about the efficacy is probably related to the disease rather than the MOA. Interestingly, what they showed in that study is they evaluated two different dose intervals: a Q4-week dose, which provided the deep B-cell depletion and receptor occupancy for most of that dosing interval, and a Q12-week dosing interval, which provided the B-cell depletion but not the receptor occupancy throughout the dosing interval. The Q4-week interval performed much stronger than the Q12-week, which missed, showing the importance of receptor occupancy against the BAFF receptor in driving efficacy. We do think with JADE101, by design, its extended half-life and ability to cover the BAFF receptor through an extended dosing interval may provide some efficacy advantages relative to ianalumab. But we're not sure whether, for the reasons we talked about, the complexity of the disease, the heterogeneity, the challenges with the endpoints and placebo responses, whether that would be a prioritized indication for Jade right now. Got you. One minute left, so I want to sneak one in on 301. I guess, why are you excited about this drug? We now have an approved product in the indication that certainly a lot of people are excited about. But beyond that, what's going to be the unmet need, do you think, in the future, and how can 301 sort of ultimately fit that? Yeah, happy to take it. So, exciting that brepocitinib is approved, and I think that will raise disease awareness. But touching on what Tom said, dermatomyositis is a disease of both very painful, itchy skin lesions and also neuromuscular issues. I think looking at the dazukibart data phase II, I give Pfizer a lot of credit because they went into a very moderate severe patient population with skin manifestations, and that's historically been more difficult to treat. If you look at the CDASI, which is the outcome measure, they had a reduction of 14.5 points or, sorry, an improvement. Compare that to brepocitinib, they were about 4.5. I think what we see, because the interferon beta signature in this disease is so strong, that you're having a much more outsized improvement with a drug that's focusing on interferon beta as opposed to a pan immune suppressor like brepocitinib. I think from the standpoint of treating the disease symptoms, which are the most impactful to patients, which are those painful, itchy lesions, they lose sleep, they're very fatigued. That in and of itself has us excited and has all the rheumatologists we've spoken to who treat this disease are similarly excited because their patients are mostly complaining about their skin symptoms. That being said, even though they had a smaller cohort of patients, numerically, they showed a higher change in that Total Improvement Score or TIS, and that's representative of the neuromuscular function as well. Seem to be beating brepocitinib on the skin, and early phase II data indicates they could possibly be better in the neuromuscular component as well. They're dosed IV, we're dosed sub Q, we're half-life extended, so hoping to have sub Q dosing that's more convenient for patients directly addressing the underlying pathogenesis of the disease. Great. Well, we're up on time. Thanks for the great overview and the discussion, and thanks for joining us. Good luck, guys. Thanks. Thank you.