Great. Good afternoon, everyone. Happy to have the Jade Biosciences team here, Tom Frohlich, CEO, and Andrew King, CSO. You know, maybe to start things off, maybe, Tom, do you want to give a brief overview of Jade, and then we'll get into a Q&A? Yeah, thanks so much, Alex and the Stifel team for hosting us here. We're really pleased to be in New York and having some great meetings over this last couple of days. Yeah, so Jade Biosciences, we are a company focused on developing best-in-class therapies for autoimmune disease. We're actually pretty recently formed. We just got started in June of 2024, but we've made a lot of progress over that short history. We've managed to assemble a really top talent team of development specialists that have a lot of experience in the therapy areas that we're going into. We've also accessed three assets from Paragon. It's an antibody protein engineering company out of Boston who really specialize in developing high affinity antibodies with half-life extension technology to develop best-in-class therapeutics. Our lead program is an anti-APRIL, JADE101. Initial indication that we'll be targeting there is IgA nephropathy. We think that is a huge market potential, $10+ billion market opportunity in the U.S. alone. We have high conviction that the selective anti-APRIL class will actually move to become foundational frontline therapy across patients. We believe that's because it has disease-modifying potential and does that without any unnecessary immunosuppression. We think JADE101 has a clear pathway of becoming the best-in-class anti-APRIL through a very potent mechanism of action that can fully maximize the efficacy available to the mechanism and do that with the most convenient dosing. We're aiming for no more injection, no more frequently than one injection every eight weeks. We've just recently initiated a phase I healthy volunteer study for that program. We announced in September we have dosed our first cohort, and we're tracking towards that phase I readout in the first half of next year. Very important readout for Jade, but also very interesting because in IgA nephropathy, it's a very biomarker-rich disease, and the biomarkers we get from the healthy volunteers should read through to really give us conviction that we've got that best-in-class possibility of clinical activity, but then also define our dose and dose interval to allow us to move forward into patient trials extremely efficiently and quickly. Also, in October, we disclosed our second program, JADE201. It's a BAFF receptor. It's an afucosylated antibody, really following the footsteps of ianalumab, which is a compound being developed by Novartis across a number of different autoimmune indications. We're moving forward very quickly with that program. Anticipate getting the first trial initiated in the first half of next year, initially in patients with rheumatoid arthritis, and then we'll decide which indications to go into subsequently after that. We also have JADE03, which we're not talking too much about, but that's another program we've accessed from Paragon and aim to get that into the clinic in the first half of 2027. That's all underpinned by the strong team, but also we have strong finances. We initially launched in April with a reverse merger where we brought in $300 million, and then in October, we actually also had a pipe where we brought in another $135 million. We are very well financed to execute on our programs. Great. Lots going on. Maybe starting off with IgA N, there's also a lot going on in that space. You know, how would you characterize where the current treatment landscape sits today and how you expect it's going to evolve over the next five years? I think in particular, you know, the implications of the updated KDIGO guidelines as well. Yeah, it's a fascinating time actually for IgAN because it is changing at a rapid pace. I think if you rewind even six or twelve months ago, most patients were treated like any other chronic kidney disease. So they're mostly put on just old ACE inhibitors or ARBs, just really treating blood pressure and the hemodynamic effects of disease, and then very quickly progress to steroids. Now in the last couple of years, there's the advent of new therapies like formulated steroids, endothelin receptor antagonists. There's more and more IgAN-specific drugs that are being used, and that's actually really driven a lot of changes in the KDIGO guidelines. We think they shape exactly how we believe the treatment landscape is going to evolve. Two main things that we really point to that are just going to completely change the dynamic. One is they're calling for every single patient to be treated with an agent that can deplete pathogenic IgA. Really to treat IgA nephropathy like an autoimmune disease. That's where we think that the selective anti-APRILs and the APRIL-BAFFs will move to frontline therapy. The second element is they're talking about having very ambitious proteinuria targets. They're saying that every patient needs to get below 0.5 g a day, preferably below 0.3 g a day, because that's what really reduces the long-term chance of disease progression. That's essentially normalization of proteinuria, right? Exactly. Below 0.3 g a day is considered normal and considered clinical remission. We think that the way it's going to evolve is every patient with IgAN is going to be prescribed an ACE inhibitor to control kind of those hemodynamic effects, and they're old and they're cheap and they're very safe, but then also use actually a selective anti-APRIL because we believe that that gets you that disease-modifying potential of reducing galactose deficient IgA, can stabilize eGFR, get those proteinuria levels extremely low, and do that without the unnecessary immunosuppression of BAFF. Yeah, so I think the other element here, coming out of ASN last week, we're getting a lot more data from the phase III programs for the BAFF and BAFF-APRIL and APRIL ones out there ahead of the sibeprenlimab PDUFA in a couple of weeks. Vera has now filed. Vertex with povetacicept is on the verge of filing. You know, what does the breadth of data kind of tell us at this point about APRIL inhibition, APRIL and BAFF inhibition as it relates to efficacy in IgA N? Yeah, it's an extremely exciting time. Do you want us to summarize it, Andrew? Yeah, happy to. We believe that selective APRIL inhibition can provide the full therapeutic benefit of B-cell modulation without any unnecessary immunosuppression as it's targeted exclusively to the plasma cell. When you look in cross-trial comparisons, first across the phase II programs, you see very similar responses between selective anti-APRILs and dual APRIL-BAFFs. Very similar biomarker responses, reductions in IgA, galactose deficient IgA1, similar reductions in proteinuria. Selective APRIL inhibitors alone can provide that full eGFR stabilization with zigakibart showing that out through two years. Historically, selective BAFF inhibitors have not been effective in IgAN, and even broad B-cell depleting approaches like rituximab have failed in randomized clinical trials. We really believe the full efficacy can be achieved with APRIL targeting the plasma cell. Our initial read on the phase III trials with atacicept and sibeprenlimab reporting out their top-line proteinuria data, the selective anti-APRIL sibeprenlimab had a numerically greater 51% reduction in proteinuria than the dual APRIL-BAFF atacicept. We have strong conviction that selective anti-APRIL, devoid of unnecessary B-cell depletion in this young patient population diagnosed in their 20s and 30s, potentially needing decades of therapy lifelong, selective APRIL can provide that with the most selective targeted approach. With this sort of foundational understanding of the space, you know, can you talk about the design of JADE101 and how that fits into this broader both where the field is going and the data sets that we have today? Yeah, so the first generation anti-APRILs have a number of potential limitations, including relatively modest potency in its ability to block APRIL, as well as relatively short clinical half-lives because of the strong influence of target-mediated drug disposition on the APRIL mechanism. JADE101 was designed really to address those limitations. It's a novel antibody discovered from a de novo antibody campaign. It's a fully human IgG1 neutralizing antibody that was selected for ultra-high binding affinity to APRIL in the femtomolar range. Its KD is 50 fM, which is approximately 750-fold higher than sibeprenlimab, over 2000-fold higher than zigakibart. So really addresses that limitation of being able to fully suppress APRIL at low plasma concentrations. In addition to that, JADE101 has the YTE half-life extending mutation incorporated into the Fc to promote antibody recycling and extend the plasma exposure with the goal of delivering the full disease-modifying efficacy to the MOA with a convenient infrequent dosing schedule. Yep. Yeah, I guess specifically this goal of getting even greater potency at APRIL versus sibeprenlimab, why is that important here? And And how is this different than just sort of slapping a YTE on sibeprenlimab? Yeah, so we actually did slap a YTE on sibeprenlimab as part of our discovery campaign and did get an incrementally longer human half-life, about twofold longer than unhalf-life extended sibeprenlimab, but we're still limited with the relatively high plasma concentrations you need to suppress APRIL and get the deep IgA reductions you want for therapeutic benefit. With JADE101, we're able to extend the half-life in non-human primates approximately fourfold from that for sibeprenlimab. Because of the ultra-high binding affinity, you don't run out of pharmacodynamic activity at low plasma concentrations. You can continue to suppress APRIL and lower IgA, which allows you to further extend the dosing interval. Our goal in this young, otherwise healthy patient population is to minimize the burden and provide the most convenient dosing schedule possible. Maybe we could talk a little bit about this goal of getting greater APRIL suppression, particularly in the context of the data we have from sibeprenlimab moving from phase II to phase III. Yeah, maybe I'll start with that. So yeah, as you point out, Alex, sibeprenlimab ran a pretty comprehensive phase II trial using IV body weight-adjusted dosing where they had three different doses, 2 mg/kg, 4 mg/kg, and 8 mg/kg. And they did see a clear dose response across the three dose levels where at the highest 8 mg/ kg dose, they were getting full APRIL suppression throughout the dosing interval, and that did translate into slightly higher reductions in proteinuria overall. And then what we think is very important, which you pointed at the beginning, they had nearly twice as many patients get into clinical remission, so below that 0.3 g a day as they did in their middle dose. When they move forward from their phase II body weight-adjusted IV dosing into a flat sub Q, they actually fit as much as they could into a single vial that they're dosing every four weeks, so 400 mg, which they have stated is roughly equivalent to their middle dose, that 4 mg/ kg. They're not completely optimizing the dosing to get the full efficacy available in the mechanism. That's why Andrew and his team have designed JADE101 to be ultra potent and be able to capture that full efficacy across the entire dosing interval. We also saw just recently at the ASN over the weekend, sibeprenlimab did provide an update of their phase III continuation of the top line that they announced in June at the European Renal Association meeting. They showed very consistent results. They showed that same 51% reduction in proteinuria at nine months, continued decrease over time. At 12 months, they did get up to 54%, which we expect to see with this entire class of medications that over time you get deeper lowering of proteinuria. When they ran this subgroup analysis, it was very consistent across age, race, sex, but when they looked at geographic distribution, there was a slight difference within North and South America. What's going on there? It's hard to say, and it could be as simple as it's very small patient numbers. I think the North American patient numbers were just about 20, which is a small group, so there will inherently be a lot of variability. We've also always thought that potentially in North America, where people tend to be a bit larger, there's more of a male to female prevalence of IgA N, that that's where not having that body weight-adjusted dosing could result in different exposures. We're not sure. Very early, that's very speculative, but we do believe that with JADE101, where we are getting more potent inhibition and getting that full suppression can lead to potentially the highest available clinical activity to the mechanism. The other thing at ASN, just to point out as well, which we do think about with JADE101, is a lot of the discussion between the KOLs and between the companies was really around differentiating around convenience, which is going to be extremely important in this patient population because IgA N patients are typically diagnosed in their 20s and 30s. They have lifelong treatment that's required. They do not have any symptoms, so having something really convenient is important. We started seeing that between the different players in the space, trying to differentiate around injection volume or the dosing format or the device, but we think having a longer dosing interval is actually going to be the ultimate differentiator on convenience. We are really bullish on achieving that clinical activity and doing it with one injection, no more frequently than every eight weeks. Heading into your phase I update early or first half of next year, I guess, you talked about the biomarker-rich element here. You've presented some more data now at ASN too talking about those correlations. Can you walk through that and what you would expect to see coming out of the phase I readout? Yeah, so the translational analysis we performed was on all of the publicly available data for the first generation anti-APRILs, anti-APRIL BAFFs. What we observed was highly consistent PK and PD responses in healthy volunteers and IgA N patients. We do believe what you see in healthy volunteers in this phase I study will be predictive of the PK/PD biomarker response in terms of APRIL suppression and IgA reduction that we will see in IgA N patients. Those mechanistic biomarkers, both APRIL reduction and IgA reduction, are highly predictive of future clinical efficacy in terms of proteinuria reductions and eGFR preservation. Really consistent observations that PK leads to free APRIL suppression, leads to IgA reduction, proteinuria, and eGFR. We believe we can use this phase I healthy volunteer data set to select the dose and the dose interval, which will be able to be advanced quickly into IgA N development. Based on your modeling, how are you thinking about dose interval coming out of the phase I? What kind of a half-life would you need to see in humans to get to every eight week or less frequent dosing? Yeah, we do think half-life is important, but it's really a combination of half-life exposure and then potency that allows you to suppress APRIL. Obviously we will be measuring half-life, but we're really more focused on the biomarker responses. It's the depth and duration of APRIL suppression and then the accompanying deep IgA reduction that follows that that will define essentially the profile that can provide the full therapeutic benefit to this MOA at the least frequent, most convenient interval. What's great is we'll just see the data to help us make that decision. We think from our preclinical data, we're confident in delivering a Q8 week dosing interval, which we believe will be highly differentiated and valuable, just six injections per year for IgA N patients over multiple decades with potential to see more depending on how the data translates from NHP to humans. Coming out of phase I, what does the path look like then towards your later stage development? Can you move right into a pivotal trial? How are you thinking about that? It's a great question. To be frank, we haven't guided on this. A lot of it will be dependent on the data that we get out of phase I. We also need to interact with regulators to define that path forward. We do think there's a very efficient development pathway. As Andrew mentioned, out of that phase I, we will define the dose and dose interval. There is no need for dose range finding in a phase II. We do think we can do something extremely efficient. Our base case is something similar to what Alpine did with povetacicept, where we do a very targeted open label phase II. I believe they had six patients' worth of data at 36 weeks, which then allowed them to trigger their phase III. That's a possibility of doing something like that. We also do want to explore other areas where we can potentially accelerate things as well. We want to try to move as quickly as possible. We're pretty bullish on our ability to execute quickly. We do have a very talented team that has a lot of experience in IgA N. Actually, we want to learn from what povetacicept just did in their phase III. They actually managed to enroll 600 IgA N patients in just under 15 months, which we do think sets a new benchmark for the speed of enrollment that's possible. We talked to a lot of investigators about how they did it so quickly. We do believe there's huge demand for these B-cell modulators, specifically anti-APRILs. We do think there's an excellent clinical trial infrastructure now built out in IgA N that we can tap into very readily. There is also a resourcing model that we can employ to try to accelerate that phase III to get it recruited really quickly and establish an efficient path to market. We are also hearing some buzz around what that development pathway looks like. I do not know if you want to expand on that, Andrew. Yeah, a really encouraging update out of ASN was from the IgAN Network Consortium where it was shared that the FDA has requested to reconvene the KHI in the first quarter of next year, which is the body that did the analysis leading to the recognition of proteinuria as a surrogate endpoint to support accelerated approval with eGFR confirmation at two years. The FDA has publicly commented on the challenges of running two-year placebo-controlled trials in this new environment with multiple approvals and is looking for guidance from additional data analysis and the experts that could support kind of continued innovation in IgAN in that setting of new approved treatments. One of the areas we think could be of discussion is the duration of follow-up needed for that eGFR confirmation. What we're encouraged by with the APRIL mechanism of action is you do get large and early separations in eGFR from placebo without any confounding hemodynamic effects. Also, one potential outcome of this analysis and conversation could be shorter duration of follow-up for eGFR and full approval, which would obviously be very advantageous to Jade given the timing of our program. Interesting. I want to spend some time now on 201, your new program. I guess maybe to sort of lay the groundwork, why is this BAFF receptor targeting antibody approach interesting and kind of how has it been validated by ianalumab to date? Yeah, we think there's a lot of potential for 201. I think it's been clearly demonstrated that getting deeper B-cell depletion across indications leads to better activity. We do believe with the BAFF receptor mechanism of action that there's possibility of doing so in a very patient-friendly way. Do you want to describe the BAFF receptor mechanism? Yeah, so J201 is a half-life extended afucosylated anti-BAFF receptor monoclonal antibody, which is a B-cell depleting strategy through a dual mechanism of action. First, through afucosylation, it delivers enhanced effector function mediated ADCC for direct B-cell killing of BAFF- R expressing B-cells, resulting in deep sustained circulating B-cell depletion. However, one of the limitations of other B-cell depleting strategies is following B-cell depletion, you get this large compensatory increase in BAFF that serves to drive B-cell repopulation and is also thought to be an important initiator and driver of maintaining autoreactivity. The other B-cell depleting approaches leave that BAFF unopposed, whereas J201, in addition to driving ADCC, binds and pharmacologically blocks the BAFF receptor. It will block that upregulation of BAFF that occurs following B-cell depletion. This is particularly important in the tissues where effector cells are more sparse and the ability to conduct ADCC is more limited. At least in that setting, you'll be able to block this really important B-cell activating and survival signal and ultimately result in B-cell depletion through starvation from BAFF. Novartis has validated that clinically. Mechanistically, in Sjogren's disease patients, you'd not only see deep circulating B-cell depletion, but you see significant depletion in the salivary gland, demonstrating the ability to really get at that source of autoreactivity and tissue injury. How is 201 both similar and differentiated from ianalumab? Yeah, ianalumab has attractive pharmacologic characteristics in terms of high affinity for the BAFF receptor and potent B-cell depletion. It has a relatively short human half-life. However, it's only 10 days, which limits the duration by which it can cover the BAFF receptor to not only drive B-cell depletion, but to block that compensatory BAFF upregulation. JADE201 was designed to maintain those pharmacological attributes of ianalumab that are strong, but address the short half-life. We've incorporated the LS mutation into the Fc to promote antibody recycling, extend pharmacokinetic half-life while retaining enhanced effector function to deplete B-cells. That gives JADE201 an approximately twofold longer non-human primate half-life than ianalumab and offers us the potential to provide more complete and sustained BAFF receptor coverage with a less frequent and more convenient subQ administration in the clinic. What does the phase I design look like and how do you then move towards patient studies? Yeah, we are on track to initiate a phase I first in human study in the first half of next year. Because this is an enhanced B-cell depleter, it's not appropriate to go into healthy volunteers from a benefit-risk perspective. So we've selected rheumatoid arthritis as the patient population that can be most efficiently, most feasibly enrolled to justify this benefit-risk to generate a clean first in human data set. There'll be six sequential cohorts looking at single ascending doses with the primary endpoints focused on safety, tolerability, secondary and exploratory endpoints looking at pharmacokinetics, BAFF receptor occupancy, using flow cytometry to look at B-cell subpopulations for the depth and duration of B-cell depletion. Because RA responds quickly therapeutically to B-cell depletion, we've also included DAS28 as an exploratory endpoint to capture the potential for JADE201 to impact joint pain, swelling, and CRP at the higher doses that are therapeutically active. This RA is really more around the ability to generate this data set conveniently and feasibly. It doesn't necessarily indicate RA prioritized as a future indication, but we feel like the PK/PD data set that we can generate in RA patients would set up for prioritized indications in phase II to follow, whether they're fast follower indications to ianalumab, depending on how those data sets read out, or potentially first-in-class opportunities where ianalumab is not being evaluated and agents like rituximab are currently standard of care. How do you plan to, or how are you thinking about disclosing data out of this phase I RA study? Obviously, you're going to have a lot of different doses. Some of them will be subtherapeutic. At what point will you be able to say something about the molecule and next steps? Yeah, I think we haven't quite guided on that yet. I think we'll have to get this study up and running. Unfortunately, it's not like a healthy volunteer study where you can warehouse patients and deploy all at once and you have a pretty good line of sight. This is going to be a multi-center study in RA patients that enroll as they come in. Just consistent to what we're doing with 101, we want to have a pretty healthy, fulsome data set and disclose when we have a good PK/PD profile and safety profile. Great. So then following your recent financing, where are you at now with cash runway and what does that get you to from an update perspective? Yeah, we're actually disclosing tomorrow, but our last for the quarter, the Q3 is tomorrow. But as of June 30th, we had $221 million in cash and we brought in this $135 million. So pro forma, you can kind of do the math there. It does not count the burn for Q3, but that gets us through or into the first half of 2028. So through the meaningful data readout in the first half of next year and gets us underway on 201 and 03. Great. Tom, Andrew, thank you very much.