Great. Good afternoon, everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much for joining TD Cowen's I&I Summit for our next session. Very excited to be hosting Jade Biosciences. It's my pleasure to introduce Andrew King, the Chief Scientific Officer of Jade, as well as Brad Dahms, the Chief Financial Officer. Andrew and Brad, thank you very much for joining me. Thanks for having us. For those of you in the audience, if you have questions, you can go ahead and submit them via the web portal, and I'll do my best to get them asked. We've got a relatively short time here, 20-plus minutes. We'll go ahead and get straight into it, starting with JADE101. I think Jade is still a relatively new story for most investors. It would be helpful if you guys could start by giving just a very brief history of the company and an overview of lead asset JADE101. Yeah, yeah, sure. Yeah, thanks again, Tyler, for having us. Appreciate that. Yeah, so Jade's a relatively new company. Actually just founded last year. We're the fourth spin-out of Paragon Therapeutics. Paragon Therapeutics is a Boston-based team of very high-caliber protein engineers and drug discoverers. They try to develop best-in-disease biologics for several different areas. We're the fourth spin-out. We're spun out with three assets: JADE101, which is an anti-APRIL that we're studying for IgA nephropathy; Jade 201, which is an APRIL-class-related monoclonal antibody targeting BAFF-R, following the footsteps of inanalumab. We have a third program, which is JADE-003, which we haven't disclosed yet. We'll disclose that next year, but another exciting program. JADE101 was selected as the first asset, I think, really for a couple of different reasons. I think, number one, the Paragon team looked and saw a very high unmet need in IgA nephropathy. To this day, there are no approved disease-modifying therapies, though there are several in the pipeline, which I'm sure we'll get to later today. It is a very large market opportunity. There is a very high unmet need for patients. I think as they looked across the landscape, they saw really two areas to really improve upon. One was potency. You want to have the highest and longest coverage of APRIL, which is the main cytokine that we're targeting, which is implicated in IgAN. You also want to have a longer half-life. We use Paragon's YTE half-life extension technology to hopefully have the best-in-class dosing profile as well. Really solving for the potency and convenience that's lacking across the rest of the competitive landscape. On the financial backgrounds, we did a reverse merger that closed in April of this year. It was a $200 million pipe coupled with a $95 million convertible note. We just recently closed a financing with a very strong syndicate of investors of $135 million. Those closed last month. That's great. Thank you very much for that introduction. I want to ask about half-life. I guess, how long do you expect the human half-life for JADE101 to be, and what type of dosing intervals are you targeting relative to those in development right now? Yeah, so I can start there. What we disclosed so far is we have a 27-day NHP half-life. Typically, you see something like two- to four-fold. Though I'll let Andrew comment on this in a bit. There are some nuances to that, especially when you're targeting APRIL. Andrew, do you want to talk through some of that and how we're thinking about the dosing interval? Yeah, we haven't provided guidance on our projections of human half-life. As Brad mentioned, it's generally a two- to four-fold increase from non-human primate. Target-mediated drug disposition has been challenging for the first-generation anti-APRILs as it results in rapid nonlinear clearance and loss of pharmacodynamic activity. We selected JADE101 as a novel antibody in an effort to mitigate that TMDD with a novel epitope that avoids large molecular weight complex formation when binding APRIL. That's observed with the first-generation anti-APRILs in an effort to mitigate that TMDD risk. Half-life is important, obviously, in defining an extended dosing interval. So is potency. It's really the combination of those two that enables you to fully suppress APRIL for an extended period, which is really what's going to define the dosing interval. The great part about the APRIL MOA is it's so biomarker-rich, and the healthy volunteer data is extremely predictive of what you see in IgAN patients. By following these biomarkers, APRIL reduction, IgA suppression, we'll really be able to define that dose and dose interval to move forward into IgAN development. It'll be really those biomarker responses, which are the combination of the high affinity, 750 times higher binding affinity than sibeprenlimab, and the extended half-life. We think we can deliver a Q8-week dosing interval at least with the potential to extend beyond that. The phase I healthy volunteer data will provide the definitive guide on that. Great. Thanks for that. We'll get to the healthy phase I data and healthy volunteers here shortly and discuss biomarker responses. The ERA presentation in June, I believe it was, been screaming that from the rooftops because I feel like not enough people are aware of the significance of that. You mentioned TMDD and the significance of that. Maybe you could just elaborate on that, right? Why are you seeing specifically a different effect there? What data did you show in comparison to CBI when you think about different dose levels as well? Yeah, so we did disclose JADE101 as a novel anti-APRIL monoclonal antibody at ERA. It came from a de novo antibody discovery campaign, fully human IgG1 with new composition of matter patents that would support exclusivity through mid-2040s or patent term extension. There's really three properties. Brad highlighted two of them. Ultra-high binding affinity, which is important to potently suppress APRIL at low concentrations. YTE half-life extension to slow linear clearance and extend the dosing interval. The third is target-mediated drug disposition mitigation. APRIL is a trimeric protein, and when monoclonal antibodies bind trimeric proteins through this daisy-chaining-like phenomenon, you can form large immune complexes. These large immune complexes are predisposed for rapid clearance, resulting in this hallmark characteristic of rapid nonlinear clearance, which terminates the pharmacologic activity, and you need to dose again to engage the target. With JADE101, we selected a novel epitope, which precludes and prevents the formation of large immune complexes. We believe that strategy mitigates the potential impact of TMDD, and we've seen that in our non-human primate PK studies. Excited to see the translation of those three characteristics into humans, the ultra-high binding affinity, the YTE half-life extension, and the novel binding epitope to avoid large complex formation. Wonderful. Now getting to the update coming early next year in the first half. You talked about, so it's going to be phase I data in healthy volunteers. Obviously, we've now seen a fair amount of phase I PKPD data from YTE extended antibodies. What is a little bit different about this update? What biomarkers are you focusing on? What would you like to see? Yeah, yeah, it's a really good question. I think this is not the kind of typical phase I healthy volunteer update that you see in biologics. IgAN is very biomarker-rich, as you alluded to. We've seen this historic translation from NHPs into healthy volunteers and into patients. In fact, we just presented a translational analysis at ASN over the weekend detailing just that. Perhaps we can touch on that later. I think there are a lot of interesting updates at ASN. For this first data readout, I think we're really looking for maximal coverage of APRIL and for the extended dosing interval. As Andrew mentioned, our target is eight weeks. We'll be looking at APRIL reductions across that eight-week dosing interval. We'll also be looking at IgA levels and other biomarkers. Obviously, the primary endpoints are safety and PK. I think those biomarkers really inform our dose and our dose interval selection for subsequent development of JADE101 into patient trials as well. What sort of APRIL and IgA reductions do you think would be impressive or exciting? Yeah, yeah, that's a good question. Yeah, I mean, I think getting the maximum benefit is going to be predicted by maximum APRIL reductions. When you look across the competitive landscape, there aren't any of the molecules out there that can fully inhibit APRIL throughout their dosing interval. There have been some studies at higher doses of povetacicept. We know that they were able to fully suppress APRIL in their 240 dose. Unfortunately, they saw a high infection signal, so they took 80 mg forward. Similarly for sibeprenlimab, but for a different reason. In their phase II study, they used IV body weight-adjusted dosing. It was 2 mg for 1 mg per kg and then 8 mg per kg. At that top dose, they were able to fully suppress APRIL. In that top dose, they had greater than 60% proteinuria reductions. They also had 26% of patients go into clinical remission, which is, by the way, important with the recently adopted new KDIGO guidelines. 26% of patients going below 0.3 grams per day of proteinuria versus only 12% in that mid-dose. We think that getting full suppression of APRIL is very important, and that can influence the efficacy. That is really what we are trying to target with having this kind of high potency coupled with this extended dosing interval. We will be looking at those biomarkers in our first half 2026 readout next year. Great. Obviously, if you see that in healthies, one would hope you would see that in patients too, especially those with elevated levels. Hopefully that translates to proteinuria. I mean, I guess I feel like there's very little debate now, given all the data we've seen, that it's going to translate to proteinuria. I feel even weird asking the question if it's going to translate. I don't know if there's anything to keep in mind as you think about how it's going to translate to actual patients and proteinuria. Is it a pretty straightforward kind of linear translation, or do you think there are other things to keep in mind? Yeah, it is a pretty straightforward linear translation. You kind of look across the class. Whether you're looking at the selective anti-APRILs, we looked at Zigakibart, for example, which is actually not very potent. You still see pretty high proteinuria reductions, and you still see eGFR stabilization out to two years. If you look at the APRIL paths, you kind of see similar efficacy levels there. We do think that selective anti-APRIL is where you want to go, and that maximal suppression of APRIL will lead to the greatest efficacy. Just to add on that, Tyler, we did present a translational analysis of this at ASN last week in Houston, really leveraging the publicly available data across healthy volunteers and IgA nephropathy patients to establish those correlations and associations. The biomarker responses in healthy volunteers are highly predictive of the biomarker responses in IgA nephropathy patients. Those biomarkers, both APRIL suppression, IgA, Gd-IgA1 reduction, are highly predictive of clinical benefit. The great aspect of the APRIL mechanism of action, as you highlighted, is it's so validated in its disease-modifying potential. It's a direct line between pharmacokinetics, pre-APRIL suppression, IgA, Gd-IgA1 reduction, proteinuria reduction, eGFR stabilization. We do really feel confident if you can show the biomarker responses, you've got strong conviction you'll deliver disease-modifying efficacy in IgA nephropathy patients. Perfect. Yeah, very strong correlation with that data. I thought it was very interesting. Thanks for adding that. Maybe just briefly on safety. Obviously, the cleaner, the better. What are you guys most focused on with this class of drugs as you evaluate safety? Yeah, the APRIL mechanism has historically demonstrated a very favorable safety profile, even through chronic therapy at doses that completely suppress APRIL for up to a year with sibeprenlimab at that high dose in the phase II IgAN trial. In that study, the safety profile was very similar to placebo. Most importantly, no increased risk of overall infections relative to placebo control, even in the setting of full APRIL suppression. This is important because these are young adults when they're diagnosed with IgAN. They're 20, 30 years old. They need lifelong, potentially decades of therapy to be disease-modifying and safe and well tolerated. We really want to be able to deliver that profile with JADE101 to match what we've seen with the class, to be well tolerated and support this chronic dosing necessary to provide this long-term clinical benefit. At ASN, we did provide a poster on the preclinical safety of JADE101, demonstrated high selectivity to APRIL binding, a very favorable non-human primate toxicology profile, safe, well tolerated through all doses, establishing the high dose, no adverse effect level. We also demonstrated what I think is really important to this MOA, that it's really targeted immunomodulation. It's not broadly immunosuppressive. JADE101, even at these toxicological doses, had no impact on circulating B cells. Vaccination responses were well maintained, comparable to that of placebo control. It has this relatively modest reduction in IgG, a biological max reduction of 30%-40%. It really does set up well to deliver disease-modifying efficacy in a safe, well tolerated, not broadly immunosuppressive way. Our goal with the JADE101 healthy volunteer data is to really match what we've seen with the class and support a safe profile for chronic therapy in these young IgAN patients. Great. That obviously supports the pure APRIL approach as opposed to the APRIL BAFF [dual] approach. Maybe on that topic, can I ask you about some of the takeaways that you had from the ASN conference over the weekend and the additional APRIL and APRIL BAFF data that we saw? Yeah, maybe I can start. Yeah, so I think it was really encouraging to see all of the data presented at ASN. I mean, I think at a high level, I think IgAN was, I'll admit that I was looking for it, right? But I think IgAN might have been the sort of buzziest topic of discussion at that meeting. There was really a lot of enthusiasm around the kind of the two phase IIIs that were being presented and then also some POV data and others. We are really encouraged by just the level of engagement. I think this is just really like a renaissance for the field right now. It just has not seen these disease-modifying therapies that are soon to be on the market. I think overall, I think we walked away encouraged, right? We did not learn too much, but there were some nuggets there, right? I think there was a lot of discussion around the sibeprenlimab subgroup analysis, but we were still really encouraged. They presented some additional 48-week data showing continued proteinuria reductions, which is consistent with the class, and we believe, again, supports these anti-APRILs as being the sort of next first-in-class therapies here. There was definitely some discussion around some of the perceived safety signals and some of the others. I think it is too early to say whether those are meaningful. We were really encouraged by the overall enthusiasm for the class. I think the other thing we noticed was lots of discussion around patient convenience, around sort of more minor ways for patient convenience, like needle gauge size and other things like that. It really supports what we want to do, which is, I think, really optimized for patient convenience in the context of having the fewest doses per year, so no more than six doses per year. Yeah, I think we walked away really, really encouraged by all of the data readouts there. Okay. I guess just to follow up, though, on the povataciceb safety, is that something you were kind of expecting? Even though it's early, you've got to see how it plays out over the longer term, just does that support your strategy? I'm just curious to get brief thoughts on that. Yeah, maybe I can start, and then Andrew can definitely add on here. I mean, I think, yeah, it is our hypothesis that IgAN, because it's a plasma cell-mediated disease, you don't need to add this layer of BAFF on top, which could have more adverse events. We're not suggesting that that was causal here, but unnecessary immune suppression for these patients. We believe, Andrew mentioned, they're young, they're otherwise healthy. You typically want to avoid that. If all the clinical data support that it is APRIL that's actually driving all of the efficacy. We believe that that'll be potentially challenging for uptake for the duals because they're adding this layer of unnecessary immune suppression with this inhibition of a broader B cell compartment that, again, isn't adding anything to the efficacy. But Andrew, do you want to layer onto that at all? No, I think you covered it well. APRIL's selective inhibition gives the full disease-modifying efficacy without any unnecessary immunosuppression. Great. I want to get to 201, of course. Time's going quickly. If the phase I data look good in the first half of next year, what's the path to approval like? How quickly do you think you could get to market? Do you think you'll have the same approval pathway? How do you think about the landscape with several products ahead of you guys? Yeah, so I'll say a broad comment, and then Andrew, we wish you some interesting color from a KOL at ASN. Broadly speaking, we want to get to market as soon as possible. I think the precedent that we typically guide folks to is looking at what Alpine did, right? They presented six patients at nine months in a phase II before meeting with the FDA and getting the phase III going. I think that's broadly what we think. It is an evolving landscape. Maybe I'll pass it to Andrew, who had some interesting intel from a KOL over the weekend. Yeah, what we had was a public disclosure. The FDA has reconvened the Kidney Health Initiative, which is the ASN-FDA partnership that led to the validation of proteinuria and eGFR surrogates to drive innovation in IgAN. The FDA recognizes, with multiple approvals, a two-year placebo-controlled trial is becoming more challenging. They are exploring alternative innovative designs to ensure continued focus and development of new therapies. Really encouraged by that, given the timing of the JADE101 program with this group set to convene in Q1 of next year. That gives us confidence that there will continue to be a feasible and efficient path towards development and registration of new IgAN therapies. What we are hearing from these KOLs is it is really the duration of placebo control that is challenging. The potential to get eGFR endpoints through shorter follow-up. That sets up really well for the APRIL mechanism of action. That has large separation of eGFR from placebo early without any acute hemodynamic effects, confounding interpretation. We will be following this very closely. It could set up really well for JADE101 to continue to have perhaps an even more efficient development path. Wonderful. Last two or three minutes here. I have to touch on 201. It's pretty, I guess, maybe ironic with 101 that you're avoiding BAFF. And now with 201, you've announced that you're going after BAFF. So maybe you could talk about the antibody, why you're going after the BAFF receptor, what's unique about it, and what's differentiated, and the early clinical proof of concept for this class. Yeah, Andrew, do you want to? Yeah, Jade 201 is a half-life extended YTE-modified anti-BAFF-R receptor monoclonal antibody. It drives enhanced ADCC-mediated B cell depletion of BAFF-R-positive cells, which really are the plasmablast through the plasmablast stage, but avoiding depletion of the immature pre- and pro-B cells that are antigen naive in the bone marrow. It also binds the BAFF receptor and pharmacologically blocks the BAFF signal. In the setting where ADCC is not accessible, and this is particularly important in tissues where effector cells like NK cells are more sparse, Jade 201 can still bind the BAFF receptor and block BAFF signaling. This important pro-activation, pro-survival signal provides deeper depletion long-term through starvation of BAFF signaling. We think this is a unique mechanism of action that can directly address some of the limitations of other B cell depleting strategies to deliver not just deep and sustained peripheral circulating B cell depletion, but get into the tissues and deplete pathogenic autoreactive tissue-injuring B cells. Great. Maybe quickly on the design, sorry, Tyler, I missed the second part of your question. We're really following in the footsteps of inanalumab from Novartis, which is in a broad phase III program across six or seven different systemic autoimmune diseases with positive phase III readouts in Sjögren's and ITP reported recently, and a number of others are still ongoing. That drug has very desirable pharmacologic characteristics in terms of its binding affinity and its potency at depleting B cells. We recognized it has a relatively short human half-life of only 10 days, which limits the duration by which BAFF-R occupancy can be maintained to deliver the optimal therapeutic benefit with a convenient sub-queue dosing schedule. With Jade 201, we engineered it to retain those desirable pharmacologic characteristics of inanalumab, but incorporate LS, half-life extension into the FC to provide a twofold increased half-life in non-human primates relative to inanalumab to give us the opportunity to provide more complete and sustained BAFF-R coverage to deliver the full efficacy available to this MOA with a convenient infrequent sub-queue dose. Great. Why do you choose RA as the first indication to go into in the phase I? When might we be able to get phase I data from that study, and what might it look like? Yeah. Yeah. So because Jade 201 delivers enhanced B cell depletion, it's not appropriate to begin in healthy volunteers. We identified an autoimmune patient population where the benefit-risk is justified. That was really how we looked to establish RA. That's similar to Novartis's approach in their phase I. The trial is going to be placebo-controlled, single ascending dose. Obviously, we're looking at safety, tolerability, and PK. It's also very biomarker-rich. We're looking at BAFF-R occupancy, soluble BAFF levels. We'll also be looking at depth and duration of B cell depletion measured by flow cytometry. Also, because RA patients rapidly respond to B cell depletion, we can include some exploratory measures such as DAS28. We can potentially get some additional insight into Jade 201 even at the early stage. As far as your timing for data, once we start the study, we'll guide to that. It's just pretty mature at this point. Fair enough. I have to ask one more, even though we're well over time. You've got this slide in your deck with the potential indications, and the opportunity is massive, right, between all these indications. I understand you're going to want to get this phase I data first. How do you even begin to think about selecting between these different indications? Are you going to do some sort of basket trial, or how do you plan on making those decisions? Yeah, again, premature, I think you talk about the design of how we would run those potential studies. Yeah, you're right. We do have our eye on several indications, some of which inanalumab is currently being studied. As a reminder, it's in six different phase IIIs, a couple of read-out and a few more to read out next year and in the first half of 2027. I think we'll be in the fortunate position where we'll be executing on our RA study while monitoring the competitive landscape, not just within inanalumab, but in the broader competitive landscape before we decide where Jade 201 fits. The potential is great, right? We looked at 23 indications, and it's something like an $80 billion potential opportunity. Lots of enthusiasm, I think, across the board. We'll sit tight, and we'll start guiding into the next phase of the development as we get through our phase I study. Wonderful. One of these days, we'll learn more about the JADE-003 program. With that, Andrew and Brad, I thank you for your time. Thanks to everyone in the audience for attending our discussion. Thanks for having us, Tyler. Have a great--