Thank you for joining us to have a conversation with Mr. Tom Frohlich, the CEO of Jade Biosciences, and Dr. Andrew King, the Chief Scientific Officer and the Head of R&D. Both Tom and Andrew are industry veterans and worked together at Chinook Therapeutics, which acquired BioNovartis in 2023. Tom was the Chief Business Officer, and Andrew was the Chief Scientific Officer. Jade Biosciences is focused on developing best-in-class therapies to address critical unmet needs in autoimmune diseases. Its lead candidate Jade101 targets APRIL for the treatment of IgA nephropathy. Good afternoon, Tom and Andrew. Welcome. Thanks so much for hosting us and having a conference that's actually focused on kidney disease. We think this is a very underserved area, so really appreciate you shining the spotlight on it. Thanks. Sure. Tom, to kick things off, could you give us an overview of Jade's pipeline? Sure. I think you did a nice job, actually in the intro there. Jade is a company where we're dedicated to becoming best-in-class across a number of different autoimmune diseases. We started the company just over a year ago, actually in June of 2024, really focused on autoimmune disease with three assets that we have access to from Paragon, a company out of Boston that is really a specialist in protein engineering, has capacity to develop extremely potent binding monoclonal antibodies, and has this expertise in half-life extension technology, really looking to have best-in-class therapeutics across a number of different diseases. Our lead program, as you discussed, is Jade101. That's what we're going to be the development candidate. Jade101 is sort of the total program for anti-APRIL. It is focused on anti-APRIL, really with the lead indication around IgA nephropathy. I'm sure we'll talk a lot about that during the conversation today, but really, we believe we're developing a best-in-disease therapeutic. The stage of the asset right now is preclinical. We aim to get into the clinic this year, in 2025, with a very meaningful readout in the first half of 2026, which is really going to help us characterize the dose and dose interval for that product, as well as have really good biomarker data that will allow us to move very quickly into later- stage studies with Jade101. We also have two other assets that we have not actually disclosed the targets for, really for competitive reasons, but Jade02, what we are saying about that asset, it's not specifically a kidney disease indication. It is something that's broader. It is a B-cell depleting target that we are looking to get in the clinic in the first half of next year. We will disclose more about that target and the early development plan towards the end of this year. Jade03 as well, we have access to as well from Paragon, another Paragon -like target, which we're not disclosing, but there is a more advanced asset out there that does show clinical validation of the target. We believe through that protein engineering that we can really develop a best-in-disease profile with that asset as well. That's currently anticipated to get in the clinic in 2027. Early days for Jade, but a really exciting time with a really healthy pipeline at the outset of the company. Thanks, Tom. Let's focus on the IgA N space first. In the last couple of years, multiple drugs have been approved for the disease with multiple players and later- stage assets. How do you view the overall commercial opportunities in general for the space and also for Jade? Yeah, it's a great question. As you mentioned about the panel earlier today with IgA N, it's a very rapidly evolving space. Sorry, I'm trying to turn off my team's messaging here. It's making some noise. Yeah, we believe that it's a large commercial opportunity. It has likely over a $10 billion branded opportunity. There's 170,000 patients in the U.S. 60% to 70% of those need further treatment. They're above that 0.5- gram- a- day threshold. We believe that the anti-APRIL mechanism is really going to come to the forefront of treatment and become a foundational therapy within IgA N. We see a very large commercial opportunity here within the space. None of the currently available medications actually are disease- modifying. They currently play on different elements of nephron protection, but they don't actually hit that galactose- deficient IgA and take away that root cause of disease. None of them have been able to show actually preservation of kidney function as measured by eGFR. We believe there's going to be a really large demand for the APRIL class of therapeutics as they continue to evolve. I see. Let's speak of the Jade101 and the APRIL pathway. How does Jade101 differentiate from the other anti-APRIL or BAFF-APRIL dual inhibitors? What potential clinical advantage could that feature of the Jade101 translate to? That's really a key focus for Jade. We believe that the APRIL class is really going to dominate. We have seen the recently proposed updates to the KDIGO guidelines. Those are the clinical guidelines for the management of IgA N. They really do call for therapeutics that allow for that depletion of pathogenic IgA. We do believe that there is going to be large usage of both the APRIL and potentially the APRIL-BAFF. They're also calling for very ambitious proteinuria- lowering targets, really asking for every patient to get below 0.5 grams a day, preferably actually back into that clinical remission range to below 0.3 grams a day. Really, the only agents that have shown to have that large proteinuria- lowering and getting rid of the pathogenic forms of IgA are the APRILs or the APRIL-BAFF. We believe there's going to be a large preference for the selective anti-APRIL inhibitors. That really is because nephrologists want to minimize immune modulation. In the past, they have actually been scarred by immunomodulators or immunomodulators like steroids. We believe they're going to choose the most targeted agents. What we've seen between APRIL and APRIL-BAFF, it seems like all of the efficacy in IgA N specifically is coming from the APRIL component. If you look at the use of CD20, so broad B-cell modulating agents, they don't really have any effect on IgA nephropathy, either reductions in total IgA or proteinuria levels. Similarly, with specific anti-BAFF inhibitors like leucidamide, they've shown no effect in IgAN. When you look at cross-trial comparisons, looking at selective anti-APRILs versus the dual anti-APRIL-BAFFs, the results actually across all of those biomarkers look remarkably similar, really indicating that all of the efficacy is being driven by APRIL and BAFF is really not adding any additional efficacy. This has recently actually been confirmed with two large phase III trials looking at atacicept, which is a dual APRIL-BAFF, looking at that proteinuria reduction in their phase III interim analysis versus sibeprenlimab from Otsuka. The results actually look fairly similar. In fact, numerically higher reductions in proteinuria for the selective anti-APRIL. We really believe that all the efficacy is being driven by APRIL and that physicians and patients are really going to choose the more selective immunomodulator, especially for these patients that are in their 20s and 30s and really need decades and decades of treatment. We believe the more selective agents are going to be selected. We believe anti-APRILs are going to win. Within that, and Andrew can probably elaborate on this more when we talk about the preclinical profile of Jade101, we believe that there's room for the most efficacious anti-APRIL, sibeprenlimab, which is Otsuka's medication, really transferred from an IV body weight adjusted dosing in phase II into a flat subcu 400 mg dose in phase III. We believe they're not optimizing the dosing and leaving efficacy on the table. We want to differentiate by having the most effective anti-APRIL and doing that with a half-life extended molecule where we can dose it at much less frequency. Highest forms of clinical activity with the least number of doses. In fact, no more than one subcu injection every eight weeks. I see. Thanks, Tom. I guess, and Andrew, that it's a good leading to for the next question for you. For the preclinical data-wise, could you give us an overview about the 101? Yeah, so Jade101 is a fully human monoclonal antibody that neutralizes APRIL. As Tom mentioned, it has YTE modifications incorporated into the Fc, clinically validated half-life extension strategy. We actually presented a detailed characterization of Jade101 recently at the European Renal Congress annual meeting, which we think supports the best-in-class properties that deliver this best-in-class clinical activity with a convenient infrequent dosing schedule. We highlighted the ultra-high binding affinity of Jade101, a femtomolar binder, so extremely high binding affinity, about 750-fold or more higher binding affinity than the other anti-APRILs currently in development. Jade101 has a novel binding epitope that functionally blocks BCMA and TACI binding. It's two receptors that drive plasma cell survival and IgA class switching, respectively. We think that this epitope is important because it avoids the formation of large immune complexes that happen with the first- generation anti-APRIL antibodies, and happens frequently with antibodies that bind trimeric proteins like APRIL through this daisy- chaining-like phenomenon. You can produce large immune complexes that are rapidly cleared and contribute to this target-mediated drug disposition effect, or TMDD, that results in rapid non-linear clearance of those agents and limits the pharmacologic activity. Jade101 was selected specifically to avoid large complex formation and therefore potentially mitigate this TMDD effect that's been challenging for first- generation anti-APRILs to navigate. We also report that Jade101 completely blocks the binding and signaling through BCMA and TACI in translational model systems, prevents APRIL-mediated plasma cell proliferation and IgA production, the key mechanism of action by which anti-APRIL provides therapeutic benefit in IgA N. Maybe most impactfully is the very differentiated non-human primate PK/PD profile. NHPs are considered translational for both YTE half-life extended antibody but also the biomarker-rich response to anti-APRIL. What we observe with Jade101 is slow linear clearance with a half-life of 27 days, nearly four-fold longer than that of sibeprenlimab. We mitigate TMDD, so maintain pharmacologically active concentrations for a long runway. This results in deep and sustained IgA reductions. Really pleased with this combined profile supporting the potential for best-in-class properties. Thanks, Andrew. Given you guys are looking to push Jade101 into the clinic this half and getting the data in the first half of next year, could you give us more color on the trial design for the Phase 1? I guess it's Phase 1a in the healthy volunteers, and what kind of data we could expect next year? Yeah, the design is fairly conventional, single-ascending dose study in healthy volunteers. It's a double-blind, placebo-controlled study to establish safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics following sequential single-ascending doses administered subcutaneously to healthy volunteers. It's fairly typical, although we'll include extended follow-up to characterize the extended half-life of Jade101. Most importantly, the pharmacodynamics are very biomarker-rich, where we'll be able to track free APRIL reductions over time, so a direct measurement of target engagement and the accompanying immunoglobulin changes that represent downstream modulation of plasma cells. We do plan to report interim data from this study in the first half of next year, which will include the initial safety and tolerability and pharmacokinetics that you typically get out of a phase one healthy volunteer. Where we think this study will be especially informative and provide a very detailed characterization of Jade101 will be in the biomarker profile. We're really aiming at using this phase one healthy volunteer study to define the dose and the dose frequency for which we'll advance into clinical development in IgA N because historically the PK/PD in healthy volunteers for the APRIL mechanism has been highly consistent and predictive of efficacy in IgAN patients. In particular, as Tom highlighted, we'll be looking for the dose that provides full suppression of APRIL and the dosing interval will be defined by the duration by which that full APRIL suppression can be maintained. I see. Speaking of the biomarker now, especially for the IgA reduction, in your perspective, what level of that reduction in the healthy volunteer would be a strong proof of concept signal for Jade101's efficacy in the IgAN patient? Yeah, we're really fortunate to have two anti-APRIL monoclonal antibodies with published phase one healthy volunteer data to really benchmark around for expectations for Jade101. In those studies with sibeprenlimab and zigakibart, a range of doses were tested intravenously, including very high intravenous doses of sibeprenlimab and zigakibart that resulted in full suppression, complete inhibition of APRIL for a sustained period of time. These high IV doses were not feasible to be continued in clinical development, particularly as these programs transition to subcu administration. By fully inhibiting APRIL, they do provide the maximal biological effect available to the APRIL MOA. What we saw with these high IV doses of those two agents were IgA reductions that peaked at around 50% or so reduction from baseline. With Jade101, we think a strong data set would be able to match this full APRIL inhibition and maximal IgA reduction in this 50%-ish range. We hope to be able to achieve that with a feasible subcutaneous dose that we can advance further into clinical development. While we don't expect to be able to reduce IgA below the biological max, we do believe that we'll be able to maintain that deep IgA suppression for an extended period of time due to the half-life extension incorporated into the Jade101 framework. Gotcha. Tom, I guess another big picture question is we all know the IgA, the prevalence is different in the Western world and the Asia-Pacific market. What's your strategy for the ex-US market, especially in the Asia region? Yeah, great point. As mentioned, there's 170,000 patients in the U.S., several hundred thousand in Europe, but then millions in Asia. Asia is an extremely important region for IgA nephropathy. Not only commercially, we're going to pay close attention to that, but particularly for the development pathway to be able to enroll patient trials at a rapid rate. We want to have a close focus there. For now, we have global rights to Jade101 and really unencumbered, and our plan is to move forward ourselves there. We'll be looking for different methods to access those markets in a very efficient way. Gotcha. The last question regarding the Jade101, could you give us a little bit of flavor regarding the IP landscape about the 101? Yeah, it's a de novo antibody, so completely newly discovered by Paragon. We did file IP on that last year. We expect to have runway out to 2040 in the mid-2040s. Okay, gotcha. Just a quick question regarding the Jade02 and Jade03 program. As far as I understand, Jade currently is the only exclusive option for those two programs or asset-wise. What was the strategy behind the structure of these as an option? What kind of factor will influence your decision to exercise the option to take the asset in-house? Yeah, we do have full options to Jade02 and Jade03, and we can exercise those really whenever we would like. It's really just a simple matter of sending an option exercise notice and then fully executing the license agreement. Many of those terms were actually pre-recorded in the option. It's a very straightforward element that's completely in our control. Gotcha. For closing, could you remind us what's the major catalyst for Jade in the next 12 to 18 months and your cash position right now? Yeah, as mentioned, the biggest catalyst for us is getting into the clinic with Jade101 by the end of this year. That phase one healthy volunteer readout in the first half of 2026 is a very meaningful catalyst for us in the sense that it will fully characterize the compound and allow us to move forward very quickly into patient trials. That's the big one. We also anticipate getting into the clinic with Jade02 in the first half of next year. That is going to be a really meaningful event for the company to have multiple clinical programs ongoing. Later this year, we will disclose the target of Jade02 as well as the clinical development pathway, which we think will be of interest to investors as well. Cash runway, I think we're in a very fortunate position. We closed this reverse merger at the end of April. At the time of the last quarter close, we had $50 million in cash at the end of March. With the reverse merger closing, we brought in a PIPE of $205 million. Obviously, there's some bankers' fees, but we're well capitalized to fund our current development plan through 2027. Awesome. Tom and Andrew, thank you very much for taking the time to talk to our audience today. I really appreciate your great insight. I'd also like to thank all the audience who are tuning in online today. Thank you again from the HCLA and RIT. Thanks. Thanks.