Good morning, welcome to the Jade Biosciences conference call and webcast to discuss JADE101 phase I healthy volunteer study results. Please note that this call is being recorded and will be available for replay on our website, jadebiosciences.com. At this time, all participants are on a listen-only mode. Following the formal remarks, we will open the call for questions. Now I'd like to turn it over to Tom Frohlich, Chief Executive Officer of Jade Biosciences. Please go ahead. Thank you, and good morning, everyone. Earlier today, we announced positive interim results from our phase I trial for JADE101, a potentially best-in-class, fully human monoclonal antibody designed to selectively inhibit a proliferation-inducing ligand or APRIL. APRIL is a key driver of pathogenic IgA production in patients with IgA nephropathy, a progressive autoimmune kidney disease that presents a lifetime risk of kidney failure. On today's call, we'll walk you through interim results for the phase I trial for JADE101 and our development plans for this candidate. Moving to slide two. Before we begin, I'd like to note that today's discussion will include forward-looking statements. These include statements about Jade's development plans and the therapeutic profile and potential of JADE101 and our cash runway. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements. We will also be making comparisons of data across separate non-head-to-head studies, and caution should be exercised when drawing conclusions from such comparisons, as the data may not be directly comparable. For a full discussion of risks and uncertainties associated with our business, please review the cautionary language included on the disclaimer slide of this presentation and in our latest SEC filings. I'm joined today by Dr. Andrew King, Jade's President of Research and Development. Slide three. Let me start with the main takeaway from today's call. I'm very pleased to present that the data from the JADE101 phase I trial exceeded our expectations. The JADE101 results demonstrated deep and durable reductions in IgA, a favorable tolerability profile, and support the potential for every 12-week maintenance dosing with a single subcutaneous injection. The emerging profile of JADE101 is highly differentiated and has the potential to provide a meaningful advance for patients with IgAN. These are patients who are often diagnosed as young adults and require lifelong therapy. These results are especially meaningful as biomarkers from healthy volunteer studies translate closely to anticipated results in IgAN patients and provide an extensive characterization of JADE101's profile. This phase I tested whether the design features of JADE101 with its ultra-high potency, engineered half-life extension, and selective anti-APRIL MOA could deliver a differentiated target product profile in IgAN. Results of this phase I trial met or exceeded all four of our key objectives. The first objective was to design a dosing interval of at least every eight weeks, determined by the duration of IgA suppression prior to recovery. I'm pleased to report, and as Andrew will describe in more detail, we believe the depth and duration of IgA reductions observed with a single dose of JADE101 supports the potential for a maintenance dosing interval of every 12 weeks. The second objective was to demonstrate a favorable, well-tolerated safety profile, generally consistent with prior experience with selective anti-APRILs. JADE101 did in fact have a favorable safety result at all tested doses, was well tolerated locally with only infrequent mild or moderate injection site reactions, and no cases of hypogammaglobulinemia. The safety profile was generally consistent with what was seen with selective APRIL inhibition, which selectively targets pathogenic plasma cells involved in IgAN without impacting the rest of the B-cell repertoire. Third, most importantly, the aim was to achieve IgA reductions of 55% sustained for eight weeks. 55% was our target as it approximates the largest IgA reduction previously observed after a single dose of first-generation anti-APRILs in healthy volunteers. JADE101 performed above our 55% IgA reduction objectives, demonstrating rapid reductions in IgA of approximately 70% following a single dose of JADE101 at 700 milligrams, which was sustained at 12 weeks. This magnitude of reduction is the result of the IgA-lowering potency of JADE101, which is estimated to be 375-fold higher than sibeprenlimab and 26-fold higher than povetacicept. Our pharmacodynamic modeling suggests we can sustain these reductions with a single 350-milligram injection every 12 weeks. This gives us a high degree of confidence in JADE101 delivering best-in-class IgA reductions with a Q12-week dosing interval. IgA reductions in healthy volunteers have been shown to be highly correlated with the expected clinical activity in IgAN patients. Notably, these IgA reductions were the result of potent, rapid, complete, and sustained suppression of APRIL, the upstream driver of IgA and pathogenic IgA production. Fourth, we wanted to see a dose-dependent exposure, an extended half-life, and mitigation of target-mediated drug disposition, or TMDD, which has substantially influenced first-generation anti-APRILs. We also wanted to see minimal impact of immunogenicity on exposures or pharmacodynamic responses. The JADE101 PK demonstrate dose-dependent exposure and as compared to separate prior third-party studies, a half-life approximately 8.7-fold longer than povetacicept and 2.6-fold longer than sibeprenlimab. We also observed mitigation of TMD with JADE101, with a threshold estimated to be approximately two and a half-fold lower than what has been reported for sibeprenlimab. In addition, we have not observed any apparent impact of anti-drug antibodies on PK and PD, whereas clinically meaningful impact of ADA and plasma exposure has been reported with sibeprenlimab. These data, which Andrew will review in more detail, supports JADE101's potential to deliver best-in-class clinical activity with an infrequent Q12-week dosing profile for IgAN patients. With these data in hand and a high degree of conviction in the clinical profile and dosing regimen, we've initiated a phase II trial of JADE101, with results anticipated in 2027. We also plan to initiate a phase III pivotal trial of JADE101 in the first half of 2027, pending FDA requirements. Turning to slide four now. The phase I results are a direct reflection of the novel JADE101 design. JADE101 was selected through a de novo antibody discovery campaign and binds APRIL with ultra-high affinity in the femtomolar range. This level of binding affinity is intended to enable potent and rapid APRIL neutralization at low drug concentrations. In addition, JADE101 is designed to be selective for APRIL. That matters because in IgAN, the goal is to reduce pathogenic IgA while avoiding broader immune suppression that may come with less selective B-cell pathway modulation. JADE101 is a fully human antibody designed to bind to a novel epitope, which avoids the formation of large molecular weight complexes observed in the first-generation anti-APRIL monoclonal antibodies. Large complexes can increase risk of immunogenicity, which has been observed with sibeprenlimab. Furthermore, JADE101 was designed to support durable and predictable exposure. The molecule incorporates a validated YTE Fc modification for half-life extension to support a longer dosing interval. By combining ultra-high affinity, avoidance of large complex formation, and half-life extension, JADE101 was designed to have best-in-class clinical activity and a convenient dosing regimen. On slide five, IgAN represents a substantial commercial opportunity with approximately 169,000 patients in the U.S. and more than 1 million patients globally. Based on international guidelines, we estimate that 60%-75% of patients in the U.S. may be eligible for treatment. With recent approvals, increasing recognition of the disease, and evolving treatment guidelines, we believe the U.S. IgAN market alone has the potential to exceed $20 billion, with significant additional opportunity outside the U.S. Moving to slide six. IgAN is a serious progressive autoimmune kidney disease with a high lifetime risk of kidney failure. Patients are often diagnosed as young adults between the ages of 16 and 35, and many require treatment over decades. Convenience is crucial in this disease, as IgAN patients are often otherwise healthy young adults living with a generally asymptomatic but progressive kidney disease. For this population, a therapy that can deliver sustained disease control with less frequent dosing could represent an important advance. Persistent proteinuria is associated with an increased risk of kidney failure, with higher levels of proteinuria linked with a greater lifetime risk. This risk begins at a low threshold of proteinuria that historically may have been viewed as relatively modest. There remains a need for a new medication that can meaningfully reduce proteinuria, preserve kidney function, and be suitable for long-term use. On slide seven, the KDIGO guidelines, which direct the treatment of IgAN globally, were updated in 2025, putting greater emphasis on the earlier diagnosis and intervention to prevent kidney failure and highlighting the need for effective disease-modifying medication. They call for IgAN patients to be treated with an agent that depletes galactose-deficient IgA1, the pathogenic immune driver for IgAN, in addition to agents that offer supportive care by acting locally in the kidney to slow nephron loss. The guidelines now identify patients with proteinuria greater than half a gram per day as being at risk of progressive kidney function loss, compared with a previous target of greater than one gram per day. KDIGO also lowered the treatment target, recommending proteinuria be reduced to less than half a gram per day and ideally less than 0.3 grams per day. These changes position B-cell modulators, such as anti-APRIL therapies, to become foundational treatment in IgAN, given their ability to significantly reduce pathogenic IgA, proteinuria, and stabilize kidney function. Moving to slide eight. This slide shows two important relationships which highlight the predictive nature of healthy volunteer data to clinical outcomes in IgAN. On the left, you can see that IgA reductions observed in healthy volunteers with APRIL neutralization are highly correlated with the IgA reductions subsequently observed in IgAN patients. That means that healthy volunteer IgA data are not just a pharmacodynamic signal in isolation. They have shown strong consistency with what is observed in patients. On the right, this shows the link between biomarker response and clinical activity. Early IgA reductions in IgAN patients is highly correlated with later reductions in proteinuria. That is why the depth and durability of IgA reductions we observed with JADE101 support our confidence in the clinical profile and dosing regimen as we advance JADE101 into IgA patient studies. With that, I'll turn it over to Andrew to walk through the phase I data in detail. Thank you, Tom, and good morning, everyone. I'm excited to walk you through the positive interim results for JADE101. On slide 10 now. First, I'll describe the trial design. This is a first-in-human, randomized, double-blind, placebo-controlled, single ascending dose study in 32 healthy volunteers. Each participant received a single subcutaneous dose of JADE101 or placebo. The four cohorts studied spanned a wide exposure range. The dose levels were intentionally selected to map to our intended clinical dosing strategy. A high concentration formulation of JADE101 at 175 mg per mL was administered subcutaneously, which enables a 350 mg dose to be delivered in a single injection, compatible with future prefilled syringe or auto-injector delivery. Cohort 1 was administered a low dose of 175 mg, intended to be transiently pharmacologically active to capture the onset and recovery of APRIL-mediated responses. The cohort 2 dose of 350 milligrams was designed to represent a potential maintenance dose, aligned with a convenient, patient-friendly, single subcutaneous injection. This is our planned maintenance dose for phase II and phase III clinical trials. The 700-milligram dose in the third cohort is our planned induction dose for phase II and phase III. Finally, cohort 4 received a 1,400-milligram dose to enable full characterization of the safety profile of JADE101. This interim analysis presents data with five to eight months of follow-up across the sequentially dosed cohorts as of the data cutoff of April 14, 2026. This study randomized participants 6 to 2 active to placebo per cohort. As the trial is ongoing, the interim baseline and safety data today are presented in a blinded format, pooling active and placebo. PK and PD data are reported per treatment group. This approach allows individual treatment assignments to remain blinded, preserving ongoing study integrity. The primary objective of the study is to characterize the safety and tolerability of JADE101. The secondary objective is to assess JADE101's PK profile. Of most translational relevance, we are characterizing the depth and duration of IgA reduction. We are also assessing target engagement through free APRIL reductions and measuring other immunoglobulins, including IgG, M, and E. Finally, we are exploring whether immunogenicity has any impact on the pharmacokinetics and pharmacodynamics of JADE101. On slide 11, the baseline characteristics observed were consistent with a typical healthy volunteer population and were generally balanced across dose groups. Gender distribution was even overall, with comparable BMI across cohorts. The population included a mix of racial backgrounds. These baseline characteristics support the generalizability of these phase I findings. Moving to slide 12. JADE101 demonstrated a favorable safety profile and was well-tolerated across all evaluated dose levels. Across the full study population, there were no deaths, no serious adverse events, no severe treatment emergent adverse events, and no discontinuations due to adverse events. All treatment emergent adverse events were mild or moderate in severity. We also observed no clinically significant changes in ECGs or vital signs and no trends or signals in safety labs. JADE101 was well-tolerated locally following subcutaneous administration, with infrequent mild or moderate injection site reactions. Injection site erythema was reported in three of 32 participants, or 9%, and mild injection site pain was reported in one of 32 participants, or 3%. We observed no hypogammaglobulinemia, defined as IgG less than or equal to three grams per liter. This is consistent with JADE101's selective anti-APRIL mechanism, not showing evidence of broad immunosuppression. Importantly, we observed no apparent impact of anti-drug antibodies on PK or PD. The table on the right summarizes the overall safety results. Across all cohorts, 24 of 32 participants, or 75%, experienced at least one treatment emergent adverse event. The most common events occurring in more than two participants were generally typical of a healthy volunteer study conducted with an up to eight-month follow-up as of the data cutoff, including headache, upper respiratory tract infection, injection site erythema, oropharyngeal pain, and pyrexia. Upper respiratory tract infection AEs were numerically slightly lower in the JADE101-treated participants than placebo. Overall, these results support the potential for a favorable safety profile of JADE101 in IgA patients. Moving to slide 13. We are especially encouraged by the magnitude and duration of IgA reductions produced by single ascending doses of JADE101, exceeding those observed with the first-generation APRIL inhibitors in healthy volunteers. On the left-hand chart, the IgA reductions observed with JADE101 were dose-dependent in both depth and duration of response. Reductions in IgA of at least 50% were observed at all doses tested, and IgA reductions of approximately 70% decrease from baseline were observed at a dose of 700 milligrams. We believe this represents the largest IgA reduction reported following a single dose for a B-cell modulator in healthy volunteers. The single 700-milligram dose is the key dose to focus on because it is predicted to reflect the depth and duration of IgA reduction in IgAN patients with repeat dosing of JADE101 in response to our planned IgAN dosing strategy, which is a 700 milligram induction dose followed by Q12-week maintenance dosing of 350 milligrams beginning four weeks after induction. We will present additional details on this dosing strategy in the following slides, including our pharmacodynamic modeling and simulations. At the 700-milligram dose, JADE101 produced an approximately 70% reduction in serum IgA that was sustained at 12 weeks post-dose. The IgA profile observed at the 700-milligram dose supports the potential for Q12-week maintenance dosing with JADE101. Notably, similar peak IgA reductions are seen with both the 700 milligram and 1,400 milligram dose, which suggests we are maximizing the clinical activity available to the mechanism with our go-forward dosing strategy. On the right-hand side, we put this into competitive context using publicly available data. Cross-trial comparisons have limitations and should be viewed as hypothesis-generating. However, this comparison is useful because it shows the comparative magnitude of IgA reduction at clinically relevant single doses in healthy volunteers. At their respective phase III doses, suvorexant and povetacicept produced peak IgA reductions of between 50% and 55% following a single dose, numerically lower than the approximately 70% reduction observed with JADE101 at 700 milligrams, the planned induction dose. Higher doses of suvorexant and povetacicept, which were not advanced into phase III, also did not match the approximately 70% reduction observed with JADE101 at the 700-milligram induction dose. Turning to slide 14. The exposure response observed for JADE101 to drive and sustain IgA reductions in this phase I study allows for a comparative assessment of JADE101's in vivo IgA lowering potency relative to the first-generation anti-APRILs based on an analysis of their publicly available data. JADE101 demonstrated remarkable in vivo IgA lowering potency with an EC50 to reduce serum IgA in humans of approximately 10 picomolar. JADE101 demonstrated a lower IgA EC50 than reported for the first-generation agents, including 26-fold lower than povetacicept and 379-fold lower than suvorexant. The figure on the right side of this slide shows a strong association between in vitro binding affinity to human APRIL and in vivo potency to reduce serum IgA in humans with an R squared value of 0.9. This suggests that the in vivo potency of each agent to lower IgA can be largely explained based solely on APRIL binding affinity. JADE101's ultra-high binding affinity is now manifesting in this healthy volunteer study as ultra-potent in vivo IgA lowering and resulting in rapid, deep, and sustained IgA reductions. As a result of JADE101's IgA lowering potency in humans, only very low plasma concentrations of JADE101 are needed to sustain IgA reductions. In this chart, you can also see the relationship between potency and dosing interval. Atacicept and zigakibart have relatively low APRIL binding affinities, and therefore must be dosed every week or every two weeks, respectively. Suvorexant is a more potent than both and is dosed every four weeks. Povetacicept, more potent still, is also dosed every four weeks, though it only has a 2.8-day human half-life. JADE101 is more potent than povetacicept to lower IgA and has an 8.7-fold longer half-life, again, giving us confidence in a Q12-week dosing interval. Moving to slide 15. We further describe JADE101 pharmacodynamic modeling and clinical trial simulations. Population-based simulations were conducted leveraging all publicly available data of which we are aware across APRIL-targeted development programs to generate a representative virtual IgAN population and predict targeted biomarker responses. The model is most richly informed by the detailed exposure response analysis and data contained in the FDA review documents for sibeprenlimab's approval. This model-based framework accurately recapitulates model-based outcomes for other anti-APRIL agents and reliably captures observed serum IgA reductions in patients with IgAN across phase II and phase III clinical trials. Leveraging the entirety of our biomarker-rich first-in-human data and our planned dosing strategy, JADE101 is predicted to potentially deliver best-in-class IgA reductions more rapidly than the first generation programs and sustain those responses with convenient subcutaneous dosing as infrequently as every 12 weeks. The solid lines represent the median values across 500 simulated trials. The shaded areas represent the 95th percentile of predicted population-based variability. Although modeling is inherently limited, we believe the simulations are informative as we advance JADE101 into patients. We believe JADE101 has the potential to achieve best-in-class IgA reductions more rapidly than first generation anti-APRIL agents, which require multiple doses. The potential for a faster onset of peak IgA response offers the potential for improved benefits on key IgAN clinical endpoints, such as proteinuria reduction at nine months. The simulations also suggest the potential for overall deeper IgA reductions with JADE101 at the population level. The modeled IgA curves suggest JADE101 can maintain the deep IgA reductions that are induced by a 700 milligram induction dose with a Q12-week maintenance dosing of a single subcutaneous injection of 350 milligrams beginning at week four. Initiating maintenance dosing at week four, while TMDD is fully saturated from the induction dose, provides a strong pharmacokinetic and pharmacodynamic foundation to sustain these responses. The potential for best-in-class IgA reductions sustained with Q12-week JADE101 dosing would represent a highly differentiated profile. On slide 16, the dose-dependent pharmacokinetic profile of JADE101 and the rapid and complete free APRIL suppression across all doses enabled these deep and durable IgA reductions we just discussed. The PK profile of JADE101 is displayed in the left chart. As doses increase from 175 to 1,400 milligrams, we see increases in exposure and increasing evidence of YTE-mediated reductions in linear clearance, a hallmark of the impact of saturation of TMDD associated with the anti-APRIL MOA. We observed an extended half-life relative to the first generation agents of 24.2 days. This is meaningfully longer than publicly reported data for the first generation anti-APRIL targeting agents dosed every four weeks, including approximately 8.7-fold longer than the 2.8-day half-life reported for the povetacicept 80 milligram dose, and approximately 2.6-fold longer than the sibeprenlimab 9.3-day half-life reported on the FDA label for the 400 milligram subcutaneous dose. This extended half-life, combined with JADE101's higher in vivo potency to reduce serum IgA in humans through low JADE101 plasma concentrations, supports a Q12-week maintenance dosing interval for JADE101. The estimated TMDD threshold of JADE101 was approximately 2.5-fold lower than observed in the reported sibeprenlimab clinical PK profiles. TMDD arises from high-affinity binding of the drug to its target, in this case, APRIL, which can act as a clearance sink and drive rapid, non-linear elimination at lower concentrations. As exposure increases and target binding becomes saturated, clearance transitions towards a slower, linear, non-target mediated process. First generation anti-APRIL monoclonal antibodies appear to be substantially influenced by TMDD. In this context, it is notable that JADE101 achieves saturation of TMDD at lower concentrations than reported for sibeprenlimab. This behavior is consistent with the ultra-high binding affinity of JADE101, which likely facilitates more efficient target engagement and earlier saturation of APRIL-mediated clearance pathways. On the right free APRIL panel, you can see that JADE101 produced rapid and complete suppression of serum free APRIL across all evaluated doses. Remarkably, complete free APRIL suppression was observed as early as two hours after subcutaneous administration, reflective of very potent inhibition of APRIL, even at low serum concentrations of JADE101. The duration of free APRIL suppression was dose-dependent. At the 700 milligram dose, greater than 90% APRIL suppression was sustained for a median of 85 days based on non-compartmental analysis of individual participant profiles. Slide 17 shows the impact of JADE101 on the broader immunoglobulin profile, which is consistent with the selective anti-APRIL mechanism of action. IgG reductions were modest, consistent with a relatively IgG-sparing effect from selective APRIL inhibition. The magnitude of IgG lowering observed with JADE101 was consistent with the first-generation anti-APRILs. There were no cases of hypogammaglobulinemia. The profile of IgM reduction produced by JADE101 was similar to that observed on IgA, again, as expected with the anti-APRIL MOA and consistent with the first-generation anti-APRIL agents. We also observed an approximately 50% reduction in IgE with JADE101. Moving to slide 19, we'll walk through our dosing strategy in phase II and planned phase III clinical trials. For phase II and phase III, following an initial 700 mg induction dose intended to drive 70% IgA reduction at earlier time points, we plan to evaluate two dose intervals. A single subcutaneous 350 mg maintenance dose administered every 12 or every 8 weeks, with the goal to optimize for clinical activity and convenience in a best-in-class profile. Including two doses in future patient trials may allow us to accelerate the initiation of a pivotal phase III trial without waiting for phase II data. Incorporating multiple doses in a registrational trial supports global regulatory expectations for formal dose-finding in patients and allows us to accelerate the overall JADE101 development plan. As described on the previous slides, our Q12 maintenance dose is designed to deliver best-in-class IgA reductions with faster and numerically greater IgA reductions than first-generation B-cell modulators. We chose Q8 as our second dose interval to test if more intense dosing will add any additional clinical benefit. Our pharmacodynamic modeling demonstrates comparable IgA reductions in both duration and depth for both Q12 and Q8 intervals. We believe this dosing strategy positions us to move rapidly in the development of JADE101 while delivering a potentially best-in-class clinical profile. Turning to slide 20. We recently initiated the phase II JUNIPER trial for JADE101 in IgAN and disclosed last week that the first participant has been dosed. This is an open-label trial where all participants receive active JADE101 with a convenient and infrequent subcutaneous administration. The trial is enrolling adults who have been diagnosed with biopsy-confirmed primary IgAN, who continue to display a urine protein to creatinine ratio or UPCR level from a 24-hour urine sample of at least 0.75 grams per gram and an eGFR of 30 or higher, despite already being on a stable standard of care for at least 12 weeks. This patient population remains at high risk for disease progression and requires a foundational disease-modifying therapy. We will evaluate safety and tolerability and will also assess key efficacy measures, including UPCR over time, UPCR reductions below key proteinuria thresholds of less than 0.5 grams per day and less than 0.3 grams per day, and eGFR over time. In addition, we'll measure key pharmacodynamic biomarkers, including pathogenic galactose-deficient IgA1. All participants are expected to receive an induction dose of 700 milligrams at the start of treatment, and then randomized one-to-one to maintenance doses of 350 milligrams Q8 weeks or Q12 weeks, beginning four weeks after induction for a 100-week treatment period. We aim to enroll 30 participants in this trial and expect to report interim clinical data in 2027. With that, I'll now hand the call back to Tom. Thanks, Andrew. The phase I data reviewed today provides us with conviction that JADE101 is highly differentiated and can offer a significant advance for patients with IgAN, a large commercial opportunity representing a total addressable market of more than $20 billion in the U.S. alone. The results demonstrate JADE101 has the potential to be a best-in-disease molecule with the potential to capture the efficacy available to the anti-APRIL mechanism with convenient Q12-week dosing. As discussed, the translatability of healthy volunteer biomarker data in IgAN with the anti-APRIL mechanism gives us conviction in JADE101's profile and allows us to move very quickly into patient trials. We've started dosing participants in our phase II JUNIPER trial and anticipate interim data in 2027. We continue to explore opportunities to accelerate the initiation of a phase III trial, which we currently anticipate starting in the first half of 2027, pending FDA requirements. Beyond JADE101, we are developing potentially best-in-class therapies for several autoimmune diseases. We have two additional programs that are rapidly advancing. JADE201 is a half-life extended afucosylated monoclonal antibody targeting BAFF receptor, the B-cell Activating Factor B cell receptor. We recently initiated a first-in-human study evaluating JADE201 in patients with rheumatoid arthritis, from which we anticipate interim data in 2027. We also have a third antibody program, JADE301, which is expected to enter the clinic in the first half of 2027. Additional details on this program are expected to be shared in the second half of this year. With cash runway expected into the first half of 2028, Jade is well-capitalized to pursue an aggressive development plan for JADE101 while also advancing JADE201 and JADE301 through key data readouts. Just as importantly, we continue to build a team of highly experienced drug developers and company builders. This combination of innovative science, strong financial backing, and seasoned talent gives us the foundation to move quickly and decisively. We are proud of the progress we have made and are excited for the milestone-rich period ahead. Above all, we are motivated by the potential impact our therapies may have for patients living with autoimmune disease. With that, I'll hand it back to the operator to open the line for questions. Thank you. We will now begin the question and answer session. To ask a question, you must be dialed in by phone and press star one one on your telephone keypad. Our first question comes from the line of Akash Tewari with Jefferies. Your line is now open. Hi, this is Alexio for Akash. Thank you for taking our question. Given that we're seeing both faster and deeper IgA reduction from JADE101 versus first-generation agents, could we potentially expect to see better efficacy on proteinuria come phase II? Yeah. Thanks, Alexio. It's a good question. Yeah, definitely IgA reductions have been closely correlated to the proteinuria reductions expected at the 36-week time point. We do anticipate having that fast onset of action due to the induction dose to be able to reach those maximal reductions in IgA at very early time points. That could drive getting to peak proteinuria reductions also at an earlier time point. We have seen with the first generation anti-APRILs that you do see excellent, robust reductions in proteinuria at the week 36 or week 40 time point. It does look like it does continue to decrease at the 12-month and at the 18-month time points. We can anticipate with JADE101 to achieve those maximum reductions in proteinuria at earlier time points. We do believe that this gives us a really good opportunity to reach very significant levels of proteinuria at those earlier time points. We're very optimistic that we can show really a best-in-class profile with this convenient dosing format. Thank you. Thank you. Our next question comes from the line of Tyler Van Buren with TD Cowen. Your line is now open. Hey, guys. Good morning and congratulations on the excellent early data which clearly exceeded expectations. A couple for you. The first one is the translatability of IgA reduction to proteinuria is super strong and fairly obvious based upon the nearly perfect correlation coefficient of the 0.92. One of the more common questions I get from investors is if there's room for further improvement on eGFR, given what we've already seen with the other agents in the class. Curious to get your opinion there. The second question is, can you provide any brief preliminary thoughts on the outcome of the recent NKF meeting? What are the resulting action items and how it impacts your future interactions with the FDA, and if it's gating? Thanks, Tyler. Really great questions. Yeah, we're really encouraged by the early outcomes of that NKF workshop. Just as a quick reminder to those who may not be as familiar, the FDA asked the NKF to pull together a group of industry sponsors, patient groups, KOLs, and the FDA themselves to discuss what does a contemporary trial in IgA nephropathy look like, because there's an increasing recognition that a two-year placebo-controlled trial is not necessarily ethical for patients to keep them off drug for a two-year period in the age of these very efficacious medications being potentially available. Also the feasibility of those trials is a lot lower. Andrew, you actually attended the workshop and with the team have been looking very closely at this. Do you want to take that question and then also the question on eGFR expectations? Yeah. Thanks a lot, Tom. Really encouraged by the conversation at the NKF. Clear recognition of the need to reduce placebo exposure in IgAN patients in the clinical trial setting and really look forward to that FDA feedback Tom highlighted around guidance and directions of new study designs. We do feel confident based on the nature of those discussions and rallying around these key concepts by FDA commentary, sponsors, IgAN patients, and global KOLs, there will be an efficient path to phase redevelopment for a disease-modifying anti-APRIL like JADE101 with the potential for large treatment effects. On the eGFR side of things, what we've seen now consistently across four programs, two selective anti-APRILs and two dual APRIL/BAFF inhibitors, is effective eGFR stabilization out through 12-24 months, depending on follow-up from the individual studies. Really, eGFR stabilization is probably the best you can accomplish in the setting of treating IgAN. eGFR decline is generally a result of nephron loss. It's unlikely you're going to get nephron return. eGFR stabilization is really the key treatment goal. You may get some modest increases in eGFR associated with reduced immune complex-mediated inflammatory injury to the kidney, but that would be relatively incremental. Long-term, the goal is eGFR stabilization, and given the early data across multiple programs in a short one to two-year trial, it may be difficult to differentiate from that over that short duration of time. However, the goal for treating IgA nephropathy is not just eGFR stabilization over one to two years. It's really over decades in these young patients that have high lifetime risk of end-stage kidney disease. What we know from epidemiological studies is that residual proteinuria is the best predictor of long-term clinical outcomes in IgA nephropathy. That's why the treatment guidelines, as Tom highlighted, are really focused on producing the largest reductions of proteinuria you can to below 0.5 g per day and preferably back to within the normal range of below 0.3 grams per day because of that strong association between proteinuria and longer-term outcomes. Although we don't think there's a lot of opportunity to differentiate on eGFR over these short-term trials, since the other agents are already reporting stabilization, we do think having an agent, as Tom highlighted earlier, with these large and rapid IgA reductions, potentially delivering greater reductions in proteinuria and higher rates of clinical remission, would be preferred by nephrologists. Thank you. Our next question comes from the line of Alex Thompson with Stifel. Your line is now open. Hey, great. Let me add my congrats on the data as well, too, from us. I guess on expectations for phase III design here with 2 dose arms, should we expect a trial of similar size to sort of the contemporary phase IIIs from the first gens, or how are you thinking about that? In terms of enrolling the phase II and phase III trials today, how do you expect IgAN patients in these trials to sort of be similar or different than these other contemporary studies? Thank you. Great. Really good questions, Alex. On expectations for phase III in terms of the trial design, we haven't received that guidance yet from the FDA, so we still have to have that interaction, so it's difficult for us to provide too many details. We do think that the treatment effect sizes of this class are much better characterized than they were previously. The Vertex study was around a 600-patient trial. The Otsuka trial was in the 500 patients. We're seeing P values that really blow it out of the water. So we really do have a better understanding what treatment effect assumptions we need to make. We don't think that you need a trial size of that magnitude. You can actually really run a very efficient trial, likely sort of in the 400-patient range, even having those two dose arms involved. We will provide more guidance as we have those interactions with the FDA and start initiating that phase III trial. In terms of enrollment, Andrew, you and the team have been really looking at this and thinking about the patient selection and inclusion criteria. Do you want to provide some context? Yeah, absolutely. These are global trials. Obviously, the U.S. is an important component of these studies, the epidemiology of IgA nephropathy indicates higher prevalence and perhaps higher severity, particularly in Asian populations, these trials are truly global. Although there have been significant advances in the U.S. with multiple approvals, many of these agents are not broadly available globally, won't necessarily impact trial enrollment or the baseline characteristics of the patient population, including the concurrent medications they're on. The one exception to that is we are seeing increased uptake of SGLT2 inhibitors globally, sequentially across the studies, with more recent studies showing significantly higher concurrent SGLT2 inhibitor use. We do expect that to continue moving forward. However, we're very encouraged by the subgroup analyses that have been reported from multiple agents now that inhibit APRIL selectively or inhibit APRIL and BAFF in combination, in that you get the full disease-modifying benefit of APRIL inhibition, irrespective of background SGLT2 inhibitor use. Actually, you tend to numerically get slightly greater reductions in proteinuria if patients are on background SGLT2 inhibitors, perhaps due to better hemodynamic control in that population. We do think there'll be some evolution in that background therapy, but think it still shapes up very well for the potential of a selective anti-APRIL, particularly given the global nature of these studies. Thank you. Our next question comes from the line of Julian Harrison with BTIG. Your line is now open. Let me add my congratulations on these results, and thank you for taking the questions. First, definitely could appreciate the strong translatability from IgA reductions to proteinuria reductions. In light of that, I'm wondering if it's your expectation that you could likely command significant preference even at parity efficacy versus the approved precedent in IgAN with one-third the injection burden, or do you maybe view better efficacy as an important success factor as well at this point? Second, it seems like you have line of sight to quarterly dosing and maintenance. I'm wondering if you could help us better understand the Q8 week maintenance arms in your phase II and phase III trials. Is this really just for the sake of dose ranging, or do you maybe envision Q8 week could be beneficial as an approved option for some patients? Thanks, Julian. Two important issues. We've done some market research to look at what are the choice drivers for uptake of the class of drugs in IgAN. Really, the convenience and efficacy are both going to be key choice drivers for clinicians to drive market share. Obviously, if we can achieve greater levels of proteinuria, that would be highly attractive and drive share because as Andrew pointed out, that really does define that lifetime risk of disease progression. If you're getting more patients down to below the KDIGO target of half a gram a day or even back into clinical remission, which is considered below 0.3 g a day, that type of a medication would clearly drive a lot of uptake and preference. We are seeing that convenience actually is also driving a lot of selection. We actually hear it from the current agents that are in development. There's a lot of attempts to differentiate around some elements like injections, volume, the format of the presentation of the auto-injector versus prefilled syringe. We really know that the ultimate factor in driving convenience is the number of injections, as you point out. We really do believe that having fewer injections over time for this generally asymptomatic young population is actually going to drive a lot of preference. We have done a small market research to show that that is in fact the case. Even if you kept efficacy fairly constant, that a less frequent dosing interval would drive a lot of uptake for patients. Given the fact that this is such a large and growing market, we've referenced the figure of $20 billion TAM in the U.S. several times. There's going to be multiple winners here. We do believe with the emerging profile of JADE101, we can capture a significant part of that. A non-answer there where it's both efficacy and convenience are both very, very important drivers of differentiation. We feel like we're extremely well positioned on both. In terms of the Q12 versus the Q8 weeks, very high level, we're moving very quickly here. We do plan to initiate that phase III in the first half of 2027. We're moving very, very quickly off of phase I data. It is very prudent to take two doses forward in that type of a situation. There's obviously other advantages. Andrew, do you want to talk through the rationale between the Q12 week and why the Q8 week was selected as the second dose? Yeah. It's really to support acceleration of the program into that pivotal trial. The pharmacodynamic modeling supports the Q12-week maintenance dose, sustains those 70% plus IgA reductions induced by the induction dose of 700 milligrams using a 350-milligram Q12 dose. We believe that will provide the full efficacy available to IgA lowering to the anti-APRIL MOA. When thinking about the second dose to move forward to do formal dose finding in patients to satisfy global regulatory expectations, commercially, the extended dosing interval would be Q24. That would make sense. Due to the impact of TMDD, we don't think that's feasible with JADE101, which makes Q8-week dosing the choice for that second dose arm to explore whether there's any possibility that more intense dosing provides any additional clinical benefit. From our PK/PD modeling, we don't think there'll be any difference in IgA reduction between Q8 week and Q12. To satisfy formal dose exploration and assess whether more intense dosing provides any meaningful clinical benefit is the rationale for Q8. Very helpful. Thank you, and congrats again. Thank you. Our next question comes from the line of Laura Chico with Wedbush. Your line is now open. Morning. Congrats on the data, and thanks very much for taking the questions. One for me first on ADAs. I'm not sure if this should be Andrew or Tom, but it doesn't sound like there's any impact on the PK for JADE101 due to ADAs. Perhaps you could remind us on when these impacts manifest with sibeprenlimab. Just trying to understand what gives you the most confidence that JADE101 can avoid ADA interactions. Then separately on Oh, I'm sorry. Go ahead. I'll ask a follow-up then. Oh, sorry. I was just going to say, Andrew, do you want to take that question? Sure thing. What we saw with the sibeprenlimab profile is ADAs that peaked at around six months following initiation of treatment of sibeprenlimab in phase III. What was particularly impactful of ADA positivity in that study was the clinical impact it had, with a 40% decrease in plasma exposure and an approximately 10% decrease in proteinuria reduction versus ADA negativity. It's really the impact that ADAs have on PK/PD or safety that's of clinical consequence. JADE101 was designed to be a fully human anti-APRIL monoclonal antibody and was also selected with a novel epitope to avoid the formation of large immune complexes, which can happen when monoclonal antibodies bind trimeric proteins like APRIL and happens when sibeprenlimab binds APRIL. These large immune complexes can increase the risk of immunogenicity. By design, we tried to limit the risk of immunogenicity with JADE101 and are very encouraged by this first-in-human data set where we've seen no impact of ADA on PK or PD. Obviously we'll continue to follow this closely as we move into phase II and phase III to assess repeat dosing in IgAN patients. Thanks, Andrew. Just one follow-up on JUNIPER. I know you're guiding to data in 2027, but I'm trying to understand perhaps what type of data should emerge here. Would this be six-month results, both cohorts? I don't know if you can give a little bit more color on what we should be looking for from JUNIPER in 2027. Thanks, guys. Thanks, Laura. Yeah. Andrew, do you want to talk to that as well? Happy to. We do want to make sure that first disclosure is relatively robust and provides a good reflection of JADE101's profile at both dose levels that have been randomized simultaneously. It will be a very biomarker-rich initial disclosure including the IgA and pathogenic IgA reductions, which give you high conviction that you will translate into longer-term clinical benefit given the consistency which pathogenic IgA depletion has resulted in large reductions in proteinuria and eGFR stabilization. We haven't really defined yet what that minimum data set is necessary for that first disclosure, it will be biomarker rich and include the important clinical endpoints of UPCR and eGFR as well as obviously the safety moving into IgAN patients. Look forward to that first disclosure next year. Thanks, guys. Congrats. Thank you. Our next question comes from the line of Matt Phipps with William Blair. Your line is now open. Morning, guys. Thanks for taking my questions. Congrats on great data and execution here. You guys, how confident are you in the ability of this profile from healthy volunteers to be maintained across a wider distribution of patient body weights given CIBINQO does seem to struggle in higher body weight patients? Then it's kind of asked, but if both doses are successful in the phase III and show similar profiles based on your modeling of IgA reduction, would you seek approval of both doses to give physicians some flexibility in case maybe they have patients with higher body weight or a higher baseline proteinuria? Thank you. Thanks, Matt. Yeah, maybe I'll take the second question first and then pass it to Andrew to talk about the modeling and how we have confidence across the population and again, with JADE101. Yeah, we are taking the Q12 week forward and believe that that's the dose that will provide the levels of IgA reduction required for robust proteinuria lowering and then stabilization of eGFR. Frankly, if that data continues to look as we expect, that will be the dose that we aim to commercialize and to as well just put on the label and the Q8 potentially will not be necessary. We do anticipate potentially that there could be a scenario where some physicians may want to intensify dosing in some patients. We really do need to see how the data plays out to understand, is there any additional benefit from intensifying the dose down to that Q8. Right now as you saw, and Andrew walked through the modeling, it's not clear there will be more efficacy based off of that intensification just because we are really maximizing the IgA reductions based on that Q12 week dose. In our interactions with the steering committee and KOLs when we talked through this dose design, they do like that we are testing this and really understanding what is that dose exposure response and how does that translate to the clinical activity. With JADE101, we're actually in this quite unique position where we can test that. That has not been done with other agents. Because of the profiles of the drug, we can really understand what is driving activity in IgAN. Andrew, do you want to talk a little bit about the modeling across body weights and expectations there? Yeah, happy to. Thanks for the question, Matt. We do think the points you raised around sibeprenlimab at the population level do leave an opportunity for JADE101 to capture more of the full efficacy available across the population for the anti-APRIL MOA. Patients with the higher body weight half in the phase III study had about 10% or so less proteinuria reduction than the leaner half of that phase III population, suggesting the potential for an agent that addresses the population at a whole more effectively. The way we built these pharmacodynamic models was really using the sibeprenlimab exposure response as a foundation, both for the APRIL-mediated IgA reductions, but also to establish what a virtual IgAN patient population looks like for the clinical trial simulations we ultimately captured. That IgAN population variability is built in to these pharmacodynamic models. As we showed, the 350 milligram dose doesn't just do really well at maintaining IgA reductions in that 70%ish range for the median patient, but does it very well at the population level. We do feel confident based on these simulations, that we have the potential to more broadly impact the patient population as a whole to optimize the efficacy available to anti-APRIL. Thank you. Our next question comes from the line of Rami Katkhuda with LifeSci Capital. Your line is now open. Yes. Just wanted to pass along Mike's congratulations on the data as well. Two quick ones from me. First, can you touch on whether you expect there to be any safety implications associated with the more rapid and deep IgA reductions observed with JADE101? Then given the reductions across IgM and IgE as well, do you expect to pursue 101 in additional indications? Thanks, Rami. I think the short answer to the first question is no. We don't anticipate any safety concerns with rapid and robust IgA depletion. We have seen across this mechanism now with four other agents, either the selective APRILs or the APRIL/BAFFs, that really robust lowering in IgA, especially with the selective anti-APRILs, it does not increase risk of infection. It seems to be very safe and well-tolerated. Also, we're very reassured by the fact that the IgG levels are not going down below three grams per liter, and so haven't seen any cases of hypogammaglobulinemia. We feel really confident with this mechanism that it's going to be safe and well-tolerated. Yeah, really good call out on the IgM and IgE. IgM, we definitely feel like there are life cycle opportunities here. There are a number of IgM-mediated diseases that we are looking into. Of note is one called Multifocal Motor Neuropathy, which is an indication where several companies are testing complement inhibitors. We think that going upstream and targeting IgM, which is the pathogenic driver of the disease, could be very beneficial for patients. We're looking at potentially looking at a signal-seeking trial in MMN. There's also anti-MAG neuropathy and Cold Agglutinin Disease, which are all IgM-mediated diseases. IgE, we're still looking at it and trying to understand what would be the value in terms of IgE-mediated diseases, but very intriguing finding that there are good reductions in IgE. We will think about what can we do with that. Just to note as well, the other potential life cycle opportunity that we have on our radar is Otsuka has started a phase II trial with sibeprenlimab in children's, and they're anticipating reading out that data around the middle of next year. We'll be looking for that data, understanding should we move quickly into that indication as well. Lots of really good potential life cycle opportunities for JADE101. Thank you. Our next question comes from the line of Vamil Divan with Guggenheim Partners. Your line is now open. Great. Thanks for taking my questions. Congrats again on the data. Maybe a couple of just clarification things from questions I'm getting from investors here. One on the ADAs, I know you're saying there's no apparent impact on the PK or PD, can you provide the percentage of patients that had ADAs in the trial? Second one was around the URIs that you mentioned. I think you said the rates were slightly lower in patients who got JADE101 as opposed to placebo, maybe you can just clarify or provide any more details on those cases. Finally, my question was actually around just the presentation of the product, especially with the 700 milligram loading dose. Whatever you can share in terms of the phase II, the phase III, how you plan to present the product, because it will be a prefilled syringe, an auto-injector, and also any comments commercially how you're thinking about that. Would the loading dose be something you expect to be given by a healthcare provider, or would that also be done just by the patient? Thank you. Yeah, thanks, Vamil. Maybe I'll take that last question about the presentation of the product. Andrew, you could talk about respiratory tract and then ADAs. Our goal is to make JADE101 as convenient as possible for patients. The goal is at-home administration for the induction doses as well as the maintenance doses. We are setting up our patent development pathway to enable that potentially. Right now, we do just have a liquid and vial format for the formulation. We are looking at a prefilled syringe and an auto-injector, and we're working out the development pathway. The plan is at launch to have a very convenient device that is really suitable for patients to inject at home. Andrew, do you want to take the question on infections and ADAs? Yeah. Thanks, Tom. Yeah, just to clarify, upper respiratory tract infections were generically slightly lower in the JADE101 group relative to the placebo. Encouraged by that, consistent with the class, that long-term anti-APRIL has not shown broad immunosuppressive effect, including on upper respiratory tract infections. On the ADA, we haven't disclosed rates for this ongoing study, but really encouraged by the lack of any impact of ADAs on PK and PD. We've seen nothing in the profile to date that provides us any concern around repeat dosing in IgA nephropathy patients. As I mentioned, by design, JADE101 was intentionally designed to reduce the risk of immunogenicity as a fully human IgG1, as well as that novel epitope to avoid large immune complex formation. We do think that's playing out in an encouraging way in the immunogenicity profile in phase I. We'll continue to follow, obviously, with repeat dosing in IgA patients, but nothing of concern. Okay. Thank you. Thank you. Our next question comes from the line of Arthur He with H.C. Wainwright. Your line is now open. Hey, guys. Congrats. Just one question from my side. I just noticed that if we look at the JADE101 concentration as well as IgA reduction, within the intended dosing interval, the variability for those two concentration is very tight. Andrew, maybe can you speak to how this can differentiate JADE101 from the sibeprenlimab and the povetacicept in terms of efficacy-wise? Thanks. Yeah. Thanks, Arthur. We have been able to use the exposure response that you highlighted there for JADE101, plasma concentrations versus IgA reductions over time. You do this using indirect response modeling, since the IgA reduction is not a direct result of the PK, but secondary to APRIL suppression. What we're really excited by is the remarkable in vivo IgA lowering potency of JADE101. You can calculate using those analyses an in vivo EC50 of about 10 picomolar. You really require very little JADE101 to get these deep and sustained reductions in IgA. We think that's really the property that's manifesting in these more rapid and deeper IgA reductions than observed with those first-generation agents, including povetacicept and sibeprenlimab. Do think this differentiated potency profile is really key for us to be able to achieve this potentially best-in-class profile, with the potential for faster, deeper, and sustained IgA reductions, hopefully translating into better clinical activity. Oh, thanks, Andrew. Congrats again. Thanks, Arthur. Thank you. Our next question comes from the line of Kaveri Pohlman with Clear Street. Your line is now open. Yes. Good morning. Congrats on the excellent results, and thanks for taking my questions. Maybe just a couple. Regarding the faster onset of IgA reduction, how much of this you believe is due to higher affinity versus higher dose, and how much benefit faster onset can provide, how meaningful or important it is to physicians? With the healthy volunteer data and the overall IgA reduction, which I understand correlates well with patients' overall IgA reductions, but what read-through it provides to actual reduction in Gd-IgA1 levels and autoantibodies that patients develop, and how much of that reduction specifically correlates with patient benefit? Thank you. Thanks, Kaveri. Yeah. On the total IgA to Gd-IgA, we have seen historically that they translate very closely. The correlation is extremely high, and it's pretty much a one-to-one. Correct me if I'm wrong on that one, Andrew. No, that's correct. At ASN last year, we provided our analysis of all of the publicly available data, and a very strong association between total IgA and Gd-IgA1. We do feel like total IgA provides the full information available. You asked how clinicians would see this faster onset. For physicians, definitely the goal is to control kidney function over the long term. They haven't said, "Oh, I want an agent that acts within the first couple of months." What we do know is it does take a significant amount of time for the other agents to reach their peak reductions of IgA and their peak reductions of proteinuria. If a clinician is, in fact, waiting 9 to 12 months to understand the full effect of the medication, and if it's really providing that benefit, hitting those proteinuria goals, like below 0.5 grams a day or below 0.3. We do know that something that does have an earlier onset really will help them understand how is the medication performing. We also think that from a comparative point of view, looking at those nine-month interim analysis of proteinuria, if we can capture more of the efficacy that's available to the mechanism at an earlier time point, that will compare very favorably when clinicians are assessing which medication to use based off of those initial nine-month protein uria analysis. We could look quite good in comparison. Andrew, do you want to take the question on faster onset? Is it driven by the affinity or the dose? Yeah. We do think that rapid onset of IgA reduction is driven by the ultra-high binding affinity to really potently and quickly, fully inhibit APRIL. We see this when we look at the free APRIL profiles. Remarkably, following a subcutaneous dose of JADE101, you can get full systemic APRIL suppression below the limits of quantification within two hours of that dose. It really does show very potent APRIL suppression at very low concentrations of JADE101, which triggers the very early and rapid IgA reduction. That's helpful. Thank you. Thank you. That concludes the question and answer period. I'll now turn it back to CEO, Tom Frohlich. Thank you. On behalf of the Jade Biosciences team, thank you for joining us today. A replay of this webcast will be available on our website. If you have any further questions, feel free to reach out to our investor relations team at ir@jadebiosciences.com. This concludes today's conference. Thank you for your participation. You may now disconnect.