Good morning and welcome to Climb Bio Investor Event focused on Climb 116 and the IgA nephropathy opportunity. At this time, all participants are in a listen-only mode. A question and answer session will follow with prepared remarks. Please note this call is being recorded. I would now like to turn the conference over to Dr. Carlo Danzi of Investor Relations. Please go ahead. Thank you and good morning. Prior to today's webcast, the company posted a presentation to its website, which may be found under the Investors and News section. Please note that various remarks that may be made during today's presentation about future expectations, plans, and prospects for Climb Bio constitute forward-looking statements, including statements about the timing of future data readouts from our ongoing and planned clinical trials, our clinical development plans for Climb 116, our expectations for the commercial opportunity for IgA nephropathy, our cash runway, and other statements which are not historical facts. Actual results may differ materially from those contained in these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our recent quarterly report on Form 10-Q, which is on file with the SEC. In addition, any forward-looking statements made on today's call represent Climb Bio's views as of today only and should not be relied upon as representing its views as of any subsequent date. While we may elect to update these statements at some point in the future, we specifically disclaim any obligation to do so unless required by law. Any forward-looking statements should not be relied upon as representing Climb Bio's estimates or viewed as of any date subsequent to today. Today, with prepared remarks, I'm joined by Dr. Aoife Brennan, Climb Bio's President and CEO, and Dr. Edgar Charles, Chief Medical Officer. In addition, we are pleased to include Dr. Craig Gordon, a practicing nephrologist and professor at Tufts University School of Medicine. Following the presentation, we will open the call to a Q&A session, which will also include an additional member of the Climb Bio management team, Dr. Perrin Wilson, Chief Business Officer. With that, I'll pass the call on to Aoife. Good morning, everyone, and thank you for joining us today. I'm excited to welcome you to the first of several planned R&D spotlight calls where we will share updates on our pipeline programs. On today's call, we are shining the spotlight on our newest candidate, Climb 116, discussing the opportunity in IgA nephropathy, sharing data from recently completed preclinical studies, and discussing next steps in development for this exciting program. At Climb Bio, our strategy is focused and deliberate. We're developing differentiated monoclonal antibodies against validated B-cell targets with clear development paths and indications that offer meaningful therapeutic and commercial potential. We set a high bar for success, and we're making meaningful progress across our portfolio. Our approach is grounded in scientific rigor. We prioritize clinically validated targets, leverage the established monoclonal antibody modality, and focus on diseases with well-defined endpoints and established regulatory pathways. We move forward when we're confident we have an opportunity to make a real difference for patients with immune-mediated diseases. Our pipeline is anchored by BDO PROTEG, a B-cell-depleting DD19 monoclonal antibody that has potential in many B-cell-mediated diseases and is being developed in both IV and subcutaneous formulations. The BDO PROTEG team at Climb Bio has hit multiple milestones already this year, including dosing the first patients in the systemic lupus erythematosus and immune thrombocytopenia trials in the first half and initiating the primary membranous nephropathy and subcutaneous trials earlier this month. All four trials are now actively enrolling, and we're looking forward to continuing to share progress and data with you in future communications as part of this spotlight series. Today, we're turning the spotlight to our second program, Climb 116, which we expect will enter the clinic later this year, subject to regulatory clearance. This program is a strong strategic fit, complementary to our lead assets and aligned with our core focus. We in-licensed Climb 116 from Mabwell in January of this year. It checked every box: a high unmet need indication, a large commercial opportunity, and early preclinical data that pointed to a potential best-in-class profile. We're co-developing the program with Mabwell, who retain rights in Greater China, while we maintain rights and lead development and commercialization in the rest of the world. We plan to continue to partner with Mabwell throughout development and leverage their operational footprints and capabilities to expedite progress. IgA nephropathy is an important cause of end-stage renal disease. There are over 170,000 patients with IgA nephropathy in the U.S. alone, and that number has the potential to grow based on updated guidelines, which lower the threshold for diagnostic kidney biopsy in patients with proteinuria, as you will hear about later from Dr. Gordon. IgA nephropathy is mostly diagnosed in asymptomatic patients, so a medicine that can address the root cause of the kidney damage that has the potential to be safely taken over long periods of time with low patient burden and high compliance has the potential to be the cornerstone of future treatments. In addition to representing a large and growing commercial opportunity, IgA nephropathy has other features that are favorable from a drug development perspective, including an established regulatory pathway. Thanks to work done to demonstrate the relationship between proteinuria and long-term kidney outcome by others in the IgA nephropathy space, there is an established accelerated approval pathway based on reduction of proteinuria at nine months. You'll hear more today about why we believe Climb 116 is a compelling opportunity in IgA nephropathy. Sweeper antibodies have been developed successfully, targeting other soluble biological targets. As the only sweeper antibody targeting APRIL in development, we're excited to evaluate how Climb 116 can address some of the gaps in therapy that currently exist for patients. Earlier this year, when we announced the collaboration with Mabwell, at the time, we had an exciting molecule with a novel design and mechanism of action. Today, we will outline how those design features translate in vivo in a highly relevant animal model in non-human primates. Given the competitive space, we want to put Climb 116 to the test with rigorous head-to-head studies versus the first-generation anti-APRIL monoclonal antibody. We're thrilled to share the preclinical results today that demonstrate that Climb 116 may offer meaningful advantages over first-generation approaches, including the potential for a differentiated profile with both longer PK and deeper and more durable IgA reductions, translating the theoretical advantages of this new mechanism into in vivo differences in activity and kinetics. We're on track for phase 1 initiation in Q4 this year and expect to have initial data from the trial mid-year 2026. Prior to jumping into the data, we're pleased to be joined by Dr. Gordon to provide some background context on IgA nephropathy based on his extensive clinical and research experience in renal medicine. Dr. Craig Gordon is a nephrologist and Co-Director of Evidence Review at the KDIGO Clinical Practice Guidelines for the Treatment of IgA Nephropathy. Our discussion today is timely, coming on the heels of the recently published practice recommendation on which Dr. Gordon was an author. Over to you, Dr. Gordon. Thank you so much. IgA nephropathy is a common condition compared with all of the other glomerular disorders. Its incidence is at least 2.5 per 100,000 individuals, with higher incidences in Asian-Pacific populations. The median age of diagnosis is 40 years of age, and data from the UK Radar Registry revealed the median kidney survival time is 11.4 years. Combined with the early age of diagnosis and this short survival time, IgA nephropathy is a major cause of kidney failure during a patient's lifetime. Can we do better than the time-honored ACE inhibitor and ARB therapy? With the answer being an emphatic yes, there are so many new treatments available, ranging from hemodynamic treatments listed here to immunosuppressive treatments listed in the second bullet. The question remains, though, which combinations will be used? Will we combine hemodynamic and immunosuppressive therapies? Very likely yes. What about multiple immunomodulating treatments? Again, likely yes. Finally, for which patients, when in the disease course, and for how long? Here is the data from the UK Radar Registry. You can see in panel A that with adults represented in the pink line, on the x-axis is time from diagnosis to kidney failure or death, and on the y-axis is the probability. You can see here around the 11-year mark, 50% of people have progressed to kidney failure. If we look out further at the 30-year mark, over 75% of people have progressed to kidney failure. For those in panel G who are young of age at diagnosis and with rapid annual EGFR decline, the chances of experiencing kidney failure are nearly 100%. Here is a patient case that's a recent patient of mine that highlights the challenges. This 46-year-old male was referred for hematuria, proteinuria, decreased GFR, and importantly, no symptoms. His blood pressure was elevated, as you can see, and his urinalysis revealed both blood and protein. Urine protein to creatinine ratio was 2.9 grams, which is substantially higher than some of the values we'll be speaking about later in the talk. His EGFR was reduced from normal at 58 mL per minute. I want to emphasize that the disease progression in the form of decreased GFR that's occurred in the absence of symptoms. The patient underwent biopsy, which revealed IgA nephropathy. On the Oxford classification or MET C-score, he scored an M1 E0 S1 T0 C0, and you can see what these terms represent in the subsequent line. He was initiated on an angiotensin receptor blocker, and then we held discussions with him regarding additional treatment options. One of the tools we used to discuss his risk of progression was the International IgA Nephropathy Prediction Tool. This is something that very easily can be done using information obtained at the time of the biopsy, including the GFR and proteinuria, systolic and diastolic blood pressure, demographic features of the patients, their treatments, and the use of the MET score. When we plugged this in for our patient, choosing a five-year time horizon, he had a risk of 50% decline in GFR or progression to kidney failure, 47%. This very high value informed many of our discussions about treatment. Let's turn to the pathogenesis of IgA nephropathy. Here we turn to the 4-HIT model, where various antigens, infections, and other GI exposures in the Peyer's patches of the gut tissue of the terminal ileum, these antigens result in both T-cell independent and T-cell dependent conversion to IgA positive B cells and plasma cells under the stimulus of BAFF and APRIL. These IgA positive plasma cells release the Gd-IgA1 in HIT 1. In HIT 2, autoantibodies are directed against the Gd-IgA1, resulting in HIT 3, the immune complex formation. In HIT 4, these immune complexes deposit in the kidney, resulting in inflammation and injury. There are a number of treatments that are under development or already approved targeting this 4-HIT model. You can see the HITs represented with HIT 1 on the bottom left, HIT 2 in the upper left, and HIT 3 and 4 to the right. Those represented in this slide in green are treatments that have been FDA approved, including renoprotective therapies up there in the upper right and enteric-coated or time-released budesonide targeting HIT 1 in the lower left. Older treatments that have not been FDA approved and likely won't be include treatments like systemic corticosteroids targeting the inflammation in HIT 4. You can also see in blue a number of inhibitors of various components of the complement cascade represented in blue and blocking HIT 4, as well as in the upper left, some of the anti-APRIL and BAFF inhibitors that likely impact HIT 1 in the disease onset. I want to mention the important role of surrogate outcomes in IgA nephropathy. The FDA recognized the need for surrogate outcomes in studies of IgA nephropathy due to it being a slowly progressive disease. As a result, the FDA has allowed accelerated approval recently of treatments based on the improvement in proteinuria, with full FDA approval requiring subsequent determination of whether there's an improvement in the slope of estimated GFR or kidney function. This pathway has been true for time-released budesonides, barcentin, and lifelong apixaban, and likely will be the pathway for all new agents studied in IgA. Finally, I want to emphasize that outcomes that are of scientific interest may include decreases in GDIGA1 and APOB. This brings us to a recent publication earlier this month of the KDIGO clinical practice guidelines in IgA nephropathy. KDIGO is an international organization responsible for the development and publication of clinical practice guidelines in nephrology across a wide range of conditions. The IgA guidelines were published in early September, and I should disclose for the purposes of this talk that I served on the Evidence Review team and was one of the authors of the publication. KDIGO has statements regarding a number of areas related to IgA. I'm going to cover a few of them today, including those related to diagnosis in this slide. Importantly, IgA can only be diagnosed by a kidney biopsy at this point. There's no validated biomarkers for its diagnosis. Importantly, to allow early diagnosis and early treatment of IgA, which is very different than what happened with my patient, a kidney biopsy should be considered in all adults with greater than 0.5 grams of proteinuria in whom IgA is a considered diagnosis. Shifting to treatment, how do we define those at risk of rapid progression? Those are really defined by proteinuria. Proteinuria greater than 0.5 grams in this first practice point here is someone in whom we can initiate or intensify treatment. This is substantially lower than the level in the patient I presented earlier. When we talk about treatment goals, the goal here is to slow and reduce the risk of progressive loss of kidney function, with the idea being that during the patient's lifetime, they don't progress to kidney failure. At present, the only validated biomarker that we can use for clinical decision-making is the level of protein excretion in the urine, which should be reduced to a minimum of 0.5 grams per day or less, and ideally 0.3 grams per day or less. Important, although not underlined here, is that this likely will require multiple treatment strategies. Consequently, the treatment of IgA nephropathy in patients at risk of progressive loss of kidney function is to simultaneously reduce the immunoglobulin A-containing immune complexes and their glomerular injury and simultaneously manage the consequences of existing nephron loss. The second bullet point is that we should use treatments proven to reduce the galactose-deficient IgA1. Presented as an algorithm, you can see at the top individuals at risk of progressive kidney function loss, and to the right, we move to the generic treatments of nephron loss, including RAS inhibitor therapy, DRAS, and SGLT2 inhibitors. On the left side are the IgA-specific drivers of nephron loss, separated into treatments that reduce the synthesis of pathogenic IgA and those that slow the IgA immune complex-mediated kidney injury. You can see here Nefacon, or the time-released budesonide, is listed as one that is thought to reduce the GDIgA1, whereas there's no data for this with systemic corticosteroids. Finally, the bottom of the slide highlights the importance of clinical trials. I should emphasize that although the guidelines were published in September of 2025, the literature date cutoff for them was over a year ago, just due to the delays in publication and getting things to press. Some of the newer therapies that have been published or are under FDA approval are not listed in this algorithm. I'm going to shift to discussing our current understanding of the BAFF and APRIL pathways that are an exciting new and novel pathway that's being targeted in IgA nephropathy. APRIL is a molecule that stimulates plasma cell proliferation and antibody class switching, which themselves lead to the production of the galactose-deficient IgA1, or GDIgA1. Blockade of this through the use of APRIL blocking therapy very likely reduces GDIgA1 and all the downstream hits from there. BAFF and APRIL antagonists have been developed, and in this slide, you can see BAFF, the molecule, is represented in blue and APRIL in green. The BAFF and the APRIL interact with a bunch of receptors on B cells and later-stage B cells and plasma cells, as you can see on the bottom. BAFF interacts more with more immature B cells and APRIL with more mature, later-stage B cells and plasma cells, which are thought to be very important in the release of the GDIgA1 in IgA nephropathy. In the middle of the slide, you can see a number of agents under development that are both BAF and APRIL inhibitors, and to the right, those that are APRIL inhibitors alone. I will emphasize that all of these and many other BAF and APRIL inhibitors are under active investigation, ranging from phase 1 to phase 3 trials, with exciting evidence expected. All of them are administered parenterally, generally subcutaneously, and usually with dosing frequency of every two to every four weeks. In comparison of our current treatment armamentarium in 2025, I wanted to summarize some of what I've been speaking about. I've tried to use the same color coding from my earlier slide to represent things that were either under FDA approval, FDA investigation, or likely not going to be. For instance, corticosteroids are in yellow because they're not going to be submitted to the FDA for approval. The items listed in green, the time-released budesonide and endothelin antagonists, have received full FDA approval based on the presentation of proteinuria and GFR data. On the bottom, apixaban is under accelerated approval as the UPCR or proteinuria data is available, but the GFR data is not currently available. Finally, all of the BAF and APRIL inhibitors we've been discussing are awaiting the data, both on proteinuria and GFR. I'd like to emphasize that the first four groups of medications are all generally orally administered, whereas all of the BAF and APRIL inhibitors are parenteral. When we look at efficacy data, we can see the proteinuria and GFR data for some of the earlier treatments, and those that are relatively new either have just proteinuria or treatment results and efficacy to be determined. Finally, when we look at safety, and safety is very important in this condition, as it's very likely that the treatments we use will be long-term treatments targeting HIT 1 as well as HIT 4 in particular. You can see here that there are safety concerns to be aware of for these various agents, including infections with systemic corticosteroids, steroid-like side effects with budesonide, so there is some absorption. There's the need for monitoring. You can see some of these items are starred, requiring REMS monitoring for some of the other treatments. This is to be determined for the BAF and APRIL inhibitors. To conclude, where are we going in the future? I am going to turn back to the KDIGO clinical practice guidelines, which propose here in this box that we use combinations of medications targeting different points in the IgA pathways. It is likely going to be more effective. Also, maintenance immunological therapy, similar to what we do in other glomerular diseases, for instance, lupus nephritis, is likely to be required. This is really because none of the drugs approved alone reduce the proteinuria or improve the GFR slope sufficiently to prevent dialysis in the lifetime of IgA nephropathy patients. Likely in the future, we are going to move to combinations of medications and needing data requiring combinations of those treatments and likely an update to the IgA guidelines. Thank you, I will turn over to Dr. Charles next. Thank you, Dr. Gordon, for your comprehensive overview of the pathogenesis and treatment of IgA nephropathy. As you've highlighted, there have been tremendous advances in our understanding of IGAN over the past decade. As a result, there have been recently approved treatments for IGAN, with several promising investigational therapies in late clinical development. Even with these advances, however, there remains a need for therapies that are yet more effective, safe, and well-tolerated, and offer less frequent, more convenient dosing for patients. Over the next several minutes, I'm going to describe why we at Climb Bio believe that Climb 116, our investigational anti-APRIL antibody, has the potential to be a best-in-class therapy for patients with IGAN. As Dr. Gordon described, APRIL, since it drives the generation of pathogenic Gd-IgA1, is critical for hit 1 in IgA nephropathy pathogenesis, as it sits on top of the pathogenic cascade. APRIL also contributes to hit 2 of the cascade, as it impacts the generation of autoantibodies, which react with Gd-IgA1 and form immune complexes that deposit in the glomeruli causing kidney injury. Targeting APRIL offers the potential for a disease-modifying approach in IGAN. It acts early and through multiple steps of the IGAN cascade. The causal link between IgA production and specifically Gd-IgA1 production with IGAN pathogenesis, combined with the fact that these immunoglobulins can robustly be measured quantitatively, makes them informative dynamic biomarkers for early-stage clinical studies. We believe their use allows for rapid ascertainment of proof of concept in dose selection. Proteinuria reduction is a strong predictor of eGFR stabilization, which itself is a robust indicator of kidney function. Thus, longitudinal assessment of proteinuria in early clinical trials allows for predictions of efficacy in stage-gated decision. APRIL has been validated as a therapeutic target for IGAN in several early and late-stage clinical trials. Selective anti-APRIL monoclonal antibodies like sibecrilimumab, as well as dual inhibitors of APRIL and B-cell activating factor or BAFF, such as etafazept, have shown significant reductions in proteinuria, as measured by the urine protein creatinine ratio, or UPCR. Comparing across different clinical trials, noting that caution should be exercised when comparing cross-trial data, reductions in UPCR with sibecrilimumab have been numerically better than what has been observed with etafazept. This suggests that BAF inhibition does not provide an efficacy benefit beyond APRIL inhibition alone in IgA nephropathy. This is perhaps not surprising, as BAF's role in IgA nephropathy is less well established than that of APRIL. Thus, an APRIL-only targeting approach appears to be a cleaner way to target IgA nephropathy. It avoids the potential immunosuppression associated with BAF inhibition, and it does not appear to incur a trade-off in efficacy in the case of sibecrilimumab. As first-generation anti-APRIL agents such as sibecrilimumab have set the bar for the anti-APRIL class, next-generation anti-APRIL agents have the opportunity to deliver differentiated profiles based on improved efficacy and less frequent dosing with acceptable safety and tolerability. In the phase 2 study of sibecrilimumab and IgA nephropathy, dose-dependent effects on APRIL suppression, IgA suppression, and proteinuria were observed. Importantly, dose-dependent effects were also observed for the percentage of patients who went into complete proteinuric remission, which is defined as less than 0.3 grams per day of proteinuria, and which is a key therapeutic goal. However, only approximately 12% of patients who received 4 mg/kg every four weeks, which approximates the fixed dose regimen of 400 mg every four weeks that's been used in phase 3, reached complete proteinuric remission at month 12. Approximately 26% of patients who received 8 mg/kg, the dose that more completely aggregated APRIL, achieved complete proteinuric remission. Importantly, the safety profile was similar across the dose groups, even in the high dose group that fully suppressed APRIL. These results suggest that deeper APRIL suppression may lead to more robust proteinuria reduction and higher proteinuric response rates. Next-generation anti-APRIL agents have the potential to provide deeper APRIL suppression and get more patients into proteinuric remission, and they also have the potential to provide more prolonged APRIL suppression while maintaining the favorable safety and tolerability profile of the first-generation anti-APRIL agents. Importantly, a minimally adverse therapeutic profile is critical for patients with IgA nephropathy, as they will likely require lifelong treatment. Less frequent dosing and acceptable safety tolerability would be expected to result in durable treatment compliance and consistent long-term real-world efficacy. Climb 116 is a next-generation anti-APRIL monoclonal antibody that, to our knowledge, is the only anti-APRIL sweeper in development. To function as a sweeper, Climb 116 has been designed to facilitate its own recycling through high-affinity binding to the neonatal Fc receptor, or FCRN, as well as to eliminate APRIL through high-affinity pH-dependent APRIL binding. It has also been engineered to selectively target APRIL solely for neutralization and elimination. Validated Fc mutations have been introduced to diminish the effector function with minimization of off-target immune activation. For these reasons, we believe that Climb 116's design offers the potential for best-in-class efficacy. We will be presenting in a few moments our data that supports this mechanism. Let's dive a little deeper into the Climb 116 sweeper mechanism of action. Climb 116 can be likened to a targeted iterative APRIL disposal mechanism. Climb 116 binds with high affinity to APRIL at neutral pH. Its binding affinity for APRIL dramatically declines as pH declines. Thus, Climb 116 is engineered to bind to circulating APRIL in extracellular space. Following endocytosis of the Climb 116 APRIL complex, the design of Climb 116 allows it to release APRIL in the acidic environment of the endosome, and APRIL is free to be subsequently degraded in the lysosome. Meanwhile, the design of Climb 116 allows it to bind to FCRN at the acidic pH within the endosome, and it is shuttled back to the cell surface, freeing it to participate in further rounds of APRIL degradation. This sweeper mechanism of action has the potential to provide more profound and prolonged APRIL suppression following each dose, which in turn could result in clinical benefit. An in vitro study supports the sweeper mechanism of action and shows how it is mechanistically differentiated from the first-generation APRIL inhibitors, sibecrilimumab and zikaglibin. Here, Climb 116 demonstrated binding to APRIL in a pH-dependent fashion in contrast to the other APRIL inhibitors. In all panels, concentration-dependent binding of anti-APRIL antibody to APRIL was shown. The curves with the solid symbols represent binding at pH 7.4, and the curves with the open symbols or lines in pink represent binding at pH 5.8. Climb 116, depicted on the left, shows high potency for APRIL binding in neutral pH. However, when the pH is lowered to 5.8, which mimics the acidity of the endosomal compartment, Climb 116 has markedly abrogated binding to APRIL. In contrast, neither sibecrilimumab on the top right panel nor zikaglibin on the bottom right panel have meaningfully reduced potency for APRIL when pH is reduced to 5.8. Building upon this in vitro experiment, our in vivo experimental work provides additional evidence supporting the sweeper mechanism of action. The next set of experiments were designed to test the activity of the sweeping mechanism. They interrogated whether Climb 116 more effectively eliminated APRIL and whether Climb 116 more efficiently recycled itself compared to first-generation anti-APRIL antibodies. In the study depicted on the left, anti-APRIL antibodies, either Climb 116 or sibecrilimumab, were administered to mice. Thirty-six hours later, the mice were injected with human APRIL, and concentrations of serum APRIL were subsequently measured longitudinally. As you can see from the green line, serum APRIL was maintained at low concentrations in the mice that had been administered Climb 116. In contrast, in the mice administered sibecrilimumab, APRIL levels were initially reduced, but they increased by almost threefold by six hours. Thus, in this study, Climb 116 demonstrated more effective APRIL depletion and clearance compared to sibecrilimumab. This study was followed up by a study designed to assess the efficiency of recycling of Climb 116 following its binding to APRIL. In the study depicted on the right, mice with human FCRN were used since human antibodies bind to mouse FCRN less efficiently. These mice were administered anti-APRIL antibodies, either Climb 116 or sibecrilimumab. Forty-eight hours later, mice were injected with either human APRIL or buffered saline at the time point noted by the vertical dashed line. Serum concentrations of the anti-APRIL antibodies were measured over time. In mice that had received Climb 116, depicted in green, the exposure of Climb 116 continued to be maintained after the addition of human APRIL. Climb 116 concentrations were similar to those in the mice that had been injected with Climb 116 but did not receive APRIL, supporting the efficient recycling mechanism of Climb 116. Put another way, in the presence of APRIL, the PK profile of Climb 116 was similar to its PK profile in the absence of APRIL. The results are consistent with our in vitro data and suggest that Climb 116 is able to dissociate from APRIL effectively under low pH conditions, such as in late endosomes after internalization, leading to the effective recycling of Climb 116. In contrast, in the mice that had been injected with sibecrilimumab, depicted in gray, the exposure of sibecrilimumab decreased by over 90% after the addition of APRIL compared to the mice that had been injected with sibecrilimumab but not APRIL. Taken together, both of these studies provide experimental evidence for the Climb 116 sweeper mechanism, and they support the potential of Climb 116 to provide deeper and more durable degradation of APRIL. On the next slide, the in vivo PK and PD effects of Climb 116 were assessed in non-human primates. This pilot study in NHBs was ongoing when we in-licensed Climb 116 this past January. In this study, the PK and PD of either Climb 116 or sibecrilimumab administered as a single dose of 100 mg/kg were studied in two animals per cohort. Data were censored for the one animal in each cohort to develop antidrug antibodies, or ADA. Of note, ADA often occurs when NHBs are administered humanized antibodies, and the presence of ADAs in NHBs is not reliably predictive of human immunogenicity. Climb 116 demonstrated markedly prolonged exposure compared to sibecrilimumab in the evaluable animals. This was matched to a deep and prolonged reduction of IgA. IgA suppression with Climb 116 reached 80%, and this level of suppression was maintained for over 168 days. In contrast, sibecrilimumab reduced the IgA by only approximately 65%, and IgA began to rebound substantially after only 70 days. These data demonstrate the potential for Climb 116 to have a longer half-life with deeper, more durable IgA reductions compared to first-generation anti-APRIL agents. Although this was a small pilot study, it really excited us at Climb Bio since it produced evidence of differentiation. We were eager to conduct additional research to demonstrate that these results could be replicated across studies and across different doses. We decided to build upon the pilot study with a larger head-to-head study of single matched doses of Climb 116 versus sibecrilimumab in NHBs with four to six animals per dose. The objectives of the study were to confirm the bioavailability of subcutaneous Climb 116, as well as to assess tolerability, PK, and dose response, including assessment of biomarkers such as IgA, which is felt as core to the pathology of IgA nephropathy. Climb 116 showed a favorable subcutaneous profile. The bioavailability was approximately 85%, which we were very pleased to see. Moreover, the prolonged exposure observed in the pilot study was confirmed. Importantly, there were no local tolerance issues or Climb 116-related safety findings, which was consistent with findings from our other NHB studies. The good bioavailability, prolonged exposure of subcutaneous Climb 116 observed here, coupled with the formulation's high concentration, low viscosity, and good thermal stability, support the potential for convenient at-home dosing. This study further showed that Climb 116 had dose-dependent prolonged exposure in NHBs. At both doses tested, 6 mg/kg and 30 mg/kg, Climb 116 demonstrated lower clearance and approximately a two to three times longer half-life across doses compared to sibecrilimumab. At 6 mg/kg, Climb 116 had a half-life of 19.5 days compared to 7.5 days for sibecrilimumab. At 30 mg/kg, Climb 116 had a half-life of 24.2 days compared to 8.4 days for sibecrilimumab. The phenomenon of target-mediated drug disposition, or TMDD, has been observed with many monoclonal antibodies, including anti-APRILs. It occurs when a drug binds with high affinity to a target, and this interaction alters its pharmacokinetics. As you can see here, TMDD occurred at a similarly low plasma concentration for both Climb 116 and sibecrilimumab. It had minimal impact on Climb 116 clearance, and thus we believe it is unlikely to be clinically meaningful for Climb 116. We sought to compare the impact of Climb 116 and sibecrilimumab on IgA in NHBs, which, as I mentioned earlier, is core to the pathology of IgA. After a single dose administered at 6 mg/kg subcutaneously, Climb 116 demonstrated over a 70% reduction in IgA, and a greater than 50% reduction in IgA was continued out for approximately three months. In contrast, a single matched 6 mg/kg dose of sibecrilimumab achieved a maximal IgA reduction of only 50%, and by approximately two months, IgA levels had returned to over 75% of baseline. Taken together, these results indicate Climb 116 has the potential to result in deep, prolonged reduction in IgA at relevant clinical doses. Robust translational correlations from NHBs to healthy human volunteers to patients with IGAN suggest that Climb 116 has the potential for improved efficacy with less frequent dosing compared to first-generation anti-APRIL antibodies. Again, the same caution regarding cross-trial comparisons. Sibecrilimumab achieved a maximal 60 to 70% IgA reduction in NHBs with doses of 2.5 to 10 mg/kg IV weekly for four weeks. Of note, this dosing schedule in NHBs was more intensive than the every-four-week administration that has been studied in phase two and phase three. Etazepam, a dual BAFF-APRIL inhibitor, achieved a maximal 50% IgA reduction in NHBs with single doses of 9 mg/kg IV. These IgA reductions in NHBs corresponded to approximately a 50% IgA reduction in healthy volunteers. They also corresponded to a 50 to 60% IgA reduction and a 58 to 64% UPCR reduction in patients with IgA nephropathy in phase 2 clinical trials. In contrast, Climb 116, at a potentially clinically relevant single dose of 6 mg/kg subcutaneously, achieved over a 70% maximal IgA reduction in NHBs, suggesting a prospect for improved IgA and UPCR reductions in patients with IgA nephropathy. These results support a differentiated profile for Climb 116, with the potential to be a best-in-class anti-APRIL therapy. Based on the strength of the preclinical package, we're excited to move Climb 116 forward into the clinic. We intend to initiate a first-in-human study of Climb 116 by year's end, subject to regulatory clearance. This study is intended to assess sequentially ascending doses of Climb 116 versus placebo in healthy volunteers, and it is expected to be a randomized, double-blind, and placebo-controlled study in order to robustly ascertain safety, tolerability, and PD effects. The planned primary objective is to assess safety and tolerability. Planned secondary objectives include PK and PD responses, such as APRIL reduction, IgA reduction, and impacts on IgM and IgG. Importantly, given the demonstrated translatability from healthy volunteers to IgA nephropathy patients observed in prior anti-APRIL studies, we expect this study to provide PK and PD data to guide dose, dosing frequency, and a comprehensive study of efficacy and safety in patients with IgA nephropathy. We plan to share more details about the study design following study initiation. Our strategy for Climb 116 is a clinical development program geared for rapid progression and minimal white space between trial phases. Initial data from our phase 1 trial is expected mid-year 2026. Our decision to proceed into patients with IgA nephropathy will be based upon the depth and duration of APRIL suppression, as well as IgA suppression, in addition to safety and tolerability. These data are expected to inform dosing regimen, dosing frequency, predicted efficacy, and predictive safety and tolerability in patients with IgA nephropathy. Internal and validated external biomarker data provide opportunities for development program efficiencies. These data sets include first, PD clinical efficacy correlations between APRIL suppression, IgA suppression, and UPCR reduction, and linked to eGFR stabilization. Second, the observed safety tolerability profile of anti-APRIL monoclonal antibodies. Moreover, we expect that parallel execution of early-stage studies of Climb 116 by Mabwell in China will provide a complementary independent data set that will allow fulsome stage-gate decisions. Finally, the established regulatory precedent for approval in IgA nephropathy provides a path for the clinical development steps required to support an application for marketing authorization. We are extremely excited about the results we have shared with you today. In preclinical studies, Climb 116 has demonstrated clear improvements in pharmacokinetic and pharmacodynamic measures, namely a longer half-life and deeper and more durable IgA reductions as compared to sibecrilimumab, suggesting the potential for a differentiated efficacy profile with less frequent dosing. We intend to leverage all of the above to help accelerate the development of Climb 116 and work to bring this potentially best-in-class therapy to patients. Thank you for your attention. Eva, I'll hand it back over to you for a summary and close. Thank you, Dr. Gordon, and thank you, Edgar, for the excellent overview of the Climb 116 program. As you've heard today, we believe Climb 116 has the potential to be a best-in-class anti-APRIL antibody. As you heard from Dr. Gordon, APRIL is an important target in IgA nephropathy and has been shown to address the underlying pathology driving the disease. The non-human primate data we presented demonstrates that Climb 116 has both longer half-lives and deeper and more durable IgA reductions compared to first-generation APRIL monoclonal antibodies. Based on these data, we believe that Climb 116 has tremendous potential to be a leading therapy in the large and growing IgA nephropathy market. There's an established regulatory path and multiple biomarkers that can be measured early in development to support dose selection and rapid progression. We're moving carefully but quickly with the clinical trial expected to start later this year and initial data expected mid-year 2026. We're excited about the potential of this program to make a meaningful difference for patients with IgA nephropathy. Thank you again for joining us today. We will now open the webcast for Q&A. Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Our first question comes from Colleen Cussie with Bayard. Your line is open. Hi, good morning. Thanks for all the information and thanks for taking our questions. Maybe the first one for Dr. Gordon, just with the current state of IgA nephropathy today, what rate of patients with suspected IGAN are getting kidney biopsies today? Just wondering if there's room for growth on the diagnosis side. Just curious on your view on the therapeutic landscape and which of these endpoints you think will be most informative for your future treatment decisions. Yeah, great question, and thank you for that. The first one about the biopsy is something I believe very strongly in, which is that as a specialty, we have to substantially increase the number of biopsies done. I think there's a number of years of sort of diagnostic nihilism about these types of things, which has led to people just assuming people had IgA but not proving it. The KDIGO guidelines and I think a lot of other inputs into the system are pushing nephrologists more and more to perform biopsies at lower levels of proteinuria. I think we're going to see, and we're already seeing, to be honest, a quite substantial increase in the number of biopsies. If I talk to my pathologist at my local institution, she's seeing probably a 20-30% increase already, partially driven by this. Regarding the second part of your question, I think our current situation, obviously, there's a number of FDA-approved or agents under accelerated approval. One of the challenges, and I think KDIGO helps with this, but we'll need a revision and an update to that, is to sort of tease apart the wheat from the chaff, I suppose, as far as who needs which treatment at which point in time and which combination of treatments. I think if we imagine in the future, it's going to be even more therapeutic options as things that are accelerated approval reach full approval. Very likely, we'll see APRIL inhibitors coming down the pike, and I think there'll very much be a need for experts in the guidelines and others to guide us as to which and which combinations of medications to use. Does that answer your question, Colleen? That does. Thank you. Maybe if I can squeeze a couple in for the company, some really compelling data, you know, the two to three times longer half-life. Just curious if you have any initial thoughts on dosing frequency you'd be targeting. If you can just provide a little bit more color on the ADAs that you saw in the non-human primate models and what your expectations are for your immunogenicity of 116 in humans. Sure. Maybe I'll take the first part and then hand over to Edgar to tackle the ADA question. I think first and foremost, Colleen, what's most important for us is that we achieve full APRIL suppression. We do believe that there's potential for additional activity here with this class. I think that we want to make sure that we have absolutely maximized that component before we start talking about dosing interval. Obviously, what we've seen today really leads us to believe that we can address both and we can really do something that's very meaningful for patients and that's very clearly differentiated from first-gen approaches. I think until we get more experience with the biomarkers and with the PK in healthy volunteers, we'll kind of postpone providing guidance on what that dosing frequency and dosing interval is going to be. That's going to come pretty quickly. As we shared today, we're going to have top-line data mid-year next year. I think with human data, we'll be able to give much more precise answers to how that therapeutic kind of profile is going to play out. I think we're going to wait until we have those data in hand before providing any guidance around injection interval. Obviously, a really important component, but not quite as important as getting the optimal efficacy for these patients to make sure we can truly stabilize kidney function over a long period of time for patients who are diagnosed mid-life. We want to make sure that we're really getting good efficacy with this therapeutic class. Maybe I'll hand over to Edgar to address the second part of your question. Sure. We did observe ADAs in our NHB model, which isn't too surprising. We have a humanized antibody in the form of Climb 116, and that's, you know, not unexpectedly can produce ADAs in NHBs. ADAs in NHBs is commonly observed when humanized monoclonal antibodies are administered. We and others have noted immunogenicity in NHBs is poorly predictive of immunogenicity in humans. Going forward, we're going to be closely looking at ADAs in clinical trials, but we have low suspicion that we will be immunogenic in humans. Super helpful. Thanks for taking our questions. I'll hop back in the queue. Thanks, Colleen. The next question will come from Thomas Smith with Leerink Partners. Your line is open. Hey, guys. Good morning. Thanks for putting this event together, and thanks so much for taking the questions. Maybe first one for Dr. Gordon. I was wondering if you could just elaborate a bit on how you expect to select between really the multitude of agents targeting APRIL and BAFF-APRIL, and specifically, what's the most important consideration for you across efficacy, safety, tolerability, and injection frequency? Yeah, great. Thank you for the question. Obviously, we need information about the differentiation of these different treatments as that information scientifically comes out. I imagine what we're really looking for is, you know, among these various agents, is going to be the level of clinical efficacy as far as proteinuria and GFR. Is there any differentiation there? Somewhat related to that is the impact on IgA and Gd-IgA1 levels. I think equally important, I think, is the safety side of things because this is very likely going to be quite long-term therapies, possibly years, if not decades, in length. That question of safety, tolerability is going to be very important. Finally, I think with all of these BAFF and APRIL agents being administered parenterally, the dosing frequency is going to be very important. I think something that is dosed less frequently would be a potential big advantage in this area. Got it. That makes sense. One for the Climb Bio team, if I could. Very interesting non-human primate data this morning. Could you maybe just clarify and comment on the Climb 116 epitope binding site and how that compares to sibecrilimumab? Is it the same site or a different site? Any specific considerations you would call out there? Yes. I think very important considerations, Tom. It's a different site to Cibi. We will be sharing additional non-clinical data later this year at a medical conference that I think will really help tease apart some of the nuances here around the epitope binding site and how that may contribute to high molecular weight complex formation. It's important, but we're sharing top-line data today around kind of the PK/PV. I think there are several layers underneath that as well that we'll share in due course. To answer your question directly, different binding sites to Cibi. Understood. That's helpful. Just a last question, if I could, for the company, and maybe Dr. Gordon would want to comment here as well. Just given the number of agents that are coming that are likely to seek accelerated approval here over the next couple of years in IgA nephropathy, can you talk about some of the clinical plans with respect to trial enrollment and how you're planning to achieve efficient enrollment in a world with multiple approved advanced therapies? Thanks so much. Yeah, I think that's probably I'll get Edgar to answer that question, Tom, for you, if that's okay, because it's something obviously we've put a lot of thought into here as a company. Edgar, do you want to talk to that? Sure. You know, IgA nephropathy is a highly prevalent condition, and it's currently underdiagnosed and undertreated. We think that there are fairly many patients who could stand group treatments and could be well served by going into clinical trials as recommended by the KDIGO clinical practice guidelines. We're going to be looking at how we perform in our clinical trials against standard of care, on top of standard of care, and then from sparing regimens as those regimens have been recommended in the KDIGO clinical practice guidelines. We will be going to clinical trials. We will be having inclusion/exclusion criteria that are reflective of those who carry the disease. Of course, we'd be conducting global clinical trials. Yeah, and I would add on to that, Tom, just to call that as a key advantage I think we have is our collaboration with Mabwell. As you guys are all aware, about 60% of patients in the prior late-phase studies were Asian because of the prevalence of this disease in Asian populations. We've executed a non-clinical program that supports IND both in China as well as globally. We're kind of global from the outset in terms of thinking about how to develop this asset, which I think will be very advantageous when it comes time to open up enrollment in the patient population once we get through these two phase 1 studies in healthy volunteers, one in China, one outside of China. We really have a great data set that will allow us to move very quickly, not just in the U.S., but also in Asia and some of the regions of the world that have been the most important contributors to the late-phase development programs that have been executed to date. I think that's something that we've absolutely been cognizant of from the outset. Got it. That makes sense. Super helpful. Thank you guys so much for taking the questions. The next question will come from Julian Harrison with BTIG. Your line is open. Hi, good morning. Thank you for hosting this and for taking my questions. I have a few, and I'll just ask them all at once. First, I'm wondering if you believe 116 is sufficiently out of the woods with regards to risk of target-mediated drug disposition. Is that something you could sufficiently rule out with the NHB data shared today, or does that maybe require additional confirmation in the clinic? Second, I'm wondering how wide the expected therapeutic window is of 116 in humans. I understand you plan to share more details in the not-so-distant future about your upcoming trial, but are you able to give us a sense now for the dosing range that you plan to initially study? Then, Dr. Gordon, I'm curious how you envision the typical treatment sequence in IgA nephropathy relative to endothelin receptor antagonists when APRIL inhibitors become commercially available. It looks like there are profound opportunities to combine both classes, but I'm curious about how you're thinking about which treatment class you would maybe start first on a typical basis. Thank you. Great. I'm going to hand to Edgar first because I think we can knock off your first two questions pretty quickly, and then I'll hand it over to Dr. Gordon. Sure. We're really pleased with what we saw in the NHB. As you know, TMDD has been observed with many monoclonal antibodies, including anti-APRIL monoclonals. It occurred at similarly low concentrations for Climb 116 and sibecrilimumab, approximately 5 micrograms per mL. This is similar to what's been reported for JADE-01. Some differentiating factors for us seem to be that sibecrilimumab has a shorter half-life above 5 micrograms per mL. JADE had a similar half-life and overall exposure to 116 above the TMDD threshold. Below the TMDD threshold, JADE-01 appeared to have a shorter half-life based on data from the 30-milligram dose. We think we're differentiated from the other anti-APRIL. When we looked at our own data, TMDD had minimal impact on Climb 116 clearance, and we believe it's unlikely to be clinically meaningful for patients in the clinic. Getting to your therapeutic window question, our tox studies are complete, and we're really looking forward to going into the clinic at the end of the year. Anti-APRIL antibodies historically have shown a large therapeutic index. We have established safety and tolerability of the anti-APRIL class. You certainly expect that to carry forward over in our compound. Climb 116 certainly has shown good pharmacokinetics and PD effects in NHBs, and we fully expect that to carry forward into healthy volunteers as well as patients with IgA nephropathy. We expect to be able to dose at convenient doses and infrequent dosing goals and achieve a very fulsome APRIL and IgA survival. You wanted to speak to the. Absolutely. You asked a really key question, and I think the challenging thing in IgA is the heterogeneity of the patients. People have said if you've seen one IgA patient, you've seen one IgA patient. Our job in clinical practice is to determine how much of that proteinuria is from active disease and active inflammation versus prior damage. That's going to inform our approach. I think if we're seeing a lot of active inflammation, we might pick agents that target the inflammatory side of things, sort of the HIF3 and 4. This could be even systemic corticosteroids or complement inhibitors. When we're talking about the generic, you know, hemodynamic effects, that's maybe something we're going to use in all patients, for sure in those with less active disease, mostly proteinuria without hematuria, and that's including the endothelin antagonists there. I do think there's going to be a big role in this condition for lowering that HIF1, blocking APRIL, blocking the formation or excretion of the Gd-IgA1. My suspicion is, Agents that target that part of the pathway are going to be really the strongest and most important part of our algorithm material. Excellent. Very helpful all around. Thank you. The next question will come from Leland Gershol with Oppenheimer. Your line is now open. Good morning. Thank you for holding this event and sharing the preclinical data. A couple of questions. First, I want to ask, with respect to the upcoming phase 1 data, it looks like from the other agents in the IgA category, there's fairly good translation from preclinical to clinical in terms of IgA suppression. I want to ask, as we look forward to those data, are you expecting to see 70% plus? Maybe if you could share just what you would like to see in terms of level of suppression and other efficacy metrics you're looking at as you look to take Climb 116 into phase 2 and then follow up. Thanks. Great question. We're really excited. We'll be moving into the clinic by the end of the year. As you mentioned, we'll be looking at PK and PD viral markers, which have good translatability into patients with IgA nephropathy. We're certainly going to be looking at APRIL suppression. We're going to be looking at IgA suppression, which will give us a read-through to UPCR and eGFR stabilization in larger numbers of patients. We certainly want to see a very competitive profile in terms of IgA suppression. We think that we have the ability to have full APRIL suppression over the course of the dosing interval, which will translate to a result in very competitive IgA suppression. We have that clearly in mind as a criterion for advancement. Okay, thanks. I just wanted to ask, there's another candidate in development, you know, for which one of the attributes is avoidance of immune complex formation. I just wanted to know if you could speak to the importance of this aspect in this setting and what your thoughts are with respect to any interference that you may experience from the potential for immune complex formation with Climb 116. Thank you. Great question. Yes, others have reported high molecular weight complex formation and a reaction of the anti-APRILs with the trimer APRIL, which can obviously bind to multiple antibodies and create a daisy chain-like effect of high molecular weight antibody complexes. We are not seeing evidence of significant HMW, and we are going to be presenting more data at a future medical conference this year to elaborate on this concept. I think you can see from our PK and PD data and NHPs that we have a very competitive profile. At the rate of TMDD that we are having at a very low level that's not affecting PK, we do not anticipate an HMW effect being important. We do have some other. Thanks very much. We'll share later in the year that really put the points on that. We just didn't include it in today's top line data presentation. More to come and more to this space for some of our in vitro work, just kind of really showing the importance of the epitope and how that impacts Climb 116. Great. Thanks for the added info. The last question will come from Matthew Phipps with William Blair. Your line is open. Good morning. Thank you for all the detail today and for Dr. Gordon's overview. I was wondering, you mentioned that Mabwell is doing a parallel execution here. What data do you think will be available to help guide decisions kind of mid-next year after your own data? Given this highly consistent data across these different programs from NHBs to healthy volunteers and IgA nephropathy patients, how much data do you need before really trying to step your foot on the pedal and accelerate into a registration and trial? Thank you. Yeah, great question. I think from a strategic perspective, what we've seen already, we believe is very compelling in terms of the historical data showing how the non-human primates translate to humans and then into patients with disease, as well as the data that we have and that we've highlighted today as part of our presentation. We're moving, it's all gas, no brakes here from an investment perspective. We've initiated all of the studies that are going to be required to do clinical trials of longer duration. We're actively working with Mabwell to really design a very efficient late-phase development program. I do think it's going to be important to demonstrate proteinuria reduction in a cohort of patients with IgA nephropathy before enrolling several hundred patients in a phase III blinded study. At some point along the way, we're going to provide those data as an interim read-out on the overall development plan. You can expect that this is going to be very seamless with regard to stage of development, and it's going to be very seamless with regard to geography. That's how we thought about this from the outset. It really enables, with our collaboration that we've established with Mabwell, that we're very excited about. More to come as we get into next year and we start to generate data and have some of those regulatory engagements that are going to be really important to determine how quickly we can move here. We're definitely moving with intention to develop this rapidly. Now, I would like to turn the call back over to management for closing remarks. Great. Thank you so much, everybody. Sorry, we ran a little bit over time, but hopefully some great information. We're certainly excited to keep everyone updated as we move forward to generate some human data and then subsequently data in patients. Thank you so much for your time and attention this morning. Thank you, operator. Thank you. This concludes today's conference call. Thank you for participating, and you may now disconnect.