Good morning, and welcome to the Climb Bio R&D spotlight event focused on CLYM116 and the APRIL opportunity in IgA Nephropathy. At this time, all participants are on the listen-only mode. A question and answer session will follow the prepared remarks. Please note that this call is being recorded. I would now like to turn the call over to Julia Keefe, Director of Communications and Investor Relations at Climb Bio. Please go ahead. Thank you, operator, and good morning, everyone. Prior to today's webcast, the company posted the presentation on its website, available under the Investors and News section. Before we begin, I would like to remind you that various remarks made during today's presentation may constitute forward-looking statements within the meaning of the federal securities laws. These statements include, but are not limited to, statements regarding the therapeutic potential, clinical profile, and development plans for CLYM116 and Budoprutug, expectations with respect to CLYM116 regarding APRIL suppression, dosing profile, durability, efficacy, safety, immunogenicity, and convenience of CLYM116, anticipated timelines for reporting clinical data, potential commercial opportunities, market size, and differentiation in IgAN and other immune-mediated diseases, expectations regarding formulation and device readiness, and the sufficiency of the company's cash resources. Actual results may differ materially from those expressed or implied by these forward-looking statements due to a variety of risks and uncertainties described in the company's SEC filings. Joining me today are Dr. Aoife Brennan, President and CEO, and Dr. Edgar Charles, Chief Medical Officer. Following the prepared remarks, we will be joined for Q&A by additional members of the management team, including Dr. Perrin Wilson and Dr. Susan Altschuller. Today's event will focus on the evolving IgAN treatment landscape, the scientific rationale for APRIL inhibition, the emerging phase I and translational data for CLYM116, and our development strategy moving forward. With that, I'll turn the call over to Aoife. Thank you, Julia, and thank you for joining us today for this R&D spotlight event focused on CLYM116 and its potential in patients with IgA nephropathy. 18 months ago, we introduced CLYM116 as a potential next generation anti-APRIL antibody with the goal of building upon the validated biology of the APRIL class to deliver a differentiated product for patients with IgA nephropathy. Our conviction was based on the novel mechanism of action of CLYM116, an antibody that not only binds circulating APRIL, but also drives its targeted degradation. We believed this sweeper mechanism could help address key limitations of first-generation molecules by providing strong efficacy alongside more convenient dosing frequency. We're pleased to share phase I data today that support the activity of the sweeper mechanism in humans and strengthen our confidence in the emerging profile of CLYM116. These data support three important observations. First, CLYM116 has a 29-day half-life and demonstrated low and steady drug clearance. Importantly, our sweeper mechanism allows us to overcome target-mediated drug disposition and the resulting increased clearance seen with other molecules in the class. Second, in addition to longer exposure, we also observed high potency with rapid, near complete, and durable suppression of free APRIL and a corresponding decrease in IgA, Gd-IgA1, and IgM, which have reached approximately 60%-75%. Third, and importantly, CLYM116 has been generally well-tolerated to date with no serious adverse events or hypogammaglobulinemia. In parallel, we have optimized our formulation, developing a 200 mg per mL product that enables 400 mg dose to be administered in a single two mL injection. This formulation is compatible with both pre-filled syringe and auto-injector presentations. When we model that dose out to our peak dose regimen in patients, CLYM116 is projected to deliver a 12-week dosing interval with APRIL suppression sustained through the entire interval, reached with only a single loading dose. We believe that's a very attractive profile that does not trade efficacy for convenience and has the potential to support best-in-class positioning. Of course, confirming that profile in patients is important, and we're already at work on that with the ongoing NAVIGATE-2 phase II study that's making great progress with enrollment. I will soon pass it to Edgar to review the data in detail, but the central message today is straightforward. APRIL is now a clinically validated targeted IgA nephropathy, and we believe CLYM116 has potential to become a best-in-class therapy within this important therapeutic class. The first generation of IgAN therapeutics has already demonstrated the enormous potential of this drug class. Over time, as we've seen with other emerging drug classes, we expect patients will migrate to newer agents with an improved profile. We believe CLYM116 is well-positioned to lead in the next wave of IgAN medicines and represents an exceptional opportunity for our company. IgA nephropathy is one of the most common forms of glomerular disease worldwide and a leading cause of chronic kidney disease and kidney failure in young adults. Because the disease is typically diagnosed between the ages of 15 and 40, many patients face decades of progressive kidney disease and have long-term treatment needs. We estimate that approximately 200,000 patients are living with IgAN in the U.S. today, with over 75% being candidates for disease-modifying therapy. The diagnosis and treatment of IgAN continues to evolve. The 2025 KDIGO guidelines encourage earlier biopsy and treatment consideration and recommend a more stringent target proteinuria of less than 0.3 grams per day to achieve optimal disease control. We believe these recommendations, together with increasing disease awareness and the availability of targeted therapies, will expand the diagnosed and treated population over time. Based on our estimates of the diagnosed population, the proportion of patients who may be candidates for disease-modifying therapy, anticipated treatment rates, net pricing, we estimate that the U.S. IgAN market opportunity could exceed $20 billion on an annualized basis. The evolution of the IgAN treatment landscape has been remarkable, and perhaps no development illustrates that more clearly than the progress in APRIL inhibition. Sibeprenlimab, marketed by Otsuka as Voyxact, received accelerated approval in the United States in November 2025 and is now commercially available with strong update to date. Across separate phase III studies, first-generation agents Sibeprenlimab, atacicept, and povetacicept have each demonstrated statistically significant placebo-adjusted reductions in proteinuria in the range of roughly 42%-51%. Importantly, the reductions in proteinuria observed in patients tracked closely with the reductions in IgA in healthy volunteers, supporting IgA as a predictive biomarker. As the APRIL class has matured, the question has shifted from whether APRIL biology works in IgAN to how effectively that biology can be harnessed. The data with selective APRIL-targeted therapies suggest that robust APRIL suppression alone may be sufficient for efficacy, increasing the importance of optimizing depth of suppression, durability, convenience, and safety. Together, these clinical findings have established APRIL as an increasingly important therapeutic target in IgAN, and we believe it meaningfully de-risked the opportunity for a differentiated next-generation entrant, such as CLYM116. Validation is not the ceiling. First-generation agents have shown what is possible. The opportunity now is to do better. That's the profile that CLYM116 is designed to deliver. CLYM116 is the only APRIL sweeper antibody currently in clinical development. Its design combines pH-dependent binding, engineered recycling, and extended half-life properties with the goal of achieving deeper and more sustained suppression of APRIL to support less frequent dosing. Put simply, CLYM116 is designed to bind APRIL, bring it into the cell, release it for degradation, and then recycle back into the circulation to bind additional APRIL molecules. This is intended to allow each antibody molecule to disappear its target repeatedly rather than binding only once, potentially enabling deeper and more sustained target suppression with lower and less frequently administered dose. From the moment we in-licensed this program, our objective was to create a differentiated product profile, not merely another APRIL inhibitor. The data we're presenting today provide encouraging clinical evidence that CLYM116 is performing as designed. While the ultimate clinical profile will need to be established in patients, the emerging findings support continued evaluation of the potential best-in-class profile within the APRIL class, finding efficacy, convenience, and safety. On efficacy, single subcutaneous doses produced deep and durable APRIL inhibition that was observed at 12 weeks, which we believe is critical to achieve the best profile for this class. On convenience, CLYM116 has a long 29-day half-life consistent with the differentiated dosing profile described earlier, and thereby supporting extended dosing. On safety, the antibody was well-tolerated, with no serious adverse events or hypogammaglobulinemia observed. Together with our translational modeling, we believe these results support continued evaluation of the 400 mg every 12-week dose regimen, initiated with only a single loading dose in patients. With that, I'll turn the presentation over to Edgar, who will walk through our phase I study, the data supporting CLYM116, how the observed findings compare with our own translational predictions, and the rationale behind our development strategy moving forward. Thank you, Aoife. Good morning, everyone. Today, I will walk you through what we have learned so far from the CLYM116 phase I program and how these emerging data has shaped our development plan. I will start with the biology, because it is an important foundation for interpreting our data set. APRIL is a key regulator of immunoglobulin class switching, particularly IgA class switching, as well as IgA production and the survival of antibody-secreting cells, plasmoblasts, and plasma cells. Making it a central driver of pathogenic IgA generation in IgA nephropathy. In IgAN, pathogenic galactose-deficient IgA1, or Gd-IgA1, plays a key role in the formation of immune complexes that deposit in the kidney and lead to inflammation, proteinuria, and progressive loss of kidney function. Consistent with the known biology, in the clinic, the magnitude of serum APRIL suppression has been shown to correlate with the magnitude of serum IgA reduction. The magnitude of APRIL suppression matters. Deep APRIL suppression is required to drive the greatest reductions in IgA, reinforcing that near complete APRIL suppression is critical to achieving an optimal profile. Following administration of an anti-APRIL agent, we should expect to first see a reduction in free APRIL, followed by a subsequent downstream reduction in IgA. Prolonged suppression of IgA is dependent upon continued prolonged suppression of APRIL, as illustrated in the plot on the left. After APRIL suppression starts to wane, IgA levels begin to rebound. This sequence is exactly what we are looking to see with CLYM116. Rapid APRIL suppression followed by a deep reduction in IgA with durable APRIL suppression throughout the dose interval, providing continued reduction of IgA. That is what is meaningful for patients. Sustained control through every dosing interval, giving more patients a chance to reach target proteinuria levels over time. With that context, I will turn to our phase I study design. The data we are presenting today are from our ongoing phase I study in Australia. This study is evaluating CLYM116 across 25 mg, 80 mg, 160 mg, 320 mg, and 480 mg single-dose cohorts, as well as a MAD cohort in which 320 mg is administered twice, once on day one, and then on day 15. In each cohort, participants have been randomized to receive either blinded study drug or placebo. Participants are followed for 12 weeks after receipt of CLYM116 or placebo. In this study, a 160 mg per mL drug concentration was used. However, as Aoife shared, we have successfully developed a high concentration, 200 mg per mL formulation that enables a 400 mg dose to be delivered in a single 2 ml injection, and we plan to use this formulation moving forward in the registrational studies. As of this presentation, we have 12 weeks of data available up to and including the 320 mg dose in the SAD cohort. We will also be sharing emerging data from the 480 mg SAD and 320 mg MAD cohorts. For our analyses, placebo has been pooled from the individual cohorts. Demographics were generally well-balanced across dose cohorts and consistent with a healthy volunteer population. Overall, the mean age was approximately 35 years, and there were slightly more females than males, and most participants were White and approximately one-third were Asian. There were no meaningful demographic differences among the cohorts that affect the interpretation of the pharmacokinetic or pharmacodynamic findings. Similarly, baseline characteristics were generally well-balanced across dose cohorts and were consistent with a healthy volunteer population. Mean body weight was approximately 70 kg. Of note, serum IgA was generally consistent with what one would expect to see in a healthy population, although there was some variability among the cohorts. We observed that CLYM116 has a favorable safety and tolerability profile. There have been no dose-limiting toxicities, no serious adverse events, no grade 3 or higher AEs, and no AE-related discontinuations observed. All AEs were mild to moderate, grade 1 or 2. No clear dose-dependent pattern of AEs was observed. The most frequently reported treatment-emerging AE across CLYM116 cohorts were headache, upper respiratory tract infection, and injection site reactions. Injection site reactions occurred in 5 participants. In these participants, all of the events were mild, grade 1, and resolved without intervention. APRIL biology also affects other immunoglobulins besides IgA. We have closely monitored IgG from a safety perspective, since low levels of IgG can predispose patients to infection. No participant developed hypogammaglobulinemia, which is an important consideration for a therapy intended for chronic use. We expect to provide a readout of anti-drug antibodies at a future medical meeting, as those data are not yet available. Turning to PK, CLYM116 showed the exposure profile that we believe could deliver leading efficacy and support our patient-friendly extended dosing interval. Exposure increased with dose in a dose-proportional manner. The time to maximum concentration was approximately one week, and the half-life was approximately 29 days. This prolonged half-life is approximately three-fold longer than that of Sibeprenlimab, and we believe it validates the sweeper mechanism of CLYM116. Notably, there was linear clearance of concentrations above 1 mcg per mL. Target-mediated drug disposition, or TMDD, was not observed at clinically relevant concentrations. We did not see TMDD at concentrations above 1 mcg per mL, which was not reached during the 12-week follow-up period with doses of 160 mg and above. The occurrence of TMDD only at low exposures is likely due to effective clearance of APRIL by CLYM116 at clinically relevant exposures, and we believe it further validates the sweeper mechanism of CLYM116. The take-home message here is that the observed half-life and overall PK profile for CLYM116 provide the foundation for evaluating extended dosing interval well beyond the current once-monthly standard. The next question is whether this extended exposure translates into sustained target engagement. Consistent with its exposure profile, CLYM116 produced rapid, robust suppression of free APRIL on day four. This effect was sustained, with free APRIL levels remaining suppressed by greater than 90% through week 10 and greater than 75% at week 12 after a single 320 mg dose. This demonstrates robust target engagement and a prolonged pharmacodynamic effect. These data indicate that the extended exposure we observed in the PK profile translated into robust and prolonged biological effects, with deep and durable suppression of the attended target throughout the available follow-up period. Importantly, at the 320 mg dose level, where 12 weeks of follow-up are available, near-complete APRIL suppression was maintained through the full 12-week observation period, indicating that therapeutic administration of doses as low as 320 mg every 12 weeks could lead to near-complete APRIL suppression throughout the dosing interval. This is precisely the bar we established at the outset. APRIL suppression maintained through the exposure trough at week 12, supportive of extended dosing. The observed temporal relationship between concentration and APRIL suppression following a single dose illustrates the PK and PD advantages of CLYM116 versus first-generation APRIL agents. The favorable PK of CLYM116, including its long half-life, led to an exposure that robustly suppresses APRIL for 12 weeks. Here we show our model-derived estimate of APRIL EC75, which is the concentration required to achieve a 75% reduction in APRIL. The calculated EC75 for CLYM116 is 3.65 mcg per mL, which is well below the exposure observed with a single 320 mg dose through week 12. We believe the long half-life and durability of APRIL suppression of CLYM116 in healthy volunteers offer a clear advantage compared to the first-generation anti-APRIL monoclonal antibody, Sibeprenlimab. Following a single dose of Sibeprenlimab 400 mg sub-Q in healthy volunteers, exposures started dropping below APRIL EC75 around week six, with a rise in APRIL above 75% reduction from baseline around week eight. We next evaluated whether the deep and prolonged target engagement observed with CLYM116 translated into clinically relevant PD activity further downstream of APRIL. Consistent with the known biology of APRIL and the data I've just outlined for APRIL suppression following administration of CLYM116, we observed a 60%-75% reduction from baseline in several important immunoglobulins. IgA was reduced by approximately 60%, with suppression maintained through 12 weeks. Thus, IgA suppression was maintained across a time frame encompassing a potential 12-week dosing interval. Of note, for the 480 mg SAD and 320 mg MAD groups, nadir may not yet have been reached by week 10, suggesting potential for further reduction in these dose groups. Consistent with the expected downstream effects of APRIL suppression and particularly relevant to IgAN pathophysiology, CLYM116 also resulted in a deep and durable reduction in pathogenic Gd-IgA1. We observed reductions in Gd-IgA1 of over 70% after a single dose of 320 mg. Also consistent with the expected downstream effects of APRIL suppression and consistent with the IgA and Gd-IgA1 observations, CLYM116 resulted in deep and durable reduction in IgM. In the 320 mg single-dose cohort, we observed reductions of approximately 75%, with suppression maintained through 12 weeks. The observed temporal relationship between APRIL suppression and downstream PD effects of IgA, Gd-IgA1, and IgM reduction further illustrates the PK and PD advantages of CLYM116 versus first-generation APRIL agents. The prolonged suppression of APRIL by CLYM116, confirmed by the favorable PK properties and in vivo potency as measured by EC75 for APRIL of CLYM116, led to a robust and sustained IgA, Gd-IgA1, and IgM reductions through a 12-week dosing interval. The durability of APRIL suppression following CLYM116 administration and downstream durable reductions in IgA, Gd-IgA1, and IgM in healthy volunteers offer a clear advantage compared to first-generation anti-APRIL agents. As noted previously, following a single dose of Sibeprenlimab 400 mg sub-Q in healthy volunteers, APRIL started to rise above 75% reduction from baseline by week eight. By week 10, approximately two weeks following the rise in APRIL levels, IgA and IgM started to increase above nadir. When we focus on the dose groups that are most clinically relevant for CLYM116, the 320 mg and 480 mg SAD groups and the 320 mg MAD group, we saw consistent, robust, and sustained effects across the relevant PD biomarkers. A rapid and sustained reduction in free APRIL occurred. This rapid reduction was followed by a robust decrease in IgA, Gd-IgA1, and IgM. Based on the consistency of effects across these dose groups, we predict the anticipated effects of a 400 mg, Q12W dosing regimen supports this regimen in clinical studies of patients with IgAN. Using our integrated PK/PD model, we simulated longer-term dosing scenarios through 48 weeks of repeat dose treatment with CLYM116. The model is also intended to evaluate whether a single initial loading dose has the potential to bring exposures more rapidly to target, and whether exposures above target can more consistently be reached in a broad population. Our simulations predict that CLYM116, when administered as a 400 mg dose every 12 weeks following an initial 800 mg loading dose, has the potential to result in CLYM116 exposure that is well above the APRIL EC75 throughout the dosing intervals and result in a rapid, substantial, and durable suppression of APRIL throughout the dosing intervals. These modeled results support a potential best-in-class profile for CLYM116. Our approach, now being evaluated in our ongoing NAVIGATE-2 IgAN phase II study, is to translate this profile into a dose regimen that provides robust APRIL, Gd-IgA1, and IgA suppression and meaningfully improved convenience compared to first generation anti-APRIL agents, while building upon the established safety record of the APRIL class. The totality of our data support continued advancement of CLYM116 in IgAN. Our phase II NAVIGATE-2 study is already ongoing, having achieved first patient in in August. We are pleased to report that enrollment is progressing well. NAVIGATE-2 is being conducted in China in collaboration with our partner Mabworks, and it provides us an opportunity to move quickly and evaluate CLYM116 directly in our target population while follow-up in the healthy volunteer studies continues. NAVIGATE-2 was designed before we had the results of this data readout, and it is evaluating two dosing regimens. CLYM116 400 mg administered every 12 weeks or every eight weeks following an initial 800 mg loading dose. It also has an optional third arm to further inform dosing regimen selection. We expect initial data from this study in the first half of 2027. Together with the integrated PK/PD model from our ongoing healthy volunteer studies, these data are intended to support selection of a single dosing regimen for a registrational study. Based on the data generated to date, our goal is to advance the every 12-week regimen into phase III. We anticipate initiation of a phase III registrational study in 2027, pending regulatory feedback. Taken together, we believe our data tell a clear story. Favorable safety profile and deep, durable PD activity in phase I support best-in-class potential for CLYM116. That promise is already translating into action. Our phase II NAVIGATE-2 study in IgAN patients is enrolling, and there is potential to move rapidly to phase III with a single regimen. On the device side, our prefilled syringe is ready for phase III with an auto-injector in development for a patient-friendly launch. With that, I'll turn it back to Aoife to close the session. Thank you, Edgar. IgA Nephropathy is a progressive disease with substantial unmet needs. Although the treatment landscape has advanced considerably, many patients remain undiagnosed or undertreated, and too many continue to progress towards chronic renal failure. Furthermore, our conversations with treating physicians indicate substantial demand for next generation therapies with improved profiles, including less frequent dosing. Within that landscape, we believe CLYM116 has the potential to offer a best-in-class profile based on three attributes. Deep and durable APRIL, IgA, and Gd-IgA1 suppression sustained through dosing intervals, our projected 12-week dosing regimen with only a single loading dose, and favorable safety and tolerability profile. The next step is to further evaluate how CLYM116 translates into meaningful biological clinical activity in IgAN. That evaluation is underway with the first patient dose in the ongoing NAVIGATE-2 IgAN phase II study. In parallel, our high concentration formulation and planned auto-injector presentation are intended to support convenient administration and future development. Looking ahead, we expect additional data from Australia phase I study and initial data from Mabworks China phase I study at a major medical meeting in the fourth quarter, with initial data from our phase II NAVIGATE-2 study in patients with IgAN expected in the first half of 2027. Those data, together with regulatory feedback, will inform our global registrational development strategy. While IgAN is our near-term focus, we believe the depth and durability of APRIL suppression achieved with CLYM116 may also extend to other B cell-mediated diseases, and we look forward to exploring that broader potential as our data mature. CLYM116, along with our CD19 monoclonal antibody, Budoprutug, reflect Climb Bio's strategy of developing differentiated antibodies against validated immune targets where we believe improved molecular design can translate into meaningful benefits for patients. The results shown today in today's presentation mark an important step in the development of CLYM116 and comes as Climb Bio continues through a data-rich period across both CLYM116 and Budoprutug. We look forward to sharing additional progress from both programs over the coming months. Thank you again for joining us today and for your continued interest in Climb Bio. We will now move to the live Q&A portion of the webcast. Thank you. To ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. We ask that you please limit to one question and one follow-up. Please stand by while we compile the Q&A roster. The first question comes from Chris Raymond with Raymond James. Your line is open. Hey, thanks for taking my question and congrats on this impressive data. Just maybe a question on the doses that you guys tested. Can you walk through why the 800 mg induction dose was not tested? Is there anything that you can sort of talk to with your modeling work that might predict what that IgA reduction would be? Then I have a follow-up. Yeah. Thanks so much, Chris, for the question. We are limiting the questions to one per person for now, but I am happy to answer that initial question for you and then hand it over to Edgar. I can give you the background on the doses. When we initially developed the product, it was formulated at a 165 mg per ml formulation, and we started the study with that. A lot of our doses are multiples of that formulation and really based on where we were when we initiated both of the phase I studies. In parallel, obviously, like all drug companies, we are looking to make sure we optimize manufacturing for devices and concentrations to really drive the lowest possible volume with the highest dose delivered. That work was occurring in parallel with the phase I study. During the study, we achieved a breakthrough, had success in developing a 200 mg per mL formulation, which we will be taking forward into future studies. That is why we kind of halfway through the study focused on the 400/800 kind of realm. So that is kind of the history of how we got here. For the second part of the question, I will hand it over to Edgar to take you through some of the ways we have been thinking about kind of bridging that from a modeling perspective. I will draw your attention to the Maverick phase I trial. They will be studying the 800 mg dose in their phase I also, so we will have data in healthy volunteers with the 800 mg loading dose. Nonetheless, we feel that what we have from our study is really adequate for us to understand how that 400/800 regimen is going to perform in humans, given all of the doses that we have around those doses. I'll turn it over to Edgar Charles to provide a little bit more insight on that. Yeah, I think that's absolutely right. We've covered a full dose range going from 25 through 320 mg, single dose. We've even gone up to 320 mg, multiple dose. We've gone up to 480 single dose, 320 mg times two in the SAD. That really allows us to project with confidence what we'd expect to see with a 400 mg, Q12W regimen with an 800 mg load. I think the 320 mg MAD cohort gives us a good idea of what to expect with 800 mg load in terms of safety and tolerability. We see really good consistency with a single injection of 320, and I think it gives us further information as we model at 800 mg load. The purpose of the load is really to bring more patients to target more quickly and get to a quicker APRIL suppression in a greater proportion of patients, and we think that's going to translate into a best-in-class profile for APRIL as well as IgA reduction. I think the bottom line here is that this is a very well-behaved molecule, very predictable and well-behaved in all of the studies that we've done so far, and we would expect it would continue to well-behaved molecule as we move through development. Great. Thank you. Thank you. Our next question is going to come from Yatin Suneja with Guggenheim. Your line is open. Hey, guys. Thank you for taking my question and congrats on the data. Perhaps maybe if I can squeeze in two questions and up to you if you guys want to answer it. For the IgA reduction, if you eyeball the 320 mg, I think it seems like it's close to 55%. The question is, do we need to get to higher number than that, given that what we see with the Sibeprenlimab and other drugs that are being developed? If you can also just maybe talk a little bit about the correlation between the free APRIL and the sustained IgA reduction, at what time point is one the leading indicator or not? I do see that you have pretty nice suppression of free APRIL out to. If you look at the 480 out to six week, a little bit of a bounce back at eight, but 320 is a little bit higher. Just curious if you can tie those two things for us. Thank you so much. Yeah. We think APRIL is the most precise readout, being most proximal to a biology of APRIL inhibition. Our 320 mg showed greater than 90% reduction of free APRIL through week 10, and then at week 12, we had up to 75% reduction of free APRIL. With a 400 mg dose, we could do even better with that. As we have modeled out our free APRIL suppression and the impact on IgA, again, we see what we think is a best-in-class profile. Again, we have extremely rapid and durable suppression of free APRIL throughout a 12-week dosing regimen. That would be expected to translate into best-in-class IgA reduction based upon that real-type biology between APRIL inhibition and IgA reduction. By our reasoning, that near complete free APRIL suppression throughout the single dosing interval, throughout the entire dosing interval for a single dose, would yield best-in-class IgA reduction. Thank you. The next question is going to come from Laura Chico with Wedbush. Your line is open. Good morning. Thanks very much for taking the question. One related to the IgA reductions that you are seeing. Edgar, Aoife, it looks like you are achieving similar IgA drops with the 480 and the 320 single doses. I am just wondering if you could talk a little bit more about the baseline characteristics in these subjects, and just trying to figure out if the 400 mg should mirror these. Related to that, for the simulations you are doing, what are the baseline assumptions that are incorporated there? Thanks very much. Yeah, it is a really good question. First of all, there is going to be some wobble in IgA. It is downstream of APRIL, so we think APRIL is really the tighter marker, particularly when you look at a small number of patients. It is known that baseline IgA can affect response of IgA percent change from baseline. In fact, we did see some imbalances amongst the cohorts according to baseline IgA, and that could be partially or fully explanatory. I think going forward, as we look in a broader population, we would expect to see certainly IgA reductions in line with our modeling for 400 mg dose. Thanks very much. Thanks, Laura. Thank you. The next question is going to come from Matt Phipps with William Blair. Your line is open. Good morning. Congrats on strong profile here. I was wondering, how much data do you have from the Mabworks SAD in doing this modeling? Do you have 480 and 640 out to a full 12 weeks, and maybe what level of IgA reduction has been achieved by them in their SAD study? Thank you. Right now, Matt, our modeling just incorporates our phase I data, but we have guided to having both full data sets available at a medical conference in the fourth quarter. We will see the full 12-week data. What I can say at a high level is what I've said earlier. It's a very well-behaved molecule, very predictive when we look at the precise biomarkers of exposure and APRIL neutralization. We're seeing an absolutely consistent profile with what we projected based on the non-human primate data. We expect that to continue across both studies and all territories. This is a molecule that very potently does what it's designed to do, which is inhibit free APRIL. We expect that all of the downstream markers will be associated with that once you see the full data set. I think wait a couple more weeks and you will see the full 12-week data. I will say, our SAD and 480 dose has not completed that 12-week follow-up yet, so we still don't know today how deep the IgA and APRIL suppression will continue through that second part of dosing interval. We're all anxious to see those data. But I think we can predict and plot out based on the graphics that we've shown you where that's all going to end based on just what we've seen so far with the lower doses. Super excited at the emerging profile here. Thank you. Thank you. Our next question is going to come from Danielle Brill with Truist. Your line is open. Hi, guys. Good morning. Congrats on the update, and thanks so much for the question. Mine's on the PD effects here. They look quite compelling, but we noticed the error bars across IgA, Gd-IgA1, and IgM response curves appear fairly wide given the small cohort sizes. Can you help us understand whether this reflects a few outliers or meaningful inter-subject variability? Have you identified any baseline characteristics, PK parameters, or other factors that distinguish the strongest from the weakest responders? Thank you. Yeah, so it's a good question. Overall, the results are consistent amongst individuals. The wide error bars are really a function of small sample size. As usual, there's going to be some heterogeneity in biology, particularly as you get further downstream. But overall, the results are pretty consistent amongst individuals. Yeah, Danielle, we didn't see any outlier patients when it comes to exposure. The exposure curves are very tight and consistent. Obviously, if you go further downstream in biology, IgA does multiple things. You can have a GI infection or something else that drives up IgA. So it's not unexpected that you will see more variability as you go downstream, and you'll get that a little bit wider error bars. But we look at exposure, we look at APRIL inhibition, I think we're seeing a very nice, tight, consistent story. So, very encouraging. Thank you. Thank you. Our next question is going to come from Leland Gershell with Oppenheimer. Your line is now open. Oh, great. Thanks. Good morning, and congrats as well to the team for the strong data this morning. Just a question, Aoife. You mentioned that we would be, or Edgar, you mentioned we'd be seeing anti-drug antibody data in upcoming meetings. Should we presume that the ADA data will be shown at the meeting in the fourth quarter? Thank you. Our ADA assay is still in development, so we are not putting a time to when we will have those data available. We still have some things to work out with the assay before we're able to analyze those results and share them with the public. What I will say, Leland, is we've seen nothing concerning so far in the data that we've seen. As I mentioned earlier, all the PK curves are super consistent, even out to the later time points of 10 and 12 weeks. We have no reason to suspect an issue, but obviously important to complete and round out the profile to have those data. We'll get them out as soon as they're ready. Great. That's helpful. Thank you very much. Thank you. The next question is going to come from Brian Skorney with Baird. Your line is open. Hey, good morning, team. Thanks for taking the question. Congrats on a really strong data set. I am just wondering, in NAVIGATE-2, is the high concentration formulation being used at all? I am just trying to read through on injection site pain and reactions from that if it gets to phase III. Is the viscosity of the high concentration formulation any different than what is being used in studies right now? How many mLs is the 320 mg dose being injected with in this study? Yeah, great question. The NAVIGATE-2 is using the 160 mg per mL concentration. We have done extensive biocompatibility between the 160 and 200 mg per mL concentrations, and there are no meaningful differences, and we think the viscosity is certainly acceptable. As we look at injection site reactions, we did not see dose-dependent changes or increases in injection site reactions through our dose ranging. We would not expect an increase in injection site reactions with this modest increase in concentration going from 160 to 200. With 320, we are looking at a 2 mL injection, 400 mg, 160 mg per mL. With 400 mg, we are looking at a 2 mL injection at a 200 mg per mL concentration. Great. Thank you. Thank you. The next question is going to come from Tom Smith with Leerink. Your line is open. Hey, team. Good morning. Congrats on these nice early data. Thanks for taking our questions. Just one clarifying, if I could. You mentioned that Mabworks is studying the 800 mg dose in their phase I. Should we expect to see those data later this year with that phase I healthy volunteer presentation? In the longer term, just assuming your early PD results here translate similarly to what we've seen from Sibeprenlimab and their longer-term impact on eGFR, what's your expectation for how clinicians and patients are going to select between these next-gen APRIL mono and dual targeted agents? Do you think it'll be mostly driven by dosing interval or presentation or some other factor? Thanks so much. Tom, the answer to the first question is yes. Those data will be available in the fourth quarter. Stand by for those. Maybe I'll hand it over to Perrin to answer your question around commercial read-through and what we've heard from some of the KOLs and prescribers we've spoken with. Yeah, sure. Thanks, Tom, for the question. As we think about what's required from either a patient, a clinician, or a commercial perspective, we come back to the three legs of the stool that we focused on from the beginning: efficacy, convenience, and safety. While we don't believe you need to differentiate on all three legs to be successful, I think our phase I data really shows that we do. On efficacy, we've observed best-in-class APRIL suppression, and it's that near complete APRIL suppression over the dosing interval that's going to result in robust downstream effects on IgA, pathogenic IgA, and these are what ultimately is going to lead to benefits on proteinuria, eGFR, and R stabilization. On convenience, our data demonstrate a clear every 12-week dosing interval, which represents a significant improvement from the once-monthly dosing regimen of the first-generation agents. This is particularly important when we think about the IgAN patient population. It is a young patient population that is going to require chronic therapy for their lifetime to ensure that they are preventing progression to kidney failure. On safety, our safety profile is consistent with the APRIL class. We have not seen any surprising signals and have not observed any hypogammaglobulinemia, which we know has been a concern when targeting BAFF in addition to APRIL. Overall, we believe that phase I data show that 116 is differentiated from the first-gen approaches and really represents a compelling value proposition in a market that are emerging from. Yeah, the only thing I would add there, Tom, is I think, when we have asked ourselves in debates a lot about how can you do better than the Sibeprenlimab profile, which shows complete stabilization. But actually, if you look at that profile, there were patients who continued to progress despite Sibeprenlimab. So I do think the field is going to turn to aggressively getting patients to target. That is really going to open up space for new entrants, I think, of people who are not necessarily getting to target proteinuria. That is going to become, I think, an important driver of switch and of choosing the initial therapy once somebody is diagnosed. So that is something we are really going to continue to focus on as we move forward in development. Thank you. The next question will come from Julian Harrison with BTIG. Your line is now open. Hi. Good morning. Congratulations on these results, and thank you for taking the question. I understand there are pending regulatory interactions before you start phase III, but I am wondering if maybe the recent 24-month eGFR data from Sibeprenlimab perhaps change expectations at all going forward regarding the timeline to accelerated approval. Then maybe relative to other or prior registrational trials in IgAN, but from others, are you able to talk about any key differences in trial design you are hoping to achieve alignment with the FDA on? Yeah. Great question, Julian. I'll take the first part around the current regulatory environment. The FDA have already moved off the two-year full approval eGFR endpoint. What they've communicated to not just us, but to the field, is that the accelerated approval pathway continues to be open despite approval of first-gen products. That has been answered. The second piece they have communicated is that they're open to moving to a shorter endpoint, not the two-year eGFR, but a maybe 18-month, 12-month endpoint on eGFR, assuming that the effect size is large enough that it can be detected at that 12-month endpoint. Obviously, we would assume that our effect size would be in that range. That's already something I think that's been communicated. You can see that's already been pulled through in some of the decisions that have been communicated around other agents in a class and in similar classes. I do think it's a moving space, and it's becoming even more open for next-gen entrants, which I think is a real positive read-through for our future plans. Obviously, we'll have to engage with FDA and get their alignment on what we're planning to do and then communicate that externally. But I think it's a really interesting space from a regulatory perspective, and we're absolutely going to take advantage of that kind of opening. On the second part, I'll turn it over to Edgar to maybe share some of his initial thoughts on what that phase III might look like. Yeah. Overall, I think there's great precedent so far for what works in IgAN. And I think there is, as Aoife mentioned, a potential for an earlier time point. I think the overall design and study population inclusion criteria can be mapped pretty similarly to what's been done before with some minor adjustments as the field is moving forward. I think you could look to something fairly similar to what's been done before in terms of the overall design. Thank you. The next question is going to come from Nevin Varghese with RBC. Your line is open. Hey, thank you so much, team, for taking my questions, and congrats on all the progress so far. Just wondering if I could follow up on some of the prior questions. Curious how you're thinking about what the competitive dynamics might be moving forward, just given that Otsuka has expressed interest in developing a longer-acting version of Sibeprenlimab, and Vertex has also indicated that they might be working on a longer-acting version of povetacicept. How are you seeing the kind of dynamics playing out? Additionally, if I could squeeze in one more, are we able to comment at all on what the half-life looks like in some of the SAD cohort? Yeah. So for the competitive dynamics, I'll ask Perrin to address that. Obviously, that comes back to our differentiation approach, and we will be coming behind sibi. Sibi is a great drug. That's why we've benchmarked it to it in all of our slides. But Perrin, anything you've heard from the market or from KOLs that could help inform that approach? Yeah. I think, Aoife, it goes back to one of the points you made earlier as well. There's a first generation that's coming, and we think that's going to be a tremendous improvement for patients and allow them the first shot, really, at a disease-modifying approach for this disease. But certainly, they've validated the class. But as we've said, validation is not enough, and there is an opportunity to do better across those three legs of the stool that we discussed earlier. So we do think this is a market where there will be opportunities for patients who perhaps aren't adequately controlled on first-generation agents, as well as the opportunity to start off on an agent like CLYM116 that truly has a best-in-class profile. Thank you. Our next question will come from Mayank Mamtani with B. Riley. Your line is open. Mayank, your line is now open. If you're on mute, can you please unmute your line? Mayank? Thanks so much, Michelle. I think Mayank may be having technical difficulties, but I think we can wrap up here and thank everyone for their participation this morning. I am super excited to move this forward and to keep everyone informed of our progress as we go through the rest of this year first and then into 2027. So thank you so much, and have a wonderful holiday weekend. This concludes today's conference call. Thank you for participating, and you may now disconnect.