Climb Bio, Inc. Common Stock Study result

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 milligram per mil product that enables 400 milligram dose to be administered in a single 2 mil 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 Voxzogo, 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 milligram 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, Eva. 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.