Climb Bio (NASDAQ:CLYM) executives outlined the company’s development strategy for its renal and autoimmune disease pipeline during a Jefferies conference discussion, emphasizing upcoming data readouts for its anti-APRIL antibody program and its CD19 antibody, Budoprutug.
Susan Altschuller, CFO of Climb Bio, described the company as a clinical-stage developer with “two antibody approaches in renal disease and other autoimmune diseases.” The lead program, Budoprutug, is in Phase 2 development for PMN and Phase 1b development for ITP and SLE. The company’s second clinical-stage asset is CLYM116, an APRIL-only monoclonal antibody designed with a pH-dependent “sweeper” mechanism.
Climb Bio Sees Opportunity for Next-Generation APRIL Therapy
Altschuller said Jade’s data showed potential for every-eight-week dosing and, with modeling, every-12-week dosing. She added that every-two-month or every-three-month dosing could be compelling for patients diagnosed in their 20s or 30s who may require chronic therapy.
An unnamed Climb Bio company representative said the company’s target product profile for CLYM116 prioritizes safety, efficacy and dosing convenience. The representative said APRIL has shown a favorable safety and tolerability profile and that Climb Bio wants to ensure its program can meet or exceed efficacy benchmarks established by earlier agents.
The representative said the company will evaluate APRIL suppression and IgA suppression in healthy volunteers over the dosing interval. Altschuller said every-eight-week or every-12-week maintenance dosing “remains the possibility” for Climb Bio’s program.
Proteinuria Reduction and Long-Term Targets in IgAN
Altschuller also pointed to evolving views among regulators and kidney specialists on proteinuria reduction. She said a recent National Kidney Foundation and FDA summit reflected “growing recognition” that lowering proteinuria and keeping it below 0.3 grams translates into eGFR stabilization. She said the issue is not only median proteinuria response, but whether more patients can reach target levels over the long term.
The unnamed Climb Bio representative said data from sibeprenlimab suggest there is room for improvement in proteinuria reduction, particularly if higher and more consistent exposure can help more patients reach target levels. Altschuller noted that KDIGO updated guidelines target 0.3 grams rather than 0.5 grams because even low levels of proteinuria may contribute to kidney damage over time.
Upcoming CLYM116 Data Expected This Year
Climb Bio said it is running a healthy volunteer SAD/MAD study in Australia, while its partner Mabworks is conducting a parallel study in China with SAD in healthy volunteers and MAD in IgAN patients. Altschuller said the collaboration with Mabworks is an “underappreciated” part of the company’s development path because it could provide additional dose-ranging data and help accelerate development.
The company said its ERA presentation would include translational modeling from non-human primate data to healthy volunteers, the design and doses being evaluated in Phase 1, what Mabworks is evaluating and some initial safety data from ongoing studies. The unnamed representative said the more anticipated PK/PD data are expected later in the summer.
Altschuller said there is also potential for additional Climb Bio and Mabworks data disclosures later this year, including around the ASN kidney meeting, though the company has not yet laid out a specific plan.
Budoprutug Strategy Centers on CD19 Antibody Approach
Turning to Budoprutug, Altschuller said the company sees an opportunity for a “naked monoclonal antibody” approach to CD19, in contrast with more complex modalities such as CAR-T therapies or T-cell engagers that may carry risks including cytokine release syndrome or ICANS and require treatment at academic centers.
Altschuller said a CD19 antibody could be administered by community nephrologists or hematologists. She cited UPLIZNA as an analog for uptake of a CD19 antibody, while noting that Climb Bio believes Budoprutug’s potential subcutaneous formulation and indication strategy are differentiators.
Altschuller highlighted prior low-dose Phase 1b proof-of-concept data in five patients, saying Climb Bio observed complete B-cell response, PLA2R seronegativity and a 60% complete renal response. She said the study was stopped early, but follow-up data on four patients showed that three of the four did not need additional immunosuppression for three years after initial Budoprutug doses.
“The question is, with an antibody approach that’s safe, for some patients, do you have a treatment-free interval?” Altschuller said. “Can it be a reset?”
Altschuller said Climb Bio believes full B-cell depletion may be important for achieving an immune reset and that the company has developed a high-sensitivity B-cell assay capable of assessing 0.4 cells per microliter. She said the company is dosing up to explore how many patients can reach deeper depletion levels and whether an antibody approach can produce efficacy comparable to more intensive modalities at appropriate doses.
Combination Therapy Not a Near-Term Focus
Asked about potential combinations involving Budoprutug and the anti-APRIL program, Altschuller said Climb Bio expects combinations to emerge in autoimmune and renal disease, citing complement and APRIL as one possible trend. However, she said the company has not focused on combining Budoprutug with CLYM116, noting that the dosing paradigms differ.
Altschuller also said Climb Bio views CD19 as a “Goldilocks target” for certain diseases because it depletes plasmablasts while preserving long-lived plasma cells. She said that feature is one reason the company does not see CD38 or BCMA approaches as the right fit for PMN.
About Climb Bio (NASDAQ:CLYM)
Climb Bio Therapeutics, Inc is a clinical-stage biotechnology company focused on the discovery and development of engineered protein therapeutics for the treatment of cancer and immune-mediated disorders. The company’s mission centers on designing biologics with enhanced specificity and functional activity to engage key cellular targets and improve patient outcomes in areas of high unmet need.
At the heart of Climb Bio’s approach is its proprietary protein engineering platform, which combines mammalian cell display, directed evolution and computational modeling.
