Slide 1: R&D Spotlight: CLYM116 and the IgAN Opportunity
R&D Spotlight: CLYM116 and the IgAN Opportunity SEPTEMBER 29, 2025 Exhibit 99.2
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding: future expectations, plans and prospects for Climb Bio, Inc. (“Climb Bio”); expectations r
Slide 3: Webcast Agenda
Webcast Agenda Corporate Strategy & CLYM116 Opportunity Aoife Brennan, M.B., Ch.B. President and CEO, Climb Bio IgAN Disease Overview & Evolving Treatment Landscape Craig Gordon, M.D., M.S. Nephrologist; Professor, Tufts University School of Medicine Co-director, Evidence Review Team for KDIGO clini
Slide 4: Our Mission: Scaling New Heights in Transformative Immune Medicines
Deliver high impact, disease-modifying medicines for individuals living with immune-mediated diseases Scaling New Heights in the Development of Transformative Immune Medicines OUR MISSION
Slide 5: Pipeline of Highly Differentiated mAbs
Pipeline of Highly Differentiated mAbs *Climb Bio has worldwide rights outside Greater China (defined as mainland China, Hong Kong, Macau, and Taiwan); Partner: Beijing Mabworks Biotech Co., Ltd. CLYM116 Phase 1 initiation subject to regulatory clearance. APRIL = a proliferation-inducing ligand, H =
Slide 6: CLYM116: History and Perspective
CLYM116: History and Perspective Program aligns closely with our strategy and is complementary to our lead program APRIL = a proliferation-inducing ligand, IgAN = IgA nephropathy, mAb = monoclonal antibody Greater China defined as mainland China, Hong Kong, Macau, and Taiwan. Complementary to budopr
Slide 7: IgAN Represents a Significant Opportunity
Most common primary glomerular disease worldwide – ~170,000 patients in the US alone1,2 Diagnosed early in life (typically, ages 15-40)3; patients at risk for renal failure as disease progresses Lifelong disease – patients likely to require chronic therapy Progressive, lifelong renal disease IgAN Re
Slide 8: CLYM116 is Rapidly Advancing to the Clinic
CLYM116 is Rapidly Advancing to the Clinic CLYM116 Phase 1 initiation subject to regulatory clearance. CTA = clinical trial application, HV = healthy volunteer, NHP = nonhuman primate, Q = quarter Initial clinical data expected mid-year 2026 NHP data demonstrated potential for deep and durable IgA s
Slide 9: IgA nephropathy – an overview of pathogenesis and treatment
IgA nephropathy – an overview of pathogenesis and treatment Craig E. Gordon, MD MS, FASN Professor of Medicine Tufts University School of Medicine
Slide 10: IgA nephropathy
IgA nephropathy Common condition compared with other glomerular diseases Incidence: >2.5 per 100,000 individuals Higher in Asian Pacific populations Median age of diagnosis: 40 years of age UK National Registry of Rare Kidney Diseases (RaDaR) Median kidney survival time of 11.4 y (10.5-12.5y) Conseq
Slide 11: UK RaDaR – high risk of kidney failure with IgAN
UK RaDaR – high risk of kidney failure with IgAN Pitcher, CJASN 2023
Slide 12: A patient case to highlight the challenges
A patient case to highlight the challenges… 46 yo M referred for hematuria, proteinuria, decreased GFR, no symptoms Blood pressure 138/84 mmHg Urinalysis revealed 3+ blood, 3+ protein UPCR 2.9 g/g eGFR 58 ml/min/1.73m2 Note the disease progression (i.e. decreased GFR) in absence of symptoms Underwen
Slide 13: The International IgA Nephropathy Prediction Tool
The International IgA Nephropathy Prediction Tool For our patient: At 5 years: Risk of a 50% decline in eGFR or progression to kidney failure = 46.5% Figure 1 | The data elements included in the International Immunoglobulin A Nephropathy (IgAN) Prediction Tools. Modified from Barbour, JAMA Int Med,
Slide 14: Pathogenesis of IgAN
Pathogenesis of IgAN Current disease model in 2025
Slide 15: Four hit model
Cheung, Front in Nephr, 2024 “Four hit” model
Slide 16: Treatments impacting the four hit model
Treatments impacting the four hit model Gleeson, NDT, 2023
Slide 17: Surrogate outcomes in IgA nephropathy
Surrogate outcomes in IgA nephropathy FDA recognized need for surrogate outcomes in studies of IgA nephropathy (slowly progressive disease) Recent accelerated approval by FDA of treatments based on improvement in proteinuria True of TRF-budesonide, sparsentan, iptacopan Presumably will be the pathwa
Slide 18: Executive summary of the KDIGO 2025 Clinical Practice Guideline for IgAN
Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)
Slide 19: Diagnosis of IgAN
Diagnosis of IgAN 1.2 Diagnosis Practice Point 1.2.1: KDIGO 2025 CPG on IgA nephropathy
Slide 20: Treatment of IgAN
Treatment of IgAN 1.4 Treatment KDIGO 2025 CPG on IgA nephropathy
Slide 21: Treatment of IgAN
Treatment of IgAN Practice Point 1.4.2.2:
Slide 22: KDIGO 2025 CPG on IgA nephropathy
KDIGO 2025 CPG on IgA nephropathy Driver for nephron loss Treatment goal Interventions with reported efficacy across populations Interventions with reported efficacy in specific populations
Slide 23: Current understanding of BAFF/APRIL pathways
Current understanding of BAFF/APRIL pathways
Slide 24: Downstream impact of APRIL blockade
Downstream impact of APRIL blockade Mathur, J Clin Med, 2023
Slide 25: BAFF and/or APRIL antagonists
BAFF and/or APRIL antagonists Muto, Int J Mol Sci, 2024
Slide 26: Comparison of current treatment (2025)
Comparison of current treatment (2025) Remember that based on slow progression, treatments will likely be long-term (those targeting hit 1 and hit 4, particularly). Administration Efficacy data Safety considerations Corticosteroids Oral UPCR/GFR PJP, infections TRF budesonide Oral UPCR/GFR Acne, HTN
Slide 27: Where are we going in the future?
Where are we going in the future? KDIGO 2025 CPG on IgA nephropathy
Slide 28: Thanks!
Thanks!
Slide 29: CLYM116 Anti-APRIL monoclonal antibody
CLYM116 Anti-APRIL monoclonal antibody
Slide 30: APRIL is a Potentially Disease Modifying Approach in IgAN
APRIL is a Potentially Disease Modifying Approach in IgAN In IgAN, APRIL inhibition has been demonstrated to prevent the production of pathogenic IgA and the consequent immune complex formation that leads to kidney damage APRIL = a proliferation-inducing ligand, eGFR = estimated glomerular filtratio
Slide 31: Selective APRIL Inhibition Has Been Clinically Validated in IgAN
Selective APRIL Inhibition Has Been Clinically Validated in IgAN Anti-APRIL mAb, sibeprenlimab, demonstrated numerically better proteinuria (UPCR) reductions as compared to anti-BAFF/APRIL antagonist, atacicept, in Phase 3 IgAN studies Table above reflects cross-trial comparisons and not data from h
Slide 32: Next Gen Anti-APRILs Have Potential to Deliver Improved Profiles
Next Gen Anti-APRILs Have Potential to Deliver Improved Profiles *Adapted from Mathur NEJM 2024. Sibeprenlimab Phase 3 dose (400 mg SC) equivalency based on average 80 kg weight and 75% bioavailability (Zhang Clin Pharm Drug Dev 2023). APRIL = a proliferation-inducing ligand, IV = intravenous, mo =
Slide 33: CLYM116 Is The Only Known Sweeper Anti-APRIL In Development
CLYM116 Is The Only Known “Sweeper” Anti-APRIL In Development Potential best-in-class anti-APRIL mAb, designed for improved activity, less frequent dosing, and favorable safety profile APRIL = a proliferation-inducing ligand, mAb = monoclonal antibody pH-dependent binding to APRIL Clinically validat
Slide 34: CLYM116 Sweeper MoA Provides Potential for Clinical Benefits
APRIL Endocytosis APRIL degradation pH 6.0 pH 6.0 pH 6.0 FcRn pH 7.4 CLYM116 Antibody recycling CLYM116 “Sweeper” MoA Provides Potential for Clinical Benefits CLYM116’s recycling degrader ‘sweeper’ mechanism of action provides potential for improved activity and less frequent dosing vs. first genera
Slide 35: CLYM116 Demonstrated Potent, pH-Dependent Binding of APRIL
CLYM116 Demonstrated Potent, pH-Dependent Binding of APRIL In vitro binding assay showed CLYM116 potently bound APRIL at neutral pH, but not acidic pH, supporting sweeper mechanism, whereas first gen anti-APRIL mAbs did not demonstrate this profile APRIL = a proliferation-inducing ligand, gen = gene
Slide 36: CLYM116 Showed Enhanced APRIL Elimination and Ab Recycling
CLYM116 Showed Enhanced APRIL Elimination and Ab Recycling In vivo APRIL degradation assay (left) and antibody exposure assay (right) support potential for enhanced APRIL elimination and antibody recycling through sweeper mechanism of action Ab = antibody, APRIL = a proliferation-inducing ligand, hu
Slide 37: Early CLYM116 SC NHP Data Signaled Potential for Differentiation
Early CLYM116 SC NHP Data Signaled Potential for Differentiation In a pilot NHP study, CLYM116 demonstrated potential for a longer half-life and deeper, more durable IgA reductions as compared to benchmark first generation anti-APRIL antibody ADA = anti-drug antibody, APRIL = a proliferation-inducin
Slide 38: Larger Study in NHPs Further Evaluated CLYM116 Profile
Larger Study in NHPs Further Evaluated CLYM116 Profile 4-6 animals per arm per dose Single dose administration CLYM116 SC and IV at matched doses CLYM116 SC and sibeprenlimab SC at matched doses Pharmacokinetic and pharmacodynamic measures assessed daily through day 8 and weekly thereafter Additiona
Slide 39: CLYM116 Showed a Favorable Subcutaneous Profile in NHPs
CLYM116 Showed a Favorable Subcutaneous Profile in NHPs CLYM116 SC demonstrated high bioavailability and favorable tolerability; formulation optimized to support potential for convenient, at-home dosing ADA = anti-drug antibody, IV = intravenous, NHPs = nonhuman primates, SC = subcutaneous Data from
Slide 40: CLYM116 Showed Dose-Dependent, Prolonged Exposure in NHPs
CLYM116 Showed Dose-Dependent, Prolonged Exposure in NHPs ADA = anti-drug antibody, APRIL = a proliferation-inducing ligand, mAbs = monoclonal antibodies, NHPs = nonhuman primates, SC = subcutaneous, TMDD = target mediated drug disposition; Data from a head-to-head study in nonhuman primates; single
Slide 41: CLYM116 Showed Robust and Durable IgA Reduction in NHPs
ADA = anti-drug antibody, NHPs = nonhuman primates, SC = subcutaneous Data from a head-to-head study in nonhuman primates; single subcutaneous administration. Sibeprenlimab analog generated from publicly available sequence. CLYM116 demonstrated >50% reduction in IgA out to 3 months after a single 6
Slide 42: CLYM116 Has The Potential For A Best-in-Class Profile in IgAN
CLYM116 Has The Potential For A Best-in-Class Profile in IgAN CLYM116 development ongoing, NHP data support potential for a differentiated profile Sibeprenlimab (anti-APRIL mAb) Povetacicept (BAFF/APRIL trap) IgA – Percent Reduction From Baseline UPCR Reduction, Week 36* CLYM116 (anti-APRIL mAb) Tab
Slide 43: Planned CLYM116 Phase 1 Study In Healthy Volunteers
Planned CLYM116 Phase 1 Study In Healthy Volunteers Pharmacodynamic biomarker data (APRIL, IgA) expected to guide dose and dose frequency for studies in IgAN patients; Phase 1 study expected to initiate in Q4 2025 Population Healthy volunteers Primary Objective Safety and tolerability Secondary Obje
Slide 44: Our Goal: Quickly progress from Phase 1 to studies in IgAN patients
Our Goal: Quickly progress from Phase 1 study in healthy volunteers to studies in IgAN patients Decision to progress based upon PD (depth and duration of APRIL and IgA suppression) and safety readouts, which will inform: Dosing regimen/frequency Predicted efficacy Predicted safety/tolerability in Ig
Slide 45: CLYM116 is a promising investigational therapy for IgAN
CLYM116 is a promising investigational therapy for IgAN, with a unique ‘sweeper’ mechanism of action APRIL represents a validated target with potential to address underlying IgAN pathology CLYM116 is the only known ‘sweeper’ anti-APRIL mAb in development New CLYM116 NHP data demonstrated improvement
Slide 46: Q&A Session
Q&A Session Aoife Brennan, M.B., Ch.B. President and CEO, Climb Bio Craig Gordon, M.D., M.S. Professor, Tufts University School of Medicine Edgar Charles, M.D. Chief Medical Officer, Climb Bio Perrin Wilson, Ph.D. Chief Business Officer, Climb Bio