iBio (IBIO) Study update summary

Program rationale and disease focus

• The bispecific antibody program targets myostatin, GDF11, and activin A to address heart failure with preserved ejection fraction (HFpEF), especially the pulmonary hypertension (PH-HFpEF) subset, where unmet need and biological validation are strongest.

• The approach is rooted in targeting the underlying biology of obesity-related disease, focusing on functional decline, organ fibrosis, and cardiometabolic risk rather than just weight loss.

• Recent industry moves, such as GSK's $950M acquisition of 35Pharma and Merck's positive CADENCE trial results, validate the activin pathway as a therapeutic target.

• The program aims to extend beyond PH-HFpEF to broader cardiometabolic HFpEF populations, leveraging overlapping biology and existing expertise.

Mechanistic insights and differentiation

• The TGF-β superfamily, including activin A, myostatin, and GDF11, drives fibrosis, vascular remodeling, and functional decline in PH-HFpEF.

• Ligand traps like sotatercept have shown clinical efficacy but carry safety risks due to broad inhibition, particularly of BMP9 and BMP10.

• The bispecific antibody is engineered for high selectivity, sparing BMP9, BMP10, and activin B to reduce bleeding and metabolic side effects.

• The antibody's two arms allow specific targeting: one for activin A, the other for both GDF8 (myostatin) and GDF11, exploiting their homology.

Preclinical data and development strategy

• Preclinical studies show high-affinity blockade of the three targets, sparing non-target ligands at relevant concentrations.

• In rodent HFpEF models, selective blockade reduced cardiac remodeling, as measured by the Fulton index, supporting disease-modifying potential.

• Candidate selection is ongoing, focusing on manufacturability, stability, and suitability for chronic subcutaneous administration.

• The next milestone is the declaration of a development candidate, targeted for announcement in Q3.