iBio (IBIO) investor relations material

Program rationale and disease focus

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

• Obesity-driven cardiometabolic dysfunction and organ fibrosis are central to disease progression, making the activin pathway a compelling therapeutic target.

• The program aims to improve quality of weight loss and address functional decline, not just reduce BMI.

• The biology underlying obesity, HFpEF, and PH-HFpEF converges on the same TGF-β superfamily ligands and tissue targets.

Scientific and clinical validation

• Activin A, myostatin, and GDF11 are implicated in fibrosis, vascular remodeling, and functional decline in PH-HFpEF.

• Sotatercept, a ligand trap, showed significant efficacy in PAH and PH-HFpEF, validating the activin pathway as a therapeutic target.

• GSK's $950M acquisition of 35Pharma and Merck's CADENCE trial results highlight industry conviction and the need for more selective activin pathway inhibitors.

• Current therapies manage symptoms but do not address underlying vascular remodeling; activin pathway targeting could fill this gap.

Differentiation and design strategy

• The bispecific antibody is engineered for high-affinity, selective blockade of GDF8 (myostatin), GDF11, and activin A, while sparing BMP9, BMP10, and activin B to avoid bleeding risks and preserve metabolic benefits.

• Selectivity is intentional, aiming to deliver efficacy with improved safety for chronic use.

• The antibody's dual-targeting arm binds both GDF8 and GDF11 due to their homology, while the other arm targets activin A.

• Balanced inhibition of all three targets is sought, as their roles may vary among patients.