Executives at iBio (NASDAQ:IBIO) outlined the scientific and strategic rationale for a myostatin/activin A bispecific antibody program that the company believes could become a next-generation therapy for heart failure, with an initial focus on pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF).
On a conference call led by Martin Brenner and Cory Schwartz, iBio’s Director and Head of Research and Early Development, the company emphasized that interest in the activin pathway has increased recently, pointing to GSK’s agreement to acquire 35Pharma for $950 million as external validation of the space. Management said it views the transaction, along with clinical data from Merck’s sotatercept program, as support for pursuing more selective activin-pathway targeting approaches.
Linking iBio’s obesity work to PH-HFpEF
As iBio expanded its work on the TGF-β superfamily, the company concluded that the biology underlying functional decline in obesity overlaps with mechanisms implicated in PH-HFpEF. Schwartz described this convergence as involving shared ligands—activin A, myostatin (GDF8), and GDF11—and shared tissue targets including pulmonary vasculature, myocardium, and skeletal muscle.
HFpEF landscape and iBio’s entry point
Schwartz characterized HFpEF as a heterogeneous syndrome in which ejection fraction is preserved but the heart does not relax properly, leading to elevated filling pressures and symptoms such as breathlessness, fatigue, and exercise intolerance. He said HFpEF now accounts for approximately half of heart failure cases and is strongly associated with obesity, diabetes, hypertension, and aging.
iBio’s initial target is PH-HFpEF, a severe subset in which elevated left-sided filling pressures lead to pulmonary hypertension and progressive pulmonary vascular remodeling (often termed combined post- and pre-capillary pulmonary hypertension, or CPCPH). Schwartz said pulmonary hypertension may occur in a significant fraction of HFpEF patients, with some studies reporting 50% or higher, and is linked to worse outcomes including mortality.
Management framed PH-HFpEF as the clearest place to start due to clinical validation of the activin pathway and the lack of disease-modifying therapies. Schwartz said diuretics remain central for symptom control but do not modify disease, while RAS inhibitors, beta blockers, and aldosterone antagonists have shown limited efficacy in large HFpEF trials. He noted SGLT2 inhibitors as a meaningful advance that reduces hospitalizations and cardiovascular death, and said GLP-1 receptor agonists may provide metabolic benefits in obese HFpEF patients, though durable structural cardiac reversal remains to be established.
Clinical validation: sotatercept and industry activity
Schwartz cited ligand traps as proof-of-concept for modulating activin signaling, highlighting sotatercept, now approved as Winrevair for pulmonary arterial hypertension (PAH). He pointed to the Phase III STELLAR trial in PAH, where sotatercept improved six-minute walk distance by 40.8 meters compared to placebo on top of background therapy, and said the product has become a commercial success with more than $1 billion in sales in its first full year.
More directly relevant to PH-HFpEF, Schwartz said Merck reported top-line results in November 2025 from the Phase II CADENCE trial evaluating sotatercept in CPCPH due to HFpEF. According to Schwartz, CADENCE met its primary endpoint, showing a statistically significant and clinically meaningful reduction in pulmonary vascular resistance at 24 weeks versus placebo, and Merck has indicated it intends to proceed to Phase III development given the lack of approved treatment options in PH-HFpEF.
iBio also discussed GSK’s planned acquisition of 35Pharma. Schwartz said 35Pharma’s lead asset, HS235, is designed with enhanced selectivity and reduced binding to BMP9 and BMP10—ligands he said are associated with bleeding and vascular adverse events observed with broader ligand-blocking approaches. He also relayed that GSK referenced an $18 billion pulmonary hypertension market forecast by 2032 and anticipated activin signaling inhibitors representing roughly half of that market.
iBio’s approach: selective blockade of three ligands
Management said iBio is developing a bispecific antibody intended to block activin A, myostatin (GDF8), and GDF11 while sparing BMP9, BMP10, and activin B. Schwartz described BMP9 and BMP10 as important for vascular tone and endothelial homeostasis and linked their inhibition to bleeding and hemodynamic side effects seen with broader ligand traps. He said iBio chose to spare activin B because it is reported to induce FGF21 expression and contribute to improved glucose handling and insulin sensitivity, which the company does not want to undermine in metabolically compromised populations.
In Q&A, Schwartz explained the bispecific’s structure: one antibody arm targets activin A, while the other arm is dual-targeting and blocks both GDF8 and GDF11, which he said have significant homology enabling a single binding domain to address both.
On tolerability considerations raised by analysts referencing prior activin A antibody programs, Schwartz said iBio is designing the molecules with pharmacokinetics intended for subcutaneous dosing and reduced peak-to-trough exposure. He contrasted this with higher-Cmax intravenous dosing in prior programs discussed on the call.
Schwartz also said iBio’s antibody binds very potently to both GDF8 and GDF11, reaching limits of detection in its assays, and that the relative contribution of each ligand to disease likely varies by patient. Brenner added that the company is pursuing a “balanced” inactivation of the pathway and is exploring whether patient selection strategies could improve early clinical studies.
iBio described internal preclinical work supporting its hypothesis, including cell-based assays in human cardiac fibroblasts showing activin A, GDF8, and GDF11 driving pro-fibrotic signaling markers such as collagen synthesis and myofibroblast activation via SMAD2/3 phosphorylation. Schwartz also cited results from an internal rodent HFpEF model combining high-fat diet and hypertensive stress, where selective blockade of the three ligands reduced the Fulton index, a measure of heart enlargement. Management cautioned that rodent models are imperfect surrogates for human disease.
Looking ahead, Schwartz said iBio’s next forecasted public milestone is declaring a development candidate, targeted for the third quarter of the year. He said the company is evaluating multiple candidates and is now focusing on selecting the best option for manufacturability and developability, with a goal of chronic subcutaneous administration. Management said it is still early to define the precise target patient population for clinical trials in PH-HFpEF, and it has not yet provided guidance on dosing frequency or Phase I design.
On business strategy, management said it is too early for a concrete decision on partnering versus advancing the program independently, though it is evaluating options. Brenner closed by reiterating PH-HFpEF as a severe condition without approved disease-modifying therapies and positioned the company’s intentionally selective approach as aiming to match meaningful efficacy while improving safety for chronic administration.
About iBio (NASDAQ:IBIO)
iBio, Inc, a biotechnology company, provides contract development and manufacturing services to collaborators and third-party customers in the United States. The company operates in two segments: Biopharmaceuticals and Bioprocessing. Its lead therapeutic candidate is IBIO-100 that is being advanced for investigational new drug development for the treatment of systemic scleroderma and idiopathic pulmonary fibrosis. The company is also developing vaccine candidates comprising IBIO-200 and IBIO-201, which are in preclinical development for the prevention of severe acute respiratory syndrome coronavirus 2; and IBIO-400 for the treatment of classical swine fever.
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