PROBLEM

Chronic heart failure following myocardial infarction (MI) afflicts ~6.7 million US adults and is driven by maladaptive immune activation, particularly persistent activation and proliferation of CD4⁺ T cells. Existing anti-inflammatory and immunomodulatory approaches have largely failed to improve outcomes and, in some cases, worsen disease due to a lack of specificity and suppression of beneficial immune responses needed for healing. There remains a significant unmet need for therapies that can selectively dampen pathological CD4⁺ T cell populations to prevent adverse cardiac remodeling and disease progression.

SOLUTION

Researchers at The Ohio State University have developed a novel small molecule, OSU-ERβ-012, for the selective modulation of pathological T cell responses via estrogen receptor-beta (ERβ) activation. OSU-ERβ-012 inhibits CD4⁺ T cell activation and proliferation while sparing other immune cell populations, enabling precise immune control rather than broad suppression. In validated preclinical mouse models of chronic heart failure post-MI, treatment with OSU-ERβ-012 significantly reduced harmful cardiac remodeling and preserved heart function to stop progressive cardiac dysfunction.

APPLICATIONS

• Treatment of chronic heart failure after myocardial infarction

ADVANTAGES

• Highly selective: >100-fold selectivity for ERβ over ERα, thus minimizing off-target effects and adverse events
• Targeted immune suppression & disease stage specificity: designed to precisely suppress pathological CD4⁺ T cell activation during the maladaptive post-MI remodeling phase to preserve immune-mediated healing in the acute phase
• Demonstrated safety profile with dosages up to 200 mg/kg in rodents
• Favorable pharmacokinetic properties: Previous studies with OSU- ERβ -12 in mice, research hounds, and mini pigs demonstrated an advantageous PK profile compared to clinically used ERβ agonists
• Orally bioavailable at easily translatable doses (~10 mg/kg)

Seeking opportunities for out-licensing, co-development, and collaboration