PROBLEM

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ damage, affecting women at a 9:1 rate as compared to men. The etiology of SLE is complex and incompletely understood; however, the susceptibility of women during the years in which estrogen levels are at their highest may suggest a significant and critical contribution to the development of SLE. Current treatments include corticosteroids and immunosuppressants, often causing severe side effects and failure to regulate disease flare ups. There is an urgent need for safer and more targeted therapies to address the underlying immune dysregulation to better treat patients with SLE.

SOLUTION

In the pursuit of a drug that is tailored to have a favorable selective estrogenic effect, the OSU Drug Development Institute developed a novel selective estrogen receptor modulator, OSU-Erβ-012. This ERβ agonist exhibits potent binding of human ERβ (Ki = 2.0 nM) and is highly selective for the specific activation of Erβ. In vivo studies with humanized lupus mouse models demonstrate a significant reduction in heart and kidney inflammation and suppression of pro-inflammatory cytokines following treatment with OSU- Erβ-012, performing better than prednisone and without toxicity.

APPLICATIONS

• Treatment of SLE and other lupus subtypes (e.g. Cutaneous Lupus Erythematosus), and other autoimmune conditions

ADVANTAGES

• Highly selective: >100-fold selectivity for ERβ over ERα, thus minimizing off-target effects and adverse events
• Highly effective: in vivo data shows OSU-Erβ-012 is as effective as prednisone in modulating inflammation in SLE
• 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)
• Demonstrated safety profile with dosages up to 200 mg/kg in rodents

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