Hollis-Eden Pharmaceuticals, Inc (SAN DIEGO, California), developing a proprietary new class of small molecule compounds that are metabolites or synthetic analogs of adrenal steroid hormones, announced data on an experimental drug candidate, HE3286, an orally active, second-generation, synthetic steroid hormone currently in preclinical study for the treatment of autoimmune diseases and inflammatory disorders. In a rodent, collagen-induced arthritis model, HE3286, when compared to placebo, significantly reduced the severity of disease, facilitated the repair of joint damage, and decreased disease over the course of the study. Histological analysis of joint tissue conducted at the end of the study indicated a marked reduction of tissue damage (erosion and loss of articular cartilage) in the HE3286-treated animals compared to placebo.

Hollis-Eden's compounds are based on naturally occurring human steroid hormones derived from dehydroepiandrosterone, which in turn is produced by pregnenalone. The company has in vivo and in vitro data linking the anti-inflammatory activity of HE3286 to the regulation of the NF-kappaB pathway and the production of regulatory T-cells (Treg cells). Additionally, Hollis-Eden's class of immune regulating hormones appears to have potent anti-inflammatory properties without side effects such as immunosuppression and bone loss commonly associated with corticosteroids such as dexamethasone. 

Positive attributes associated with HE3286 include the following: 1) in vitro, HE3286 inhibited NF-kappaB signal transduction pathways at concentrations lower than that of the widely used corticosteroid dexamethasone; 2) in a LPS-stimulated mouse model of inflammation, HE3204 decreased activated NF-kappaB in the spleen and TNF-α in the blood; 3) in a preclinical model of multiple sclerosis, a cell-mediated (Th1) autoimmune disorder, orally administered HE3204 decreased disease and production of antigen-specific responses of TNF-α, IL-6, and the Th1 cytokine IFN-gamma; 4) in a preclinical model of rheumatoid arthritis, an antibody-mediated (Th2) autoimmune disorder, orally administered HE3286 decreased joint swelling scores and increased the production of antigen-specific IFN-gamma and TNF-alpha responses in the spleen, indicative of a shift away from Th2 responses and toward Th1 immunity; 5) HE3286 demonstrates good oral bioavailability in primates; and (6) HE3286 is not immunosuppressive in a number of in vitro and in vivo immune-stimulation assays.

—A. Techman

E-mail any comments to .