Disease Benefit with HE3286 in Model of Multiple Sclerosis Highlighted at 2nd International Congress on Immune-Mediated Diseases

Hollis-Eden Pharmaceuticals Reports on Anti-Inflammatory Activity with HE3286 in Models of Diseases of Inflammation

SAN DIEGO--(BUSINESS WIRE)—

Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH) is presenting new data this week showing that its drug candidate HE3286, a novel orally bio-available small molecule compound that has previously demonstrated significant benefit in rodent models of rheumatoid arthritis (RA), also provided benefit in an animal model of multiple sclerosis (MS). The Company is presenting data this week at the 2nd International Congress on Immune-Mediated Diseases being held in Moscow, Russia. In addition the Company is presenting preclinical data demonstrating that HE3286, along with other novel compounds under investigation, HE3413 and HE3177, appear to act by limiting the activation of the pro-inflammatory transcription factor NF-kappaB.

In the data presented, HE3286 showed marked benefit in a SJL/J female mouse model of experimental autoimmune encephalitis (EAE), a model widely used in industry and academia to test agents as potential treatments for multiple sclerosis. In the study, mice were treated orally at disease onset with either HE3286 or placebo for approximately 20 days.

HE3286-treated mice, at doses as low as 4 mg/kg, had markedly reduced disease scores in comparison to placebo-treated animals. Importantly, benefit was maintained for over two weeks, even after treatment was discontinued. The Company also presented previously reported data showing that HE3286 could provide significant benefit in the DBA mouse model of rheumatoid arthritis, even when treatment was delayed until disease was well established.

Additional data presented this week at the conference demonstrate that recently identified compounds in the Company's library, HE3413 and HE3177, appear to limit NF-kappaB activation in preclinical models. Many pro-inflammatory signals, such as TNF-alpha and IL-6, are controlled by NF-kappaB. In these studies, mice were challenged with LPS (bacterial products) and levels of NF-kappaB activation in spleen were measured. Both HE3413 and HE3177 reduced levels of LPS driven NF-kappaB activation compared to placebo-treated animals.

The Company believes both compounds are adrenal steroid hormones that occur naturally in man, and which appear to be potent endogenous regulators of inflammation. HE3413, a newly discovered natural hormone, appears in preclinical models to be a particularly potent anti-inflammatory agent and to have good oral bio-availability in mice.

Dr. Halina Offner, Professor of Neurology at Oregon Health Science Center, who presented the data and is a leading expert on animal models of autoimmune diseases, stated, "We continue to be excited about researching these new steroid hormones because of their apparent ability to regulate critical inflammatory targets such as NF-kappaB and T-regulatory cells.

Previous research we conducted demonstrated that HE3286 has potent anti-inflammatory properties in models of RA, and we wanted to see this drug candidate tested in models of multiple sclerosis. These data suggest that HE3286 is regulating critical pathways that are dysregulated not only in RA and MS, but also in multiple autoimmune disorders and diseases of inflammation. We remain excited about the future role adrenal steroid hormones may play in offering patients relief from these life altering diseases."

"We are pleased that HE3286 continues to perform well in pre-clinical models of diseases of inflammation," said Richard Hollis, Chairman and CEO of Hollis-Eden Pharmaceuticals. "To date, HE3286 has demonstrated anti-inflammatory activity in animal models of rheumatoid arthritis, multiple sclerosis, lupus, ulcerative colitis and cystic fibrosis. Importantly, our recently concluded Phase I clinical study showed that the same blood levels of HE3286 that were effective in our animal models appear to be achievable in man. These observations are leading us to consider initiating pilot Phase I/II clinical studies testing HE3286 in one or more acute inflammatory conditions in the near future. If we are successful in initiating and completing these clinical studies, there may be an opportunity to potentially demonstrate the anti-inflammatory activity of HE3286 in man before the end of this year. With this in mind, we intend to file an IND to support a Phase I/II clinical trial with HE3286 in diseases of inflammation this month. This IND would enable us to potentially test HE3286 not only in RA but in additional diseases of inflammation."

Anti-inflammatory treatments are among the most frequently prescribed drugs today. Approximately 67 million prescriptions are written each year for glucocorticoid steroids to treat many inflammatory conditions despite their well-known side effects that include immune suppression and bone loss. To date, HE3286 and other Hollis-Eden compounds have demonstrated in preclinical models of inflammatory diseases, the anti-inflammatory activity associated with glucocorticoids, but without these side effects. Unlike glucocorticoids that act through the glucocorticoid receptor to completely block NF-kappaB activation which may cause immune suppression and bone loss, HE3286 does not interact with the glucocorticoid receptor and only partially inhibits NF-kappaB.

Hollis-Eden Pharmaceuticals

Hollis-Eden Pharmaceuticals, Inc. is a world leader in the development of a proprietary class of adrenal steroid hormones as novel pharmaceuticals for human health. Through its Hormonal Signaling Technology Platform, Hollis-Eden is developing a new series of small molecule compounds that are metabolites or synthetic analogs of endogenous hormones derived by the adrenal glands from the body's most abundant circulating steroid. These steroid hormones, designed to restore the biological activity of cellular signaling pathways disrupted by disease and aging, have been demonstrated in humans to possess several properties with potential therapeutic benefit -- they regulate innate and adaptive immunity, reduce nonproductive inflammation and stimulate cell proliferation. The Company's clinical drug development candidates include HE3286, a next-generation compound currently in a clinical trial for the treatment of type 2 diabetes and being prepared for potential clinical trials in rheumatoid arthritis, and HE3235, a next-generation compound selected for cancer. In addition to these clinical development candidates, Hollis-Eden has an active research program that is generating additional new clinical leads that are being further evaluated in preclinical models of a number of different diseases.