Hollis-Eden Pharmaceuticals Announces Filing of IND with APOPTONE™ in Hormone Sensitive Cancers to Commence Phase I/II Clinical Trial in Late-Stage Prostate Cancer

Business Wire, Feb 19, 2008

SAN DIEGO -- Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH) announced today that it has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to begin clinical trials with its oral drug candidate APOPTONE[TM] (HE3235) for the treatment of hormone receptor sensitive cancers. Assuming clearance of the IND by the FDA, Hollis-Eden plans to initiate a Phase I/II dose ranging clinical trial of APOPTONE in prostate cancer patients during the second quarter of 2008. The patient population for this initial clinical trial will be considered "late stage," which is defined as patients failing at least one round of chemotherapy.

"We are excited to be filing an IND for APOPTONE for hormone sensitive cancers to enable us to initiate our clinical trial in prostate cancer," said Richard B. Hollis, Chairman and CEO of Hollis-Eden Pharmaceuticals. "This is the fourth IND we have filed in less than a year, and assuming the FDA clears our IND, we plan to begin enrolling patients for this clinical trial by the second quarter of 2008. The indications we are targeting, including type 2 diabetes, ulcerative colitis, prostate cancer, and rheumatoid arthritis, are major market opportunities for Hollis-Eden. By initiating clinical trials in these multiple indications we are leveraging our Hormonal Signaling Technology Platform with the goal of delivering novel, first-in-class pharmaceuticals. I am extremely proud of our clinical and regulatory teams as they continue to execute our corporate goals for our two leading drug candidates TRIOLEX[TM] (HE3286) and APOPTONE (HE3235), strategically positioning us to possibly deliver initial data from these clinical trials this year. Our goal is to successfully emerge from these clinical trials with breakthrough products that offer patients better, safer, and more cost effective pharmaceuticals that will greatly enhance their quality of life and position Hollis-Eden as the next emerging high growth company."

"The preclinical activity we observed with APOPTONE in androgen-independent and hormone-independent prostate cancer tumor models gives us confidence as we enter into clinical trials in prostate cancer patients," stated Dr. Dwight Stickney, Hollis-Eden's Chief Medical Officer. "These prostate cancer preclinical models are representative of later stage prostate cancer where traditional hormonal blockade therapy cease working. This initial dose ranging clinical study in prostate cancer is designed to understand the safety, pharmacokinetics, activity and maximum tolerated dose of APOPTONE in this patient population."

As Hollis-Eden has previously reported, in preclinical models of prostate and breast cancer, treatment with APOPTONE significantly inhibited the incidence, growth and progression of tumors. In studies conducted by Hollis-Eden using the LNCaP human prostate cancer cell line, treatment with APOPTONE reduced the incidence of LNCaP tumors in a dose dependent fashion and, in the high-dose group, completely prevented tumor growth, compared to 92% tumor incidence in vehicle-treated animals. In a separate model, mice with established LNCaP prostate tumors were randomized to receive treatment with either APOPTONE or placebo, and tumors were then tracked for three weeks. At the end of the study, tumor volume in the animals receiving placebo was on average over 7 times larger than in animals treated with APOPTONE (p < 0.001), with 2 out of the 9 treated animals becoming completely tumor free.

In a preclinical study of late-stage human prostate cancer conducted by Eva Corey, Ph.D., Research Associate Professor Department of Urology, University of Washington, APOPTONE significantly inhibited the rate of tumor growth. In that study, animals were injected with the human prostate cancer cell xenograft LuCaP 35V, a tumor cell type that is known to grow independently of any hormone stimulation. Once tumors reached 100 cubic millimeters, animals were separated into APOPTONE treatment and control groups and dosed for 28 days. The results of this study showed that APOPTONE significantly inhibited the rate of tumor growth in comparison to untreated tumors by the third week of the study (p = 0.038), with a greater difference in the rate of growth achieved between the APOPTONE treatment and control groups during week four (p = 0.005). Hollis-Eden considers this LuCaP 35V data to be particularly exciting because it extends the activity of APOPTONE beyond the previously described activity in models of hormone sensitive tumors to a model of hormone-independent tumors, which are associated with late-stage prostate cancer disease.

Hollis-Eden believes the mechanism of APOPTONE in inhibiting prostate tumor growth in these preclinical studies appears to be due to the tumor cells undergoing programmed cell death, or apoptosis. Analysis of gene expression from tumors in the preclinical studies indicate APOPTONE appears to act as an apoptotic agent, down regulating genes that protect tumor cells from apoptosis such as Bcl-2 while increasing the expression of pro-apoptotic genes such as caspases. Preclinical findings also show that APOPTONE may increase the susceptibility of tumor cells to chemotherapeutic agents by down-regulating the gene for the multi-drug resistant protein MDR2, originally known as the Breast Cancer Resistance Protein (BCRP).