Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH), the world leader in the development of a new class of small molecule compounds based on endogenous adrenal steroid hormones, announced that it has commenced a Phase I/II clinical trial with its oral drug candidate APOPTONE™ (HE3235) in late-stage prostate cancer patients who have failed hormone therapy and at least one round of chemotherapy treatment.
The Phase I/II open-label dose ranging study, being conducted with the Prostate Cancer Clinical Trial Consortium (PCCTC), will evaluate the safety, tolerance, pharmacokinetics and potential activity of APOPTONE when administered twice daily for 28 days in up to 44 late-stage prostate cancer patients. Potential activity of the compound will be measured by standard prostate-specific antigen (PSA) tests and effect on well-established markers of progression free survival (PFS). In addition, in conjunction with Memorial Sloan-Kettering Cancer Center, the clinical trial will evaluate circulating tumor cell (CTC) enumeration as a marker for effectiveness for tumor treatment. Previous studies have shown that metastatic prostate cancer patients with less than 5 CTCs per 7.5 ml of blood have statistically better survival than patients with greater than 5 CTCs.
APOPTONE has been tested in a number of preclinical cancer models and has been shown to date to be active in controlling the incidence, growth and development of new tumors. Hollis-Eden believes that APOPTONE may be directly inducing apoptosis, or cell death, in tumor cells, as opposed to traditional hormone blockade therapies directed at simply interrupting either the synthesis or the signaling of the tumor cell growth through the androgen or estrogen receptor. While hormone blockade therapy can effectively control prostate cancer for a period of time, it will eventually fail and the cancer can continue to grow and spread. Analysis of gene expression from tumor cells in preclinical studies conducted to date 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.
“The preclinical data generated to date suggest that APOPTONE may offer a unique therapeutic approach to late-stage prostate cancer where traditional therapies have failed,” said Howard Scher, M.D., Chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center.
“Advancing APOPTONE into a Phase I/II clinical trial for late-stage prostate cancer is another significant achievement for Hollis-Eden,” stated Richard B. Hollis, Chairman and Chief Executive Officer. “The patients entering our initial clinical trial will be in the later stages of prostate cancer having failed at least one round of chemotherapy. Based on our previously reported positive data from testing APOPTONE in preclinical models of late stage prostate cancer, we are excited to study the compound’s unique therapeutic approach in a patient population with limited treatment options. We will be assessing the activity of APOPTONE therapy by measuring PSA levels before and over the course of treatment, as well as the standard markers of progression-free survival. In addition, we will be evaluating the ability of APOPTONE treatment to impact circulating tumor cells. This new marker is used as a prediction of PFS and overall survival (OS) in patients treated with therapies for metastatic breast, prostate and colorectal cancer. We are also pleased to be conducting this study in collaboration with the Prostate Cancer Clinical Trial consortium, made up of some of the finest prostate cancer clinics in the world.”
Hollis added, “This should be an exciting second half of the year for Hollis-Eden as we generate clinical data in prostate cancer with APOPTONE and with our novel anti-inflammatory drug candidate TRIOLEX in patients with type 2 diabetes, ulcerative colitis and rheumatoid arthritis. In addition to these major market opportunities, our goal is also to establish ourselves as a world leader in treating or preventing diseases related to aging based on our hormonal signaling technology expertise.”
Preclinical Trial Results To Date
In preclinical models of mice implanted with the human prostate cancer cell line LNCaP, treatment with APOPTONE at the time of tumor cell challenge reduced the incidence of LNCaP tumors in a dose dependent fashion. In the high-dose group, APOPTONE completely prevented tumor growth, compared with 92% tumor incidence in placebo-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 more than seven times larger than in animals treated with APOPTONE (p ≤ 0.05). Two out of the nine treated animals became completely tumor free.
In a preclinical model of late-stage prostate cancer using the human xenograft LuCaP 35V, a tumor cell type that is known to grow independently of any hormone stimulation, treatment with APOPTONE showed marked suppression of tumor growth from day 21 until the end of the 28-day study vs. control (p ≤ 0.05). This LuCaP 35V data is noteworthy because it extends the activity of APOPTONE beyond the previously described activity in models of hormone-dependent tumors to hormone-independent tumors, also known as castration-resistant tumors, which are associated with late-stage prostate cancer.
APOPTONE also was tested in a novel model of prostate cancer bone disease developed by the Company’s collaborators at the University of Washington. The study was designed to see if APOPTONE could kill castrate-resistant prostate tumor cells transplanted directly to the bone of experimental animals. In this model of metastatic prostate cancer, C42B castrate-resistant human prostate cancer cells were implanted into the tibia bone of castrated mice and allowed to grow. Once animals expressed prostate-specific antigen (PSA) in their serum, indicating that the prostate cancer cells were growing in the bone, the animals were randomized to daily treatment with either APOPTONE or placebo. At the end of the four-week treatment period there was a statistically significant lowering of PSA levels in APOPTONE-treated animals of greater than 50% (p ≤ 0.05) relative to the placebo-treated animals. More importantly, the weight of the tumored tibia from APOPTONE-treated animals was significantly lower when compared with the placebo-treated animals (p≤ 0.05), indicating that tumor growth in the bone was inhibited by APOPTONE treatment.
Prostate Cancer Market
Approximately 234,000 patients are diagnosed with prostate cancer each year in the United States. The pharmaceutical market for treating prostate cancer is approximately $7 billion per year. Current treatments for prostate cancer focus on blocking testosterone and other hormones associated with disease progression and range in annual sales from $500 million to $1.8 billion. With approximately 30,000 men in the United States dying from prostate cancer each year, there remains a tremendous unmet medical need where novel treatments are needed.
Prostate Cancer Clinical Trial Consortium (PCCTC)
The membership of the PCCTC presently includes: Dana Farber Cancer Institute; Johns Hopkins University: Memorial Sloan-Kettering Cancer Center: University of California San Francisco; The Regents of the University of Michigan; Oregon Health & Sciences; The University of Texas, M.D. Anderson Cancer Center; University of Wisconsin; Duke University and University of Washington.
About Hollis-Eden Pharmaceuticals, Inc.
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 adrenal 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 TRIOLEX™ (HE3286), a next-generation compound currently in clinical trials for the treatment of type 2 diabetes and ulcerative colitis and being prepared for a clinical trial in rheumatoid arthritis, and APOPTONE™ (HE3235), a next-generation compound in a clinical trial for late-stage prostate 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. For more information on Hollis-Eden, visit the Company’s website at www.holliseden.com.
This press release contains forward-looking statements within the meaning of the federal securities laws concerning, among other things, the potential and prospects of the Company’s drug discovery program and its drug candidates. Any statement included in this press release that are not a description of historical facts are forward-looking statements that involve risks, uncertainties, assumptions and other factors which, if they do not materialize or prove correct, could cause the Company's actual results to differ materially from historical results or those expressed or implied by such forward-looking statements. Such statements are subject to certain risks and uncertainties inherent in the Company’s business, including, but not limited to: the ability to complete preclinical and clinical trials successfully and within specified timelines, if at all; the ability to obtain regulatory approval for TRIOLEX (HE3286), APOPTONE (HE3235) or any other investigational drug candidate; the Company’s future capital needs; the Company’s ability to obtain additional funding; the ability of the Company to protect its intellectual property rights and to not infringe the intellectual property rights of others; the development of competitive products by other companies; and other risks detailed from time to time in the Company’s filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Except as required by law, the Company undertakes no obligation to update or revise the information contained in this press release as a result of new information, future events or circumstances arising after the date of this press release.
Contacts:
Hollis-Eden
Pharmaceuticals, Inc.
858-587-9333
