Hot watch list for biotech microcap
Harbor BioSciences, Inc., (HRBR.OB) a development stage pharmaceutical company, engages in the discovery, development, and commercialization of products for the treatment of diseases related to aging. The company focuses on developing a series of steroid hormone analogs that are derived from the human adrenal metabolome. Its clinical drug development candidates include APOPTONE (HE3235), a compound that is in Phase I/IIa clinical trials for late-stage prostate cancer; and TRIOLEX (HE3286), a compound that is in early Phase II clinical trials for the treatment of type 2 diabetes, as well as in Phase II clinical trials for the treatment of ulcerative colitis and rheumatoid arthritis diseases. The company was formerly known as Hollis-Eden Pharmaceuticals Inc. and changed its name to Harbor BioSciences, Inc. in February 2010. Harbor BioSciences was founded in 1992 and is headquartered in San Diego, California.
HRBR has really interesting and bright science in basis of their drugs. The company scientists discovered very unique and promising way to fight the prostate cancer.
What is HRBR’s APOPTONE?
I can compare this drug with delayed-action mine. Prostate cancer cell growth is fueled by androgen hormones (mostly by testosterone). The standard hormone therapy for late-stage prostate cancer blocks the production or activity of these hormones and in such way suppresses the tumor growth. While hormone therapy can effectively control prostate cancer for a period of time, it will eventually fail and the cancer can continue to grow and spread. Unfortunately, the castration-resistant prostate cancer (CRPC) (formerly hormone-resistant or hormone-refractory prostate cancer) is prostate cancer kind that not responding to androgen deprivation. In case of CRPC tumor cells are almost independent from androgen. During androgen-independent progression, prostate cancer relies on various cellular pathways, some involving the androgen receptor and others bypassing it. The androgen receptor may be amplified and therefore may be activated by reduced levels of dihydrotestosterone. The numerous studies indicate that enhanced intracellular conversion of adrenal androgens to testosterone and dihydrotestosterone is a mechanism by which prostate cancer cells adapt to androgen deprivation and suggest new therapeutic targets.
The standard systemic treatment for prostate cancer patients is androgen deprivation therapy. Although serum testosterone concentrations were significantly reduced after androgen deprivation therapy, levels of intraprostatic androgens are reproducibly measured at concentrations sufficient to activate androgen receptor and stimulate tumor growth, suggesting that prostate cancer cells may survive androgen deprivation therapies by increasing intracrine androgen synthesis within the prostate.
In simple words any prostate cancers cells like testosterone and dihydrotestosterone. They need them to grow and divide. If they are deprived of androgens they will start produce it by themselves.
It’s possibly to use steroidal androgen synthesis inhibitors (Abiraterone) that selectively inhibits the 17,20 lyase enzyme, but it can’t completely suppress androgen synthesis.
HRBR scientists proposed the original way to fight prostate cancer. May be they were thinking in such way: if prostate cancer cells like androgens let just give them androgen, but different androgen.
For example, some people like sugar like crazy and they can’t eat un-sweet cakes or drink un-sweet drinks. How is it possibly to cut their sugar consumption smoothly? They may use the artificial sweeteners instead of sugar. Thus, they will decrease the sugar consumption and decrease the probability of diabetes. Actually some of these artificial sweeteners are good; I’m using Stevia and cut the daily sugar consumption at least twice. But I don’t use pure Stevia powder, I mix it with sugar. If you usually use 4 teaspoon of sugar in one glass of coffee, instead of it you can mix 2 teaspoon of sugar and 1 packet of Stevia. One Packet of SteviaPlus = Two Teaspoons of Sugar! http://www.stevia.com/
HRBR scientist designed androgen metabolite that structurally similar to androgens. Prostate cancers cells cannot make out the real androgen and APOPTONE. Because the APOPTONE is steroid analog of a testosterone metabolite i.e. the “fake androgen”). Prostate cancer cells swallow up the big amount of fake androgen that is actually a poison for them. APOPTONE is causing tumor cells to undergo programmed cell death, or apoptosis. This drug should be harmless to non-prostate cells because they don’t need androgens.
The APOPTONE phase I/IIa trial.
Taxane-Resistant Patient Group
A total of 42 taxane-resistant prostate cancer patients with progressive (metastatic) disease were enrolled into the clinical trial at 7 dose levels. As previously reported, 28 (67%) reached the first reassessment (two 28-day cycles); 15 (54%) of these had stable disease or improvement of metastatic soft tissue and/or bone lesions by imaging and have received 1 to 8 additional treatment cycles before disease progression. These include patients who are taxane resistant and who failed prior hormonal, chemotherapy and/or experimental forms of therapy including Abiraterone(R) and MDV-3100. Prior treatment with ketoconazole (41.5% of patients) had no effect on the activity of Apoptone to stabilize disease. The drug was well tolerated at all doses with no overt dose-limiting toxicities observed.
Just look at the pre-conditions of patients. All known and experimental therapies couldn’t help them including Abiraterone (J&J bought this drug for $1B) and MDV-3100 (last hope for MDVN).
“Twenty-two chemotherapy-naive patients were enrolled in two cohorts of eleven patients each, receiving either 100 mg or 350 mg of Apoptone per day. Ten patients of each cohort reached their first reassessment at eight weeks with stable disease and have received one to eight additional cycles of Apoptone. Three patients in the 100 mg group and eight patients in the 350 mg group remain on study.
One patient in the 350 mg group has a confirmed partial overall response of the disease. The patient had a target tumor (by RECIST criteria) that was 1.1 centimeters in the longest diameter, which disappeared after 56 days. This response was confirmed with a repeat scan 8 weeks later.
"The response in this patient was impressive and rapid and his bone scan remains stable," commented Michael Gordon, M.D., Oncologist and Associate Professor of Clinical Medicine at the University of Arizona College of Medicine. "Other non-target tumors that do not qualify by RECIST criteria at baseline also decreased in size, indicating the response to the soft tissue was more widespread than to the one target tumor. I expect continued regression of tumor in the upcoming radiographic assessments. Apoptone continues to show a good safety profile and is well tolerated at these higher doses," Dr. Gordon added.
The trial is continuing.
Dose escalation to 700 mg has been initiated based on both the quantitative response and experience with the 350 mg dose, which demonstrate that the drug is safe and well tolerated.
The intermediate phase I trial results: One patient in the 350 mg group has a confirmed partial overall response of the disease. The median time to progression (TTP) for the 100 mg cohort is 24 weeks. The median TTP has not been reached for the 350 mg dose. TTP is a measure of time after a disease is diagnosed (or treated) until the disease starts to get worse.
Wait a minute; it seems like that hopeless patients treated by 350 mg of APOPTONE didn’t start to get worse. What about 700 mg dose? May be APOPTONE is stronger drug than Abiraterone and MDV-3100?
Disclosure: HRBR is a penny stock now ($0.15 at 12/01/10), Shares Out. 35.5M and Market Cap ($) 5.3M. HRBR’s APOPTONE is a promising prostate cancer drug. HRBR is small biotech company that just had a bad luck to be at early stage of development at this hard time. This company is still fighting to survive and bring the new drug to prostate cancer patients. I don’t have the positions in HRBR, but I’m thinking about to buy it for long in nearest future.
It seems like that market ignored the recent HRBR news.
"Harbor BioSciences Signs Pharmaceutical Development Agreements With China State Institute of Pharmaceutical Industry (CIPI)
CIPI to Finance 100% of Product Development in China.
Clinical drug development candidates licensed to CIPI include Triolex (HE3286), which has completed Phase IIa clinical trials in patients with Type 2 diabetes and is in early stage development for ulcerative colitis and rheumatoid arthritis; Apoptone (HE3235), which has demonstrated activity in Phase I/IIa trials of prostate cancer; and HE2000, which has shown to limit opportunistic infections, including tuberculosis, in humans infected with the HIV-1 virus, to reduce parasite levels in patients with uncomplicated malaria and to attenuate non-productive lung inflammation in animal models."
Strange, but China is not licensed Abiraterone or MDV-3100... Or Dreamboat... They are buying the best innovative biotech products, recent example BSD-2000 from BSDM. It seems like they were impressed by last APOPTONE (HE3235) results in phase I/IIa trial. So, may be it's time to increase HRBR positions...
One more speculation...
If China licensed USA drugs in early stage they definitely know that these drugs are very effective. How they know? Don't be naive, each USA pharma company has scientists of Chinese origin, drug chemical formulas are simple (you can find them in patents), so they already tested all these drugs on humans. But they can't just stole these drugs so they are licensed them. With 1.3B population China needs cheap and effective drugs against prostate cancer and diabetes. Provenge with annual cost $93k per patient is not for China republic with may be more than 700,000 prostate cancer new patients per year(number is just an approximation from USA data: "more than 192,000 men are diagnosed with the disease each year and more than 27,000 die from it, according to the American Cancer Society." - USA population is 300M and China 1.3B).
Question is why they didn't licensed Abiraterone or MDV-3100?
"time to PSA progression (TTPP) [median 10.2 months for abiraterone acetate vs. 6.6 months for placebo, HR=0.58 (95 percent CI: 0.46, 0.73); p<0.0001] and an increase in radiographic progression-free survival (rPFS) [median 5.6 months for abiraterone acetate vs. 3.6 months for placebo, HR=0.67 (95 percent CI: 0.58, 0.78); p<0.0001]. Total PSA response, defined as greater than or equal to a 50 percent decrease from baseline, was achieved in 38 percent of patients treated with abiraterone acetate vs. 10 percent in the prednisone/prednisolone plus placebo group [p<0.0001]."
So, +3 months of life...
MDV-3100 is a product of MDVN that is well-known by Alzheimer's drug Dimebon.
MDV 3100 was found clinically active for metastatic castration-resistant prostate cancer patients in a phase II trial. PSA level decreased more than 50 percent in 40/65 chemo-naive patients and 38/75 chemotherapy-trated patients.
Well, phase II of Abiraterone also showed that "44% (patients) met the criteria of >50% PSA decline". But finally this drug showed to prolong survival time just 4-5 months...
It seems like that pumped MDV-3100 is not so strong prostate cancer drug...
Again will repeat here what is APOPTONE treated group:
"...these include patients who are taxane resistant and who failed prior hormonal, chemotherapy and/or experimental forms of therapy including Abiraterone(R) and MDV-3100."
Disclosure: I have the position in HRBR.OB Low risk, but very high reward is possible.