Rock Creek Pharmaceuticals Inc. (fka RCPIQ)

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New article just out on RCPI from Dr John Faessel


Rock Creek Pharmaceuticals - Updated timeline: Tobacco > Nicotine > Anatabine > Anatabloc
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Dr. John L. Faessel

ON THE MARKET

Commentary and Insights

Updated 10-22-2014

Timeline* / What We Know / and Beyond


* Timeline: Tobacco > Nicotine > Anatabine > Anatabloc




·As of 6/4/2014 Star Scientific has a new name; Rock Creek Pharmaceuticals(RCPI), Nasdaq. Therefore, throughout the lengthy timeline of this report I will refer to the company as Rock Creek rather than Star Scientific.

The tortuous history of drug discovery and development is filled with examples of long, quirky, unpredictable and often serendipitous discoveries and then, much as the substance in a mosaic reveals itself, its relevance and significance becomes vibrantly clear. To view a celebrated mosaic link here.

Major medical breakthroughs never happen overnight. Science marches to the beat of its own drum, and discoveries typically emerges over the course of years, decades, or even centuries, before culminating in disruptive technologies and important medical advances.

A striking example of a major medical advance occurring over a long timeline is the discovery and development of statins, the class of medicines that are now the first-line treatment for lowering cholesterol levels. In the late 1800's, German scientist Rudolf Virchow discovered that large amounts of cholesterol were deposited on the artery walls of patients who died from cardiovascular disease. Fast forward 50-years to the celebrated Framingham heart study, which demonstrated a correlation between blood cholesterol levels and coronary heart disease. Yet it took another 20 years until Japanese researchers discovered the first compounds that inhibited the biosynthesis of cholesterol in the 1970's, and still another 20-years until the development of Lipitor, the biggest selling medicine off all time. Lipitor sales exceeded $12.8 billion in 2006 alone, and have been worth over $100 billion to Pfizer (PFE) since receiving FDA approval in 1996. Aside from the astonishing sales figures, the statins have saved countless lives by preventing hyperlipidemia and associated cardiovascular diseases.

The story of anatabine, the active component of Rock Creek Pharmaceuticals(RCPI), Anatabloc, is no different. Anatabine is a minor alkaloid found in the solanaceae plant family (potato, pepper, eggplant, tomato), as well as tobacco and nightshade. The science surrounding anatabine has been now been evolving for over 25 years, and Anatabloc has been unequivocally demonstrated to effect many important pathways of inflammatory, neurological, and autoimmune diseases such as diabetes, inflammatory bowel disease, cancer, rheumatoid arthritis, Alzheimer's disease, and Parkinson's disease. Let's take a retrospective examination of the science, the timeline, and at what we now know, and then look toward what the future holds.


1988 - Researchers at the University of Colorado Health Sciences Center in Denver found that smoking slowed disease progression in ulcerative colitis patients, with lower rates of flares-ups and hospitalization. They published their findings in The Scandinavian Journal of Endocrinology. Link here.

1998 - The Mayo Clinic publishes positive results of a clinical trial using nicotine as a treatment for ulcerative colitis. “Ulcerative colitis is predominantly a disease of nonsmokers. Transdermal nicotine may help control clinical manifestations of this condition.” Link here.

The lead investigator of this study was the renowned William J Sandborn, MD, formerly Professor of Medicine and Vice Chairman of the Division of Gastroenterology and Hepatology at the Mayo Clinic, Rochester, MN and now Chief, Division of Gastroenterology and Director of the UCSD Inflammatory Bowel Disease Center at the University of California, San Diego. Dr. Sandborn has published over 487 articles in peer reviewed journals. His research interests are clinical trials and clinical pharmacology related to inflammatory bowel disease.

1999 - A publication in the British Journal of Clinical Pharmacology describes the positive effects of tobacco use in patients with inflammatory bowel disease. “…there is overwhelming epidemiological evidence that smoking protects against ulcerative colitis, the risk of developing the disease being significantly lower in smokers than in non-smokers or former smokers.” Link here

2003 - Dr. Paul Ladenson, director of the division of Endocrinology at Johns Hopkins discloses the results of a large epidemiological study on over 16,000 people demonstrating that tobacco use has a beneficial effect on autoimmune thyroid conditions such as Hashimoto's disease. Link here

2004 – Dr. Paul Ladenson and his team at Johns Hopkins publish the results of a study conducted among a group of flight attendants with chronic exposure to cigarette smoke. This pivotal study found a reduction of autoimmune thyroiditis (Hashimoto's disease) related to inhalation of second hand cigarette smoke. To link the study of 18,148 persons who underwent thyroid testing go here.

2007 - A Harvard School of Public Health study showed that smokers were 73% less likely to suffer from Parkinson's than people who didn't smoke. According to Dr. Honglei Chen, the study's lead researcher “the information could guide the development of studies on various tobacco components ... to help understand the relationship between smoking and Parkinson's disease … further research could determine which chemicals are responsible for bolstering the brain against the illness.” Link here.

2009 - 2010 - Researchers Rock Creek Pharmaceuticalsdiscover that anatabine, one of the 4000 chemicals found in tobacco, has the capacity to reduce the urge to smoke. Scientists at Star have subsequently determined that anatabine, the active ingredient in Anatabloc, has numerous additional benefits and is likely the key active component of tobacco responsible for its positive effects on autoimmune and inflammatory diseases.

2010 - Harvard University's McLean Hospital completes a comprehensive two year preclinical research program demonstrating the safety and tolerability of anatabine, as well as complete absence of addictive potential. Link here.

2010 – Rock Creek begins test marketing CigRx™ an anatabine based compound the company believes will reduce the urge to smoke. This product is intended for consumption by tobacco users, and the amount of anatabine in each lozenge is similar to what a smoker would get from one cigarette.

October 2010 - The Roskamp Institute begins clinical trials of RCP-006 (anatabine) for the treatment of Alzheimer's disease. In addition, Roskamp scientists begin collaboration with Johns Hopkins to investigate additional therapeutic applications of RCP-006.

“Roskamp scientists are working with researchers at Johns Hopkins School of Medicine for other medical applications of RCP-006.” here

Links here and here.

March 2011 - Star Scientific (STSI) files an international patent application (WO 2011/119722 A2) describing the use of anatabine to lower key inflammatory biomarkers. From the summary: “A pharmaceutical composition comprising a therapeutically effective dose of an isolated form of anatabine or a pharmaceutically acceptable salt thereof can be administered to an individual to reduce a symptom of a disorder comprising an NF-kB mediated inflammatory component or to reduce the risk of developing such a disorder.” Link here.

March 2011 - The Roskamp Institute demonstrated the striking anti-inflammatory effects of anatabine, as evidenced by the reduction of key pro-inflammatory cytokine IL-1beta. Anatabine was shown to over three times more effective than Lipitor at lowering this marker of inflammation. Link here.

July 2011 - Researchers at The Roskamp Institute disclose the results of a study demonstrating that anatabine (RCP-006) is over four times more effective than both Celebrex and Voltarol in reducing levels of damaging pro-inflammatory cytokines. Link here.

August 2011 - Rock Creek begins marketing of Anatabloc® via a dedicated product website.

September 2011 - The Roskamp Institute demonstrates anatabine's ability to decrease LPS-induced NF-kB activity. More importantly, anatabine was shown to be safe / effective at dose equivalent levels where Celebrex and aspirin demonstrate severe toxicity. Link here.

November 2011 - Researchers at The Roskamp Institue publish a peer-reviewed manuscript in European Journal of Pharmacology entitled “Anatabine lowers Alzheimer's Aß production in vitro and in vivo.” For a brief abstract link here. For a pdf of the entire 19-page peer-reviewed abstract, email a request here.

January 2012 - Rock Creek Pharmaceuticalsreports first completion of clinical trial showing anatabine lowers chronic inflammation measured by C-reactive protein [CRP] blood levels in humans. Up to this point in the timeline there had been no clinical evidence that anatabine worked as well in human studies as it did in cell and animal studies. Link here.

February 2012 –Rock Creek Pharmaceuticals makes Anatabloc® available for purchase via the GNC Internet storefront. Link here.

April 2012 – GNC offers Anatabloc® in select stores. Link here.

May 23, 2012 – GNC expands distribution to all of its US-owned retail locations in 2,922 locations. Link here.

May 2012 – Researchers at the Roskamp Institute completed a successful animal study of nutritional supplementation anatabine in an animal model of multiple sclerosis [MS]. Preliminary data all suggest the Rock Creek specially formulated anatabine supplement has a highly beneficial effect in this model of MS. Link here.

The animal data showed that anatabine crosses the blood-brain barrier rapidly and easily, and it has potential uses in central nervous system [CNS] conditions. To wit, two videos of animal studies from animals “engineered” to be models of multiple sclerosis [MS] were shown. Take 85 seconds to see the example of a condition that typifies MS and to see why there is continuing interest in anatabine:

·No anatabine: Link here

·With anatabine: Link here

July 2012 - A Johns Hopkins team led by Dr. Paul Ladenson publish a peer-reviewed manuscript in the Endocrinology journal entitled “Anatabine Ameliorates Experimental Autoimmune Thyroiditis.” The Johns Hopkins team found that anatabine was able to completely prevent the (thyroid) disease in many mice and significantly reduce the severity of disease in the entire population that received the treatment. In addition, the team found that the treatment with anatabine significantly reduced the presence of numerous proinflammatory agents such as interluken-1 receptors, interluken-18, COX2, and others.


“Department of Pathology (P.C., A.D.R., M.A.L.-S., S.I., S.-C.T.), and Divisions of Endocrinology and

Metabolism (P.C., P.W.L.) and Cardiology (M.F.), Department of Medicine, Johns Hopkins University

School of Medicine, and Feinstone Department of Molecular Microbiology and Immunology (P.C.), Johns

Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205” Link here.

September 2012 - Rock Creek launches Anatabloc® face cream “that’s been demonstrated to considerably improve the appearance of the skin in a broad variety of volunteers in a case series conducted by leading dermatologist Dr. Susan H. Weinkle of Bradenton, Florida, past President of the American Society for Dermatologic Surgery.”Link here.

October 2012 – Researcher at the Roskamp Institute reported that in the “Flint” CRP study that “11 of 18 (61%) diabetic subjects onmetformin (the first-line drug of choice for the treatment of type 2 diabetes) had a CRP reduction, as did 31 of 81 (38%) subjects in the general trial population not taking metformin. Overall, 42 of 99 (42%) subjects had a decrease in CRP after only one month with anatabine supplementation.” The committee reviewing the data found that “the administered doses of anatabine were safe, well-tolerated, and showed clear evidence of a biological effect on CRP and the immune system, as manifested by CRP and an inflammatory marker called Tumor Necrosis Factor Alpha (TNF-alpha).” Link here and here.

January 2013 - Researchers at the Roskamp Institute publish a peer-reviewed manuscript in European Journal of Pharmacology [EJP] entitled“Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation.” The study demonstrated the effect of anatabine on the JAK-STAT pathway by suppressing STAT3 phosphorylation, inhibiting TNF-alpha and NF-kB levels in-vitro. Link the EJP abstract here.See an informative video re JAK-STAT link here.

January 7, 2013 –Rock Creek Pharmaceuticals in a trial on humans publishes positive preliminary results of their research entitled “Anatabloc Supplementation Autoimmune Prevention.” Results from the trial disclose that the anatabine science has demonstrated proof of concept and efficacy in all human study subjects in trials supervised by the distinguished physician / scientist Dr. Paul Ladenson, as senior endocrinological consultant for the study. Dr. Ladenson, stated, "Data from this rigorously conducted, placebo-controlled, double blind trial show that anatabine-treated subjects had progressive decreases in circulating thyroglobulin antibody levels, which became significant by the end of the trial.” Assays for TgAbs and TPOAbs and the 3 interleukins were performed at Johns Hopkins Immunological Disorder Laboratory (Baltimore, Maryland). Link here and here.

January 30, 2013 - Researchers at the Roskamp Institute publish a peer-reviewed manuscript in PLOS ONE entitled “Amelioration of Experimental Autoimmune Encephalomyelitis [EAE] by Anatabine.” The abstract revealed that; Orally administered anatabine markedly suppressed neurological deficits associated with EAE while significantly reducing Th1 and Th17 cytokines known to contribute to the development of EAE. Anatabine appears to significantly suppress STAT3 and p65 NF?B phosphorylation in the spleen and the brain of EAE mice and found that anatabine alleviated the infiltration of macrophages/microglia and astrogliosis and significantly prevented demyelination in the spinal cord of EAE mice. To view the 26 page PLOS ONE peer-review, link here.

October 31, 2013 -In a human trial published in The Journal of Clinical Endocrinology and Metabolism entitled “Anatabine Supplementation Decreases Thyroglobulin Antibodies in Patients With Chronic Lymphocytic Autoimmune (Hashimoto's) Thyroiditis: A Randomized Controlled Clinical Trial” in a study funded by Rock Creek Pharmaceuticals of 146 patients recruited from 9 endocrinology clinics in 5 study sites in visits over 4 months researchers found that the “study shows that nutritional supplementation with anatabine significantly reduces circulating TgAb levels in patients with Hashimoto's thyroiditis.” “These results demonstrate an immunological effect of anatabine on TgAb levels.”The results of the trial show that dietary supplementation with anatabine induces a statistically significant reduction in thyroid autoimmunity. The anatabine supplementation was safe and well tolerated. Overall the study documented excellent results. The absolute change in mean TgAb levels between baseline and weeks 4, 8, and 12 revealed a significantly greater TgAb reduction in patients taking anatabine relative to those taking placebo. Thyroid antibody assay testing was done at Johns Hopkins Immunological Disorder Laboratory (Baltimore, MD). Link here.

July 31, 2014 -Rock Creek Pharmaceuticals announced that it has initiated the development of Anatabine Citrate research in Europe and that it has selected United Kingdom based Quotient Clinical to run its early development programs. The Quotient Clinical team will provide safety and tolerability studies to investigate escalating doses of anatabine and to identify the next generation of oral anatabine formulations. Link here.

August 11, 2014 - In a clinical and regulatory update Rock Creek Pharmaceuticals announced that it is voluntarily suspending its sale of CigRx® and Anatabloc® until such time as the company can complete its review of the FDA's response to the company's pending NDIN, which has not yet been received. The company is coordinating with the FDA and working diligently at attaining an effective IND so as to begin clinical safety trials as soon as practicable. The company will continue to prosecute a parallel clinical development program in the United Kingdom under a Clinical Trial Application (CTA) currently anticipated to be filed by the end of the third quarter of 2014. Upon CTA approval, the company expects to conduct European clinical safety trials shortly thereafter.

Link here.

September 12, 2014 - Rock Creek announced that it has received a written response from the U.S. Food and Drug Administration (FDA) in response to the New Dietary Ingredient Notification (NDIN) for the formulations of Anatabloc® and CigRx® submitted by the company in June 2014. The letter indicated that the FDA considers anatabine citrate, a principal ingredient in these products, to be a drug, because anatabine citrate is intended to provide anti-inflammatory support, and is the subject of a previously filed Investigational New Drug Application (INDA). Link here.

In addition and especially notable in this timeline is that there is ongoing and extensive research underway at the Roskamp Institute on traumatic brain injuries [TBI] using anatabine, among other agents, as a therapeutic intervention targeting neuroinflammation following a TBI. From the Roskamp website re TBI; “Anatabine shows great promise at rescuing memory in animals, even when taken at long-term time points after the initial insult.” Link here.

At the moment there are no approved drugs available for reducing secondary injury after TBI.

Notable is that the Roskamp Institute is presenting four abstracts re anatabine at the up-comingSociety for Neuroscience 44th annual meeting; Neuroscience 2014 (Nov 15-19, Washington D.C.)

Two are on the effects of anatabine on Alzheimers disease, one on anatabiine re the effects TBI and one on the effects anatabine on Gulf War Illness. Link here and here.

There are currently four active TBI research projects underway at Roskamp. Two are funded by the U.S. Department of Defense and one is funded by the U.S. Department of Veterans Affairs. Another is funded by a joint grant from the Veterans Affairs & the Department of Defense.

~~~~~~~~

Quotes of relevance:

Dr. Paul Ladenson, Johns Hopkins Director of Endocrinology

1.Re tobacco; “there must be something in there that’s good for you.”

2.“That aside from RCP-006 (anatabine) there is no known compound that stops thryoiditis.”

Watch the narrated animation to learn more about the anatabine inflammation, link here.

The science of anatabine / Anatabloc has now progressed from lab bench through animal models and more recently into the clinic with humans demonstrating success at every stage signifying clear signals of efficacy in major disease areas. The scientific and clinical data indicates that the compound is safe, effective, and well-tolerated. As interest compounds exponentially in the scientific and medical community, with clinical and anecdotal evidence piling up, anatabine / Anatabloc is taking its rightful place front and center in the fight against “inflammaging” driven by immunological and inflammatory diseases.

Anatabloc has now been consumed by roughly several hundred thousand people taking over 50,000,000 lozenges. I have heard reports of many wonderful benefits; however anecdotal results do not qualify as science per se so we won’t repeat them here though numerous testimonials are accessible on the web.

As the science relevant to anatabine has progressed so also has the company, evolving from its founder-management, to a company with a new, first-class research/scientific management team led by Dr. Michael Mullan, MD, PhD, as CEO and Dr. Christopher Chapman, MD as President. The board of directors has also evolved to reflect the new direction of the company as a serious biotech enterprise with a large portfolio of intellectual property. Now the science will be the key driver of Rock Creek Pharmaceuticals.

Last but not least:

See the latest (10-10-2014) commentary below from biotech guru Patrick Cox (John Mauldin’s Transformational Technology Alert) relevant to the Rock Creek / FDA kerfuffle concerning the “drug” status of anatabine / Anatabloc and more re anatabine’s remarkable beneficial impacts on inflammatory diseases and aging. (Mauldin’s highly acclaimed Thoughts from the Frontline and Outside the Box) is read by over one million readers each week. It’s a must read by students of the global markets and the drivers of the world economy - and the subscription is free – link here.)

Until recently, a powerful anti-inflammatory compound, anatabine citrate, was available as Anatabloc. With a remarkable safety record, including toxicity studies from Harvard, it has been used widely with remarkable beneficial impacts on inflammatory diseases. I am confident in my prediction that, once widely adopted, anatabine citrate will increase health spans by five to ten years and possibly more. Unfortunately, the FDA viewed this natural product, found in eggplants and other food plants, as a drug and pressured the company that owns it to take it off the market.

This has provoked considerable dismay and panic among users, such as this plea from one user. In the meantime, the world’s leading neurological research organization continues to publish quite remarkable information about anatabine citrate, including this report on traumatic brain injury. Additionally, research on NF-kB activation, which anatabine citrate moderates to healthy levels, is expanding.

The Albert Einstein College of Medicine has published research showing that down-regulation of NF-kB in the hypothalamus seems to slow our primary clock of aging. Work from the Ohio State University Wexner Medical Center implicates NF-kB over-activation as an important mechanism whereby cancers protect themselves from the immune system. Anecdotal evidence from anatabine citrate users supports that theory. If you haven’t watched this overview of the effects of anatabine citrate, you should. There has never been anything, drug or not, that produces this kind of benefits.

Anatabine citrate may be the best example of our system’s misplaced emphasis on diseases rather than aging. The company that owns the rights to the compound had to declare a disease target, but the FDA then used that fact to treat the natural substance as a drug. This, in turn, forced the company to withdraw it from the market. This is madness and people will suffer and die prematurely until we change the focus from diseases to the relatively easy and inexpensive ways of preventing them.

For the entire Pat Cox report link here:

For Rock Creek’s 46-page PowerPoint in pdf (10MB) send request to: [e-mail]

The Rock Creek website: http://www.rockcreekpharmaceuticals.com/

Anatabloc can still be acquired at eBay. Link here

Disclosure: I purchased shares of RCPI in the open market and will likely buy more. I have no affiliation with the company.