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Breaking News For Star Scientific: Anatabine Is Effective In Models Of Inflammatory Bowel Disease

|Includes: Rock Creek Pharmaceuticals, Inc. (RCPI)

Breaking News: Anatabine is Effective in Models of Inflammatory Bowel Disease

Star Scientific (STSI) Nasdaq

"Phenomenology is very different than pharmacology" - Dr. Phil Needleman, The Ten Commandments of Drug R&D

Star Scientific recently announced that anatabine, the active ingredient in their flagship product Anatabloc was demonstrated to be effective in a mouse model of ulcerative colitis in research performed at the University of Virginia (link here). This adds to a growing list of autoimmune and inflammatory diseases for which anatabine has been shown to be effective in either a preclinical or clinical setting.

First let's discuss this mouse model* of ulcerative colitis and the implications of the study, then let's talk about the above quote from Dr. Philip Needleman, inventor of Celebrex, professor emeritus at Washington University School of Medicine, and former Chief Scientist of Pharmacia, and see how it applies to Star Scientific's Anatabloc™ And let's not forget the numerous risks that loom large for Star's Anatabloc going forward.

First the ulcerative colitis model: While I seldom focus on the precise details of the animal model and how the study designs are structured, in this case it will bring a fuller understanding of the relevancy in its ensuing use on patients in the clinic. In this model, mice are given a chemical called dextran sodium sulfate (NYSEMKT:DSS) in their drinking water. This chemical causes a disruption in the barrier of the colon that provides protection from bacteria that reside within the digestive tract of the mouse, as well as inside each and every one of us. With the protective mucosal barrier being ulcerated, these normally beneficial digestive tract bacteria are then able to penetrate inside the body, causing a major inflammatory response. This disruption and ulceration of the protective barrier combined with the infiltration of gut bacteria is an excellent model of what happens in patients with inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. What the researchers at University of Virginia did was test the ability of anatabine to prevent or reduce the severity of the disease in two manifolds: (NYSE:A) protection against disease development and (NYSE:B) treatment of existing disease.

In the first manifold, the animals are given DSS and antabine concurrently at the beginning of the model, and these mice are compared to those given only DSS. In this case they saw that the animals given anatabine and DSS developed a less severe disease than those given DSS alone, demonstrating the protective effect of anatabine in development of the colitis. In the second mode, the animals were first given only DSS and the disease was allowed to develop. The diseased animals were then separated in two groups, and one group was given anatabine while the other was given nothing. Given the results of the first manifold, it would be expected that the mice treated with anatabine would also have a faster recovery from the DSS-induced colitis than those given no drug. However, this aspect of the experiment was inconclusive in this regard because the diseased animals did not drink sufficient anatabine-containing water during the course of treatment to provide proper dosing. Keep in mind that these are top-line results, and histological analysis and pathological scoring of colon tissue is generally part of this experiment; once the full results are in then a more complete conclusion can be drawn. However, the strength of these preliminary data clearly implicates that anatabine may be effective for the treatment of ulcerative colitis in humans, and suggest the possibility of piloting a clinical investigation.

The implications are great in scope. Patients with inflammatory bowel disease (NYSEARCA:IBD) represent an enormous unmet medical need, and existing treatments are expensive, often ineffective, and come with major safety risks. Current gold-standard treatment options are biologic anti-TNF therapies such as J&J's Remicade and Abbott's Humira. These treatments are expensive (over $20K/year), require intravenous infusions in a clinical setting, and carry severe risks such as serious infection and malignancies (cancer). Imagine the potential of a safe, effective compound that could be taken as a pill and would be effective in both the prevention of disease and the treatment of existing occurrences. This type of treatment would be transformational for patients and have an enormous market advantage over the existing treatment paradigm. Also consider that the market for IBD was estimated to be $5.1 billion in 2012 alone, and is predicted to reach $6.2 billion by 2017. Link here.

It should be noted that chronic inflammation of the colon is a major risk factor for colon cancer. Nearly 10% of patients with inflammatory bowel disease (IBD) eventually develop colon cancer, the second leading cause of cancer death in the United States. Link here. The treatments for IBD; Humira, Remicade, corticosteroids, also cause a much higher cancer risk. Link here.

Now let's get back to the quote from the distinguished Dr. Needleman. (Link here). When he says that "phenomenology is very different than pharmacology", he is saying that seeing a drug work is very different than understanding how it works, and this understanding is critical to supporting the clinical development required to bring a medicine to market. In the context of anatabine, recent research from the Roskamp Institute has shown that anatabine effects important inflammatory pathways and biomarkers, and importantly that this effect comes from its ability to prevent the activation of STAT3. This suppression of STAT activity occurs concurrently with the reduction of numerous inflammatory factors such as TNF-αlpha, NF-kB, and pro-inflammatory interleukins. This is the "how" to which Dr. Needleman refers - and it is quite ironic that in these Roskamp studies anatabine was found to be even more effective than Celebrex, the drug invented by Dr. Needleman. Link here. Furthermore, Anatabine's proven ability to modulate the inflammatory JAK-STAT pathway places it broadly in the same pharmacological class as the JAK inhibitors such as Pfizer's recently approved Xeljanz. While certainly effective in the clinic, Xeljanz comes with serious safety risks and an FDA mandated "black box warning" that may limit its use and provide a barrier to market share. In contrast, anatabine has been clinically proven to be safe and well-tolerated, and is unlikely to carry any such safety limitations because it's STAT modulatory activity appears to result from nicotinic receptor agonism rather that JAK inhibition. Link here. This mechanistic distinction seems to allow anatabine to suppress STAT activation while circumventing the nasty safety concurs inherent to the JAK inhibitors.

Now to the risks. Drug development is tricky business, and having solid science in place is no guarantee that a new medicine will be brought to the market. Let's take a look at some of the perils that Star will face going forward:

· Effective corporate governance. Star is currently under investigation for actions relating to stock placements, and while these types of investigations often resolved without consequence, there is uncertainty and risk associated with this situation. This includes a litany of nuisance lawsuits that almost automatically follow such an investigation. Based on Star's stated level of cooperation with the regulatory officials, and vociferous response to the private-party suits, it is my belief that this situation will resolve sooner rather than later. Link here.

· Ability to execute. Even the best ideas and most promising technologies can fail to reach the marketplace if the development and business plans are not painstakingly formulated and perfectly executed. This is especially true in the world of biotech; there are many ways to fail while the path to success can be very narrow and unforgiving.

· Defense of intellectual property. If anatabine continues to encounter success in the clinic, there will no doubt be legal challenges regarding the validity of the patents. This is standard procedure in the pharma business, and as soon as you start making money it's assured that people will start suing you. For example, oftentimes companies file nuisance lawsuits that challenge intellectual property hoping for quick payoffs. Furthermore, potential competitors may look for holes in the patent protection, and try to devise their own competing intellectual property around any gaps.

· There is inherent uncertainty that surrounds experimental medicines and clinical trials. Promising performance in preclinical models does not guarantee success in clinical trials, and success in early, biomarker-driven clinical trials does not ensure that clinically-relevant endpoints will be reached in later, outcome-driven trials.

To summarize, these new results from the University of Virginia demonstrate anatabine's potential for preventing and treating inflammatory bowel disease. This is an important addition to the developing collection of clinical and preclinical science around anatabine that highlights it's potential to treat debilitating autoimmune and inflammatory conditions such as rheumatoid arthritis, thyroiditis, IBD, and well as neuroinflammatory diseases such as Alzheimer's and Parkinson's disease. In support of this, a stream of research emerging from the Roskamp Institute, as well as other academic institutions such as Johns Hopkins and University of Virginia, is elucidating the pharmacological basis of anatabine's anti-inflammatory actions at the molecular level, and providing an understanding of "how" that Dr. Needleman highlights as being critical to bringing a drug to market.

Anecdotal, nonetheless worthy of note; a Big Pharma Ph.D. scientist who specializes in ulcerative colitis research and is out in front of the anatabine science emailed me commenting on the press release. He said. "If I had ulcerative colitis or Crohn's, I would be popping this stuff like M&M's." The "stuff" he mentions is Anatabloc.

* Re studies on mice; we know in the hierarchy of scientific investigations that animal studies do not carry the weight of human studies, nonetheless there is an approximate 80% correlation. Remarkable for example is that 99% of mouse genes have an equivalent in humans making mice ideal for studying. Intriguing from the above link; "More so than any other genetically tractable organism, the mouse offers a close glimpse of humankind in terms of similarity in the underlying physiology, tissue structure and organization." The 2007 Nobel Prize in Physiology and Medicine was awarded to Mario Capecchi, Sir Martin Evans and Oliver Smithies for their pioneering work on gene targeting in the mouse.

Disclosure: I am long STSI. I bought the stock in the open market and have no business relationship the company.

Disclosure: I am long STSI. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.