Dr. John Faessel
ON THE MARKET
Commentary and Insights
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Redux > Roskamp II: Star Scientific / Rock Creek Pharmaceuticals
Part A: Some highlights of the corporate presentation relevant to the science
Part B (to follow): The new Star business strategy / timeline re FDA / partnership & licensing
Star Scientific (STSI) Nasdaq
redux (ˈriːdʌks)
adj
1.(Usually postpositive) presented in a new way.
"This is how it works" * and the importance of understanding how it works
·Cellular level study is of inestimable value
·Anatabine mimics acetylcholine [ACh] – a chemical messenger
·Key takeaway - Mechanism of action demonstrated
On Thursday March 20, 2014, I attended the Star Scientific, [soon to be Rock Creek Pharmaceuticals (RCPI)] Investor and Analyst Meeting at the distinguished Roskamp Institute in Sarasota, Florida. Link here for access to the entire video webcast of the event.
The Roskamp Institute is a nonprofit medical research organization funded by NIH, Alzheimer's Association, Department of Defense, Veterans Administration and the Roskamp Foundation.
A lot has been happening at Star Scientific since the first Roskamp meeting that I attended on June 1, 2011. That's a long story for another day. Today, I'll just give you my brief takeaway from Thursday's meeting.
The meeting was an in-depth scientific and corporate presentation to about 60 investors, analysts and scientists that was led by Michael Mullan, MD, Ph.D., the new named CEO and Chairman of Star Scientific. I also understand that several hundred more attended the live webcast. Straightaway, Dr. Mullen stated that this would be a "thorough immersion" into the basic science. He then delved into the science of anatabine that has been one of his principal fields of investigation for the past several years in his impressive work of 25 years on Alzheimer's disease.
At the Roskamp Institute Dr. Mullan has pursued significant and far-reaching research on many fronts centering on anatabine. He has been CEO of the Institute for over a decade.
The order of the March 20 meeting presentation reflected Dr. Mullan's longstanding interest in studying central nervous systems [CNS] and brain conditions, and he made clear that this did not necessarily mean that CNS would be the primary target of further research. He went on to say that it's more likely that at Star he would focus on research capable of demonstrating results in a more expeditious manner, as in peripheral conditions such as inflammatory bowel disease [IBD].
The essence of the science of anatabine lies at the cellular and molecular level. Dr. Mullan's presentation demonstrated with slides and videos the novel fashion anatabine works: it mimics the action of the naturally occurring (ligand) neurotransmitter acetylcholine in opening up the cell to agents / 'ions' that change its cellular function.
[img src="file:///C:UsersAdminAppDataLocalTempmsohtmlclip1 1clip_image003.jpg" height="227" border="0" width="340">
One presentation slide (see above) showed in a three-dimensional way how closely anatabine resembled acetylcholine.
[img src="file:///C:UsersAdminAppDataLocalTempmsohtmlclip1 1clip_image004.jpg" height="286" border="0" width="491">
The electrostatic charge depiction of anatabine (see above) also shows how closely it resembles acetylcholine; to be noted is that it binds in the molecule at exactly the same location as acetylcholine.
* In addition, the chemical structure is quite similar.
Wikipedia: Acetylcholine is one of many neurotransmitters in the autonomic nervous system [ANS]. It acts on both the peripheral nervous system [PNS] and central nervous system [CNS] and is the only neurotransmitter used in the motor division of the somatic nervous system. Acetylcholine is also the principal neurotransmitter in all autonomic ganglia.
The main function of acetylcholine is to relay or to communicate different messages to the nerve system.
* Note also the similarities between the chemical structures of anatabine and nicotine.
[img src="file:///C:UsersAdminAppDataLocalTempmsohtmlclip1 1clip_image005.png" height="160" border="0" width="281">
[img src="file:///C:UsersAdminAppDataLocalTempmsohtmlclip1 1clip_image006.jpg" height="194" border="0" width="291">
Observably, the cellular / molecular and biochemistry science "immersion" was well beyond the understanding of much of the audience. But it was of inestimable importance for showing how anatabine mimics acetylcholine's actions of opening up cell gateways at the molecular level, thus allowing anatabine's mode of action to accomplish its anti-inflammatory mission.
More specifically: on binding / introduction of acetylcholine, a change in shape takes place as the receptor opens up cellular gateways and change occurs inside the cell depending on the particular 'ion' that enters the gateway, and with different types of results depending upon the intervention's cellular / molecular "mission" (i.e. inflammation, nicotine addiction, etc.).
Vitally, the demonstration of this mechanism of action is a key proof of principle, and is mandatory for attracting Big Pharma's interest in partnership and/or the licensing of anatabine or its isomer.
Dr. Mullan stated that because anatabine crosses the blood-brain barrier rapidly and easily, it has potential uses in central nervous system [CNS] conditions. To wit, two videos of animal studies that I had seen previously were shown, but much more amplification was given in these presentations than I had seen before. Many of the references to the results of anatabine in the video demonstration were from animals "engineered" to be models of Alzheimer's and multiple sclerosis [MS]. Take 85 seconds to see why Dr. Mullan calls "par excellence" the example of a condition that typifies inflammation, and to see why there is so much interest in anatabine:
·No anatabine: Link here
·With anatabine: Link here
Anatabine reduces the incidence of hind limb paralysis in the standard mice model of multiple sclerosis [MS] and reduces the levels of peripheral cytokines associated with the model, maintaining them at normal levels. These data are consistent with the reduction of NF-kB regulated inflammation seen in the Alzheimer mouse model, and suggests that the overall mechanism is one of reduced cytokine production secondary to reduced NFK-B activity.
As mentioned above, it was suggested that Star is more likely to focus now on research where results can be demonstrated more expeditiously, such as in peripheral conditions like inflammatory bowel disease [IBD], arthritic conditions, auto-immune disorders, and others. The progression of Alzheimer's disease is a slow process and a trial would last 18-months or longer, whereas research on ulcerative colitis / inflammatory bowel disease and some others can be accomplished in a few months.
* The KEY takeaway of the conference
Dr. Mullan spent a great deal of time demonstrating what happens at the molecular and cellular level and notably how anatabine mimics not only the action of acetylcholine but how it is so very closely resembles acetylcholine in both three-dimensional and electrostatic charge representations (see images again); this also gives more credence to mechanism of action.
This is the critical core of a necessary proof of principle that is transferrable to other conditions because, given that what is demonstrated is happening at the cellular and molecular level, it is independent of the attributes of any specific disease.
Said another way: cellular action, regardless of the particular condition being studied, is what is fundamental to anatabine's mechanism of action. It follows that its application or use as a modality of treatment suggests an abundance of potential targets, of which those Dr. Mullan mentioned are only a partial list.
Briefly now to that "essence" and mechanism of action:
On binding / introduction of acetylcholine a change in shape takes place and the receptor opens up and change occurs inside the cell depending on the particular 'ion' that enter the gateway with different types of results depending upon the cell / molecules mission i.e. addiction or inflammation…
* "This is how it works"
* In the Q & A section of the presentation Dr. Mullan made a statement, "this is how it works" referencing generically how a drug could be demonstrated to a drug company regarding proof of principal (and attendant pharmacodynamics) and stated that here lies the real value going forward to gain the interest of Pharma.
For more amplification on this important proof of principle and mechanism of action see the report I wrote regarding Dr. Philip Needleman's, The Ten Commandments of Drug R&Dwhere he references "Commandment Number Two"; "Phenomenology is very different than pharmacology." Dr. Needleman's 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. Dr. Needleman is the inventor of
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