Most Sirtuin Investor Readers Using Resveratrol

The SI Blog Resvertrol Usage Poll is has closed. Not suprisingly 80% of those polled are taking resveratrol. Almost 1/2 of those polled are taking in excess of 200mg per day. Here are the final results:

I don't take any --- 19%
Up to 100 mg ----- 11%
Up to 200 mg ---- 20%
Up to 1,000 mg -- 26%
Over 1,000 mg --- 22%

Given that Sirtris dosed at 5,000 mg and 2,500 mg in its recent Type 2 Diabetes clinical trial without any significant adverse effects it does not seem surprising that those somewhat knowledgable about sirtuins are taking rather high doses.

Cancer and Sirtuins: Activate or Supress??

There seems to be some conflicting ideas with regard to targeting sirtuins to fight cancer. Sirtris is researching how activation of sirtuins can stop cancer growth while others are looking to de-activate sirtuins to achieve the same result:

From Sirtris 2/20/08:

CAMBRIDGE, Mass., Feb 20, 2008 (BUSINESS WIRE) -- Sirtris Pharmaceuticals, Inc.
(NASDAQ: SIRT), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced that Sirtris co-founder David Sinclair, PhD, Harvard Medical School Associate Professor of Pathology, will present data showing that SIRT1 activation can suppress tumor formation and growth in the intestine and colon in a preclinical model of colon cancer. These are the first in-vivo data showing that SIRT1 overexpression can suppress tumor formation and growth. These data are the work of Sirtris Scientific Advisory board co-chairs Sinclair and Leonard Guarente, PhD, the Novartis Professor of Biology at the Massachusetts Institute of Technology

From Sirtris 2/21/08:

The National Cancer Institute will test the compounds in well-established cancer cell lines which were previously used in the development of novel and existing chemo-therapeutics. The cell lines to be tested include some of the most common cancer types. The program will also test Sirtris' compounds using in-vivo mouse tumor models to determine if the compounds reduce or limit the growth of the tumor cells. Previous studies have shown that calorie restriction--a method which has been shown to increase SIRT1 activation--can exert strong tumor suppressor effects in mammals and increase lifespan in organisms. Through direct activation of the SIRT1 enzyme with Sirtris' compounds, researchers in this study will be able explore the enzyme's role in tumor suppression along multiple pathways.

Exerpt from From University of Bath press announcement (undated, but recent):

"...Studies have shown that increased levels of these enzymes, known as sirtuins,
are found in tumours from a range of different cancer types.

This suggests that, by finding a way of preventing these enzymes from working, it may be possible to halt the progression of cancer by stopping tumour cells from
dividing and growing. "

Sirtuins In Men's Skin Beauty Product??

Sirtuin activation has now found its way into men's high end skin care products as a company called Alford & Hoff has jumped on to the band wagon. As sirtuin research expands exponentially and continues to show expanding potential health benefits, the roster of companies looking to capitalize also continues to expand. Are we in the early stages of a mania? Time will tell. An interesting aspect of this sirtuin based product expansion is whether any of these companies are researching patent infringement issues before coming to the market. The other angle is whether these products really do anything!

Chris Westphal Comments on Stock Price

At the BIO CEO & Investor conference today, Chris Westphal commented on the stock price action of SIRT since the IPO. He mentioned how the stock rallied strongly after the IPO and corrected down significantly after the 6 month lock-up expired and venture capitalists sold off 20% of the market capitalization over the last six weeks. Of most interest to the Sirtuin Investor was his comment regarding SIRT's stock price... "...has corrected down significantly. We view this as a buying opportunity for the company."

I'm glad to hear Dr. Westphal say this and I expect that he and other top SIRT employees will refrain from any further insider sells, 105b-1 plan or not, for the forseeable future as discussed in previous blog entry dated January 31st.

SRT501 Not Likely a Stand Alone Type 2 Diabetes Drug

In the Q&A at the BIO CEO & Investor Conference, Christoph Westphal mentioned that SRT501's future as a drugable treatment of Type 2 Diabetes may lie in the pairing of it with other drugs such as metamorfin. The NCE, which is 1,000 times more potent than SRT501, is viewed within the company as the better candidate for stand alone type 2 diabetes treatment. Data in the next few months should provide the information necessary to make this determination on SRT501.

Do your own DD.

SRT501 To test Against Cancer in 2008

At the BIO Investor & CEO Conference today, Dr. Chris Westphal disclosed that Sirtris Pharmacueticals would commence SRT501 clinical trials in humans for the treatment of cancer. He mentioned that many resveratrol studies have shown effects on cancer.

From Wikipedia:

Cancer Prevention
In some lineages of cancer cell culture, resveratrol has been shown to induce apoptosis, which means it kills cells and may kill cancer cells.[35][36][37][38][39][40] Resveratrol has been shown to induce Fas/Fas ligand mediated apoptosis, p53 and cyclins A, B1 and cyclin-dependent kinases cdk 1 and 2. Resveratrol also possesses antioxidant and anti-angiogenic properties.[41][42]

Resveratrol is under extensive investigation as a cancer chemopreventive agent.[43][44] Indeed, there are studies showing that small doses of dietary resveratrol can reduce colon carcinogenesis in rats and mice.[45] One German study has already been shown to that under special conditions, resveratrol induces apoptosis in human fat cells. In addition, it inhibits production of cytokines which are involved in the development of obesity-related disorders.[46]

Do your own DD.

Hopping onto the Sirtuin Bandwagon

We are now seeing other groups hopping onto the sirtuin bandwagon. Here are a couple of non profit research centers, one in India and one in PA that are combining forces in the area of sirtuins.

Press Release
Wistar on Sirtuins

SI projects that before this year is done we will begin to see one or more OTC Bulletin Board stocks pop up (probably through reverse mergers) with no real hope of commercial success but with fantastic claims of grandeur. Their press releases will focus on the huge size of the market of drugs related to diseases of the aging. It happens all the time once a great idea catches fire.

Basic Foundation of Type 2 Diabetes Treatment Crumbles

In a startling development in Type 2 diabetes treatment, a wide held pillar of belief that aggressively keeping one measure of blood sugar (called HbA1c) below 6 instead of the standard 7.5 would reduce heart attacks and other cardiovascular events has crumbled. Businessweek has a very thorough article on this startling development.

How this will effect Sirtris Pharmaceutical’s SRT501 and NCE diabetes drug candidates cannot be known at this time. However, I find this excerpt from the Businessweek article particularly interesting:

"However, the evidence that aggressive blood sugar control using drugs brings benefits has always been weak. Proponents of more intensive drug treatment cite a landmark study started back in the 1970s called the U.K. Prospective Diabetes Study (UKPDS). In that trial, researchers followed thousands of patients with type 2 diabetes for more than a decade, comparing those who merely got advice on diet and lifestyle to those who took drugs to lower their blood sugar and keep it under tighter control. The researchers claimed the more aggressive treatment worked to reduce the complications of diabetes, which include kidney failure, blindness, amputation of infected limbs, and cardiovascular disease.

But in fact, the benefits seen in the trial were tiny or nonexistent. The study's authors had to torture the data to reach their conclusions, charges Dr. Robert Ewart, associate professor of family and community medicine at Southern Illinois University School of Medicine. "The UKPDS was a particularly egregious example of data manipulation," he says. "There just isn't any evidence that tight control of type 2 diabetes improves outcomes."

Ewart has plenty of company in doubting the trial. No oral diabetes drug "has ever been shown to do anything really good for any patient," adds Dr. Nortin Hadler, professor of medicine at the University of North Carolina at Chapel Hill. "No leg, eye, kidney, heart, or brain have ever been spared." And in a recent New England Journal of Medicine commentary, Dr. Clifford Rosen, chair of the Food & Drug Administration advisory committee that evaluated one such drug (GlaxoSmithKline's (GSK) Avandia), wrote that "the two largest randomized, placebo-controlled trials in patients with type 2 diabetes, the United Kingdom Prospective Diabetes Study and the University Group Diabetes Program, failed to find a significant reduction on cardiovascular events even with excellent glucose control.""

It is nearly impossible to come to any firm conclusions, with any level of certainty, that can interpret this new data. However, no one can argue that the best treatment for type 2 diabetes is what most humans seemingly don't want to hear: EAT LESS AND EXCERCISE MORE! In other words, live a healthy lifestyle. That is where it seems that targeting sirtuins may have advantages over other drug treatments. The basic premise behind sirtuin research is that the activation of certain sirtuins can mimic a calorie restriction diet (CRD). Long time readers on this blog understand that there are many studies that indicate that a CRD has been proven to increase longevity and fight off disease in many mammals (new readers should review early entries on the SI blog to learn about CRD). Could it be that mimicking a healthy diet may be the best way to treat Type 2 Diabetes for those who cannot live a healthy lifestyle on their own? Only time will tell. Interesting stuff.

Sirtris Signs Leonard P. Guarente to Exclusive

Sirtris Pharamcueticals today announced today Leonard P. Guarente, PhD, Novartis Professor of Biology at the Massachusetts Institute of Technology, has signed a new, exclusive consulting agreement with Sirtris Pharmaceuticals. Dr. Guarente first joined Sirtris’ Scientific Advisory Board as Co-Chair in November 2007. Prior to joining Sirtris, Dr. Guarente was formerly a co-founder of Cambridge, Mass. based Elixir Pharmacueticals, another sirtuin focused startup. Elixir recently postponed its planned IPO. Sirtris has establish a leading edge roster of sirtuin research expertise and this new agreement further solidifies its position.

SIRT High Price Poll Closed - 2008 Thoughts

The results of the poll conducted on this blog regarding expectations for the 2008 high stock price of SIRT are now final. No consensus was formed. If you ignore the $10 choice, which is already incorrect, the other choices: $20 -> 23%, $30-> 29% & $40 or above-> 27% or above were pretty much the same.

One year is an eternity in stock market time and the ultimate correct prognostication will be determined by three main factors:

1) Progress in clinical trials and any other related news (i.e., big pharma deals).
2) Level of insider selling.
3) General market conditions.

Sirtuin Investor has a personal 2008 price target of $33 per share with the caveat that insider selling remains somewhat muted throughout the year. Now a little commentary. IMHO, at this early timeframe in SIRT's business business plan, employee and executive insiders have not yet earned the right to sell their shares, from a moral standpoint, despite limited legal restrictions from doing so under SEC regulations. Employee insiders will only legitimately earn the windfall that comes from sales of cheap SIRT stock when at least one of the following occurs:

1) 4 years have passed from the IPO date.
2) Average monthly volume exceeds 500,000 shares for a three month period.
3) The company is on a clear path to profitability.

My logic for these parameters is as follows:

1)4 years have passed from the IPO date.
Once 4 years have passed from the IPO date, the investing public will likely have all
the data it needs to make an informed decision on whether SIRT will ultimately achieve its goals. By this time, any hype created by SIRT management will either have been validated or disproved and a true legimate measurement SIRT's efforts will be reflected in its stock price. In other words, the playing field will have been reasonably leveled between insiders and outside shareholders with regard to where this company is ultimately headed as substansive results of clinical trials will be available.

2)Average monthly volume exceeds 500,000shs for a three month period.
This will be an indication that the company has generated sustainable widespread market interest and will allow insiders to sell without significantly effecting the stock price.

3)The company is on a clear path to profitability.
In the final analysis, this is the only true measurement of management and
employee effectiveness. Until SIRT reaches this, albeit subjective, moment in its history, employee insiders will not have legitimately earned the proceeds of windfall personal stock sales to the public, IMHO.

If 2007 is any indication, 2008 will be a volatile year. As always, do your own due dilligence.
Comments are welcome!

Smoking Linked to Sirtuin Destruction

As reported in Science Daily, the importance of sirtuins to health continues to expand. Now, A University of Rochester scientist has discovered that the toxins in cigarette smoke wipe out the SIRT1 gene. The research shows that without this gene we not only lose a bit of youthfulness -- but the lungs are left open to destructive inflammation and diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer.

With each new resveratrol study, it becomes more clear that sirtuins play a vital role in the many aspects of health and vitality. Harnessing the power of these genes will likely play a critical role in future treatments for many diseases of the aging, a basic premise in the business plan of Sirtris Pharmacueticals.

It is interesting to see that, based on the resveratrol usage poll being conducted on this blog, that many are not waiting for long term studies to get the benefits of resveratrol. Do your own due dilligence.

Sirtris Releases New NCE Mice Study

Sirtris Pharmacueticals reported today that one of its new chemical entities, which is 1,000 times more potent than resveratrol, reduces fat, boosts exercise endurance and improves insulin sensitivity in mice on a high-fat diet. Aside from the diabetes potential of the NCE, Sirtuin Investor wonders: Could SIRT's NCE, at some point, could become the next performance enhancing drug to hit the sports world? Only unlike, steroids it may have a safe profile without steroid side effects. Time will tell.

Nonetheless, while preliminary with regard to human trials, this is certainly good news for SIRT and they will present the data this Saturday at the Keystone Symposia on Diabetes Mellitus, Insulin Action and Resistance Conference.

Elixir Pharmacueticals Postpones IPO

As speculated on the SI blog on January 8th, Elixir Pharmaceuticals has been forced to postpone its IPO, scheduled for this week, as plunging equity markets made a successful offering unrealistic. It is not clear when, or if, the IPO will move forward. Interestingly, it appears that underwriters pulled the plug at the last minute as a NASDAQ ticker symbol, ELXR, was set up today. It is unclear how ELXR will respond to its failed capital raising efforts. Timing is everything.

New Poll on Resveratrol Usage

Many of those who are interested in sirtuins and the possibility of investment opportunities in the same are also likely to be interested in the potential health benefits of taking resveratrol, an activator of sirtuins. The Sirtuin Investor Blog has set up a new poll to find whether readers are taking resveratrol and, if so, how much. The results should be interesting.

Encouraging Price Action on SIRT

After rallying sharply and immediately on the positive SRT501 clinical data on January 8th, SIRT shares subsequently relinquished most of its gains. However, as the market has had time to digest the SRT501 data and the implications of potential future value, the subsequent price action has been very encouraging, given the weak overall markets:



Sirtuin Investor believes that SIRT could easily move towards the upper teens ($17-$19)within the next two weeks as institutional interest increases. Importantly, based on the low volume observed during this rise, the advent of irrational exuberance is still a way off (see SI BLOG 12/17/07).

Do your own due diligence and remember the SI proverb: immortality is expensive.

ELIXIR Pharmacueticals Prices IPO

In an amendment to its S-1 filing with the SEC, Elixir Pharmaceuticals revealed that it hopes to sell 5,750,000 shares at $16 or $92,000,000, an increase of $1 per share over an earlier filing. Apparently, ELXR and its underwriters hope to ride the wave of excitement generated by both Sirtris and other companies that presented at the JP Morgan Health Care conference.
ELXR S-1A Filing
The Sirtuin Investor speculates that the current equity market anxiety will make a successful IPO difficult. If the IPO is successful, Elixir will become the third public company that has announced a formal research program that focuses on sirtuins in the development of new drugs, Pharmion and Sirtris are the others.

Due your own due dilligence and remember....immortality is expensive

SI Blog Covers the JPMorgan Presentation

A few of the Sirtuin Investor observations from the JP Morgan presentation (readers can review the actual press release on the Sirtris news feed shown in right column):

-Christoph Westphal, M.D., Ph.D., CEO and Vice Chair of Sirtris made an eloquent and highly well thought out step by step presentation that took the audience from the first studies on calorie restriction in the 1930s to the just released clinical data on SRT501.

-SRT501 provides a 5 fold exposure to resveratrol than the natural substance.

-Mr. Westhpal's most significant quote: "...to summarise the data, we are certainly positively surprised."

-Finally, here is the prospective news flow calendar:



As the chart shows, the news flow will remain healthy throughout the year.

Carefully do your own due dilligence because immortality is expensive.

As Predicted on SI Blog : SRT501 Clinical Results Released

As speculated on this blog, Sirtris Pharmacueticals released the results of its Phase 1b clinical study of SRT501 at the 26th Annual JPMorgan Healthcare Conference. The news was terrific:

"This 28-day Phase 1b study was designed to assess the safety, tolerability and pharmacokinetics of once-daily, orally administered doses of either 2.5 g or 5 g of SRT501 in patients with Type 2 Diabetes who were naïve to other diabetes drug treatments. Both doses of SRT501 were found to be safe and well-tolerated, and pharmacokinetics, a measure of drug levels in the blood, were identical at days one and 28, suggesting no drug accumulation. There were no serious adverse events and no dose-related adverse events. Importantly, SRT501 showed a statistically significant improvement in an oral glucose tolerance test on day 28 at two hours and a trend towards lower fasting plasma glucose levels."

For SIRT investors the good news translated into a 14% gain in after hours trading as SIRT rose sharply from $13.19 at the close to $15 at 5:00PM. Tomorrow should be a very interesting day.

SIRT SEC Filing - Emphasis on Change in Control

In an 8-k filing filed yesterday changes were made to the employment agreements of senior management. The most interesting aspect was related to a change in control:

"On January 2, 2008, upon a recommendation of the Compensation Committee of the Board of Directors, the Company entered into amended and restated employment agreements with Christoph Westphal, Garen Bohlin, Peter Elliott and Michael Jirousek, to make the payments and benefits payable to these executive officers in certain circumstances more consistent with each other and reflective of current market terms for similarly situated executives. The agreements provide that a certain percentage of the options and restricted stock held by each of these executive officers, other than Mr. Westphal, will vest upon a change in control (as defined in the agreements), and the remainder of the options and restricted stock will vest upon termination by the Company without cause (as defined in the agreements) or by the employee for good reason (as defined in the agreements) within a certain time period following the change in control. Mr. Westphal's employment agreement was amended to provide that all of Mr. Westphal's unvested options, in addition to his restricted stock, will fully vest upon a change in control. Additionally, if any of Messrs. Westphal, Bohlin, Elliott or Jirousek is terminated during a specified period following a change in control without cause or for good reason, each officer, other than Mr. Westphal, will each receive a lump sum payment equal to 12 months base salary. Mr. Westphal will receive a lump sum payment equal to 18 months of base salary. Each executive officer will also receive a pro-rata portion of the target bonus he would have received for the year in which the termination occurs."

Those who have closely followed SIRT and this blog are aware that big Pharma has been keenly interested in the progress Sirtris has made on Sirtuin research. These amendments to management compensation agreements appear to be a tacit acknowledgement that at as SIRT progresses as the leader in sirtuin research, it will further position itself as an attractive acquisition target.

Do your own DD.

Small Float: The Good, the Bad and the Ugly

For investors in SIRT, the last month and a half has seen both titillating exhilaration and stomach churning pain. This stock chart clearly illustrates this:



We all love to feel the exhilaration and loathe to feel the pain. However, a story stock such as SIRT with low float and limited liquidity, where the future is unlimited but the risks are high, tends to act in this schizophrenic manner. Throw in some venture capital sales of cheap stock and a lull in the news flow and the SIRT stock chart speaks for itself. The interesting thing about story stocks like SIRT is that when substantive good news comes along, sharp declines are often followed by steep climbs. One way to deal with this volatility is to own a long term core position and an equal trading position. Own no more in total than you can afford to lose and take the trading position off the table after a sharp rise. How sharp a rise? Who the hell KNOWS!!! That is the $501,000,000 question.

With SRT501 clinical trials from India due out any day now and with a little luck, we could see the chart turn upside down!!



On January 7th, SIRT is presenting at the 26th Annual JPMorgan Healthcare Conference. Clould this be the day they announce the SIRT501 clinical trial results?

Good luck and do your own due diligence.....and please visit our sponsors on this blog. Remember, immortality is expensive!