Wednesday, April 30, 2008

Cancer and SRT1: Elixir Versus Sirtris??

Based on seemingly conflicting statements from competing biotechnology companies, it appears that Sirtris Pharmaceuticals and Elixir Pharmaceuticals have conflicting views on the mechanism of how the modulation of SIRT1 expression may one day be used as a cancer treatment. Judge for yourself:

Excpert from Sirtris press release dated April 16, 2008 :

Sirtris Pharmaceuticals, Inc. (NASDAQ: SIRT), a biopharmaceutical company
focused on discovering and developing small molecule drugs to treat diseases of
aging, announced that a research team led by the company's two Scientific
Advisory Board co-chairs has demonstrated that overexpression of the
SIRT1 enzyme can suppress tumor formation
and growth in a preclinical
mouse model of colon cancer, providing the first in-vivo data that SIRT1 can
suppress tumor cell development. The paper, titled SIRT1 Deacetylase Suppresses
Intestinal Tumorigenesis and Colon Cancer Growth, appears in today's issue of
the scientific journal PLoS One.



Excerpt from Elixir website:
Conversely, blocking the amount or activity of SIRT1 has recently been
shown to reverse "epigenetic silencing," a phenomenon that decreases the
expression of important tumor suppressor genes. The implication of these
findings is that blocking SIRT1 could be important in combating several types of cancer.
These observations highlight the large potential, and explain the recent interest, in the discovery and development of compounds which could either
increase or decrease the enzymes of this important class of SIRT targets.


If anyone with technical knowledge of this topic has a logical explanation for this seemingly conflicting information, please post a comment to explain.

Wednesday, April 23, 2008

Will Another Sirtuin Suitor Emerge?

It has now been confirmed by the market, that the intellectual property of the sirtuin platform Sirtris has put together over the last several years has a definitive minimum value of $720,000,000. However, based upon the total lack of buying in advance of the $22.50 buyout offer it is unlikely that Chris Westphal actively shopped the company around to other big pharmaceutical companies. This was an extremely well kept secret. In fact, on the trading day preceding the announcement of the offer, SIRT shares actually declined by over 4%. These observations lead me to believe (and hope) that another large drug company bid is NOT out of the question. If you follow the industry, the drug pipelines at many companies in big pharma have been seen as weak by analysts. It is the pipeline that drives value at these companies.

A review of all the diseases of the aging that are potential targets of the sirtuin platform will make it clear why Glaxo made its bid and why another drug company might feel compelled to take a close look at the bid and carefully evaluate whether a higher bid is in order. A higher bid is still a long shot but it is not out of the question.

Tuesday, April 22, 2008

GlaxoSmithKline offers $22.50 Cash for Sirtris - HOLD OUT FOR MORE!!

In a surprise move, Sirtris Pharamacueticals agreed to a sell out its future for $22.50 per share in an all cash deal worth $720,000,000. This offer certainly substantiates the sirtuin technology platform that Sirtris has been developing over the past several years. However, this is a bittersweet deal for the Sirtris faithful. As posited many times on this blog, the potential of this stock is immeasurable.

The Sirtuin Investor is taking a position on this deal: DON'T SELL @ $22.50!! While this may be a futile attempt as 21.84% of the shares are held by insiders with institutional investors owning another 30.40%, I believe Sirtris shareholders would be better off riding this thing for a few years. Chris Westphal had been guiding for some time now that a joint venture deal with big pharma was possible within a year or so. Readers of this blog KNOW that a future SI hope for SIRT, aside from its potential of becoming a successful drug company, was the potential for irrational exuberance to take hold at some point. Those dreams end with a cash buyout!

When those proxies come in the mail....VOTE NO! And let your views be known by voting in the SI new poll regarding the buyout. Comments about the deal are encouraged.

Friday, April 18, 2008

Second Clinical Trial Results of SRT501 Released

Sirtris Pharmacueticals reported the results of its second Phase 1b clinical study yesterday on SRT501, which involved twice daily dosages of 1.25 grams and 2.50 grams. This study follows up on the safety results of the first study, released this past January, of a single daily doses of 2.50 grams and 5.0 grams. The only difference between the two clinical trials were a single daily dose versus a twice daily dose of the same aggregate daily dosage. Both clinical results demonstrated no significant safety issues. Both studies also showed a lowering of glucose in Type 2 Diabetic patients and signs of efficacy and dose response although the primary focus of the studies were safety.

While this is good news it is hardly unexpected given the safety results of the first study. The more important test of SRT501's viability, will be later on this year when phase 2a data on the effectiveness of SRT501 in combination with the standard of care, metformin will be released. Even if SRT501 does well in this 2a trial, SIRT's 1,000 times more potent NCE may be the more likely candidate to become a stand alone diabetes drug candidate.

In any case, it is the potential of the vastness of the sirtuin platform and the role that Sirtris seemingly plays as gatekeeper with its numerous patents, that makes this a very promising play in biotechnology.

Do your own due diligence.

Monday, April 7, 2008

Home Garden Resveratrol Experiment

The recent announcement by Sirtris regarding its licensing agreement with Bayer Life Sciences got me thinking about my tomato garden. Every spring, I plant six tomato plants and by July the plants bear fruit. There is nothing like the taste of home grown tomatoes. If you've ever grown tomatoes you've probably observed that, in some years, the leaves on the plant may discolor, from the bottom up, and eventually fall off. If it gets really bad the entire plant can die off. The fruit is typically not effected in mild cases but tomato yields may suffer. This is usually caused by a plant fungus that often hits tomato plants called septoria.

I plan on performing my own personal experiment in this year's crop. When I plant my tomato plants this year, I plan on sprinkling 100mg of resveratrol onto the soil surrounding the eventual root spread of 3 out of the 6 tomato plants. Since, resveratrol is a phytoalexin produced naturally by several plants when under attack by bacteria or fungi, it will be interesting to see whether providing resveratrol directly to the roots will have any effect. I'll be reporting on the results as the plants grow. If any SI readers wish to perform the same experiment we can compare notes.

Tuesday, April 1, 2008

Highlight of the Barbara Walters Sirtris Interview

When Barbara asked David Sinclair.. "I think a lot of people will say you're raising expectations, this can't possibly happen." Sinclair answered "My answer to that is, I agree but its TRUE. What else can I say. Aging is really a set of diseases and if we slow them down and cure them, people will live longer, healthier lives." CEO Westhphal added " The major diseases of western society are EXACTLY the diseases that should be able to be treated with the drugs we're developing."

With that the three of them raised their wine glasses and toasted "To the future".........Martin Scorsese couldn't directed a better script, IMHO.

Are you convinced? Skeptical? Are Sirtuins the answer? Is Sirtris the real deal? Vote your your opinion on the new poll to the right and share the actual program excerpt below with friends.


As always, do your own due diligence.