Bumping up its offering from 5 million to 6 million shares, Sirtris Pharmaceuticals Inc. brought in the $60 million in gross proceeds anticipated when filing for an initial public offering in March. (See BioWorld Today, March 2, 2007.)

The Cambridge, Mass.-based firm priced its shares at $10 each, the midpoint of the $9 to $11 price range set last month. Net proceeds are expected to total about $54.1 million, or $62.4 million if underwriters exercise their 900,000-share overallotment option in full, and funds will be used to support preclinical and clinical development of existing product candidates, discovery and development work and other company purposes.

In its Nasdaq debut, Sirtris' shares (SIRT) traded as high as $11.40 before closing at $10.76, up 76 cents.

In the company's prospectus it designated about $13.5 million of the proceeds for continued development of SRT501 into Phase II studies in diabetes and other indications. SRT50 is a formulation of resveratrol, which is a natural substance found in red wine that can activate the sirtuin SRT1, an enzyme that affects caloric intake.

While natural resveratrol is unstable and poorly absorbed by the gastrointestinal tract, SRT501 is formulated with excipients to stabilize the substance in its active form and in a particle size that can ensure adequate levels of resveratrol reach the blood.

Following promising preclinical data, SRT501 entered clinical testing, most recently starting a Phase Ib trial in October. That trial is enrolling 90 Type II diabetes patients to receive SRT501 once-daily for 28 days, and data are expected in the second half of this year. A second Phase Ib trial evaluating twice-daily dosing is expected to begin soon, with results in the first half of 2008.

In addition to diabetic patients, Sirtris also plans to test SRT501 in MELAS syndrome (mitochondrial encephalopathy lactic acidosis and stroke-like episodes), an inherited disorder resulting from a mutation in the DNA of mitochondria.

Since MELAS primarily effects muscles and nerves, leading to reduced exercise capacity, many MELAS patients also develop Type II diabetes.

Sirtris intends to seek orphan drug status in that indication and plans to begin a Phase Ib trial in MELAS by the end of this year.

The company earmarked about $14.4 million in proceeds for preclinical and potential clinical development of other drug candidates targeting SIRT1, and another $9 million for research and preclinical work on any of the other sirtuins and related pathways.

Remaining funds will be used to repay existing debt facilities - about $6.9 million - and for general corporate purposes.

Sirtris, which reported a net loss of $5.8 million, for the first three months of 2007, ended the first quarter with $80.2 million in cash, cash equivalents and short-term securities. Those existing resources, plus the IPO proceeds, are expected to sustain company operations through at least the end of 2009.

Prior to the offering, Sirtris' largest shareholder was Waltham, Mass.-based Polaris, which owns 3.2 million shares.

After the offering, Polaris' stake totaled about 11.7 percent. Other principal stockholders include TVM V Life Sciences Ventures GmbH & Co., which holds 2.6 million shares, or 9.3 percent after the offering; John W. Henry Trust, which holds 2.3 million shares, or 8.2 percent; CHP II LP, with 2.1 million shares, or 7.5 percent; Skyline Ventures Management, with 1.8 million shares, or 6.6 percent; Three Arch Management, with 1.7 million shares, or 6 percent; and Wellcome Trust, with 1.1 million shares, or 4 percent.

Following the offering, the company had about 27.8 million shares outstanding.

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