With the apoptosis drug AT-101 in several Phase II cancer trials, Ascenta Therapeutics Inc. raised $50 million in a Series C financing.

The San Diego-based company received $30 million in its first tranche; the remaining $20 million will be payable upon the completion of certain undisclosed development milestones. Altogether, the money should last "over a couple of years" and be sufficient to complete several Phase II trials with AT-101 as well as advance Ascenta's two preclinical programs into the clinic, according to CEO Mel Sorensen.

Interest in apoptosis-based cancer drugs has surged over the past decade or so, based on recognition that cancer is a disease not only of unregulated cell proliferation, but of unregulated cell survival. Many biotech and pharma companies are evaluating a variety of approaches to restoring the natural cell death process of apoptosis in cancerous cells, but Mike Powell, general partner with Sofinnova Ventures, said that's not a bad thing.

"Cancer is a big space - there's room for plenty of players," he said. Powell added that he would rather be second or third to pursue a target than first, quipping that the difference between pioneers and settlers is that the pioneers "are the ones with the arrows in their backs."

Ascenta's AT-101 approaches apoptosis through Bcl-2 inhibition. The drug's combination of oral administration, a small-molecule mechanism, and inhibition of all five known anti-apoptotic Bcl-2 proteins help to differentiate it from Bcl-2 inhibitors in development by Genta Inc., Gemin X Biotechnologies Inc., Abbott Laboratories and Santaris Pharma A/S.

AT-101 currently is being studied in Phase II prostate cancer trials both as a monotherapy and with docetaxel and prednisone, in Phase II chronic lymphocytic leukemia and non-Hodgkin's lymphoma trials with Rituxan (rituximab, Genentech Inc. and Biogen Idec Inc.), and in a Phase II small-cell-lung cancer trial with topotecan. The National Institutes of Health is conducting additional clinical trial work. Initial data have demonstrated clinical responses in CLL and decreases in prostate-specific antigen levels in prostate cancer.

"We try to let the science guide us," Sorenson said. "We're doing several trials, but we're seeing activity, so we're following that activity."

Sorensen added that the Series C will fund the ongoing Phase II trials to completion. As for selecting a Phase III indication, that will depend on the Phase II efficacy and the regulatory hurdles in each potential indication.

Beyond Bcl-2, Ascenta's lead preclinical program seeks to restore apoptosis by interfering with the ability of MDM2 to bind and control the non-mutated version of pro-apoptotic protein p53. A lead candidate in the program is undergoing late preclinical studies. A second preclinical program centers on small-molecule mimetics of the recently-identified smac/DIABLO protein, which binds and inhibits the apoptosis-suppressing X-linked inhibitors of apoptosis proteins (XIAPs).

Like Bcl-2, MDM2 and XIAP are the focus of considerable drug discovery interest. F. Hoffmann-La Roche Ltd. and Novelix Pharmaceuticals Inc. are among those in the MDM2 space, while Aegera Therapeutics Inc. and TetraLogic Pharmaceuticals Corp. are joined by big players like Genentech Inc. in the XIAP space.

Another differentiating factor for Ascenta is its business model. Founded in 2003 out of the University of Michigan, the company conserves cash by conducting its discovery work in alliance with universities and its preclinical work in Shanghai, China, where about 20 of its 50 employees are based. Clinical work comes back to the United States to be managed by groups in San Diego and Malvern, Penn.

Powell said that many companies have tried and failed to co-develop a drug overseas, but that Sorensen "put the right people and the right studies in China."

Sorensen added that Perseus LLC, the lead Series C investor, was "equally interested" in Ascenta's compounds and business strategy.

New investor Perseus was joined in the Series C round by all of Ascenta's existing investors: Domain Associates, Sofinnova Ventures, Enterprise Partners, Scale Venture Partners (formerly BA Venture Partners) and US Venture Partners.

The Series C follows a $30 million Series B in late 2004 and a $5.5 million Series A in late 2003, bringing Ascenta's total raised to a hefty $85.5 million.

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