With a closed Series A round and its first product in a Phase I study, Proacta Inc. is working to develop a treatment to attack tumor hypoxia, a condition in which patients have very few options.

The San Diego-based company is developing a new generation of cancer drugs that target the physiological processes of solid tumors. The approach uses a prodrug designed to be activated only in a certain region of the tumor, which reduces potential side effects in normal tissues.

"We’re interested in treating tumors that are hypoxic," said Paul Cossum, president and CEO of Proacta. "They have a low concentration of oxygen, and that makes them particularly difficult to treat with current therapies."

The company has started a Phase I study of PR-104, a hypoxia-targeted small-molecule prodrug expected to improve the outcomes of treatment regimens such as chemotherapy and radiotherapy. It is designed to be activated in the low-oxygen environment of hypoxic tumors.

The study is being conducted at the Waikato Hospital in Hamilton, New Zealand, and at the Peter MacCallum Cancer Centre in Melbourne, Australia. Proacta expects to add a U.S. site to the trial in the near future. It will be a dose-escalating safety study in patients with a range of tumor types, and will use PET imaging with Fluorodeoxyglucose, as well as an imaging agent, to determine PR-104’s impact on tumors. Proacta expects to start a separate trial in the middle of this year to assess the safety of the compound in combination with a standard chemotherapy agent.

Preclinical studies have demonstrated that PR-104, when activated, causes the death of the hypoxic tumor cells and the surrounding tumor cells. That "bystander" effect is what makes PR-104 unique. It also has shown in preclinical models the ability to add to the antitumor activity of other chemotherapy drugs and of radiotherapy, and it has a good preclinical safety profile.

Tumor hypoxia happens in most solid tumors and can make treatment with conventional chemotherapy and radiation less likely to succeed. More than 65 percent of the 10 million people diagnosed each year with cancer have areas of significant hypoxia in their tumors.

Since the compound is at an early stage, Proacta is holding out for more data before naming its partnership strategy.

"We haven’t made any decisions either way," Cossum said. "We’re just waiting to see what the profile of our drug is before making those types of determinations. We will be open to all of the options."

Early investors in the company include South San Francisco-based Genentech Inc. and F. Hoffmann-La Roche Ltd., of Basel, Switzerland, both of which participated in the $12 million Series A round completed in January. Genentech and Roche were joined by lead investor GBS Ventures, of Melbourne, Australia; New Zealand firms Endeavour i-Cap and No8 Ventures; and Alta Partners, of San Francisco. In connection with the financing, David Mack, of Alta Partners, joined Proacta’s board.

The Series A round began in June 2004 when $8 million was raised. In December 2005, Alta Partners "were invited," Cossum said. "So they contributed $4 million."

Proacta expects to conduct a Series B round later this year, he added.

The company was founded by Bill Denny and Bill Wilson, of the University of Auckland, and Martin Brown and Amato Giaccia, of Stanford University, all cancer researchers. It has more than 20 patents, as well as scientific collaborations with Genentech, Manchester University, Stanford University, the University of Auckland and Onyx Pharmaceuticals Inc., of Richmond, Calif. (See BioWorld Today, March 6, 2002.)

Proacta originally was established in New Zealand and focused on gene therapy, but "that ended up not being fundable, so there was a reworking of the business model around the small-molecule program," Cossum said.

Now, with headquarters in San Diego, Proacta conducts drug discovery efforts at its wholly-owned subsidiary, Proacta Therapeutics Ltd., located in Auckland, New Zealand.

The company currently has eight employees and is named for the words "prodrug" and "activation," which describe the PR-104 series. Cossum expects the company to begin development of another compound from the series soon.

"We hope to have identified one by mid-year," he said.

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