West Coast Editor

Portola Pharmaceuticals Inc., three months after in-licensing a venous-thrombosis program from Millennium Pharmaceuticals Inc. (the company from which it was spun), raised $46 million in a Series B financing to advance the oral Factor Xa inhibitor and the ADP receptor agonist.

With the cash now on hand, "we think we can get into important Phase II data in Factor Xa and early-to-mid Phase II data with the ADP program," said Charles Homcy, president and CEO of South San Francisco-based Portola.

The once-daily Factor Xa blocker - which acts directly on the blood coagulation enzyme, a target involved in making thrombin - is expected to enter Phase II trials next year, and the ADP receptor antagonist, an arterial-thrombosis therapy being developed in oral and intravenous forms for acute and chronic coronary syndromes, is bound for Phase I in the first quarter of next year also.

"If we were to expand into the broader trials for real large markets [such as secondary prevention of acute coronary syndromes], that would ultimately require finding the right partner" for Factor Xa, Homcy said - although in the first indication to be tested, prophylaxis of deep-vein thrombosis, the company might go into Phase III on its own.

"We'll be assessing partners along the way," he said.

But with the ADP receptor antagonist, "if Phase I looks good, we would very quickly look for a partner to help us do the right trials," Homcy said.

Portola hopes to show superiority to Plavix (clopidogrel bisulfate), from the Sanofi-Aventis Group, of Paris, and New York-based Bristol Meyers Squibb Co., which targets the same receptor and sells about $6 billion per year.

"When a patient comes in with unstable angina, [he] gets seen in the emergency room and gets a stent or gets bypass surgery and then goes home on medication," Homcy noted. But the doctor needs time to figure out which will be done, and for that requires a compound that provides "high levels of blockade immediately on seeing the patient, and then allows flexibility as to where the patient will be triaged."

Plavix, because it's irreversible, presents problems in that regard. If bypass surgery rather than a stent is decided upon, the Plavix patient must wait about six days for his body to make more platelets, which is the situation in which President Clinton found himself.

As a physician, "you want to know [the patient's] anatomy and fix it quickly," Homcy said. "The idea is to have the interventional cardiologist feel this is the best molecule he can use."

The intravenous and oral forms of Portola's drug will be developed together, in the same trial, going head to head with Plavix.

Portola's third compound, at the preclinical stage, inhibits platelet adhesion to artery walls and targets a potentially broad range of vascular disorders, including atherosclerosis.

"But it's also an anti-thrombotic, and that's how we would develop it," Homcy told BioWorld Today. "The first two molecules are pharmaceutically validated targets, but in this third program, we're talking about a novel target for which no inhibitor exists today. Without going into the details, we think we can get the efficacy without the risk of bleeding."

During the summer, Portola - spun from Millennium in 2003, when it took thrombosis-focused platelet biology research from the Cambridge, Mass.-based firm and raised $21 million in a Series A financing - licensed from its progenitor the Factor Xa program, which targets venous thrombosis, to complement its research. For rights to develop, market and commercialize Factor Xa inhibitors worldwide, Portola agreed to make milestone and royalty payments to Millennium, but there was no up-front payment. (See BioWorld Today, Aug. 9, 2005.)

Advanced Technology Ventures, of Waltham, Mass., led the Series B syndicate. Also participating in the round were Alta Partners, of San Francisco, and all of Portola's previous major investors including Abingworth Management, of London; Frazier Healthcare Ventures, of Seattle; MPM Capital, of Boston; Prospect Ventures, of Palo Alto, Calif.; and Sutter Hill Ventures, also of Palo Alto. Jean George, of ATV, and Farah Champsi, of Alta Partners, will be joining Portola's board of directors.

Mersana Adds To Cash Position

Mersana Therapeutics Inc., of Cambridge, completed an oversubscribed $21 million financing to boost its efforts in cancer therapeutics. Formerly Nanopharma Corp., the privately held, venture-backed firm bases its work on Fleximer, a biodegradable "stealth" material that lets drugs circulate up to three times longer without losing their activity or safety - and "in some cases even longer than that," said Julie Olson, CEO of the company.

"Our strategy is really to take compounds that went to the clinic and showed activity in humans, but couldn't make it all the way to market because of a therapeutic-window problem - because it had a poor half-life, and may have had some side effects," she told BioWorld Today.

The approach is to "smooth out the exposure over a longer period of time," keeping the efficacy high and toxicity low, she said. "In some cases, they are generic compounds and in other cases proprietary."

The Fleximer patents and six related patent families are licensed from the Massachusetts General Hospital, where Mikhail Papisov pioneered the research, and Mersana's pipeline includes compounds with activity against multiple tumor types.

Fleximer "works with small molecules and proteins," Olson said. "With interferon, it acts much the same as [pegylation] does, except that PEG isn't biodegradable. We have a lead candidate that's had proof of concept [work finished]. We're in the IND-enabling stage with that, and a couple of others are in earlier stages."

Nanopharma's new name derives from a Russian word meaning "goddess of the ripe harvest," Olson said. Why the change?

"We'd felt for a while that nano' is somewhat overused, and it's confusing for many people," she said.

Fidelity Biosciences, of Boston, and ProQuest Investments, of Princeton, N.J., led the Mersana round, with New York-based Rho Ventures and the company's previous investors taking part, including PureTech Ventures, of Boston; Harris & Harris Group Inc., of New York; and private investors Ron Cape and John Zabriskie.