West Coast Editor

After going public this summer to the tune of $96 million, Coley Pharmaceutical Group Inc. said two Phase III studies have begun with the drug formerly known as ProMune in first-line, non-small-cell lung cancer.

"We feel very good that our drug is in the hands of Pfizer," which will steer the Phase III program, said Robert Bratzler, president and CEO of Wellesley, Mass.-based Coley.

Studies will evaluate the toll-like receptor 9 agonist, renamed PF-3512676, combined with current standard-of-care chemotherapy, as compared to chemo alone. The primary endpoint for both studies is overall survival, and each will enroll about 800 adult patients with Stage IIIb or Stage IV NSCLC.

The deal in March with New York-based Pfizer Inc. gave Coley $50 million up front, in exchange for worldwide rights to ProMune, which is injected subcutaneously. Coley's Phase II study in 112 patients showed potential for both of the major histologic subtypes of NSCLC when added to chemo, and the Pfizer pact could mean as much as $505 million in total, making it one of the larger Phase II cancer deals. (See BioWorld Today, March 25, 2005.)

Another drug, already approved for colorectal cancer, also has shown benefit in Phase II trials when added to chemo for NSCLC - Avastin (bevacizumab), from South San Francisco-based Genentech Inc. And this spring, Phase III data showed Avastin plus paclitaxel and carboplatin improved survival in first-line non-squamous NSCLC by 2.3 months, or 23 percent, over chemotherapy alone. (See BioWorld Today, March 16, 2005.)

"The numbers on histologic subtypes are not well agreed upon," Bratzler noted, but the squamous subtype is said to comprise 30 percent to 50 percent of patients.

"We don't view Avastin as competition because our drug, in principle, can be added on top of other drug regimens," he told BioWorld Today. "Avastin is yet another antibody directed at cancer cells, and we believe that, in the fullness of time, [the Coley compound] will be found to be additive if not synergistic with Avastin."

As with other diseases, combination or "cocktail" therapy is likely to be the way to attack NSCLC, Bratzler said. The condition carries a dismal prognosis - the median life expectancy is seven months to 11 months, "and that's with chemotherapy," he said.

TLR9, found in plasmacytoid dendritic cells and B cells, detects a DNA pattern of invading intracellular bugs called a CpG motif and triggers the immune response. PF-3512676 also is known as CPG 7909.

"We're making big bets on TLR therapeutics," Bratzler said. Coley has four drug candidates based on TLRs, which help immune cells to sense intracellular and extracellular pathogens and start the Th1 response to fight them. Other than cancer, indications include viral diseases, asthma and allergy.

With the firm's whopper initial public offering - 6 million shares at $16 each - came another $10 million raised through a private placement with Pfizer, which bought 625,000 shares for the same price. (See BioWorld Today, Aug. 11, 2005.)

Coley has deals not only with Pfizer but also with the Paris-based Sanofi-Aventis Group, Chiron Corp., of Emeryville, Calif., and GlaxoSmithKline plc, of London, as well as the U.S. government.

"We've had a pretty good cash year in 2005," Bratzler said, estimating the firm holds "multiple years worth of cash at our current spend."

Efforts continue to develop Actilon, the lead TLR therapeutic for hepatitis C virus, which he said is "proceeding nicely in the clinic." Earlier this month, at the American Association for the Study of Liver Diseases meeting in San Francisco, Coley reported Phase Ia and Phase Ib data that show encouraging antiviral activity at doses well tolerated by patients.

Coley's stock (NASDAQ:COLY) closed Monday at $15.98, down $1.11.