West Coast Editor

The growing-hotter field of Toll-like receptors (TLRs) garnered another research contract from the National Institutes of Health for Coley Pharmaceutical Group Inc., this one for $16.9 million, to make drugs for defense against biological terrorism.

Titled "Innate Immune Receptors and Adjuvant Discovery," the contract from the National Institute of Allergy and Infectious Diseases (one of the NIH's institutes) brings to $35 million the total of such awards gained by Coley.

"We're not a vaccine company, and our strategy is to use the funding we get from sources like the government to expand our technology base, to the extent that it's consistent with our products-driven mission," Robert Bratzler, president and CEO of Wellesley, Mass.-based Coley, said.

"We have three distinct [government-funded] programs," he told BioWorld Today. "The most advanced is ready for the clinic, where we are boosting an anthrax vaccine, hoping you can take a six-dose regimen down to a two-dose regimen."

TLRs, which have inspired efforts by a handful of biotechnology firms, are found on cells that direct immune response by detecting and recognizing specific classes of pathogens. Coley already has shown that its therapeutics targeting TLR9 can stimulate protective immunity against bugs that could be used by terrorists, such as anthrax. (See BioWorld Today, March 23, 2004.)

The company's lead drug, ProMune, a synthetic agonist for TLR9, is in late Phase II studies against advanced non-small-cell lung cancer, malignant melanoma and cutaneous T-cell lymphoma, as a monotherapy and as part of multidrug regimens. ProMune also is known as CPG 7909. "CpG" stands for "cytosine and guanine separated by a phosphate" that links the pair of nucleotides.

Bratzler said the drug is "ready for Phase III," adding that Coley is discussing partnerships. "We'll see how it works out." Asked whether the firm has enough cash to conduct Phase III trials on its own, he declined comment and said Coley would have "another press release about cash in the next week."

By stimulating TLR9, ProMune acts directly and selectively on plasmacytoid dendritic cells and B cells to reverse immune tolerance to malignant cells and drive specific, sustained antitumor responses by antigen-specific cytotoxic T cells and antibodies.

"The second product moving forward nicely is our Phase Ib-stage drug, Actilon, for chronic hepatitis C," Bratzler said. Also a TLR9 agonist, Actilon is designed to induce overproduction of interferon alpha.

"Our goal in Actilon is to establish Phase II proof of concept," he said, noting that "anything is possible" regarding partners. "We'll have something more to say [about Actilon] at a scientific meeting here in Boston in the next few weeks," he added.

The company's efforts have bagged Coley a deal worth up to $260 million with the Strasbourg, France-based Sanofi-Aventis Group, which yielded a $5 million milestone payment earlier this month when a Phase I trial began in allergic respiratory disease. That compound is designed to redirect aberrant immune reactions to allergens by TLR9 activation of dendritic and B cells.

"It's given directly to the lung," Bratzler said.

Other arrangements are in place with GlaxoSmithKline plc, of London, and Emeryville, Calif.-based Chiron Corp.

GSK has a coexclusive license to develop several preventative and therapeutic infectious disease vaccines, as well as a nonexclusive license to develop vaccines in three cancer indications. The pharmaceutical company has started early stage clinical studies of cancer vaccines containing TLR9 agonists, providing Coley with about $15 million so far, with milestone payments and royalties included in the deal.

Chiron's vaccine unit has had a nonexclusive license since December for use of Coley's VaxImmune vaccine adjuvant for use in several infectious disease vaccine candidates. Coley got an up-front license fee, and milestone payments are part of that deal, as well.

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