By Mary Welch

When Lawrence Shaw was hired in December 1996 to turn around Xytronyx Inc., he wasted no time.

First, he renamed the San Diego-based company Pacific Pharmaceuticals Inc. Then, he moved the focus of the firm away from the Periodontal Tissue Monitor (PTM, Xytronix's product to diagnose and monitor gum disease), and took aim at cancer therapies — making two deals to acquire or gain rights to proprietary technologies.

From the Wound Healing Group of Oklahoma City, Shaw acquired an exclusive license to a technology that injects a combination of infrared absorbing dye and an immunoadjuvant directly into the tumor, followed by a laser jolt to destroy cancer and other rapidly growing cells — all done with minimal damage to the surrounding, benign tissue.

From Binary Therapeutics Inc., a virtual company, he acquired photodynamic therapy (PDT) technology, which he put to work with Pacific's own photosensitizers, called boronated porphyrin compounds (BOPP).

"We've been busy," Shaw said.

By the end of this year, he expects to begin clinical tests on three anti-cancer therapies in the clinic — and begin to find out whether his steady effort will pay off for Pacific, which raised $10 million in the first quarter of 1997 in a private placement.

"We are doing things one at a time," Shaw said. "We like to think of ourselves as Avis. We're a little company now, but we're working harder."

BOPP, used with PDT, begins a human safety study for brain cancer patients at the Royal Melbourne Hospital, in Australia, this month.

PDT combines light-activated drugs and non-thermal light to achieve a photochemical destruction of cancer cells with little damage to surrounding normal tissue. After light-absorbing dye (or other photosensitizing drug) is injected, the PDT drug heads straight for the cancer cells. A laser is then used to illuminate the tumor with light at the specific wavelength required for absorption by the drug. The light, like the drug, is non-thermal and has no therapeutic effect. However, the light energy of the drug creates a reaction that destroys the cancer cells in a highly controlled manner.

BOPP Aimed At Metastatic Nests Of Brain Cancer

Shaw believes BOPP may be effective in targeting the metastatic nests of brain cancer, which remain embedded in the periphery of the primary tumor but are not detectable or accessible for surgical removal. Preclinical data show BOPP is highly selective for tumor cells and, because it requires a low level of light for activation, may be more effective and require shorter procedure times in comparison to other photodynamic agents.

"The other photodynamic drugs take at least 25 minutes to work," Shaw said. "Ours [works] in a matter of minutes. It's a rapid light activating agent and it's solvable in water, which physicians should like."

Pacific's second project is a cancer immunotherapy treatment aimed at breast, lung and prostate cancer. It involves injecting a green infrared absorbing dye (the photosensitizing drug) and an immunoadjuvant directly into a tumor, followed by illumination with an infrared laser. The light absorbed by the dye raises the temperature within the tumor and destroys it. Perhaps even more importantly, the process triggers the patients' immune response and the cancer cells continue to be destroyed.

"What we've seen is an incredible stimulant of the immune system that doesn't just destroy the primary cells but other ones as well," Shaw said. "We've found that when animals that have recovered are re-challenged with 10 times the dose [of cancer cells], they've had a 100 percent success with those tumors. Usually you hope that 10 to 30 percent survive a re-challenge."

This treatment is expected to enter Phase IA/II trials by the end of the year.

Shaw, a graduate of the University College Hospital Medical School, in London, was corporate vice president of research and development for C.R. Bard Inc., of Murray Hill, N.J., before joining Pacific Pharmaceuticals. He said the animals' ability to develop a mechanism to reject the tumor cells — thus producing a self-generating immune reaction — is "very unusual, and we don't understand it."

And that's good, he added. "If it's for real, and a novel mechanism, then we wouldn't understand it," he said. "If we did understand it, then someone else would have discovered it already."

Chemosensitizer Also Under Development

Pacific is also developing a chemosensitizer that will be mainly aimed at fighting brain cancer. The treatment uses O6 benzyl guanine (BG), which is a class of compounds that enhance the effectiveness of chemotherapeutic agents or O6 alkylators.

The company has worldwide rights to BG and intends to initiate Phase II/III efficacy studies in cancer.

Cancer cells often build up a resistance to O6 alkylators, which act by causing damage to the tumor's DNA. AGT (O6 alkylguanine-DNA0) repairs the damaged DNA and protects the cancer cells. The company's proprietary BG binds irreversibly to the tumor AGT repair protein and blocks the tumor DNA repair process — and the inactivation of the AGT protein by BG overcomes tumor resistance to the O6 alkylating chemotherapeutic agents.

Pacific also signed a five-year agreement with Steri-Oss Inc., of Yorba Linda, Calif., for the European distribution of its PTM kit, known as PocketWatch. PTM is an eye-readable, chair-side disposable test for use in the dental office to assist in the early detection and diagnosis of periodontitis.

"In the next year, we'll have all this data produced and we'll be able to move forward very rapidly," Shaw said. "We'll also be tidying up the corporate structure so that we'll be more viable for institutions to follow us."

On his five-year agenda are plans to have the products approved, develop more products, perhaps enter into some joint ventures and maybe spin off a few companies. The company is a little low on cash, with about $3 million on hand, but a private placement is expected shortly, Shaw said.

"We are carefully raising the appropriate money, and we're thinking of a second offering at the end of 1999," Shaw said. So far, the company has not formally been approached by would-be partners, but a few companies are "sniffing around," he added. *