West Coast Editor

Hana Biosciences Inc. is backfilling its already hearty pipeline with a preclinical product for skin rash associated with epidermal growth factor receptor inhibitor therapy, and putting the name of a scientific pioneer into the headlines again.

Roman Perez-Soler discovered the activity of menadione, a small-molecule phosphatase blocker (vitamin K3), in his lab at the Albert Einstein College of Medicine in New York, where he is chief of the oncology division.

"I don't think there is anybody who's done any molecular biology work [in the area]," said Alex Tkachenko, senior director of business development and operations planning for South San Francisco-based Hana.

For undisclosed terms, Hana acquired from Einstein College a worldwide, exclusive, royalty-bearing license to menadione, with the right to grant sublicenses to patent applications relating to the topical drug.

Menadione, the backbone of vitamin K, lends itself well to development as a pharmaceutical lead, unlike vitamins K1 and K2, which are sold as miracle cures for spider veins and wrinkles - though Tkachenko noted there is "no evidence" they have any effect.

Formulation might have a lot to do with that.

"It was a new area for us, but when we started digging a little bit, it turns out for topical compounds, formulation makes a huge difference," he said. "Normal skin is built not to let stuff through. It's fair to assume that none of the natural cures' have been formulated with that in mind." Hana likely will use Dowpharma, the San Diego-based biotechnology unit of Dow Chemical Co., for its formulation of menadione, Tkachenko said.

Einstein College's Perez-Soler has been involved with EGFR drugs since about 1992, helping with some research on Iressa (gefitinib, AstraZeneca plc's tyrosine kinase inhibitor pill for advanced non-small-cell lung cancer) and Erbitux (cetuximab for colorectal cancer, from ImClone Systems Inc. and Bristol-Myers Squibb Co.), and even more with Tarceva (erlotinib, also for NSCLC, from Genentech Inc. and OSI Pharmaceuticals Inc.), with which he conducted a Phase II trial.

Scientists offered results at the American Society of Clinical Oncology meeting this year that showed menadione reversed EGFR inhibition caused by cancer treatments Erbitux and Tarceva, and the compound also rescued EGFR signaling activity in animals treated systemically with Tarceva.

Another EGFR drug that recently made news is Amgen Inc.'s Vectibix (panitumumab) for colorectal cancer, approved late last month. (See BioWorld Today, Sept. 29, 2006.)

As long ago as May 2004, Perez-Soler told BioWorld Today he was "convinced that the patients who develop rash are those who live longer." With menadione, they might be able to live longer and be rash-free.

At the ASCO meeting in 2003, OSI said Tarceva data from a Phase II trial showed "very strong correlations of [skin] rash to survival outcome in lung, ovarian and head and neck cancer. In essence, those patients [who developed the skin rash side effect] did markedly better from a survival outcome perspective than those who didn't." Erbitux researchers already had noted this, although OSI's were the first to find it, in late 2002, said OSI's CEO Colin Goddard.

"In patients who have the most profound rash, the last thing you want to do is stop therapy," said Mark Ahn, CEO of Hana, because those patients are getting the most benefit.

Tkachenko said no one is certain why. "The least elegant explanation is that, for the EGFR inhibitor to work, the patient's overall well being and immune status has to be at a certain level," he said. Possibly, once therapy starts, EGFR-expressing cells in the skin begin to die, which triggers - in the healthy immune system - a cytokine cascade, and then "all manner of bad stuff starts happening," such as the rash, Tkachenko said.

Another idea: Perhaps the patients who respond to such therapies simply have more EGFRs not only in their tumors but elsewhere, including the skin. Like the others, that theory is "as valuable as what you are paying for it," Tkachenko said.

"This area is so new and the molecular biology is so relatively ill understood, anything people are saying is mostly speculation," he added.

Hana submitted in July a new drug application for its lead product, oral spray Zensana (ondansetron) to prevent postoperative and chemotherapy-related nausea and vomiting, with a launch targeted for early next year.

Hana plans to start a Phase III trial with Marqibo (sphingosomal vincristine) in acute lymphocytic leukemia by the end of this year or by January, and another Phase III in non-Hodgkin's lymphoma in 2007.

Tkachenko cited a "decent chance" the ALL program will begin in December, but the timing depends on tweaks in the trials that the FDA might require. A meeting with the agency is slated for Oct. 31 - about a week after the 45-day deadline expires for London-based GlaxoSmithKline plc to file suit charging Hana with infringement of the patent related to Zofran, GSK's pill version of ondansetron.

Analyst Adam Walsh, with Jefferies & Co. in New York, rated Hana's stock "buy" and set the price target at $13. "Our patent attorneys believe that the '658 patent does not apply to Zensana and that GSK will not bring suit," Walsh wrote in a research report Monday.

Also for cancer, Hana has the orphan drug Talvesta (talotrexin) for acute lymphoblastic leukemia. A non-polyglutamatable antifolate licensed about four years ago from Dana-Farber Cancer Institute Inc. in Boston and Ash Stevens Inc., of Detroit, Talvesta is undergoing a Phase I/II trial in relapsed or refractory ALL.

Three more compounds are in Phase I trials, or nearly, for various cancers.

"Of all the segments in oncology, supportive care is the largest and the fastest growing," Ahn said, though his firm will not emphasize the space over drugs aimed at tumors. Instead, Hana will develop "whatever the oncologist would write [prescriptions] for" in order to manage a cancer patient, he said.

"Some would could call this [approach] technologically agnostic, some would call it technologically promiscuous," Ahn said. "We're not putting on any boundaries, except that it's all oncology, all the time."

Hana's stock (NASDAQ:HNAB) closed Monday at $8.01, down 20 cents.