Global development of YM BioSciences Inc.'s nimotuzumab continued to advance with the start of two late-stage trials by its European partner.

Oncoscience AG started a Phase III trial of the humanized EGFR-targeting monoclonal antibody in patients with glioblastoma multiforme and a Phase IIb/IIIa trial in chemotherapy-naïve patients with advanced pancreatic cancer. Oncoscience, of Wedel, Germany, recently said it completed enrollment in a Phase III trial in children with inoperable brain cancer.

YM BioSciences, of Mississauga, Ontario, gained rights to the product in North American, Europe and the Pacific Rim (excluding China) from the Centre for Molecular Immunology in Havana. It has rights to nimotuzumab in the U.S and Canada and has four partnerships for its other territories, while seven other companies have rights elsewhere.

The epidermal growth factor receptor-targeting drug candidate, also known as TheraCIM, is the subject of about 10 trials, mostly Phase IIs, in at least 10 solid-tumor indications, said David Allan, chairman and CEO of YM BioSciences. He said the new study is the product's first in a randomized Phase III trial, and added that both Oncoscience studies - as well the earlier one in children with brain cancer (diffuse intrinsic pontine glioma) - are designed to support registration.

"This is one more example of how significantly this drug has advanced over the past two or three years," Allan told BioWorld Today. "Every step of the way, we've managed to do things with our partners that I don't think the Street or community expected us to do. To have gotten this drug into Phase III trials, with the prospect of a wave of Phase III trials coming behind it, is quite an achievement.

Allan said a sign of the cooperation among companies developing nimotuzumab is YM's plan to expand the new pancreatic cancer trial into Canada, a move that could lead to quicker recruitment and lower costs. YM already is using that model with Korean partner Kuhnil Pharmaceutical Co. in non-small-cell lung cancer trials.

"The community," Allan said, "will see us doing more and more cooperation between members of the nimotuzumab family," including with Japanese partner Daiichi Sankyo Co. Ltd., of Tokyo, which licensed the product in Japan last year. "It's an interesting model. Small companies like us have the opportunity to participate in and get registration on large trials we couldn't contemplate on our own."

One of the new Oncoscience trials is a randomized, first-line Phase III study comparing nimotuzumab and the current standard of care (radiotherapy and temozolomide) to that care alone in 150 patients with glioblastoma multiforme. The primary endpoint is progression-free survival. Secondary endpoints are response rates and symptom control.

Oncoscience's randomized, placebo-controlled Phase IIb/IIIa study in chemotherapy-naive patients with locally advanced or metastatic pancreatic cancer is comparing gemcitabine plus nimotuzumab to gemcitabine plus placebo. Primary endpoints of the 188-patient trial are time to tumor progression and overall survival. Secondary endpoints include quality of life and response rates.

Oncoscience gained European rights to nimotuzumab through a November 2003 deal with YM. Oncoscience is covering all trial and registration costs in its territory. YM is entitled to at least $30 million in sublicense fees and/or a royalty premium on initial sales, and then tiered royalties after that.

YM's fourth licensing partner on nimotuzumab is Innogene Kalbiotech Ltd., of Singapore, which has rights in certain countries in Southeast Asia. The product is approved for treating certain head and neck cancers in India, China and a few Latin American countries, areas where others have rights - including Biocon Ltd., of Bangalore, India.

YM's ownership in nimotuzumab actually is through its CimYM BioSciences Inc. subsidiary, of which YM owns 80 percent. The remainder is owned by the center in Cuba, which got its stake in exchange for the original license deal.

Allan said one of the potential advantages of nimotuzumab vs. other EGFR-targeting drugs - including Erbitux, Tarceva and Vectibix - is its superior side-effect profile, most notably that it doesn't result in the severe rash characteristic of the other drugs. Several other side effects also appear to be reduced vs.. the approved drugs, he said.

Going forward, Allan said he anticipates a significant expansion of the nimotuzumab program within the five-company group of licensees, and ideally among the seven other "cousin" companies that also have rights. A goal is to have all companies developing the drug under a common, stringent protocol, so data generated by one company could be used to support development by the others.

YM intends to move nimotuzumab forward itself in the U.S. and Canada, although Allan said it is possible that plan could change. The company already had started to put in place marketing and manufacturing infrastructures before its former lead product, the chemosensitizer tesmilifene, failed in a Phase III trial earlier this year. (See BioWorld Today, Feb. 1, 2007.)

YM's other significant product in development is AeroLEF, an inhaled-delivery composition of free and liposome-encapsulated fentanyl for treating moderate to severe pain. It has completed a Phase IIb trial in Canada. An investigational new drug application has been cleared in the U.S., and YM anticipates an end-of-Phase II meeting with the FDA by the end of the year to be followed by registrational Phase III trials in 2008.

YM's stock (AMEX:YMI) gained 8 cents Tuesday to close at $1.58.

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