Biotica Technology Ltd. partnered a preclinical program targeting mTOR (mammalian target of rapamycin) in a potential $195 million deal with Wyeth Pharmaceuticals to develop compounds against multiple indications, including inflammatory diseases and cancer.

It marks the first major drug collaboration for Biotica, which was established about a decade ago as a technology-based spinout of Cambridge University. Three years ago, the company made the transformation into a drug discovery firm, and the Wyeth agreement is expected to be "the first of our significant licensing deals," said Mark Bodmer, Biotica's CEO.

Wyeth gains rights to Biotica's portfolio of rapamycin analogues, as well as access to Biotica's polyketide biosynthetic engineering platform to discover additional compounds. Wyeth will handle development and commercialization of selected candidates. In exchange, Biotica is entitled to up to $195 million in up-front and milestone payments and research support. Cambridge, UK-based Biotica also would receive royalties.

The companies will work together on a discovery program using Biotica's technology, which is designed to alter the biosynthetic pathways of polyketides, a class of natural molecules used against several therapeutic areas, to create compounds with improved efficacy and reduced toxicity.

As natural molecules, those polyketides typically are hard to modify using conventional chemistry approaches, but Biotica's platform enables the structural modification of polyketides through the extension or contraction of the polyketide chain.

"That allows us to reverse engineer the chemistry and make the molecules that we want," Bodmer told BioWorld Today.

The company's mTOR inhibitor program, which Bodmer said is at a "fairly advanced preclinical stage," focuses on creating rapamycin analogues with improved profiles to existing mTOR inhibitors.

Wyeth's interest in the program comes as no surprise. The Madison, N.J.-based firm markets Rapamune (sirolimus), an mTOR inhibitor for transplant rejection, and is in Phase III development with temsirolimus to improve survival in advanced renal-cell carcinoma.

Wyeth is "keen to expand on this franchise," Bodmer said, and the new compounds "should complement what they already have."

MTOR, which has been shown to regulate cell growth, has become a popular target to provoke immune suppression in transplant patients, as well as to block nutrients and blood flow to tumor cells. Other companies working in the mTOR inhibitor space include Edmonton, Alberta-based Isotechnika Inc., which reported positive Phase I results in August for its rapamycin prodrug, TAFA93, and Cambridge, Mass.-based Ariad Pharmaceuticals Inc., which reported positive Phase II data in June showing that its intravenously administered mTOR inhibitor, AP23573, more than doubled progression-free survival rates in patients with metastatic and/or unresectable soft-tissue and bone sarcomas. (See BioWorld Today, June 7, 2006.)

"MTOR seems to play a role in a variety of indications," Bodmer said. "We think there's a lot of potential there, and that's why Wyeth was interested in licensing" Biotica's portfolio of mTOR inhibitors.

Beyond that portfolio, Biotica's pipeline has two oncology programs in the lead optimization stage. The first is targeting heat-shock protein 90 (Hsp90), another area that is "garnering a lot of interest in oncology at the moment," Bodmer said.

He said Hsp90 inhibitors involve molecules similar to rapamycin, making them ideal candidates for Biotica's biosynthesis technology.

The company also is working on a research-based program exploring the anti-angiogenesis mechanism for small molecules.