Ariad Pharmaceuticals Inc. has been systematically developing a trio of cancer drugs, reaching Phase II with its lead product, AP23573. Now that drug also is partnered with device company Medinol Ltd. in a deal valued at up to nearly $40 million.

AP23573, which Cambridge, Mass.-based Ariad hopes will affect solid tumors and hematological cancers, in the Medinol deal will be aimed at preventing restenosis - re-blockage of blood vessels after stent-assisted angioplasty.

Harvey Berger, Ariad's chairman and CEO, said the agreement "represents an important use of our lead oncology drug."

"We're looking to do partnerships with medical device and stent companies, of which Medinol is a good example," he said. "We chose Medinol based on the strength of their technology, their capabilities in the marketplace and their manufacturing."

If two products are commercialized, Ariad would receive license fees and regulatory, clinical and commercial milestones equaling $39.25 million, plus royalties. Berger said Ariad "wanted a significant royalty based on user sales" in its medical device deals, but would not disclose the rate with Medinol.

Moving ahead, Ariad simply supplies the drug to Medinol, which will be responsible for developing the medical devices to deliver it. Ariad retains the right to enter two nonexclusive agreements with other device companies using AP23573 in vascular disease. So while the deal is nonexclusive, Ariad will, at best, set up three medical device partnerships for AP23573 in that field.

Medinol, of Tel Aviv, Israel, has a stent technology that increases the uniformity of drug concentration in tissues. The company "had a long-standing relationship with Boston Scientific," a major stent developer, Berger said, and thus is plenty experienced.

Medinol and Boston Scientific, of Boston, were in a supply agreement, but the relationship has deteriorated into a court case that is set to be heard in June.

Now Medinol can look to deliver AP23573, a small molecule designed to inhibit the cell-signaling protein mTOR. The tasks of mTOR include controlling tumor blood supply and angiogenesis by affecting vascular endothelial growth factor. It also mediates tumor cells' response to nutrients and growth factors. But, more importantly for the Medinol deal, it is thought to block the proliferation and migration of vascular smooth muscle cells, which apparently is behind the narrowing and blocking of injured arteries. It's also an analogue of sirolimus, an mTOR inhibitor already approved for use on drug-eluting stents.

In cancer, AP23573 is in Phase II work "in various leukemias and lymphomas and sarcomas," Berger said. "We anticipate initiating clinical trials in several other solid tumors, and we'll talk more about that in the future."

With a deal for devices, is there a partnership in the works for oncology, too?

"Yes and no," Berger told BioWorld Today. "Our plans are to retain all rights in the U.S., but after efficacy data, we'll look at partnering the drug outside the U.S. in oncology."

Beneath AP23573, Ariad has AP23841, a bone-targeted mTOR inhibitor aimed at primary bone cancer and bone metastases, and AP23464, an oncogenic kinase inhibitor being investigated in solid tumors, cancer metastases and leukemia. Both are in preclinical work and Ariad is not "providing guidance on the timing of [investigational new drug applications] at this point," Berger said.

The company is poised to release fourth-quarter and year-end results Feb. 1, but in its third-quarter report it listed a cash position of about $87.4 million, leaving Ariad "in a strong financial position for our plans going forward," Berger said.

Ariad raised $37.4 million in a public offering in March, selling 4.4 million shares at $8.50 apiece, a small premium to the stock's price at the time. The market has stripped some value from the stock (NASDAQ:ARIA) since then, and it closed Thursday at $7.45, up 28 cents. (See BioWorld Today, March 25, 2004.)