West Coast Editor

While MedImmune Inc. awaits word from the FDA on the supplemental biologics license application for its flu vaccine and seeks ways to pump sales of Synagis, the firm signed a potential $500 million deal with Infinity Pharmaceuticals Inc. focused on small-molecule cancer drugs targeting heat-shock protein 90 (Hsp90) and the Hedgehog cell-signaling pathway.

"They had an interest in every program we had in the pipeline," said Arlene Perkins, vice president and chief business officer for Cambridge, Mass.-based Infinity. Her company had not planned to take on a partner so early but found MedImmune's offer hard to refuse.

MedImmune, for its part, "wanted something that could be on the market in the next three or four years," she said.

The lead product in the agreement, intravenous IPI-504, is an Hsp90 inhibitor undergoing Phase I trials in multiple myeloma and refractory gastrointestinal stromal tumors.

Infinity gets $70 million up front from MedImmune for coexclusive, shared rights to the Hsp90 and Hedgehog programs, and could get up to $430 million more as milestones are met. The firms will share equally all costs and profits.

For each of the Hsp90 and Hedgehog pathway programs, Infinity is to handle discovery, preclinical development and translational clinical development through proof of concept in humans, with the firms jointly steering clinical work through approval of the first product.

MedImmune, of Gaithersburg, Md., will lead worldwide regulatory strategy, as well as sales and marketing, though Infinity has an option to co-promote in the U.S., contributing up to 35 percent of the total effort.

Hsp90 stabilizes and maintains proteins in the cancer cell. The Hedgehog pathway, normally active during embryo growth, can go wrong in adults and help cancers thrive, including some of the more deadly tumors - those of the pancreas, prostate, lung, breast and brain.

Among those working in the Hsp90 space include San Diego-based Conforma Therapeutics Corp., which Biogen Idec Inc., of Cambridge, Mass., agreed in May to buy for $150 million, plus as much as $100 million in milestone payments. Another is Kosan Biosciences Inc., of Hayward, Calif., which provided data in June from three Phase I trials of its two Hsp90 inhibitors, KOS-953 and KOS-1022, under development with Basel, Switzerland-based F. Hoffmann-La Roche Ltd. (See BioWorld Today, May 4, 2006.)

"We don't believe there's anyone ahead of us," Perkins said.

Notable in the Hedgehog area is the potential $240 million partnership entered three years ago by Genentech Inc., of South San Francisco, and Cambridge, Mass.-based Curis Inc., which last month decided not to advance its topical drug for basal-cell carcinoma but will determine another path for approaching the target, and keep working on a systemic antagonist for solid tumors. (See BioWorld Today, June 12, 2003.)

In the Hedgehog and the Hsp90, Perkins said, she is confident about the potential for compounds to become "the first in class and the best in class."

Dirk Reitsma, vice president of clinical development in oncology at MedImmune, said the time is too early to predict which cancers might be targeted first, but the three-year to four-year goal to market with a compound is realistic.

"If you pick the correct indications, it's definitely within grasp," he said. "With all the caveats [that go with] being in a dose-escalation trial, I think certainly [a Phase II study] with IPI-504 is reasonable." Infinity is working on an oral formulation of that compound, as well. A drug from the Hedgehog program could be in the clinic in a year or a year and a half, Reitsma added.

Infinity is privately held but not for much longer, thanks to its reverse merger with publicly traded Discovery Partners International Inc., of San Diego, disclosed in the spring. (See BioWorld Today, April 13, 2006.)

Infinity will own about 69 percent of the combined business after the merger, will keep the Infinity name and will continue its existing operations, with a post-money valuation of about $235 million.

"The proxy vote is scheduled for Sept. 12, and we're moving full steam ahead," Perkins said, noting that Infinity viewed the Discovery deal mainly as a financing event that will bring between $70 million and $75 million.

Infinity also has a potential $400 million deal with Basel, Switzerland-based Novartis AG to create natural compounds that modulate the Bcl-2 family of proteins, which includes Bcl-2 and Bcl-xL. The protein family is known to mediate cancer cell survival. (See BioWorld Today, March 7, 2006.)

No new alliances are on the horizon, Perkins said.

"Right now, we're going to focus on becoming a public company and capturing the value of these two programs [with MedImmune]," while collaborating with Novartis, she said.

In late July, MedImmune submitted to the FDA the sBLA for use of CAIV-T (cold adapted influenza vaccine, trivalent) in children ages 12 months to 59 months who do not have a history of wheezing or asthma.

CAIV-T is the refrigerator-stable formulation of FluMist, a frozen vaccine approved to prevent influenza in people ages 5 to 49. MedImmune filed for approval of CAIV-T in older subjects about a year ago and received a complete response letter in July from regulators who wanted more information about data already submitted. (See BioWorld Today, July 19, 2006.)

Also in July, MedImmune reported a second-quarter loss per share of 27 cents, more than expected by analysts such as Brian Lian with CIBC World Markets in New York, who forecast 22 cents.

The company, which chalked up lighter than predicted revenues from the monoclonal antibody Synagis (palivizumab) for respiratory syncytial virus, "guided flat year-to-year sales growth" with the compound, Lian wrote in a research note.

"We believe the key questions for MedImmune remain how to re-invigorate the RSV franchise and how to drive the adoption of CAIV-T through label expansion to younger (and eventually older) patients," he said.

Lian called the Infinity deal a "modest positive."