Agouron Pharmaceuticals Inc., which has generated the mostattention with its HIV drug, got all it wanted out of its cancerprogram Thursday in a deal potentially worth much more than $75million.
Agouron, of La Jolla, Calif., and Hoffmann-La Roche Inc. signed abinding letter of intent for worldwide development of two cancerdrugs Agouron is developing _ one in pivotal studies and the secondnearing clinical trials. A third area of the collaboration involves ananti-cancer program both companies are researching.
The deal calls for an initial license fee of $15 million for Thymitaq(AG337) and the preclinical compound, AG3340, with milestonepayments up to $40 million. In addition Roche, of Nutley, N.J., willpay 80 percent of further development costs for the two drugs.Agouron retained the right to share in marketing of the drugs in NorthAmerica and would get 50 percent of profits.
For the third program, focused on cell cycle control, Roche willprovide $3 million in annual research support and offer milestones of$20 million, as well as contributing 80 percent of post-researchdevelopment costs.
Agouron's stock, which has skyrocketed over the past year as thecompany advanced the HIV protease inhibitor Viracept, gained 75cents Thursday to close at $40. The company has about 10.4 millionshares outstanding.
"We've been working a long time on getting a deal that had thesedynamics," Agouron President and CEO Peter Johnson toldBioWorld Today. "We set some objectives for ourselves and arepleased Roche found our objectives in line with theirs."
Johnson said the three primary objectives were being rewarded forthe investment Agouron made to date through significant front-endand milestone payments, which was accomplished through the $75million potential. A second factor was retaining a sales and marketingrole for the cancer products in North America, while getting a partnerthat can reach most of the rest of the world. And thirdly Agouronwanted to off-load some of the $100 million to $200 million indevelopment costs these programs will require, as well as gainingtechnical assistance, he said.
Thymitaq, which inhibits the enzyme thymidylate synthase, recentlywas taken into pivotal Phase II/III studies for head and neck cancersand liver cancer. Enrollment of about 400 patients is under way at 20centers in the U.S., with other sites being readied in Asia and Europe.Johnson said under a best-case scenario a new drug applicationwould be filed at the end of 1997.
Agouron studied Thymitaq in six Phase II trials against six solidtumor types. Results in head and neck and liver cancers appearedmost encouraging, so those were taken forward into pivotal studies.Primary endpoints in the trials are objective responses as measuredby changes in tumor mass, quality of life for patients and survival.
The second compound in the deal, AG3340, is from a class of drugsthat inhibit selected matrix metalloprotease (MMP) enzymes. Phase Istudies are expected to begin this fall.
The third part of the deal initially centers around small moleculedrugs that inhibit cdk4, from the family of enzymes called cyclindependent kinases that has been implicated in proliferation of cancercells. Both Roche and Agouron have research programs in cdk4inhibitors.
Another part of the deal gives Agouron the right to commercialize aRoche anti-cancer product to be named later. Roche will leadcommercialization of the compounds outside North America and willpay sales royalties to Agouron (in some cases Agouron will shareprofits).
Johnson said the shared marketing rights in North America wereimportant to Agouron, particularly since the company has retained allmarketing rights there for its HIV protease inhibitor. He said sales ofcancer and HIV products can be complementary because of thedegree of geographical overlap, allowing them to be addressed withthe same, small marketing organization.
Agouron's lead product, the HIV drug Viracept, is in a pivotal studyin more than 700 patients. Assuming results are positive Agouron ison track for a new drug application for Viracept early in 1997,Johnson said. Results to date have suggested the product may bebetter than the protease inhibitors that have been approved in the pastsix months.
Johnson said its no coincidence Agouron is focusing on two life-threatening diseases (HIV and cancer) that enjoy favorable regulatoryenvironments.
The second area of the Roche collaboration _ inhibition of matrixmetalloprotease _ has been well publicized because of the positiveresults seen to date of marimastat, the lead drug in the class beingdeveloped by British Biotech plc, of Oxford, England.
MMP inhibitors don't kill tumors but stop them from spreading,offering the potential for long-term control of diseases such as breastand prostate cancer, Johnson said. An advantage of Agouron's MMPinhibitor over others in development, he said, is that it is highlyselective, so it doesn't inhibit MMP enzymes involved in normalprocesses. n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.