These excerpts taken from the ARRY 10-K filed Aug 15, 2008.
AstraZeneca - AZD6244 / MEK Program
We initiated an anti-cancer research program targeting MEK in July 2001, and quickly identified AZD6244, an orally active clinical candidate. AZD6244 and other compounds have shown tumor suppressive or regressive activity in multiple preclinical models of human cancer, including melanoma, pancreatic, colon, lung, and breast cancers. Potential advantages of MEK inhibitors over current therapies include potential improved efficacy and reduced side effects.
In December 2003, we entered into an out-licensing and collaboration agreement with AstraZeneca to develop our MEK program solely in the field of oncology. Under the agreement, AstraZeneca acquired exclusive worldwide rights to our clinical development candidate, AZD6244, together with two other compounds we developed during the collaboration for oncology indications. We retain the rights to all non-oncology therapeutic indications for MEK compounds not selected by AstraZeneca for development. In April 2009, we or AstraZeneca may independently undertake research, development and commercialization of small molecule inhibitors of MEK for any therapeutic indication; however both of us will continue to work exclusively with each other for the development and commercialization of AZD6244 and the other two compounds selected by AstraZeneca in oncology. To date, we have earned $21.5 million in up-front and milestone payments. The agreement also provides for research funding, which is now complete, and potential additional development milestone payments of approximately $75 million and royalties on product sales. AstraZeneca is responsible for further clinical development and commercialization for AZD6244, and for clinical development and commercialization for the other two compounds it licensed.
Under our collaboration with AstraZeneca, we conducted Phase 1 clinical testing in 2004. The trial evaluated tolerability and pharmacokinetics of AZD6244 following oral administration to patients with advanced cancer. In addition, the trial examined patients for indications of biological activity as well as pharmacodynamic and tumor biomarkers. Phase 1 testing showed that AZD6244 inhibited the MEK pathway in tumor tissue at the dose that was later selected for the Phase 2 studies and provided prolonged disease stabilization in a number of cancer patients that had previously received numerous other cancer therapies.
In June 2006, AstraZeneca initiated a Phase 2 study for AZD6244 in malignant melanoma, resulting in a $3 million milestone payment to us. The trial was a randomized Phase 2 study that compared AZD6244 to Temodar® (temozolomide) in the treatment of stage III / IV melanoma patients. AstraZeneca enrolled approximately 180 patients at 40 centers worldwide. AstraZeneca also initiated additional Phase 2 studies for AZD6244 in colorectal, pancreatic and non-small cell lung cancer during 2006.
During fiscal 2008, AstraZeneca reported the following progress on the program:
· AstraZeneca presented Phase 1 clinical trial results at the 2008 American Society of Clinical Oncology, or ASCO, annual meeting of a new AZD6244 capsule formulation that replaces the mix/drink formulation used in all prior trials to date. The new capsules maximum tolerated dose was 25 percent lower yet provided, on average, higher exposure than historical values for the mix/drink formulation. The study also reported a complete response in one of the patients.
· AstraZeneca also presented Phase 2 clinical trial results of AZD6244 at ASCO:
o In Phase 2 trial results comparing AZD6244 to Alimta® (pemetrexed) in 84 non small cell lung cancer, or NSCLC, patients, neither of these drugs demonstrated superior efficacy.
o Phase 2 results showed no difference between the two treatment arms in the overall population comparing AZD6244 to Temodar® (temozolomide) in patients with advanced melanoma. The safety and tolerability profile for AZD6244 was found to be consistent with that reported from the Phase 1 trial.
o Phase 2 results comparing AZD6244 to Xeloda® (capecitabine) in patients with metastatic colorectal cancer showed that AZD6244 was generally well tolerated, with neither of these drugs demonstrating superior efficacy.
· AZD6244 is also being investigated in a number of studies conducted by the National Cancer Institute in collaboration with AstraZeneca.
AstraZeneca also announced two additional Phase 2 trials of AZD6244 at ASCO. Preclinical data suggests that the potential benefit of AZD6244 may be maximized in some tumors when delivered as combination therapy. The two planned trials will be exploring combinations in advanced melanoma and non-small cell lung cancer, or NSCLC patients. Patient enrollment is expected to begin during the first quarter of calendar 2009.
We initiated an
In December 2003, we
Under our collaboration
In June 2006, AstraZeneca initiated a Phase 2
During fiscal 2008, AstraZeneca reported the following