ARRY » Topics » AstraZeneca - AZD6244 / MEK Program

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.

 

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Table of Contents

 

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 capsule’s 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.

 

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.



 



6
















Table of
Contents



 



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 capsule’s 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.



 



EXCERPTS ON THIS PAGE:

10-K (2 sections)
Aug 15, 2008
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