•
Spruce is an investigator-sponsored study in combination with carboplatin/pemetrexed therapy in
patients with previously untreated Stage IV non-squamous NSCLC. Enrollment is estimated to be
155 patients and began inAugust 2013.
•
Cedar is an investigator-sponsored study in combination with carboplatin/gemcitabine therapy in
patients with previously untreated advanced Non-squamous lung cancer. Enrollment is estimated to be
140 patients and began inAugust 2014.
•
Rainier is an investigator-sponsored study in combination withABRAXANE and gemcitabine therapy
in patients with previously untreated metastatic pancreatic cancer. Enrollment is estimated to be
130 patients and began inAugust 2013.
ISIS-STAT3-2.5
Rx
—We designed ISIS-STAT3-2.5
Rx
, also calledAZD9150 and formerly ISIS-STAT3
Rx
, to
treat cancer by inhibiting the production of a gene critical for tumor cell growth and survival. Signal transducer
and activator of transcription 3, or STAT3, is over-active in a variety of cancers, including brain, lung, breast,
bone, liver and multiple myeloma and promotes tumor cell growth and prevents cell death.
ISIS-STAT3-2.5
Rx
is our first drug to incorporate our new generation 2.5 chemistry. We believe the
significant potency we observed in our preclinical studies with ISIS-STAT3-2.5
Rx
broadens the therapeutic
opportunities for ISIS-STAT3-2.5
Rx
into many different types of cancer where STAT3 is implicated.
In preclinical studies, ISIS-STAT3-2.5
Rx
demonstrated antitumor activity in animal models of human cancer
with an attractive safety profile. We reported interimPhase 1 data in patients with cancer who did not adequately
respond to prior chemotherapy treatment. In this study, we showed that ISIS-STAT3-2.5
Rx
treatment resulted in
clear responses in patients with advanced cancer with an acceptable safety profile. Based on these data, we
initiated a Phase 2 study in focused patient populations with advanced cancer, including patients with advanced
lymphomas. We plan to report data from this Phase 2 study at a future scientific meeting.
In 2012, we licensed ISIS-STAT3-2.5
Rx
toAstraZeneca as part of a broad alliance to discover and develop
anti-cancer drugs. AstraZeneca is conducting a Phase 1/2 study of ISIS-STAT3-2.5
Rx
in patients with advanced
metastatic hepatocellular carcinoma, or HCC, a type of liver cancer. In November 2014 at the European Cancer
Symposium, AstraZeneca presented results from this study showing that treatment with ISIS-STAT3-2.5
Rx
provided evidence of antitumor activity in patients with HCC. In this late-stage population, several patients
experienced stable disease and one patient experienced a durable, partial response (78% tumor shrinkage) while
on ISIS-STAT3-2.5
Rx
treatment.
AstraZeneca plans to evaluate ISIS-STAT3-2.5
Rx
as an immunomodulatory agent in combination with
MEDI4736, AstraZeneca’s investigational human monoclonal antibody designed to counter tumors’ immune
evading tactics.
ISIS-AR-2.5
Rx
—ISIS-AR-2.5
Rx
, also calledAZD5312 and formerly ISIS-AZ1
Rx
and ISIS-AR
Rx
, is an
antisense drug we designed to inhibit the production of the androgen receptor, or AR, for the treatment of
patients with prostate cancer. Prostate cancer growth, proliferation and progression are all androgen-dependent,
andAR function is involved in disease progression at all stages of prostate cancer. For patients diagnosed with
metastatic prostate cancer, current treatments largely involve opposing the action of androgens by blocking the
androgen receptor or removing circulating androgens. Although androgen deprivation therapy approaches are
initially effective in delaying disease progression in patients with metastatic prostate cancer, over time the course
of the disease will progress in many of these patients. Resistance to current therapies is frequent and can occur
through a variety of mechanisms including the activation of AR signaling in tumor cells through the
amplification, over expression and mutation of theAR gene. Because ISIS-AR-2.5
Rx
can inhibit the production
of all known forms of AR, including variants of theAR gene, we believe that this drug has the potential to be an
effective treatment for all stages of prostate cancer, including prostate cancer patients who are resistant to current
therapies.
In preclinical studies, ISIS-AR-2.5
Rx
demonstrated antitumor activity in animal models of prostate cancer,
including a model resistant to enzalutamide, a small molecule antagonist often used in patients with
castration-resistant prostate cancer. In November 2014 at the European Cancer Symposium, AstraZeneca
presented preclinical results of ISIS-AR-2.5
Rx
showing ISIS-AR-2.5
Rx
can substantially reduce levels of all forms
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