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Custirsen
—Custirsen, formerlyOGX-011, nowunder license toTevaPharmaceutical IndustriesLtd., or Teva, is a second-
generation antisense drug that targets clusterin, a secretedprotein that acts as a cell-survival protein and is over-expressed in response
to anti-cancer agents.We andOncoGenex jointlydiscovered and conducted the initial development of custirsen. InDecember 2009,
OncoGenex licensed custirsen toTeva as part of a global license and collaboration agreement to develop and commercialize custirsen.
Teva andOncoGenex are studying custirsen for use as an adjunct therapy to enhance the effectiveness of chemotherapy. Custirsenhas
shownpromising results in combinationwith currently available chemotherapies in several tumor types. TheFDAgrantedFast Track
Designation to custirsen for the treatment ofmetastatic prostate cancer in combinationwithdocetaxel.
Teva andOncoGenex are collaboratingon a global Phase 3 clinical program in patientswithmetastatic castrate resistant
prostate cancer, or CRPC, andmetastatic non-small cell lung cancer, orNSCLC. OncoGenex andTeva are evaluating custirsen in two
Phase 3 clinical studies for first- and second-line chemotherapy inpatientswithmetastaticCRPC. OncoGenex andTeva are also
evaluating custirsen in aPhase 3 study as a second-line treatment in patientswithNSCLC. Teva andOncoGenexhave completed
enrollment for the SYNERGY study as a first-line treatment inpatientswithCRPC. OncoGenexhas stated that the FDAhas agreedon
the designof theSYNERGY trial, aPhase 3 study evaluating custirsen, via the special protocol assessment, or SPA, process. ASPA
is an agreement between theFDA and the drugdeveloper that the design andplanned analysis of a study is sufficient to address
objectives in support of a regulatory submission. Teva andOncoGenex expect to report results for the survival primary endpoint from
theSYNERGY study in2014.
OncoGenex and collaborating investigators evaluated custirsen in five Phase 2 studies in combinationwith various cancer
therapies for prostate cancer,NSCLC, andbreast cancer. OncoGenex reported results from a randomizedPhase 2 studyof custirsen in
patientswith advancedmetastaticCRPC. In this study, OncoGenex reported amedianoverall survival of 23.8months inpatients
treatedwith custirsenplus docetaxel compared to 16.9months for patients treatedwithdocetaxel alone. In addition, OncoGenex
reported that the unadjusted hazard ratio, ameasure used todetermine the difference in survival between treatment groups, was 0.61,
representing a 39percent reduction in the rate of death for patients treatedwith custirsen. OncoGenex also reported that patients
treatedwith custirsen in combinationwithdocetaxel tolerated custirsenwell.
OncoGenexhas also evaluated custirsen in aPhase 1/2 combination study in patientswithNSCLC. In January2012,
OncoGenex reported that one- and two-year survival rateswere 54percent and 30percent, respectively, and12percent of patients
were still alive at amedian follow-upof 41months. Themedianoverall survivalwas 14.1months andprogression-free survival was
4.3months.
ISIS-EIF4E
Rx
—
ISIS-EIF4E
Rx
targets the gene that is responsible for producing the protein eukaryotic initiation factor-4e,
or eIF-4E, which cells over-express in a varietyof cancers, includingprostate, lung, ovarian, liver, breast, head andneck, bladder,
colon, thyroid and lymphoma. eIF-4E facilitates the synthesis of factors in the body that support the development, growth, progression
and survival of cancer. In preclinical studies, we and collaborators demonstratedmarked anti-cancer activity in a broad range of
animalmodels of cancer andprovided the first evidence in animals that tumor growthmaybemore susceptible to eIF-4E inhibition
thangrowthof normal tissue. Targeting eIF-4Ehas beenof great interest to the pharmaceutical industry and the oncology community.
However, the pharmaceutical industry considers eIF-4E a difficult protein to targetwith traditional pharmaceutical approaches.
Eli Lilly andCompany completed aPhase 1 studyof ISIS-EIF4E
Rx
inpatientswith cancer that showed that the subjects
tolerated the drugwell at doses up to1200mgperweek. Eli Lilly andCompanyhas rights to license ISIS-EIF4E
Rx
fromus on
predefined terms.
In2010, we initiated aPhase 2programof ISIS-EIF4E
Rx
inpatientswithNSCLC andprostate cancer. The endpoints for both
studies include progression-free survival, overall survival, response rates, time to progression and the reductionof a varietyof
biomarkers. We plan to report data from thePhase 2program in 2014.
Apatorsen
—Apatorsen, formerlyOGX-427, is a second-generation antisense drug targetingheat shockprotein27, or
Hsp27, which is a cell survival protein that cells over-produce in response tomany cancer treatments, includinghormone ablation
therapy, chemotherapy and radiation therapy. Studies have shown that increasedHsp27production is prevalent inmanyhuman
cancers, includingprostate, NSCLC, breast, ovarian, bladder, renal, pancreatic,multiplemyeloma and liver cancers. Studies have also
linked increasedHsp27production to faster rates of cancer progression, treatment resistance and shorter survival duration.
OncoGenex is evaluating apatorsen inpatientswith cancer. In June 2010,OncoGenex reported results from a Phase 1 study
of apatorsen inpatientswith a varietyof cancers. In this study, patients treatedwith apatorsen as a single agent and in combination
withdocetaxel tolerated the drugwell. In addition, apatorsen, when used as a single agent, demonstrateddeclines in circulating tumor
cells at all doses and in all types of cancerOncoGenex evaluated. Apatorsen alsodemonstrated evidence of reduction in tumor
markers defined as declines of prostate-specific antigen, or PSA, levels inprostate cancer and cancer-antigen-125 levels inovarian
cancer.
