Israeli Teva Pharmaceutical Industries, Ltd and OncoGenex Pharmaceuticals, Inc. Develop New Cancer Treatment
December 22nd, 2009 by Elijah





Teva Pharmaceutical Industries, Ltd., plans to spend $60 million as an equity investment on a new cancer-fighting treatment. The experimental drug, custirsen sodium (OGX-011), is set to enter Phase III clinical trials in 2010 and early 2011. Teva Pharmaceutical Industries, Ltd. has just entered a global licensing and collaboration agreement for the new medication with Washington, USA and Vancouver, Canada based OncoGenex Pharmaceuticals, Inc. The new medication has completed a successful Phase II program in patients with advanced prostate cancer and advanced non-small cell lung cancer. The two companies will collaborate together on a global Phase III clinical trial in patients with the same diagnoses. Researchers are hoping to use the new treatment to boost the effectiveness of chemotherapy.

Under the agreement, OncoGenex retains the right to co-promote the new medication in the United States and Canada. Teva will add the new treatment to its family of branded oncology products elsewhere in the world, including Israel. OGX-011 is a second-generation antisense drug that was co-discovered by OncoGenex and Isis Pharmaceuticals, Inc., which will receive a $10 million payment from OncoGenex as a result of the deal with Teva.

OGX-011 is designed to block production of clusterin, a cell survival protein. Increased clusterin production is observed in many human cancers and in response to many cancer treatments as well. It is linked to faster rates of cancer progression, treatment resistance and shorter survival. OncoGenex conducted five Phase II trials studies in which OGX-011 demonstrated effectiveness in fighting prostate and advanced non-small cell lung cancers. It also appeared to show potential benefit when added to therapy for breast cancer.

They currently have five product candidates in development: OGX-011, OGX-427, OGX-225, SN2310 and CSP-9222.

OGX-011, also known as custirsen sodium, inhibits the production of clusterin, a protein that is associated with treatment resistance in a number of solid tumors, including prostate, breast, non-small cell lung, ovarian, and bladder cancers. It has potential applicability as a therapeutic in a broad number of cancers at different stages and can potentially be used in combination with a variety of commonly used cancer treatments, including chemotherapy, radiation therapy, and hormone ablation therapy. Preliminary data in a Phase 2 clinical trial evaluating OGX-011 in combination with second-line chemotherapy in patients with hormone refractory prostate cancer has shown that retreatment with docetaxel in combination with OGX-011 may reverse docetaxel resistance and improve patient survival. In July 2008, OncoGenex reached an agreement with the U.S. Food and Drug Administration (FDA) on the design of a Phase 3 registration trial of OGX-011 via the Special Protocol Assessment (SPA) process;

OGX-427 is designed to reduce production of Hsp27, a protein that is over-produced in response to many cancer treatments including hormone ablation therapy, chemotherapy and radiation therapy. Hsp27 production has been shown to inhibit cell death in tumor cells through a variety of mechanisms. OGX-427 is in a Phase 1 clinical trial for the treatment of solid tumors including prostate, non-small cell lung, breast, ovarian, and bladder cancers. The company anticipates that the safety profile for OGX-427 as a single agent will be completed in the second half of 2008, and for OGX-427 in combination with chemotherapy in the first half of 2009. Like OGX-011, this product candidate has potential as a treatment in a broad number of cancers;

SN2310 is a novel prodrug of SN-38, which is a potent anti-cancer drug belonging to the class of topoisomerase I inhibitors. SN2310 is designed to enhance the delivery and exposure of SN-38 to the tumor by providing greater prodrug conversion and a longer half-life than achieved with irinotecan. It is currently in a Phase 1 trial and progress is being made to determine its safety and pharmacokinetic profile, in addition to the maximum tolerated dose;

CSP-9222 is a caspase activator presently in pre-clinical development. Caspase activators consist of small molecules that have been identified in preclinical research as activators of programmed cell death. Unlike normal cells, many tumor cell types have lost the ability to undergo the normal process of programmed cell death, known as apoptosis. CSP-9222 has demonstrated anti-tumor activity in a range of pre-clinical animal tumor models, including taxane-resistant tumors, following both intravenous and oral administration. The company expects to move this compound into Phase 1 clinical development within 12-18 months. The caspase program was in-licensed in August 2008 through an exclusive agreement with Bayer HealthCare LLC; and

OGX-225 aims to reduce the production of both Insulin-Like Growth Factor Binding Protein -2 and Insulin-Like Growth Factor Binding Protein -5 with a single product to enhance treatment sensitivity and delay tumor progression. IGFBP-2 and IGFBP-5 are both hormones that make an alternate hormone, IGF-1, available to the tumor that facilitates continued tumor growth. Employing OGX-225 as a single product to simultaneously inhibit the production of both IGFBP-2 and IGFBP-5 has the potential to delay disease progression in a number of cancers that are dependent upon IGF-1 for tumor growth. OGX-225 is in pre-clinical development and has completed pre-clinical pharmacology.

OGX-427 is a second generation antisense drug which in preclinical experiments, inhibits production of Heat Shock Protein 27 (Hsp27) a cell survival protein found at elevated levels in many human cancers including prostate, lung, breast, ovarian, bladder, renal, pancreatic, multiple myeloma and liver cancer. Many anti-cancer therapies are known to further elevate Hsp27 levels. For example, Hsp27 levels increased four-fold in prostate cancer patients after treatment with chemo- or hormone therapy. Increased levels of Hsp27 in some human cancers are associated with metastases, poor prognosis and resistance to radiation or chemotherapy.

Preclinical studies show that OGX-427 significantly decreases levels of Hsp27, induces apoptosis in several human cancer cell lines, has single agent anti-tumor activity, and acts as a chemosensitizer in combination with several cytotoxic drugs including docetaxel.

OGX-427 is being evaluated in a Phase 1 study in patients with breast, prostate, ovarian, non-small cell lung, or bladder cancer who have failed potentially curative treatments or for which a curative treatment does not exist. Patients are being enrolled at clinical sites in Canada and the United States.

Preliminary results of this phase 1 trial were presented during an oral presentation at the ASCO 2009 Annual Meeting. OGX-427 treatment was well tolerated as a monotherapy. No evidence of altered cardiac activity was observed. A majority of adverse events were mild and mainly occurred during the loading doses. The combination of OGX-427 with docetaxel at both dose levels was also well tolerated. This data is subject to further analysis.

Circulating tumor cells (“CTCs”), an emerging metric to assess treatment effect, were evaluated at baseline before treatment and during OGX-427 treatment as a monotherapy. Both total and Hsp27-positive CTCs were evaluated. Declines of 50% or greater in both total and Hsp27-positive CTCs were observed in over one-half of the patients in each cohort and in each type of cancer. Declines in Hsp27 CTCs to 5 or less cells occurred in 27% of patients who had greater than 5 CTCs at baseline. Reduction in tumor markers defined as declines of prostate specific antigen, or PSA, levels in prostate cancer or CA-125 levels in ovarian cancer were also observed. A reduction in PSA level was observed in 7 of 20 patients (35%) with prostate cancer and a reduction in CA-125 levels was observed in 3 of 5 patients (60%) with ovarian cancer.

A second investigator-sponsored phase 1 clinical trial evaluating OGX-427 when administered directly into the bladder in patients with bladder cancer was initiated in August 2009. The study, which will enroll up to 30 patients with bladder cancer, is designed to determine the safety and potential benefit of OGX-427 administered directly into the bladder using a catheter, which is known as intravesical instillation. In addition, the study will measure the direct effect of OGX-427 on expression of Hsp27 in bladder tumor cells as well as determine the pharmacokinetics and pharmacodynamics of OGX-427 when delivered by intravesical instillation. This investigator-sponsored study is funded by the National Cancer Institute of Canada (“NCIC”).

SN2310 is a novel camptothecin for the treatment of cancer. Camptothecins are potent anticancer agents that belong to the family of drugs called topoisomerase I inhibitors that bind reversibly to the TOPO-I-DNA complex causing breaks in the DNA strands during replication resulting in cell death.

There are two camptothecins approved by the FDA: irinotecan (Camptosar) and topotecan (Hycamtin). Irinotecan is approved for the treatment of metastatic colorectal cancer when used as a component of first-line therapy with 5-FU and leucovorin or when disease has recurred or progressed following initial 5-FU- based therapy. Topotecan is approved for second-line treatment of ovarian cancer and small-cell lung cancer. The combined sales of the two drugs were over $1 billion in 2006, with irinotecan sales of over $900 million.

SN-38 is the active metabolite of irinotecan. A major limitation of irinotecan is that the pro-drug requires enzymatic hydrolysis to the active drug, SN-38, and only approximately 3% is hydrolyzed. Based on literature reports, SN-38 is 200 to 2000 times more cytotoxic than irinotecan. SN-38 has not been successfully developed, at least in part due to its poor solubility.

SN2310 Injectable Emulsion is an oil-and-water emulsion that incorporates a new derivative of SN-38, SN2310. The conjugation of SN-38 to Vitamin E succinate enables increased solubility in a vitamin E-based, oil-in-water emulsion that can be administered without dilution. The difference in the structure is shown in the right sidebar.

SN2310 Injectable Emulsion is being developed with the objective of demonstrating improved anti-tumor activity as a result of increased exposure to SN-38 based on a longer half-life. In addition, the product is more convenient, with a shorter duration of administration and no requirement for reconstitution.

In preclinical studies, comparable or better cytotoxic activity in vitro was observed when results after administration of SN2310 were compared to results after administration of irinotecan or topotecan. Similarly, the anti-tumor activity of SN2310 was comparable or better than activity of irinotecan when compared in human tumor xenograft studies. To-date, we have demonstrated that SN2310 provides similar exposure of SN38 as irinotecan at approximately a 15-fold lower dose, with a half-life that is approximately seven-fold higher. Additionally, the Vitamin E chain is separated from SN38 via both enzymatic and hydrolytic cleavage, and in vitro studies suggest that this results in conversion of about 10 times more prodrug to active drug than irinotecan.

In September 2006, Sonus initiated a Phase 1 study of SN2310 which is presently ongoing.

CSP-9222 is the lead compound from a family of caspase activators that have been in-licensed from Bayer Healthcare LLC. These novel, small molecules have been identified as activators of programmed cell death.

Unlike normal cells, many tumor cell types have lost the ability to undergo the normal process of programmed cell death, known as apoptosis. By activating the caspase pathway, tumor cells can be triggered to undergo apoptosis resulting in cell death.

Preclinical data with CSP-9222 in numerous preclinical animal models, including taxane-resistant tumor cells, indicate anti-tumor activity across a broad spectrum of tumor cell types. Both intravenous and oral administration of CSP-9222 has resulted in anti-tumor activity in various animal models. Thus, CSP-9222 offers the potential for a novel therapy in the treatment of a variety of cancers.

They have conducted five Phase 2 clinical trials to evaluate the ability of custirsen sodium (OGX-011), our lead product candidate, to enhance the effects of therapy in prostate, non-small cell lung and breast cancers. Data from these Phase 2 studies demonstrates the potential benefit of adding OGX-011, a second generation antisense molecule, to existing cancer therapies. Based on our Phase 2 results in 294 patients, we believe that registration trials for market approval of OGX-011 are warranted in Castrate Resistant Prostate Cancer (CRPC) and Nonsmall Cell Lung Cancer (NSCLC). Our initial registration trials will focus on the CRPC indication.

OGX-011 is designed to block production of clusterin, a cell survival protein that is over-produced in several cancer indications and in response to many cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. Increased clusterin production is observed in many human cancers, including prostate, non-small cell lung, breast, ovarian, bladder, renal, pancreatic, anaplastic large cell lymphoma and colon cancers and melanoma. Increased clusterin production is linked to faster rates of cancer progression, treatment resistance and shorter survival duration. Clusterin levels may be further increased in response to standard cancer therapies, including hormone ablation therapy, chemotherapy and radiation therapy. Clusterin expression is linked to disease progression, treatment resistance, poor prognosis and survival in scientific publications. For example, increased expression of clusterin in prostate cancer is closely correlated with increasing Gleason score, which is a strong prognostic factor for poor survival of patients with prostate cancer.

A broad range of preclinical studies show that OGX-011 decreases clusterin levels and sensitizes tumor cells to standard chemotherapeutic drugs, resulting in increased rates of tumor cell death. Preclinical results also show that reducing clusterin production sensitizes prostate tumor cells to hormone ablation therapy and sensitizes prostate and non-small cell tumor cells to radiation therapy. The Clinical program for OGX-011 is summarized below.

Three Phase 1 clinical trials, involving a total of 75 patients, have been completed with OGX-011. In all of these clinical trials, OGX-011 was well tolerated by the patients.

In the first Phase 1 clinical trial, OGX-011 was intravenously administered once per week in combination with hormone ablation therapy to patients with localized prostate cancer in advance of surgery to remove the prostate gland. This clinical trial showed that once weekly administration of OGX-011 reduced clusterin mRNA levels by approximately 92 percent in prostate cancer tissue and approximately 98 percent in lymph node tissue, and more than doubled the rate of prostate tumor cell death compared to hormone ablation therapy alone.

In the second Phase 1 clinical trial, OGX-011 was intravenously administered once per week in combination with docetaxel chemotherapy to patients with solid tumors known to express clusterin. This clinical trial showed that serum clusterin levels dropped in patients while on treatment with 640 mg OGX-011 in combination with docetaxel.

In the third Phase 1 clinical trial, OGX-011 was intravenously administered once per week in combination with two commonly used chemotherapeutic agents to patients with advanced non-small cell lung cancer. The one-year survival rate for patients that received at least one dose of OGX-011 in combination with these chemotherapies was approximately 60 percent. This compares with results from prior published Phase 3 clinical trials which reported one-year survival rates of 33 to 43 percent for patients that received chemotherapy treatment alone.

They have conducted five phase 2 clinical trials to evaluate the ability of OGX-011 to enhance the effects of therapy in prostate, non-small cell lung and breast cancer. Data is available from each of the five phase 2 studies which demonstrate that adding OGX-011 to therapy shows potential benefit of OGX 011:

  • longer survival duration when adding OGX-011 to first-line docetaxel compared to first-line docetaxel alone in patients with CRPC within a randomized phase 2 trial;
  • longer survival duration when adding OGX-011 to either mitoxantrone or docetaxel as second-line chemotherapy compared to survival duration observed in two published studies of CRPC patients receiving second-line chemotherapy;
    increased frequency and duration of pain palliation when adding OGX-011 to either mitoxantrone or docetaxel as second-line chemotherapy compared to the frequency and duration of pain palliation observed in the TAX 327 Study for first-line chemotherapy alone in patients with CRPC;
  • and longer survival duration when adding OGX-011 to gemcitabine and a platinum-containing chemotherapy compared to the survival duration reported in prior published results from randomized clinical trials in NSCLC patients receiving gemcitabine and a platinum-containing chemotherapy.

Final results of a randomized phase 2 trial evaluating the benefit of combining OGX-011 with first-line docetaxel chemotherapy were presented during an oral presentation at the American Society of Clinical Oncology (“ASCO”) 2009 Annual Meeting. Analyses indicating a survival benefit in patients treated with OGX-011 in combination with first-line docetaxel compared to docetaxel alone, the latter of which being the current standard care for patients with advanced, progressive metastatic prostate cancer, are described below:

  • The median overall survival in patients with advanced metastatic prostate cancer who were treated with OGX-011 plus docetaxel in a randomized phase 2 trial was 23.8 months compared to 16.9 months for patients treated with docetaxel alone, indicating a 6.9 month survival advantage in the OGX-011 arm;
  • The unadjusted hazard ratio (“HR”), a measure used to compare the death rates between treatment groups, was 0.61, representing a 39% lower rate of death for patients treated with OGX-011;and
  • A prospectively defined multivariate analysis indicated that the significant predictors of overall survival were treatment arm, performance status and presence of metastases other than in bone or lymph nodes. In the multivariate analysis, patients treated with OGX-011 had a rate of death of 51% lower than patients treated with docetaxel alone (HR=0.49; p=0.012).
  • Additional exploratory analyses found that the lower rate of death was associated with the effect of OGX-011 treatment even when varying amounts of chemotherapy were administered (i.e. OGX-011 treatment resulted in a lower rate of death when compared to the control arm for patients receiving 6 or less cycles of chemotherapy as well as for patients receiving 10 cycles of chemotherapy).
    OGX-011 is being developed to work in combination with therapies that are broadly used by clinicians and considered highly effective in the treatment of each cancer indication that we are targeting with the intent of delaying treatment resistance to those therapies. Since production of clusterin and the resulting treatment resistance occurs in an array of cancer indications and in response to a variety of cancer treatments, we believe that our development options for OGX-011 are numerous.

Phase 1 Clinical Results

  • OGX-011 in Combination with Hormone Ablation Therapy in Patients with Localized Prostate Cancer (Clinical Trial OGX-011-01)

For men with localized prostate cancer, hormone ablation therapy with surgery remains the initial standard of care. Hormone ablation causes death of prostate tumor cells.

The purpose of this clinical trial was to:

  • determine safety and tolerability and define the recommended Phase 2 dose of OGX-011 when given in combination with hormone ablation therapy;
  • determine the concentration and elimination profile of OGX-011 in serum and in the prostate when administered in combination with hormone ablation therapy;
    measure clusterin mRNA and protein levels in the prostate and other tissues and correlate with dose of OGX-011;
    measure serum clusterin levels and correlate with dose of OGX-011; and
  • attempt to establish possible correlations between plasma and/or prostate concentrations of OGX-011 with patient response or toxicity measures.
    In order to determine these objectives, OGX-011 was administered in combination with hormone ablation therapy to patients with localized prostate cancer in advance of a surgical procedure to remove the prostate gland.

There were a total of 25 patients enrolled into treatment groups who received increasing doses of OGX-011 from 40 milligrams (mg) up to 640 mg. There was no dose limiting toxicity observed during OGX-011 dose escalation and adverse events were mild to moderate (grade 1 or 2). In summary, the results of the Phase 1 clinical trial of OGX-011 in combination with hormone ablation therapy were that:

  • OGX-011 achieved high drug concentrations in the prostate and lymph nodes through once weekly intravenous administration;
  • clusterin mRNA was inhibited in prostate tumor cells by more than 92 percent in patients receiving the highest dose of OGX-011 (640 mg);
  • approximately double the amount of tumor cell death occurred in the prostate of patients receiving the highest dose of OGX-011 (640 mg) compared to hormone ablation therapy alone;
  • OGX-011 was well-tolerated, with no dose limiting toxicity observed; and
  • the recommended Phase 2 dose of OGX-011 was established at 640 mg.
  • OGX-011 concentration in prostate tissue increased with higher doses, as shown in Figure 1 above. Dose-dependent decreases in clusterin mRNA in prostate tissue were also observed. At the highest dose (640 mg) of OGX-011, clusterin mRNA was decreased by more than 92 percent in prostate tissue when compared to the lowest dose level and other historical controls (patients with no prior hormone ablation therapy and patients with less than two months of hormone ablation therapy).
  • Similarly, clusterin mRNA was decreased by approximately 98 percent in lymph node tissue when compared to the lowest dose level (data not shown).

To determine whether suppression of clusterin levels by OGX-011 treatment could increase tumor cell death in prostate cancer tissue, the percentage of dying tumor cells per high powered field of the microscope were counted as shown in Figure 3 below. At the Phase 2 dose (640 mg) the addition of OGX-011 more than doubled the percentage of dying tumor cells compared to hormone ablation therapy alone.

These data demonstrate that OGX-011 was able to:

  • be delivered to prostate tumors and lymph nodes;
    get inside tumor cells where it is required in order to potentially have a therapeutic effect;
  • significantly decrease clusterin production; and
    increase tumor cell death when combined with hormone ablation therapy.
  • Based on achieving high drug concentration in prostate tissue and over 92 percent inhibition of clusterin mRNA in prostate tumor cells and lymph nodes, and a favorable safety profile, 640 mg was selected as the optimal dose for Phase 2 clinical trials of OGX-011.

Patients in this clinical trial experienced various “adverse events”, the majority of which are known to be associated with the other treatments in the protocol (hormone ablation therapy or prostate surgery). An adverse event is any unfavorable and unintended clinical laboratory value or symptom which is encountered during or after the use of an investigational product (i.e. OGX-011). These events may or may not be related to the patient’s disease, other therapies administered to the patient or the investigational product.

None of the events that occurred resulted in patients discontinuing OGX-011 and the majority of the adverse events were considered mild. The adverse events thought to be possibly related to OGX-011 occurred mainly within the first week and decreased with continued dosing. These events included mild suppression of white blood cell counts; flu-like symptoms that included fever, fatigue, and rigors; and mild elevations in liver enzyme levels. Most symptoms went away after one to three weeks despite continued administration of OGX-011.

There were no “serious adverse events” reported during this clinical trial. Serious adverse event means any adverse experience that results in any of the following outcomes: death, a life-threatening experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.

OGX-011 in Combination with Docetaxel Chemotherapy in the Treatment of Solid Tumors (Clinical Trial OGX-011-02)

OGX-011 treatment in animal models has been shown to enhance chemosensitivity and to reverse chemotherapy resistance to docetaxel, a chemotherapeutic agent used in a number of cancers including lung, breast, ovarian, bladder, renal cell and hormone refractory prostate cancer. This clinical trial was undertaken to evaluate the safety profile of OGX-011 in combination with docetaxel chemotherapy.

The purpose of this clinical trial was to:

  • determine safety and tolerability and define the recommended Phase 2 dose of OGX-011 when given in combination with docetaxel chemotherapy given either weekly or every three weeks;
  • determine the concentration of OGX-011 and docetaxel in serum when administered in combination;
    measure evidence of the effect of OGX-011 on serum clusterin levels; and
  • document any objective tumor responses.

In order to determine these objectives, OGX-011 was administered in combination with docetaxel chemotherapy to patients with cancers known to over-produce clusterin (prostate, non-small cell lung, breast, ovary, bladder and renal cell).

There were a total of 40 patients enrolled into treatment groups who received increasing doses of OGX-011 from 40 mg up to 640 mg. In addition to OGX-011 treatment, patients also received docetaxel chemotherapy given either as a weekly or every three week schedule as one cycle. The clinical trial was conducted at multiple clinical sites.

Although this was a group of patients with various cancer types, responses and stable disease were documented. OGX-011 treatment resulted in a trend towards dose dependent decreases in serum clusterin levels with the 640 mg dose level having the greatest change from baseline. There was no evidence that administration of OGX-011 affected the metabolism of docetaxel chemotherapy or that docetaxel chemotherapy affected the metabolism of OGX-011.

The recommended OGX-011 dose for treatment in combination with docetaxel chemotherapy was determined as 640 mg, based on acceptable safety results, documented responses/stable disease, and lowering of serum clusterin levels observed from this Phase 1 clinical trial.

Patients in this clinical trial experienced various adverse events, the majority of which are known to be associated with the other treatment in the protocol (docetaxel chemotherapy). Adverse events associated with docetaxel chemotherapy include reduced appetite, nausea, hair loss and decrease in blood counts.

Adverse events were primarily mild to moderate. The incidence of reduced appetite, nausea and hair loss increased as the OGX-011 dose levels increased. The decrease in white blood cell counts was consistent with other trials using docetaxel and did not decrease further with increased doses of OGX-011. Five of the 40 patients experienced dose-limiting toxicity. Four of these events were attributed to the docetaxel chemotherapy and one, fatigue, was attributed to the combination of OGX-011, docetaxel and the disease. Six of the 40 patients experienced a serious adverse event. All of these events were attributed to the docetaxel chemotherapy, except a case of upper gastrointestinal bleeding which was attributed to the combination of OGX-011 and docetaxel chemotherapy.

Phase 2 Clinical Trial Results

The Phase 1 clinical trials evaluated the safety and established the recommended Phase 2 dose of OGX-011 in combination with either docetaxel chemotherapy (two different schedules), gemcitabine/cisplatin chemotherapy or hormone ablation therapy. In all clinical trials, 640 mg was established as the Phase 2 dose.

They have conducted five Phase 2 clinical trials of OGX-011 to further evaluate the safety and efficacy of OGX-011 in combination with various cancer therapies for prostate, non-small cell lung and breast cancer, as further described below on the OncoGenex web site.

Prostate Cancer
Final Results of Phase 2 Clinical Trial in Patients Receiving
First-Line Chemotherapy Treatment for Castrate Resistant Prostate Cancer (Study OGX-011-03)
Phase 2 Clinical Trial – Hormone Ablation Therapy in Patients with Localized Prostate Cancer (Study OGX-011-04)
Preliminary Results of a Phase 2 Clinical Trial in Patients Receiving Second-Line Chemotherapy for Treatment of Hormone Refractory Prostate Cancer (Study OGX-011-07)

Lung Cancer
Preliminary Results of Phase 2 Clinical Trial in Patients Treated with First-Line Chemotherapy for Non-Small Cell Lung Cancer (Study OGX-011-05)

Breast Cancer
Preliminary Results of Phase 2 Clinical Trial in Patients with Advanced Breast Cancer (OGX-011-06)

G-d Bless Israel: Teva shares trading on the Tel Aviv Stock Exchange on December 22, 2009, rose 2.42% from their previous day’s level, and continued to rise in after hours trading. The stock reached its all time high on the TASE Tuesday, closing at 206.5 shekels a share. The rise was partially due to Teva’s announcement of its purchase on Monday of OncoGenex.



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