On November 5, 2015 Geron Corporation (Nasdaq: GERN) reported financial results for the third quarter ended September 30, 2015 (Filing, 8-K, Geron, NOV 5, 2015, View Source [SID:1234508051]).

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For the third quarter of 2015, the company reported net income of $27.2 million, or $0.17 per share, compared to a net loss of $9.5 million, or $(0.06) per share, for the comparable 2014 period. Net income for the first nine months of 2015 was $8.5 million, or $0.05 per share, compared to a net loss of $26.7 million, or $(0.18) per share, for the comparable 2014 period. The company ended the third quarter of 2015 with $151.8 million in cash and investments.

Revenues for the third quarter of 2015 were $35.4 million compared to $160,000 for the comparable 2014 period. Revenues for the first nine months of 2015 were $36.2 million compared to $975,000 for the comparable 2014 period. Revenues for the three and nine month periods ending September 30, 2015 included the full recognition of the $35.0 million upfront payment from Janssen Biotech, Inc. (Janssen) as collaboration revenue upon the company’s transfer of the imetelstat license rights and completion of technology transfer-related activities outlined under the imetelstat collaboration agreement with Janssen. The upfront cash payment was received in December 2014 and recorded as deferred revenue at that time.

Total operating expenses for the third quarter of 2015 were $8.3 million compared to $10.1 million for the comparable 2014 period. Research and development expenses for the third quarter of 2015 were $4.1 million compared to $6.0 million for the comparable 2014 period. General and administrative expenses for the third quarter of 2015 were $4.3 million compared to $4.1 million for the comparable 2014 period.

Total operating expenses for the first nine months of 2015 were $28.1 million compared to $28.3 million for the comparable 2014 period. Research and development expenses for the first nine months of 2015 were $13.8 million compared to $16.4 million for the comparable 2014 period. General and administrative expenses for the first nine months of 2015 were $12.9 million compared to $11.9 million for the comparable 2014 period. Year-to-date operating expenses for 2015 also included restructuring charges of $1.3 million in connection with the company’s organizational resizing announced in March 2015.

The decrease in research and development expenses for the three and nine month periods ending September 30, 2015, compared to the same periods in 2014, was primarily the net result of lower costs for the manufacturing of imetelstat and reduced personnel-related costs resulting from the organizational resizing, partially offset by increased costs for the development of imetelstat for hematologic myeloid malignancies in collaboration with Janssen. The company expects research and development expenses to increase during the remainder of the year as the development of imetelstat continues in collaboration with Janssen. The increase in general and administrative expenses for the three and nine month periods ending September 30, 2015, compared to the same periods in 2014, was primarily the result of higher non-cash stock-based compensation expense and increased legal costs associated with the company’s patent portfolio.

Interest and other income for the third quarter of 2015 amounted to $187,000 compared to $91,000 for the comparable 2014 period. Interest and other income for the first nine months of 2015 was $481,000 compared to $273,000 for the comparable 2014 period. The increase in interest and other income for the three and nine month periods ending September 30, 2015, compared to the same periods in 2014, primarily reflects higher yields on the company’s investment portfolio. The company has not incurred any impairment charges on its investment portfolio.

Recent Company Events

● Two papers were published in the September 3, 2015 issue of The New England Journal of Medicine (NEJM) with results from two clinical studies in which imetelstat was shown to have disease-modifying activity thought to be associated with the selective inhibition of the malignant progenitor cell clones responsible for the underlying disease in two hematologic myeloid malignancies, essential thrombocythemia (ET) and myelofibrosis (MF). The papers are available online at www.NEJM.org.

● In September 2015, the first patient was dosed in the IMbark study, a Phase 2 clinical trial to evaluate the activity of two dose levels of imetelstat in patients with DIPSS intermediate-2 or high-risk myelofibrosis who have relapsed after or are refractory to a JAK inhibitor. Multiple medical centers across North America, Europe and Asia are planned to participate in this clinical trial. For more information about the IMbark study being conducted by Janssen, please visit View Source

● Three abstracts describing clinical and non-clinical data on imetelstat were accepted for presentation at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition to be held in Orlando, Florida from December 5-8, 2015. The abstracts were published on November 5, 2015 on the ASH (Free ASH Whitepaper) website at www.hematology.org.

On November 5, 2015 National Cancer Institute reported two findings from The Cancer Genome Atlas (TCGA) Research Network were recently published on papillary renal cell carcinoma and prostate cancer (Press release, National Cancer Institute, NOV 5, 2015, View Source [SID:1234508089]). See below for specifics:

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Improved Understanding of the Genetic Drivers of Papillary Renal Cell Carcinoma

A comprehensive genomic analysis of 161 tumors from people with papillary renal cell carcinoma (PRCC) – the second most common form of kidney cancer –provided insights into the molecular basis of this cancer and may inform its classification and treatment. PRCCs are divided into two main subtypes, Type 1 and Type 2, which are traditionally defined by how the tumor tissue appears under a microscope. Findings from this genomic analysis, carried out by investigators from The Cancer Genome Atlas (TCGA) Research Network, have confirmed that these subtypes are distinct diseases distinguished by certain genomic characteristics. This molecular information could be important in managing patients clinically, identifying new therapies, and designing clinical trials.

The researchers found that Type 1 PRCC is characterized by alterations in cell signaling involving the MET gene that are known to drive cancer cell growth, the growth of tumor blood vessels, and cancer metastasis or spread. MET gene mutations or other alterations that affect its activity were identified in 81 percent of Type 1 PRCCs examined. This finding suggests that it may be possible to treat Type 1 PRCCs with specific inhibitors of the MET cell signaling pathway, including the MET/VEGFR inhibitor foretinib, which is currently being tested in phase II clinical trials in PRCC and other cancer types. Type 2 PRCC was found to be more genomically heterogeneous. A specific characteristic, referred to as the CpG island methylation phenotype (CIMP), was found almost exclusively in Type 2 PRCC and defined a distinct Type 2 subgroup that was associated with the least favorable outcome. CIMP is marked by increased DNA methylation, which is a chemical modification of DNA that inhibits gene expression. Across all Type 2 PRCCs examined, 25 percent demonstrated decreased expression of CDKN2A, a tumor suppressor gene that helps regulate the cell cycle. Loss of CDKN2A expression was also associated with a less favorable outcome. The TCGA researchers were led by Paul Spellman, Ph.D., Oregon Health and Science University, Portland, and Marston Linehan, M.D., NCI. Their findings were published online first November 4, 2015, in the New England Journal of Medicine.

TCGA Study Identifies Seven Distinct Subtypes of Prostate Cancer

A comprehensive analysis of 333 prostate cancers identified key genetic alterations that may help improve classification and treatment of the disease. While 90 percent of prostate cancers are now identified as clinically localized tumors, once diagnosed, these cancers tend to have a heterogeneous and unpredictable course of progression, ranging from slow-growing to fatal disease. The new analysis, by investigators from The Cancer Genome Atlas (TCGA) Research Network, revealed seven new molecular subtypes of prostate cancer based on known and novel genetic drivers of the disease. These subtypes may therefore have prognostic and therapeutic implications. Of the seven subtypes, four are characterized by gene fusions (in which parts of two separate genes are linked to form a hybrid gene) involving members of the ETS family of transcription factors (ERG, ETV1, ETV4, and FLI1), and the other three are defined by mutations of the SPOP, FOXA1, and IDH1 genes. Notably, the IDH1 mutation was identified as a driver of prostate cancers that occur at younger ages. Although most (74 percent) of the analyzed tumors could be categorized into one of the seven molecular subtypes, the remaining 26 percent of prostate tumors in this analysis could not be categorized because molecular alterations driving their growth were not identified. Prostate cancer is expected to be diagnosed in over 220,000 men in the U.S. this year and is the fourth most common tumor type worldwide.

Another finding from this analysis was that gene expression profiles differed based on whether the tumors were driven by gene fusions or by mutations. Within the mutation-driven tumors, the SPOP and FOXA1 gene subtypes shared similar patterns of DNA methylation, a chemical modification of DNA that inhibits gene expression; somatic copy-number alteration, or change in the number of copies of a gene in a cell; and messenger RNA expression, which is a measure of gene activity. These genomic commonalities suggest that mutations in SPOP and FOXA1 genes cause similar disruptions in the cell to bring about cancer. Additionally, the SPOP and FOXA1 subtypes showed the highest levels of androgen receptor-mediated gene expression, suggesting potential preventive and therapeutic possibilities targeting androgens, which are male sex hormones that can stimulate the growth of prostate cancer. The researchers, led by Chris Sander, Ph.D., Memorial Sloan-Kettering Cancer Center, New York, published their results online November 5, 2015, in Cell. TCGA is a collaboration jointly supported and managed by the National Cancer Institute and the National Human Genome Research Institute, both parts of the National Institutes of Health.

(Filing, 10-Q, Celgene, NOV 5, 2015, View Source [SID:1234508040])

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On November 5, 2015 Oncolytics Biotech Inc. (TSX:ONC, OTCQX:ONCY) ("Oncolytics" or the "Company") reported its financial results and operational highlights for the third quarter ended September 30, 2015 (Press release, Oncolytics Biotech, NOV 5, 2015, View Source [SID:1234507971]).

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"During the quarter, we announced exciting initial clinical data from our multiple myeloma study showing statistically significant increases in the production of caspase-3 and upregulation of PD-L1 along with an early objective response rate of 100%," said Dr. Brad Thompson, President and CEO of Oncolytics. "We also announced one and two-year survival data versus historical controls from our pancreatic (REO 017) cancer trial. This data is very often suggestive of broader immune system involvement which led us to file a US Phase 1b study in pancreatic adenocarcinoma; the first to examine REOLYSIN in combination with the checkpoint inhibitor KEYTRUDA."

Selected Highlights

Since July 1, 2015, selected highlights announced by the Company include:

Clinical Program

A poster presentation at the 15th International Myeloma Workshop titled "Combination Carfilzomib and the Viral Oncolytic Agent REOLYSIN in Patients with Relapsed Multiple Myeloma: A Pilot Study Investigating Viral Proliferation," highlighting data including 100% of patients (8 of 8) experiencing an objective response as measured by changes in blood monoclonal protein and significant increases in the production of caspase-3 (p=0.005) and upregulation of PD-L1 (p=0.005);

An oral presentation at the International Association for the Study of Lung Cancer (IASLC) 16th World Conference on Lung Cancer titled "Oncolytic Reovirus in Combination with Paclitaxel/Carboplatin in NSCLC Patients with Ras Activated Malignancies, Long Term Results," covering updated results, including one- and two-year survival data, from the Company’s REO 016 Phase 2 study in Non-Small Cell Lung Cancer (NSCLC);

Presentation of final data from a single arm clinical study examining the use of REOLYSIN in combination with gemcitabine in patients with advanced pancreatic cancer (REO 017), which showed an increase in median overall survival, as well as an approximate two-fold increase in one-year survival rates, and a five-fold increase in two-year survival rates when compared to gemcitabine therapy alone as seen in historical data;

Completion of enrollment in two randomized Phase 2 studies sponsored and conducted by the NCIC Clinical Trials Group; IND 211 is a study of REOLYSIN in combination with chemotherapy in patients with previously treated advanced or metastatic non-small cell lung cancer and IND 209 is a study of REOLYSIN in combination with chemotherapy in patients with recurrent or metastatic castration resistant prostate cancer;

Subsequent to quarter end, confirmation that, following submission to the U.S. Food and Drug Administration ("FDA") for review, the Investigational New Drug Application containing the protocol titled "A Phase Ib study of pembrolizumab (KEYTRUDA) in combination with REOLYSIN (pelareorep) and chemotherapy in patients with advanced pancreatic adenocarcinoma", the Company’s first trial examining REOLYSIN in combination with a checkpoint inhibitor, was active; and

Financial

At September 30, 2015 the Company reported $30.0 million in cash, cash equivalents and short-term investments. At November 5, 2015, the Company had approximately $28.7 million in cash, cash equivalents and short-term investments, which is expected to provide sufficient funds to support several small early-stage immunotherapy combination studies as well as both a run-in and a registration study in muscle invasive bladder cancer.

On November 5, 2015 BioLineRx Ltd. (NASDAQ, TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported positive results from the dose escalation part of BL-8040’s Phase 2 clinical trial in relapsed or refractory acute myeloid leukemia (r/r AML) (Press release, BioLineRx, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107352 [SID:1234507989]). The results will be presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, to be held December 5-8, 2015 in Orlando, Florida.

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Results showed that BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well tolerated at all doses tested up to and including the highest dose level of 1.5 mg/kg, with no major adverse events. The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving only one cycle of BL-8040 treatment at doses of 1 mg/kg and higher (n=16). Patients included in this part of the study were patients that had undergone a significant number of prior treatment cycles or that were refractory to induction treatment.

Treatment with BL-8040 had a triple effect on the leukemic cells. First, following only two days of monotherapy, BL-8040 triggered an average 40-fold mobilization of immature AML progenitor cells from the bone marrow to the peripheral blood, thereby sensitizing these cells to the Ara-C chemotherapy and improving its efficacy. Second, BL-8040 showed a direct and significant apoptotic effect on the immature leukemia progenitor cells in the bone marrow following the two days of monotherapy. Last, BL-8040 induced leukemia progenitor cells towards differentiation, as evidenced by a 58% median decrease in the number of bone marrow leukemia progenitor cells, along with a three-fold increase in differentiated granulocytes, in the bone marrow biopsy conducted on Day 3 of the treatment cycle prior to the Ara-C treatment, as compared to the biopsy performed at baseline.

Dr. Jorge Cortes, Chief of the AML and CML Sections at the MD Anderson Cancer Center in Houston, stated, "The clinical results from the dose escalation stage of the Phase 2 study for BL-8040 in r/r AML are very encouraging and fully support continued development of the compound in the AML space."

Dr. Kinneret Savitsky, CEO of BioLineRx, commented, "We are very pleased and encouraged by the positive results from the first part of this Phase 2 trial with BL-8040 for the treatment of r/r AML, especially in light of the severity of the patient population recruited and the short treatment regimen of one cycle. The results continue to demonstrate that BL-8040 not only significantly induces mobilization of leukemic cells from the protective microenvironment of the bone marrow into the peripheral blood, but also directly leads to apoptosis of leukemic progenitor cells and triggers terminal differentiation of the cells into granulocytes. Combined with the reported 38% remission rate from subjects receiving BL-8040 doses of at least 1 mg/kg, the results strongly suggest that BL-8040 has potent anti-leukemic activity and, in combination with Ara-C, may improve the response typically achieved in this advanced AML population." Dr. Savitsky continued, "In light of the encouraging results, we look forward to discussions with the regulatory authorities regarding the future development plan for AML. We currently anticipate reporting topline results from the full study by early next year."

"In order to further expand and enhance the potential of this unique oncology platform, we are continuing to perform and plan multiple additional clinical studies for BL-8040. These include a Phase 2b study which we recently initiated for BL-8040 as an AML consolidation treatment; a Phase 2 study in the planning stages as a novel stem cell mobilization treatment, based on input that we received from the FDA last month; and two additional studies in certain bone marrow failure indications and for the treatment of AML patients with the FLT3-ITD mutation," concluded Dr. Savitsky.

About the r/r AML Phase 2 study

The Phase 2 trial is a multicenter, open-label study under an IND, conducted at ten clinical sites in the U.S. and Israel, and is designed to assess the safety, efficacy pharmacodynamics and pharmacokinetic parameters of BL-8040 in combination with Cytarabine (Ara-C) for the treatment of adult relapsed or refractory AML patients. Twenty-two patients with r/r AML were enrolled in the dose escalation stage of the study (16 of which received a dose of 1 mg/kg and higher), which includes a dose escalation stage followed by an expansion stage. In the dose escalation stage, each patient received a once daily dose of BL-8040 monotherapy (from 0.5 to 1.5 mg/kg) on days 1-2 followed by the same dose of BL-8040 plus Ara-C on days 3-7. Extensive pharmacodynamic parameters, such as mobilization of leukemic cells and induction of apoptosis, were assessed after monotherapy with BL-8040 using peripheral blood sampling and bone marrow aspirates at baseline and on Day 3 prior to Ara-C administration. Clinical response to treatment was evaluated by bone marrow biopsy on Day 30.

About BL-8040

BL-8040 is a clinical-stage drug candidate for the treatment of acute myeloid leukemia, as well as other hematological indications. It is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis (growth of new blood vessels in the tumor), metastasis (spread of the disease to other organs or organ parts) and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a Phase 1/2, open-label, dose escalation, safety and efficacy clinical trial in 18 multiple myeloma patients, BL-8040, when combined with G-CSF, demonstrated an excellent safety profile at all doses tested and was highly effective in the mobilization of hematopoietic stem cells and white blood cells from the bone marrow to the peripheral blood. Additionally, in a Phase 1 stem-cell mobilization study in healthy volunteers, BL-8040 as a single agent was safe and well tolerated at all doses tested and resulted in efficient stem-cell mobilization and collection in all study participants. Importantly, the results of this study support the use of BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care.

BL-8040 also mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer effect by inducing apoptosis. Pre-clinical studies show that BL-8040 inhibits the growth of various tumor types including multiple myeloma, non-Hodgkin’s lymphoma, leukemia, non-small cell lung carcinoma, neuroblastoma and melanoma. BL-8040 also significantly and preferentially stimulated apoptotic cell death of malignant cells (multiple myeloma, non-Hodgkin’s lymphoma and leukemia). Significant synergistic and/or additive tumor cell killing activity has been observed in-vitro and in-vivo when tumor cells were treated with BL-8040 together with Rituximab, Bortezomib, Imatinib, Cytarabine and the FLT-3 inhibitor AC-220 (in NHL, MM, CML, AML, and AML-FLT3-ITD models, respectively). In addition, the current Phase 2 clinical trial in AML patients has demonstrated robust mobilization and apoptosis of cancer cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. According to the American Cancer Society, approximately 19,000 new cases of AML were diagnosed in the United States in 2014, and the median age of AML patients was 67 years old. The first treatment line for patients with AML includes a combination of chemotherapy drugs and is called induction treatment. The median survival for AML patients receiving induction chemotherapy is less than two years, with shorter survival for patients over the age of 60 or for those with certain gene or chromosome aberrations. Due to relapsed or refractory disease (where the disease is not responsive to standard treatments), the overall five-year survival rate for AML is between 10 and 40 percent.