1stOncology™: Cancer Intelligence Service – Page 16421 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

JUNO THERAPEUTICS EXECUTES LICENSE FOR PHASE I CAR T PRODUCT CANDIDATE TARGETING CD22 FOR HEMATOLOGICAL MALIGNANCIES

On December 5, 2014 Juno Therapeutics reported that it has entered into an agreement to obtain a license from Opus Bio, Inc. for a CAR-T cell product candidate targeting CD22, a protein expressed on most B cell leukemias and lymphomas (Press release Juno, DEC 5, 2014, View Source [SID:1234501086]). The CD22-targeted CAR T cell product candidate was developed by the National Cancer Institute (NCI) under cooperative research and development agreement (CRADA) with Opus Bio. The NCI has begun enrollment in a Phase I trial evaluating pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL) or non-Hodgkin’s lymphoma (NHL).

“This fully-human CD22 directed product candidate complements our existing CD19 directed portfolio, representing another important opportunity to investigate an immunotherapy addressing B cell malignancies,” said Juno CEO, Hans Bishop.

The NCI-sponsored trial is designed to enroll patients with CD22 positive cancers, with both CD19 positive and CD19 negative patients eligible for treatment.

CAR T cell therapy has the potential to address an important unmet need, according to Crystal Mackall, M.D., Chief, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health. There is still much to learn about these immunotherapies, but the early results are hopeful.

Financial terms were not disclosed. The license will not become effective until certain closing conditions are satisfied, including obtaining consent from the NCI.

About Juno’s Chimeric Antigen Receptor and High-affinity T Cell Receptor Platform
Juno is developing cell-based immunotherapies based on its chimeric antigen receptor, or CAR, and high-affinity T cell receptor, or TCR, platform to genetically engineer T cells to recognize and kill cancer cells. T cells are a type of white blood cell that identify and kill infected or abnormal cells, including cancer cells, in healthy individuals. Juno leverages its CAR and TCR platform to activate a patient’s own T cells so that they attack cancer cells. Through genetic engineering, a gene is inserted for a particular CAR or TCR construct into the T cell enabling it to better recognize cancer cells. The CAR technology directs T cells to recognize cancer cells based on the expression of specific proteins located on the cell surface, whereas the TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. CAR construct typically uses a single chain variable fragment, or scFv, to recognize a protein of interest. The modified T cells can be infused into the patient or frozen and stored for later infusion.

Xenetic Biosciences Announces OncoHist™ Preclinical Data to be Featured in a Poster Presentation at the American Society of Hematology Annual Meeting

On December 4, 2014 Xenetic Biosciences, Inc. (OTCBB:XBIO), a biopharmaceutical company focused on developing next-generation biologic drugs and novel oncology therapeutics, reported that the mechanism of action of OncoHist in acute myeloid leukemia (AML) will be the subject of a poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 56th ASH (Free ASH Whitepaper) Annual Meeting & Exposition (Press release, Xenetic Biosciences, DEC 4, 2014, View Source [SID1234537816]). The meeting is being held December 6-9, 2014 in San Francisco and the poster presentation will be from 6:00 p.m. to-8:00 p.m. local time on December 8. The abstract, available here, also will be published in Blood on December 5.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

Researchers from Dana-Farber Cancer Institute (DFCI), one of the world’s leading cancer institutes, will be presenting the abstract, entitled "OncoHist, an rh Histone 1.3 is cytotoxic to acute myeloid leukemia cells and results in altered downstream signaling (Suiyang Liu, Surender Kharbanda and Richard Stone)." The researchers conclude that their findings support the development of OncoHist alone and in combination with chemotherapy for the treatment of AML. Richard M. Stone, M.D., will present the poster. He is Director of the Adult Acute Leukemia Program at Dana-Farber, Professor, Department of Medicine, Harvard Medical School and, serves on the Medical Oncology Board of the American Board of Internal Medicine, and is Chair, Alliance Leukemia Committee. In February 2013, Xenetic Biosciences signed a broad research agreement for OncoHist with Dana-Farber.

"We are very encouraged by the conclusions of the Dana-Farber researchers and are planning a Phase 1 study with OncoHist in conjunction with Dana-Farber Cancer Institute ultimately to support a New Drug Application filing with the U.S. Food and Drug Administration," said M. Scott Maguire, chief executive officer of Xenetic Biosciences. "Dr. Stone and his colleagues have noted in their preclinical research that OncoHist inhibits and induces necrosis of a number of AML cell lines. We believe this research validates the continuation of the Phase 1/2 trial with OncoHist in combination with cytarabine for the treatment of AML in refractory patients, which is underway in Russia by our partner Pharmsynthez. We look forward to filing our Investigational New Drug application with the FDA during the first half of 2015 and to beginning testing OncoHist in the U.S. for the treatment of AML," added Mr. Maguire.

About OncoHist

OncoHist is a novel patent-protected platform technology that utilizes the special properties of human histone H1.3 for the development of a broad range of cancer indications. OncoHist is based on a molecule occurring naturally in the human cell nucleus, and is therefore expected to be less toxic and immunogenic than other oncology therapies. OncoHist has strong anti-proliferative properties in cancer cells of different histological origins, including hematologic malignancies such as leukemias, lymphomas and myelomas. OncoHist also has the potential to be broadly applied across a spectrum of other cancers.

About Dana Farber Cancer Institute

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women’s Hospital as Dana-Farber/Brigham and Women’s Cancer Center and it provides pediatric care with Boston Children’s Hospital as Dana-Farber/Children’s Hospital Cancer Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Twitter: @danafarber or Facebook: facebook.com/danafarbercancerinstitute.

FDA Approves Jakafi (ruxolitinib) for the Treatment of Patients with Uncontrolled Polycythemia Vera

On December 4, 2014 Incyte reported that the U.S. Food and Drug Administration (FDA) has approved Jakafi (ruxolitinib) for the treatment of patients with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea (Press release Incyte, DEC 4, 2014, View Source [SID:1234501068]). Jakafi, an oral medication, is the first and only product approved by the FDA for PV, a rare and progressive blood cancer.

“The approval of Jakafi represents an important advance for patients with uncontrolled PV. For the first time we are able to provide these patients a treatment that has been shown to provide effective and consistent control of their blood counts and reduce spleen volume,” said Srdan Verstovsek, M.D., Ph.D., Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center.

PV is a myeloproliferative neoplasm (MPN) and is typically characterized by elevated hematocrit, the volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of blood clots, as well as an elevated white blood cell and platelet count1. PV may occur at any age but often presents later in life, with a median age at diagnosis of 60 years.

Approximately 100,000 patients in the U.S. are living with PV3. Current standard treatment for PV is phlebotomy (the removal of blood from the body) plus aspirin. When phlebotomy can no longer control PV, chemotherapy such as hydroxyurea, or interferon, is utilized4,5. Approximately one in four (~25,000) patients with PV are considered uncontrolled6,7 because they have an inadequate response to or are intolerant of hydroxyurea, the most commonly used chemotherapeutic agent for the treatment of PV.

Patients with PV who fail to consistently maintain appropriate blood count levels, including appropriate hematocrit levels, have an approximately four times higher risk of major thrombosis (blood clots) or cardiovascular death8. Patients with PV can also suffer from an enlarged spleen, and a significant symptom burden which may be attributed to thickening of the blood and a lack of oxygen to parts of the body9. These symptoms commonly include fatigue, itching, night sweats, bone pain, fever, and weight loss5.

“Being diagnosed with a serious disease affects a person in a way that cannot be predicted,” said Robert Rosen, a patient living with PV and Founder and Chairman of the MPN Research Foundation. “The FDA approval of this drug is good news for our community and provides a new treatment option for those patients who do not respond to other therapies. This news confirms the ongoing importance of continued research, and the critical role that the MPN Research Foundation plays in improving the lives of patients.”

Jakafi is also the first and only FDA-approved product for the treatment of intermediate or high-risk myelofibrosis, a closely related blood cancer. Jakafi is a JAK1 and JAK2 inhibitor that targets overactive JAK pathway signaling, which plays a critical role in the development of both myelofibrosis and polycythemia vera10.

“The team at Incyte is proud that a second indication has been approved for Jakafi, further confirming the strength of our science and our commitment to discovering and developing innovative treatments for patients with cancer,” said Hervé Hoppenot, Incyte’s President and Chief Executive Officer.

The approval of Jakafi for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea was based on data from the pivotal Phase III RESPONSE trial, which was conducted under a Special Protocol Assessment from the FDA. In this trial, patients treated with Jakafi demonstrated superior hematocrit control and reductions in spleen volume compared to best available therapy. In addition, a greater proportion of patients on the ruxolitinib treatment arm achieved complete hematologic remission – which was defined as achieving hematocrit control, and lowering platelet and white blood cell counts. In the RESPONSE trial, the most common hematologic adverse reactions (incidence > 20%) were thrombocytopenia and anemia. The most common non-hematologic adverse events (incidence >10%) were headache, abdominal pain, diarrhea, dizziness, fatigue, pruritus, dyspnea and muscle spasms.

FDA Approves BLINCYTO™ (Blinatumomab) Immunotherapy for the Treatment of Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

On December 3, 2014 Amgen reported that the U.S. Food and Drug Administration (FDA) has granted approval of BLINCYTO (blinatumomab) for the treatment of patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) (Press release Amgen, DEC 3, 2014, View Source;p=RssLanding&cat=news&id=1994704 [SID:1234501069]). This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials. With this approval, BLINCYTO becomes the first FDA-approved bispecific CD19-directed CD3 T-cell engager (BiTE) antibody construct product, and the first single-agent immunotherapy to be approved for the treatment of patients with Ph- relapsed or refractory B-cell precursor ALL, a rare and rapidly progressing cancer of the blood and bone marrow.1-3

"The FDA’s breakthrough therapy designation and accelerated approval of BLINCYTO underscores the critical need for new treatment options for patients with relapsed or refractory B-cell precursor ALL, who are often young adults," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "BLINCYTO is the first clinical and regulatory validation of the BiTE platform, a new and innovative approach that helps the body’s own immune system fight cancer."

The BLINCYTO approval is based on results of Amgen’s ‘211 trial, a Phase 2, multicenter, single-arm open-label study. Eligible patients were > 18 years of age with Ph- relapsed or refractory B-cell precursor ALL. Relapsed or refractory was defined as relapsed with first remission duration of < 12 months in the first salvage, or relapsed or refractory after first salvage therapy, or relapsed within 12 months of allogeneic hematopoietic stem cell transplantation (HSCT), and had > 10 percent blasts in bone marrow. Of the 185 patients evaluated in the trial, 41.6 percent (77/185; 95 percent CI: 34.4-49.1) achieved complete remission or complete remission with partial hematologic recovery (CR/CRh*) within two cycles of treatment with BLINCYTO, which was the primary endpoint of the study. The majority of responses (81 percent [62/77]) occurred within the first cycle of treatment. Among patients who achieved CR/CRh*, 39 percent (30/77) went on to HSCT, and 75.3 percent (58/77 95 percent CI: 64.2-84.4) achieved minimal residual disease (MRD) response, a measure of eradication of residual disease at the molecular level.

"The approval of BLINCYTO represents a significant milestone in immunotherapy research, providing clinicians the opportunity to offer a new single-agent therapy to patients fighting this highly aggressive cancer with previously limited options," said Anthony S. Stein, M.D., clinical professor, Hematology/Oncology at City of Hope.

Array To Regain Worldwide Rights To Binimetinib

On December 3, 2014 Array BioPharma reported that it has reached a definitive agreement with Novartis International Pharmaceutical Ltd. to regain full worldwide rights to binimetinib, a MEK inhibitor in three Phase 3 trials (Press release Array BioPharma, DEC 3, 2014, View Source;p=RssLanding&cat=news&id=1994724 [SID:1234501062]). This agreement is conditional on the closing of transactions announced by Novartis and GlaxoSmithKline PLC (GSK) on April 22, 2014, which are expected in the first half of 2015, and remain subject to regulatory approval. Array had previously granted Novartis worldwide exclusive rights to develop and commercialize binimetinib under a 2010 License Agreement, which will terminate and be superseded by a new set of agreements between the parties.

"Regaining full worldwide rights to binimetinib, an innovative late-stage oncology product, represents a tremendous opportunity for Array," said Ron Squarer, Chief Executive Officer, Array BioPharma. "Binimetinib is currently advancing in three Phase 3 clinical trials and, we expect to file for our first regulatory approval during the first half of 2016. With this agreement, we are in a strong position to successfully develop and commercialize binimetinib to the benefit of cancer patients."

Novartis stated, "Binimetinib has demonstrated promising results for cancer patients across several different clinical trials. We are committed to supporting a successful transition to Array."

Upon deal close, Array will receive up to $85 million and Novartis’ global, exclusive license to binimetinib will terminate with all rights reverting to Array. Novartis has agreed to provide transitional regulatory, clinical development and manufacturing services as specified below and will assign to Array patent and other intellectual property rights it owns to the extent relating to binimetinib. All clinical trials involving binimetinib, including the COLUMBUS, NEMO and MILO pivotal trials, will continue to be conducted as currently contemplated.

Novartis will be responsible for continued conduct and funding of the COLUMBUS trial. This obligation will transfer to any future owner of LGX818 (encorafenib). Following deal close, Novartis will reimburse Array for all remaining out-of-pocket expenses and half of all remaining fully-burdened full time equivalent (FTE) costs associated with MILO, which Array will continue to conduct. For NEMO and all other ongoing and planned clinical trials, Novartis will conduct and solely fund each trial, until a mutually agreed-upon transition date to Array. Following this transition, Novartis will reimburse Array for all remaining out-of-pocket expenses and half of all remaining fully-burdened FTE costs required to complete these studies.

Novartis will remain responsible for conducting and funding development of the NRAS melanoma companion diagnostic until Premarket Approval is received from the U.S. Food and Drug Administration. Following approval, Novartis will transfer the product and Premarket Approval to a diagnostic vendor of Array’s designation.

Novartis also retains binimetinib supply obligations for all clinical and commercial needs for up to 30 months after closing and will also assist Array in the technology and manufacturing transfer of binimetinib. Novartis will also provide Array continued access to several Novartis pipeline compounds including, but not limited to, LEE011 (CDK 4/6 inhibitor) and BYL719 (a-PI3K inhibitor), for use in currently ongoing combination studies, and possible future studies, including Phase 3 trials, with binimetinib.