On September 7, 2016 Fate Therapeutics, Inc. (NASDAQ:FATE), a biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported a partnership with Memorial Sloan Kettering Cancer Center for the development of off-the-shelf T-cell product candidates using engineered pluripotent cell lines (Press release, Fate Therapeutics, SEP 7, 2016, View Source [SID:1234515009]). Research and development activities under the multi-year collaboration will be led by Michel Sadelain, M.D., Ph.D., Director of the Center for Cell Engineering and the Stephen and Barbara Friedman Chair at Memorial Sloan Kettering Cancer Center.

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"This partnership brings together Memorial Sloan Kettering’s excellence in the manufacture and delivery of cell-based immunotherapies, and our established expertise in pluripotent cell generation, engineering and differentiation," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "Together, we are at the forefront of an off-the-shelf paradigm shift, seeking to broaden patient access to revolutionary T-cell immunotherapies through a renewable, robust and standardized product approach."

"Engineering therapeutic attributes into pluripotent cell lines, such as antigen specificity, lack of alloreactivity, enhanced persistence and histocompatibility, is a breakthrough approach to renewably generate potent T-cell immunotherapies," said Dr. Sadelain. "This unique approach offers the prospect for off-the-shelf delivery of T-cell immunotherapies with enhanced safety and therapeutic potential at the scale necessary to serve significant numbers of patients."

The collaboration unites research, preclinical development and manufacturing work currently being conducted independently at Fate Therapeutics and Memorial Sloan Kettering to accelerate the clinical translation of T-cell product candidates derived from engineered pluripotent cells. Collectively, the groups have amassed significant and complementary expertise necessary to deliver off-the-shelf T-cell immunotherapies, including the engineering, maintenance and expansion of induced pluripotent cell lines and the scalable generation of T cells with enhanced safety profiles and effector functions.

In connection with the partnership, Fate Therapeutics has exclusively licensed from Memorial Sloan Kettering foundational intellectual property covering induced pluripotent cell-derived immune cells, including T cells and NK cells derived from pluripotent cells engineered with chimeric antigen receptors, for human therapeutic use. Additionally, Fate Therapeutics maintains an option to exclusively license intellectual property arising from all research and development activities under the collaboration.

Off-the-Shelf Immunotherapy Opportunity
Cellular immunotherapies are poised to transform the treatment of cancer and immunological conditions. However, cellular immunotherapies currently undergoing clinical investigation are patient-specific and their delivery requires the extraction, engineering, expansion and re-introduction of each individual patient’s T cells. This multi-step manufacturing process is logistically challenging and complex, and significant hurdles remain to ensure that patient-specific T-cell immunotherapies can be efficiently and consistently manufactured, and safely and reliably delivered, at the scale necessary to support broad patient access and wide-spread commercialization.

Induced pluripotent cells possess the unique dual properties of self-renewal and differentiation potential into all cell types of the body including T cells. Similar to master cell lines used for the manufacture of monoclonal antibodies, engineered pluripotent cell lines can repeatedly deliver clonal populations of T cells with broad histocompatibility and enhanced effector functions. These highly-stable pluripotent cell lines have the potential to serve as a renewable cell source for the consistent manufacture of homogeneous populations of effector cells for the treatment of many thousands of patients.

Exclusive License & Development Plan
Through the three-year collaboration, the group aims to leapfrog the field’s current patient-specific approach to T-cell immunotherapy. Over the last decade, Fate Therapeutics has developed a proprietary, patent-protected platform to efficiently generate, genetically engineer, isolate and bank pluripotent cell lines. Memorial Sloan Kettering is leading the field in generating pluripotent cell-derived, tumor-targeting T cells that are capable of profound tumor clearance in vivo. The scientific teams will combine forces to create pluripotent cell lines that have been engineered for enhanced antigen specificity and functionality, optimize T-cell differentiation protocols, and clinically translate off-the-shelf engineered T-cell product candidates.

New Subsidiary Formed
Fate Therapeutics has also launched a new venture company, Tfinity Therapeutics, Inc., which will focus exclusively on the advancement of off-the-shelf T-cell immunotherapies across a wide range of diseases using Fate’s proprietary, patent-protected pluripotent cell platform. Fate Therapeutics has an intellectual property portfolio consisting of over 60 issued patents and 90 pending patent applications, which are owned or exclusively licensed by Fate Therapeutics, that cover compositions and methods critical for deriving, engineering, maintaining and differentiating induced pluripotent cells. Tfinity Therapeutics is a majority-owned subsidiary of Fate Therapeutics, and holds an option to license from Fate Therapeutics intellectual property covering pluripotent cell-derived T-cell immunotherapies.

On September 6, 2016 (GLOBE NEWSWIRE) Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), a biopharmaceutical company developing oral therapies that target various phases of cell cycle control for the treatment of cancer and other serious disorders, reported the presentation of preclinical data demonstrating that both Cyclacel’s CYC065, a clinical stage, second generation, cyclin-dependent kinase CDK2/9 inhibitor, and CCT68127, a preclinical stage CDK2/9 inhibitor, prolong survival in MYCN-addicted neuroblastoma models (Press release, Cyclacel, SEP 6, 2016, View Source [SID:1234514936]). The data were presented at the Childhood Cancer Meeting, September 5 — 7th in London, UK.

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"This study adds to the growing evidence of the value of CDK inhibition as an approach to treating cancer. MYCN is an important therapeutic target in oncology and a major oncogenic driver of neuroblastoma, a childhood cancer. There are no approved drugs that act against MYCN or MYC proteins," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "We are encouraged by the preclinical data, which extend and support earlier findings, showing that CYC065 and CCT68127 reduce MYCN transcription and protein levels and have antitumor activity in neuroblastoma models. Additionally, we have demonstrated in other preclinical studies, that our transcriptional CDK2/9 inhibitors target key molecular features of cancers with poor prognosis, such as MLL-r leukemias or MYC-driven lymphomas. Furthermore, evidence from early clinical trials show that CDK2/9 inhibitors can have a synergistic effect with other anticancer agents. We look forward to reporting data from our ongoing Phase 1 study of CYC065 in patients with solid tumors."

In this preclinical study, an international group of researchers led by Prof. Louis Chesler from The Institute of Cancer Research, London, explored in vitro and in vivo the sensitivity of neuroblastoma cells to CYC065 and CCT68127. Neuroblastoma cells with MYCN amplification and overexpression were found to be particularly sensitive to both CDK2/9 inhibitors. The mechanism of action of CYC065 and CCT68127 included inhibition of MYCN transcription, downregulation of N-MYC protein, blocking neuroblastoma cell proliferation and induction of apoptosis. Treatment with either CYC065 or CCT68127 significantly reduced tumor burden and prolonged survival in several neuroblastoma models in vivo.

Citation

Poon E, Jamin Y, Walz S, Hakkert S, Kwok C, Hallsworth A, Thway K, Barker K, Sbirkov Y, Pickard L, Urban Z, Tardif N, Webber H, Box G, Valenti M, De Haven Brandon A, Petrie K, Ebus M, Molenaar J, Eccles S, Robinson SP, Zheleva D, Eilers M, Workman P, Chesler L. The small molecule CDK2 and CDK9 inhibitors CYC065 and CCT68127 are potent inhibitors of MYCN via transcriptional repression. Childhood Cancer Meeting 2016, September 5 — 7th, London, UK, Abs. 1-19.

About MYCN

The MYCN gene encodes a transcription factor that is expressed in fetal brain and neural crest and is critical for normal development of the brain and nerves. The MYCN oncogene is over-expressed in a number of different types of cancer, most notably neuroblastoma, and also rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor and small cell lung cancer. Amplification of the MYCN oncogene is the most common genomic alteration in aggressive neuroblastomas and is associated with poor clinical outcome. There are no approved drugs that directly target MYCN prompting the investigation of indirect approaches such as exploitation of a synthetic lethal relationship between MYCN amplification/overexpression and inhibition of CDK2.

About Neuroblastoma

According to the American Cancer Society, neuroblastoma is the most common cancer in infants less than one year old and it accounts for about six percent of all pediatric cancers or about 700 cases per year. The disease has a fatal outcome in one out of every seven children diagnosed with it. Preclinical data from an international investigator group demonstrated that Cyclacel’s CYC065 and CCT68127 target MYCN gene expression and have potent in vitro and in vivo anti-tumor activities, suggesting therapeutic potential in neuroblastoma, including high-risk patients with MYCN amplification.

About CYC065

CYC065 is a highly-selective, orally- and intravenously-available, second generation inhibitor of CDK2 and CDK9 and causes apoptotic death of cancer cells at sub-micromolar concentrations. Antitumor efficacy has been achieved in vivo with once a day oral dosing at well tolerated doses. Evidence from published nonclinical studies show that CYC065 may benefit patients with adult and pediatric hematological malignancies, including certain Acute Myeloid Leukemias (AML), Acute Lymphocytic Leukemias (ALL), Chronic Lymphocytic Leukemias (CLL), B-cell lymphomas, multiple myelomas, and certain solid tumors, including breast and uterine cancers. Independent investigators published nonclinical evidence that CYC065 induced regression or tumor growth inhibition in a model of HER2-positive breast cancer addicted to cyclin E that is resistant to trastuzumab, reduced tumor growth in models of CCNE1-amplified uterine serous carcinoma and reduced tumor burden and prolonged survival in several neuroblastoma models in vivo.

CYC065 is mechanistically similar but has much higher dose potency, in vitro and in vivo, improved metabolic stability and longer patent protection than seliciclib, Cyclacel’s first generation CDK inhibitor. Translational biology data support development of CYC065 as a stratified medicine for solid and liquid cancers. CYC065 has been shown to reverse drug resistance associated with the addiction of cancer cells to cyclin E and may inhibit CDK9-dependent oncogenic and leukemogenic pathways, including malignancies driven by certain oncogenes and mixed lineage leukemia rearrangements (MLL-r). CYC065 causes prolonged down regulation of the Mcl-1-mediated pro-survival pathway in cancer cells.

On September 6, 2016 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that new preclinical data as well as early clinical data from an ongoing Phase 1 study will be presented for IPI-549, an immuno-oncology development candidate that selectively inhibits PI3K-gamma, during the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper): Translating Science into Survival taking place September 25-28, 2016, in New York City (Press release, Infinity Pharmaceuticals, SEP 6, 2016, View Source;p=RssLanding&cat=news&id=2199662 [SID:1234514950]).

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The following two presentations will take place during the poster session being held on Monday, September 26, from 5:15 p.m. – 7:45 p.m. ET:

Title: IPI-549-01: A Phase 1/1b first-in-human study of IPI-549, a PI3K-gamma inhibitor, as monotherapy and in combination with an anti-PD1 antibody in subjects with advanced solid tumors
Poster Board: B070
Presentation Time: Monday, September 26, 6:15 p.m. – 7:15 p.m. ET

Title: The PI3K-gamma inhibitor, IPI-549, increases antitumor immunity by targeting tumor-associated myeloid cells and remodeling the immune-suppressive tumor microenvironment
Poster Board: B032
Presentation Time: Monday, September 26, 6:15 p.m. – 7:15 p.m. ET

About IPI-549
IPI-549 is an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 inhibits immune-suppressive macrophages within the tumor microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.

On September 6, 2016 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies and advancing its proprietary R&D pipeline, reported that the National Comprehensive Cancer Network (NCCN) Oncology Research Program (ORP) has awarded three grants to investigators to support research of bavituximab in combination with other therapeutics for the treatment of glioblastoma, head and neck cancer, and hepatocellular carcinoma (Press release, Peregrine Pharmaceuticals, SEP 6, 2016, View Source [SID:1234514951]).

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NCCN, a not-for-profit alliance of 27 of the world’s leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Funding for the three investigator-initiated clinical studies will take place through a $2 million research grant made by Peregrine to NCCN’s ORP. NCCN will be responsible for oversight and monitoring of the clinical studies through the research grant. It is expected that the selected trials will be initiated in early 2017.
"NCCN is excited to initiate three studies by accomplished investigators at NCCN Member Institutions that will explore the effect of this novel immunotherapy in three different cancers with significant unmet need," said Robert C. Young, MD, Interim Vice President, NCCN ORP.
The following NCCN-affiliated researchers were recipients of the grant awards:
Jessica Frakes, MD, Moffitt Cancer Center, "A Phase I Trial of Sorafenib and Bavituximab Plus Stereotactic Body Radiation Therapy (SBRT) for Unresectable Hepatitis C Associated Hepatocellular Carcinoma"

Elizabeth Gerstner, MD, Massachusetts General Hospital Cancer Center, "Phase I/II Clinical Trial of Bavituximab with Radiation and Temozolomide for Patients with Newly Diagnosed Glioblastoma"

Ranee Mehra, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, "Phase II Study of Pembrolizumab and Bavituximab for Progressive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck"
"Our collaboration with NCCN provides the unique opportunity to support the group’s highly-regarded research institutions and advance our understanding of the potential role of bavituximab in the treatment of various cancers. With this in mind, we were very pleased by the level of interest shown in bavituximab from the NCCN community and are grateful to all those who submitted their projects for rigorous evaluation by the ORP scientific review committee," said Joseph Shan, MPH, vice president, clinical and regulatory affairs of Peregrine. "We’d like to extend our congratulations to the three investigators who were selected for their unique and innovative concepts. These studies align with our development strategy for bavituximab which is currently focused on small, early stage clinical trials evaluating the drug in combination with other cancer treatments. Collaborators such as NCCN play a central role in this strategy and we look forward to integrating the valuable clinical data generated by these investigators to expand our knowledge regarding bavituximab-focused cancer treatment combinations."
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab is believed to override PS mediated immunosuppressive signaling by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses.

On September 6, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that data from six abstracts will be presented at the 2016 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) annual meeting, October 7 to October 11, 2016, in Copenhagen (Press release, TESARO, SEP 6, 2016, View Source [SID:1234514953]). In addition, TESARO will webcast an investor and analyst briefing from Copenhagen on Saturday, October 8 at 7:00 PM local time in conjunction with the ESMO (Free ESMO Whitepaper) annual meeting.

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Please plan to visit TESARO at Booth #415 for information about our pipeline.

Presentation Details (all times local):

Niraparib

Saturday, October 8, 2016, 4:30 PM to 6:00 PM — Presidential Symposium 1
A randomized, double-blind phase 3 trial of maintenance therapy with niraparib vs placebo in patients with platinum-sensitive recurrent ovarian cancer (ENGOT-OV16/NOVA trial)
Presentation: LBA3_PR, Presidential Symposium 1, Location: Copenhagen Room, Time: 5:30 PM
Results selected for inclusion in the ESMO (Free ESMO Whitepaper) Press Programme

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Modeling maintenance therapy in ovarian cancer
Poster: 1043P, Location: Hall E

Niraparib is an investigational product candidate that has not been approved by any regulatory agencies.

Rolapitant

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Efficacy and safety of rolapitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in elderly patients
Poster: 1441P, Location: Hall E

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with gastrointestinal and colorectal cancers
Poster: 1440P, Location: Hall E

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving Breast Cancer Resistant Protein (BCRP) substrate chemotherapy agents
Poster: 1442P, Location: Hall E

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Systematic review of the efficacy and safety of neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: identification of the relevant clinical trials
Poster: 1443P, Location: Hall E

Rolapitant is marketed in the United States under trade name VARUBI. Rolapitant has not been approved by any regulatory agencies outside of the United States.

Investor Briefing and Webcast
TESARO will webcast an investor and analyst briefing in Copenhagen on Saturday, October 8 at 7:00 PM local time in conjunction with the ESMO (Free ESMO Whitepaper) annual meeting. At this briefing, TESARO management will review the niraparib development program and data presented at ESMO (Free ESMO Whitepaper) and answer questions from investors and analysts. This event will be webcast live and archived for 30 days, and may be accessed from the TESARO Investor Events and Presentations webpage at www.tesarobio.com.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in four ongoing pivotal trials. TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes the Phase 3 trial in patients with recurrent ovarian cancer (the NOVA trial); a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial); a Phase 3 trial for the treatment of patients with BRCA-positive breast cancer (the BRAVO trial); and a Phase 3 trial in patients with first-line ovarian cancer (the PRIMA trial). Several collaborator-sponsored studies are also underway, including combination trials of niraparib plus pembrolizumab and bevacizumab. Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

About VARUBI (Rolapitant)
Rolapitant is marketed in the United States under trade name VARUBI. VARUBI is a substance P/neurokinin-1 (NK-1) receptor antagonist indicated in the U.S. in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6 substrate. The inhibitory effect of a single dose of VARUBI on CYP2D6 lasts at least seven days and may last longer. Avoid use of pimozide; monitor for adverse events if concomitant use with other CYP2D6 substrates with a narrow therapeutic index cannot be avoided. Please see full prescribing information, including additional important safety information, available at www.varubirx.com.

An intravenous formulation of rolapitant is also being developed. TESARO licensed exclusive rights for the development, manufacture, commercialization, and distribution of VARUBI (rolapitant) from OPKO Health, Inc.