News Article | May 4, 2017
(New York, NY - May 4, 2017) -- Immunotherapy, which has achieved remarkable results in late-stage lung cancer patients, can also hold great hope for newly diagnosed patients, cutting the deadly disease off before it has the chance to take hold and offering a potential cure, according to a new Mount Sinai study published today in Cell. Researchers at The Tisch Cancer Institute at Mount Sinai discovered that some of the same immune cells that allow immunotherapy to turn around some late-stage lung cancers are also present just as the disease takes hold. Before now, little was known about the immune response in early lung cancer, said Miriam Merad, MD, PhD, Professor of Oncological Sciences and of Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at Mount Sinai. Dr. Merad and a multidisciplinary team of thoracic surgeons, pathologists, and scientists devised a comprehensive study that began when patients went into surgery to have cancerous lesions removed. The patients' lung tumor samples, samples of surrounding healthy lung tissue, and blood samples were immediately analyzed on a cellular level to map out the immune system components present. The team of researchers crafted a barcoding method that attaches cells in each sample to a different metal isotope, allowing the samples to be pooled for a simultaneous analysis of cells from all three tissue types. The scientists combined this barcoding approach with high-dimensional profiling to map the complete immune landscape to search for tumor-driven changes that would be vulnerable to targeted immunotherapy. The analysis of the samples showed that stage I lung cancer lesions already harbor immune system components that likely compromise anti-tumor T cells' ability to fend off cancer. These single-cell analyses offered unprecedented detail of tumor-driven immune changes, providing a powerful tool for the future design of immunotherapies such as checkpoint inhibitors, particularly those that target the PD-1 and PD-L1 proteins that shield cancer from the immune system; these checkpoint inhibitors have shown great promise in later-stage cancers. "Immunotherapy has mostly been used in advanced or metastatic lung cancer, but its benefit in early-stage tumors remains unknown," Dr. Merad said. "The standard treatment for early lung cancer is normally surgical removal of the lesions--sometimes with chemotherapy and radiation. Our study reveals that early lung lesions are heavily infiltrated with many different immune cells, suggesting that immunotherapy could also work on very early lesions and potentially lead to a cure by heading cancer off at the pass before it really takes root in the lungs." This new research also identified a multitude of additional immunotherapy targets to increase the number of patients that would significantly benefit from immunotherapy, which at the moment remains fairly small. This research is being used to develop immunotherapy trials with early lung cancer patients. "About 50 percent of patients with small lung cancer lesions relapse," Merad said. "And when lung cancer is advanced, chemotherapy does not have a great success rate, so knowing how to attack the cancer at an early stage could have huge impacts on the number of patients relapsing and their overall survival. Our research further corroborates the belief that immunotherapy agents are most efficient at early stages of cancer, particularly in patients who have never been treated with chemotherapy." Raja M. Flores, MD, Chair of the Department of Thoracic Surgery at Mount Sinai Health System, and his team contributed significantly to the study by identifying patients and providing their tissue samples. Mount Sinai's Human Immune Monitoring Center (HIMC) also played an integral role, by providing a platform to analyze patient samples using quality control assays and cutting-edge technology. Through the HIMC, Dr. Merad plans to build a portal to share the results of this study and of other HIMC research to collaborate with colleagues at other cancer centers in the hopes of promoting further cancer and immunology research. This study was funded by Foundation pour la Recherche Medicale DEA20150633125 and NIH grants R01, R01 CA173861, U19AI128949, U24 AI 118644, U19 AI 117873-01. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is on the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. or find Mount Sinai on Facebook, Twitter and YouTube.
CEA response is associated with tumor response and survival in patients with KRAS exon 2 wild-type and extended RAS wild-type metastatic colorectal cancer receiving first-line FOLFIRI plus cetuximab or bevacizumab (FIRE-3 trial)
PubMed | Klinikum Chemnitz, Ludwig Maximilians University of Munich, University of Greifswald, Practice for Hematology and Medical Oncology and 6 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
To examine the relation of carcinoembryonic antigen (CEA) response with tumor response and survival in patients with (K)RAS wild-type metastatic colorectal cancer receiving first-line chemotherapy in the FIRE-3 trial comparing FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab.CEA response assessed as the percentage of CEA decrease from baseline to nadir was evaluated for its association with tumor response and survival. Receiver operating characteristic analysis revealed an optimal cut-off value of 75% using the maximum of sensitivity and specificity for CEA response to discriminate CEA responders from non-responders. In addition, the time to CEA nadir was calculated.Of 592 patients in the intent-to-treat population, 472 were eligible for analysis of CEA (cetuximab arm: 230 and bevacizumab arm: 242). Maximal relative CEA decrease (%) significantly (P = 0.003) differed between the cetuximab arm (median 83.0%; IQR 40.9%-94.7%) and the bevacizumab arm (median 72.3%; IQR 26.3%-91.0%). In a longitudinal analysis, the CEA decrease occurred faster in the cetuximab arm and was greater than in the bevacizumab arm at all evaluated time points until 56 weeks after treatment start. CEA nadir occurred after 3.3 months (cetuximab arm) and 3.5 months (bevacizumab arm), (P = 0.49). In the cetuximab arm, CEA responders showed a significantly longer progression-free survival [11.8 versus 7.4 months; hazard ratio (HR) 1.53; 95% Cl, 1.15-2.04; P = 0.004] and longer overall survival (36.6 versus 21.3 months; HR 1.73; 95% Cl, 1.24-2.43; P = 0.001) than CEA non-responders. Analysis of extended RAS wild-type patients revealed similar results.In the FIRE-3 trial, CEA decrease was significantly faster and greater in the cetuximab arm than in the bevacizumab arm and correlated with the prolonged survival observed in patients receiving FOLFIRI plus cetuximab.NCT00433927 (ClinicalTrials.gov); AIO KRK0306 FIRE-3.
News Article | February 15, 2017
Physicians’ Education Resource®, (PER®), will host the 21st Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and Myeloma, and the symposium will be co-chaired by Andre Goy — who is professor of medicine, chief of lymphoma and director at John Theurer Cancer Center, chair of oncology for Hackensack Meridian Health Network in Hackensack, New Jersey — and Sager Lonial, who is a professor and chair of the Department of Hematology and Medical Oncology at Emory School of Medicine, chief medical officer of the Winship Cancer Institute of Emory University in Atlanta, Georgia. “We are in the midst of unprecedented changes in medicine particularly in oncology,” said Goy. “Symposiums such as Miami Hematology, offer an opportunity for each attendee to share directly with world experts how such changes can truly reshape patients’ care.” The 21st Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and Myeloma is designed to facilitate application of the rapid changes seen in oncology while treating hematological malignancies. As health care continues to rapidly evolve, it becomes critical not only to be able to choose the best option for each patient precision medicine but also in an era with so many options available— to appreciate the best sequence of therapies to optimize outcome. This will be addressed throughout the three-day-conference during the well-known and highly interactive Medical Crossfire® discussion panels and real-world case discussions. In addition, Amy E. Herman, will speak on “The Art of Perception and its Connection to the Art of Clinical Medicine.” Herman is a leading expert in professional development, training some of the most influential industry leaders around the world, including the FBI, CIA, Scotland Yard and the Peace Corps. Previously, Herman was the director of the educational development for Thirteen/WNET, the public television station, serving New Jersey and New York. The three-day symposium will be held at the Trump International Miami on Feb.23-25 in Sunny Isles Beach, Florida, located 3.5 miles from the Miami International Airport and 13 miles from the Fort Lauderdale International Airport. About PER® Since 1995, PER® has been the educational resource of choice for live and online activities focusing on oncology and hematology. PER® provides high-quality, evidence-based activities featuring leading national and international faculty with a focus on practice-changing advances and standards of care in treatment and disease management. Activities also include topics on emerging strategies currently under investigation, supportive care, diagnosis and staging, prevention, screening and early detection, and practice management. With the rapid advances occurring in the field of oncology, understanding how to use molecular data to diagnose and stage patients, selecting the most appropriate candidates for novel therapeutic agents, individualizing treatment based on tumor type, and referring patients to clinical trials will continue to ensure the highest level of patient care is provided. PER® serves the oncology health care community, including physicians, fellows, advanced practice nurses, nurses, physician assistants, pharmacists, and researchers. PER® is part of the Cranbury, N.J.-based Michael J. Hennessy Associates, Inc. family of businesses. Learn more at http://www.gotoper.com and http://www.mjhassoc.com
News Article | October 28, 2016
BATON ROUGE, LA--(Marketwired - October 24, 2016) - OncBioMune Pharmaceuticals, Inc. ( : OBMP) ("OncBioMune" or the "Company"), a clinical stage biopharmaceutical company engaged in the development of novel cancer products and a proprietary vaccine technology, is pleased to announce that, effective immediately, Dr. Brian Barnett has joined the OncBioMune Scientific Advisory Board. Dr. Barnett currently serves as Senior Medical Director, Neratinib, Medical Affairs at Puma Biotechnology. Prior to accepting his position at Puma Biotechnology, Dr. Barnett held numerous senior level positions at Roche Group subsidiary Genentech providing oversight in the FDA approval and launch of the potential blockbuster breast cancer drug Kadcyla. These positions at Genentech included Associate Medical Director, Kadcyla, U.S. Medical Affairs; Medical Director, Kadcyla, U.S. Medical Affairs; and Medical Director, Kadcyla, Global Product Development Oncology. Before his time at Genentech, Dr. Barnett served as Director of Medical Oncology at the Elliott, Barnett, Head Breast Cancer Research and Treatment Center. Throughout his career, Dr. Barnett has authored and been integral to many peer-reviewed publications on immunotherapy and delivered oral and poster presentations at leading oncology conferences on regulating cancer with immunotherapy approaches. Dr. Barnett earned a Bachelor of Science (BS) degree in Chemistry from Millsaps College, a Doctor of Medicine (MD) degree from the University of Mississippi School of Medicine and completed his medical training as a Fellow, Hematology and Medical Oncology at Tulane University Health Sciences Center. He is an active member of the American Association of Cancer Research and the American Society of Clinical Oncology. "I'm well aware of the potential of the vaccine technology that OncBioMune is developing after working closely with Drs. Head and Elliott at their breast cancer center," said Dr. Barnett. "I am impressed with what I see in the clinical data of ProscaVax as a novel prostate cancer vaccine and look forward to sharing my clinical experiences going forward as ProscaVax commences mid-stage studies." "On behalf of our entire team, I'd like to formally welcome Dr. Barnett to our Scientific Advisory Board," said Dr. Jonathan Head, Chief Executive Officer at OncBioMune. "Brian is highly-respected as a thought leader in the immunotherapy space and brings years of highly relevant experience to our team in Phase 2 and Phase 3 clinical research. His knowledge and network will be a invaluable assets as we move forward with not only ProscaVax, but our entire pipeline." Sign up for OncBioMune email alerts at: http://oncbiomune.com/email-alerts/. OncBioMune Pharmaceuticals is a clinical-stage biopharmaceutical company engaged in the development of novel cancer immunotherapy products, with a proprietary Vaccine Technology that is designed to stimulate the immune system to attack its own cancer while not hurting the patient. Our lead product, ProscaVax® is scheduled to commence a Phase 2 clinical study in 2016. OncBioMune also has a portfolio of targeted therapies, some of which are biosimilars to blockbuster drugs. OncBioMune is headquartered in Baton Rouge, LA. This press release does not constitute an offer to sell or a solicitation of an offer to buy the securities in this offering, nor will there be any sale of these securities in any jurisdiction in which such offer solicitation or sale are unlawful prior to registration or qualification under securities laws of any such jurisdiction. This press release contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 that involve risks, uncertainties and assumptions that could cause OncBioMune Pharmaceuticals' actual results and experience to differ materially from anticipated results and expectations expressed in these forward looking statements. OncBioMune Pharmaceuticals has in some cases identified forward-looking statements by using words such as "anticipates," "believes," "hopes," "estimates," "looks," "expects," "plans," "intends," "goal," "potential," "may," "suggest," and similar expressions. Among other factors that could cause actual results to differ materially from those expressed in forward-looking statements are OncBioMune Pharmaceuticals' need for, and the availability of, substantial capital in the future to fund its operations and research and development; the fact that OncBioMune Pharmaceutical's vaccines and therapeutics may not successfully complete pre-clinical or clinical testing, or be granted regulatory approval to be sold and marketed in the United States or elsewhere. A more complete description of these risk factors is included in OncBioMune Pharmaceutical's filings with the Securities and Exchange Commission. You should not place undue reliance on any forward-looking statements. OncBioMune Pharmaceuticals undertakes no obligation to release publicly the results of any revisions to any such forward-looking statements that may be made to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events, except as required by applicable law or regulation.
News Article | March 1, 2017
Late-Breaking Presentation Highlighting Interim Phase 2b Selinexor Data in Patients with Relapsed or Refractory DLBCL (SADAL Study) Overview of Key Selinexor Myeloma Data Also Featured at the 16th International Myeloma Workshop NEWTON, Mass., March 01, 2017 (GLOBE NEWSWIRE) -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today announced that 12 abstracts describing the Company's product candidates in development for hematological and solid tumor malignancies have been selected for presentation at the 2017 Annual Meeting of the American Association for Cancer Research (AACR) taking place April 1-5, 2017 in Washington, DC. The abstracts, which represent both company- and investigator-sponsored studies, describe data related to Karyopharm’s lead product candidate, selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export / SINE™ compound, as well as two of its promising Phase 1 oncology programs, KPT-8602, a second-generation oral SINE compound, and KPT-9274, a first-in-class oral dual inhibitor of PAK4 and NAMPT. “The ongoing randomized Phase 2b SADAL study, which was initiated based on encouraging Phase 1 data in patients with diffuse large B-cell lymphoma (DLBCL), was designed to evaluate the overall response rate of single-agent oral selinexor in patients with relapsed or refractory DLBCL,” said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. “We look forward to presenting interim results from this important trial at AACR this year.” Karyopharm is also presenting an overview of selinexor myeloma data at the 16th International Myeloma Workshop (IMW) held March 1-4, 2017 in New Delhi, India. In an oral presentation, titled “Oral Selinexor Shows Single Agent Activity Enhanced with PI or IMiD Combinations in Refractory Multiple Myeloma,” (Abstract #234) Sagar Lonial, MD, FACP, Professor and Chair, Hematology and Medical Oncology, Emory University, provided an overview of clinical data demonstrating selinexor’s activity in combination with proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) for the treatment of relapsed or refractory multiple myeloma. The 2017 IMW is a prestigious biannual event where myeloma experts from around the world gather to discuss basic, preclinical and clinical aspects in the biology and treatment of multiple myeloma. Title: A Phase 2b randomized study of selinexor in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) demonstrates durable responses in both GCB and non-GCB subtypes Presenter: Marie Maerevoet, Institute Jules Bordet Poster Board #: 13 Session: Phase I-III Clinical Trials and Pediatric Clinical Trials Location: Convention Center, Halls A-C, Poster Section 33 Date and Time: Tuesday, April 4, 2017 from 1:00 PM - 5:00 PM Title: KPT-9274 inhibits cellular NAD and synergizes with doxorubicin to treat dogs with lymphoma Presenter: Cheryl London, Tufts University Poster Board #: 16 Session: Late-Breaking Research: Experimental and Molecular Therapeutics 2 Location: Convention Center, Halls A-C, Poster Section 34 Date and Time: Wednesday, April 5, 2017 8:00 AM - 12:00 PM Title: Selinexor or KPT-8602 mediated XPO1 inhibition synergizes with dexamethasone to repress convergent pathways in the mTORC1 signaling network and drive cell death in multiple myeloma Presenter: Christian Argueta, Karyopharm Therapeutics Inc. Poster Board #: 15 Session: Molecular and Cellular Biology/Genetics – Cell Growth Signaling Pathways 1 Location: Convention Center, Halls A-C, Poster Section 14 Date and Time: Sunday, April 2, 2017 1:00 PM - 5:00 PM Title: Novel role of XPO1 in regulating microRNAs related to pancreatic ductal adenocarcinoma invasion and metastasis Presenter: Asfar Azmi, Wayne State University Poster Board #: 5 Session: Molecular and Cellular Biology/Genetics – MicroRNA Regulation of Cancer Biology 1 Location: Convention Center, Halls A-C, Poster Section 19 Date and Time: Sunday, April 2, 2017 1:00 PM - 5:00 PM Title: Synergistic effects of the XPO1 inhibitor selinexor with proteasome inhibitors in pediatric high-grade glioma and diffuse intrinsic pontine glioma Presenter: John DeSisto, University of Colorado Denver Poster Board #: 18 Session: Tumor Biology: Pediatric Cancer 1: Biomarkers, Preclinical Models, and New Targets Location: Convention Center, Halls A-C, Poster Section 42 Date and Time: Monday, April 3, 2017 8:00 AM - 12:00 PM Title: Anti-tumor activity of selinexor is enhanced by palbociclib in preclinical models of HER2+ breast cancer Presenter: Hua Chang, Karyopharm Therapeutics Inc. Poster Board #: 12 Session: Experimental and Molecular Therapeutics – Combination Therapy 1 Location: Convention Center, Halls A-C, Poster Section 2 Date and Time: Monday, April 3, 2017 8:00 AM - 12:00 PM Title: Disruption of nuclear export with selinexor or KPT-8602 reduces androgen receptor expression and leads to potent anti-tumor activity in preclinical models of androgen-independent prostate cancer Presenter: Christian Argueta, Karyopharm Therapeutics Inc. Poster Board #: 13 Session: Endocrinology – Prostate Cancer Biology and Therapy Location: Convention Center, Halls A-C, Poster Section 25 Date and Time: Monday, April 3, 2017 8:00 AM - 12:00 PM Title: p21 activated kinase 4 (PAK4) as a novel therapeutic target for non-Hodgkin's lymphoma Presenter: Asfar Azmi, Wayne State University Poster Board #: 9 Session: Molecular and Cellular Biology/Genetics – Cell Growth Signaling Pathways 4 Location: Convention Center, Halls A-C, Poster Section 14 Date and Time: Monday, April 3, 2017 8:00 AM - 12:00 PM Title: Nuclear export of E2F7 in squamous cell carcinoma is an actionable event that reverses resistance to anthracyclines Presenter: Alba Natalia Saenz Ponce, University of Queensland, Brisbane, Australia Poster Board #: 28 Session: Experimental and Molecular Therapeutics: Reversal of Drug Resistance Location: Convention Center, Halls A-C, Poster Section 6 Date and Time: Monday, April 3, 2017 8:00 AM - 12:00 PM Title: Exportin-1 (XPO1) is a novel therapeutic biomarker for patients with neuroblastoma Presenter: Basia Galinski, Albert Einstein College of Medicine Poster Board #: 10 Session: Pediatric Cancer 1: Biomarkers, Preclinical Models, and New Targets Location: Convention Center, Halls AC, Poster Section 42 Date and Time: Monday, April 3, 2017 8:00 AM - 12:00 PM Title: Combined targeting of estrogen receptor alpha and nuclear transport pathways remodel metabolic pathways to induce apoptosis and overcome tamoxifen resistance Presenter: Eylem Kulkoyluoglu-Cotul, University of Illinois Urbana-Champaign Poster Board #: 14 Session: Endocrinology: Nuclear Receptors and Endocrine Oncology Therapies Location: Convention Center, Halls A-C, Poster Section 25 Date and Time: Tuesday, April 4, 2017 8:00 AM - 12:00 PM Title: Selinexor synergizes with DNA damaging agents through down-regulation of key DNA damage response genes Presenter: Trinayan Kashyap, Karyopharm Therapeutics Inc. Poster Board #: 26 Session: Experimental and Molecular Therapeutics – New Targets and New Drugs Location: Convention Center, Halls A-C, Poster Section 5 Date and Time: Tuesday, April 4, 2017 1:00 PM - 5:00 PM Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE™ compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 1,900 patients have been treated with selinexor and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Karyopharm plans to initiate a pivotal randomized Phase 3 study of selinexor in combination with bortezomib (Velcade®) and low-dose dexamethasone (BOSTON) in patients with multiple myeloma in early 2017. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company's clinical development priorities for selinexor. The latest clinical trial information for selinexor is available at www.clinicaltrials.gov. Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport and related targets for the treatment of cancer and other major diseases. Karyopharm's SINE™ compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). In addition to single-agent and combination activity against a variety of human cancers, SINE™ compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm, which was founded by Dr. Sharon Shacham, currently has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com. This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company's current expectations. For example, there can be no guarantee that any of Karyopharm's SINE™ compounds, including selinexor (KPT-330), KPT-8602 and KPT-9274, will successfully complete necessary preclinical and clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, which was filed with the Securities and Exchange Commission (SEC) on November 7, 2016, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
News Article | December 14, 2016
(New York, NY - December 12, 2016) -- Even before tumors develop, breast cancer cells with a few defined molecular alterations can spread to organs, remain quiet for long periods of time, and then awaken to form aggressive, deadly breast cancer metastasis, says a team of investigators led by researchers at Icahn School of Medicine at Mount Sinai and the University of Regensburg in Germany. They say their finding, published in two papers in the journal Nature, and conducted in animal models and tested in human samples, now solves the mystery of how breast cancer metastasis forms without a primary tumor in this new model of early dissemination and metastasis. Furthermore, a clinical primary tumor may never develop, investigators say. The University of Regensburg team had discovered that cancer cells could spread not only from a highly mutated, overtly evolved and pathologically-defined invasive tumors, but also from early stage cancers commonly considered incapable of spreading cells. However, how these early cancer lesions could spawn cells with traits of malignant tumors was unknown. In two papers published in the journal Nature, and conducted in animal models and tested in human samples, the two teams now have identified the first mechanisms that allow cells to spread early in cancer progression and contribute to metastasis. In the study from Mount Sinai, two changes in mammary cancer cells -- a switched-on oncogene and a turned-off tumor suppressor-- motivated cells to travel from breast tissue to the lungs and other parts of the body. There, the cells stayed quiet until a growth switch was activated and metastases developed in lungs. "This research provides insight into the mechanisms of early cancer spread and may shed light into unexplained phenomena -- among them, why as many as 5 percent of cancer patients worldwide have cancer metastases but no original tumor, and most importantly, why it is so difficult to treat cancer that has spread," says the study's senior investigators, Julio A. Aguirre-Ghiso, PhD, Professor of Medicine, Hematology and Medical Oncology, Maria Soledad Sosa, PhD, Assistant Professor of Pharmacological Sciences, and graduate student Kathryn Harper of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "Biologically, this new model of early metastasis challenges everything we thought we knew about how cancer spreads and forms metastasis. It feels like we are going to have to adjust our ideas about the subject of metastasis," he says. "Our hope is that these findings will reshape the way we think about how metastasis should be treated." An important finding from the Mount Sinai team is that most early spread cells remain dormant and most chemotherapy and targeted therapies are aimed at those cells that are proliferative. So early spread cancer cells would escape these conventional therapies even if it kills a primary tumor, Dr. Aguirre-Ghiso says. The work also poses new questions on how early spread cancer cells support metastasis development. Do they do it on their own, do they set the soil for later arriving cells from tumors not caught early, or do they cooperate with later arriving cells? This study reveals a new biological mechanism of early dissemination that must be explored to fully understand how to target the seeds of metastasis. The companion paper headed by Dr. Christoph Klein at the University of Regensburg in Germany, published in the same issue of Nature and co-authored by Dr. Aguirre-Ghiso and members of his team provides additional key mechanistic clues on how early spread is controlled and proof in human cancer cells and tumors of the preclinical findings in this study. Researchers from both teams arrived at their findings independently and then collaborated on the project. Researchers from both teams studied very early stages of breast cancer including DCIS (ductal carcinoma in situ), a noninvasive breast lesion, since 2-3 percent of women who have been treated for DCIS die of metastasis without ever developing a primary tumor. "The best explanation for this phenomenon is that early metastasis occurs before or as DCIS develops. A key finding from this second paper is that in the mouse models, 80% of metastasis originated from the early spread cells and not from the large tumors. In fact, the Klein group identified a mechanism by which spread is more efficient in early lesions than in large tumors. In both studies, investigators found that early cancer cell spread is an extension of the normal process of creating a branching tree of breast milk ducts in females. Two major pathways are activated in this ancient process -- p38, a tumor suppressor, and HER2, an oncogene. Switching off p38 and turning on HER2 activates a module of the EMT (epithelial to mesenchymal transition) signaling pathway. EMT promotes movement of cells during embryogenesis and tissue development. The Klein paper also shows that progesterone receptor signaling, which controls branching of the mammary tree, is important for this early spread by regulating cues involved in EMT and growth programs, a mechanism that was hinted in his earlier studies. As a mammary tree develops, p38, HER2, and EMT are alternatively turned on and off. This, in cooperation with progesterone signaling, allows mammary cells to move through the mammary gland, hollow out a tubular, branching network of milk ducts that flow to the nipple. "Tweaking these pathways are a normal way of forming hollow branching tubes," Dr. Aguirre-Ghiso says. But in their experiments, they found that if HER2 is over-activated (not switched off) or mutated, and p38 is permanently turned off, EMT was continually activated, allowing cells to move out of the mammary gland and into the animal's body through the blood. "We were able to use organoids in three-dimensional cultures, and high resolution imaging directly in the live animal models to actually see these cells enter the blood stream from the mammary tree and travel to the lung, the bone marrow, and other places," he says. "We hadn't thought about oncogenes and tumor suppressors in this way before. This is a new function for these pathways." John S. Condeelis, PhD, co-Director of the Gruss Lipper Biophotonics Center and its Integrated Imaging Program at Einstein, where the high resolution intravital imaging was performed, noted that "We were surprised to learn that cancer cells from DCIS-like lesions could show such robust dissemination using similar machinery found in tumor cells from invasive carcinoma. This is a new insight with implications beyond our expectations." Also David Entenberg MSc, Director of Technological Development and Intravital Imaging who led the imaging efforts within the same Center said, "A few years ago, it would not have been possible to image these disseminating cells inside a living animal with this level of detail. We're pleased that Einstein's imaging technology could, through this collaboration, contribute to the definitive proof of early dissemination." And while both studies focus on the mechanisms of early dissemination in breast cancer, similar processes could control early dissemination and metastasis in other human cancers, including melanoma and pancreatic cancer. In fact, pancreatic cancer early dissemination has also been linked to an EMT process, Dr. Aguirre-Ghiso says. Among the critical avenues they are investigating, Mount Sinai researchers are looking for the growth switch that pushes early spread of dormant cancer cells to form metastases. "While our findings add a whole new level of complexity to the understanding of cancer, they also add energy to our efforts to finally solve the big issue in cancer -- stop the metastasis that kills patients," Dr. Aguirre-Ghiso says. Study contributors include lead co-authors Kathryn L. Harper, PhD, Maria Soledad Sosa, PhD, Julie F. Cheung, BSc, Rita Nobre MSc, Alvaro Avivar-Valderas, PhD, Chandandaneep Nagi, MD, and Eduardo F. Farias, PhD, from Icahn School of Medicine at Mount Sinai; Christoph Klein, MD and Hedayatollah Hosseini, PhD from the University of Regensburg, Germany; Nomeda Girnius, PhD and Roger J. Davis, PhD from Howard Hughes Medical Institute at the University of Massachusetts Medical School; and David Entenberg, MSc and John Condeelis, PhD from Albert Einstein College of Medicine in New York. The study was supported by grants SWCRF, CA109182, CA196521, CA163131, CA100324, F31CA183185, BC132674, BC112380, NIH 1S10RR024745 Microscopy CoRE at ISMMS, the Integrated Imaging Program at Einstein, HHMI, DFG KL 1233/10-1 and the ERC (322602). For a video on this release: https:/ The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is on the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. or find Mount Sinai on Facebook, Twitter and YouTube.
News Article | December 5, 2016
(San Diego, CA - December 1, 2016) - Physicians and researchers from Mount Sinai Health System are presenting influential research and study updates at the American Society of Hematology's Annual Meeting and Exposition in San Diego, CA, December 3-6, 2016. Additionally, two Mount Sinai Health System researchers will be speakers at the ASH meeting and are available for interviews. Miriam Merad, MD, PhD, Professor of Oncological Sciences and Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, is a speaker at the Scientific Committee on Immunology and Host Defense on Saturday, December 3. Saghi Ghaffari, MD, PhD, Associate Professor of Medicine and Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, is a speaker at the Scientific Committee on Stem Cells and Regenerative Medicine on Saturday, December 3, and Sunday, December 4. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. , or find Mount Sinai on Facebook, Twitter and YouTube.
News Article | December 5, 2016
--Updated Median Duration of Complete Response of 8 Months in All Responding Patients-- NEWTOWN, Pa., Dec. 05, 2016 (GLOBE NEWSWIRE) -- Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, today announced the presentation of data from a Phase 2 clinical trial of oral rigosertib and azacitidine in higher-risk myelodysplastic syndromes (HR-MDS) at the 58th American Society of Hematology (ASH) Annual Meeting in San Diego, California. “The complete remission rate amongst HMA-naïve HR-MDS patients is higher and responses occur more rapidly and durably with the oral rigosertib combination compared to historic single-agent azacitidine,” commented Lewis R. Silverman, M.D., lead investigator in the trial and Associate Professor of Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mount Sinai. “Furthermore, the addition of oral rigosertib to azacitidine does not substantially change the adverse event profile of single-agent azacitidine, and thus may overcome the limitations identified in other HMA-based combinations.” The current standard of care for higher-risk MDS patients is one of two approved hypomethylating agents (azacitidine and decitabine, approved by the FDA in 2004 and 2006). Although these drugs are currently the standard of care in HR-MDS therapy, their overall response rate and duration of benefit is limited to a subset of eligible patients and all responding patients ultimately progress. Thus, there is an urgent need for improving therapeutic options for newly diagnosed HR-MDS patients. The 09-08 trial tested oral rigosertib in combination with injectable azacitidine in a dose ranging study (Phase 1), followed by an expansion cohort (Phase 2) to evaluate the efficacy and safety of the combination. Both 1st-line and 2nd-line HR-MDS patients were included in the study. Summary of Presented Data from the 09-08 Combination Therapy Trial The poster entitled, “Combination of Oral Rigosertib and Injectable Azacitidine in Patients with Myelodysplastic Syndromes (MDS): Results from a Phase II Study,” was presented by Dr. Shyamala Navada of Mount Sinai School of Medicine at the Myelodysplastic Syndromes Session on Sunday, December 4, 2016 at the ASH Annual Meeting in San Diego, California. A copy of the poster is available by visiting the Scientific Presentations section under the Investors & Media tab of Onconova’s website. “We are pleased by the positive efficacy signal observed over extended periods of treatment, and the acceptable tolerability of oral rigosertib and azacitidine in 1st-line HR-MDS,” stated Ramesh Kumar, Ph.D., President and CEO of Onconova. “We presented Phase 2 data to the FDA as part of our End-of-Phase 2 meeting in September 2016, and based on these discussions, we are designing a randomized, placebo controlled Phase 3 clinical trial comparing the combination of oral rigosertib plus azacitidine to azacitidine plus placebo in 1st-line HR-MDS patients with the primary composite endpoint of CR and PR rate per 2006 IWG criteria. Based on our discussions with the FDA the primary efficacy endpoint of this trial will be composite response and not survival, permitting accelerated evaluation of outcomes.” In a second poster at the conference a safety review of 557 MDS/AML patients treated with rigosertib in clinical studies, including the randomized Phase 3 ONTIME trial was presented. The poster entitled, “Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML),” can be accessed by visiting the Scientific Presentations section under the Investors & Media tab of Onconova’s website. Onconova Therapeutics is a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer. Onconova's clinical and pre-clinical stage drug development candidates are derived from its extensive chemical library and are designed to work against specific cellular pathways that are important in cancer cells, while causing minimal damage to normal cells. The Company’s most advanced product candidate, rigosertib, is a small molecule inhibitor of cellular signaling and acts as a RAS mimetic. These effects of rigosertib appear to be mediated by direct binding of the compound to the RAS-binding domain (RBD) found in many RAS effector proteins, including the Raf and PI3 kinases. Rigosertib is protected by issued patents (earliest expiry in 2026) and has been awarded Orphan Designation for MDS in the United States, Europe and Japan. In addition to rigosertib, two other candidates are in the clinical stage, and several candidates are in pre-clinical stages. For more information, please visit http://www.onconova.com. The oral form of rigosertib provides a more convenient dosing for use where the duration of treatment may extend to multiple years. To date, more than 350 patients have been treated with the oral formulation of rigosertib, either as a single agent or in combination with other drugs. Phase 1 studies with oral rigosertib were conducted in hematological malignancies, lower-risk MDS and solid tumors. Combination therapy of oral rigosertib with azacitidine and chemoradiotherapy has also been explored. The intravenous form of rigosertib has been employed in Phase 1, 2, and 3 clinical trial involving more than 800 patients, and is currently being evaluated in the randomized Phase 3 global INSPIRE trial as 2nd-line treatment for patients with higher-risk MDS, after failure of hypomethylating agent, or HMA, therapy. This formulation is suited for patients with advanced disease and provides long duration of exposure and ensures adequate dosing under a controlled setting. 1Fenaux et al for the international Vidaza High risk MDS survival study group, Lancet Oncology 2009, 10:223-232. Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. These statements relate to future events or Onconova Therapeutics, Inc.'s future operations, clinical development of Onconova's product candidates and presentation of data with respect thereto, regulatory approvals, expectations regarding the sufficiency of Onconova's cash and other resources to fund operating expenses and capital expenditures, Onconova's anticipated milestones and future expectations and plans and prospects. Although Onconova believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Onconova has attempted to identify forward-looking statements by terminology including “believes,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “should,” “approximately” or other words that convey uncertainty of future events or outcomes. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including Onconova’s need for additional financing and current plans and future needs to scale back operations if adequate financing is not obtained, the success and timing of Onconova’s clinical trials and regulatory approval of protocols, and those discussed under the heading “Risk Factors” in Onconova’s most recent Annual Report on Form 10-K and quarterly reports on Form 10-Q. Any forward-looking statements contained in this release speak only as of its date. Onconova undertakes no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.
Wijesinghe D.S.,Virginia Commonwealth University |
Wijesinghe D.S.,Hunter Holmes ire Veterans Administration Medical Center |
Brentnall M.,Hematology and Medical Oncology |
Mietla J.A.,Virginia Commonwealth University |
And 6 more authors.
Journal of Lipid Research | Year: 2014
In these studies, the role of ceramide-1-phosphate (C1P) in the wound-healing process was investigated. Specifi cally, fi broblasts isolated from mice with the known anabolic enzyme for C1P, ceramide kinase (CERK), ablated (CERK mice) and their wild-type littermates (CERK +/+ ) were subjected to in vitro wound-healing assays. Simulation of mechanical trauma of a wound by scratching a monolayer of fi broblasts from CERK +/+ mice demonstrated steadily increasing levels of arachidonic acid in a time-dependent manner in stark contrast to CERK fi broblasts. This observed difference was refl ected in scratch-induced eicosanoid levels. Similar, but somewhat less intense, changes were observed in a more complex system utilizing skin biopsies obtained from CERK-null mice. Importantly, C1P levels increased during the early stages of human wound healing correlating with the transition from the infl ammatory stage to the peak of the fi broplasia stage (e.g., proliferation and migration of fi broblasts). Finally, the loss of proper eicosanoid response translated into an abnormal migration pattern for the fi broblasts isolated from CERK. As the proper migration of fi broblasts is one of the necessary steps of wound healing, these studies demonstrate a novel requirement for the CERK-derived C1P in the proper healing. © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
Keng M.K.,Hematology and medical oncology |
Wenzell C.M.,Cleveland Clinic |
Sekeres M.A.,Cleveland Clinic
Clinical Advances in Hematology and Oncology | Year: 2013
In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.