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News Article | February 15, 2017
Site: www.eurekalert.org

A new investigational delivery method for localized vaginal estrogen therapy that utilizes an applicator free softgel to alleviate moderate-to-severe vaginal pain during intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA), received high rates of patient satisfaction among post-menopausal women, according to post-trial survey results published in the journal Menopause. "These survey results show that something as simple as a change to a more elegant delivery system that is easier to use and not messy might empower more post-menopausal women to seek prescription treatment for VVA, and perhaps help them stay with the application guidelines for longer," said study first author Sheryl Kingsberg, PhD, Division Chief, OB/GYN Behavioral Medicine, UH Cleveland Medical Center; Professor of Obstetrics and Gynecology and Psychiatry, Case Western Reserve University School of Medicine; and first author of the survey analysis. "We still have to find better ways to educate the millions of women suffering with VVA about the symptoms, however, so that more of them know it is common, decide to discuss treatment with their healthcare professional, and seek symptom relief with appropriate treatment." The new results were part of a multi-center randomized, placebo-controlled phase 3 clinical trial for TX004HR, an investigational bio-identical 17β-estradiol applicator free vaginal softgel capsule. Previous publications have shown TX004HR to be safe and effective at alleviating symptoms of VVA. The survey, which included 731 respondents with a 96 percent response rate, sought to quantify participants' satisfaction with the application method and overall treatment delivery system. The majority of women taking either TX004HR or placebo (85.4 - 92.1 percent) found the product easy to use. VVA is a chronic condition associated with genitourinary syndrome of menopause (GSM). VVA affects 50 to 70 percent of post-menopausal women, and is characterized by pain with sexual activity, dryness, and discomfort. Current on-the-market treatments for VVA include both over-the-counter creams and moisturizers as well as several safe and effective prescription treatments in cream, tablet, ring or oral form. Previous survey research completed by Dr. Kingsberg and others has shown that while 32 million women may be experiencing symptomatic VVA and suffering from related impacts on sexual function, interpersonal relationships, self-esteem and overall quality of life, only 7 percent are currently using a prescription therapy to alleviate symptoms. Though they may suffer from physical and emotional pain as a result of VVA, women may not feel comfortable discussing these symptoms with a healthcare professional, may not recognize the symptoms as treatable, may not fully understand the treatment options available, or if they did receive treatment, found the current prescription treatment options inconvenient, messy, or uncomfortable to use. Financial disclosure: Dr. Kingsberg has served as a consultant for TherapeuticsMD, the manufacturer of TX004HR, as well as Acerus Pharmaceuticals, AMAG Pharmaceuticals, Bayer Healthcare, Emotional Brain, Materna, Novo Nordisk, Nuelle, Palatin Technologies, Pfizer, Sermonix Pharmaceuticals, Shionogi Inc. and Valeant Pharmaceuticals. Founded in 1866, University Hospitals serves the needs of over 1 million patients per year through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, dermatology, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org.


CLEVELAND: Researchers from University Hospitals Seidman Cancer Center and Case Western Reserve University School of Medicine presented significant new research findings in multiple myeloma, lymphoma and other hematologic disorders at the 58th Annual Meeting of American Society of Hematology (ASH) in San Diego. "The breadth and depth of this innovative cancer research presented at ASH is truly outstanding," says Stan Gerson, MD, Director of UH Seidman Cancer Center and Case Comprehensive Cancer Center at Case Western Reserve. "Our faculty members are making tremendous advances in multiple myeloma, lymphoma and other hematologic malignancies which is reflected in their being selected for oral and poster presentations." Major advances have been made in treating multiple myeloma (MM) over the last 12 years and early phase clinical trials have played a key role in this progress according to an oral presentation (Abstract #1146) by Ehsan Malek, MD, of UH Seidman Cancer Center. Phase I trials, in addition to moving progress forward for new treatments, also have demonstrated therapeutic success for patients and are well tolerated. Dr. Malek and a team of researchers analyzed data from 2,408 MM patients who participated in 74 phase I clinical trials from 2004-2015 to determine the overall benefit and risks for patients. The analysis indicated that "the therapeutic benefit for patients recruited onto MM phase I trials was significantly higher than that reported for phase I trials of all cancer types." The team further found that patients' response rates supported earlier patient entry onto these early phase trials. "Multiple myeloma has seen tremendous progress over the past 12 years with the advent of new agents and survival rates have more than doubled," says Dr. Malek, Instructor at Case Western Reserve School of Medicine. "However in spite of advancements there still is an unmet need for drug discovery and phase I trials are critical to continued progress. Our research shows that these trials provide therapeutic benefit for patients who participate. Also these new therapies can be more beneficial the earlier patients enroll and no longer need to be thought of as a last resort." A team of researchers also presented an oral abstract (Abstract #105) finding that obese and older patients with a common form of lymphoma are more likely to develop heart disease following treatment. The researchers conducted a retrospective analysis of more than 400 patients with Diffuse Large B Cell Lymphoma (DLBCL) to determine the incidence of heart failure, heart attack, stroke and other cardiovascular events. They linked patients over age 60 and those with body mass index (BMI) greater than 30 with poorer outcomes and an elevated incidence of cardiovascular events. "Identification of patients at high risk for cardiovascular events is key to helping prevent complications after treatment and increasing long-term survival," says Paolo Caimi, MD, of UH Seidman Cancer Center and senior author of the study. "While further studies are needed, these findings provide important guidance on stratifying who is at risk and how to best tailor treatment. For patients who have advanced age or higher BMI, we can provide increased monitoring and identify ways to reduce their risk such as medications and other preventative measures." Dr. Malek and a team also presented a poster session (Abstract #1862) on the efficacy of a newly identified prognostic tool for newly diagnosed multiple myeloma. The researchers analyzed a ratio of white blood cells in 337 MM patients and found that those with a higher ALC (absolute lymphocyte count) /AMC (absolute monocyte count) at diagnosis had longer survival. "This biomarker is linked with the strength of a patient's immune system," says Dr. Malek. "Based on these new findings, we may be able to predict who will respond better and tailor immunologic therapies for patients for optimum response." Dr. Caimi's team also had two other related posters which used the same patient cohort to further determine risk stratification in DBCL patients. In Abstract #3611, they showed that patients who experienced venous thrombotic events after diagnosis had poorer outcomes and also validated a method to identify patients at risk of venous thromboembolic events (VTEs). In Abstract #1863, the researchers found that DBCL patients older than 75 have a higher mortality risk following diagnosis. These patients respond equally well to treatment but have additional risk for complications such as heart attacks and blood clots. "These studies in total provide us with important new information on how to modify treatments for certain patients," says Dr. Caimi, who is also Assistant Professor at the School of Medicine. "For lymphoma patients at risk for clotting and those over age 75, we are better able to provide targeted therapies to improve long-term outcomes." Abstract #105 Cardiovascular Toxicity after Therapy for Diffuse Large B Cell Lymphoma Occurs Early and Results in Decreased Overall Survival. Saturday, December 3, 2016: 10:00 AM https:/ Authors: Sabarish Ram Ayyappan, MBBS, Akiva Diamond, MD, Vinita Gupta, MD, Brenda Cooper, MD, Ben Tomlinson, MD, Ehsan Malek, MD, Leland Metheny, MD, Hillard Lazarus, MD, Stanton Gerson, MD, Marcos De Lima, MD and Dr. Caimi. Abstract #1862 Immunologic Status Evaluated By the Absolute Lymphocyte/Monocyte Ratio Provides a Powerful Prognostic Tool for Newly Diagnosed Multiple Myeloma Saturday, December 3, 2016, 5:30 PM-7:30 PM https:/ Authors: Dr. Malek,Talib Dosani, MD, Raisa Pinto, MD, Fahrettin Covut, MD, Hugo Akabane, MD, James J. Driscoll, MD, PhD, and Marcos De Lima, MD. Abstract #3611 Venous Thromboembolic Events in Diffuse Large B Cell Lymphoma Patients: Risk Factors and Outcomes Sunday, December 4, 2016, 6:00 - 8:00 PM https:/ Authors: Sabarish Ram Ayyappan, MBBS, Vinita Gupta, MD, Akiva Diamond, MD, Brenda Cooper, MD, Ben K. Tomlinson, MD, Ehsan Malek, MD, Leland Metheny, MD, Hillard Lazarus, MD, Stanton Gerson, MD, Marcos De Lima, MD, and Paolo F. Caimi, MD. Abstract #1863 Treatment of Diffuse Large Cell Lymphoma (DLBCL) Patients Older Than 75 Years: Higher Mortality and Risk of Complications without Increased Risk of Relapse after Treatment Saturday, December 3, 2016, 5:30 - 7:30 PM https:/ Authors: Akiva Diamond, MD, Sabarish Ram Ayyappan, MBBS, Raisa Pinto, MD, Ehsan Malek, MD, Ben K. Tomlinson, MD, Leland Metheny, MD, Brenda Cooper, MD, Stanton Gerson, MD, Hillard Lazarus, MD, Marcos De Lima, MD and Paolo F. Caimi, MD. Founded in 1866, University Hospitals serves the needs of over 1 million patients per year through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, dermatology, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org.


New Agreement Focuses on Improved System Efficiency at University Hospitals Cleveland Medical Center DUBLIN and CLEVELAND - Nov. 29, 2016 - Medtronic plc (NYSE:MDT), the global leader in medical technology, today announced the signing of its first Integrated Health Solutions agreement in the United States with University Hospitals (UH), one of the nation's leading healthcare systems, designed to improve delivery of care and patient experience. Together the organizations will implement innovative operational models that will optimize workflow and redefine operational efficiency for catheterization (cath) and electrophysiology (EP) laboratories at the University Hospitals Cleveland Medical Center.  Medtronic brings its international expertise from managing cath labs and operating rooms for over 100 hospital systems around the globe to manage clinical support operations in UH select labs. The agreement signals the expansion of Medtronic's managed services offering to U.S. health systems. Hospitals systems continue to find that operational efficiency is a prerequisite for clinical excellence. UH expects to optimize its operations with Medtronic involvement to continue to deliver excellent care and better manage rising healthcare costs. "Our collaboration with Medtronic gives us a unique opportunity to learn from their international best practices in inventory management and scheduling optimization," said Jeffrey Peters, M.D., UH chief operating officer. "We are excited to embed their expertise into our clinical operations, allowing our clinical staff to focus on providing the highest level of cardiovascular care for our patients." In cath labs and EP labs, clinical-support operations - lab management, scheduling, materials management, room turnover and process optimization - play a vital role in ensuring cardiologists are able to identify and diagnose cardiovascular conditions for their patients. The patient journey starts before the patient enters the hospital and continues after discharge. Addressing the needs of patients throughout the continuum of care is a priority of new models of care delivery. "Our Integrated Health Solutions business was formed as part of a commitment to advance healthcare delivery in more cost-effective ways," said Mike Genau, senior vice president and president, Americas Region, for Medtronic. "Our goal in collaborating with UH is to enhance patient care and system efficiency through the unique combination of operational insights, data, medical technology, and services. Medtronic has more than 65 years of experience to bring to the table, and we intend to be a close associate in implementing innovative solutions along the way." Medtronic plc (www.medtronic.com), headquartered in Dublin, Ireland, is among the world's largest medical technology, services and solutions companies - alleviating pain, restoring health and extending life for millions of people around the world. Medtronic employs more than 88,000 people worldwide, serving physicians, hospitals and patients in approximately 160 countries. The company is focused on collaborating with stakeholders around the world to take healthcare Further, Together. Founded in 1866, University Hospitals serves the needs of over 1 million patients per year through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, dermatology, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org. Any forward-looking statements are subject to risks and uncertainties such as those described in Medtronic's periodic reports on file with the Securities and Exchange Commission. Actual results may differ materially from anticipated results.


News Article | November 10, 2016
Site: www.marketwired.com

Editors: An online press kit is available at www.NCCN.org/justbagit As part of its mission to improve the quality, effectiveness, and efficiency of cancer care so that patients can live better lives, the National Comprehensive Cancer Network® (NCCN®) today announced the launch of Just Bag It: The NCCN Campaign for Safe Vincristine Handling. This campaign encourages health care providers to adopt a policy to always dilute and administer vincristine in a mini IV-drip bag to prevent a deadly medical error. Vincristine is a chemotherapy agent, widely used in patients with Leukemia or Lymphoma, which should be administered intravenously, or directly into the patient's vein. When it enters the blood, it is highly effective at blocking the growth of cancer by preventing cells from separating. However, vincristine is a neurotoxin that causes peripheral neuropathy when given intravenously and profound neurotoxicity if given into the spinal fluid, which flows around the spinal cord and brain. Many patients who receive vincristine have a treatment regimen that includes other chemotherapy drugs that are administered intrathecally, or injected into the spinal fluid with a syringe. If vincristine is mistakenly administered into the spinal fluid, it is uniformly fatal, causing ascending paralysis, neurological defects, and eventually death. In 2005, NCCN Chief Executive Officer Robert W. Carlson, MD, a medical oncologist, witnessed such a tragedy with a 21 year-old patient with Non-Hodgkin's Lymphoma named Christopher Wibeto. Wibeto was transferred to Carlson's care after receiving incorrectly administered vincristine at another hospital. Carlson watched the young man go from having a likely curable condition to deteriorating and dying within four days. Motivated by this tragic experience, Carlson spearheaded a national effort to address this deadly error when he arrived at NCCN, enlisting the help of its Best Practices Committee, which is dedicated to improving cancer treatment protocols. To ensure that vincristine is always administered properly, NCCN has issued guidelines advising health care providers to always dilute and administer vincristine in a mini IV-drip bag and never use a syringe to administer the medication. This precaution renders it impossible to accidentally administer the medication into the spinal fluid and greatly decreases the chances of improper dosage. All 27 NCCN Member Institutions have adopted policies in line with these guidelines, which are also recommended by the Institute for Safe Medication Practices, the Joint Commission, the World Health Organization, and the Oncology Nursing Society. "We are proud of this achievement and grateful for the support and participation of our Member Institutions in reaching this goal," Carlson said. "Our efforts will not stop here. We challenge all medical centers, hospitals, and oncology practices around the nation and the world to implement this medication safety policy so this error never occurs again." Surveys issued by the Institute for Safe Medication Practices (ISMP) show that over time, more hospitals have adopted a policy to always bag vincristine. According to ISMP data, the number of hospitals that have fully implemented the policy across their practice nearly doubled between February 2014 and February 2016. Earlier surveys indicated a similar increase between 2005 and 2012. Still, only about half of all respondents indicated that they have implemented the policy in all treatment settings, indicating that there is a long way to go. With 125 known cases of accidental death in the U.S. and abroad since the inception of vincristine use in the 1960s, this error is relatively rare. Still, it is unique in its level of mortality. Improvements in practice over the years, including manufacturer- and pharmacist-issued warning labels, have reduced the number of deaths, but the error continues to occur. Diluting vincristine into a mini IV-drip bag may entail a change in practice for some providers, but it is well worth the outcome of avoiding preventable deaths, according to Michael Cohen, RPh, MS, FASHP, President of ISMP. "One more life taken is one too many," Cohen said. "We are glad an organization of NCCN's influence has stepped up to bring this issue to national attention. Ending this devastating error should be a priority for all of us who care for and advocate on behalf of patients and their families." Some health care providers may associate the use of an IV bag with a heightened risk of extravasation, or the leaking of a chemotherapy drug into the tissue surrounding the intravenous administration site. But research shows that the risk of extravasation is extremely low. [1] "The Just Bag It campaign is the latest of NCCN's long-standing efforts to improve the safe use of drugs in cancer care," said F. Marc Stewart, MD, Medical Director of the Seattle Cancer Care Alliance and Member of the Fred Hutchinson Cancer Research Center, Professor of Medicine at University of Washington, and Co-Chair of the NCCN Best Practices Committee. "For more than 15 years, the Best Practices Committee has worked to ensure the highest standards of safety for patients." In 2008, the Best Practices Committee led the charge for NCCN to begin publishing Chemotherapy Order Templates (NCCN Templates®), which detail the most common regimens for many cancers and highlight safety parameters. These resources enable practitioners to standardize patient care, reduce medication errors, and anticipate and manage adverse events. There are more than 1,500 NCCN Templates® for 86 cancer types, and they are used by more than 10,000 subscribers. For more information about Just Bag It: The NCCN Campaign for Safe Vincristine Handling, or to report that a medical facility has adopted a vincristine policy, visit www.NCCN.org/JustBagIt. The National Comprehensive Cancer Network® (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. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The NCCN Member Institutions are: Fred & Pamela Buffett Cancer Center, Omaha, NE; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; City of Hope Comprehensive Cancer Center, Los Angeles, CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Mayo Clinic Cancer Center, Phoenix/Scottsdale, AZ, Jacksonville, FL, and Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UC San Diego Moores Cancer Center, La Jolla, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; Vanderbilt-Ingram Cancer Center, Nashville, TN; and Yale Cancer Center/Smilow Cancer Hospital, New Haven, CT. [1] ISMP. Death and neurological devastation from intrathecal vinca alkaloids: Prepared in syringes = 120; Prepared in minibags = 0. ISMP Medication Safety Alert! 2013;18(18):3. The following files are available for download:


CLEVELAND: A researcher from University Hospitals Seidman Cancer Center will discuss his upcoming immunotherapy clinical trial for triple-negative breast cancer at the 2016 San Antonio Breast Cancer Symposium. The annual symposium is the premier meeting for more than 7,500 physicians and scientists dedicated to breast cancer treatment, featuring state-of-the-art breast cancer research such as experimental biology, etiology, prevention, diagnosis, and therapy of both breast cancer and premalignant breast disease. Joseph Baar, MD, PhD, Director of Breast Cancer Research at UH Seidman Cancer Center and Associate Professor at Case Western Reserve University School of Medicine, will share details about a phase II clinical trial testing the effectiveness of combining the chemotherapy drugs carboplatin and nab-paclitaxel with an immunotherapeutic agent called pembrolizumab (Keytruda) for use in patients with metastatic triple-negative breast cancer. Dr. Baar's poster presentation will be part of the Ongoing Trials-Targeted Therapy session on December 8, 2016 from 5 pm to 7 pm. "Up until now, women with triple-negative breast cancer have only had one treatment option, which is chemotherapy. However, more recently, we've seen that the immune modulator pembrolizumab improves outcomes in patients with metastatic triple-negative breast cancer," said Dr. Baar. "As a result, it is now critical to explore how the addition of pembrolizumab to chemotherapy might improve survival in patients with this type of breast cancer." Triple-negative breast cancer is a highly aggressive form which comprises 10-15 percent of newly diagnosed early-stage breast cancer. Most triple-negative tumors are high grade and have a high incidence of recurrence and metastases (spreading to other organs). Unlike other types of breast cancer, there is no standard follow-up treatment for triple-negative breast cancer to prevent recurrence. As triple-negative breast cancer progresses, tumor cells express a protein ligand called PD-L1, which interacts with the PD-1 receptor on T-cells. T-cells are the immune system's primary mechanism for fighting back against harmful foreign invaders. The PD-L1 to PD-1 interaction prevents the T-cell from responding to the tumor as a threat. Pembrolizumab binds to the T-cell's PD-1 receptors and therefore blocks the PD-1 to PD-L1 interaction, allowing the T-cells to be activated against the tumor cells. The research team hypothesizes that the addition of such an immunotherapeutic agent to chemotherapy will allow the body's natural immune response to reduce disease recurrence to a greater extent than either modality alone. This is the first phase II trial to study the effectiveness of combining these two chemotherapeutic agents with the immunotherapeutic agent pembrolizumab for this type of cancer. The trial will enroll approximately 30 patients beginning in early 2017. Eligible patients must have radiologically measurable and documented metastatic triple negative breast cancer, be mostly functional day to day as measured by an ECOG performance status of between zero and one, must not have received more than two prior therapies for this disease, and must be willing to undergo a preliminary biopsy for research purposes. The trial is sponsored by Merck, which produces pembrolizumab as Keytruda. "Trials our faculty members present at SABCS and other research meetings around the world illustrate the remarkable advances in oncology taking place today," says Neal J. Meropol, MD, Chief, Division of Hematology and Oncology, University Hospitals Seidman Cancer Center and Associate Director for Clinical Research, Case Comprehensive Cancer Center at Case Western Reserve. The symposium takes place December 6-10, 2016, and is hosted by The Cancer Therapy & Research Center at the University of Texas Health Science Center at San Antonio, the American Association for Cancer Research, and Baylor College of Medicine. Founded in 1866, University Hospitals serves the needs of over 1 million patients per year through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, dermatology, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org.


- Diverse Data Continue to Reinforce the Efficacy and Safety of Selinexor in Patients with Heavily Pretreated Refractory Multiple Myeloma - NEWTON, Mass., Nov. 03, 2016 (GLOBE NEWSWIRE) -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today announced that 21 abstracts have been selected for presentation, including 9 oral presentations, at the American Society of Hematology (ASH) 2016 annual meeting being held December 3-6, 2016 in San Diego.  Two key abstracts being presented at the meeting will feature updated data from Karyopharm’s Phase 2b STORM and Phase 1b/2 STOMP studies, which are evaluating selinexor (KPT-330), the Company’s lead, novel, oral Selective Inhibitor of Nuclear Export (SINE™) compound, for the treatment of patients with multiple myeloma (MM). Selinexor has demonstrated robust and durable responses with favorable safety profiles in both studies and these data will be updated for presentation at the meeting. “The STORM and STOMP studies continue to demonstrate robust response rates, with selinexor showing tolerability, both as a single-agent and in combination with other widely used therapies in heavily pretreated patients with MM,” said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. “Collectively, the MM data being presented at ASH this year continue to support the efficacy and safety of oral selinexor, as well as our planned development path in MM, and we look forward to presenting even more mature data at the meeting in December.” In an oral presentation titled, “Selinexor and Low Dose Dexamethasone in Patients with Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib and Anti-CD38 Ab Refractory MM STORM Study,” Dan T. Vogl, MD, MSCE, Assistant Professor of Medicine, Perelman School of Medicine, University of Pennsylvania, will present updated clinical data from the ongoing Phase 2b STORM study, a single-arm clinical trial evaluating selinexor in combination with low-dose dexamethasone in heavily pretreated patients with quad-refractory or penta-refractory disease. Patients with quad-refractory disease have documented evidence that they have previously received two PIs (bortezomib (Velcade®) and carfilzomib (Kyprolis®)) and two IMiDs (lenalidomide (Revlimid®) and pomalidomide (Pomalyst®)), and their disease is refractory to at least one PI, at least one IMiD, and has progressed following their most recent therapy.  Patients with penta-refractory myeloma have quad-refractory disease that is also refractory to an anti-CD38 monoclonal antibody, such as daratumumab (Darzalex™) or isatuximab. All responses were adjudicated by an Independent Review Committee (IRC).  Among the 78 evaluable patients (median seven prior treatment regimens) at September 6, 2016, the overall response rate (ORR) was 21%, and included very good partial responses (VGPR) and partial responses (PR).  Among the 48 patients in the quad-refractory group, the ORR was 21%. For comparison, in a similar quad-refractory patient population, Darzalex had an ORR of 21% and isatuximab had an ORR of 20%.  Among the 30 patients in the penta-refractory group, the ORR was 20%.  Clinical benefit rate (ORR + MR) was 32% (all patients), 29% (quad-refractory), and 37% (penta-refractory).  Median overall survival (OS) was 9.3 months for all patients, greater than 11 months (median not reached) for responders (≥PR), and 5.7 months for non-responders.  Median duration of response (DOR) was approximately 5 months.  The progression free survival (PFS) in this heavily pretreated population was 2.1 months. Grade ≥3 cytopenias were the most common side effects and were generally not associated with clinical sequellae. There were low rates of Grade ≥3 non-hematologic toxicities, with no new safety signals identified.  In particular, there was one reported case of Grade ≥4 infection (1.3%) and there was one reported case of sepsis (1.3%). Dr. Vogl said, “Patients with penta-refractory myeloma are no longer responding to any of our most effective myeloma agents. This is a growing population for whom we currently have no specific therapy, representing an unmet need.   To my knowledge, selinexor is the first agent to show durable activity in this difficult-to-treat population.  The results are particularly intriguing because the response rate to oral selinexor is comparable to that achieved with daratumumab or isatuximab.  In addition, the overall survival seen in patients responding to selinexor is better than one would expect in this very refractory population. We look forward to further elucidating the potential benefits of selinexor in the STORM trial expansion, which will include approximately 120 additional patients with penta-refractory disease.” To Karyopharm's knowledge, no agent has previously shown activity in patients with penta-refractory MM. As a result, the Company has expanded the STORM study to include approximately 120 additional patients with penta-refractory MM and expects to report top-line data from the expanded cohort in early 2018.  Assuming a positive outcome, Karyopharm intends to use the data from the expanded STORM study to support a request that the FDA consider granting accelerated approval for selinexor in MM. In an oral presentation titled, “Selinexor in Combination with Bortezomib and Dexamethasone Demonstrates Significant Activity in Patients with Refractory Multiple Myeloma Including Proteasome-Inhibitor Refractory Patients,” Nizar Bahlis, MD, Associate Professor of Hematology, Southern Alberta Cancer Research Institute, will present updated clinical data from the selinexor + Velcade (bortezomib) + dexamethasone (SVd) arm of the ongoing Phase 1b/2 STOMP study in heavily pretreated relapsed/refractory MM patients. A summary of data from all 22 patients receiving selinexor in combination with Velcade and dexamethasone in the dose-escalation portion of the study treated as of July 25, 2016 is outlined in the following table and described below. Of the 22 patients enrolled in the SVd combination arm (median of four prior treatment regimens), 17 responded (1 patient with a complete response (CR), five patients with a very good partial response (VGPR) and 11 patients with a partial response (PR)) for an overall response rate (ORR) of 77%.  An additional three patients achieved a minor response (MR), for a clinical benefit rate (CBR) of 91%.  Only one patient had progressive disease.  All 10 patients with non-refractory disease responded (5 patients with a VGPR and 5 patients with a PR) for an ORR and CBR of 100%.  Twelve of the 22 patients in the SVd combination arm had MM previously refractory to a proteasome inhibitor and some patients had high-risk cytogenetics including deletion of chromosome 17p.  Seven of these 12 patients responded (1 CR and 6 PR) for an ORR of 58%.  An additional three patients achieved a MR for a CBR of 83% in this subgroup. Of note, the expected ORR for bortezomib-dexamethasone combination in patients with myeloma that is not refractory to a proteasome inhibitor is approximately 50%, and the ORR for those with refractory disease would be less than 10%. The most commonly reported adverse events were fatigue, anorexia, nausea and diarrhea, which were primarily grade 1 or 2 and reversible. Four grade 3 and two grade 4 incidences of thrombocytopenia (without bleeding) were also reported.  There was one reported case of grade 1 peripheral neuropathy in the selinexor (80 mg bi-weekly) cohort. “We continue to be impressed with the high level of durable activity of selinexor in combination with bortezomib, especially in patients whose disease is already refractory to proteasome inhibitors,” said Dr. Bahlis.  “The tolerability profile of the combination was quite favorable with low rates of neuropathy and cytopenias, particularly in this heavily pretreated population. Selinexor appears to have one of the most potent synergistic effects with bortezomib reported to date.” Based on the robust data from the SVd arm of the Phase 1b portion of the STOMP study, the Company plans to initiate a pivotal, randomized Phase 3 study, known as the BOSTON (Bortezomib, Selinexor and dexamethasone) study, which will evaluate SVd at the recommended dose compared to bortezomib and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy.  Karyopharm has identified the combination dose of selinexor (100mg weekly), bortezomib (1.3 mg/m2 weekly given sub-cutaneously for 4 of 5 weeks) and dexamethasone (40mg weekly) to be used in the BOSTON study.  The study will be conducted worldwide and will enroll approximately 360 patients.  Based on feedback from the FDA, the protocol is currently being finalized and the Company remains on track to commence the BOSTON study in early 2017. Dr. Bahlis continued, “To our knowledge, this is the only Phase 3 study evaluating a triple combination therapy incorporating once-weekly Velcade.  We anticipate that this regimen will continue to show reduced rates of cytopenias, neuropathy and gastrointestinal side effects based on the continuing STOMP results.  From a patient convenience as well as a health economic perspective, these data are very exciting because the combination of oral selinexor and bortezomib requires fewer doses and fewer hospital visits, making this treatment regimen much more patient friendly, and potentially more cost effective than currently established therapies.” In addition to these updated data from the STORM and STOMP studies, other key multiple myeloma abstracts selected for presentation at ASH include an oral presentation describing a Phase 1 study evaluating the combination of selinexor with proteasome inhibitor Kyprolis (carfilzomib) and dexamethasone in relapsed/refractory MM (Andrzej Jakubowiak, University of Chicago; Pub ID 973) and a poster presentation describing data from the selinexor + Pomalyst (pomalidomide) + dexamethasone arm of the Phase 1b dose-escalation portion of the STOMP study, also in patients with relapsed/refractory MM (Christine Chen, Princess Margaret Hospital; Pub ID 3330). Karyopharm to Host Multiple Myeloma-focused Dinner Reception and Webcast at ASH 2016 On Monday, December 5, 2016, Karyopharm will host an investor and analyst dinner reception, which will feature a moderated panel discussion with recognized thought leaders in the treatment of MM, updated selinexor data in MM, and a live Q&A session.  The event will take place during the ASH 2016 annual meeting and interested parties can access a live webcast of the event beginning Monday, December 5, 2016 at 8:15 p.m. PT by going to the “Investors” section of the company's website at http://investors.karyopharm.com/events.cfm. Several other key abstracts focused on the investigation of selinexor for the treatment of AML were selected for presentation at ASH, including two oral and two poster presentations.  The first oral presentation describes updated data from the Phase 2 SAIL study evaluating the combination of selinexor, with Ara-C and Idarubicin in patients with relapsed/refractory AML (Walter Fiedler, University Medical Center Hamburg; Pub ID 341) and the second oral presentation highlights data from a clinical trial evaluating the combination of selinexor with high-dose cytarabine and mitoxantrone in patients with AML (Amy Wang, University of Chicago; Pub ID 212).  The two poster presentations (Bhavana Bhatnagar, Ohio State University; Pub ID 1651 and Kendra Sweet, Moffitt Cancer Center, Tampa FL; Pub ID 4040) highlight early-stage clinical data demonstrating the feasibility and tolerability of selinexor in combination with other standard of care agents in patients with AML, including in elderly patients, as well as early signs of clinical activity, including response rates that are superior to historical data. Details for the full list of ASH presentations are as follows: Title:  Selinexor and Low Dose Dexamethasone in Patients with Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib and Anti-CD38 Ab Refractory MM STORM Study Presenter:  Dan Vogl, Abramson Cancer Center, University of Pennsylvania Publication ID:  491 Session:  653. Myeloma: Therapy, excluding Transplantation: New Agents for Multiple Myeloma; Sunday, December 4, 2016; 4:30-6:00 PM PT Location:  San Diego Convention Center, Hall AB Date and Time:  Sunday, December 4, 2016 at 5:30 PM PT Title:  Selinexor in Combination with Bortezomib and Dexamethasone Demonstrates Significant Activity in Patients with Refractory MM Including Proteasome-Inhibitor Refractory Patients Presenter:  Nizar Bahlis, Southern Alberta Cancer Research Institute, University of Calgary Publication ID:  977 Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Approaches; Monday, December 5, 2016; 2:45-4:15 PM PT Location:  Manchester Grand Hyatt San Diego, Seaport Ballroom BC Date and Time:  Monday, December 5, 2016; 3:45 PM PT Title:  Final Results of Phase 1 MMRC Trial of Selinexor, Carfilzomib, and Dexamethasone in Relapsed/Refractory MM Presenter:  Andrzej Jakubowiak, University of Chicago Publication ID:  973 Session:  653. Myeloma: Therapy, excluding Transplantation: Novel Approaches; Monday, December 5, 2016; 2:45-4:15 PM PT Location:  Manchester Grand Hyatt San Diego, Seaport Ballroom BC Date and Time:  Monday, December 5, 2016; 2:45 PM PT Title:  Phase II Results of Ara-C and Idarubicin in Combination with the Selective Inhibitor of Nuclear Export Compound Selinexor in Patients with Relapsed or Refractory AML Presenter:  Walter Fiedler, University Medical Center Hamburg, Hamburg, Germany Publication ID:  341 Session:  613. Acute Myeloid Leukemia: Clinical Studies: Optimizing Current AML Therapy; Sunday, December 4, 2016; 9:30-11:00 AM PT Location:  Marriott Marquis San Diego Marina, Pacific Ballroom Date and Time:  Sunday, December 4, 2016; 10:30 AM PT Title:  Combination of Selinexor with High-Dose Cytarabine and Mitoxantrone for Remission Induction in AML Is Feasible and Tolerable Presenter:  Amy Wang, University of Chicago Publication ID:  212 Session:  613. Acute Myeloid Leukemia: Clinical Studies: Innovations in Induction Therapy; Saturday, December 3, 2016; 4:00-5:30 PM PT Location:  Marriott Marquis San Diego Marina, San Diego Ballroom AB Date and Time:  Saturday, December 3, 2016; 4:15 PM PT Title:  Selective Inhibition of Nuclear Cytoplasmic Transport as a New Treatment Paradigm in Myelofibrosis Presenter:  Dongqing Yan, Huntsman Cancer Institute, University of Utah Publication ID:  636 Session:  635. Myeloproliferative Syndromes: Basic Science: Translational Studies; Monday, December 5, 2016; 7:00-8:30 AM PT Location:  Marriott Marquis San Diego Marina, Pacific Ballroom Salons 15-17 Date and Time:  Monday, December 5, 2016; 8:15 AM PT Title:  XPO1 Inhibition By Selinexor Synergizes with BCR Inhibition, Blocks Tumor Growth and Prolongs Survival in a Bioluminescent Animal Model of Primary Central Nervous System Lymphoma Presenter:  Marta Crespo, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain Publication ID:  463 Session:  625. Lymphoma: Pre-Clinical—Chemotherapy and Biologic Agents: Novel Therapeutic Strategies Location:  San Diego Convention Center, Room 5AB Date and Time:  Sunday, December 4, 2016; 4:30 PM PT Title:  The mechanism by which mutant NPM1 creates Leukemic self-renewal is readily reversed Presenter:  Yogen Saunthararajah, Cleveland Clinic and Case Comprehensive Cancer Center, Cleveland, OH Publication ID:  444 Session:  603. Oncogenes and Tumor Suppressors: Transcriptional Networks Contributing to Leukemogenesis Location:  San Diego Convention Center, Room 6DE Date and Time:  Sunday, December 4, 2016; 5:45 PM PT Title:  Bromodomain and Extra-Terminal Motif Proteins (BETs) Mediate 5-Azacitidine Resistance in Myeloid Leukemia through Recruitment of an Active RNA Polymerase II Complex Presenter:  Li Chen, University of Chicago Publication ID:  746 Session:  604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Novel Epigenetic Modulators Location:  San Diego Convention Center, Room 24 Date and Time:  Monday, December 5, 2016; 10:45 AM PT Title:  Selinexor Shows Synergy in Combination with Pomalidomide and Low Dose Dexamethasone in Patients with Relapsed / Refractory Multiple Myeloma Presenter:  Christine Chen, Princess Margaret Hospital, Toronto, ON Publication ID:  3330 Location:  San Diego Convention Center, Hall GH Date and Time:  Sunday, December 4, 2016; 6:00-8:00 PM PT Title:  A Phase 1 Clinical Trial of Selinexor in Combination with Decitabine in Patients with Newly Diagnosed and Relapsed or Refractory AML Presenter:  Bhavana Bhatnagar, Ohio State University Publication ID:  1651 Location:  San Diego Convention Center, Hall GH Date and Time:  Saturday, December 3, 2016; 5:30-7:30 PM PT Title:  A Phase I Study of Selinexor in Combination with Daunorubicin and Cytarabine in Patients with Newly Diagnosed Poor-Risk AML Presenter:  Kendra Sweet, Moffitt Cancer Center, Tampa FL Publication ID:  4040 Location:  San Diego Convention Center, Hall GH Date and Time:  Monday, December 5, 2016; 6:00-8:00 PM PT Title:  A Phase 1/2 Study of the Second Generation Selective Inhibitor of Nuclear Export Compound, KPT-8602, in Patients with Relapsed Refractory MM Presenter:  Frank Cornell, Vanderbilt Ingram Cancer Center, Nashville; TN Publication ID:  4509 Location:  San Diego Convention Center, Hall GH Date and Time:  Monday, December 5, 2016; 6:00-8:00 PM PT Title:  Combination of Selective Inhibitor of Nuclear Export Compounds, Selinexor and KPT-8602, with Venetoclax (ABT-199) Displays Enhanced Activity in Leukemia and Large Cell Lymphoma Presenter:  Melissa Fischer, Vanderbilt University, Nashville, TN Publication ID:  3949 Location:  San Diego Convention Center, Hall GH Date and Time:  Monday, December 5, 2016; 6:00-8:00 PM PT Title:  Synergistic anti-tumor effects of KPT-8602 and Panobinostat a pan-HDAC inhibitor in multiple myeloma Presenter:  Christian Argueta, Karyopharm Therapeutics, Newton, MA Publication ID:  3298 Location:  San Diego Convention Center, Hall GH Date and Time:  Sunday, December 4, 2016; 6:00-8:00 PM PT Title:  Selinexor in combination with chemotherapy or Idelalisib elicits a synergistic cytotoxic effect in Primary CLL Cells and overcoming intrinsic and stromal cells-mediated Fludarabine resistance Presenter:  Marta Coscia, A.O.U. Città della Salute e della Scienza, University of Torino, Torino, Italy Publication ID:  3210 Location:  San Diego Convention Center, Hall GH Date and Time:  Sunday, December 4, 2016; 6:00-8:00 PM PT Title:  Combination therapy with Bortezomib or Carfilzomib and Selinexor Induces Nuclear Localization of IκBα and overcomes acquired proteasome inhibitor Resistance in Human Multiple Myeloma Presenter:  Joel Turner, Moffitt Cancer Center, Tampa FL Publication ID:  3299 Location:  San Diego Convention Center, Hall GH Date and Time:  Sunday, December 4, 2016; 6:00-8:00 PM PT Title:  Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T Cell Effector Function in Mice: Implications for Combination with Immunotherapy Presenter:  Yosef Landesman, Karyopharm Therapeutics, Newton, MA Publication ID:  2525 Location:  San Diego Convention Center, Hall GH Date and Time:  Sunday, December 4, 2016; 6:00-8:00 PM PT Title:  Combination of selinexor and the proteasome inhibitor, bortezomib shows synergistic cytotoxicity in Diffuse Large B-Cells Lymphoma Cells In vitro and in vivo Presenter:  Trinayan Kashyap, Karyopharm Therapeutics, Newton, MA Publication ID:  4131 Location:  San Diego Convention Center, Hall GH Date and Time:  Monday, December 5, 2016; 6:00-8:00 PM PT Title:  XPO1 target occupancy measurements using Fluorescence Cross Correlation Spectroscopy (FCCS) support the Selinexor Recommended Phase 2 Dose Presenter:  Marsha Crochiere, Karyopharm Therapeutics, Newton, MA Publication ID:  1563 Location:  San Diego Convention Center, Hall GH Date and Time:  Saturday, December 3, 2016; 5:30-7:30 PM PT Title:  Identification of Specific HnRNPs as Novel Therapeutic Targets and Responsive Indicators of KPT330 (selinexor) in Leukemia Presenter:  Adam Cloe, University of Chicago Publication ID:  1657 Location:  San Diego Convention Center, Hall GH Date and Time:  Saturday, December 3, 2016; 5:30-7:30 PM PT 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 1,800 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 acute myeloid leukemia (SOPRA), 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), 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 June 30, 2016, which was filed with the Securities and Exchange Commission (SEC) on August 4, 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. Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited Revlimid® and Pomalyst® are registered trademarks of Celgene Corporation Kyprolis® is a registered trademark of Onyx Pharmaceuticals, Inc. Darzalex™ is a trademark of Janssen Biotech, Inc.


News Article | September 8, 2016
Site: www.sciencenews.org

President Barack Obama’s “Cancer Moonshot” now has a scientific flight plan. It calls for better cooperation among researchers and institutions, aggressive pursuit of immunotherapy and making better use of proven cancer prevention strategies. Called the Blue Ribbon Panel Report, the document was approved September 7 by the National Cancer Advisory Board, part of the National Cancer Institute. Five months in the making, the report’s 10 recommendations for research priorities were put together by a 28-member group of cancer experts appointed last April. It’s the most specific direction yet for the moonshot (SN: 4/2/16, p. 20), launched when Obama announced the intention to make the United States “the country that cures cancer once and for all” in his State of the Union address in January. Vice President Joe Biden, whose son Beau died in 2015 from brain cancer at age 46, has been leading the charge. If the vice president formally adopts the recommendations, they could form the foundation for research grants awarded through the National Institutes of Health. But that depends largely on the U.S. Congress providing funding for the moonshot, which has not yet happened. The report doesn’t contain dramatic surprises and doesn’t veer far off course from current cancer research. That’s largely by design. The goal of the panel was to come up with a plan to make “10 years of progress in five years” by hastening those areas with the most promise, which also stand to affect large numbers of patients. “We want it to be a pushy evolution, not a revolution,” says Stan Gerson, director of the Case Comprehensive Cancer Center in Cleveland, who was not on the panel. “There are some things here that are right on the money where we ought to be focused.” The Cancer Moonshot’s Blue Ribbon Panel presented 10 research recommendations to the National Cancer Advisory Board on September 7. Patients would enter genetic information about their cancer into a national database, making it easier to find and participate in clinical trials. A clinical trials network devoted exclusively to immunotherapies would focus on what’s considered one of the most promising advances in cancer treatment. More research is needed to understand drug resistance, a major cause of death from cancer. This system would link many of the nation’s largest data repositories, enabling free, one-stop access for researchers, doctors and patients to share data. Intensify research on the major drivers of childhood cancers More research into the biology of pediatric and adolescent cancers could lead to improved treatments. Guidelines are needed to minimize and manage the often excruciating side effects of treatment. Expand use of proven prevention and early detection strategies Researchers need to identify ways to increase adherence to proven strategies, such as the HPV vaccine, especially in medically underserved populations and those with inherited genetic risks. Researchers should analyze stored tumor tissue from patients who received standard treatment to search for genetic and other factors that predict which people would benefit from standard care versus experimental treatment. Aweb-based catalog that maps the genetic and cellular evolution of tumors would enable researchers to develop predictive models of tumor progression and response to treatment. More public–private sector collaborations are needed to develop new technologies to help doctors deliver more effective therapies to patients. If there is any underlying thread to the report, it is that progress depends on greater cooperation in research and improvements in patient engagement. “There’s not a lot new under the sun in terms of the areas they have targeted. The most important concept here with the vice president’s efforts is that he can serve as an accelerant at a time when we’re at an inflection point in treating cancer,” says Gary Gilliland, president and director of the Fred Hutchinson Cancer Research Center in Seattle. “Within 10 years if we don’t get to a place where we’ve got curative approaches to essentially all cancers then we’ve failed — and shame on us.” For treatment, the report singles out immunotherapy, which harnesses a patient’s own immune system to fight cancer. The strategy is widely regarded as one of the most significant advances in cancer care, even though so far only 10 to 20 percent of patients receiving such treatments show long-term benefit. “When I speak to my patients, I tell them that the greatest risk is disappointment,” says medical oncologist David Gerber of the University of Texas Southwestern Medical Center in Dallas. Nonetheless, he and others remain optimistic about immunotherapy’s potential, and he agrees with recommendations to speed up research. In proposing an immunotherapy clinical trials network, the report states that current treatments “represent only the tip of the iceberg of what is possible.” Since the moonshot began, Biden has crisscrossed the country, touring cancer research centers, holding photo ops and meeting with doctors. In June, he presided over a cancer summit at Howard University in Washington, D.C. One theme Biden has stressed at these events — and was reflected in the panel’s report — is the need for better data sharing. Traditionally, raw scientific data remains the property of the institutions and researchers who conduct studies. But this can impede collaboration — between institutions or across disciplines — and make it harder to find patterns within genetics and biology that might reveal how cancer appears and grows. The new report acknowledges the problem with research silos, stating that “our ability to accelerate progress against cancer demands that researchers, clinicians and patients across the country collaborate in sharing their collective data and knowledge about the disease.” Among the recommendations is the creation of a National Cancer Data Ecosystem, a one-stop, free collection of data that will allow patients to upload and receive data about their specific type of tumor. While Obama heralded the moonshot as a cure for cancer, Gerson, from the Case Comprehensive Cancer Center, would also like to see more scientists take on less flashy issues, finding better ways to save lives in known ways. Among them: “How do we get people to stop smoking?” he says. “We’re not doing it well.” Tyler Jacks, the report cochair and director of the Koch Institute for Integrative Cancer Research at MIT, said during a news conference that the panel recognizes that progress against cancer is about “emphasizing the use of known prevention strategies. It’s not just about treatment.” In discussing prevention, the report notes low rates of adoption for the human papillomavirus vaccine, which protects against the virus that causes cervical and other cancers, and for colorectal cancer, or CRC, screening. “If we understood better the reasons these proven cancer prevention strategies are not being widely used and how we could increase uptake of these strategies,” the report states, “we could reduce deaths due to cervical cancer by 90 percent, CRC by up to 70 percent and lung cancer by as much as 95 percent.” The authors also note that many people carry inherited genetic risks for cancer and don’t know it, and improved screening for genetic predisposition could save lives. What happens to the moonshot after this year depends largely on Congress. The report will eventually be forwarded to the vice president and the moonshot task force he oversees. The panel did not say how much the recommendations would cost. But in his budget request for fiscal year 2017, Obama asked for $680 million for additional funding to pay for the moonshot. The panel members confined themselves to scientific matters but noted that barriers to cancer progress are not just about research. Disparities keep many patients from getting treatments today, much less improvements coming tomorrow. “The one concern I have is that they put off the side policy issues as being out of scope for the Blue Ribbon Panel. I think it’s appropriate, but in the end it’s the policy issues that are going to determine the success of the entire program,” says Gilliland. “How do you get coverage and reimbursement? How do you ensure privacy if you’re sequencing everybody’s genome? How do you address access to clinical trials? Those are some of the very hardest problems, and if we don’t solve them it’s not going to matter how clever we are in the laboratory or how sensitive our techniques are for early detection.”


News Article | November 8, 2016
Site: www.sciencedaily.com

A multi-institution academic-industrial partnership of researchers led by Case Western Reserve University School of Medicine has developed a new method to broadly assess cell communication networks and identify disease-specific network anomalies. The computer-based method, called InFlo, was developed in collaboration with researchers at Philips, the leading health technology company, and Princeton University and predicts how cells send signals across networks to cause cancer or other disease. Details about the new method were recently published in Oncogene. "Cellular signaling networks are the mechanisms that cells use to transfer, process, and respond to biological information derived from their immediate surroundings," said Vinay Varadan, PhD, assistant professor at Case Western Reserve University School of Medicine, member of the Case Comprehensive Cancer Center, and senior corresponding author on the study. "InFlo can be viewed as modeling the flow of information within these signaling networks." InFlo works by assessing gene activity levels in tissue samples and predicting corresponding protein levels. It then uses statistical probabilities and other mathematical models to build activity webs showing how the proteins interact. Researchers can use InFlo to compare diseased and healthy tissues and pinpoint signaling differences. InFlo is tissue-specific and accounts for genetic alterations associated with disease, unlike other methods. It represents a major step forward in deciphering the activities of multi-tiered signaling networks commonly used by cells. "Complex diseases such as cancer involve the simultaneous disruptions of multiple cellular processes acting in tandem," said Varadan. "We developed InFlo to robustly integrate multiple molecular data streams and develop an integrative molecular portrait of an individual cancer sample." InFlo incorporates data related to each level of cell communication within a single sample, including DNA, RNA, proteins, and molecules commonly attached to proteins such as chemical methyl groups. The method also includes strategies to reduce "noise" and only highlight the signaling networks most likely to cause disease. Analisa DiFeo, PhD, senior co-corresponding author on the study, Norma C. and Al I. Geller Designated Professor of Ovarian Cancer Research at Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center, validated InFlo using ovarian cancer tumor cells that were resistant to platinum-based chemotherapy. InFlo pinpointed the interaction between two proteins called cAMP and CREB1 as a key mechanism associated with platinum resistance. "Following up on InFlo's predictions, we showed that inhibiting CREB1 potently sensitizes ovarian cancer cells to platinum therapy and is also effective in killing ovarian cancer stem cells. We are therefore excited about this discovery and are currently evaluating whether this could lead to a potential therapeutic target for the treatment of platinum-resistant ovarian cancer," said DiFeo. InFlo is being incorporated into Philips IntelliSpace Genomics platform, and will soon be available for widespread use in basic and translational research settings. Case Western Reserve University researchers will continue to develop the IntelliSpace Genomics InFlo module and the next step will be to expand InFlo to incorporate other data streams. "We are currently collaborating with the Imaging Informatics research group in the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University to integrate InFlo with imaging-features derived from pathology and radiology data," said Varadan. Such an addition would result in one of the most comprehensive tools available to researchers to infer mechanisms underlying complex diseases such as cancer.


News Article | November 10, 2016
Site: www.eurekalert.org

A multi-institution academic-industrial partnership of researchers led by Case Western Reserve University School of Medicine has developed a new method to broadly assess cell communication networks and identify disease-specific network anomalies. The computer-based method, called InFlo, was developed in collaboration with researchers at Philips and Princeton University and predicts how cells send signals across networks to cause cancer or other disease. Details about the new method were recently published in Oncogene. "Cellular signaling networks are the mechanisms that cells use to transfer, process, and respond to biological information derived from their immediate surroundings," said Vinay Varadan, PhD, assistant professor at Case Western Reserve University School of Medicine, member of the Case Comprehensive Cancer Center, and senior corresponding author on the study. "InFlo can be viewed as modeling the flow of information within these signaling networks." InFlo works by assessing gene activity levels in tissue samples and predicting corresponding protein levels. It then uses statistical probabilities and other mathematical models to build activity webs showing how the proteins interact. Researchers can use InFlo to compare diseased and healthy tissues and pinpoint signaling differences. InFlo is tissue-specific and accounts for genetic alterations associated with disease, unlike other methods. It represents a major step forward in deciphering the activities of multi-tiered signaling networks commonly used by cells. "Complex diseases such as cancer involve the simultaneous disruptions of multiple cellular processes acting in tandem," said Varadan. "We developed InFlo to robustly integrate multiple molecular data streams and develop an integrative molecular portrait of an individual cancer sample." InFlo incorporates data related to each level of cell communication within a single sample, including DNA, RNA, proteins, and molecules commonly attached to proteins such as chemical methyl groups. The method also includes strategies to reduce "noise" and only highlight the signaling networks most likely to cause disease. Analisa DiFeo, PhD, senior co-corresponding author on the study, Norma C. and Al I. Geller Designated Professor of Ovarian Cancer Research at Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center, validated InFlo using ovarian cancer tumor cells that were resistant to platinum-based chemotherapy. InFlo pinpointed the interaction between two proteins called cAMP and CREB1 as a key mechanism associated with platinum resistance. "Following up on InFlo's predictions, we showed that inhibiting CREB1 potently sensitizes ovarian cancer cells to platinum therapy and is also effective in killing ovarian cancer stem cells. We are therefore excited about this discovery and are currently evaluating whether this could lead to a potential therapeutic target for the treatment of platinum-resistant ovarian cancer," said DiFeo. InFlo is being incorporated into Philips IntelliSpace Genomics platform, and will soon be available for widespread use in basic and translational research settings. Case Western Reserve University researchers will continue to develop the IntelliSpace Genomics InFlo module and the next step will be to expand InFlo to incorporate other data streams. "We are currently collaborating with the Imaging Informatics research group in the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University to integrate InFlo with imaging-features derived from pathology and radiology data," said Varadan. Such an addition would result in one of the most comprehensive tools available to researchers to infer mechanisms underlying complex diseases such as cancer. The research was supported in part, by public health service awards Career Development Program of Case GI SPORE (P50 CA150964) award to V.V. and Career Development Program in Computational Genomic Epidemiology of Cancer (R25T CA094186) award to V.V. Additional support included funding from Philips Healthcare to V.V.; the Rosalie and Morton Cohen Family Memorial Genomics Fund of University Hospitals to V.V.; Ohio Cancer Research award to V.V.; VelaSano Bike for Cure Funds award to A.D. and V.V.; and the Norma I. and Al G. Geller Endowment in Ovarian Cancer Research to A.D. For more information about Case Western Reserve University School of Medicine, please visit: http://case. .


News Article | November 21, 2016
Site: www.scientificcomputing.com

A multi-institution academic-industrial partnership of researchers led by Case Western Reserve University School of Medicine has developed a new method to broadly assess cell communication networks and identify disease-specific network anomalies. The computer-based method, called InFlo, was developed in collaboration with researchers at Philips and Princeton University and predicts how cells send signals across networks to cause cancer or other disease. Details about the new method were recently published in Oncogene. "Cellular signaling networks are the mechanisms that cells use to transfer, process, and respond to biological information derived from their immediate surroundings," said Vinay Varadan, PhD, assistant professor at Case Western Reserve University School of Medicine, member of the Case Comprehensive Cancer Center, and senior corresponding author on the study. "InFlo can be viewed as modeling the flow of information within these signaling networks." InFlo works by assessing gene activity levels in tissue samples and predicting corresponding protein levels. It then uses statistical probabilities and other mathematical models to build activity webs showing how the proteins interact. Researchers can use InFlo to compare diseased and healthy tissues and pinpoint signaling differences. InFlo is tissue-specific and accounts for genetic alterations associated with disease, unlike other methods. It represents a major step forward in deciphering the activities of multi-tiered signaling networks commonly used by cells. "Complex diseases such as cancer involve the simultaneous disruptions of multiple cellular processes acting in tandem," said Varadan. "We developed InFlo to robustly integrate multiple molecular data streams and develop an integrative molecular portrait of an individual cancer sample." InFlo incorporates data related to each level of cell communication within a single sample, including DNA, RNA, proteins, and molecules commonly attached to proteins such as chemical methyl groups. The method also includes strategies to reduce "noise" and only highlight the signaling networks most likely to cause disease. Analisa DiFeo, PhD, senior co-corresponding author on the study, Norma C. and Al I. Geller Designated Professor of Ovarian Cancer Research at Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center, validated InFlo using ovarian cancer tumor cells that were resistant to platinum-based chemotherapy. InFlo pinpointed the interaction between two proteins called cAMP and CREB1 as a key mechanism associated with platinum resistance. "Following up on InFlo's predictions, we showed that inhibiting CREB1 potently sensitizes ovarian cancer cells to platinum therapy and is also effective in killing ovarian cancer stem cells. We are therefore excited about this discovery and are currently evaluating whether this could lead to a potential therapeutic target for the treatment of platinum-resistant ovarian cancer," said DiFeo. InFlo is being incorporated into Philips IntelliSpace Genomics platform, and will soon be available for widespread use in basic and translational research settings. Case Western Reserve University researchers will continue to develop the IntelliSpace Genomics InFlo module and the next step will be to expand InFlo to incorporate other data streams. "We are currently collaborating with the Imaging Informatics research group in the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University to integrate InFlo with imaging-features derived from pathology and radiology data," said Varadan. Such an addition would result in one of the most comprehensive tools available to researchers to infer mechanisms underlying complex diseases such as cancer.

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