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News Article | May 5, 2017
Site: www.eurekalert.org

Platelets promote immune tolerance to certain cancers by suppressing T cells and adoptive T cell therapy may be enhanced by adding antiplatelet drugs, report researchers at the Medical University of South Carolina in Science Immunology Blood platelets help disguise cancer from the immune system by suppressing T cells, report scientists at the Medical University of South Carolina (MUSC) in the May 5, 2017 issue of Science Immunology. In extensive preclinical tests, a promising T cell therapy more successfully boosted immunity against melanoma when common antiplatelet drugs such as aspirin were added. Zihai Li, M.D., Ph.D., senior author on the article, is chair of the MUSC Department of Microbiology and Immunology, the program leader for the Cancer Immunology Research Program at MUSC Hollings Cancer Center, and the SmartState® Sally Abney Rose Chair in Stem Cell Biology & Therapy. Li studies how tumors hide themselves from the immune system. Li's team found that platelets release a molecule that suppresses the activity of cancer-fighting T cells. That molecule, unsurprisingly, was TGF-beta, which has been recognized for decades for its role in cancer growth. Yet this study is the first of its kind. Most TGF-beta is inactive. Li and his group found that the surface of platelets has a protein called GARP, a molecular hook that is uniquely able to trap and activate TGF-beta. Platelets, which are small cell fragments that circulate throughout the blood and are normally involved in clotting, become the major source of activated TGF-beta that invading tumor cells use to suppress T cells. In other words, platelets help give tumors their invisibility cloak from the immune system. Scientists have known for several years that certain cancers suppress T cells to avoid the immune system. That is why adoptive T cell therapy is one of the most promising advances in modern cancer treatment. It is a type of immunotherapy that awakens the immune system by retraining a patient's T cells to recognize their cancer. T cells are isolated from a patient's blood and retrained, or "primed," to recognize tumor cells. They are then injected back into the patient's bloodstream where they can now hunt and fight cancer. There was some evidence that platelets might make cancer worse. For example, patients who have excessive clotting related to their cancer almost always have a worse prognosis, according to Li. "Over the years, it has become appreciated that platelets are doing more than just clotting," says Li. The first clue that cancer-fighting T cells might be suppressed by the body's own clotting system came when the researchers gave melanoma to mice with genetically defective platelets. Melanoma tumors grew much more slowly and primed T cells were much more active than in mice with normal platelets. Next, the team isolated platelets and T cells from blood drawn from humans and mice. In both cases, platelets with activated clotting activity suppressed T cell response. It then used mass spectrometry to thoroughly identify the molecules released by activated platelets that most suppressed T cell activity. The molecule with the most T cell suppression was TGF-beta. Li and his team then studied how platelets activate TGF-beta. In genetically modified mice without GARP, the molecular hook on the surface of platelets, adoptive T cell therapy was more successful at controlling melanoma. This meant that platelets without the ability to grab and activate TGF-beta were not able to suppress cancer-fighting T cells. Similar experiments confirmed this result in mice with colon carcinoma. Finally, mice with normal platelets that were given melanoma and then adoptive T cell therapy survived longer and relapsed less when aspirin and clopidogrel, two antiplatelet drugs, were added. The researchers noted that antiplatelet drugs by themselves were not successful in combating melanoma in their experiments. This study could inform future treatment of melanoma and other cancers and offers a sound reason to test antiplatelet drugs in clinical trials of adoptive T cell therapy. In patients with melanoma or other cancers, adoptive T cell therapy may be successful if highly available platelet-blocking drugs such as aspirin are added to the treatment. However, the current standard of care for melanoma is not adoptive T cell therapy, but so-called checkpoint inhibitors. Li and his group want to know if combination therapy with antiplatelet drugs could improve existing cancer treatment. They are waiting for approval to begin a clinical trial that will test certain checkpoint inhibitors in combination with aspirin and clopidogrel for the treatment of patients with advanced cancers. Li's trial will complement clinical trials that are already testing adoptive T cell therapy as a single treatment for cancer. "I'm very excited about this," says Li. "We can test simple, over-the-counter antiplatelet agents to really improve immunity and make a difference in how to treat people with cancer." Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents in six colleges (Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing, and Pharmacy), and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion, with an annual economic impact of more than $3.8 billion and annual research funding in excess of $250 million. MUSC operates a 700-bed medical center, which includes a nationally recognized children's hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute-designated center), Level I Trauma Center, Institute of Psychiatry, and the state's only transplant center. In 2016, U.S. News & World Report named MUSC Health the number one hospital in South Carolina. For more information on academic programs or clinical services, visit musc.edu. For more information on hospital patient services, visit muschealth.org.


TEL-AVIV, Israel, April 20, 2017 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today announced the publication of an article describing the positive results from the Phase I clinical study with YELIVA® (ABC294640)1 in advanced solid tumors. The article2, entitled “A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in Patients with Advanced Solid Tumors”, was authored by scientists from the Medical University of South Carolina (MUSC) Hollings Cancer Center and Apogee Biotechnology and was published in Clinical Cancer Research. The article is available online on the journal’s website3. YELIVA® is a Phase II-stage, proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor with anticancer and anti-inflammatory activities, targeting multiple oncology, inflammatory and gastrointestinal indications. By inhibiting the SK2 enzyme, YELIVA® blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation. The open-label, dose-escalation, pharmacokinetic (PK) and pharmacodynamic (PD) first-in-human Phase I study with YELIVA® treated 21 patients with advanced solid tumors, most of whom were gastrointestinal cancer patients, including pancreatic, colorectal and cholangiocarcinoma cancers. The Phase I study was conducted at the MUSC Hollings Cancer Center and led by Principal Investigators Melanie Thomas, MD, and Carolyn Britten, MD. The primary objectives of the study were to identify the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) and to evaluate the safety of YELIVA®. The secondary objectives of the study were to determine the pharmacokinetic (PK) and pharmacodynamic (PD) properties of YELIVA® and to assess its antitumor activity. Final results from the Phase I study with YELIVA® in patients with advanced solid tumors confirmed that the study successfully met its primary and secondary endpoints, demonstrating that the drug is well-tolerated and can be safely administered to cancer patients. There was one partial response in a patient with cholangiocarcinoma and six patients had stable disease as their best response. The study included the first-ever longitudinal analyses of plasma S1P levels as a potential PD biomarker for activity of a sphingolipid-targeted drug. The administration of YELIVA® resulted in a rapid and pronounced decrease in S1P levels over the first 12 hours, with return to baseline at 24 hours, which is consistent with clearance of the drug. A Phase II study with YELIVA® for the treatment of advanced hepatocellular carcinoma (HCC) is ongoing at MUSC Hollings Cancer Center. The study is supported by a grant from the NCI, awarded to MUSC, which is intended to fund a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, with additional support from RedHill. A Phase Ib/II study with YELIVA® for the treatment of refractory or relapsed multiple myeloma is ongoing at Duke University Medical Center. The study is supported by a $2 million grant from the NCI Small Business Innovation Research Program (SBIR) awarded to Apogee, in conjunction with Duke University, with additional support from RedHill. A Phase I/II clinical study evaluating YELIVA® in patients with refractory/relapsed diffuse large B-cell lymphoma and Kaposi sarcoma patients is ongoing at the Louisiana State University Health Sciences Center. The study is supported by a grant from the NCI awarded to Apogee, with additional support from RedHill. A Phase Ib study to evaluate YELIVA® as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is planned to be initiated in the third quarter of 2017. YELIVA® recently received FDA Orphan Drug designation for the treatment of cholangiocarcinoma. RedHill plans to initiate a Phase IIa clinical study with YELIVA® in patients with advanced, unresectable, intrahepatic and extrahepatic cholangiocarcinoma in the third quarter of 2017. A Phase II study to evaluate the efficacy of YELIVA® in patients with moderate to severe ulcerative colitis is planned to be initiated in the second half of 2017. About YELIVA® (ABC294640): YELIVA® (ABC294640) is a Phase II-stage, proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anticancer and anti-inflammatory activities. RedHill is pursuing with YELIVA® multiple clinical programs in oncology, inflammatory and gastrointestinal indications. By inhibiting SK2, YELIVA® blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid-signaling molecule that promotes cancer growth and pathological inflammation. SK2 is an innovative molecular target for anticancer therapy because of its critical role in catalyzing the formation of S1P, which is known to regulate cell proliferation and activation of inflammatory pathways. YELIVA® was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as the ABC-101 Phase I clinical study in cancer patients with advanced solid tumors. The Phase I study included the first-ever longitudinal analysis of plasma S1P levels as a potential pharmacodynamic (PD) biomarker for activity of a sphingolipid-targeted drug. The administration of YELIVA® resulted in a rapid and pronounced decrease in S1P levels, with several patients having prolonged stabilization of disease. YELIVA® received Orphan Drug designation from the U.S. FDA for the treatment of cholangiocarcinoma. The development of YELIVA® was funded to date primarily by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including the U.S. National Cancer Institute, the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), the U.S. Department of Defense and the FDA Office of Orphan Products Development. About RedHill Biopharma Ltd.: RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) is a specialty biopharmaceutical company headquartered in Israel, primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer. RedHill has a U.S. co-promotion agreement with Concordia for Donnatal®, a prescription oral adjunctive drug used in the treatment of IBS and acute enterocolitis, as well as an exclusive license agreement with Entera Health for EnteraGam®, a medical food intended for the dietary management, under medical supervision, of chronic diarrhea and loose stools. RedHill’s clinical-stage pipeline includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study, a completed proof-of-concept Phase IIa study for multiple sclerosis and QIDP status for nontuberculous mycobacteria (NTM) infections; (iii) BEKINDA® (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study for acute gastroenteritis and gastritis and an ongoing Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA® (ABC294640) - a Phase II-stage, orally-administered, first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications; (vi) MESUPRON - a Phase II-stage first-in-class, orally-administered protease inhibitor, targeting pancreatic cancer and other solid tumors and (vii) RIZAPORT® (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in two EU member states under the European Decentralized Procedure (DCP). More information about the Company is available at: www.redhillbio.com. 1 YELIVA® is an investigational new drug, not available for commercial distribution. 2 The article was authored by Carolyn D. Britten, Melanie B. Thomas, Elizabeth Garrett-Mayer, Steven H. Chin, Keisuke Shirai, Besim Ogretmen, Tricia A. Bentz, Alan Brisendine, Kate Anderton, Susan L. Cusack, Lynn W. Maines, Yan Zhuang and Charles D. Smith. This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to successfully market Donnatal® and EnteraGam®, (vi) the Company’s ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and of the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (ix) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; and (xii) estimates of the Company’s expenses, future revenues capital requirements and the Company’s needs for additional financing; (xiii) competitive companies and technologies within the Company’s industry. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 23, 2017. All forward-looking statements included in this Press Release are made only as of the date of this Press Release. We assume no obligation to update any written or oral forward-looking statement unless required by law.


News Article | February 21, 2017
Site: www.eurekalert.org

Fibrosis investigators at the Medical University of South Carolina show that a caveolin-1 surrogate peptide, known to be anti-fibrotic in the skin and lung, also reverses cardiac fibrosis in a preclinical model Cardiac fibrosis, an abnormal thickening of the heart wall leading to congestive heart failure, was not only halted but also reversed by a caveolin-1 surrogate peptide (CSD) in a preclinical model, report researchers at the Medical University of South Carolina (MUSC) in an article published online on January 23, 2017 by Laboratory Investigation. CSD was able to decrease the fibrotic ventricular wall thickness and improve heart function, all with apparently no toxicity and minimal off-target effects. The MUSC research team included pulmonary fibrosis investigators Stanley Hoffman, Ph.D., and Elena V. Tourkina, Ph.D., who had previously shown caveolin-1's anti-fibrotic properties in the skin and lung. For this project, they joined forces with MUSC congestive heart failure researchers in the laboratory of Dhandapani Kuppuswamy, Ph.D., to show that caveolin-1's anti-fibrotic properties in skin and lung also hold in yet another organ: the heart. More than a decade ago, Hoffman and Tourkina noted that the skin and lung cells producing excess collagen in scleroderma, leading to fibrosis, were deficient in caveolin-1. Supplementing these cells with a caveolin-1 surrogate peptide (CSD; caveolin-1 scaffolding domain peptide), a truncated version of the original compound, showed a reversal of fibrosis. MUSC has obtained a patent to test CSD on fibrotic diseases across organs which they have licensed to Lung Therapeutics, Inc. The company intends to support research involving CSD and fibrosis in the Hoffman and Kuppuswamy laboratories. Kuppuswamy's laboratory focuses on hypertrophic overgrowth and profibrogenic signaling of the cardiac muscle in pressure overload. Fibrosis that develops under these conditions is detrimental to the heart's pumping efficiency as it causes a stiffer and less compliant cardiac muscle, leading to the progression of congestive heart failure. "Currently, there are no therapeutic options for congestive heart failure that specifically target the causative cardiac fibrosis. Everyone is looking for this," said Kuppuswamy, an associate professor at the Gazes Cardiac Research Institute. According to the Centers for Disease Control and Prevention, heart failure affects almost six million Americans, and half of those with heart failure die within five years of diagnosis. To mimic the cardiac fibrosis typical of heart failure, Kuppuswamy used a transverse aortic constriction mouse model to create pressure overload hypertrophy that then led to the development of fibrosis. Treatment with CSD not only halted the progression of the cardiac fibrosis but also led to its reversal with improved ventricular function. Although promising, these findings are preliminary -- only reflecting outcomes in mice. The researchers plan to run larger preclinical studies using the same approach to generate more definitive data, and if all goes as expected, to move forward to the large-animal studies necessary to take a compound forward into clinical trial. They also note that they are testing CSD in a different congestive heart failure model, the angiotensin II infusion model, which also affects the kidneys. CSD is showing promising anti-fibrotic effects on both the heart and the kidneys in this model. "Fibrotic diseases are related to each other no matter the affected organ. In our case, we were studying lung and skin fibrosis," explained Hoffman. "We got the opportunity to test the same reagent in heart fibrosis and, lo and behold, it worked even better than in lung and skin fibrosis models. And there are plenty of other diseases with a fibrotic element to them where we think the CSD peptide might be useful." The co-authors thank the MUSC College of Medicine Enhancement of Team Science (COMETS) for helping support this work. Without this support, this work would not have been possible. Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion. MUSC operates a 750-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute designated center) Level I Trauma Center, and Institute of Psychiatry. For more information on academic information or clinical services, visit musc.edu. For more information on hospital patient services, visit muschealth.org.


News Article | February 21, 2017
Site: www.eurekalert.org

Investigators at the Medical University of South Carolina and elsewhere report that myxoma virus, a rabbit virus, reduced tumor burden in preclinical studies, completely eradicating disease in a quarter of animals Treating multiple myeloma (MM) with myxoma virus (MYXV) eliminated a majority of malignant cells in preclinical studies, report investigators at the Medical University of South Carolina (MUSC) and elsewhere in an article published online on December 7, 2016 by Molecular Therapy -- Oncolytics. Furthermore, introduction of MYXV elicited a strong immune response that eradicated disease in some animals. Multiple myeloma is a cancer of plasma B cells, a cell type within the body's immune system. MM is the second most common blood cancer and, unfortunately, remains difficult to treat. Even with the introduction of new chemotherapy regimens, most patients still succumb to disease relapse either from reinfusion of cancerous cells during stem cell transplant or expansion of drug-resistant disease after chemotherapy In the recent study, Eric C. Bartee, Ph.D., an assistant professor of Microbiology and Immunology at MUSC, and his colleagues at MUSC and the University of Oslo took a novel approach to treating MM: using viral oncolytics to specifically target and destroy cancer cells. "What I thought was really interesting here was that we could actually get rid of disease and it didn't appear to ever come back," said Bartee. For the past several years, Bartee has been using myxoma virus to treat MM in cell culture. MYXV exclusively infects rabbits and is therefore noninfectious to humans. However, previous work from the Bartee laboratory showed the MYXV was able to kill human MM cells. Currently, stem cell transplants, using a patient's own stem cells, are used as a treatment for MM, but patients often relapse from residual cancer cells within the transplant sample. Bartee showed that treatment with MYXV was successful in eradicating MM cells in patients' stem cell samples prior to re-engraftment, thereby preventing relapse of MM. In the recent study, they took this one step further by assessing whether treatment with MYXV also has a benefit on disease outside the context of transplantation. Using a preclinical mouse model, Bartee showed that systemic treatment with MYXV reduced tumor burden and led to a modest decrease in disease progression in 66% of mice. More impressively, in 25% of mice, there was a complete eradication of disease with no evidence of relapse. Since MYXV does not replicate in MM cells, it was postulated that eradication of disease was caused by the host's immune system. Investigation of the bone marrow, a compartment that helps produce red and white blood cells, showed that it was unaffected by treatment with MYXV. This suggested that the immune system remained functional and could combat the cancer cells. Indeed, treatment with MYXV led to an increase in CD8+ ¬T cells, a type of white blood cell, within the bone marrow compartment, indicating a strong anti-tumor response. While this preclinical work suggests that MYXV has the potential to cure some patients of MM, there are many hurdles that need to be overcome before this option is available in the clinic. One significant barrier is large-scale production of clinical-grade virus. Another considerable hurdle when moving from preclinical studies in mice to clinical trials in humans is demonstrating a high response rate. "I think the major next question is 'How do you get that response rate from 25% to 50% to 80% to 100%?'" said Bartee. "How do you define the patients in which it works?" One unique advantage of treating MM with MYXV is that the response rate observed in this study is not mediated by the virus. It is actually mediated by the patient's own immune system. Combining MYXV treatment with other immunomodulatory therapies that have been shown to boost anti-tumor response could provide a novel treatment regimen that significantly improves patient outcome compared to the current treatment model. Another advantage is that it is extremely difficult for myeloma to develop resistance to killing by MYXV. One of the challenges with standard chemotherapeutic agents is that many tumors often develop resistance through small changes in the cell, leading to relapse of disease. Because MYXV has evolved for thousands of years to override anything the cell can do, there is no real evidence that tumors can develop resistance to oncolytic infections. "I think what our findings, and oncolytics in general, really highlight is that some of these non-traditional therapies can really offer the benefit of complete disease eradication," said Bartee. "You're not just moving the curve to the right a little bit; you're bending the survival curve up. And you're really fundamentally changing how you can look at cancer treatment." Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion. MUSC operates a 750-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute designated center) Level I Trauma Center, and Institute of Psychiatry. For more information on academic information or clinical services, visit musc.edu. For more information on hospital patient services, visit muschealth.org.


News Article | February 23, 2017
Site: www.eurekalert.org

Policy changes in South Carolina recommended by the South Carolina Act Early Team led to a 5-fold increase in the number of autistic children younger than 3 receiving early intensive behavioral therapy and could serve as a model for other states In the February 2017 issue of Pediatrics, investigators representing the South Carolina Act Early Team report a five-fold increase in the number of children with autism spectrum disorder (ASD) eligible for early intensive behavioral therapy (also known as applied behavior analysis therapy or ABA) after statewide implementation of a two-tiered screening process to identify who children who were "presumptively eligible" for intervention. ABA is the gold standard for treating children with ASD and is known to, sometimes dramatically, improve outcomes and quality of life. However, ABA can be expensive and so is out of the reach of many families without governmental support. In South Carolina, BabyNet is the IDEA Part C program, with state-level intervention, that pays for early behavioral interventions for children three and under. Prior to the policy changes, a formal diagnosis of ASD was required before BabyNet would pay for early intervention. However, the requirement of a formal diagnosis led to delays in treatment. "The big issue with autism is that the waitlist for ASD evaluation is typically six months," said Act Early team member Jane M. Charles, M.D., an MUSC Children's Health developmental pediatrician who holds the Jeffrey Edwin Gilliam Memorial Chair for the Study of Developmental Disabilities. As a result, early intervention was delayed as children waited for a formal diagnosis. The team, which also included David A. Rotholz, Ph.D., of the University of South Carolina School of Medicine, Anne M. Kinsman, Ph.D., of the Greenville Health System, and Kathi K. Lacy of the South Carolina Department of Disabilities and Special Needs (SC DDSN), as well as other leaders from key public and private stakeholder organizations from across the state, saw a way to remove this barrier. "If the eligibility of children under three could be determined more promptly, then ABA therapy, which is between $60,000 and $70,000 yearly, could be done at no cost to families and these children could get the treatment they need," explained Charles. At the team's request, and with the close collaboration of two state agencies (BabyNet/First Steps and the SCDDSN), approval was granted by the U.S. Department of Education to use BabyNet funds to pay for ABA therapy for children who failed a two-stage screening process, even if they had not yet received a formal diagnosis. Children were first screened (typically by a primary care physician) with the Modified Checklist for Autism in Toddlers (M-CHAT); if that screen showed they were at high risk for ASD, they then underwent the Screening Tool for Autism in Toddlers and Children (STAT). Because STAT must be performed by experienced evaluators to be effective, the SCDDSN developed a training program for STAT evaluators to ensure an adequate pool to meet the demand. After implementation of these policy changes in South Carolina, the number of children aged 18 to 36 months receiving ABA therapy grew from 53 children in 2010 to more than 265 children in 2015, a five-fold increase. Providing early ABA to children presumed to have ASD is critical because it is the only intervention that can potentially improve the IQ of an ASD child. The two-stage screening process was highly effective at identifying the children in need of these services and had a very low false-positive rate. Only 16 (2.5%) of the children deemed "presumptively eligible" for ABA were later found not to have ASD. In South Carolina, a Medicaid waiver enables Medicaid-eligible children aged three to 11 years to receive ABA therapy, and state funds pay for ABA therapy for eligible children in that age group who do not receive Medicaid. The state (SCDDSN) agreed that any child who was deemed "presumptively eligible" for ABA through BabyNet and later received a diagnosis of ASD would continue to receive ABA therapy after reaching age three under the Medicaid waiver or through the special state appropriations. This also included having the child bypass the lengthy waiting list for Medicaid waiver ASD services. As a result, children with ASD not only receive ABA early, when it is most effective, but can continue treatment uninterrupted as they grow older. "One thing we know is that when intervention is done early and intensely, especially among children with the most significant deficits, there is improved social interaction and communication," Charles said. The simple policy changes instituted in South Carolina with recommendations from collaborative stakeholders effectively removed barriers to early provision of such services to children with ASD. It is a model that could be replicated by other states. "The collaborative effort of our South Carolina Act Early Team has dramatically increased the number of children at risk for ASD who receive early intervention (ABA services) in a way that is nationally unique," said Rotholz. "It provides a tremendously important service to these children and demonstrates the innovation of our South Carolina partner universities, organizations and agencies." Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents in six colleges (Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing, and Pharmacy), and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion, with an annual economic impact of more than $3.8 billion and annual research funding in excess of $250 million. MUSC operates a 700-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute-designated center), Level I Trauma Center, Institute of Psychiatry, and the state's only transplant center. In 2016, U.S. News & World Report named MUSC Health the number one hospital in South Carolina. For more information on academic programs or clinical services, visit musc.edu. For more information on hospital patient services, visit muschealth.org.


News Article | February 23, 2017
Site: globenewswire.com

TEL-AVIV, Israel, Feb. 23, 2017 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today reported its financial results for the fourth quarter and full-year ended December 31, 2016. Revenues for the fourth quarter of 2016 were $0.1 million, compared to immaterial revenues for the fourth quarter of 2015. Research and Development Expenses for the fourth quarter of 2016 were $7.5 million, up 51% compared to the fourth quarter of 2015. The increase was mainly due to the ongoing Phase III and Phase II studies with BEKINDA® for gastroenteritis and IBS-D, respectively, the ongoing Phase III study with RHB-104 for Crohn’s disease and ongoing studies with YELIVA® for multiple indications. General, Administrative and Business Development Expenses for the fourth quarter of 2016 were $1.6 million, down 6.9% compared to the fourth quarter of 2015. The decrease was mainly due to a decrease in professional services. Operating Loss for the fourth quarter of 2016 was $9 million, up 33% compared to the fourth quarter of 2015. The increase was mainly due to an increase in research and development expenses, as detailed above. Financial Income, net for the fourth quarter of 2016 was $0.6 million, up 214%, compared to the fourth quarter of 2015. The increase was mainly due to a fair value gain on derivative financial instruments. Net Cash Used in Operating Activities for the fourth quarter of 2016 was $10.1 million, up 69% compared to the fourth quarter of 2015. The increase was mainly due to the increase in operating loss, as detailed above. Net Cash Provided by Investment Activities for the fourth quarter of 2016 was $21.3 million, up 206% compared to the fourth quarter of 2015. The increase was mainly due to maturity of bank deposits. Net Cash Provided by Financing Activities for the fourth quarter of 2016 was $35.9 million compared to an immaterial amount for the fourth quarter of 2015. The increase was mainly due to the December 2016 public offering. Revenues for 2016 were $0.1 million, compared to immaterial revenues in 2015. Research and Development Expenses for 2016 were $25.2 million, up 42% compared to 2015. The increase was mainly due to the ongoing Phase III MAP US study with RHB-104 for Crohn's disease, the ongoing Phase III and Phase II studies with BEKINDA® for gastroenteritis and IBS-D, respectively, and the ongoing studies with YELIVA® for multiple indications. General, Administrative and Business Development Expenses for 2016 were $5.4 million, up 31% compared to 2015. The increase was mainly due to an increase in professional services, compensation and other operating expenses. Operating Loss for 2016 was $30.5 million, up 39% compared to 2015. The increase was mainly due to an increase in research and development expenses, as detailed above. Financial Income, net for 2016 was $1.2 million, up 29% compared to 2015. The increase was mainly due to a fair value gain on derivative financial instruments. Net Cash Used in Operating Activities for 2016 was $28.2 million, up 59% compared to 2015. The increase was mainly due to an increase in operating loss, as detailed above. Net Cash Provided by Investment Activities for 2016 was $24.5 million, up 215% compared to 2015. The difference was mainly due to maturity of bank deposits. Net Cash Provided by Financing Activities for 2016 was $36 million, down 34% compared to 2015. The decrease resulted primarily from the two public offerings in February and July 2015 of the comparable period. Cash Balance3 as of December 31, 2016 was $66.3 million, an increase of $8.2 million compared to $58.1 million as of December 31, 2015 and an increase of $25.8 million compared to $40.5 million as of September 30, 2016. Micha Ben Chorin, RedHill’s CFO, said: “Our strong cash position of approximately $66 million at the end of 2016 should allow us to continue to execute our strategic plans for 2017. We are looking forward to an important year ahead, including the planned initiation of a confirmatory Phase III study with RHB-105 for H. pylori infection, a second independent DSMB meeting for the ongoing MAP US Phase III study with RHB-104 for Crohn’s disease, top-line results from the ongoing Phase III and Phase II studies with BEKINDA® for gastroenteritis and IBS-D, respectively, and commencement of our promotional activities in the U.S. with Donnatal®." The Company will host a conference call on Thursday, February 23, 2017, at 9:00 am EST to review the financial results and business highlights. To participate in the conference call, please dial the following numbers 5-10 minutes prior to the start of the call: United States: +1-877-280-1254; International: +1-646-254-3366; and Israel: +972-3-763-0145. The access code for the call is 4402478. The conference call will be broadcasted live and available for replay on the Company's website, http://ir.redhillbio.com/events.cfm, for 30 days. Please access the Company's website at least 15 minutes ahead of the conference to register, download, and install any necessary audio software. RHB-105 - H. pylori bacterial infection (confirmatory Phase III) (QIDP status)         Following the announcement of the successful final results from a first Phase III clinical study with RHB-105 for the eradication of H. pylori infection (the ERADICATE Hp study) in March 2016, RedHill concluded two positive Type B meetings with the U.S. Food and Drug Administration (FDA) regarding RHB-105. The first meeting, announced in April 2016, confirmed the path to marketing approval of RHB-105 and the planned confirmatory Phase III study. A second Type B meeting, announced in November 2016, discussed the chemistry, manufacturing and controls (CMC) aspects of the RHB-105 Phase III development program towards filing the CMC package as part of the potential U.S. New Drug Application (NDA) to be submitted for RHB-105, subject to successful completion of the planned confirmatory Phase III study. The two-arm, randomized, double-blind, active comparator confirmatory Phase III study, comparing RHB-105 against a dual therapy amoxicillin and omeprazole regimen at equivalent doses, is planned to be initiated in the second quarter of 2017, subject to the successful completion of the ongoing supportive pharmacokinetic (PK) program and submission of the Clinical Study Report to the FDA. The confirmatory Phase III study is planned to enroll approximately 440 patients in up to 55 clinical sites in the U.S. In October 2016, RedHill provided an update on the RHB-104 Phase III Crohn’s disease development program, planned enhancements to the ongoing MAP US Phase III study and expected milestones, including an increase in the total number of patients planned to be enrolled in the MAP US study from 270 to 410, and the addition of an open-label extension study offering patients who complete 26 weeks of study participation and remain out of remission (Crohn’s disease active index (CDAI) >150) the opportunity to receive treatment with RHB-104 for a 52-week period. The open-label extension study is expected to be initiated in the coming weeks. Following a pre-planned review of safety data from its ongoing MAP US study by an independent Data and Safety Monitoring Board (DSMB), RedHill announced in December 2016 that it had received a unanimous recommendation to continue the MAP US study as planned. A second independent DSMB meeting of the MAP US study, expected in the second quarter of 2017, will include an interim efficacy analysis and will evaluate the option for an early stop for success for overwhelming efficacy, according to a pre-specified statistical significance threshold. Taking into account the increase in the total number of patients planned in the MAP US study, and assuming the MAP US study is not stopped for success or inefficacy following the independent DSMB meeting in the second quarter of 2017, completion of recruitment is expected by the end of 2017. In December 2016, RedHill announced encouraging top-line final results of a Phase IIa, proof-of-concept clinical study, evaluating RHB-104 as an add-on therapy to interferon beta-1a in patients treated for relapsing remitting multiple sclerosis (the CEASE MS study). The top-line final results (48 weeks) were consistent with previously announced interim results, suggesting meaningful positive safety and clinical signals upon 24 weeks of treatment with RHB-104 as an add-on therapy, thereby supporting further clinical development. In January 2017, RedHill announced that RHB-104 had been granted Qualified Infectious Disease Product (QIDP) designation by the FDA for the treatment of nontuberculous mycobacteria (NTM) infections. RedHill plans to consult with the FDA regarding the RHB-104 development program for NTM infections. In February 2017, RedHill announced that the last patient enrolled in the randomized, double-blind, placebo-controlled Phase III clinical study with BEKINDA® 24 mg in the U.S. for acute gastroenteritis and gastritis (the GUARD study) had completed the treatment course and observation period for the primary endpoint evaluation. Top-line results are expected in the second quarter of 2017. A randomized, double-blind, placebo-controlled Phase II clinical study with BEKINDA® 12 mg for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) is ongoing in the U.S. with top-line results expected in mid-2017. In June 2016, RedHill announced positive final results from a Phase I study with YELIVA® in patients with advanced solid tumors. The Phase I study, conducted at the Medical University of South Carolina Hollings Cancer Center, successfully met its primary and secondary endpoints, demonstrating that the drug is well-tolerated and can be safely administered to cancer patients at doses predicted to have therapeutic activity. In September 2016, RedHill announced a research collaboration with Stanford University School of Medicine for the evaluation of YELIVA®. The research collaboration is intended to complement RedHill’s planned Phase Ib clinical study to evaluate YELIVA® as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy. The Phase Ib study is planned to be initiated in mid-2017. In October 2016, RedHill announced the initiation of a Phase II clinical study with YELIVA® for advanced hepatocellular carcinoma at the Medical University of South Carolina. In December 2016, RedHill announced that the first patient was dosed in a Phase Ib/II study with YELIVA® for refractory or relapsed multiple myeloma, conducted at Duke University Medical Center. A Phase I/II clinical study evaluating YELIVA® in patients with refractory/relapsed diffuse large B-cell lymphoma is ongoing at the Louisiana State University Health Sciences Center and was recently amended to address overall recruitment prospects and to include Kaposi sarcoma patients in the study. A Phase II study to evaluate the efficacy of YELIVA® in patients with moderate to severe ulcerative colitis is planned to be initiated in the second half of 2017.    In 2016, RedHill and its co-development partner, IntelGenx Corp., entered into exclusive license agreements for the commercialization of RIZAPORT® oral thin-film for acute migraines with Grupo JUSTE S.A.Q.F (now Exeltis Healthcare, S.L.) for Spain and with Pharmatronic Co. for South Korea. Re-submission of the RIZAPORT® NDA to the FDA is expected in the third quarter of 2017. In January 2017, RedHill announced the signing of a new collaboration agreement with the Department of Molecular Biology and Genetics of Denmark-based Aarhus University for the evaluation of RedHill’s Phase II-stage oncology drug candidate, MESUPRON. The new research collaboration follows previous non-clinical studies conducted with Denmark’s Aarhus University and is designed to identify additional high affinity molecular targets of MESUPRON. Further evaluation of MESUPRON, together with Aarhus University, may allow for selection of appropriate sub-populations of patients toward demonstrating the activity of MESUPRON in planned clinical trials. RedHill is currently preparing a protocol for a Phase I/II study of the safety, efficacy and dose evaluation of MESUPRON in combination with chemotherapy in patients receiving adjuvant chemotherapy for resected pancreatic cancer. The Phase I/II study is expected to be initiated in the second half of 2017 in up to six sites in Germany. As part of RedHill’s strategic initiative to become a revenue-generating, gastrointestinal-focused, specialty pharmaceutical company with a commercial presence in the U.S., the Company entered in January 2017 into an exclusive co-promotion agreement with a subsidiary4 of Concordia International Corp., granting RedHill certain U.S. promotional rights for Donnatal®, a prescription oral drug used with other drugs in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis (inflammation of the small bowel)5. RedHill expects to initiate promotion of Donnatal® in the coming months. In December 2016, RedHill closed an underwritten public offering and a registered direct offering of American Depositary Shares (ADSs) and warrants to purchase ADSs for aggregate net proceeds, after deducting underwriting discounts and commissions, placement agent fees and other offering expenses, of $35.9 million. Investors in the public offering included, among others, Sabby Management, LLC, DAFNA Capital Management, Rosalind Advisors, Inc., Koramic Holding, Lincoln Park Capital, and Nexthera Capital LP. About Donnatal®: Donnatal® (Phenobarbital, Hyoscyamine Sulfate, Atropine Sulfate, Scopolamine Hydrobromide), a prescription drug, is classified as possibly effective as an adjunctive therapy in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis. Donnatal® slows the natural movements of the gut by relaxing the muscles in the stomach and intestines and acts on the brain to produce a calming effect. Donnatal® comes in two formulations: immediate release Donnatal® Tablets and immediate release Donnatal® Elixir, a fast acting liquid. Donnatal® is contraindicated in patients who have glaucoma, obstructive uropathy, obstructive disease of the gastrointestinal tract, paralytic ileus, unstable cardiovascular status, severe ulcerative colitis, myasthenia gravis, hiatal hernia with reflux esophagitis, or known hypersensitivity to any of the ingredients. Patients who are pregnant or breast-feeding or who have autonomic neuropathy, hepatic or renal disease, hyperthyroidism, coronary heart disease, congestive heart failure, cardiac arrhythmias, tachycardia or hypertension should notify their doctor before taking Donnatal®. Side effects may include: dryness of the mouth, urinary retention, blurred vision, dilation of pupils, rapid heartbeat, loss of sense of taste, headache, nervousness, drowsiness, weakness, dizziness, insomnia, nausea, vomiting and allergic reactions which may be severe. Further information, including prescribing information, can be found on www.donnatal.com. Please see the following website for important safety information about Donnatal®:           http://www.donnatal.com/professionals/important-safety-information/ About RedHill Biopharma Ltd.: RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) is a specialty biopharmaceutical company headquartered in Israel, primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer. RedHill has a U.S. co-promotion agreement with Concordia for Donnatal®, a prescription oral adjunctive drug used in the treatment of IBS and acute enterocolitis. RedHill’s clinical-stage pipeline includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study, a completed proof-of-concept Phase IIa study for multiple sclerosis and QIDP status for nontuberculous mycobacteria (NTM) infections; (iii) BEKINDA® (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study for acute gastroenteritis and gastritis and an ongoing Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA® (ABC294640) - a Phase II-stage, orally-administered, first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications; (vi) MESUPRON - a Phase II-stage first-in-class, orally-administered uPA inhibitor, targeting gastrointestinal and other solid tumors and (vii) RIZAPORT® (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in Germany in October 2015. More information about the Company is available at: www.redhillbio.com. This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to successfully market Donnatal®, (vi) the Company’s ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and of the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (ix) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; and (xii) estimates of the Company’s expenses, future revenues capital requirements and the Company’s needs for additional financing; (xiii) competitive companies and technologies within the Company’s industry. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 25, 2016. All forward-looking statements included in this Press Release are made only as of the date of this Press Release. We assume no obligation to update any written or oral forward-looking statement unless required by law. 1 All financial highlights are approximate and are rounded to the nearest hundreds of thousands. 2 All financial highlights are approximate and are rounded to the nearest hundreds of thousands. 5 Donnatal® (Phenobarbital, Hyoscyamine Sulfate, Atropine Sulfate, Scopolamine Hydrobromide) is a prescription drug, classified as possibly effective as an adjunctive therapy in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis.  For more information, please see the prescribing information: http://www.donnatal.com/wp-content/uploads/2015/02/2015-02-18-Risk-Benefit-information-DTC-REV.-SE.pdf.


TEL-AVIV, Israel, Dec. 19, 2016 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) (“RedHill” or the “Company”), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today announced that the first patients have been screened and a first patient has been dosed in the Phase Ib/II clinical study evaluating YELIVA® (ABC294640) in patients with refractory or relapsed multiple myeloma. The open-label, dose escalation Phase Ib/II study is being conducted at Duke University Medical Center and is expected to enroll up to 77 patients with refractory or relapsed multiple myeloma who have previously been treated with proteasome inhibitors and immunomodulatory drugs. Dr. Yubin Kang, MD, Associate Professor in the Division of Hematologic Malignancies and Cellular Therapy in the Department of Medicine at Duke University School of Medicine, is the lead investigator for the study. The study is supported by a $2 million grant from the National Cancer Institute (NCI) Small Business Innovation Research Program (SBIR) awarded to Apogee Biotechnology Corp. (Apogee), in conjunction with Duke University, with additional support from RedHill. YELIVA® is a proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor, with anti-cancer and anti-inflammatory activities. By inhibiting the SK2 enzyme, YELIVA® blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation. RedHill is pursuing and evaluating multiple clinical programs in oncology, inflammatory and gastrointestinal indications with YELIVA®, as well as potential collaboration opportunities with larger pharmaceutical companies to evaluate YELIVA® as an add-on therapy to existing oncology treatments. Results from a Phase I study with YELIVA® in patients with advanced solid tumors confirmed that the study, conducted at the Medical University of South Carolina Hollings Cancer Center (MUSC), successfully met its primary and secondary endpoints, demonstrating that the drug is well-tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity. A Phase II study with YELIVA® for the treatment of advanced hepatocellular carcinoma (HCC) was initiated at MUSC Hollings Cancer Center, following ethics approval and successful submission to the U.S. FDA. The study is supported by a $1.8 million grant from the NCI, awarded to MUSC, which is intended to fund a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, with additional support from RedHill. A Phase I/II clinical study evaluating YELIVA® in patients with refractory/relapsed diffuse large B-cell lymphoma was initiated at the Louisiana State University Health Sciences Center in New Orleans in June 2015 and was recently amended to address overall recruitment prospects. The study will now also include Kaposi sarcoma patients. The study is supported by a grant from the NCI awarded to Apogee, with additional support from RedHill. A Phase Ib study to evaluate YELIVA® as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is planned to be initiated in the first half of 2017. Additional Phase I/II studies with YELIVA® for other indications are in various stages of preparation. The ongoing studies with YELIVA® (ABC294640) are registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health, which provides public access to information on publicly and privately supported clinical studies. About Multiple Myeloma:    Multiple myeloma is a malignant plasma cell disorder which is usually not curable1.  Symptomatic multiple myeloma is characterized by a clonal proliferation of plasma cells preceding clinical findings that include bone lesions, fractures, anemia, renal failure and hypercalcemia2. Approximately 30,000 new cases of multiple myeloma are expected to be diagnosed in the U.S. in 2016, accounting for 1.8% of all cancers. The 5-year survival rate of myeloma is estimated at 48.5% and approximately 95,000 people are living with myeloma in the United States3. The risk of multiple myeloma increases as people age. Most patients diagnosed with this cancer are at least 65 years old4, making treatment with the most effective therapies problematic. The worldwide sales of multiple myeloma therapies are estimated to exceed $12 billion in 20165. About YELIVA® (ABC294640): YELIVA® (ABC294640) is a Phase II-stage, proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anti-cancer and anti-inflammatory activities. RedHill is pursuing with YELIVA® multiple clinical programs in oncology, inflammatory and gastrointestinal indications. By inhibiting the SK2 enzyme, YELIVA® blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation. SK2 is an innovative molecular target for anticancer therapy because of its critical role in catalyzing the formation of S1P, which is known to regulate cell proliferation and activation of inflammatory pathways. YELIVA® was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as the ABC-101 Phase I clinical study in cancer patients with advanced solid tumors. The Phase I study included the first-ever longitudinal analysis of plasma S1P levels as a potential pharmacodynamic (PD) biomarker for activity of a sphingolipid-targeted drug. The administration of YELIVA® resulted in a rapid and pronounced decrease in S1P levels, with several patients having prolonged stabilization of disease. The development of YELIVA® was funded to date primarily by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including the U.S. National Cancer Institute, the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), the U.S. Department of Defense and the FDA Office of Orphan Products Development. About RedHill Biopharma Ltd.: RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) is a biopharmaceutical company headquartered in Israel, primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer. RedHill’s pipeline of proprietary products includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study and a completed proof-of-concept Phase IIa study for multiple sclerosis; (iii) BEKINDA® (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study for acute gastroenteritis and gastritis and an ongoing Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA® (ABC294640) - a Phase II-stage, orally-administered, first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications; (vi) MESUPRON - a Phase II-stage first-in-class, orally-administered uPA inhibitor, targeting gastrointestinal and other solid tumors and (vii) RIZAPORT® (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in Germany in October 2015. 1 Ludwig, H., et al. Survival and years of life lost in different age cohorts of patients with multiple myeloma. J Clin Oncol 28, 1599-1605 (2010). This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to establish and maintain corporate collaborations; (vi) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (vii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and of the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (viii) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (ix) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (x) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; (xi) estimates of the Company’s expenses, future revenues capital requirements and the Company’s needs for additional financing; (xii) competitive companies and technologies within the Company’s industry; and (xiii) the impact of the political and security situation in Israel on the Company's business. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 25, 2016. All forward-looking statements included in this Press Release are made only as of the date of this Press Release. We assume no obligation to update any written or oral forward-looking statement unless required by law.


News Article | October 24, 2016
Site: www.biosciencetechnology.com

Researchers at the Medical University of South Carolina Hollings Cancer Center have discovered a mechanism that confers resistance to drugs used to treat certain types of acute myeloid leukemia (AML). Targeting this pathway with a novel lipid-based therapeutic showed efficacy in a preclinical model of AML. These findings were reported in an article published in the October 13, 2016 issue of Blood. "There are not many successful therapeutics at the moment for the treatment of patients with AML due to the problem of drug resistance," said Besim Ogretmen, Ph.D., SmartStateTM Endowed Chair in Lipidomics and Drug Discovery at the Medical University of South Carolina (MUSC) Hollings Cancer Center and the senior author on the article. In the Blood article, Ogretmen and his colleagues, including clinicians at the MD Anderson Cancer Center who provided patient samples, report that ceramide-dependent mitophagy plays a key role in chemotherapeutic-mediated AML cell death. "Ceramide, a pro-cell death lipid, kills cancer cells by causing them to eat their own mitochondria," said Ogretmen. "This is called mitophagy." Patient cells with the FLT3 mutation inhibit ceramide synthesis and thereby become resistant to cell death. To combat this resistance, a number of FLT3 inhibitors have been developed and trialed in patients with AML. "Unfortunately, regardless of the inhibitor, the problem of resistance to FLT3 targeted therapy has persisted," said Mohammed Dany, MD/PhD student and the first author on the article. By adding a synthetic ceramide analogue, LCL-461, the researchers were able to reactivate mitophagy and kill drug-resistant AML cells in a dish. Mice with drug-resistant human AML tumor xenografts--that is, mice into which drug-resistant tumor cells from AML patients had been grafted-were also treated with LCL-461. The treatment eliminated AML cells from the mice's bone marrow. LCL-461 has clinical appeal because it is able to specifically target cancer cells. A positively charged molecule, LCL-461 is attracted to the mitochondria of cancer cells, which become negatively charged through the "Warburg effect." This limits off-target effects that can occur with less specific inhibitors of FLT3 signaling. Previous studies in Ogretmen's laboratory have tested the safety of LCL-461, finding that it had no major side effects at therapeutically active doses. These results suggest the promise of LCL-461 as a potential therapeutic for patients with FLT3 mutated AML. LCL-461 was developed at MUSC in the Lipidomics Core. The MUSC Foundation for Research Development, MUSC's technology transfer enterprise, has patented it and licensed it to Charleston-based startup SphingoGene, Inc. Ogretmen and his colleagues are next seeking to perform large animal studies with LCL-461 to achieve Investigational New Drug (IND) approval, poising LCL-461 for translation. "We are very excited about this. Head and neck cancers also respond to this drug very well," said Ogretmen. "What we are trying to do is really cure cancer one disease at a time, and we are digging and digging to understand the mechanisms of how these cancer cells escape therapeutic interventions so that we can find mechanism-based therapeutics to have more tools for treatment."


News Article | March 1, 2017
Site: www.eurekalert.org

The ability to quit smoking is influenced by a brain circuit that is responsible for inhibiting automated behavior, report researchers at the Medical University of South Carolina Hollings Cancer Center in the March 1, 2017 issue of JAMA Psychiatry Quitting smoking is hard. Yet success is more likely with strong communication between parts of the brain that inhibit and execute automated behavior, report researchers at the Medical University of South Carolina (MUSC) in the March 1, 2017 issue of JAMA Psychiatry. Smoking becomes an automated behavior over time, according to Brett Froeliger, Ph.D., an addiction scientist in the MUSC Department of Neuroscience and Hollings Cancer Center and first author on the study. In the brain, the urge to smoke begins the same way your foot automatically moves to the gas pedal when a red stoplight turns green. "A pack-a-day smoker places a cigarette in their mouth a few hundred times a day over years," said Froeliger. "It becomes automated." One way the brain inhibits automated behavior is through a pathway called the inhibitory control network, which starts in the right inferior frontal gyrus and travels through the prefrontal cortex to the thalamus. Communication through this pathway is often disrupted in the brains of smokers. The researchers wanted to know if this pathway was involved when smokers attempted to quit. The work began when Froeliger was a postdoctoral researcher in the laboratory of Joseph F. McClernon, Ph.D., at Duke University. The laboratory examined inhibitory control networks in the brains of 81 nicotine-dependent adults committed to trying a 10-week smoking cessation program. Before the program started, the researchers used functional MRI to monitor brain activity while patients were performing a task of inhibitory control. The patients were instructed to strike a computer key each time a colored circle appeared on screen, except on the rare occasion when a circle of a certain color appeared. A higher blood oxygenation level-dependent (BOLD) response in the inhibitory control circuit meant that the brain was using more resources to inhibit the automatic response of striking the key when the rare circle appeared. After 10 weeks, about half of the smokers had quit successfully. Intriguingly, it turned out that they had lower BOLD responses in their inhibitory control networks before trying to quit. In particular, BOLD responses were lower in the right inferior frontal gyrus and right thalamus. They also had stronger functional connections between those regions. Patients who relapsed had scored just as well on the inhibition control task as those who quit successfully. It seemed that their automated behavior may have required more effort to inhibit. Froeliger continued the work with a new twist when he became faculty at MUSC. He wondered if the same thing happened to smokers who had not committed to quitting. Specifically, could this pattern appear in smokers who were paid to quit for just an hour? The group measured BOLD signals in 26 smokers performing the same task. This time, however, each person was then presented with an open pack of their preferred brand of cigarettes, a lighter, and an ashtray. They were paid one dollar for every six minutes they did not smoke, up to an hour. The idea was to give each person a small incentive to resist the temptation to smoke. The results converged nicely. In general, the lower the BOLD response during the task of inhibitory control, the longer the person resisted smoking. Those who resisted temptation longer also had stronger functional connections in their inhibitory control networks. This study is the first to link the strength of communication in a brain circuit that inhibits automated behavior with the ability to resist smoking. This does not mean that smoking itself is the cause of the differences the researchers observed. Rather, this study was designed to learn how to better help smokers who want to quit. Froeliger's group is now evaluating the potential of certain behavioral and pharmacological treatments that could strengthen communication in the inhibitory control pathway of people who smoke. This work highlights that differences in biology can help explain why some smokers who are trying to resist smoking have more success than others. "There are neurobiological mechanisms that are fundamental to learning new behaviors and also to stopping those that become automated, such as smoking," said Froeliger. Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion. MUSC operates a 750-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute designated center) Level I Trauma Center, and Institute of Psychiatry. For more information on academic information or clinical services, visit musc.edu. For more information on hospital patient services, visit muschealth.org. The Hollings Cancer Center at the Medical University of South Carolina is a National Cancer Institute-designated cancer center and the largest academic-based cancer research program in South Carolina. The cancer center comprises more than 120 faculty cancer scientists with an annual research funding portfolio of $44 million and a dedication to reducing the cancer burden in South Carolina. Hollings offers state-of-the-art diagnostic capabilities, therapies and surgical techniques within multidisciplinary clinics that include surgeons, medical oncologists, radiation therapists, radiologists, pathologists, psychologists and other specialists equipped for the full range of cancer care, including more than 200 clinical trials. For more information, visit www.hollingscancercenter.org


News Article | November 4, 2016
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Five-year study in Tanzania, Africa seeks to determine whether combining diabetes and hypertension screening with HIV screening will increase uptake of HIV testing and care The success of HIV treatment programs depends upon the identification, enrollment, and retention of HIV-infected individuals, but public health officials have learned that there are numerous barriers to such success at every point in this care continuum. HIV-centric programs carry a stigma, patients' transportation to the HIV clinics can be a problem, and patients tire of repeat visits to learn whether they have become eligible for HIV treatment. Chronic noncommunicable diseases such as diabetes and hyptertension are another growing global epidemic, accounting for 38 million deaths annually, with three quarters of those deaths occurring in low- and middle-income countries. Michael D. Sweat, Ph.D., professor of Psychiatry and Behavioral Sciences at the Medical University of South Carolina and director of the Center for Global Health, has worked with American and Tanzanian scientists and other colleagues since 1994 to study ways to increase HIV screening and care in Tanzania. Sweat is the principal investigator for the $3.1M NIH grant received in October by the Center for Global Health to study the integration of diabetes and hypertension screening into HIV screening. This study will evaluate the efficacy and cost-effectiveness of the novel integration of diabetes and hypertension screening and care with HIV screening and care. An earlier pilot study led by Sweat indicated that this approach is likely to increase HIV testing, a finding that is relevant throughout the world, including rural, impoverished areas of the U.S. "Global health is everyone's health," said Sweat. "The greatest burdens of disease in the world--HIV, diabetes, and hypertension, among others--know no borders. This grant will enable us to discover better and more efficient ways to address these threats to health, no matter where they arise." Sweat's institutional collaborators will be Clemson University's Department of Bioengineering, which has worked with Arusha Technical College in Tanzania in the past to develop low-cost health technology solutions for resource-poor settings, and Muhimbili University of Health and Allied Sciences, which will provide clinical services and collaborate on data collection and analysis. "HIV and AIDS continue to be a huge problem in Tanzania," said Jessie Mbwambo, M.D., professor in the Department of Psychiatry and Mental Health at Muhimbili University of Health and Allied Sciences. "However, we cannot neglect other growing health needs such as diabetes and hypertension. We believe that by integrating diabetes and hypertension care with HIV care we can likely improve health in all these domains much more effectively and at a lower cost." Delphine Dean, Ph.D., Gregg-Graniteville Associate Professor of Bioengineering at Clemson University, will direct the development of low-cost, diagnostic devices in her laboratory and provide technical support to the health clinics in Tanzania. Dean's laboratory recently developed a low-cost glucometer designed to print (on an inkjet printer) test strips on filter paper loaded with reagents to which a drop of blood is applied to determine the patient's blood sugar level. A patent on the glucometer was filed through the Clemson University Research Foundation. "The lack of medical equipment, devices, and tests in resource-poor areas such as rural Tanzania limits clinicians' ability to diagnose and treat," said Dean. "By working together, we can improve accessibility to technology and improve global health." Patient enrollment is projected to begin in the fall of 2017. Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion. MUSC operates a 750-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute-designated center), a Level 1 Trauma Center, and Institute of Psychiatry. For more information on academic or clinical services, visit musc.edu. For more information on hospital patient services, visit muschealth.org.

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