The Mazda Pharma Guide 7th October to 13th October

? ? PHARMACEUTICAL ARTICLE PHASE II TRIAL OF OMS824 IN PATIENTS WITH SCHIZOPHRENIA O meros Corporation,a clinical-stage biopharmaceutical company, has started enrollment in a phase II clinical trial of OMS824, the company's phosphodiesterase 10 (PDE10) inhibitor. The trial will evaluate the compound's tolerability, safety, pharmacokinetics, potential interactions with concomitant antipsychotic medications, and a battery of cognitive tests in patients with stable schizophrenia. The phase I clinical programme in healthy subjects established dosing regimens that were well tolerated and associated with high levels of PDE10 target engagement in the brain, supporting advancement of OMS824 into patient-directed trials. In this phase II clinical trial, OMS824 will be administered at various dose levels for two weeks to patients whose antipsychotic medications have been temporarily discontinued or who continue their usual antipsychotic regimen in order to assess the effects of OMS824 as monotherapy and in combination with antipsychotic medications. A variety of cognitive tests will be assessed, although the relatively small size of this trial will limit the ability to detect treatment effects, if present. The safety and any efficacy findings in this trial are planned for use in determining appropriate dosing regimens and selecting endpoints for subsequent phase II and phase III clinical trials in schizophrenia. Those trials are expected to evaluate OMS824 in schizophrenic patients who are psychiatrically stable with cognitive impairment, in patients with acute exacerbation of symptoms, and/or in patients with inadequate response to antipsychotic medications. "We are excited to begin assessing OMS824 in patients suffering with schizophrenia," stated Gregory A Demopulos, MD, chairman and chief executive officer of Omeros. "This phase II trial will provide us with important information on our compound's safety and, potentially, efficacy for additional phase II trials in schizophrenia and Huntington's disease. We look forward to completing the current trial later this year." PDE10 is an enzyme that is expressed in areas of the brain linked to diseases that affect cognition and psychomotor functions, including Huntington's disease and schizophrenia. Huntington's disease is a hereditary neurodegenerative disorder that leads to movement, cognition, and behavioral abnormalities and premature death. Schizophrenia is a group of severe brain disorders characterized by an abnormal interpretation of reality, which can manifest as delusions, hallucinations, and/or disordered thinking and behavior. Cognitive dysfunction is responsible for substantial disability in both of these diseases and is not meaningfully improved by current medications. Omeros' proprietary compound OMS824 inhibits PDE10 and is being developed for the treatment of cognitive disorders. In addition to potential benefits on cognition, OMS824 could also improve the 66 motor and psychiatric abnormalities in Huntington's disease as well as the positive (e.g., hallucinations) and negative (e.g., flat affect) symptoms of schizophrenia. Omeros is a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing products targeting inflammation, coagulopathies and disorders of the central nervous system. MILESTONE IN SIMPLE ANTIBODY R&D PACT WITH SHIRE : arGEN-X, a clinical stage human monoclonal antibody therapeutics company, has attained a key success milestone in its SIMPLE Antibody research and product development collaboration with the Human Genetic Therapies division of Shire Pharmaceuticals. The milestone, which triggered an undisclosed payment from Shire, was the first demonstration of in vivo proof of concept for one of the antibody discovery programmes undertaken in the collaboration. Under their February 29, 2012 agreement, the companies are collaborating to create human therapeutic antibodies against complex targets involved in severe, rare genetic diseases. Shire has an option to license the most promising antibody leads from each collaborative programme for further development a nd commercialization worldwide, in return for milestone and royalty payments. Under the terms of the license, arGEN-X has already received technology access fees and research funding and is eligible to receive preclinical success payments. “We are pleased with the excellent progress that has resulted from an outstanding joint effort between our teams,” said Hans de Haard,chief scientific officer of arGEN-X. “This collaboration milestone is testament to the superiority of our proprietary SIMPLE Antibody platform and reinforces our brand in the complex targets space.” PHASE IB/II TRIAL OF DEMCIZUMAB IN COMBO WITH PAC LITAXEL IN OVARIAN CANCER : OncoMed Pharmaceuticals, Inc., a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumour-initiating cells, has started a phase Ib/II clinical trial of its anti-cancer stem cell product candidate, demcizumab (OMP-21M18) in ovarian cancer. The trial will enroll patients at the MD Anderson Cancer Centre in Texas. It is being funded in part under an ovarian cancer National Cancer Institute SPORE Grant Programme. In this phase Ib/II trial, demcizumab is being tested in combination with paclitaxel in patients with platinum-resistant ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Following a phase Ib safety run-in, a phase II clinical trial will proceed in these patients. The primary endpoints of the phase II part of the trial will be to determine the progression-free survival and response rate of the novel demcizumab with paclitaxel combination. Key secondary and exploratory endpoints include overall survival, biomarker endpoints and safety. Dr Robert Coleman, professor & vice chair, Clinical Research, Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Centre and the Principal Investigator who treated the first patient on the study noted, "Women with platinumresistant ovarian, fallopian tube and primary peritoneal cancers are in need of new treatment options. We believe that an investigational therapy such as demcizumab, with its novel anti-cancer stem cell mechanism of action, could yield important results for these patients." "The trial includes a number of translational science and biomarker evaluations that will help to elucidate the mechanisms by which demcizumab works for the treatment of ovarian cancer patients and aims to identify predictors of response to therapy," said Dr Anil Sood, professor & vice chair, Translational Research in the Department, who will be working on the trial. The trial is OncoMed's fourth phase Ib trial of demcizumab, and the second portion of this protocol would represent the first phase II trial of demcizumab. Previous phase Ib trials combining demcizumab with chemotherapy regimens have been initiated in patients with first-line pancreatic cancer (with gemcitabine and Abraxane), first- or second-line colorectal cancer (with FOLFIRI chemotherapy) and first-line non-small cell lung cancer (with carboplatin and pemetrexed chemotherapy). The phase Ib trials in pancreatic cancer and non-small cell lung cancer are currently enrolling patients. "We believe ovarian cancer is another important cancer indication for the demcizumab clinical programme and an area of high unmet medical need," said Dr Jakob Dupont, chief medical officer of OncoMed. "We have observed strong preclinical efficacy of demcizumab and paclitaxel in patient-derived ovarian cancer xenograft models, as well as early evidence of activity of demcizumab in ovarian cancer in the phase Ia single-agent study of demcizumab." Paul Hastings, chairman and chief executive officer of OncoMed, emphasized, "The ovarian cancer trial provides the earliest opportunity to advance a demcizumab programme to phase II. As such it will represent a significant advance for this unpartnered anti-cancer stem cell asset." Demcizumab (OMP-21M18) is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway. Two phase Ib combination trials of demcizumab are ongoing. The first trial is in combination with standard-of care gemcitabine and Abraxane in first-line advanced pancreatic cancer patients, and the second trial is in combination with standard of care carboplatin and pemetrexed (Alimta) in first-line advanced non-small cell lung cancer (NSCLC) patients. OncoMed has worldwide rights to this programme. INAD APPLICATION OF PLURIPOTENT THE MAZADA PHARMA GUIDE q 7 October - 13 October 2013

The Mazda Pharma Guide 7th October to 13th October | Page 66