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Translational Medicine proved potassium channel opener for use in the treatment of partial-onset seizures," he explained. "To aid in the preclinical and potentially clinical development of SF0034, we have also developed an F-18 radiolabeled analog of SF0034 for noninvasive PET imaging." According to Dr. Edwards, "This approach allows registered medicines, compounds in clinical development that have established clinical proof of concept, to be further optimized to generate new pre-clinical candidates without an extensive drug discovery effort." The mechanistic and clinical development knowledge of the parent compounds is driving preclinical and clinical development of these new chemical entities. Elsewhere, studies being conducted at Imaging Endpoints are focused on facilitating effective clinical trial design, based on the bidirectional translational approach involving clinician feedback and preclinical response, said Ronald L. Korn, M.D., Ph.D., the frm's founder and CEO. Dr. Korn said that despite successful preclinical studies, drugs often show doserelated toxicity. He referred to his experience studying vascular disrupting drugs, which were effective in patients with metastasis, but still showed potentially damaging effects on red blood cells. "We then found the most appropriate preclinical model to test the hypothesis— an MRI using a special contrast agent that measures oxidation, to screen the preclinical agent, which showed the oxidizing effects of this agent," he explained. Dr. Korn also cited his experience with stromal disrupting agents, which were promising in early preclinical testing. "We used MRI perfusion imaging to test its mechanism of action," he said. Interestingly enough, "we also noticed that PET scans were going cold in preclinical phase, but were more appropriate for human testing," Dr. Korn added. Working in collaboration with scientists at TexRAD, Dr. Korn and colleagues at Imaging Endpoints used advanced imaging technology and software to extract information from standard medical images, to observe the heterogeneity and morphology of lesions. Quantifying treatment-related changes through texture analysis helps in the detection and measurement of tumor complexity. The resulting images correlate with the underlying biological processes such as blood fow or hypoxia, as well as tumor microarchitecture. "Once we know the clinical drivers, we communicate with our preclinical colleagues to identify the drug's mechanism of action on specifc signaling pathways," Dr. Korn explained. The results also enable linkage with genomic and proteomic data. Dr. Korn's team is currently developing noninvasive tests to measure mutational status in lung cancer and using advanced imaging tools to distinguish K-ras from wild-type Scanning electron micrograph of a cardiac cell grown on the IMEC CMOS multielectrode array. The chip is able to record intracellular action potentials from individual cells in a noninvasive manner, opening the door to novel drug screening platforms based on silicon technology. mutations in colorectal cancer, as well as ER+ from ER- breast cancer. Imaging has yet to be fully integrated into drug discovery and development, but when applied successfully, it can unearth tremendous insights into the biology and effectiveness of a drug, probing important issues like driver mutations and tumor heterogeneity. Clinical Trials Autoimmune and Infammatory Diseases > Idera Pharmaceuticals presented results of a Phase I trial of IMO-8400, a frst-in-class antagonist of Toll-like Receptors (TLRs) 7, 8, and 9 being developed for potential applications in autoimmune and infammatory diseases. In this study, IMO8400 was administered at single escalating dose levels and multiple dose levels weekly for four weeks. IMO-8400 was well tolerated at all dose levels. IMO-8400-treated subjects showed inhibition of TLR 7-, 8-, and 9-mediated cytokines, including tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interferon-alpha, and other pro-infammatory cytokines. This randomized, double-blind, placebo-controlled trial enrolled 42 subjects. The single-dose portion of the trial involved three escalating dose levels of 0.1, 0.3, and 0.6 mg/kg of IMO-8400 or placebo, with six subjects receiving each treatment. The multiple-dose portion of this trial involved two dose levels of IMO-8400, 0.3 and 0.6 mg/kg, and placebo, with six subjects receiving each treatment for four weekly doses. Safety and tolerability were monitored throughout the study. Pharmacokinetic activity and pharmacodynamic activity were monitored at specifc times. Brain Injury > Oxygen Biotherapeutics enrolled the frst subject in the second cohort of its global Phase IIb trial to investigate Oxycyte® in patients with severe, nonpenetrating traumatic brain injury (STOP-TBI). The STOP-TBI trial is a randomized, double-blind, placebo-controlled doseescalation study. The primary objective of the trial is to evaluate the safety and tolerability of Oxycyte. The secondary objec- ORMD-0801, an orally ingestible insulin capsule, in patients with type 2 diabetes. The current trial is to be a randomized, double-blind study designed to assess the safety of ORMD-0801. Oxygen BiotherapeuticsÕ Oxycyte is being evaluated in patients with severe, nonpenetrating traumatic brain injury. tive is to assess the potential of Oxycyte in ameliorating the severity of TBI and represents an opportunity for the collection of placebo-controlled efcacy data, specifcally, clinical and functional improvement. Functional status will be measured by the Glasgow Outcome Scale–Extended, a validated tool that helps to assess progress in patient recovery from their injury. Cancer > Bellicum Pharmaceuticals initiated treatment of the frst patient in a study of BPX-201 dendritic cells in combination with activating agent AP1903. The Phase I dose-escalation trial in patients with metastatic castrate resistant prostate cancer was designed to evaluate the safety, tolerability, and clinical outcomes of BPX201 and AP1903, which incorporate the company's second-generation DeCIDe™ immunotherapy technology. The trial will enroll 18 adult males from three U.S. centers with progressive metastatic castrate resistant prostate cancer who have not received prior chemotherapy. The trial consists of three cohorts of six patients each receiving escalating doses (10 million, 20 million, and 40 million cells) of BPX-201, respectively, over six treatment cycles. Patients are treated every other week with BPX-201, followed by infusion of Hemophilia A > Bayer HealthCare started to enroll patients in an international Phase II/III trial to evaluate its investigational compound BAY94-9027 for the treatment of hemophilia A in children. The PROTECT VIII (Prophylaxis in hemophilia A patients via directly pegylated long-acting rFVIII) Kids trial is designed to determine the efects of BAY949027, a recombinant human factor VIII (rFVIII), when used as prophylaxis, dosed at least once weekly and as on-demand for acute bleeding events. activating agent AP1903 approximately 24 hours after each treatment. Patients will be evaluated for safety, prostate specifc antigen response, progression-free survival, and reduction in circulating tumor cells. > VentiRx Pharmaceuticals initiated ACTIVE8, a randomized, placebo-controlled, Phase II trial evaluating VTX-2337 in combination with a standard of care regimen, cetuximab, platinum, and 5 Fluorouracil (5-FU), in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The study will randomize 175 patients to receive either VTX-2337 or placebo in combination with cetuximab, platinum, and 5-FU chemotherapy. The primary endpoint of the trial will be progression-free survival as determined by Immune Related Response Evaluation Criteria in Solid Tumors. VTX-2337 is a small molecule TLR 8 agonist that directly activates multiple components of the innate immune system. This includes activation of human myeloid dendritic cells, monocytes and natural killer cells resulting in the production of high levels of mediators known to orchestrate the integration of innate and adaptive antitumor responses. Huntington's Disease > Auspex Pharmaceuticals enrolled the frst patient in a multicenter Phase III trial of SD-809 for the treatment of involuntary movements (chorea) associated with Huntington's disease (HD). The randomized, double-blind, placebo-controlled study will test the efcacy, safety, and tolerability of SD-809 in the management of chorea symptoms in 90 HD patients who have not previously taken tetrabenazine. The primary endpoint for the study will be Total Maximal Chorea score. Secondary endpoints will include treatment success measurements based on patient and clinical global impressions of change. According to the company, SD-809 inhibits vesicular monoamine transporter type 2, decreasing the amount of dopamine available to work at nerve terminals, and thereby reducing involuntary movements. n Diabetes > Oramed Pharmaceuticals enrolled the frst patient in a Phase IIa trial of Genetic Engineering & Biotechnology News | GENengnews.com | August 2013 | 37