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San Diego, CA, United States

Ichor Medical Systems, Inc. | Date: 2011-05-24

Methods and apparatus for the reproducible, consistent and efficacious delivery of a therapeutic agent to a patient. The invention includes controlled administration of the therapeutic agent through an orifice to the patient, a plurality of penetrating electrodes arranged with a predetermined spatial relationship relative to the orifice, and an electrical signal generator operatively connected to the electrodes.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 463.08K | Year: 2006

DESCRIPTION (provided by applicant): Acute hepatitis B virus (HBV) infection is generally self-limited. However, patients who remain chronically infected are at increased risk for chronic hepatitis, cirrhosis and liver carcinoma. Only a minority of these patients can be cured by antiviral therapy. Establishing strong immune responses to HBV with a vaccine alone, or in the context of the low viral loads achievable with current antiviral drug therapy, could help induce remission or even cure the disease. Based on the ability to induce strong cellular immune responses, plasmid DNA (pDNA) vaccines are a promising modality for chronic hepatitis B. However, successful development of pDNA immunization for this indication has been hampered by the low magnitude and inconsistent responses characteristic of current pDNA delivery modalities. Using its TriGridTM electroporation (EP) DNA delivery technology, Ichor has demonstrated a dramatic increase in potency and immunogenicity of pDNA vectors encoding HBV antigens in animal models. Based on these results, it is our hypothesis that Ichor EP-based pDNA vaccination against HBV subunits can form the basis for an effective therapeutic vaccination against chronic HBV infection. In order to assess the validity of this hypothesis and demonstrate the basic feasibility of the proposed approach, we will conduct an evaluation of efficacy in an accepted disease model: Ichor has established relationships with clinicians and researchers to enable evaluation of its DNA vaccine approach in the woodchuck model of chronic viral hepatitis. Feasibility of a therapeutic HBV DNA vaccine will be assessed by characterizing immunological, virological, and safety endpoints in the woodchuck model. Additional evaluation of key safety endpoints identified by the FDA will be conducted in rabbits. The data collected in SBIR Phase I will form the basis for the submission of an IND enabling initiation of a Phase I clinical study to be conducted under SBIR Phase II. Relevance of the research to public health - Chronic infection with hepatitis B virus is associated with serious morbidity, significant health care costs, and the risk of contamination to others, which is a huge public health problem. Current antiviral therapies decrease viral loads without completely eliminating the virus. The treatment of this condition would be much improved by a safe and effective vaccine therapy that could durably eradicate the virus.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 133.98K | Year: 2006

DESCRIPTION (provided by applicant): Cardiovascular disease associated with atherosclerosis takes an enormous toll on human life and is responsible for a major portion of health care costs in the U.S. Although the advent of statin therapies has reduced the risk of mortality from coronary heart disease through both cholesterol-lowering and immunomodulatory effects, heart disease remains a major cause of death in this country. Thus, there is a critical need for new interventions capable of altering the underlying biochemical and cellular events that promote atherosclerosis. Recombinant interferon-a (IFN-a) is an approved immunomodulatory drug with an excellent safety record that has been used to safely treat thousands of patients with multiple sclerosis (MS). Based on its purported mechanisms of action in the treatment of multiple sclerosis (MS), IFN-a appears to have promise as an anti-atherosclerotic agent. In preliminary studies, recombinant IFN-a was shown to reduce aortic lesion size and inflammation in a mouse model of atherosclerosis. However, the high cost, frequent side effects, and inconvenient administration schedule associated with recombinant IFN-a protein therapy is likely to preclude its widespread use in the cardiovascular disease setting. In order to realize the potential benefits of IFN-a therapy in atherosclerosis, this proposal will evaluate an alternative method of delivery based on electroporation (EP)-mediated intramuscular transfer of plasmid DNA encoding the IFN-a gene. The basic feasibility of the proposed DNA-based IFN-a product as a treatment for atherosclerosis is dependent on demonstrating that gene-based IFN-a delivery is capable of reducing the severity of atherosclerosis. Thus, the first aim of these studies will evaluate the ability of EP-mediated gene-based IFN-a therapy to attenuate plaque formation in a well characterized mouse model of atherosclerosis. For a successful product, it will be necessary to demonstrate that the combination of gene-based IFN-a and conventional statin therapy are superior to statin therapy alone; this will be addressed in the second Aim. Additionally, these studies will characterize any adverse events associated with gene-based IFN-a administration, either alone or in combination with statin therapy. If efficacy and initial safety studies indicate that a gene-based IFN-a therapy for atherosclerosis is feasible, further non-clinical testing will be completed and a Phase I human clinical study will be initiated in SBIR Phase II. Atherosclerosis is a chronic inflammatory process that occurs within the cardiovascular system and leads to a thickening of artery walls and the formation of plaques that restrict blood flow. Atherosclerosis is linked to nearly 75% of all deaths from cardiovascular diseases, and there is a great need for new therapies that will slow its progression. The proposed studies will evaluate the potential of a gene-based interferon-beta therapy for atherosclerosis, and thus will address a very critical need in current medical care.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 299.50K | Year: 2009

DESCRIPTION (provided by applicant): Venezuelan (VEEV), eastern (EEEV), and western (WEEV) equine encephalitis viruses are arthropod-borne alphaviruses listed as CDC category B agents. There are currently no licensed human vaccines for the encephalitic alphaviruses, although conventional live-attenuated and formalin-inactivated vaccines for VEEV, EEEV, and WEEV have been developed and are currently utilized under IND status these vaccines have high reactogenicity and are poorly immunogenic. Ichor Medical Systems has demonstrated that a trivalent DNA vaccine candidate consisting of three DNA plasmids separately encoding the E1 and E2 glycoproteins of VEEV, EEEV and WEEV induce virus-neutralizing antibody responses consistent with protective immunity. Here we propose to further the development of this promising vaccine candidate by conducting IND-enabling safety/toxicology studies; this work encompasses both standard vaccine acute/chronic evaluation as well as cardiac monitoring to expand the safety database related to the clinical application of electroporation. In addition, preclinical immunogenicity experiments in nonhuman primates will be performed to facilitate the regulatory path toward approval of this product. PUBLIC HEALTH RELEVANCE: This SBIR proposes to conduct preclinical immunogenicity and safety/toxicology studies on a trivalent DNA vaccine against Venezuelan (VEEV), Eastern (EEEV), and Western (WEEV) equine encephalitis viruses. The work conducted in this project will enable clinical testing of a novel vaccine for an unmet medical need and further the development of electroporation as a broad vaccine delivery platform.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 3.31M | Year: 2009

Alzheimer's disease (AD) is the most common form of dementia in the elderly. It is estimated that there are currently more than 18 million people worldwide with AD and this number is projected to nearly double by 2025 to 34 million. The enormous, increasing worldwide healthcare burden of AD and the lack of effective drugs indicate new prophylactic and/or therapeutic approaches for treating AD are essential. One neuropathological feature of the disease is the presence of plaques composed primarily of a peptide called b- amyloid (A?). Currently, the predominant theory of the etiology of AD is that A? has a central role in the onset and progression of AD. According to this hypothesis, the accumulation of A? peptide, either by overproduction or aberrant clearance, results in the deposition of A? in plaques, which promotes the formation of neurofibrillary tangles and cell death, resulting in dementia. Many strategies for the development of therapies for AD are aimed at reducing the level of A? in the brain and/or blocking assembly of the peptide into pathological forms that disrupt cognitive function. A variety of approaches based on active (i.e., vaccines) or passive (i.e., monoclonal antibodies) immunotherapy against A? have demonstrated the capability to alter A? plaque burden in disease models and early phase clinical trials. The most advanced clinical trial evaluated an A? peptide vaccine (AN1792) developed by Elan Pharmaceuticals. Although a reduction in AD-related cognitive decline was observed in some of the immunized subjects, the trial was halted prematurely due to the occurrence of neuroinflammation in a subset of vaccine recipients. Subsequent analysis implicated the induction of autoreactive T cell responses to the A? peptide (but not antibody responses) in the development of these adverse events. Based on these findings, an A? B cell epitope DNA vaccine, ADepVac, was designed to elicit potent antibody responses to A? while avoiding the development of autoreactive T-cells. This candidate has demonstrated compelling safety and efficacy characteristics in AD murine disease models and strong synergy with electroporation-based DNA delivery technology. To evaluate the long term potential of this product as an intervention for AD, Ichor and its collaborators propose that the objective of SBIR U44 Phase I will be to verify that ADepVac can safely and effectively induce target levels of immune responses in non-human primates when delivered with electroporation-mediated delivery. If the safety and performance feasibility criteria are achieved, U44 Phase II will be initiated in order to complete the nonclinical safety/toxicological studies and regulatory filings necessary to support the initiation of a Phase I clinical trial in humans. Based on the diverse, interdisciplinary expertise assembled among the program collaborators, the project is well positioned to bring ADepVac into clinical testing.

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