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BETHLEHEM, PA, United States

Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 2.21M | Year: 2016

DESCRIPTION provided by applicant Huntingtonandapos s Disease HD is an inherited disease that results from expansion of a trinucleotide CAG cytosine adenine guanine repeat that encodes a polyglutamine tract in the huntingtin protein Psychiatric symptoms including irritability and aggression are common in HD patients These are among the most distressing aspects of the disease They have adverse effects on daily life and often result in institutionalization Despite the frequent occurrence and severe consequences of irritability and aggression in HD these symptoms have received little attention to date Effective treatments are lacking and well validated scales for measuring changes in these symptoms are not available Faced with a significant unmet need neurologists cannot currently determine whether new drug therapies might be useful in treating neuropsychiatric symptoms in HD The Phase II clinical trial we propose in HD patients n andquot A randomized placebo controlled double blind multi center study to assess the tolerability of SRX in irritable aggressive subjects wit Huntingtonandapos s Disease HD andquot will allow us to rigorously evaluate the tolerability of a potential ne drug for the treatment of irritability and aggression It will also provide additional safety data n the compound and explore various rating scales for the assessment of changes in these symptoms Thus we will obtain critical data that can be used to plan future Phase II or III clinicl trials of drugs that might blunt irritability and aggression in HD The compound that we propose to test is SRX a first in class vasopressin a V a receptor antagonist SRX crosses the blood brain barrier following oral administration exhibits high affinity and selectivity for is target receptor has a strong safety profile is well tolerated in healthy volunteers and has excellent pharmacokinetics Extensive preclinical pharmacology studies and an experimental medicine fMRI study in healthy volunteers have shown that SRX has CNS effects after oral administration and that it modulates brain circuits involved in responses to stimuli that elicit aggression fear These findings strongly suggest that SRX might have a beneficial effect on the irritability and aggression seen in a sizable proportion of HD patients The proposed project will generate data needed to plan a future clinical trial that can rigorously test SRX for efficacy as a treatment for irritability and aggression PUBLIC HEALTH RELEVANCE In Huntingtonandapos s Disease HD psychiatric symptoms including irritability and aggression adversely impact daily life and often result in institutionalization New medicines to treat these neuropsychiatric symptoms are needed because available drugs are minimally effective and several have significant side effects In the proposed clinical trial SRX a novel first in class vasopressin a V a receptor antagonist that shows promise as a treatment for irritability and aggression will be tested in HD patients to assess tolerability generate additional safety data and explore scales that measure these symptoms for use in future clinical trials


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 349.19K | Year: 2010

DESCRIPTION (provided by applicant): Vasopressin (AVP) antagonists represent a novel therapeutic class for the treatment of depression. The potential utility of these compounds has emerged from observations in depressed individuals, findings in animal models, and an understanding of changes in hypothalamic-pituitary-adrenal (HPA) axis regulation under chronic stress. This Fast Track proposal seeks support for the identification of novel mixed vasopressin 1a/1b (V1a/V1b) receptor antagonists and the preclinical development of recently discovered molecules in this class that already demonstrate excellent biological activity in vitro. The scientific basis for mixed V1a/V1b antagonists as a pharmacotherapy for depression includes: 1) the neuroadaptation and dysregulation of HPA function that accompanies chronic stress in affected humans and in animal models of depression, 2) recognition that AVP, not CRF, drives HPA function associated with chronic psychological stress, and 3) the localization of V1a and V1b receptors in regions involved in the control of social behaviors and HPA axis regulation (V1a in limbic system; V1b in limbic system and anterior pituitary). The initial development of these mixed antagonists to date has been supported by private sector venture funding. SBIR Fast Track support will enable essential preclinical development work that will advance candidate molecules to the stage where bulk synthesis and IND-enabling toxicology can be undertaken. Bringing candidates to this status will accelerate commercialization opportunities by significantly enhancing the likelihood of additional private financial investment or a co-development partnership structure with a major pharmaceutical house. PUBLIC HEALTH RELEVANCE: The public health need for new pharmaceutical treatments for depression is well documented. Depression affects some 20 million Americans each year and carries a conservatively estimated annual total economic burden of 125 billion. Existing drugs for depression are not uniformly effective, frequently have undesirable side effects, and do not help some 50% of individuals suffering from the disorder according to recent estimates. These limitations demonstrate that a new treatment approach through mixed V1a/V1b receptor antagonism may offer a significant opportunity for improved outcomes with substantial societal benefit.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 226.38K | Year: 2009

DESCRIPTION (provided by applicant): A Potential New Drug for Depression, an active SBIR Phase IIa award. The requested funds will allow additional characterization studies of three newly discovered mixed vasopressin 1a/1b antagonists, studies that were not part of the original application. These experiments will accelerate preclinical development of the novel mixed antagonists by facilitating identification of clinical candidates within this group of compounds. Arginine Vasopressin (AVP) antagonists represent a novel therapeutic class for the treatment of depression. The potential utility of these compounds has emerged from observations in depressed individuals, findings in animal models, and an understanding of changes in hypothalamic-pituitary-adrenal (HPA) axis regulation under chronic stress. The active Phase IIa award has two objectives. One is advancing the development of our lead clinical candidate, SRX246-HCl, through a Phase I Clinical Trial. SRX246 is a novel vasopressin 1a (V1a) receptor antagonist that had shown efficacy in preclinical animal models of depression and anxiety, good plasma bioavailability and CNS penetration following oral administration, a strong safety profile, and high affinity and selectivity for the target receptor, The development of this compound to date has been supported by SBIR Phase I, Phase II, and Phase IIa grants, the National Toxicology Evaluation program, a RAID grant, and Series A and Series B private sector investments. All IND-enabling toxicology and safety pharmacology has been completed and an IND application is now under review at the FDA. Assuming approval, a Phase I Clinical Trial to establish safety and tolerability in humans will start in June or July, 2009. The second objective is continued development of back-up compounds, including additional V1a antagonists and mixed AVP 1a/1b antagonists. The Revision Application seeks additional support for preclinical studies that will accelerate clinical candidate identification among newly discovered back-up compounds that are mixed V1a/V1b antagonists. Achieving these goals will enhance commercialization opportunities for Azevan by significantly advancing the likelihood of a partnership with a major pharmaceutical house and/or attracting additional private sector investment. PUBLIC HEALTH RELEVANCE: The public health need for new pharmaceutical treatments for depression is well documented. Depression affects some 20 million Americans each year and carries a conservatively estimated annual total economic burden of 125 billion. Existing drugs for depression are not uniformly effective and frequently have undesirable side effects. These limitations demonstrate that a new treatment approach through vasopressin receptor antagonism in the brain may offer significant opportunities for improved outcomes with substantial societal benefit.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.79M | Year: 2011

DESCRIPTION (provided by applicant): Vasopressin (AVP) antagonists represent a novel therapeutic class for the treatment of depression. The potential utility of these compounds has emerged from observations in depressed individuals, findings in animal models, and an understanding of changes in hypothalamic-pituitary-adrenal (HPA) axis regulation under chronic stress. This Fast Track proposal seeks support for the identification of novel mixed vasopressin 1a/1b (V1a/V1b) receptor antagonists and the preclinical development of recently discovered molecules in this class that already demonstrate excellent biological activity in vitro. The scientific basis for mixed V1a/V1b antagonists as a pharmacotherapy for depression includes: 1) the neuroadaptation and dysregulation of HPA function that accompanies chronic stress in affected humans and in animal models of depression, 2) recognition that AVP, not CRF, drives HPA function associated with chronic psychological stress, and 3) the localization of V1a and V1b receptors in regions involved in the control of social behaviors and HPA axis regulation (V1a in limbic system; V1b in limbic system and anterior pituitary). The initial development of these mixed antagonists to date has been supported by private sector venture funding. SBIR Fast Track support will enable essential preclinical development work that will advance candidate molecules to the stage where bulk synthesis and IND-enabling toxicology can be undertaken. Bringing candidates to this status will acceleratecommercialization opportunities by significantly enhancing the likelihood of additional private financial investment or a co-development partnership structure with a major pharmaceutical house. PUBLIC HEALTH RELEVANCE: The public health need for newpharmaceutical treatments for depression is well documented. Depression affects some 20 million Americans each year and carries a conservatively estimated annual total economic burden of 125 billion. Existing drugs for depression are not uniformly effective, frequently have undesirable side effects, and do not help some 50% of individuals suffering from the disorder according to recent estimates. These limitations demonstrate that a new treatment approach through mixed V1a/V1b receptor antagonism may offer a significant opportunity for improved outcomes with substantial societal benefit.


Patent
Azevan Pharmaceuticals, Inc. | Date: 2011-07-01

Compounds and compositions are described herein for treating post traumatic stress disorder.

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