Syntrix Biosystems, Inc. | Date: 2014-03-26
There is disclosed pyridine- and pyrimidinecarboxamide compounds useful as pharmaceutical agents, synthesis processes, and pharmaceutical compositions which include pyridine- and pyrimidinecarboxamides compounds. More specifically, there is disclosed a genus of CXCR2 inhibitor compounds that are useful for treating a variety of inflammatory and neoplastic disorders.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 490.03K | Year: 2016
DESCRIPTION provided by applicant Psoriasis is a chronic genetically influenced remitting and relapsing scaly and inflammatory skin disorder that affects of the worldandapos s population resulting in total annual costs of $ billion in the United States in Approximately of patients with moderate to severe chronic plaque psoriasis require phototherapy and or a variety of systemic treatments where methotrexate MTX is the mostly widely used oral systemic agent Despite the relative effectiveness of MTX as a monotherapy it does not achieve greater than a reduction in the baseline psoriasis area and severity index PASI in of patients and fails to achieve remission i e andgt PASI in of patients Furthermore up to of patients with moderate to severe plaque psoriasis discontinue oral MTX primarily because of intolerance to the drug While much effort has been directed to identifying the mechanism behind poor and or toxic responses to MTX based on genetic factor and quantitation of its active metabolites the majority of MTX failures remain unexplained Given the efficacy and safety limitations of MTX and the cost of biologics compared to MTX $ vs $ per year there is a clear market opportunity for an improved antifolate with better efficacy and or safety than MTX but that is priced between MTX and biologics LD Aminopterin LD AMT is a patented composition developed by Syntrix Biosystems that studies indicate has greater cellular uptake i e polyglutamylation to the active metabolites than MTX and less liver and CNS toxicity properties that may translate into better efficacy and or safety In addition to identifying LD AMT as a potential improvement on MTX gaining a mechanistic understanding of antifolate resistance in general has important clinical implications for treating inflammation with LD AMT or MTX by possibly identifying clinical biomarkers to predict optimal response or risk of toxicity in advance of initiating treatment This U Fast Track proposal aims to advance LD AMT to the clinic by testing LD AMT for efficacy in a placebo controlled phase trial and advancing a novel hypothesis driven mechanistic explanation for antifolate resistance PUBLIC HEALTH RELEVANCE Psoriasis is a chronic scaly and inflammatory skin disorder that affects of the worldandapos s population Current treatments often involve the use of methotrexate MTX which is not effective in many patients or causes side effects or exceedingly expensive biologic therapies that can cost $ to $ per year This proposal aim to develop a drug LD aminopterin that is better than MTX and less expensive than biologics Also we aim to carry out studies that we hope will tell us how drugs like MTX and LD aminopterin fail in patients
Syntrix Biosystems, Inc. | Date: 2015-11-23
There is disclosed a method for treating disorders modulated by at least opiate receptor activity or monoamine activity, including acute and chronic pain, comprising administering a pharmaceutical formulation comprising O-desmethyltramadol. Methods are also provided that are effective for overcoming resistance to tramadol in patients.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2015
DESCRIPTION provided by applicant Neuropathic pain is caused by damage to the peripheral nerves as occurs in diabetic neuropathy Neuropathic pain is difficult to treat and many patients have pain that is refractory to existing treatments Omnitram is a novel mixed mechanism analgesic developed by Syntrix that consists of the and enantiomers of O desmethyltramadol The enantiomer is a potent opioid receptor agonist while the enantiomer is a norepinephrine reuptake inhibitor that synergizes with the enantiomer Omnitram is inherently an opioid sparing opioid adjuvant combination therapy that is predicted to have low abuse potential O desmethyltramadol is the primary metabolite M of tramadol Omnitram provides the same net pharmacology as tramadol but in contrast to tramadol does not require metabolism by cytochrome P D CYP D for its activity i e it is metabolism independent Individuals who are CYP D poor metabolizers PMs fail to obtain pain relief from tramadol The andquot real worldandquot incidence of CYP D PM status in patients on polypharmacotherapy is as high as in Omnitram is therefore an opportunity to develop an andquot improved tramadolandquot that is effective in all patients irrespective of their CYP D metabolic status Omnitram successfully completed a Phase b randomized double blind placebo controlled trial that demonstrated Omnitram provided significant analgesia compared to placebo in an experimental pain model in healthy subjects This Fast Track application aims to further the success of the Omnitram program by demonstrating analgesic efficacy in patients suffering from neuropathic pain due to diabetic neuropathy A Cochrane systematic review concluded that tramadol is an effective treatment for neuropathic pain with efficacy similar to that reported for antidepressants and anticonvulsants Omnitram provides the same net pharmacology as tramadol and is therefore predicted to be efficacious in treating neuropathic pain PUBLIC HEALTH RELEVANCE Neuropathic pain is difficult to treat and many patients have pain that is refractory to existing treatments The most commonly studied neuropathic pain subtypes include diabetic neuropathic pain DNP postherpetic neuralgia PHN and HIV related neuropathic pain Collectively these three conditions were estimated to affect over million people across the seven major pharmaceutical markets the United States Japan France Germany Italy Spain and the United Kingdom in However the total affected population is considerably larger owing to the number of additional neuropathic pain conditions such as neuropathic lower back pain cancer related neuropathic pain complex regional pain syndrome and postoperative neuropathic pain Due to the staggering human and economic costs neuropathic pain represents a significant burden to public health This Fast Track proposal would advance a novel mixed mechanism analgesic Omnitram towards clinical evaluation in patients suffering from neuropathic pain
Syntrix Biosystems, Inc. | Date: 2015-01-30
There is disclosed is a method of treating a pulmonary disease using a pyrimidinecarboxamide compound, and a pharmaceutical composition suitable for inhalation comprising the pyrimidinecarboxamide compound.