News Article | November 21, 2016
DPP IV inhibitors are widely utilized as a treatment for type 2 diabetes. Sitagliptin, vildagliptin, saxagliptin and linagliptin are included in the drug class DPP IV. Nasopharyngitis, headache, nausea and hypersensitivity are some of the adverse effects due to the utilization of DPP IV. DPP IV inhibitors are a class of hypoglycemic agents that block the enzyme named dipeptidyl peptidase IV. Dipeptidyl peptidase IV enzyme break down the proteins that are responsible for stimulating the insulin producing cells that slows down gastric secretion. Proteins can activate the release of insulin and can control the blood sugar level if DPP IV is inhibited in our body. Moreover, DPP IV inhibitors restrict the formation of glucagon, a hormone that increases blood glucose level and thereby control the glucose levels in the body Request TOC (desk of content material), Figures and Tables of the report: http://www.persistencemarketresearch.com/toc/5453 Increasing prevalence of type 2 diabetes is a major public health concern worldwide. National Centre for Biotechnology Information in 2011 stated that in the U.S. more than 8% of the total population is diagnosed with diabetes. Diabetes is associated with a number of complications that includes cardiovascular disease, nephropathy, retinopathy, and neuropathy. Thus, the above mentioned factors derives the global DPP IV inhibitors market. However, the cost for DPP IV inhibitors is very high that might hinder the global DPP IV inhibitors market. Geographically, North America and Europe dominates the global market for DPP IV inhibitors due to high prevalence rate and rising awareness among people about the DPP IV inhibitors. Asia – Pacific is considered as a fastest growing market due to increasing obese population. Various key players contributing to the global DPP IV inhibitors market comprises Arisaph Pharmaceuticals, Inc., Boehringer Ingelheim GmbH, Eli Lilly And Company, Bristol-Myers Squibb, Merck & Co, Inc., AstraZeneca Plc, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited and Novartis AG.
News Article | November 16, 2016
The report provides comprehensive information on the therapeutics under development for Type 2 Diabetes Disease, complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Additionally, the report provides an overview of key players involved in therapeutic development for Type 2 Diabetes Disease and features dormant and discontinued projects. The report helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. Complete report on Type 2 Diabetes Disease - Pipeline Review, H2 2016 addition with 249 market data tables and 17 figures, spread across 1298 pages is available at http://www.reportsnreports.com/reports/747717-type-2-diabetes-pipeline-review-h2-2016.html This report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data and information sourced from Global Markets Directs proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources. Drug profiles featured in the report undergoes periodic review following a stringent set of processes to ensure that all the profiles are updated with the latest set of information. Additionally, various dynamic tracking processes ensure that the most recent developments are captured on a real time basis Addex Therapeutics Ltd, Adocia ,Advinus Therapeutics Ltd ,Aegis Therapeutics, LLC ,AFFiRiS AG Alize Pharma SAS ,AlphaMab Co., Ltd ,Alteogen Inc. ,Amarantus Bioscience Holdings, Inc. ,Ambrx, Inc. ,Amgen Inc. ,Anchor Therapeutics, Inc. ,AntriaBio, Inc. ,Aphios Corporation ,APT Therapeutics, Inc. ,Araim Pharmaceuticals, Inc. ,Arisaph Pharmaceuticals, Inc. ,ArisGen SA ,Artery Therapeutics, Inc. ,Astellas Pharma Inc. ,AstraZeneca Plc ,Aus Bio Ltd ,Bayer AG ,Beta-Cell NV ,Betagenon AB,Biocon Limited ,Biodel Inc. ,Biogenomics Limited ,BioLingus AG ,BioRestorative Therapies, Inc. BioTherapeutics Inc. ,Biscayne Pharmaceuticals, Inc. ,Boehringer Ingelheim GmbH Inquire before buying http://www.reportsnreports.com/contacts/inquirybeforebuy.aspx?name=747717(This is a premium report price at US$2000 for a single user PDF license).
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 266.64K | Year: 2012
DESCRIPTION (provided by applicant): In the United States colorectal cancer (CRC) is the third leading cause of cancer mortality. Surgery is the primary treatment for early stage CRC; but adjuvant therapy is usually needed in advanced disease. Approximately 55% of CRC patients have metastatic disease for which the prognosis is poor despite incremental improvements due to introduction of irinotecan, oxaliplatin and targeted agents. The latter include the antibodies, cetuximab and panitumumab, initially approved by the FDA for patients who fail chemotherapy. The antibodies were selected for their ability to kill tumors by blockade of the epidermal growth factor receptor (EGFR). How- ever, although the anti-EGFR antibodies promised efficacy with reduced toxicity compared to chemotherapy, less than 12% of CRC patients respond to the antibodies as single agents. Resistance is largely due to mutations that activate the KRAS oncogene to drive CRC growth independently of EGFR signaling. The FDA has restricted cetuximab and panitumumab to treatment of metastatic CRC that expresses non-mutated KRAS. A new therapeutic approach in CRC might be to exploit an alternative mechanism of action for cetuximab called antibody-dependent cellular cytotoxicity (ADCC). Cetuximab canpotentially engage innate killer cells (K cells) to kill tumor cells by ADCC, regardless of whether or not the tumor has the KRAS mutation. However, when cetuximab is used as a single agent, little clinical benefit appears to come from ADCC. One way to improve the impact of ADCC would be to combine cetuximab with an agent that can enhance the efficiency of tumor killing by K cells. ARI-4175 has been selected for this purpose because preliminary results suggest it can stimulate cetuximab-mediated ADCC to produce tumor responses in KRAS mutant CRC in mice. The Specific Aim is to demonstrate that ARI-4175 can amplify cetuximab-mediated ADCC to produce significant tumor responses in nude mice challenged with a human KRAS mutant CRC cell line (HCT-116) that is resistant to cetuximab as a single agent. Tumor responses to treatment will be measured, tumor attack by K cells will be assessed by histology and immunostaining of responsive tumors, and the effect of experimental therapy on ADCC will be assayed ex vivo. The approach will seek to substantiate preliminary evidence suggesting that ARI-4175 activates a particular type of K cell-the natural killer (NK) cell-to kill tumors by ADCC. For ARI-4175 to be a viable drug candidate it must interact with cetuximab to produce significant tumor responses in the HCT-116 model with evidence of an immune mechanism of action. If the STTR Phase I study is successful, IND-enabling studies and the initiation of a phase 1 clinical trial of ARI-4175 will be proposed for STTR Phase II. PUBLIC HEALTH RELEVANCE: In 2012, 103,170 cases of colon cancer, 40,290 cases of rectal cancer, and 51,690 deaths from colorectal cancer (CRC, accounting for 9% of all cancer deaths) are predicted to occur in the United States. The anti- epidermal growth factor (EGFR) antibodies, cetuximab and panitumumab, appeared promising, initially, for treatment of metastatic CRC (mCRC) that is not amenable to surgery and resistant to chemotherapy; but it has turned out that less than 12% of patients respondto the antibodies as single agents, largely due to KRAS mutations that drive tumor growth independently of the EGFR. This project will test the feasibility of ARI-4175 as an immunotherapeutic agent that can enable cetuximab to successfully treat mCRC by the alternative mecha- nism of antibody-dependent cellular cytotoxicity, which is not affected by KRAS mutations.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 232.85K | Year: 2013
DESCRIPTION (provided by applicant): In the United States, around 76,250 new cases of melanoma and 9,180 melanoma-related deaths are predicted for 2012. With the therapeutic options currently available, metastatic melanoma patients face the bleak prospectof at best, 10 month's survival and a one-in-ten chance of surviving for 10 years. Surgery and radiation therapy are the mainstay of treatment. Dacarbazine-based chemotherapy remains after 30 years, for want of anything better, to be the main systemic therapy. As currently used, immunotherapy affords little improvement. High dose IL-2 (Proleukin) and ipilimumab (Yervoy) can increase survival, but only in a few patients, and at the risk of severe toxicity. Mutations in the BRAF oncogene occur in 80% of melanomas and activate the B-Raf serine/threonine kinase to drive uncontrolled cell growth. The new, targeted agent, vemurafenib (PLX4032), inhibits B-Raf activated by the V600E mutation occurring in 85% of BRAF mutations in melanoma. High response rates, benign and manageable toxicities, and the availability of a companion diagnostic for the BRAFV600E mutation raised the prospect of a cure in metastatic melanoma. This hope has been thwarted by the development of drug resistance and the recurrence of malignantdisease only months after regression in response to PLX4032. The period of remission produced by PLX4032 provides a window of opportunity for immunotherapeutic approaches that might activate tumor immunity to suppress the recurrence of PLX4032-resistant melanoma. Arisaph has identified a small molecule inhibitor of the prolyl peptidase family, ARI-4175, that can activate tumor immunity to kill tumors via the induction of immunoregulatory cytokines and chemokines. Arisaph has selected ARI-417 as a second-generation drug candidate with greater activity and less toxicity than the related compound, PT-100 (talabostat). ARI-4175 is remarkably effective in producing immune rejection of tumors in mice. Therefore, if given during the period of remission produced byPLX4032, ARI-4175 might activate an immune response that can suppress reemergence of disease. This hypothesis will be tested with the Specific Aim of demonstrating that ARI-4175 can inhibit progression of tumors after the initial response to PLX4032 in a model of BRAFV600E-positive melanoma established by Dr. Philip Hinds (Tufts Medical Center). In order to be a viable drug candidate, ARI-4175 must produce a significantly greater antitumor effect than PLX4032 alone by the activation of tumor immunity afterPLX4032 treatment in BRAFV600E-positive melanoma in mice. If ARI-4175 meets the test of feasibility in STTR Phase I, IND-enabling studies and initiation of clinical trials to investigae safety and efficacy will be proposed for Phase II. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Metastatic melanoma is a lethal skin cancer with response rates to chemotherapy of only 5-20%, and although immunotherapy (Proleukin and Yervoy) provides an alternative option that can produce durable responses andlong-term survival, as currently used, immunotherapy only provides a benefit in a small proportion of patients. A newer targeted agent, vemurafenib (PLX4032), is a B-Raf kinase inhibitor that can produce remarkable responses in melanoma harboring the BRAFV600E mutation, but following the initial response, drug resistance allows the recurrence of aggressive malignant disease after only a few months. This proposal will test the feasibility of using a small molecule immunotherapeutic agent to activate a tumor-specific immune response that can suppress the recurrence of disease after the initial regression of melanoma lesions in response to PLX4032.
Tufts University and Arisaph Pharmaceuticals, Inc. | Date: 2014-12-10
Disclosed are heterocyclylalkyl-substituted and heteroaralkyl-substituted pyridines, and pharmaceutically acceptable salts and prodrugs thereof, that are active against a range of mammalian therapeutic indications.
Tufts University and Arisaph Pharmaceuticals, Inc. | Date: 2015-08-31
Disclosed are 6-(morpholinoalkyl)-substituted pyridines, and pharmaceutically acceptable salts and prodrugs thereof, that are active against a range of mammalian therapeutic indications.
Arisaph Pharmaceuticals, Inc. | Date: 2013-05-01
Disclosed are 6-(morpholinoalkyl)-substituted pyridines, and pharmaceutically acceptable salts and prodrugs thereof, that are active against a range of mammalian therapeutic indications.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 245.64K | Year: 2011
DESCRIPTION (provided by applicant): Cancer is America's second leading cause of death. Many approved cancer drugs, such as bortezomib (Velcade), are cytotoxic agents that kill normal cells as well as tumor cells. Therapeutic benefit depends on tumor cellsbeing more sensitive than normal cells, thereby allowing clinical responses to be achieved at relatively safe drug doses; however, damage to normal tissues is unavoidable and often limits treatment. Due to its remarkable efficacy in multiple myeloma (MM),bortezomib has been tested in solid cancers; but it has generally failed to produce clinical responses. Bortezomib inhibits an intracellular protein complex called the proteasome. Because the proteasome regulates cellular physiology in both normal and tumor cells, bortezomib causes many dose-dependent side effects of which sensory and motor dysfunction called peripheral neuropathy (PN) and deficiency in platelets (thrombocytopenia) are the most severe. MM patients can be treated safely, because MM cells can be killed by bortezomib at doses that are tolerated, albeit not without frequent incidence of PN. In contrast, tumor cells of solid cancers are more resistant, and PN and thrombocytopenia prevent administration of an effective dose of bortezomib with acceptable safety. ARI-3996 is a pro-drug version of a bortezomib-like cytotoxic agent designed to more selectively target the proteasome in solid tumors. ARI-3996 is relatively non-toxic to all cells and cannot kill tumor cells until it is activated by the enzyme, fibroblast activation protein (FAP). Because FAP is produced in epithelial tumors but not usually in healthy tissues, ARI-3996 should not be activated in nervous tissue or in bone marrow where platelets are generated. Therefore, ARI-3996 should killFAP-producing tumors with less severe PN and thrombocytopenia than that associated with bortezomib. If successful, ARI-3996 might be combined with chemotherapy to improve the current standards of care. FAP has been shown to specifically activate ARI-3996and unleash the bortezomib-like proteasome inhibitor to kill tumor cells in tissue culture. It is now proposed to demonstrate that ARI-3996 can kill tumors in an animal model of epithelial cancer with less systemic toxicity than bortezomib. A mouse model will be selected in which the tumor produces FAP in amounts equivalent to those in human epithelial tumors. The dose-response of ARI-3996 will be determined for reduced tumor growth, death of tumor cells, and reduced blood supply to the tumor. Mice will beexamined for toxic side effects in comparison to bortezomib. For ARI-3996 to be a viable drug candidate, it will be essential to demonstrate that treatment with ARI-3996 produces significant antitumor effects with at least 10-fold less systemic toxicity than bortezomib. PUBLIC HEALTH RELEVANCE: Bortezomib (Velcade) is an effective treatment for multiple myeloma, but its mechanism of action results in dose-limiting toxicities (DLTs) of peripheral neuropathy and loss of platelets, which prevent treatment of common solid cancers. The pro-drug, ARI-3996, is designed to remain inactive in healthy organs and to be activated to unleash a cytotoxic bortezomib-like warhead in tumors by the tumor-associated enzyme called fibroblast activation protein (FAP), thereby reducing the toxic side effects that prevent safe treatment of solid tumors with bortezomib. If ARI-3996 is shown to have a bortezomib-equivalent antitumor effect in a mouse model of FAP-producing epithelial cancer with at least a 10-fold reduction in toxicity compared to bortezomib, Phase II funding for IND-enabling studies will be applied for.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 498.79K | Year: 2015
DESCRIPTION provided by applicant Nonalcoholic steatohepatitis NASH characterized by liver steatosis with hepatocellular injury and inflammation is a potentially serious condition with up to of patients progressing to cirrhosis with complications of portal hypertension liver failure and hepatocellular carcinoma NASH is highly prevalent in patients with type diabetes T D and is an escalating health problem due to the global epidemic of T D Currently control of lipids by diet and exercise is the only approved treatment but long term effectiveness is questionable because many patients are unable to comply with the required dietary and lifestyle changes emphasizing the need for an effective pharmacotherapeutic approach The thiazolidines and vitamin E can improve liver histology in NASH patients but they are handicapped by formidable adverse effects The investigational agent obeticholic acid has been shown to improve the biochemical and histological features of NASH but drug safety requires further evaluation in the light of potentially adverse effects on blood lipids A new compound ARI MO can reverse the elevation of the enzyme markers of liver damage in hyperlipidemic hamsters and reduce circulating triglycerides and body weight ARI MO is a synthetic analog of nicotinic acid NA which itself has been reported to reverse hepatic steatosis in a hyperlipidemic model NA significantly reduced liver lipid in a small clinical trial but clinical acceptance in NAFLD NASH patients is unlikely given its association with hepatoxicity impaired insulin sensitivity and flushing ARI MO does not interact with the high affinity receptor for NA GPR A which mediates the latter two adverse effects but preclinically and clinically ARI MO retained beneficial effects on lipid levels and inflammation ARI MO did not impair glucose control cause flushing or show any signs of hepatotoxicity in human phase I trials suggesting feasibility as a drug candidate in NAFLD NASH The next step is to examine efficacy in NAFLD NASH patients with moderate biopsy proven steatohepatitis in a month study The Specific Aim is to demonstrate that ARI MO reduces intrahepatic lipid content and improves liver function via beneficial changes in liver function tests In order to advance into a placebo controlled proof of concept phase II clinical study in NASH patients SBIR phase ARI MO must meet specific Benchmarks at least a reduction in intrahepatic lipid content measured by MRI spectroscopy and a or greater reduction in the alanine transaminase marker of liver disease A study director at an advanced clinical site Beth Israel Deaconess Medical Center a homogeneous study population selected by liver histology indicative of reversible disease and the safety profile of ARI MO provide confidence that the study can be successfully executed to yield definitive measurable outcomes PUBLIC HEALTH RELEVANCE Nonalcoholic steatohepatitis NASH is an escalating public health problem linked to the global diabetes epidemic and is characterized by liver steatosis accompanied by hepatocellular injury inflammation and risk of progression to cirrhosis with complications of portal hypertension liver failure and hepatocellular carcinoma Effectiveness of diet and exercise to control NASH is limited by patient compliance moreover existing therapeutic agents such as the thiazolidines and vitamin E and an otherwise promising investigational agent obeticholic acid are handicapped by significant safety concerns Efficacy of the new investigational agent ARI MO will be tested in NAFLD NASH patients in a trial with intrahepatic lipid and liver enzyme endpoints