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Patent
Kadmon Corporation, Llc | Date: 2015-03-10

The present invention provides methods for treating tumors of the brain by administering the compounds of the Formula A and particularly N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or a pharmaceutically acceptable salt thereof, to a subject in need of such treatment. In the methods of the invention, the compounds disclosed herein were surprisingly found to cross the blood brain barrier. The method of the present invention further relates to the treatment of cancers of any type potentially responding to EGFR, HER2, VEGFR2, or Src family kinase inhibitors and that are found in the brain.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 184.62K | Year: 2012

DESCRIPTION (provided by applicant): Cytomegalovirus (CMV) causes significant disease and mortality in populations with weakened immune systems, including cancer patients, organ transplant recipients, and HIV-infected people. Additionally, it is the most common cause of congenital infection affecting about 1% of all live births worldwide, causing 20-30% of infants infected in utero to develop birth defects. Marketed CMV antivirals such as ganciclovir cause fever, diarrhea, and/or leukopenia in the majorityof treated adults, and are teratogenic in pregnancy. To address the unmet clinical need for a more safe and effective CMV treatment, Kadmon Corporation is working towards development of a novel class of antivirals that target host cell metabolic lipid metabolism, upon which the virus depends, with primary efforts examining small molecule inhibitors of Acetyl- CoA Carboxylase (ACC). We have shown that three separate small molecules that inhibit ACC block CMV replication in vitro in a dose dependent manner. This project proposes: (1) further studies of the efficacy of ACC inhibitors in vitro, against clinical isolates of CMV and mouse or guinea pig CMV; (2) metabolomic studies to identify metabolic correlates of anti-CMV efficacy; and (3) in vivo efficacy studies in animal models of CMV infection. Together these studies will validate ACC as a target for anti-CMV therapy, the overarching aim of this Phase I SBIR. The general strategy in SBIR Phase II will be to optimize an ACC inhibitor's pharmacology and to complete necessary preclinical experiments to enable IND filing. With respect to clinical development and commercialization, the initial indication will be for treatment of CMV disease in immune-compromised adults. In the long term, there is the potential also to provide a much- needed treatment for congenital CMV infection. PUBLIC HEALTH RELEVANCE: Cytomegalovirus (CMV) CMV infection is asymptomatic for most people, but the virus causes significant disease and mortality in populations with weakened immune systems, including cancer patients, organ transplant recipients, and HIV-infected people, and is the most common cause of congenital infection affecting about 1% of all live births worldwide. The present project proposes to demonstrate proof-of-concept efficacy of host cell lipid metabolism as a novel target for anti-CMV therapy.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 172.05K | Year: 2014

DESCRIPTION (provided by applicant): Many profound metabolic alterations have been described in solid tumors which present attractive therapeutic targets. One recently described metabolic oncogene is 3- phosphoglycerate dehydrogenase (PHGDH), the rate-limiting step in the pathway synthesizing serine and glycine for proteins, lipids, folate and nucleotide metabolism. The PHGDH gene is amplified at the genomic level across a wide spectrum of human cancers, and is particularly associated with certain treatment-resistant subtypes, such as triple-negative breast cancers, that present a major unmet clinical need for novel, safe and effective therapeutics. PHGDH knockdown has been demonstrated to be specifically toxic to PHGDH-amplified cell lines both in culture and in xenograft models. However, to date no specific inhibitors of mammalian PHGDH have yet been described, severely limiting investigation into this exciting new cancer target. To address this need Kadmon Corporation has initiated a project towar


Patent
Kadmon Corporation, Llc | Date: 2013-10-07

The invention relates to inhibitors of ROCK1 and/or ROCK2. Also provided are methods of treating diseases and disorders involving inhibiting ROCK1 and/or ROCK2.


Patent
Kadmon Corporation, Llc | Date: 2013-10-07

The invention relates to antibodies that bind to VEGFR-2. The antibodies are used for treating neoplastic diseases, hyperproliferative disorders, and angiogenic disorders and can be used alone or in combination with other agents.


Patent
Kadmon Corporation, Llc | Date: 2016-06-01

Disclosed are oral dosage forms containing a Ras antagonist including FTS and structural analogs thereof, and at least one pharmaceutically acceptable excipient other than a cyclodextrin, and methods of orally administering same to treat diseases and disorders responsive to the Ras antagonists.


Patent
Kadmon Corporation, Llc | Date: 2015-01-15

The invention provides antibodies that specifically bind to PD-L1 and fusion molecules comprising PD-L1 binding proteins constructed with an IL15 receptor-binding domain, nucleic acid molecules encoding the same, and therapeutic compositions thereof. The agents inhibit PD-L1-mediated immunosuppression and enhance cell and cytokine mediated immunity for the treatment of neoplastic and infectious diseases.


Patent
Kadmon Corporation, Llc | Date: 2014-10-07

The invention provides novel inhibitors of ROCK1 and/or ROCK2. Also provided are methods of treating diseases and disorders involving inhibiting ROCK1 and/or ROCK2. The present invention includes pharmaceutical compositions comprising the compounds of the invention and a pharmaceutically acceptable carrier and/or diluents. The present invention includes compositions comprising a substantially pure compound of the invention and a pharmaceutically acceptable salt, steroisomer, or hydrate thereof: and a pharmaceutically acceptable excipient and/or diluents.


Patent
Kadmon Corporation, Llc | Date: 2015-07-16

The present invention provides a method of treating breast cancer that is nonresponsive to treatment with trastuzumab, comprising administering to a subject in need of such treatment a therapeutically effective amount of compound N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or a pharmaceutically acceptable salt thereof.


Patent
Kadmon Corporation, Llc | Date: 2013-10-07

The invention provides methods of treatment of ocular disorders, including ocular disease with an angiogenic component. In certain embodiments, the treatment comprises administration of a ROCK2 inhibitor and an angiogenesis inhibitor. In certain embodiments, the ROCK2 inhibitor is ROCK2 selective. In certain embodiments, the angiogenesis inhibitor is a VEGF antagonist, for example, and VEGFR2 antibody.

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