PITTSBURGH, PA, United States

Cognition Therapeutics, Inc.

www.cogrx.com
PITTSBURGH, PA, United States
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Patent
Cognition Therapeutics, Inc. | Date: 2012-08-27

This invention relates to novel diarylamino compounds that bind to the sigma-2 receptor, to pharmaceutical compositions comprising such compounds, and to methods for inhibiting or restoring synapse loss in neuronal cells, modulating a membrane trafficking change in neuronal cells, and treating cognitive decline and neurodegenerative diseases and disorders therewith.


Patent
Cognition Therapeutics, Inc. | Date: 2015-01-30

Isoindoline sigma-2 receptor antagonist compounds, pharmaceutical compositions comprising such compounds, and methods for inhibiting Abeta-associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology are provided.


Patent
Cognition Therapeutics, Inc. | Date: 2016-10-11

Compounds that are central nervous system drug candidates for the treatment of cognitive decline and, more particularly, Alzheimers disease are provided. Methods for treatment, inhibition, and/or abatement of cognitive decline and/or Alzheimers disease with a compound or pharmaceutically acceptable salt of the invention are also provided. Also provided are methods of preparing the compounds/compositions of the invention.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 298.53K | Year: 2015

DESCRIPTION provided by applicant Cognition Therapeutics Inc andapos s mission is to develop effective therapeutics for Alzheimerandapos s disease AD Recent scientific discoveries have identified oligomers of the brain protein A as toxic culprits in disease progression Cognition in partnership with Temple University has identified a novel series of sigma receptor binding modulators that displace oligomers from neurons and block the downstream pathological signaling that inhibits memory formation These therapeutics should prevent further A oligomer induced damage and unmask existing memory capacity as synapses recover These receptor binding modulators are hypothesized to be disease modifying treatments that would be effective throughout the course of the disease and significantly impact the lives of the millions of Alzheimerandapos s patients Pharmaceutical industry efforts targeted specifically at A oligomer displacement are currently limited Cognition Therapeutics is one of the only companies uniquely focused on discovery of small molecule A oligomer displacing therapeutics We have discovered two CNS drug like lead series of A oligomer displacing compounds Analogs in these series displace oligomers from neurons and completely block A oligomer induced membrane trafficking changes and synapse loss Members of these series are highly brain penetrant and completely block oligomer induced memory deficits in Alzheimerandapos s disease mouse models Development of a clinical candidate is progressing We have now turned our attention to identifying new candidates to provide a measure of risk mitigation in the event that our current candidate falters due to unforeseen issues We propose to optimize Temple Universityandapos s series of novel sigma receptor binding modulators by synthesis and testing of new analogs designed to improve pharmacological and ADME properties This proposal will allow us to expand our portfolio of sigma receptor binding modulators with the goal of identifying orally efficacious candidates for further development as therapeutics for AD PUBLIC HEALTH RELEVANCE Amyloid beta oligomers AOs trigger synaptic dysfunction and lead to the cognitive decline in mild cognitive impairment MCI and early Alzheimerandapos s disease AD Prolonged oligomer exposure leads to more severe synaptotoxicity memory deficits and associated pathologies Novel therapeutics which displaces AOs from neurons should block and potentially reverse disease symptoms and progression Cognition Therapeutics is a pioneer in the development of high affinity sigma receptor binding modulators that displace AOs from neuronal receptors that mediate synaptotoxicity completely eliminate synapse loss and restore normal memory function in transgenic animals In collaboration with Temple University Cognition has identified a new series of sigma receptor modulators initially discovered by Temple researchers which exhibit potential to displace AOs The requested funding will enable the preparation and testing of new potent analogs of these small molecules with improved properties for oral administration These early feasibility studies will facilitate future work to optimize and develop advanced compounds for preclinical studies and eventual clinical trials An optimized sigma receptor modulator IND candidate that displaces AOs would further expand the portfolio of small molecule drugs available to reverse AD and MCI symptoms and block disease progression


Patent
Cognition Therapeutics, Inc. | Date: 2015-10-16

Compounds that are central nervous system drug candidates for the treatment of cognitive decline and, more particularly, Alzheimers disease are provided. Methods of treating, inhibiting, and/or abatement of cognitive decline and/or Alzheimers disease with a compound or pharmaceutically acceptable salt of the invention are also provided. Also provided are methods of preparing the compounds/compositions of the invention.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 222.00K | Year: 2016

Abstract Project Summary Cognition Therapeutics Inc CogRx has discovered CT a novel oligomer receptor antagonist that is the only drug candidate demonstrated to prevent and displace binding of Abeta oligomers to receptors on brain cells By stopping the initiating event in the Abeta oligomer cascade this first in class drug candidate completely blocks downstream synaptotoxicity and restores memory to normal in aged transgenic mouse models of Alzheimerandapos s disease CT displaces receptor bound Abeta oligomers by allosterically antagonizing the sigma PGRMC receptor Izzo et al a b CT thus represents the first disease modifying therapeutic that will test the oligomer hypothesis of Alzheimerandapos s disease Such a drug candidate would significantly impact the lives of the million patients worldwide suffering from AD and MCI for whom no disease modifying treatment exists This proposal seeks to identify biomarkers of CT functional target engagement The project proposes measuring changes in expression levels of proteins regulated by sigma PGRMC in the presence of Abeta oligomers that are blocked by CogRxandapos s sigma PGRMC antagonists in neurons and determining if such changes are observed in the brains CSF or serum of transgenic mice treated with CT The proposed studies will also conduct unbiased proteomic investigations on biofluids from wild type and transgenic AD mice treated with CT or vehicle to identify patterns of altered protein expression associated with drug engagement with target in settings of disease With this data we propose to construct a pathway from CT target engagement to peripherally available biomarker using targeted reaction monitoring MRM proteomics data The successful outcome of this project is the development of an assay to measure candidate biomarkers in humans for exploratory investigation in the clinic Project Narrative Cognition Therapeutics Inc has discovered a drug candidate that promises to stop and even reverse the memory loss in Alzheimerandapos s disease This drug canddi ate CT works by a completely novel mechanism to stop the binding of toxic proteins that build up in the brains of Alzheimerandapos s patients known as Abetaoligomers We are requesting funding support to identify and develop a target engagement biomarker through determination of precise measurements of biomarker proteins in biofluids such as CSF and plasma Such biomarkers would be invaluable for exploratory investigation of target engagement in the clinic of drug candidates in Alzheimerandapos s patients and would be a ot ol in the development of therapeutics which could significantly impact the lives of the million patients worldwide suffering from Alzheimerandapos s diseaseand Mild Cognitive Impairment for whom no disease modifying treatment exists


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 224.00K | Year: 2016

DESCRIPTION provided by applicant Cognition Therapeutics Inc andapos s mission is to develop effective therapeutics for Alzheimerandapos s disease Recent scientific discoveries have identified oligomers of the brain protein Abeta as toxic culprits in the disease process Cognition has discovered therapeutic molecules that displace Abeta oligomers from neurons and block the downstream pathological signaling that inhibits memory formation These therapeutic small molecules should prevent further oligomer induced damage and unmask existing memory capacity as synapses recover These molecules act through modulating a newly identified receptor target They are hypothesized to be disease modifying treatments that would be effective throughout the course of the disease and significantly impact the lives of millions of Alzheimerandapos s patients Pharmaceutical industry efforts targeted specifically at Abeta oligomer blockade are currently limited Cognition Therapeutics is one of the only companies uniquely focused on discovery of small molecule oligomer displacing therapeutics We have discovered a CNS drug like lead series of oligomer displacing compounds the CT Series Analogs in this series displace oligomers from neurons and completely block Abeta oligomer induced membrane trafficking changes and synapse loss Members of this series are highly brain penetrant and completely block oligomer induced memory deficits in Alzheimerandapos s disease mouse models Further preclinical development of these analogs is progressing However new structural variants with different physicochemical profiles will provide a measure of risk mitigation in the event that our current candidates fail to advance through the clinic due to unforeseen issues We propose to explore a new piperazine variant of the CT series This new variant would possess physiochemical properties previously unexplored in the current series This proposal will allow us to expand our portfolio of Abeta oligomer displacing compounds and establish the feasibility of these variants to be optimized with the goal of obtaining orally efficacious candidates for further development as therapeutics for AD PUBLIC HEALTH RELEVANCE Abeta oligomers trigger synaptic dysfunction and lead to the cognitive decline in MCI and early AD Prolonged oligomer exposure leads to more severe synaptotoxicity memory deficits and accumulated pathology Therapeutics which displaces oligomers from neuronal binding sites should block and potentially reverse disease symptoms and progress Cognition Therapeutics has discovered first in class high affinity oligomer displacing molecules that mediate synaptotoxicity completely eliminate synapse loss and restore memory to normal in transgenic animals The requested funding will enable the preparation and in depth testing of new variant of these molecules with different physicochemical properties from our parent series These early feasibility studies will facilitate future work for optimization and development of advanced compounds to preclinical studies and eventual clinical trials Such an optimized Abeta oligomer displacing IND candidate would be expand our portfolio of novel small molecule drugs to reverse AD and MCI symptoms and block disease progression


Patent
Cognition Therapeutics, Inc. | Date: 2016-06-13

Compounds that are central nervous system drug candidates for the treatment of cognitive decline and, more particularly, Alzheimers disease are provided. Methods of treating, inhibiting, and/or abatement of cognitive decline and/or Alzheimers disease with a compound or pharmaceutically acceptable salt of the invention are also provided. Also provided are methods of preparing the compounds/compositions of the invention.


Patent
Cognition Therapeutics, Inc. | Date: 2014-06-02

Compounds that are central nervous system drug candidates for the treatment of cognitive decline and, more particularly, Alzheimers disease are provided. Methods of treating, inhibiting, and/or abatement of cognitive decline and/or Alzheimers disease with a compound or pharmaceutically acceptable salt of the invention are also provided. Also provided are methods of preparing the compounds/compositions of the invention.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 142.04K | Year: 2012

DESCRIPTION (provided by applicant): Recent key scientific discoveries have identified oligomers of the protein Abeta 42 as the synaptotoxic culprits in the Alzheimer's disease process. With increasing age, decline in brain levels of Abeta binding and clearance proteins and elevations in enzyme activity responsible for producing Abeta combine to produce an elevation of monomeric Abeta 42 levels. The hydrophobic C-terminus of this peptide then self-associates to form metastable oligomers that bind with highaffinity to receptors located on a subset of neurons. Once bound, synaptotoxic Abeta oligomers alter glutamate receptor trafficking to the plasma membrane and inhibit long term potentiation, resulting in transient regression of spines, synapse loss and memory deficits (reviewed in Catalano et al., '06, Li et al., '10). Blocking Abeta oligomer effects is expected to prevent these memory deficits and slow or reverse neurodegeneration and Alzheimer's disease progression in humans. We have discovered first-in-class selective high affinity receptor antagonists that compete with human AD patient-derived oligomers for access to receptors that mediate synaptotoxicity, completely eliminate synapse loss and restore memory to normal in transgenic animals. These small molecules have excellent plasma stability and blood-brain- barrier permeability, but exhibit limited oral bioavailability due to oxidation by liver enzymes (first pass metabolism). While further preclinical development of these analogs is possible via alternate routes of systemic administration, improved oral bioavailability and oral formulation will significantly improve patiet compliance and increase the numbers of patients who could be helped by this therapeutic strategy. We propose to optimize the oral bioavailability of the CT0109 series by synthesis and testing of analogs designed to improve metabolic stability. Successful advancement of an orally bioavailable candidate could significantly impact the lives of the 35 million patients worldwide sufferingfrom AD and MCI, for whom no disease-modifying treatment currently exists. PUBLIC HEALTH RELEVANCE: Abeta oligomers trigger synaptic dysfunction and lead to the cognitive decline in MCI and early AD. Prolonged oligomer exposure leads to more severe synaptotoxicity, memory deficits and accumulated pathology. Therapeutics targeting oligomers should block and potentially reverse disease symptoms and progress. Cognition Therapeutics has discovered first-in-class high affinity receptor antagonists thatcompete with oligomers for access to neuronal receptors that mediate synaptotoxicity, completely eliminate synapse loss and restore memory to normal in transgenic animals. The requested funding will enable optimization of these promising molecules for oraladministration, facilitating their advancement to IND-enabling preclinical studies and eventual clinical trials. Such an optimized IND Abeta oligomer receptor antagonist candidate would be among the first small molecule drugs to reverse AD and MCI symptoms and block disease progression.

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