COGNITION THERAPEUTICS, INC.

www.cogrx.com

914-556-3347

jdoyle@COGRX.COM

JOHN DOYLE

P1054484

5CQK3

Active

Non-Manufacturer

2024-04-09

2029-04-09

2025-04-05

JOHN DOYLE

+1 914-556-3347

2022-08-01

View on USAspending

Department of Health and Human Services

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, PHASE 2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF CT1812 IN SUBJECTS WITH DEMENTIA WITH LEWY BODIES - ABSTRACT: COGNITION THERAPEUTICS, INC. (COGRX) IS DEVELOPING CT1812 FOR NEURODEGENERATIVE CONDITIONS, INCLUDING DEMENTIA WITH LEWY BODIES (DLB). THIS FIRST-IN-CLASS SMALL MOLECULE DRUG CANDIDATE SELECTIVELY DISPLACES ASS OLIGOMERS BOUND TO NEURONAL RECEPTORS AT SYNAPSES AND PROTECTS SYNAPSES FROM TOXIC OLIGOMER EFFECTS, CLEARING THEM FROM THE BRAIN INTO THE CEREBROSPINAL FLUID (CSF). CT1812 ALSO DISPLACES A-SYNUCLEIN OLIGOMER BINDING TO NEURONS IN VITRO. CT1812 IS CURRENTLY IN A PHASE 2 TRIAL IN PATIENTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE (AD), WHERE IT HAS BEEN FOUND TO BE SAFE AND GENERALLY WELL-TOLERATED. WHEN ADMINISTERED ONCE DAILY FOR 28 DAYS TO AD PATIENTS, CT1812 SIGNIFICANTLY REDUCED CONCENTRATIONS OF SYNAPTIC DEGENERATION MARKERS IN CSF. SIMILAR TO ASS OLIGOMERS, A-SYNUCLEIN OLIGOMERS BIND TO NEURONS AND CAUSE SYNAPTIC DYSFUNCTION AND LOSS, SPREADING THROUGHOUT THE BRAIN AS DISEASE PROGRESSION IS OBSERVED IN DLB. EIGHTY PERCENT OF PATIENTS WITH DLB REFLECT BOTH ASS AND A-SYNUCLEIN PATHOLOGY AT AUTOPSY. PATIENTS WITH DLB LIKELY HAVE BOTH TYPES OF OLIGOMERS AND SHOULD BENEFIT FROM TREATMENT WITH CT1812. THIS CLINICAL TRIAL PROJECT PROPOSES TO CONDUCT A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, SIX-MONTH STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND EXPLORATORY EFFICACY OF CT1812 AT 100 MG AND 300 MG DAILY DOSES IN MILD TO MODERATE DLB PATIENTS (N=40/GROUP). TRIAL ENDPOINTS WILL INCLUDE SAFETY AS WELL AS EXPLORATORY EFFICACY MEASURES (MONTREAL COGNITIVE ASSESSMENT [MOCA], COGNITIVE DRUG RESEARCH BATTERY [CDR], CLINICIAN ASSESSMENT OF FLUCTUATION [CAF], EPWORTH SLEEPINESS SCALE [ESS], MOVEMENT DISORDER SOCIETY – UNIFIED PARKINSON'S DISEASE RATING SCALE – PART III [MDS-UPDRS3], THE ALZHEIMER'S DISEASE COOPERATIVE STUDY – CLINICAL GLOBAL IMPRESSION OF CHANGE [ADCS-CGIC], ADCS-ACTIVITIES OF DAILY LIVING [ADL], AND NEUROPSYCHIATRIC INVENTORY [NPI]) AT BASELINE, 3 MONTHS, AND 6 MONTHS. ADDITIONAL MEASUREMENTS OF PLASMA AND CSF CONCENTRATIONS OF DRUG, TARGET ENGAGEMENT BIOMARKERS (INCLUDING ASS AND A-SYNUCLEIN OLIGOMERS), DISEASE PROGRESSION PROTEIN MARKERS (ASS AND A-SYNUCLEIN MONOMER, TOTAL AND PHOSPHORYLATED TAU PROTEIN) AND SYNAPTIC DAMAGE/NEURODEGENERATION BIOMARKERS (NEUROGRANIN, SYNAPTOTAGMIN, SYNAPTOSOMAL-ASSOCIATED PROTEIN 25 [SNAP-25], AND NEUROFILAMENT LIGHT [NFL]) AT BASELINE AND AT 6 MONTHS WILL ALLOW CORRELATION OF DRUG CONCENTRATIONS WITH MEASURES OF SYNAPTIC DAMAGE AND COGNITIVE PERFORMANCE. CONDUCTING A STUDY WITH THIS PATIENT POPULATION WILL LEVERAGE THE ONGOING CT1812 DEVELOPMENT EFFORTS FOR AD AND WILL PROVIDE A NEAR-TERM OPPORTUNITY TO INVESTIGATE A CLINICAL CANDIDATE THERAPEUTIC IN DLB, AN INDICATION FOR WHICH NO DISEASE-MODIFYING TREATMENTS EXIST. COMPLETION OF THIS STUDY WILL PROVIDE AN INITIAL ASSESSMENT OF CT1812 EFFICACY IN DLB PATIENTS THAT WILL INFORM DESIGN OF SUBSEQUENT PIVOTAL TRIALS NECESSARY FOR FURTHER CLINICAL DEVELOPMENT OF CT1812.

29498064.00

0.00

0.00

2022-02-14

View on USAspending

Department of Health and Human Services

HUMAN AME STUDY OF CT1812, A SMALL MOLECULE IN PHASE 2 CLINICAL TRIALS FOR THE TREATMENT OF ALZHEIMER'S DISEASE - PROJECT SUMMARY/ABSTRACT ALZHEIMER'S DISEASE (AD) AFFLICTS NEARLY SIX MILLION PEOPLE IN THE UNITED STATES (U.S), AND THIS NUMBER IS EXPECTED TO DOUBLE BY 2050. DISEASE MODIFYING MEDICAL THERAPIES FOR AD CONTINUE TO BE AN UNMET NEED. THE SYMPTOMATIC TREATMENTS CURRENTLY AVAILABLE REGULATE NEUROTRANSMITTER LEVELS, SLOWING COGNITIVE DECLINE FOR AN AVERAGE OF ONLY 6 MONTHS. COGNITION THERAPEUTICS (COGRX) IS DEVELOPING CT1812, THE FIRST BRAIN PENETRANT SMALL MOLECULE THAT SELECTIVELY CLEARS TOXIC BETA AMYLOID OLIGOMERS (ASSOS) FROM THE BRAIN INTO CEREBROSPINAL FLUID (CSF). CT1812'S MECHANISM OF ACTION HAS THE POTENTIAL TO HALT OR SLOW COGNITIVE DECLINE, SIGNIFICANTLY ALLEVIATING AD PROGRESSION. CT1812 IS CURRENTLY IN PHASE 2 TRIALS IN PATIENTS. BEFORE COGRX CAN PROCEED TO LARGER AND LONGER STUDIES THAT EVALUATE EFFICACY, A HUMAN ABSORPTION, METABOLISM, AND EXCRETION (AME) STUDY MUST BE CONDUCTED PER FOOD AND DRUG ADMINISTRATION EXPECTATIONS, TO ESTABLISH A ROBUST AND COMPREHENSIVE KNOWLEDGE OF CT1812'S PHARMACOKINETICS (PK) AND KEY METABOLITES. APPROACH. THE OVERALL RESEARCH DESIGN WILL INCLUDE (AIM 1) PURIFYING AND CHARACTERIZING RADIOLABELED CT1812 IN SUFFICIENT QUANTITIES WITH SUFFICIENT QUALITY; (AIM 2) CONDUCTING AN OPEN-LABEL AME CLINICAL TRIAL IN WHICH UP TO SIX HEALTHY MALE VOLUNTEERS ARE GIVEN ORAL [14C]-CT1812, FOLLOWED BY PLASMA, URINE AND FECES COLLECTION FOR UP TO 14 DAYS, AND (AIM 3) ANALYZING SAMPLES TO DETERMINE MASS BALANCE RECOVERY, PK, AND IDENTIFICATION AND QUANTIFICATION OF THE RELATIVE ABUNDANCES OF THE METABOLITES. COGRX'S LONG-TERM OBJECTIVE IS TO DEVELOP CT1812 AS A POTENTIAL DISEASE-MODIFYING THERAPEUTIC FOR AD TREATMENT. BECAUSE NO AD DISEASE-MODIFYING THERAPIES EXIST CURRENTLY, CT1812 WOULD SIGNIFICANTLY ADVANCE AD TREATMENT ARMAMENTARIUM. 1

1642783.00

0.00

0.00

2021-11-30

View on USAspending

Department of Health and Human Services

A PILOT SYNAPTIC VESICLE GLYCOPROTEIN 2A (SV2A) PET STUDY TO EVALUATE THE EFFECT OF CT1812 TREATMENT ON SYNAPTIC DENSITY IN SUBJECTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE - ABSTRACT. SOLUBLE OLIGOMERS OF BETA AMYLOID (ASS) PROTEIN ARE THE MOST POTENT NEUROACTIVE STRUCTURAL FORM OF THIS PROTEIN AND EVIDENCE SUGGESTS THEY CAUSE THE SYNAPTOTOXIC CHANGES RESULTING IN COGNITIVE DECLINE IN ALZHEIMER’S DISEASE (AD) (SELKOE AND HARDY 2016, VIOLA AND KLEIN 2015). A SAFE AND EFFECTIVE DRUG AGAINST ASS OLIGOMERS SHOULD PREVENT AND REVERSE THIS SYNAPTOTOXICITY. CT1812 IS THE FIRST DRUG THAT SELECTIVELY DISPLACES OLIGOMERS FROM SYNAPTIC RECEPTOR SITES AND CLEARS OLIGOMERS FROM THE BRAIN INTO THE CEREBROSPINAL FLUID (CSF). THESE FIRST-IN-CLASS DRUGS WORK BY DISPLACING ASS OLIGOMERS BOUND TO NEURONAL RECEPTORS AT SYNAPSES. THEY ACCOMPLISH THIS BY ALLOSTERICALLY MODULATING A KEY PROTEIN REGULATOR OF OLIGOMER RECEPTORS (THE SIGMA- 2/PGRMC1 PROTEIN COMPLEX), THUS DESTABILIZING THE OLIGOMER BINDING SITE AND INCREASING THE OFF-RATE OF OLIGOMERS, WHICH ARE THEN CLEARED INTO THE CSF. AS A RESULT, CT1812 RESTORES SYNAPSE NUMBER AND COGNITIVE PERFORMANCE TO NORMAL IN PRECLINICAL AD MOUSE MODELS (IZZO ET AL., 2014A, B). THIS PROJECT PROPOSES TO EVALUATE THE EFFECT OF CT1812 ON SYNAPSE NUMBER AND COGNITIVE FUNCTION IN A PHASE 1B RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL IN AD PATIENTS. BY COMBINING MEASUREMENTS OF COGNITIVE FUNCTION WITH NOVEL POSITRON EMISSION TOMOGRAPHY (PET) IMAGING OF SYNAPTIC DENSITY IN THE SAME PATIENTS, THIS TRIAL CAN DIRECTLY TEST THE MECHANISM OF ACTION OF CT1812 AND THE ASS OLIGOMER HYPOTHESIS OF AD. THE PET TRACER 11C-UCB-J, WHICH QUANTITATIVELY IMAGES THE SYNAPTIC PROTEIN SV2A, HAS BEEN USED AS A MEASURE OF SYNAPTIC DENSITY IN HUMANS (FINNEMA ET AL., 2016) AND CAN BE USED AS A BIOMARKER OF SYNAPTIC DENSITY LOSS AND REGROWTH IN ALZHEIMER’S PATIENTS. WE PROPOSE TO CONDUCT A CLINICAL TRIAL IN 20 ASS-POSITIVE MILD TO MODERATE ALZHEIMER’S PATIENTS (MMSE 18-26) RECEIVING CT1812 OR PLACEBO ONCE DAILY FOR 3 MONTHS, WITH SYNAPTIC DENSITY MEASURED VIA 11C-UCB-J SCANS AND COGNITIVE TESTING (ADAS-COG14, ADCS-ADL, CDR-SB) AT BASELINE AND 3 MONTHS. OUR PRIMARY AIM IS TO EVALUATE THE CORRELATION BETWEEN CHANGES IN SYNAPTIC DENSITY AND CHANGES IN COGNITIVE FUNCTION. OUR SECONDARY AIM IS TO EVALUATE THE CORRELATION BETWEEN CHANGES IN SYNAPTIC DENSITY AND CHANGES IN GLUCOSE METABOLISM. WE HYPOTHESIZE THAT INCREASES IN SYNAPTIC DENSITY AS MEASURED WITH PET WILL BE DEMONSTRATED IN THIS COHORT, AND THAT THESE CHANGES WILL CORRELATE WITH COGNITIVE IMPROVEMENT. COMPLETION OF THIS PILOT STUDY IN AD PATIENTS WILL INFORM THE DESIGN AND METHODS OF THE SUBSEQUENT PHASE 2A PROOF OF CONCEPT TRIALS WITH CT1812. ADVANCEMENT OF CT1812 CLINICAL DEVELOPMENT WOULD SUBSTANTIALLY IMPROVE THE LIVES OF THE 36 MILLION PEOPLE WORLDWIDE SUFFERING FROM AD AND MCI DUE TO AD, FOR WHOM NO DISEASE-MODIFYING PHARMACOLOGICAL TREATMENTS EXIST.

4682259.45

0.00

0.00

2022-07-25

View on USAspending

Department of Health and Human Services

RANDOMIZED DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP TRIAL TO EVALUATE THE SAFETY AND EFFICACY OF CT1812 IN EARLY ALZHEIMER'S DISEASE OVER 18 MONTHS - COGNITION THERAPEUTICS, INC. (COGRX) IS DEVELOPING CT1812, A DISEASE-MODIFYING DRUG FOR ALZHEIMER’S DISEASE. CT1812 IS THE FIRST HIGHLY BRAIN PENETRANT SELECTIVE SIGMA-2 RECEPTOR ANTAGONIST SMALL MOLECULE. THIS DRUG CANDIDATE SELECTIVELY DISPLACES AMYLOID-SS OLIGOMERS BOUND TO NEURONAL RECEPTORS AT SYNAPSES AND PROTECTS SYNAPSES FROM TOXIC OLIGOMER EFFECTS, CLEARING OLIGOMERS FROM THE BRAIN INTO THE CEREBROSPINAL FLUID. WHEN ADMINISTERED ONCE DAILY FOR 28 DAYS TO MILD TO MODERATE AD PATIENTS, CT1812 SIGNIFICANTLY INCREASES CSF CONCENTRATION OF ASSOS, INCREASES PLASMA CONCENTRATIONS OF LIPIDS AND METABOLITES, AND REDUCES CONCENTRATIONS OF SYNAPTIC DEGENERATION MARKERS IN AD PATIENT CSF, CONSISTENT WITH THE DISEASE-MODIFYING AND SYNAPTOPROTECTIVE MECHANISM OF ACTION ESTABLISHED IN PRECLINICAL STUDIES. NO OTHER THERAPEUTIC CURRENTLY IN DEVELOPMENT SELECTIVELY TARGETS THE MOST TOXIC FORM OF THE ASS PROTEIN – OLIGOMERS (ASSOS) AND HAS DEMONSTRATED SELECTIVE CLEARANCE OF ASSO INTO CSF IN AD PATIENTS. NO OTHER AD DRUG CANDIDATE HAS DEMONSTRATED NORMALIZATION OF DYSREGULATED PROTEIN AND LIPID/METABOLITE ANALYTES IN AD PATIENT BIOFLUIDS OR REPORTED REDUCTION OF SYNAPTIC DAMAGE MARKERS IN AD PATIENTS AS MUCH, AND AS RAPIDLY, AS CT1812. WE HYPOTHESIZE THAT THE EFFECTS OF OLIGOMER DISPLACEMENT AND CLEARANCE ON COGNITIVE FUNCTION WIL L BE DETECTABLE IN SYMPTOMATIC PATIENTS, AND THE EFFECT ON DISEASE MODIFICATION WILL BE DETECTABLE IN PRESYMPTOMATIC PATIENTS. COGRX DISCOVERED CT1812, ITS MECHANISM OF ACTION AND THE ROLE OF THE SIGMA-2 RECEPTOR COMPLEX IN AD. NO OTHER GROUP IS PURSUING THIS MECHANISM OF ACTION FOR ALZHEIMER’S DISEASE TREATMENT. CT1812 HAS BEEN DEMONSTRATED TO BE SAFE AND WELL TOLERATED IN HEALTHY VOLUNTEERS AND MILD-TO MODERATE AD PATIENTS IN PLACEBO-CONTROLLED PHASE 1B/2A TRIALS. ADVERSE EVENTS WERE PREDOMINANTLY MILD AND INCLUDED HEADACHE AND GI DISTURBANCES. TWO DOSES OF CT1812 ARE CURRENTLY BEING EVALUATED IN FOLLOW-ON SAFETY TRIALS IN MILD TO MODERATE AD PATIENTS (Q.D. FOR 6 MONTHS, MMSE 18-26). THESE SAME TWO DOSES WILL BE TESTED IN EARLY AD PATIENTS (MMSE 20-30) IN THE CURRENT TRIAL, WITH TREATMENT DURATION EXTENDED TO 18 MONTHS. THIS PROJECT PROPOSES TO CONDUCT A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 TRIAL TO EVALUATE THE SAFETY AND TOLERABILITY OF TWO DOSES OF CT1812 IN PATIENTS WITH EARLY AD (MMSE 20-30, CORRESPONDING TO FDA LATE STAGE 2 TO EARLY STAGE 4) GIVEN Q.D. OVER 18 MONTHS. THIS TRIAL WILL DETERMINE WHETHER CT1812 BENEFICIALLY AFFECTS COGNITION AS MEASURED BY CDR-SB AND OTHER SECONDARY COGNITIVE MEASURES, AS WELL AS MEASURING THE IMPACT OF CT1812 ON BIOMARKERS OF TARGET ENGAGEMENT (CSF CONCENTRATIONS OF ASS OLIGOMERS AND SYNAPTIC DEGENERATION PROTEINS) AND DISEASE MODIFICATION (CSF CONCENTRATIONS OF TOTAL TAU AND NFL, SERUM NFL AS WELL AS HIPPOCAMPAL AND WHOLE BRAIN VOLUME CHANGE BY MRI). COMPLETION OF THIS STUDY IN EARLY AD PATIENTS WILL INFORM THE DESIGN AND METHODS OF THE SUBSEQUENT LONG TERM DISEASE MODIFICATION PHASE 3 TRIALS WITH CT1812.

52281054.00

0.00

0.00

2022-08-26

View on USAspending

Department of Health and Human Services

A PILOT ELECTROENCEPHALOGRAPHY (EEG) STUDY TO EVALUATE THE EFFECT OF CT1812 TREATMENT ON SYNAPTIC ACTIVITY IN SUBJECTS WITH MILD TO MODERATE ALZHEIMER?S DISEASE - ABSTRACT. COGNITION THERAPEUTICS, INC. (COGRX) IS DEVELOPING ELAYTATM (CT1812), A DISEASE-MODIFYING DRUG FOR ALZHEIMER’S DISEASE (AD). CT1812 IS THE FIRST HIGHLY BRAIN PENETRANT SELECTIVE SIGMA-2 RECEPTOR ANTAGONIST SMALL MOLECULE. THIS FIRST-IN-CLASS DRUG CANDIDATE SELECTIVELY DISPLACES AMYLOID-SS OLIGOMERS BOUND TO NEURONAL RECEPTORS AT SYNAPSES AND PROTECTS SYNAPSES FROM TOXIC OLIGOMER EFFECTS, CLEARING THEM FROM THE BRAIN INTO THE CEREBROSPINAL FLUID (CSF). WHEN ADMINISTERED ONCE DAILY FOR 28 DAYS TO MILD TO MODERATE AD PATIENTS, CT1812 SIGNIFICANTLY REDUCES CONCENTRATIONS OF SYNAPTIC DEGENERATION MARKERS IN AD PATIENT CSF. BASED ON OUR REVIEW OF PUBLICLY-DISCLOSED CLINICAL TRIAL DATA, NO OTHER THERAPEUTIC CURRENTLY IN DEVELOPMENT SELECTIVELY TARGETS THE MOST TOXIC FORM OF THE ASS PROTEIN – OLIGOMERS. NO OTHER AD DRUG CANDIDATE REDUCES SYNAPTIC DAMAGE MARKERS AS MUCH, AND AS RAPIDLY, AS CT1812 IN ALZHEIMER'S PATIENTS. OUR AIM IN THE PROPOSED TRIAL IS TO IDENTIFY NON-INVASIVE MEASURES TO QUANTIFY THE CNS IMPACT OF CT1812 DEMONSTRATED ABILITY TO REDUCE SYNAPTIC DAMAGE IN AD PATIENTS. THIS PILOT TRIAL PROJECT PROPOSES TO EVALUATE THE EFFECT OF ONE MONTH OF CT1812 TREATMENT ON QUANTITATIVE EEG IN A PHASE 1B RANDOMIZED DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER CLINICAL TRIAL IN AD PATIENTS. WE HYPOTHESIZE THAT THE RAPID REDUCTION IN SYNAPTIC DAMAGE CSF BIOMARKERS SEEN IN PREVIOUS CLINICAL TRIALS WILL BE ACCOMPANIED BY A REDUCTION IN GLOBAL THETA POWER AND PROVIDE INFORMATION ON THE SUITABILITY OF THIS SENSITIVE NON-INVASIVE QEEG METHOD OF MEASURING SYNAPTIC FUNCTION FOR MEASURING PATIENT RESPONSE TO DRUG TREATMENT IN FUTURE EFFICACY STUDIES. COMPLETION OF THIS PILOT STUDY IN AD PATIENTS WILL INFORM THE DESIGN AND METHODS OF THE SUBSEQUENT PHASE 2A PROOF OF CONCEPT TRIALS WITH CT1812.

5445051.00

0.00

0.00