UG3DA052166
Cooperative Agreement
Overview
Grant Description
CVL-354, a Kappa Opioid Receptor Antagonist for Treatment of Opioid Use Disorder, Withdrawal, and Relapse - Project Summary
Kappa Opioid Receptors (KOR) are expressed in brain areas that control reward, motivation, and anxiety. Dynorphin (DYN), an endogenous KOR agonist, controls KOR activity to promote physiological acute aversive states such as fear and anxiety to promote escape. Furthermore, upon opioid drug withdrawal and abstinence, dysregulated DYN/KOR signaling can result in aversive physical and affective states that are a major driver of relapse.
Preclinically, KOR antagonists have demonstrated efficacy in reducing the physical signs of acute opioid withdrawal. The current standard of care administered to reduce the physical symptoms of opioid withdrawal is the alpha 2A adrenergic receptor agonist, lofexidine. Although approved, lofexidine is only modestly effective at withdrawal symptom severity reduction and can have significant unwanted side effects such as hypotension, acute orthostasis and syncope, QT prolongation, and the potentiation of CNS depressant effects when taken with sedating drugs.
Cerevel Therapeutics is addressing this unmet need with the development of a short-acting, selective KOR antagonist. This compound, CVL-354, attenuated the physical signs of withdrawal in an acute opioid withdrawal model in rodents, and we have completed a comprehensive nonclinical safety package that will support dosing up to 90 days in humans.
If awarded these funds, we are poised to run single and multiple ascending dose studies to assess safety and tolerability in healthy volunteers (UG3 portion). In the UH3 portion, we will execute PET studies to further explore receptor occupancy in humans, in combination with additional nonclinical safety and manufacturing work that will support a Phase 2 clinical trial aimed at providing a more effective treatment option to mitigate the physical symptoms of opioid withdrawal.
Kappa Opioid Receptors (KOR) are expressed in brain areas that control reward, motivation, and anxiety. Dynorphin (DYN), an endogenous KOR agonist, controls KOR activity to promote physiological acute aversive states such as fear and anxiety to promote escape. Furthermore, upon opioid drug withdrawal and abstinence, dysregulated DYN/KOR signaling can result in aversive physical and affective states that are a major driver of relapse.
Preclinically, KOR antagonists have demonstrated efficacy in reducing the physical signs of acute opioid withdrawal. The current standard of care administered to reduce the physical symptoms of opioid withdrawal is the alpha 2A adrenergic receptor agonist, lofexidine. Although approved, lofexidine is only modestly effective at withdrawal symptom severity reduction and can have significant unwanted side effects such as hypotension, acute orthostasis and syncope, QT prolongation, and the potentiation of CNS depressant effects when taken with sedating drugs.
Cerevel Therapeutics is addressing this unmet need with the development of a short-acting, selective KOR antagonist. This compound, CVL-354, attenuated the physical signs of withdrawal in an acute opioid withdrawal model in rodents, and we have completed a comprehensive nonclinical safety package that will support dosing up to 90 days in humans.
If awarded these funds, we are poised to run single and multiple ascending dose studies to assess safety and tolerability in healthy volunteers (UG3 portion). In the UH3 portion, we will execute PET studies to further explore receptor occupancy in humans, in combination with additional nonclinical safety and manufacturing work that will support a Phase 2 clinical trial aimed at providing a more effective treatment option to mitigate the physical symptoms of opioid withdrawal.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding Agency
Place of Performance
Massachusetts
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the End Date has been shortened from 08/31/23 to 05/31/23.
Cerevel Therapeutics Holdings was awarded
CVL-354: A Short-Acting Kappa Opioid Receptor Antagonist for Opioid
Cooperative Agreement UG3DA052166
worth $5,400,000
from the National Institute of Neurological Disorders and Stroke in September 2021 with work to be completed primarily in Massachusetts United States.
The grant
has a duration of 1 year 8 months and
was awarded through assistance program 93.279 Drug Abuse and Addiction Research Programs.
The Cooperative Agreement was awarded through grant opportunity Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional).
Status
(Complete)
Last Modified 5/20/24
Period of Performance
9/30/21
Start Date
5/31/23
End Date
Funding Split
$5.4M
Federal Obligation
$0.0
Non-Federal Obligation
$5.4M
Total Obligated
Activity Timeline
Transaction History
Modifications to UG3DA052166
Additional Detail
Award ID FAIN
UG3DA052166
SAI Number
UG3DA052166-651007956
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Small Business
Awarding Office
75N600 NIH NATIONAL INSITUTE ON DRUG ABUSE
Funding Office
75NQ00 NIH NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Awardee UEI
QKDNCJEMESK5
Awardee CAGE
8F4Y6
Performance District
MA-90
Senators
Edward Markey
Elizabeth Warren
Elizabeth Warren
Modified: 5/20/24