TECHNOLOGY/BUSINESS OPPORTUNITY Modified cyclodextrins to counteract the effects of fentanyl and related opioids

Opportunity:

Lawrence Livermore National Laboratory (LLNL), operated by the Lawrence Livermore National Security (LLNS), LLC under contract no. DE-AC52-07NA27344 (Contract 44) with the U.S. Department of Energy (DOE), is offering the opportunity to enter into a collaboration to further develop and commercialize its modified cyclodextrins to counteract the effects of fentanyl and related opioids.

Background:

Fentanyl is a powerful rapid-acting opioid used to treat patients to reduce their pain. It is 50 to 100 times more potent than morphine and heroin and according to the DEA is now the leading cause of death for Americans between the ages of 18 and 45.  Due to this largely recognized fentanyl epidemic, there is a great need for treatment to counteract the effects of fentanyl for overdose cases. 

Cyclodextrins (CDs), which are sugar molecules bound together in rings of various sizes, have been shown to be capable of sequestering fentanyl and its analogues.  By binding to the fentanyl with its hollow central cavity, CDs can reduce its bioavailability, thus neutralizing the effects of the drug. Optimization of the central cavity of the cyclodextrin molecule is required for the binding of the fentanyl to be successful.  For example, FDA approved drug, sugammadex, was found to bind to another drug rocuronium effectively, but with fentanyl, the affinity was relatively low. This was due to its large interior cavity that did not allow the opioid molecule to fit tightly within.

To optimize the affinity for fentanyl, LLNL researchers used a combined experimental and computational approach to screen for modified cyclodextrins that have suitable characteristics like appropriately sized central cavity that could enhanced their affinities for fentanyl and related analogues.

Description:

After screening at least 50 different cyclodextrins, LLNL researchers found that the drug Subetadex shows enhanced affinities for fentanyl and its analogues.  Subetadex is a smaller version of sugammadex and with a smaller central cavity, allows it to bind extremely well to fentanyl by comparison.  A pharmacokinetic study showed a rapid clearance of this promising candidate from major organs, such as the heart, liver, brain and kidney, during the studies. Also, initial in vitro toxicity assessments show that Subetadex has a non-toxic profile.

Subetadex is part of a group of modified cyclodextrins that LLNL researchers have developed with the goal of developing effective broad-spectrum treatments.  This medical countermeasure candidate and its related compounds for opioid overdose treatment is an exciting advancement in the fight to counter the opioid epidemic.

Advantages/Benefits: 

• High specificity for fentanyl and its analogues
• Instead of blocking receptors, modified CDs bind directly to the opioid molecule itself
• Subetadex has a non-toxic profile, which is comparable to the already FDA-approved drug sugammadex.
• Modified CDs are expected to cut specific recovery times in half, from a little over 35 minutes to about 17 minutes for fentanyl and related opioids
• Modified CDs are expected to remains active longer than currently available treatments, thus can prevent a relapse with requiring another dose.

Potential Applications: 

• Medical countermeasure development (use of the drug to prevent overdoses as a prophylactic or therapeutic)
• Forensic research
• Environmental remediation

Development Status: 

Current stage of technology development: TRL 3-5

LLNL has patent(s) on this invention.

U.S. Patent No. 10442871 Modified cyclodextrins for the selective sequestration of fentanyl related compounds and uses thereof published 10/15/2019

LLNL is seeking industry partners with a demonstrated ability to bring such inventions to the market. Moving critical technology beyond the Laboratory to the commercial world helps our licensees gain a competitive edge in the marketplace. All licensing activities are conducted under policies relating to the strict nondisclosure of company proprietary information. 

Please visit the IPO website at https://ipo.llnl.gov/resources for more information on working with LLNL and the industrial partnering and technology transfer process.

Note:  THIS IS NOT A PROCUREMENT.  Companies interested in commercializing LLNL's modified cyclodextrins to counteract the effects of fentanyl and related opioids should provide an electronic OR written statement of interest, which includes the following:

1. Company Name and address.
2. The name, address, and telephone number of a point of contact.
3. A description of corporate expertise and/or facilities relevant to commercializing this technology.

Please provide a complete electronic OR written statement to ensure consideration of your interest in LLNL's modified cyclodextrins to counteract the effects of fentanyl and related opioids.

The subject heading in an email response should include the Notice ID and/or the title of LLNL’s Technology/Business Opportunity and directed to the Primary and Secondary Point of Contacts listed below.

Written responses should be directed to:

Lawrence Livermore National Laboratory

Innovation and Partnerships Office

P.O. Box 808, L-779

Livermore, CA  94551-0808

Attention: IL-13067