Funded Projects

Project # Project Title Sort descending Research Focus Area Research Program Administering IC(s) Institution(s) Investigator(s) Location(s) Year Awarded
1UG3DA050306-01
1-Year Sustained Release Naltrexone Implant for the prevention of relapse to opioid dependence Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Delpor, Inc. Martin, Francis South San Francisco, CA 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

There is a need for longer-acting prophylactic pharmacologic options for opioid use disorder (OUD) patients during maintenance therapy. This study tests a titanium implant loaded with a formulation of naltrexone and a naturally occurring carboxylic acid. The device is implanted subcutaneously with local anesthetic during an in-office procedure. The technology is based on a unique formulation that keeps the pH within the reservoir low and promotes passive diffusion of naltrexone. The benefits of the product include complete medication adherence for one year after administration, fewer relapses, smooth profile ensuring complete prophylaxis without sub-therapeutic plasma troughs, full reversibility, and similar efficacy with less drug exposure. This technology has been validated clinically with another drug and tested preclinically with naltrexone. This project will finalize the chemistry manufacturing and controls, produce IND supplies, conduct an IND-enabling safety study, and submit the IND.

1UG3DA048338-01A1
A Long-Acting Bioabsorbable Naltrexone Subcutaneous Implant for Opioid Use Disorder Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA DRUG DELIVERY COMPANY, LLC, THE COHEN, STEVEN M; BENNER, JEFFREY Salisbury, MD 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Naltrexone (NTX) has proven to be an important, safe, and effective therapy for helping patients overcome opioid use disorders (OUD) and for preventing overdose. Unfortunately, the therapeutic potential of NTX has been blunted by poor adherence. To combat this issue, a system must be developed to deliver NTX for longer durations than currently available and with a more patient-friendly format. To address this problem, we will develop a long-acting and bioabsorbable NTX subcutaneous implant for the treatment of OUD. The proposed research will (a) determine the optimal chemical preparation of NTX inside the implant, (b) optimize the composition and porosity of the drug delivery substrate, and (c) refine the surgical procedure and instrumentation to be used during implantation. Once the safety and efficacy of this novel NTX implant is established, we will conduct the necessary clinical trials. The proposed study is highly relevant to and complementary of other efforts, either in consideration or already deployed to stem the tide of the lingering opioid crisis. If successful, this solution has the potential to enhance health, lengthen life, and reduce illness and disability for those suffering from OUD.

1R01DA048417-01
A novel opioid receptor antagonist for treating abuse and overdose Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA UNIVERSITY OF TEXAS HLTH SCIENCE CENTER France, Charles P San Antonio, TX 2019
FOA Title: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
FOA Number: PA-18-484
Summary:

Deaths from opioid overdose continue to rise; from 2015 to 2016, there was a 28 percent increase in the number of fatal overdoses. Currently available pharmacotherapies include MOR agonists (e.g., buprenorphine) and antagonists (e.g., naloxone), all of which suffer from specific and clear limitations. To address the main deficits in these treatments, the researchers will develop and optimize medications with longer duration of action that prevent and reverse the effects of opioids in a manner that is not surmounted by increasing doses of agonist. Their pilot studies in monkeys show that the pseudo irreversible MOR selective antagonist methocinnamox (MCAM) decreases heroin but not cocaine self-administration, decreases choice for remifentanil in a food/drug choice procedure, and reverses—as well as protects against—respiratory depression by heroin, with a single injection being effective for a week or longer. Bringing a medication like this to marketable fruition could significantly improve the treatment of OUD and save lives by providing insurmountable extended protection after rescue from overdose, including from ultra-potent fentanyl analogs.

1UG3DA047680-01
A novel therapeutic to ameliorate chronic pain and reduce opiate use Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA LOHOCLA RESEARCH CORPORATION TABAKOFF, BORIS Aurora, CO 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

More than 100 million adults in the U.S. suffer from intermittent or constant chronic pain, and chronic pain affects at least 10 percent of the world’s population. The primary pharmaceuticals for treatment of chronic pain have been natural or synthetic opioids, and the use of opioids for pain treatment has resulted in what has been called an “epidemic” of opioid abuse, addiction, and lethal overdoses. Through a process of rational drug design, the research team has generated a new chemical entity (NCE) and have given it the name Kindolor, a non-opiate, non-addicting molecule that was shown to reduce or eliminate chronic pain in five animal models at doses compatible with use of Kindolor in humans. This project intends to complete the pre-clinical studies required for an IND application, which, if approved, would allow for proceeding onto the Phase 1 and 2 studies to assess safety and efficacy of the compound against osteoarthritic pain.

1UG3DA050310-01
A once-weekly oral methadone for maintenance therapy for opioid use disorder Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Lyndra Therapeutics, Inc. Bellinger, Andrew; Zale, Steve Boston, MA 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Methadone maintenance therapy has been shown to facilitate recovery and prevent deaths from opioid use disorder (OUD). This proposal is for development of a once-weekly oral methadone for maintenance therapy for OUD. Lyndra has developed an oral gastric residence dosage form that has been demonstrated to provide at least seven days of continuous delivery. A once-weekly oral methadone product could lower a major barrier to treatment for many patients, reduce the stigma and socioeconomic impact of medication-assisted therapy, and increase the capacity of methadone treatment centers by reducing the number of patient visits. This study will perform pharmaceutical development and pharmacological characterization of a once-weekly oral methadone dosage form, leading to the selection of a clinical candidate for a first-in-human trial and submission of an IND. Clinical trials will then be performed to evaluate the safety and pharmacokinetics of the once-weekly oral methadone dosage form in subjects with OUD.

1UG3DA048351-01
A Phase I/IIa Clinical Trial Testing the Safety and Immunogenicity of a Heroin Vaccine and its Efficacy Against Morphine Challenge. Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA HENRY M. JACKSON FDN FOR THE ADV MIL/MED MATYAS, GARY R Bethesda, MD 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

In order to address the opioid crisis, this group has developed a candidate heroin/opioid vaccine that induces antibodies that bind heroin/opioid upon injection and subsequently prevent the drug from crossing the blood-brain barrier and interacting with the brain's µ-opioid receptor. They completed pre-clinical testing of the vaccine candidate in mice and rats and demonstrated that the animals were protected from subcutaneous and intravenous heroin challenge. Ongoing durability studies have demonstrated that antibody titer and protective efficacy were maintained 6 months after the last vaccination. This project proposes to advance the development of the vaccine candidate by conducting a Phase I/IIa human clinical trial, by performing vaccine synthesis, nonclinical studies, and then a clinical trial. The supplemental award will allow for testing the efficacy of fentanyl haptens and of the combination heroin–fentanyl vaccine.

1UG3DA048351-01S1
A Phase I/IIa Clinical Trial Testing the Safety and Immunogenicity of a Heroin Vaccine and its Efficacy Against Morphine Challenge. Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA HENRY M. JACKSON FDN FOR THE ADV MIL/MED MATYAS, GARY R Bethesda, MD 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
1UG3DA048743-01
Advancing KNX100 for the treatment of opioid withdrawal: preclinical efficacy and toxicology, and a phase 1 clinical program. Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Kinoxis Therapeutics, PTY LTD MacGregor, Iain Camberwell, Vic, Australia 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Kinoxis has developed a novel small-molecule lead, KNX100, that reduces the severity of opioid withdrawal symptoms in preclinical animal models of opioid use disorder (OUD). KNX100 was discovered from a phenotypic screen of compounds derived from a fragment-based drug discovery program targeting the brain oxytocin system. KNX100 has a favorable pharmacokinetic and safety profile and has undergone testing for efficacy signals in two rodents and two non-human primate species. The proposed activity is to progress the development of KNX100 to treat opioid withdrawal in OUD. The overall objective of the project is to establish the safety and tolerability of KNX100 to enable human efficacy testing to commence in patients requiring treatment for opioid withdrawal. The long-term objective for this development program is to generate human efficacy data to support KNX100 as a potential treatment for opioid withdrawal symptoms and ultimately enable a New Drug Application to the FDA.

1UG3DA050923-01
AMPA Antagonism: A Novel Pharmacology for Launching Recovery from Opioid Addiction Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS Chambers, Robert Indianapolis, IN 2020
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

The excruciating multiday experience of opioid withdrawal syndrome (OWS), is exacerbated by the opioid antagonist drugs naloxone and naltrexone. This industry-academia collaboration will explore the potential of the glutamate AMPA receptor antagonist Tezampanel (TZP). Animal studies have shown reduced hyperactivity in brain circuits involved in OWS, without relying on direct stimulation or antagonism of the opioid system ,and has already been delivered to over 500 human subjects and found to be safe for a potential migraine indication. This proposal will build up the evidence needed to apply for and conduct open label and blinded placebo-controlled human trials of TZP safety and efficacy for OWS. If successful, this project will allow planning for a pivotal registration trial for TZP for OWS, and as a transitional treatment to long-term recovery on naltrexone and help us stem the tide of the opioid crisis.

1UG3DA047709-01
An ultra-long-acting oral treatment for opioid use disorder Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA LYNDRA THERAPEUTICS, INC. BELLINGER, ANDREW MARTIN Boston, MA 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Buprenorphine (BUP) is an FDA-approved medication-assisted therapy (MAT) that improves outcomes and saves lives in patients with opioid use disorder (OUD). It is available in multiple dosage forms and routes of administration, including daily sublingual (SL) and buccal tablets and films, a monthly subcutaneous (SC) injectable, and a 6-month SC implant; however, these forms leave many patients untreated or undertreated. This product, in a partnership with Lyndra Therapeutics, aims to develop a once-weekly oral BUP dosage form for maintenance therapy for OUD, using a new oral dosage formulation developed by Lyndra. A long-acting oral BUP may address important limitations of current MATs by providing improved PK with less euphoria than SL, a patient- and provider-preferred route of administration, and an optimal dosing interval for improved patient adherence with the potential for cost-effective direct observed therapy.

1UG3DA048379-01
Arylepoxamides: A new class of potent, safer analgesics Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA SLOAN-KETTERING INST CAN RESEARCH PAN, YING-XIAN New York, NY 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

The expansion of opioid prescribing in recent years to better treat pain has markedly increased their usage and availability and fueled an epidemic of abuse. Up to 80 percent of addicts reported initiating their habit through prescriptions drugs. Decreasing opioid prescriptions would lower opioid exposure, with fewer people receiving the drugs and less drug available for diversion. Study investigators have identified a novel target in the brain, distinct from any of the traditional opioid receptors capable of mediating potent analgesia without the reward behavior and side effects seen with traditional opioids. They targeted this site with a series of arylepoxamides and have identified a clinical candidate (MP1000) and backup compound. MP1000 is a potent analgesic in a range of thermal, inflammatory, and neuropathic analgesic assays. It fails to show reward behavior and does not produce respiratory depression at doses 5-fold greater than its analgesic ED50. Chronic administration does not produce physical dependence or withdrawal when challenged with an antagonist. It shows no cross tolerance to morphine and can be co-administered to subjects already on opioids for pain to lower their opioid usage (i.e., opioid sparing), facilitating the eventual discontinuation of the opioid. If successful, this project could lead to the development of a viable alternative to current opioid-based analgesics with reduced side effects (such as reward and respiratory depression) compared to opioids.

1UG3DA047700-01
Biased Mu-Opioid Receptor Analgesics to Prevent Overdose and Opioid Use Disorders Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA MEBIAS DISCOVERY, LLC KUO, LAWRENCE C Philadelphia, PA 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

The adverse effects of morphine and other mu-opioid receptor (MOR) agonists are linked to the ?-arrestin pathway, while analgesia is tied to the G-protein pathway. Pathway specific or “biased” drug development can target G-protein specific agonists that avoid the negative consequences of ?-arrestin signaling activation and produce analgesia. Highly “biased” MOR agonists have promise as effective analgesics but devoid of opioid-induced adverse effects. Preclinical studies compared two compounds, MEB-1166 and MEB-1170, against Oliceridine and morphine. Both compounds displayed no respiratory depression, even at high doses, while morphine and Oliceridine significantly reduced respiratory function. In contrast to morphine, neither MEB-1166 nor MEB-1170 produced conditioned place preference, suggesting an absence of abuse liability. This study will characterize the pharmaceutical and pharmacological profiles and perform liability studies for these compounds.

UG3DA051383-01A1
Brexpiprazole as an Adjunctive Treatment to Buprenorhpine to Treat Opioid Use Disorder Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA OTSUKA PHARMACEUTICAL DEVELOPMENT & COMMERCIALIZATION, INC. Forbes, Andy Princeton, NJ 2020
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Over 2 million Americans have an Opioid Use Disorder (OUD) and the risks associated with misuse of opioids have prompted a public health crisis. There are three effective FDA-approved drugs for medication assisted treatment (MAT) of OUD. However, while MAT can reduce overall OUD related mortality by as much as fifty percent, relapse and treatment discontinuation are common within the first 5 to 12 weeks of MAT. As longer treatment retention is correlated with better long-term outcomes, the development of an adjunctive medication to alleviate key psychiatric symptoms associated with treatment failure would address an important unmet need. This study seeks to evaluate the safety and efficacy of brexpiprazole as adjunctive treatment to buprenorphine/naloxone in OUD. If successful, this study could enhance the effectiveness of OUD treatments by extending the duration of treatment, thereby reducing the likelihood for relapse and overdose.

1UG3DA048388-01
Cannabidiol Effects on Craving and Relapse Prevention in Opioid Use Disorder Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA INSYS DEVELOPMENT COMPANY ELKASHEF, AHMED Chandler, AZ 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

To tackle the national public health emergency posed by opioid misuse, addiction, and overdose deaths, the development of effective new medications and the FDA drug approval process must be accelerated. In response to this call, INSYS Development Company, Inc. (INSYS) has developed a cannabidiol (CBD) oral solution that shows promise as a novel medication for prevention of relapse that addresses one of the five opportunities specified in the HEAL Initiative to improve treatment options. The first phase of this project involves clinical trials of CBD on cue-induced cravings, modulation of withdrawal, alterations of negative affect states, relapse to opioid use, and treatment retention in patients with OUD receiving buprenorphine treatment in a residential drug treatment facility. The findings from this phase will inform further studies in an outpatient setting. If successful, this project could advance to the development of a new monotherapy for the treatment of OUD.

1UG3DA050323-01
Cannabidiol in the treatment of opioid use disorder Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Icahn School of Medicine Mount Sinai Hurd, Yasmin New York, NY 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Responding to urgent calls for non-opioid treatment, this research group has been evaluating the therapeutic potential of cannabidiol (CBD), a non-intoxicating cannabinoid, for the treatment of some clinical aspects of opioid use disorder (OUD). Preclinical animal studies show that CBD decreases cue-induced heroin-seeking behavior during drug abstinence, associated with incubation of craving. Clinical work has also shown that CBD was safe in combination with a potent opioid agonist to address a potential relapse condition and decreased craving and anxiety associated with heroin cues in abstinent individuals with heroin use disorder. Building on this foundation, the researchers will investigate an oral CBD powered by a novel patented technology (leveraging the kinetics of long-chain fatty acid absorption) in a gelcap delivery system that improves bioavailability, reduces the incidence of gastrointestinal side effects, reduces first pass metabolism, and enhances onset time. This study could lead to the development of a non-opioid, non-intoxicating FDA-approved medication to reduce opioid craving and relapse and restore global functioning in individuals with OUD.

1UG3DA050308-01
Clinical Evaluation of C4X3256, a Non-Opioid, Highly-Selective Orexin-1 Receptor Antagonist for the Treatment of Opioid Use Disorder Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Indivior Heidbreder, Christian North Chesterfield, VA 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

There is a need for pharmacologic treatment options for opioid use disorder (OUD) that do not pose addiction liability and do not require complete withdrawal from opioids prior to treatment. Nonclinical studies support a role for the orexin system in drug seeking; compounds that selectively block signaling at the orexin-1 receptor (OX1R) reduce drug use. C4X3256, a non-opioid, highly selective OX1R antagonist, has a long residence time at the OX1R along with reduced intravenous self-administration and cue-induced reinstatement in animal models of nicotine addiction, suggesting it could be an addiction treatment. Proposed studies will move C4X3256 from preclinical development through Phase I testing in subjects with OUD. The clinical, preclinical, and supporting pharmaceutical development studies proposed will allow C4X3256 to move to Phase II studies.

1UG3DA048508-01
Combined tDCS and Cognitive Training for the Treatment of Opioid Addiction Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of Minnesota Lim, Kelvin Minneapolis, MN 2019
FOA Title: Device-Based Treatments for Substance Use Disorders (UG3/UH3, Clinical Trial Optional)
FOA Number: PAR-18-494
1UG3DA049694-01
Combining Pregabalin with Lofexidine: Can it Increase the Success of Transition to Naltrexone? Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of Pennsylvania Kampman, Kyle Philadelphia, PA 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Extended-release naltrexone (XR-NTX) reduces overdose risk; however, transitioning to XR-NTX requires detoxification, which is a major hurdle. Non-opioid detoxification with an alpha-2 adrenergic receptor agonist, such as lofexidine, may shorten detoxification time, but it does not reduce the subjective effects of withdrawal. Pregabalin potentiates the activity of glutamic acid decarboxylase, inhibits calcium influx and release of excitatory neurotransmitters, raises GABA levels, and is approved for neuropathic pain, for fibromyalgia, and as an adjunctive therapy for adults with partial onset seizures. The study will test whether pregabalin can be combined with lofexidine to better reduce the subjective effects of opioid withdrawal than lofexidine alone and increase the proportion of patients that transition to XR-NTX. Such a dosing combination could lower the detoxification hurdle for patients who are interested in antagonist treatment or who are in settings where it is unavailable or difficult to access.

1UG3DA047925-01
Development of a 3-month implantable depot pellet of Naltrexone for the treatment of Opioid Use Disorder. Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA BIOCORRX, INC. BRAR, BALBIR Anaheim, CA 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

The opioid antagonist naltrexone (NTX) is a proven treatment for opioid use disorder (OUD); however, lack of adherence is a serious limitation that has prevented NTX from reaching its maximum therapeutic potential. To address this limitation, BioCorRx is developing BICX102, a subcutaneous solid depot pellet of NTX, a single implantation of which can provide continual blockade of opioid receptors for up to 3 months. This can prevent patients from being adversely affected by almost any opioid relapse event, while improving efficacy and adherence to behavioral programs that support long-term management and recovery. This proposal comprises the steps required to achieve FDA approval. Successful development of BICX102 would result in a safe and effective 3-month subcutaneous depot pellet/implant containing NTX (1,000 mg) that would be far less reliant on patient compliance.

1UG3DA048234-01
Development of a novel drug for treating opioid use disorder Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA NIRSUM LABORATORIES, INC. TUSCHE, MICHAEL; SHAH, NIKEJ New York, NY 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

The ongoing epidemic of opioid use disorder (OUD), overdose, and death is unprecedented. Available pharmacologic therapies for OUD have failed to stem the tide, plagued by poor adherence and retention, the principal factors associated with relapse and treatment failure. More than 80 percent of individuals with OUD are untreated. More treatment options are needed. This proposal seeks to develop a better antagonist-based OUD pharmacotherapy for populations highly motivated to achieve abstinence, such as military personnel, criminal justice clients, and the currently employed. A series of novel and proprietary small molecules will be designed and synthesized to address the adherence problem by inducing effective opioid antagonism with a single injection lasting at least 2 months, and up to 4 months or more. The goal of this project is to advance to Phase 3 clinical trials toward FDA approval of our lead compound. If successful, this project could lead to a novel therapeutic with superior adherence and retention, resulting in a significant public health impact by reducing rates of relapse, overdose, and death.

1UG3DA049599-01
Development of a Potent and Highly Selective NaV1.7 Inhibitor for the Treatment of Acute Pain with the Goal of Reducing Opioid Use and Preventing Opioid Use Disorders Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of British Columbia Hunter, John; Phillips, Anthony Vancouver, BC, Canada 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
1UG3DA047708-01
Development of a safe and effective novel mechanism analgesic to treat moderate to severe pain with low or absent abuse liability. Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA ARTYS BIOTECH, LLC LARK, MICHAEL WILLIAM; ZADINA, JAMES E Plymouth Meeting, PA 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Chronic pain affects an estimated 100 million Americans, or one third of the U.S. population, and it is the primary reason Americans are on disability. Although many treatments are available for pain, the most potent class of analgesics relies on opioid analogs, whose limitations and well-known adverse effects have contributed to the present opioid crisis. New pharmacotherapies for pain management are sorely needed. MTX1604, a synthetic endomorphin analog, has emerged as a highly effective analgesic that exhibits reduced reward potential and respiratory suppression, and a robust duration of efficacy in a variety of validated animal models of acute, neuropathic, inflammatory, post-operative, and visceral pain. This project will generate additional preclinical characterization data of MTX1604 and advance clinical development toward FDA approval. If successful, this medication development project could offer patients a novel non-addictive, potent, and safe analgesic and thus have a direct impact on the opioid crisis.

1UG3DA048767-01
Development of a Soluble Epoxide Hydrolase Inhibitor to Spare or Replace Opioid Analgesics Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Eicosis, LLC Hammock, Bruce Davis, CA 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

EicOsis is developing a first-in-class analgesic with efficacy against neuropathic pain that will reduce or replace the need for opioids and thus potentially prevent opioid use disorder (OUD). The target of the small molecule inhibitor EC5026 is the soluble epoxide hydrolase, a master regulatory enzyme that modulates the activity of endogenous bioactive lipids. The study will reach the next steps in clinical human clinical trials with EC5026 through additional preclinical studies to expand the efficacy into models of chronic pain conditions. Additionally, detailed pharmacokinetic, metabolism, and distribution studies are proposed that will provide the required information to optimize drug formulation and for advanced clinical trials examining efficacy in humans. EicOsis is meeting current development goals, and EC5026 is well positioned to meet the urgent need of reducing opioid use.

1UG3DA050303-01
Development of an implantable closed-loop system for delivery of naloxone for the prevention of opioid-related overdose deaths Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Washington University Rogers, John St. Louis, MO 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Current opioid overdose treatment requires administration of naloxone by first responders, which requires timely identification of the overdose, the need for a rescue injection, and immediate availability of the medication. The development of a fail-safe treatment that would provide a life-saving dose of naloxone without the need for intervention by another party could significantly reduce mortality. The researchers aim to develop a new medical device comprising an implantable, closed-loop system that senses the presence of an opioid overdose, automatically administers a life-saving bolus injection of naloxone, and simultaneously alerts first responders.

1UG3DA047699-01
Development of ITI-333, a ?-opioid Receptor Partial Agonist and 5HT2A and D1 Receptor Antagonist, for the Treatment of Opioid Use Disorders Novel Medication Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA INTRA-CELLULAR THERAPIES, INC. VANOVER, KIMBERLY E New York, NY 2019
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: RFA-DA-19-002
Summary:

Deaths from opioid overdose continue to rise; from 2015 to 2016, there was a 28 percent increase in the number of fatal overdoses. Currently available pharmacotherapies include MOR agonists (e.g., buprenorphine) and antagonists (e.g., naloxone), all of which suffer from specific and clear limitations. To address some of the key limitations, Intra-Cellular Therapies Inc (ITI) is developing ITI-333, a novel compound with high-affinity activity at mu opiate (MOP), 5-HT2A, and D1 receptors, that lacks abuse liability and thus offers great promise for the treatment of opioid use disorders. This proposal is for a 2-year UG3 program, including a first-in-human, single ascending dose (SAD) study to assess the safety, tolerability, and pharmacokinetics of ITI-333 in healthy volunteers. This study will then be repeated in a single-center in-patient study with the goal of determining a maximally- tolerated dose (MTD) and completed with human abuse liability and functional pharmacology studies. Together, the researchers believe this clinical development plan will inform further development of ITI-333 and the selection of a cogent Phase 3 clinical path toward FDA approval as a medication for the treatment of OUD.