Funded Projects

NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
NOFO Number: PAR-19-327
Summary:

Naloxone is a safe and effective opioid antagonist, but currently available products are burdened with high cost and limited accessibility due to a need for a prescription or being kept behind-the-counter. In response to the FDA putting out an unprecedented call for an over the counter naloxone product, Pocket Naloxone Corp. is developing a novel intranasal delivery method for naloxone intended to be low-priced and widely accessible. This project will culminate in a New Drug Application to the FDA for over-the-counter approval to meet the urgent need for widespread access to a reliable, easy-to-use naloxone product for use in an emergency by non-medical individuals.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092
Summary:

The sodium channel NaV1.8 is a promising target for the development of effective, non-addictive pain medications. Recent evidence from clinical studies indicates that medications that target NaV1.8 are effective at managing postoperative, neuropathic, and inflammatory pain, but with side effects and prohibitively high cost. This project will test the safety and compatibility in the body of an NaV1.8-targeted molecule, toward developing an effective, non-addictive, once daily oral medication for the treatment of acute postsurgical pain and chronic neuropathic. 

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO 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.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)
NOFO Number: PA-18-575
Summary:

One of the current critical needs in addressing the opioid crisis is the development of new overdose-reversal interventions, including wearable technologies that can detect an (impending) overdose from physiological signals to signal for help, or trigger a coupled automated injection of naloxone. This project tests the approach of monitoring respiration by detecting the sounds of breathing in the trachea. This proposal aims to develop a machine learning algorithm that could process those sounds, detect the kinds of patterns of reduced breathing that occur during an opioid overdose, and design a miniature wireless sensor that could be used to detect those sounds. Such a sensor and algorithm could be a key component to a device to detect and intervene in overdoses.

NOFO Title: Developing Regulated Therapeutic and Diagnostic Solutions for Patients Affected by Opioid and/or Stimulants use Disorders (OUD/StUD) (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-23-021
Summary:

There are a lack of clinical tools to effectively identify and monitor opioid use disorder (OUD). This project will develop and test a clinically usable device that uses a range of data inputs and an artificial intelligence (AI) algorithm to help health care providers diagnose and treat OUD. The research aims to help providers choose treatment plans and monitor the timing of release from rehabilitation clinics.

NOFO Title: HEAL Initiative: Planning Grants for Efficacy or Effectiveness Trials of Recovery Support Services for Individuals Treated with Medications for Opioid Use Disorder (R34 Clinical Trial Optional)
NOFO Number: RFA-DA-22-034
Summary:

Many people intending to take medications for opioid use disorder, including buprenorphine, as part of their recovery pathway do not stay in treatment long enough to reduce risk for overdose. These individuals also often continue to use one or more other drugs during treatment, which may further raise their overdose risk. This project will develop and conduct a preliminary test of an innovative integrated intervention that combines buprenorphine treatment with recovery coaching and online cognitive behavioral therapy. This research will assess whether the approach reduces drug use during buprenorphine treatment and helps people stay in treatment longer.

NOFO Title: HEAL Initiative: Translational Development of Devices to Treat Pain (U18 Clinical Trial Not Allowed)
NOFO Number: RFA-EB-18-003
Summary:

This project aims to develop a next-generation noninvasive neuromodulation system for non-addictive pain treatments. The research team will build an integrated system that uses magnetic resonance image-guided focused ultrasound (MRgFUS) stimulation to target pain regions and circuits in the brain with high precision. The system will use MR imaging to locate three pain targets commonly used in clinical pain treatments, to stimulate those targets with ultrasound, and to monitor responses of nociceptive pain circuits using a functional MRI readout. Three collaborating laboratories will tackle the goals of this project: (Aim 1) Develop focused ultrasound technology for neuromodulation in humans, compatible with the high magnetic fields in an MRI scanner. (Aim 2) Develop MRI technology to find neuromodulation targets, compatible with focused ultrasound transducers. (Aim 3) Validate the complete MRgFUS neuromodulation system in brain pain regions in nonhuman primates. By the end of the project, the research team will have a fully developed and validated MRgFUS system that is ready for pilot clinical trials in pain management.

NOFO Title: HEAL Initiative: Translational Development of Devices to Treat Pain (U18 Clinical Trial Not Allowed)
NOFO Number: RFA-EB-18-003
Summary:

For patients with neuropathic pain refractory to therapy using small molecules, modulation of specific neural structures in the central or peripheral nervous system can provide effective alternative treatments. While current Food and Drug Administration–approved devices for dorsal root ganglion (DRG) stimulation are safe and effective, there have been an unfortunate number of adverse events associated with pulse generator infections and lead migration. The research team will develop a wireless, millimeter-sized nerve stimulator that can be delivered through the vasculature and stimulate the DRG to alleviate symptoms of neuropathic pain and the associated minimally invasive delivery method. This endovascular nerve stimulation (EVNS) system depends on development and integration of key novel technologies into an endovascular stent. The magnetoelectric transducers and electronic circuits will convert wireless power and data into stimulus patterns that can trigger neural activity in the DRG via miniature electrodes. After chronic demonstration of safety and functionality in large animal models, the team will prepare for regulatory discussions with the FDA. If successful, the EVNS will provide a technology platform for treating other neuropathic pain syndromes. 

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

With the entwined crises of opioid use and chronic pain, there is a need for alternative, safe therapies to manage opioid use disorder, opioid withdrawal symptoms, chronic pain, and/or associated anxiety and depression. A proof-of-concept preclinical study has already been conducted of a cannabinoid-opioid combination that demonstrated opioid-sparing and synergistic analgesic effects, with the combination providing greater analgesia in a rodent model of chronic pain than a standard dose of the opioid alone. This proposal aims to develop a fixed-dose combination (FDC) of the cannabinoid-opioid that may have improved analgesia with lower opioid doses and thereby lower the risk of dependence, withdrawal, diversion, abuse, and overdose. Preclinical pharmacokinetic and ?in vivo ?safety studies will help determine if co-administration alters the pharmacokinetics and/or respiratory depression related to either compound in rodents.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO 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.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092
Summary:

The nation’s opioid epidemic remains a public health emergency, marked by high rates of opioid use and misuse among adults and a correlated rising incidence of neonatal opioid withdrawal syndrome (NOWS) in infants exposed to opioids before they are born. There are currently no pharmacotherapies approved by the Food and Drug Administration (FDA) for the treatment of NOWS. This research will complete manufacturing and clinical trial activities to evaluate and support FDA approval of a pediatric-appropriate formulation of lofexidine, a non-opioid medication approved for mitigation of opioid withdrawal symptoms in adults, as a first line-therapy in NOWS patients through two clinical trials to (1) identify an optimal dosing regimen of lofexidine for treatment of NOWS, and (2) evaluate the risks and benefits of its use in improving withdrawal symptoms, limiting infant exposure to other off-label narcotic medications and shortening the infant’s overall stay in the hospital.

NOFO Title: Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-19-010
Summary:

Although opioid-based analgesics have been proven effective in reducing the intensity of pain for many neuropathic pain conditions, their clinical utility is grossly limited due to the substantial risks involved in such therapy, including nausea, constipation, physical dependence, tolerance, and respiratory depression. Cumulative evidence suggests that human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain with limited side effects due to its restricted expression in nociceptors within the peripheral nervous system; however, direct activation of MRGPRX1 at peripheral terminals is expected to induce itch side effects, limiting the therapeutic utility of orthosteric MRGPRX1 agonists. This finding led to the exploration of positive allosteric modulators (PAMs) of MRGPRX1 to potentiate the effects of the endogenous agonists at the central terminals of sensory neurons without activating peripheral MRGPRX1. An intrathecal injection of a prototype MRGPRX1 PAM, ML382, effectively attenuated evoked, persistent, and spontaneous pain without causing itch side effects. The goal of this study is to develop a CNS-penetrant small-molecule MRGPRX1 PAM that can be given orally to treat neuropathic pain conditions.