UG3DA059286

A therapeutic agent to lower the level of synthetic opioids in the body - 1 Project Summary

There is an urgent need for a therapeutic that rapidly deactivates and removes fentanyl from the body. As stated by Dr. Nora Volkow, "deaths from fentanyl are increasing in spite of naloxone, and overdose requires multiple naloxone doses." This is a nationwide crisis, with over 73,000 overdose deaths annually, and over 3M people living with opioid use disorder.

Naloxone blocks mu-opioid receptors for a short period of time without affecting the level of fentanyl in the body, which can result in renarcotization. A single-dose therapeutic is needed that restores respiration immediately and removes fentanyl from the body at the maximum possible rate, the glomerular filtration rate (GFR), eliminating the possibility of renarcotization.

Our therapeutic agent, CS-1103, which works differently than naloxone, meets this need. After injection, CS-1103 binds to fentanyl in the bloodstream, rapidly reversing its effects, and dramatically increases the rate of fentanyl clearance into urine to near the GFR. In small and large animal models, we have demonstrated that CS-1103 is effective against synthetic opioids, ranging from fentanyl to carfentanil, restoring respiration in 2-3 min, reversing muscle rigidity in 1 min, preventing renarcotization after a lethal dose of carfentanil, and rapidly lowering opioid levels in the body. Furthermore, CS-1103 causes milder opioid withdrawal compared to naloxone, and does not interfere with the activity of naloxone.

We are currently developing IV CS-1103 to treat acute intoxication caused by drugs of abuse including methamphetamine. We have completed all required nonclinical studies and anticipate completion of the first-in-human phase 1a clinical trial in mid-2023. Based on results to date, we believe that phase 1a has a high probability of success, as CS-1103: (1) is a single use drug; (2) has an excellent safety profile in GLP studies in rat and canine with rapid clearance, at doses 500X the expected human therapeutic dose, similar to the sequestrants BRIDION® and CAPTISOL®; and (3) is highly effective and safe in non-human primates (NHP).

Our primary goal in this effort is to develop an IV formulation of CS-1103 for treatment of fentanyl intoxication and obtain FDA approval. This will be achieved via completion of specific aims 1-5 (UG3) and 6-9 (UH3):

AIM 1 will complete a pre-IND meeting with FDA for IV CS-1103.
AIM 2 will establish the safety/toxicology profile of IV CS-1103 in the presence of fentanyl, in rat.
AIM 3 will demonstrate that IV CS-1103 lowers the level of fentanyl in a dose-dependent manner, in rat.
AIM 4 will submit IND for IV CS-1103.
AIM 5 will establish the safety/dose level of IV CS-1103, in the presence of fentanyl, in a phase 1b clinical trial.
AIM 6 will determine effective clinical dose of CS-1103 to treat fentanyl intoxication in a phase 2a clinical trial.
AIM 7 will demonstrate efficacy of IV CS-1103 in lowering the level of fentanyl and restoring respiration, in a pivotal phase 2b trial.
AIM 8 will submit NDA for IV CS-1103.
AIM 9 will perform IND-enabling studies for CS-1103 suitable for IM injection and/or in administration. AIM 9 will be completed using our own funds, to expand use to field settings.

Clear Scientific

NOT APPLICABLE

93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

Cambridge, Massachusetts 021381002 United States

Single Zip Code

Development of Medications to Prevent and Treat Opioid and/or Stimulant Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional) (PAR-22-200)

Amendment Since initial award the total obligations have increased 101% from $3,035,865 to $6,087,655.