ENA-001 / Enalare Therap - LARVOL DELTA

ENA-001 for Opioid Induced Respiratory Depression (clinicaltrials.gov) - P1 | N=62 | Completed | Sponsor: Enalare Therapeutics Inc. | Recruiting ➔ Completed | N=36 ➔ 62 | Trial completion date: Dec 2026 ➔ Aug 2026

Enrollment change • Trial completion • Trial completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

Need for Pharmacologic Targets and Therapeutics for Postoperative Respiratory Depression and Pulmonary Complications in Veterinary Medicine. (PubMed, J Pain Res) - "To counteract the problems of analgesic and other respiratory depressants used in veterinary surgery, pharmacologically targeted mitigation strategies are needed to advance perioperative respiratory safety. The use of novel (namely inhibition of BK-channels), peripherally-acting (on the carotid bodies), "agnostic" (ie, independent of the drug cause) respiratory stimulants might represent a future therapeutic option."

Journal • Review • Addiction (Opioid and Alcohol) • Anesthesia • CNS Disorders • Depression • Pain • Psychiatry • Respiratory Diseases

Targeting the Carotid Body Function With Big-K+-Channel Blocker ENA-001 in Opioid-Induced Respiratory Depression: A Scoping Review. (PubMed, Pharmacol Res Perspect) - "ENA-001 increased ventilation and attenuated respiratory depression induced by morphine and the combination of xylazine and fentanyl...In experimental human models of alfentanil- and propofol-induced respiratory depression, ENA-001 significantly improved isohypercapnic minute ventilation and fully restored the hypoxic ventilatory response, respectively, without impairing sedation or analgesia...In conclusion, ENA-001 is a first-in-class, peripherally acting respiratory stimulant that effectively reverses drug-induced respiratory depression. These findings support its continued clinical development for opioid- and anesthetic-induced respiratory compromise."

Journal • Review • Anesthesia • CNS Disorders • Depression • Mood Disorders • Psychiatry

Combination of the BK-Channel Antagonist ENA-001 and Naloxone Is More Effective Than Either Agent Alone in Reversing Fentanyl-Induced Respiratory Suppression in Rats. (PubMed, Cureus) - "Results Pretreatment with naloxone and ENA-001 together was more effective (p < 0.001) in attenuating fentanyl-induced respiratory suppression than either agent alone (p < 0.05 and 0.01, respectively), and the combination did not compromise the body rigidity recovery timeline. Conclusions In this rat model of fentanyl-induced effects associated with overdose, coadministration of the combination of the opioid antagonist naloxone and the BK channel antagonist ENA-001 represents a potentially more effective treatment of fentanyl overdose than either agent alone."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Psychiatry

ENA-001 for Opioid Induced Respiratory Depression (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Enalare Therapeutics Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Mood Disorders • Psychiatry

ENA-001 for Post Operative Respiratory Depression (PORD) (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Enalare Therapeutics Inc. | Trial completion date: Dec 2026 ➔ Jul 2027 | Trial primary completion date: Dec 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

ENA-001 for Opioid Induced Respiratory Depression (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Enalare Therapeutics Inc. | Recruiting ➔ Active, not recruiting | N=18 ➔ 36 | Trial completion date: Nov 2025 ➔ Dec 2026 | Trial primary completion date: Nov 2025 ➔ Jul 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

ENA-001 for Opioid Induced Respiratory Depression (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Enalare Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Mood Disorders • Psychiatry

ENA-001 for Opioid Induced Respiratory Depression (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Enalare Therapeutics Inc.

New P1 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry

ENA-001 for Post Operative Respiratory Depression (PORD) (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Enalare Therapeutics Inc. | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

ENA-001 Reverses Xylazine/Fentanyl Combination-Induced Respiratory Depression in Rats: A Qualitative Pilot Study. (PubMed, Cureus) - "Based on the results of this pilot study, the "agnostic" nature of ENA-001 respiratory stimulation appears to extend to XFC-induced overdose. Given the urgent clinical need, additional study seems warranted."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Mood Disorders • Psychiatry

ENA-001 improves ventilation in spontaneously breathing late-preterm lambs; Exploratory study for a novel respiratory stimulant (AAP-NCE 2024) - "In the late-preterm lamb, ENA-001 improved tidal volumes leading to better ventilation in a more stable breathing pattern, without exceeding target blood gas values (i.e., absence of hyperventilation). These exploratory data demonstrate that ENA-001 may be a promising therapy for infants with breathing abnormalities associated with immaturity. Further research is required on dosage and safety."

Prematurity

ENA-001 for Post Operative Respiratory Depression (PORD) (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: NEMA Research, Inc. | Trial completion date: Sep 2025 ➔ Dec 2025 | Initiation date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

ENA-001, an Agnostic Respiratory Stimulant, Reverses Xylazine-Fentanyl Induced Respiratory Depression in Rats (CPDD 2024) - "ENA-001 was able to completely and rapidly (<5 minutes) reverse RD associated with an overdose of xylazine mixed with fentanyl. ENA-001 thus appears to be a promising therapy for such an overdose."

Preclinical • CNS Disorders • Depression • Psychiatry

A Single Ascending-Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Respiratory Stimulant ENA-001. (PubMed, Cureus) - "Conclusions The respiratory stimulant ENA-001 demonstrated well-behaved pharmacokinetics following the two-hour infusion. Mean peak plasma concentrations and the mean total systemic exposure values were approximately dose-proportional in the dose range studied."

Journal • PK/PD data • CNS Disorders • Depression • Psychiatry

ENA-001, a BK-Channel Blocker, Stimulates Breathing Without Analeptic Side Effects (SCCM 2024) - "It has been previously reported that ENA-001 increased minute ventilation (MV) in healthy subjects and reduces arterial pCO2 in alfentanil-induced. The data from this study showed that treatment with high dose ENA-001 significantly increased the AHR compared to placebo, both with and without co-administration of clinically relevant plasma concentrations of propofol. ENA-001 did not impact propofol-induced sedation while also maintaining a favorable safety profile. These finding support that ENA-001 is a respiratory stimulant with potential for use in clinical practice, inducing stimulation of MV without antagonizing other drugs."

Adverse events • Anesthesia • Cardiovascular • CNS Disorders • Depression • Psychiatry

Reversal of propofol-induced depression of the hypoxic ventilatory response by BK-channel blocker ENA-001: a randomized controlled trial. (PubMed, Anesthesiology) - "In this pilot study, we demonstrated that ENA-001 restored the hypoxic ventilatory response impaired by propofol. This finding is not only of clinical importance, but also provides mechanistic insights into the peripheral stimulation of breathing with ENA-001 overcoming central depression by propofol."

Journal • Anesthesia • CNS Disorders • Depression • Mood Disorders • Psychiatry

ENA-001 for Post Operative Respiratory Depression (PORD) (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: NEMA Research, Inc.

New P2 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry

Influence Of Bk-channel Blocker Ena-001 On Propofol-induced Depression Of The Hypoxic Ventilatory Response (ASA 2023) - "ENA-001 is able to restore the propofol-impaired HVR increasing patient safety from a blunted HVR. This is also an important mechanistic observation in that that peripheral stimulation of breathing with ENA-001 overcomes central depression by propofol without any signs of ceiling."

Anesthesia • CNS Disorders • Depression • Mood Disorders • Psychiatry