Small Molecule · Itruvone

Itruvone

Phase 2Pherin Pharmaceuticals, Inc.
  • Fast Track

Itruvone (development code PH10) is a synthetic, odorless neuroactive 'pherine' (vomeropherine) nasal spray in development for major depressive disorder. Chemically a pregnane steroid (pregn-4-en-20-yn-3-one). Administered intranasally at microgram-level doses, it is proposed to act on chemosensory neurons in the nasal passages that modulate olfactory-amygdala neural circuits, without systemic absorption or entry into the brain. Originated by Pherin Pharmaceuticals and developed by Vistagen Therapeutics.

Also known as: Itruvone, PH10, PH-10, 21321-89-1, pregn-4-en-20-yn-3-one

Data current as of

Key facts

Modality
Small molecule
Chemical class
neuroactive steroid, pregnane steroid
DEA schedule
Unscheduled
Chemistry
Single enantiomer
Mechanism
Nasal chemosensory neuron receptor (uncharacterized) unknown
Highest phase
Phase 2
Lead indication
Major depressive disorder
Developer
Pherin Pharmaceuticals, Inc.
Designations
Fast Track

Mechanism of action#

Itruvone is a synthetic neuroactive 'pherine' (vomeropherine) delivered as an intranasal microgram-dose spray. Its proposed rapid-onset mechanism is non-systemic: it engages and activates chemosensory neurons in the nasal passages that connect to olfactory-amygdala neural circuits, increasing activity of the limbic-hypothalamic sympathetic nervous system and catecholamine release to produce antidepressant effects. Preclinical biodistribution work found radiolabeled [14C]PH10 essentially undetectable in the brain, blood, and plasma after intranasal dosing, supporting a peripheral (nasal-neuron) site of action with no measurable systemic exposure. No characterized systemic molecular receptor target has been published; the nasal chemosensory receptor mediating its effect remains uncharacterized.

TargetActionAffinity
Nasal chemosensory neuron receptor (uncharacterized)primaryUnknown—ⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
Itruvone intranasal spraynasal spray
Microgram-level intranasal doses; Phase 2A studied 3.2 µg and 6.4 µg once daily for 8 weeks
IntranasalOnce daily—

Development timeline#

20192020202120222023Phase 216 Jul 2023 — Preclinical Data — Preclinical data: itruvone acts via peripheral nasal neurons without brain entry21 Jun 2023 — phase change — Favorable safety/tolerability results from U.S. Phase 1 bridging study (single-center, randomized, double-blind, placebo-controlled, healthy adults; first dosed Jan 2023, last patient last visit Mar 2023) announced; no serious adverse events or AE discontinuations. Enables planned U.S. Phase 2B development. Program remains Phase 2 overall.21 Jun 2023 — Phase 1 Results — Favorable U.S. Phase 1 safety results for itruvone (PH10)2 Feb 2023 — Acquisition — VistaGen Therapeutics completes acquisition of Pherin Pharmaceuticals6 Dec 2022 — phase change — FDA granted Fast Track designation for development of PH10 (itruvone) to treat major depressive disorder.6 Dec 2022 — Fast Track Designation — FDA Fast Track designation for itruvone (PH10) in MDD19 Feb 2020 — readout (met) — Positive Phase 2A study of PH10 (itruvone) in MDD: statistically significant rapid-onset antidepressant effect on HAM-D-17 vs placebo24 Oct 2018 — Option exercise — VistaGen exercises option for exclusive worldwide license to PH10 (itruvone) from Pherin
Phase change Readout Event UpcomingHover a marker for details.
Phase 2Oct 2018 – Jul 2023
  1. Preclinical DataPreclinical data: itruvone acts via peripheral nasal neurons without brain entry↗
  2. Favorable safety/tolerability results from U.S. Phase 1 bridging study (single-center, randomized, double-blind, placebo-controlled, healthy adults; first dosed Jan 2023, last patient last visit Mar 2023) announced; no serious adverse events or AE discontinuations. Enables planned U.S. Phase 2B development. Program remains Phase 2 overall.↗
  3. Phase 1 ResultsFavorable U.S. Phase 1 safety results for itruvone (PH10)↗
  4. AcquisitionVistaGen Therapeutics completes acquisition of Pherin Pharmaceuticals↗
  5. FDA granted Fast Track designation for development of PH10 (itruvone) to treat major depressive disorder.↗
  6. Fast Track DesignationFDA Fast Track designation for itruvone (PH10) in MDD↗
  7. metPositive Phase 2A study of PH10 (itruvone) in MDD: statistically significant rapid-onset antidepressant effect on HAM-D-17 vs placebo↗
  8. Option exerciseVistaGen exercises option for exclusive worldwide license to PH10 (itruvone) from Pherin↗

Itruvone for Major depressive disorder#

Phase 2ActiveMajor depressive disorder indication →

Itruvone (PH10) for major depressive disorder. A positive randomized, double-blind, placebo-controlled Phase 2A study (HAM-D-17 endpoint) was conducted in Mexico and published; a U.S. Phase 1 bridging safety study in healthy adults completed in 2023 with favorable safety/tolerability, enabling planned U.S. Phase 2B development as a non-systemic, stand-alone MDD treatment. FDA Fast Track designation granted December 2022. As of 2025, staged for potential U.S. Phase 2B (Vistagen or a strategic partner).

Readouts

  • 2020-02-19ReportedFull resultsmet

    Positive Phase 2A study of PH10 (itruvone) in MDD: statistically significant rapid-onset antidepressant effect on HAM-D-17 vs placebo ↗

Sources#

  1. Vistagen Announces Closing of Pherin Pharmaceuticals Acquisition — VistaGen Therapeutics, Inc.
  2. VistaGen Announces Positive Results of Newly Published Exploratory Phase 2a Study of PH10 for Rapid-Onset Treatment of Major Depressive Disorder — VistaGen Therapeutics / PR Newswire
  3. Vistagen Announces Results of Successful U.S. Phase 1 Study of Itruvone (PH10), Enabling U.S. Phase 2B Development for Treatment of Major Depressive Disorder — Vistagen Therapeutics / Business Wire
  4. Vistagen Receives FDA Fast Track Designation for Development of PH10 to Treat Major Depressive Disorder — Vistagen Therapeutics / Business Wire
  5. Vistagen Reports New Preclinical Data Supporting Itruvone (PH10) Nasal Spray — VistaGen Therapeutics
  6. Vistagen Reports New Preclinical Data Supporting Itruvone (PH10) Nasal Spray's Potential Antidepressant Activity via Peripheral Nasal Neurons without Entry into the Brain — Vistagen Therapeutics / Business Wire
  7. VistaGen Therapeutics Acquires Worldwide Rights to Develop and Commercialize PH10, a First-in-Class Intranasally Administered Neuroactive Steroid with Rapid-onset Antidepressant Effects for Major Depressive Disorder — VistaGen Therapeutics, Inc. (GlobeNewswire)