GlyphAllo (allopregnanolone) / PureTech - LARVOL DELTA

An Open-Label Extension Study to Evaluate the Safety and Tolerability of SPT-300 (GlyphAllo) in Participants With Major Depressive Disorder, With or Without Anxious Distress (BUOY-1 OLE Study) (clinicaltrials.gov) - P2 | N=360 | Enrolling by invitation | Sponsor: Seaport Therapeutics | Recruiting ➔ Enrolling by invitation

Enrollment status • Monotherapy • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

An Open-Label Extension Study to Evaluate the Safety and Tolerability of SPT-300 (GlyphAllo) in Participants With Major Depressive Disorder, With or Without Anxious Distress (BUOY-1 OLE Study) (clinicaltrials.gov) - P2 | N=360 | Recruiting | Sponsor: Seaport Therapeutics

Monotherapy • New P2 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Study to Evaluate the Efficacy and Safety of SPT-300 (GlyphAllo) in Participants With Major Depressive Disorder, With or Without Anxious Distress (BUOY-1 Study) (clinicaltrials.gov) - P2 | N=360 | Recruiting | Sponsor: Seaport Therapeutics

Monotherapy • New P2 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A First-In-Human Phase I Study of LYT-300, a First-In-Class Orally Bioavailable Prodrug of the Neurosteroid Allopregnanolone That is Absorbed via the Lymphatic System (SOBP 2024) - P1/2 | "In this first-in-human study, allopregnanolone exposure from oral LYT-300 was ~9x greater than published data for oral allopregnanolone. LYT-300 was generally well-tolerated and resulted in exposure-dependent PD effects from GABAA positive allosteric modulation. LYT-300 has PD and PK properties that warrant further clinical development."

P1 data • CNS Disorders • Depression • Psychiatry

LYT-300, an Oral Prodrug of Allopregnanolone, Potently Reduces Salivary Cortisol Response to the Trier Social Stress Test in a Randomized, Placebo-Controlled Trial in Healthy Participants (SOBP 2024) - P1/2 | "Funding Source : PureTech Health Background: Acute stress is a contributing factor to mood and anxiety disorders, but few treatments safely address physiological stress. LYT-300 blunts physiological overreactivity to the TSST. Benzodiazepines such as alprazolam also reduce salivary cortisol reactivity after the TSST. LYT-300 was generally well-tolerated and demonstrates GABA pharmacological activity that merits further investigation in stress-related mood and anxiety disorders."

Clinical • CNS Disorders • Mood Disorders • Psychiatry

LYT-300 in Healthy Volunteers (clinicaltrials.gov) - P1/2 | N=186 | Completed | Sponsor: PureTech | Recruiting ➔ Completed | Phase classification: P1 ➔ P1/2 | N=90 ➔ 186 | Trial completion date: Apr 2023 ➔ Oct 2023 | Trial primary completion date: Dec 2022 ➔ Oct 2023

Enrollment change • Phase classification • Trial completion • Trial completion date • Trial primary completion date

PureTech Initiates Phase 2a Clinical Trial of LYT-300 (Oral Allopregnanolone) for the Potential Treatment of Anxiety Disorders (Businesswire) - "PureTech Health plc...today announced the initiation of a Phase 2a proof-of-concept clinical trial of LYT-300 (oral allopregnanolone) in healthy volunteers using a validated clinical model of anxiety....LYT-300 is an oral prodrug of allopregnanolone that was developed using PureTech’s GlyphTM platform, which harnesses the body’s natural lipid absorption and transport process to enable the oral administration of certain therapeutics that otherwise cannot be administered orally....Results for the placebo-controlled, Phase 2a, proof-of-concept trial using a validated clinical model of anxiety in healthy volunteers are anticipated by the end of 2023. Additionally, the open-label, Phase 2a, proof-of-concept clinical trial in patients with postpartum depression is expected to begin in the second half of 2023."

New P2a trial • P2a data • Trial status • CNS Disorders • Depression • Epilepsy • Essential Tremor • Sleep Disorder

"$PRTC PureTech to Advance LYT-300 (Oral Allopregnanolone) for the Potential Treatment of Anxiety Disorders and Postpartum Depression https://t.co/2Ic0yq3njW" (@stock_titan)

CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

The imidazodiazepine, KRM-II-81: An example of a newly emerging generation of GABAkines for neurological and psychiatric disorders. (PubMed, Pharmacol Biochem Behav) - "Recently, however, there has been a resurgence of efforts to bring GABAkines to patients, the FDA approval of the neuroactive steroid brexanolone for post-partum depression in 2019 being the first. Other neuroactive steroids are in various stages of clinical development (ganaxolone, zuranolone, LYT-300, Sage-324, PRAX 114, and ETX-155). These GABAkines and non-steroid compounds (GRX-917, a TSPO binding site ligand), darigabat (CVL-865), an α2/3/5-preferring GABAkine, SAN711, an α3-preferring GABAkine, and the α2/3-preferring GABAkine, KRM-II-81, bring new therapeutic promise to this highly utilized medicinal target in neurology and psychiatry...KRM-II-81 also produces anxiolytic- and antidepressant-like effects in rodent models. Other key features of the pharmacology of this compound are its low sedation rate, lack of tolerance development, and the ability to prevent the development of seizure sensitization."

Journal • Review • Anesthesia • CNS Disorders • Depression • Epilepsy • Mental Retardation • Neuralgia • Pain • Postpartum Depression • Psychiatry • Vascular Neurology

LYT-300 in Healthy Volunteers (clinicaltrials.gov) - P1; N=90; Recruiting; Sponsor: PureTech; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

LYT-300: An Orally Bioavailable Prodrug of Allopregnanolone With Anticonvulsant Activity (ACNP 2021) - "An intravenous formulation of allopregnanolone (brexanolone) was recently approved for treatment of severe postpartum depression (marketed as Zulresso®) where it is given in a hospital setting over a 60-hr infusion period. LYT-300, when given orally to a range of species, provides significant release of parent compound, allopregnanolone (ALLO). In mice, oral administration of LYT-300 produced dose-dependent increases in plasma exposure of ALLO and evidence of anticonvulsant efficacy. These data provide proof of concept that LYT-300 (p.o.) can deliver the pharmacologically active compound ALLO at levels that produce ALLO-related pharmacological effects."

Alzheimer's Disease • CNS Disorders • Depression • Mental Retardation • Psychiatry

LYT-300: An Orally Bioavailable Prodrug of Allopregnanolone With Anticonvulsant Activity (ACNP 2021) - "An intravenous formulation of allopregnanolone (brexanolone) was recently approved for treatment of severe postpartum depression (marketed as Zulresso®) where it is given in a hospital setting over a 60-hr infusion period. LYT-300, when given orally to a range of species, provides significant release of parent compound, allopregnanolone (ALLO). In mice, oral administration of LYT-300 produced dose-dependent increases in plasma exposure of ALLO and evidence of anticonvulsant efficacy. These data provide proof of concept that LYT-300 (p.o.) can deliver the pharmacologically active compound ALLO at levels that produce ALLO-related pharmacological effects."

Alzheimer's Disease • CNS Disorders • Depression • Mental Retardation • Psychiatry

LYT-300 in Healthy Volunteers (clinicaltrials.gov) - P1; N=90; Not yet recruiting; Sponsor: PureTech

Clinical • New P1 trial

GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABA receptors. (PubMed, Pharmacol Ther) - "Traditional GABAkines like diazepam have safety and tolerability concerns that include sedation, motor-impairment, respiratory depression, tolerance and dependence...The compounds that are presently being developed and commercialized include several neuroactive steroids (an allopregnanolone formulation (brexanolone), an allopregnanolone prodrug (LYT-300), Sage-324, zuranolone, and ganaxolone), the α2/3-preferring GABAkine, KRM-II-81, and the α2/3/5-preferring GABAkine PF-06372865 (darigabat)...Medicinal chemistry efforts are also ongoing to identify novel and improved GABAkines. The data document gaps in our understanding of the molecular pharmacology of GABAkines that drive differential pharmacological profiles, but emphasize advancements in the ability to successfully utilize GABA receptor potentiation for therapeutic gain in neurology and psychiatry."

Journal • Review • Anesthesia • CNS Disorders • Depression • Epilepsy • Mood Disorders • Movement Disorders • Pain • Postpartum Depression • Psychiatry