squalamine phosphate (ENT-01) / Enterin - LARVOL DELTA

A Study to Evaluate ENT-01 for the Treatment of Parkinson's Disease Dementia (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Enterin Inc. | N=40 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

Cognitive Impairment in Parkinson's Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches. (PubMed, Medicina (Kaunas)) - "Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • Movement Disorders • Parkinson's Disease • FGF21

GENERATION, CHARACTERIZATION AND SCREENING OF ENT001 A NEW THERAPEUTIC TOOL FOR IBD (UEGW 2023) - "Ent001 may represent a novel IGFBP3/TMEM219 inhibitor to be further tested and developed in in vivo models and in clinical studies as a novel therapeutic in human diseases."

Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • CASP8 • IGFBP3

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover) (clinicaltrials.gov) - P2 | N=28 | Terminated | Sponsor: Enterin Inc. | Completed ➔ Terminated; Poor recruitment/retention due to the pandemic. Data was not analyzed due to early termination.

Trial termination • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease

A Study to Evaluate ENT-01 for the Treatment of Parkinson's Disease Dementia (clinicaltrials.gov) - P1 | N=40 | Suspended | Sponsor: Enterin Inc. | Trial completion date: May 2021 ➔ Dec 2025 | Unknown status ➔ Suspended | Trial primary completion date: Mar 2021 ➔ Jun 2025

Trial completion date • Trial primary completion date • Trial suspension • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

Enterin announces FDA acceptance of an investigator sponsored IND to treat a patient with prodromal multisystem atrophy (MSA) with ENT-01 (GlobeNewswire) - "Enterin...announces the acceptance by the U.S. Food and Drug Administration (FDA) of an investigator sponsored Investigational New Drug (IND) application (166532) to treat a patient with prodromal multisystem atrophy (MSA) with ENT-01. Treatment will continue indefinitely or until significant adverse events occur that warrant discontinuation of drug....ENT-01 has been used to treat close to 200 patients with Parkinson’s disease in Phase 2a and Phase 2b (randomized) studies and dose-dependent improvement noted in the symptoms mentioned above (https://annals.org/aim/article/doi/10.7326/M22-1438). Side effects are largely confined to the GI tract, and consist of nausea, diarrhea, and vomiting. Phase 3 studies in Parkinson’s disease-related constipation and further Phase 2 studies in Parkinson’s disease-related psychosis and dementia are being planned."

IND • CNS Disorders • Dementia • Multiple System Atrophy • Parkinson's Disease

New Drug Could Ease Parkinson’s-Related Constipation - "This study, however, does not demonstrate that, said Dr. Andrew Feigin....'So you can't really draw conclusions from this,' said Feigin, who was not part of the study....'They may need to make the drug more tolerable,' he said."

Media quote

Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease : A Randomized Controlled Trial. (PubMed, Ann Intern Med) - P2 | "ENT-01 was safe and significantly improved constipation. Enterin, Inc."

Journal • Alzheimer's Disease • CNS Disorders • Constipation • Dementia • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease • Psychiatry

Enterin and Parkinson’s UK Announce Research Collaboration in Parkinson’s Dementia (GlobeNewswire) - “Enterin Inc…announces a collaboration with the Parkinson’s Virtual Biotech, the drug development and discovery arm of Parkinson's UK. A new phase 2 trial will study the effects of ENT-01 on Parkinson’s Disease (PD)-associated dementia….‘Enterin is very grateful to partner with such a prestigious and well-respected organization…We have worked closely with Parkinson’s UK and their clinical advisors to design a clinical study to evaluate ENT-01 in PD dementia. It is our hope that we can offer a new therapeutic option for these patients.’”

Licensing / partnership • CNS Disorders • Dementia • Parkinson's Disease

"Opvallend, het #ecp2022 zit vol met bijdragen over hoe psychologie geïntegreerd moet worden in 1elijn. Duidelijke kentering, iedereen botst wel op zelfde problemen. Ook in de US focus op samenwerking 1elijnsactoren, mobiel werken, vindplaatsen, competentiebevordering,… #elp" (@KoenLowet)

An overview of the active clinical trials for Parkinson's disease psychosis. (PubMed, Neurodegener Dis Manag) - "Tweetable abstract An overview of the active clinical trials for Parkinson's disease psychosis. In this article, we review the drugs currently undergoing clinical testing for Parkinson's disease psychosis and offer some perspectives on the treatment of the condition."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation (KARMET) (clinicaltrials.gov) - P2 | N=144 | Completed | Sponsor: Enterin Inc. | Recruiting ➔ Completed | Trial completion date: Sep 2021 ➔ Dec 2021 | Trial primary completion date: Jul 2021 ➔ Dec 2021

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover) (clinicaltrials.gov) - P2 | N=28 | Completed | Sponsor: Enterin Inc. | Recruiting ➔ Completed | N=50 ➔ 28 | Trial primary completion date: Nov 2021 ➔ Feb 2022

Enrollment change • Trial completion • Trial primary completion date • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease

Enterin Meets Study Endpoints for the Phase 2b (KARMET) Study Involving Patients With Parkinson's Disease (GlobeNewswire) - P2, N=152; KARMET (NCT03781791); Sponsor: Enterin Inc; "Enterin Inc...announces the conclusion of a randomized, placebo-controlled, double-blind Phase 2b (KARMET) study involving 150 patients with Parkinson's Disease (PD). Efficacy analyses were performed on all patients who had received at least 7 days of medication (n=136). The primary endpoint, defined as the change in complete spontaneous bowel movement (CSBM) from baseline to the end of the 3-week treatment period was significantly better in the treatment group compared to placebo (p=0.0001). The improvement persisted 2-weeks (p=0.02) and 6-weeks (p=0.05) after discontinuation of study medication. Secondary bowel endpoints were also significantly better in the treatment group compared to placebo....In summary, both primary and secondary bowel endpoints were met, demonstrating that even a short course of ENT-01 can restore the function of enteric nerve cells."

P2 data • CNS Disorders • Parkinson's Disease

Enterin to Announce Top-Line Results From the Phase 2b Study for Parkinson's Disease (Yahoo Finance) - "Enterin...today announced that it will host a webinar to present top-line results from the Phase 2b (KARMET) study in patients with Parkinson's disease on Thursday, Jan. 27 at 2:30 pm EST. Key opinion leaders (KOLs) in Parkinson's disease will discuss the findings in relation to the pathophysiology and to the implications for treatment."

P2 data • CNS Disorders • Parkinson's Disease

Treatment of Parkinson's Disease with Cognitive Impairment: Current Approaches and Future Directions. (PubMed, Behav Sci (Basel)) - "The only recommended treatment for PDD currently is rivastigmine, a cholinesterase inhibitor. Donepezil and galantamine-other cholinesterase inhibitors-are possibly useful...Drug repurposing (atomoxetine, levodopa, insulin, atomoxetine for PD-MCI; ambroxol and ceftriaxone for PDD) and novel medications (SYN120, GRF6021, NYX-458 for PD-MCI; ANAVEX2-73, LY3154207, ENT-01, DAAOI-P for PDD) currently have insufficient evidence. There is growing research supporting exercise in the treatment of PD-MCI, but most non-pharmacological approaches have insufficient evidence for use in PD-MCI (cognitive rehabilitation, deep brain stimulation, transcranial direct current stimulation, transcranial ultrasound, vestibular nerve stimulation) and PDD (cognitive intervention, deep brain stimulation, transcranial alternating current stimulation, transcranial ultrasound, temporal blood brain barrier disruption). Research is needed for both disease-modifying and symptomatic treatments in PD..."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Immunology • Movement Disorders • Parkinson's Disease

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation (KARMET) (clinicaltrials.gov) - P2; N=152; Recruiting; Sponsor: Enterin Inc.; Active, not recruiting ➔ Recruiting; Trial completion date: May 2021 ➔ Sep 2021; Trial primary completion date: Feb 2021 ➔ Jul 2021

Clinical • Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation (KARMET) (clinicaltrials.gov) - P2; N=152; Active, not recruiting; Sponsor: Enterin Inc.; Trial completion date: Oct 2020 ➔ May 2021; Trial primary completion date: Aug 2020 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover) (clinicaltrials.gov) - P2; N=50; Recruiting; Sponsor: Enterin Inc.; Phase classification: P2b ➔ P2

Clinical • Phase classification • CNS Disorders • Constipation • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover) (clinicaltrials.gov) - P2; N=50; Recruiting; Sponsor: Enterin Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • CNS Disorders • Constipation • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover) (clinicaltrials.gov) - P2b; N=50; Not yet recruiting; Sponsor: Enterin Inc.

Clinical • New P2b trial • CNS Disorders • Constipation • Gastrointestinal Disorder • Gene Therapies • Movement Disorders • Parkinson's Disease

"Onderzoeker RIVM: mensen met mondkapje zijn juist voorzichtiger /via @NOS Kentering?? https://t.co/5P20CB19Wt" (@FrankBroekmans)

A Study to Evaluate ENT-01 for the Treatment of Parkinson's Disease Dementia (clinicaltrials.gov) - P1; N=40; Active, not recruiting; Sponsor: Enterin Inc.; Trial completion date: Feb 2020 ➔ May 2021; Trial primary completion date: Jan 2020 ➔ Mar 2021

Clinical • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • Gene Therapies • Movement Disorders • Parkinson's Disease

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation (KARMET) (clinicaltrials.gov) - P2; N=152; Active, not recruiting; Sponsor: Enterin Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Orally Administered ENT-01 for Parkinson's Disease-Related Constipation (KARMET) (clinicaltrials.gov) - P2; N=152; Recruiting; Sponsor: Enterin Inc.; Active, not recruiting ➔ Recruiting; N=72 ➔ 152; Trial completion date: Nov 2019 ➔ Oct 2020; Trial primary completion date: Sep 2019 ➔ Aug 2020

Clinical • Enrollment change • Enrollment open • Trial completion date • Trial primary completion date