A Multicenter, Open Label Study to Evaluate Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson's Disease Dementia.

This study will be conducted as a multi-center, open label study in the US. There will be 40 patient to receive the active investigational product.

Start Date01 Mar 2024

Sponsor / Collaborator

Enterin, Inc.Startup

NCT04483479 / TerminatedPhase 2

A Multicenter, Non-Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Orally Administered ENT-01 in Improving Constipation and Neurologic Symptoms in Patients With Parkinson's Disease and Constipation Over a 14-week Period

This study will be conducted as an open-label safety follow-on to a multi-center, double-blind, randomized study. All subjects who participated in the randomized study will be offered participation in this unblinded, single-arm, safety study. Approximately 50 subjects will be entered into the study and ENT-01 will be administered daily in escalating doses followed by a fixed dose for 12 weeks. Each subject will participate for approximately 20 weeks; dosing duration will be approximately 14 weeks.

Start Date30 Jul 2020

Sponsor / Collaborator

Enterin, Inc.Startup

NCT03781791 / CompletedPhase 2

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate Safety, Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson's Disease-Related Constipation (KARMET)

This study will be conducted as a multi-center, randomized, double-blind, placebo-controlled study. Approximately 72 patients will be randomized 3:1 to treatment or placebo, with approximately 54 patients allocated to receive the active investigational product and approximately 18 patients allocated to receive placebo.
- Study Update-
Amendment 3 - In this amendment, an additional 80 patients (approximately) will be randomized 1:1 to treatment or placebo (double-blind) with approximately 40 subjects allocated to each group.

Start Date10 Dec 2018

Sponsor / Collaborator

Enterin, Inc.Startup

100 Clinical Results associated with Kenterin

100 Translational Medicine associated with Kenterin

100 Patents (Medical) associated with Kenterin

Literatures (Medical) associated with Kenterin

01 Jan 2023·Annals of Internal Medicine

Correction: Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease

01 Dec 2022·Annals of Internal Medicine

Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease

Article

Author: Barbut, Denise ; Duker, Andrew ; Kumar, Rajeev ; Chhabria, Nisha ; Eskenazi, Jonathan ; Vandersluis, Joel ; Kadimi, Srinath ; Zasloff, Michael ; Li, George ; Burdick, Daniel ; Feldman, Mary ; Goldstein, Mark ; Riesenberg, Robert ; Subramanian, Thyagarajan ; Marquez-Mendoza, Otto ; Molho, Eric ; MacDougall, James ; Shivkumar, Vikram ; Truong, Daniel ; Hughes, Mary ; Hidalgo, Gonzalo ; Grill, Stephen ; Hauser, Robert A. ; Stephenson, Sharisse ; Pfeffer, Michael ; Mandell, Howard ; Gil, Ramon ; Klos, Kevin ; Bhatia, Perminder ; Robottom, Bradley ; Walter, Benjamin L. ; Isaacson, Stuart ; Pagan, Fernando ; Tse, Winona ; Shprecher, David ; Camilleri, Michael ; Kinney, William

BACKGROUNDParkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD.OBJECTIVETo evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation.DESIGNRandomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791).SETTINGOutpatient.PATIENTS150 patients with PD and constipation.INTERVENTIONENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period.MEASUREMENTSThe primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]).RESULTSThe weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (P < 0.001). Improvement in secondary end points included SBMs (P = 0.002), stool consistency (P < 0.001), ease of passage (P = 0.006), and laxative use (P = 0.041). In patients with dementia, MMSE scores improved by 3.4 points 6 weeks after treatment in the ENT-01 group (n = 14) versus 2.0 points in the placebo group (n = 14). Among patients with psychosis, SAPS-PD scores improved from 6.5 to 1.7 six weeks after treatment in the ENT-01 group (n = 5) and from 6.3 to 4.4 in the placebo group (n = 6). ENT-01 was well tolerated, with no deaths or drug-related serious adverse events. Adverse events were predominantly gastrointestinal, including nausea (34.4% [ENT-01] vs. 5.3% [placebo]; P < 0.001) and diarrhea (19.4% [ENT-01] vs. 5.3% [placebo]; P = 0.016).LIMITATIONLonger treatment periods need to be investigated in future studies.CONCLUSIONENT-01 was safe and significantly improved constipation.PRIMARY FUNDING SOURCEEnterin, Inc.

01 Aug 2019·European Journal of Medicinal ChemistryQ1 · MEDICINE

Exploring the effect of chirality on the therapeutic potential of N-alkyl-deoxyiminosugars: anti-inflammatory response to Pseudomonas aeruginosa infections for application in CF lung disease

Q1 · MEDICINE

Article

Author: Ranucci, Serena ; Esposito, Anna ; Santangelo, Alessandra ; Palumbo, Giovanni ; Bragonzi, Alessandra ; Cabrini, Giulio ; De Fenza, Maria ; Lampronti, Ilaria ; Tironi, Matteo ; Dechecchi, Maria Cristina ; D'Alonzo, Daniele ; Lippi, Giuseppe ; Aureli, Massimo ; Munari, Silvia ; Tamanini, Anna ; Guaragna, Annalisa ; De Fino, Ida ; Loberto, Nicoletta ; Gambari, Roberto ; Bassi, Rosaria ; Rossi, Alice

In the frame of a research program aimed to explore the relationship between chirality of iminosugars and their therapeutic potential, herein we report the synthesis of N-akyl l-deoxyiminosugars and the evaluation of the anti-inflammatory properties of selected candidates for the treatment of Pseudomonas aeruginosa infections in Cystic Fibrosis (CF) lung disease. Target glycomimetics were prepared by the shortest and most convenient approach reported to date, relying on the use of the well-known PS-TPP/I₂ reagent system to prepare reactive alkoxyalkyl iodides, acting as key intermediates. Iminosugars ent-1-3 demonstrated to efficiently reduce the inflammatory response induced by P. aeruginosa in CuFi cells, either alone or in synergistic combination with their d-enantiomers, by selectively inhibiting NLGase. Surprisingly, the evaluation in murine models of lung disease showed that the amount of ent-1 required to reduce the recruitment of neutrophils was 40-fold lower than that of the corresponding d-enantiomer. The remarkably low dosage of the l-iminosugar, combined with its inability to act as inhibitor for most glycosidases, is expected to limit the onset of undesired effects, which are typically associated with the administration of its d-counterpart. Biological results herein obtained place ent-1 and congeners among the earliest examples of l-iminosugars acting as anti-inflammatory agents for therapeutic applications in Cystic Fibrosis.

News (Medical) associated with Kenterin

24 Jun 2023

·www.globenewswire.com

Enterin Presents Data Demonstrating Strong Benefit of ENT-03 on Body Weight, Adiposity and Blood Glucose Vs. Semaglutide in a Diet Induced Obesity Mouse Model

Data presented at the American Diabetes Association 83rd Scientific SessionsPHILADELPHIA, June 24, 2023 (GLOBE NEWSWIRE) -- Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, presented in vivo data demonstrating benefit on body weight, adiposity and blood glucose of ENT-03 compared to semaglutide in an obese, diabetic animal model, with persistence of benefit on weight beyond treatment. The data were presented at the American Diabetes Association’s (ADA) 83rd Scientific Sessions in San Diego. “ENT-03 differs profoundly from the GLP-1 agonists both with respect to its pharmacology and mechanism of action,” said Michael Zasloff, M.D., Ph.D., Scientific Director of the Medstar Georgetown Transplant Institute, Co-Founder and Chief Scientific Officer of Enterin and senior author of the paper. “We believe ENT-03 can add a new dimension to the management of Type 2 diabetes and obesity.” ENT-03 is a novel, endogenous, centrally acting mammalian aminosterol with Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, which normalizes glucose and causes weight loss by acting on brain circuits that regulate energy and metabolism. In obese, diabetic mice, ENT-03 rapidly lowers blood glucose, reduces food intake and adiposity, eliminates liver fat, and improves liver function. The study presented today compared the effects of subcutaneously administered ENT-03 to semaglutide on blood glucose, adiposity, and body weight over a 10-week treatment period in a diet-induced obesity (DIO) mouse model. Within one-to-two weeks of treatment with ENT-03, DIO mice exhibit a rapid and substantial fall in blood glucose, out of proportion to the loss of weight. In contrast, in semaglutide treated DIO mice, glucose falls in proportion to weight loss. Weight loss continues smoothly in the ENT-03 treatment group over the 10-week period, plateauing at lean body weight, and blood glucose remains in the normoglycemic range. In contrast, the effects of semaglutide on both weight loss and blood glucose begin to diminish between four and six weeks after initiation of treatment, since both body weight and blood glucose increase despite continued dosing. Within several days following the end of the 10-week treatment period, the semaglutide group exhibited a sharp rebound in food intake and body weight and by five weeks approached the body weight of the untreated obese mice. In contrast, ENT-03 treated animals maintained the lower weight and the reduced food intake, with no evidence of rebound in either. Body fat, which decreased significantly in both groups during treatment, increased at a faster rate in the semaglutide group post-treatment compared with the ENT-03 group. Results can be found online at www.enterininc.com and at https://diabetesjournals-org.libproxy1.nus.edu.sg/diabetes/article/72/Supplement_1/854-P/149928/854-P-ENT-03-a-Centrally-Acting-Endogenous. “Weight loss during treatment with ENT-03 is progressive, profound and outlasts the treatment period for prolonged periods, which suggests that a neuroregenerative process might be taking place,” said Denise Barbut, M.D., F.R.C.P., Co-Founder, President, and Chief Medical Officer of Enterin and first author of the paper. Phase 1 studies in obese and diabetic subjects are currently in progress (IND155001). Results of the first-in-human, randomized, double-blind, single ascending dose study involving approximately 49 subjects with obesity with or without Type 2 diabetes are expected to be available in the fourth quarter of 2023. ENT-03 is Enterin’s second compound in clinical trials. The first compound, ENT-01, has completed a successful randomized Phase 2b study in patients with Parkinson’s disease (https://www-acpjournals-org.libproxy1.nus.edu.sg/doi/10.7326/M22-1438). About Enterin Inc. Enterin Inc. is the first company to develop novel compounds that repair the dysfunctional gut-brain axis in patients with neurodegenerative diseases. Enterin Inc. is pioneering the medical community’s understanding of the link between infections, dysfunction of the enteric nervous system (ENS) and the onset and progression of neurodegenerative disease. Enterin’s lead compound, ENT-01, displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the ENS and improves neural signalling between the gut and the brain. Enterin Inc. has completed a large, randomized Phase 2b clinical trial in patients with Parkinson’s disease. The study met all the endpoints. Preparations for Phase 3 studies are currently underway. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain. It is being developed for the treatment of diabetes, obesity, and Alzheimer’s disease. For more information, please visit www.enterininc.com. Company contact:Katherine WolfChief Financial Officerk.wolf@enterininc.com

Phase 2Clinical Result

05 Jun 2023

·www.globenewswire.com

Enterin Announces the Start of a First-in-Human Study of ENT-03 in Obesity and Type 2 Diabetes

PHILADELPHIA, June 05, 2023 (GLOBE NEWSWIRE) -- Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, today announced the start of a Phase 1a study in obesity and Type 2 diabetes (IND #155001). The study is a first-in-human, single center, single dose, randomized, placebo-controlled, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneously administered ENT-03 in development for the treatment of obesity and Type 2 diabetes. It will be conducted in the U.S. and will enroll approximately 49 patients, with results expected in the fourth quarter of 2023. The first five cohorts will consist of obese but otherwise healthy volunteers and the last two cohorts will involve obese subjects with Type 2 diabetes. Each cohort will enroll five active and two placebo subjects, with a total of up to 35 subjects receiving active therapy across the seven arms and 14 subjects receiving placebo. ENT-03 is a novel, endogenous, centrally acting aminosterol with protein tyrosine phosphatase 1B (PTP1B) inhibitory activity, which normalizes glucose and causes weight loss by acting on brain circuits that regulate energy and metabolism. In obese, diabetic mice, ENT-03 rapidly normalizes blood glucose, reduces food intake and adiposity, eliminates liver fat, normalizes liver function, and increases insulin sensitivity (abstract to be presented at the American Diabetes Association, San Diego, June 25, 2023). The neural circuits affected by ENT-03 appear to differ from those impacted by semaglutide suggesting a different mechanism of action (abstract to be presented at the European Association for the Study of Diabetes, Hamburg, Germany, October 2-6, 2023). ENT-03 is Enterin’s second compound in clinical trials. The first compound, ENT-01, has completed a successful randomized Phase 2b study in patients with Parkinson’s disease (https://www-acpjournals-org.libproxy1.nus.edu.sg/doi/10.7326/M22-1438). About Enterin Inc. Enterin Inc. is the first company to develop novel compounds that repair the dysfunctional gut-brain axis in patients with neurodegenerative diseases. The Company is pioneering the medical community’s understanding of the link between infections, dysfunction of the enteric nervous system (ENS) and the onset and progression of neurodegenerative disease. Enterin’s lead compound, ENT-01, displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the ENS and improves neural signaling between the gut and the brain. Enterin has completed a large, randomized Phase 2b clinical trial in patients with Parkinson’s disease. The study met all the endpoints. Preparations for Phase 3 studies are currently underway. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain. It is being developed for the treatment of diabetes, obesity, and Alzheimer’s disease. For more information, please visit www.enterininc.com. Company contact:Katherine WolfChief Financial Officerk.wolf@enterininc.com

Phase 2Clinical ResultPhase 3

31 May 2023

·www.biospace.com

Enterin announces FDA acceptance of an investigator sponsored IND to treat a patient with prodromal multisystem atrophy (MSA) with ENT-01

PHILADELPHIA, May 31, 2023 (GLOBE NEWSWIRE) -- Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, 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. Individuals diagnosed with MSA have an average life expectancy of 6-8 years and there is no existing treatment which halts the progression of the disease. The condition, an alpha-synucleinopathy similar to Parkinson’s disease, consists of progressive autonomic failure with prominent bowel and bladder symptoms, and central nervous system manifestations include REM-behavior disorder, dysfunctional circadian rhythm, Parkinsonism, and cognitive dysfunction. 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 ( ). 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. The patient is a 42-year-old man with a single gene mutation (ATP13A2) which may impair lysosomal clearance mechanisms, and which predisposes to Parkinsonism and MSA. He has a 2-year history of constipation, urinary symptoms, erectile dysfunction, sleep disturbances suggestive of REM-behavior disorder, dysfunctional circadian rhythm and positive alpha-synuclein staining in duodenal enteric neurons. On the basis of these symptoms, he has been diagnosed as having prodromal MSA. ENT-01 (squalamine phosphate) acts locally on enteric neurons and electrostatically displaces misfolded, positively charged proteins such as alpha-synuclein from neuronal membranes, as well as preventing the formation and deposition of alpha-synuclein aggregates. Moreover, in preliminary experiments conducted on the patient’s own cells, ENT-01 completely prevented the oxidative stress response caused by rotenone, a highly toxic agent which impairs mitochondrial function, and which is used in animal models of PD. According to Dr. Denise Barbut, Co-Founder, President and CMO of Enterin, “This is the first time that any compound is being used to prevent the progression of MSA and a milestone in the development of ENT-01 for both treatment and prevention of other neurodegenerative disorders.” Dr. Robert Hauser, the treating physician and Director of the Parkinson’s Disease and Movement Disorders Center of the University of South Florida added, “We hope that ENT-01 will be helpful in preventing progression of MSA in this individual and that this work will help promote personalized medicine for neurodegenerative diseases.” About Enterin Inc. Enterin Inc. is the first company to develop novel compounds that repair the dysfunctional gut-brain axis in patients with neurodegenerative diseases. Enterin Inc. is pioneering the medical community’s understanding of the link between infections, dysfunction of the enteric nervous system (ENS) and the onset and progression of neurodegenerative disease. Enterin’s lead compound, ENT-01, displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the ENS and improves neural signalling between the gut and the brain. Enterin Inc. has completed a large, randomized Phase 2b clinical trial in patients with Parkinson’s disease. The study met all the endpoints. Preparations for Phase 3 studies are currently underway. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain. It is being developed for the treatment of diabetes, obesity, and Alzheimer’s disease and Phase 1 clinical trials in subjects with obesity and diabetes will begin in June 2023. For more information, please visit . Enterin Inc: Katherine Wolf k.wolf@enterininc.com Investors: Lee Roth/Julia Weilman Burns McClellan lroth@burnsmc.com/jweilman@burnsmc.com Media: Selina Husain/Robert Flamm, Ph.D. Burns McClellan shusain@burnsmc.com/rflamm@burnsmc.com

Phase 2Clinical ResultPhase 1

100 Deals associated with Kenterin

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple System Atrophy	IND Application	US	Enterin, Inc.Startup	31 May 2023
Dementia due to Parkinson's disease	Preclinical	US	Enterin, Inc.Startup	01 Mar 2024
Constipation	Preclinical	US	Enterin, Inc.Startup	10 Dec 2018
Parkinson Disease	Preclinical	US	Enterin, Inc.Startup	10 Dec 2018

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04483479 (Rollover, CTgov)	Phase 2	Constipation \| Parkinson Disease	27	Active Investigational Treatment ENT-01	omgvqkoslg(vfbeiqffcs) = aajekwinjp bwllicibsd (jgprpegzyp, lhhntmucqq - nngwnbkccd) View more	-	19 Mar 2024
NCT03781791 (KARMET, CTgov)	Phase 2	Constipation \| Parkinson Disease	151	Active Investigational Treatment ENT-01 (Active Treatment)	jyjqazngsf(kzuouidrqd) = ausfklbojy mncrjfjhqi (umwxvklrjz, ezwstfmixi - clxvukscwa) View more	-	04 Dec 2023
				Placebo Treatment (Placebo Treatment)	jyjqazngsf(kzuouidrqd) = xzhwqlplrq mncrjfjhqi (umwxvklrjz, lgvslbkkue - lpoqbuzijc) View more
NCT03781791 (Pubmed)	Phase 2	Parkinson Disease	150	ENT-01	(xtkasysrah) = urbtphzqsq zwghgvfjog (xxzjhrqztz ) View more	Positive	08 Nov 2022
				Placebo	(xtkasysrah) = oukxodfvup zwghgvfjog (xxzjhrqztz ) View more

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