Shy-Drager Syndrome

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

La Jolla, California, USA, December 4, 2017 (PR Newswire): Innovative California Biosciences International, Inc., (“ICBII”), announced on November 20th the submission of their Orphan Drug Designation application to the US Food and Drug Administration (FDA) for the use of α-synuclein-SMART Molecule (α-Syn-SM), a novel antibody mimic, in the treatment of Multiple System Atrophy (MSA). MSA is a rapidly progressive neurodegenerative disease with a mean survival of 6-10 years post diagnosis. This disease arises from the misfolding and accumulation of the protein α-synuclein in oligodendrocytes, where it forms glial cytoplasmic inclusions killing neurons and glial cells. Based on current census, prevalence, and National Institute of Health (NIH) data, there are estimated to be fewer than 15,000 to 50,000 MSA patients in the US. In the US and Europe, 66% to 82% of MSA patients have parkinsonian features (MSA-P). MSA-P has been designated an orphan disease. According, ICBII has requested that the FDA grant the α-Syn-SM for MSA Orphan Drug Status. MSA is a seriously debilitating disease for which there is no cure. It is characterized by a variable combination of Parkinsonism, cerebellar impairment, and autonomic dysfunction. It encompasses three presentations of a single disease, specifically Shy-Drager syndrome (which emphasized autonomic dysfunction), striatonigral degeneration (which emphasized parkinsonian symptoms), and sporadic olivopontocerebellar atrophy (which emphasized cerebellar symptoms). About SMART Molecules SMART Molecules (SMs) are novel antibody mimics that cross the blood-brain barrier (BBB) into the central nervous system (CNS) where they selectively target and inhibit the expression of pathological proteins in animals. SMART is an acronym that stands for Specific Molecular Architecture for Recognition and Therapy. The Company has developed a SMART Molecule for α-synuclein, which, when administered intravenously, allows quantitation of aberrant/misfolded α-synuclein in the brain of treated mice by a brain scan and halts its expression in a dose dependent manner. “With this Orphan Drug Designation, hopefully the FDA will fast track the development and approval process of α-Syn-SM in the treatment of MSA-P and related Parkinson’s disorders. It will be a major advancement in moving the SMART Molecules technology platform forward towards treating Parkinson’s, MSA, Alzheimer’s, Glioblastoma, and other central nervous system Diseases,” stated Ram Bhatt PhD, CEO/CSO of ICBII. ABOUT ICBII: The Company was founded in October of 2008 for the sole purpose of addressing unmet medical needs related to the diseases of the central nervous system. The blood brain barrier has effectively excluded the brain from the entire biotech revolution. With its SMs technology ICBII’s mission is to impact the lives of millions of patients worldwide by ameliorating their suffering. ICBII has currently two patents issued and seven patents pending with several more ready to be filed. Forward Looking Statements This press release may contain forward-looking statements, including ICBII’s development of SMART Molecules™ for altering the course of MSA and other α-synucleinopathies. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from those, express or implied, in these forward-looking statements. ICBII expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in ICBII expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based for any reason, except as required by law, even as new information becomes available or other events occur in the future. All forward-looking statements in this press release are qualified in their entirety by this cautionary statement. Contact Information: info@icbii.com Investor Relations: Ken Evans, kevans@icbii.com