Press Releases

Philadelphia, PA, July 10, 2017 (Newswire.com) – Enterin Inc., a Philadelphia-based biotechnology company developing novel compounds to treat Parkinson’s disease (PD), today announced the completion of a $12.7 million Series A financing round. The financing included new investors New Ventures III, as well as participation of existing investors.

“We are absolutely thrilled to have the support of New Ventures III and our current investors, and view the caliber of our investors as validation of the potential of our platform technology to transform the course of PD and of other neurodegenerative diseases,” said Michael Zasloff, M.D. Ph.D., Founder, Chairman and CEO of Enterin. He added, “The proceeds from this financing will enable us to complete the on-going Phase 2 study in PD, further expand our understanding of the role of alpha-synuclein (aS) in the pathology of PD and begin to explore other indications. We are very excited about working with this outstanding group of investors, and bringing their deep expertise and guidance to bear as we progress our development.”

Enterin also announced that Mark Finn, Founding Partner at New Ventures III, has joined the company’s Board of Directors, representing the Series A investor class.

The announcement coincides with an ongoing Phase 1/2a clinical trial, sponsored by Enterin Inc., targeting the accumulation of aS in the enteric nervous system. The trial is examining the safety, tolerability, pharmacokinetics, and pharmacodynamics of ENT-01 to relieve constipation associated with Parkinson’s disease. “While the study is focused on functional improvement of the enteric nervous system, we are closely monitoring central nervous system symptoms such as sleep, REM-behavior disorder, depression, fatigue and even motor symptoms”, said Denise Barbut, M.D. F.R.C.P., Co-Founder, President and Chief Medical Officer of Enterin. She added, “The drug has the potential to slow the progression of PD and of other neurodegenerative disorders in which dysfunction of the enteric nervous system plays a part”. Details of the RASMET study can be found on clinicaltrials.gov. ENT-01 is an oral drug that contains a synthetic derivative of squalamine.

Research recently published by Dr. Zasloff and collaborators demonstrated that squalamine both reduced the formation of toxic αS clumps and their toxicity in animal models of Parkinson’s disease. Most recently, the founders and their colleagues demonstrated that aS is induced in response to viral gastrointestinal infections in children and that it brings in the immune system to help defend the nervous system and the gut. Links to the articles and to related press coverage can be found at the Enterin website.

About Enterin Inc.

Enterin Inc. is the first company in the world to develop a novel drug that repairs the dysfunctional gut-brain axis in patients with neurodegenerative disease. Enterin Inc. is pioneering the medical community’s understanding of the link between infections, dysfunction of the enteric nervous system of the gut, and the early onset and chronic progression of neurodegenerative disease. The lead compound, ENT-01, displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the enteric nervous system and improves neural signaling between the gut and the brain in preclinical models of Parkinson’s disease. In the gut, this results in improved motility. Enterin Inc. is now progressing ENT-01 through clinical trials aimed at reversing the constipation of Parkinson’s disease. For more information, please visit www.enterininc.com.

About New Ventures III

New Ventures is a leading healthcare venture capital firm focusing on innovating and disruptive areas in life sciences and healthcare. New Ventures invests globally throughout the healthcare industry, from new businesses to royalties on developed drugs. The New Ventures team is a group of co-founders, entrepreneurial operators, and investors with over 100 years of experience. The team has a history of collaborating on various projects together building companies and investing in life sciences, healthcare and agriculture. Our team understands the science and technology breakthroughs needed to achieve radical change that improves the human condition and simultaneously creates value for our investors. To learn more about New Ventures, please visit www.newventuresfunds.com.

Philadelphia, PA, June 28, 2017 (Newswire.com) – Michael Zasloff, MD, Ph.D., Professor of Surgery and Pediatrics at Georgetown University School of Medicine, and Founder, Chairman and CEO of Enterin Inc. was the senior author of a study that has helped clarify the function of alpha-Synuclein (αS), the protein implicated in Parkinson’s disease (PD) and other neurodegenerative diseases. Denise Barbut, MD, FRCP, Co-Founder, President and Chief Medical Officer of Enterin Inc. was senior co-author of the study.

Published in the Journal of Innate Immunity, the study finds that αS is released in response to an infection in the upper GI tract in children, inducing an immune response as part of the body’s innate immune system. According to the researchers, these findings suggest that frequent or chronic upper GI infections could overwhelm the body’s capacity to clear αS, ultimately leading to Parkinson’s disease.

This research builds upon prior studies, which showed that the buildup of αS in PD patients actually begins in the enteric nervous system (nerves in the GI tract). Animal studies have further shown that microbes in the GI tract can induce formation of toxic αS aggregates in the enteric nervous system, which can then travel up to the brain.

The study showed a positive correlation between the expression of αS in enteric nerves of the upper GI tract and the degree of acute and chronic inflammation in the intestinal wall. Furthermore, the study showed that αS could potently attract immune cells such as macrophages and neutrophils, and could ‘turn on’ dendritic cells to alert the immune system of the specific pathogen encountered.

As Dr. Zasloff explains, “When expressed in normal amounts following an infection of the upper GI tract, αS is a good molecule. It is protective. The nervous system within the wall of the GI tract detects the presence of a pathogen and responds by releasing αS. αS then attracts white blood cells to the site where it has been released. In addition, αS produced in one nerve can spread to others with which it communicates thereby protecting a large field. By this means, the nervous system can protect both itself as well as the GI tract as a whole in the setting of an infection.”

He adds, “It is well-known from animal studies that αS produced in the enteric nervous system can use the nerves connecting the GI tract to the brainstem as an escalator, trafficking αS from the gut to the brain and spreading to centers within the central nervous system. But too much αS — such as from multiple or chronic infections — becomes toxic because the system that disposes of αS is overwhelmed, nerves are damaged by the toxic aggregates that form and chronic inflammation ensues. Damage occurs both within the nervous system of the GI tract and the brain.”

Dr. Zasloff says the new findings “make sense” of observations made in PD patients, such as the presence of chronic constipation from damage to the enteric nervous system that develops decades before brain symptoms become apparent and that chronic upper GI distress is relatively common in people who develop PD.

The publication of this study coincides with an ongoing Phase 1/2a clinical trial at 12 U.S. sites, sponsored by Enterin Inc., targeting the accumulation of aS in the enteric nervous system. The clinical trial is examining the safety, tolerability, pharmacokinetics, and pharmacodynamics of ENT-01 to relieve constipation associated with Parkinson’s disease. Details of the RASMET study can be found on clinicaltrials.gov. ENT-01 is an oral drug that contains a synthetic derivative of squalamine, a natural steroid made by the dogfish shark. Research recently published by Dr. Zasloff and collaborators demonstrated that squalamine both reduced the formation of toxic αS clumps and their toxicity, in animal models of Parkinson’s disease.

About Enterin Inc.

Enterin Inc. is the first company in the world to develop a novel drug that repairs the dysfunctional gut-brain axis in patients with neurodegenerative disease. Enterin Inc. is pioneering the medical community’s understanding of the link between infections, dysfunction of the enteric nervous system of the gut, and the early onset and chronic progression of neurodegenerative disease. The lead compound, ENT-01, displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the enteric nervous system and improves neural signaling between the gut and the brain in preclinical models of Parkinson’s disease. In the gut, this results in improved motility. Enterin Inc. is now progressing ENT-01 through clinical trials aimed at reversing the constipation of Parkinson’s disease. For more information, please visit www.enterininc.com.

Philadelphia, PA, May 15, 2017 (Newswire.com) – Enterin Inc., a privately-held CNS pharmaceutical company based in Philadelphia and developing novel compounds to treat Parkinson’s disease (PD), has enrolled the first patient in the RASMET study. The study is a Phase 1/2a randomized, controlled, multicenter study involving patients with PD and taking place at 12 US sites. It will enroll 50 patients over a 9-to-12-month period. The first stage is open label and involves single escalating doses in 10 patients with PD. Participating sites include Denver, Boca Raton, Tampa Bay and Cleveland. Details relating to the study can be found at ClinicalTrials.gov, and contact information is available on the Enterin website.

The study will establish the safety, tolerability and efficacy of an orally administered synthetic derivative of squalamine, which is not absorbed into the blood stream. The compound acts locally on the enteric nerve cells of the gut, stimulating gut motility and altering afferent neural signaling from gut to brain. It has the potential to ameliorate some or all of the non-motor symptoms of Parkinson’s disease, including constipation, fragmented sleep and REM-behavior disorder, and to modify disease progression.

Synthetic squalamine was recently shown to prevent the buildup and reduce the toxicity of alpha-synuclein, implicated in the pathogenesis and progression of Parkinson’s disease. The compound was shown to displace alpha-synuclein aggregates from the inner wall of nerve cells, and to prevent the stiffness which develops in C. Elegans worms engineered to produce alpha-synuclein in their muscles. The results were published online in the February 7th edition of the Proceedings of the National Academy of Sciences (Perni et al, PNAS Vol 114, no 6, 2017, doi: 10.1073/pnas.1610586114). Links to the article and to the press coverage can be found at the Enterin website.

About Enterin Inc.

Enterin Inc. is the first company in the world to develop a novel drug that repairs the dysfunctional gut-brain axis in patients with neurodegenerative disease. Enterin Inc. is pioneering the medical community’s understanding of the link between infections, dysfunction of the enteric nervous system (ENS) of the gut, and the early onset and chronic progression of neurodegenerative disease. The lead compound, ENT-01 (also known as kenterin), displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the ENS and improves neural signaling between the gut and the brain in preclinical models of Parkinson’s disease. In the gut, this results in improved motility. Enterin Inc. is now progressing ENT-01 through clinical trials in an attempt to reverse the constipation of Parkinson’s disease. For more information, please visit www.enterininc.com.

News & Press Coverage

Enterin Inc, a CNS pharmaceutical company based in Philadelphia and developing novel compounds to treat Parkinson’s disease (PD), has enrolled the first patient in the RASMET study.  The study is a Phase 1/2a randomized, controlled multi-center study involving patients with PD and taking place at 12 US sites. It will enroll 50 patients over a 9-12 month period. The first stage is open label and involves single escalating doses in 10 patients with PD. Participating sites include Denver, Boca Raton, Tampa and Cleveland. Details relating to the study can be found at ClinicalTrials.gov, and contact information is available on Enterin’s website.

The study will establish the safety, tolerability and efficacy of an orally administered synthetic derivative of squalamine, which is not absorbed into the blood stream. The compound acts locally on the enteric nerve cells of the gut, stimulating gut motility and altering afferent neural signalling from gut to brain. It has the potential to ameliorate some or all of the non-motor symptoms of Parkinson’s disease, including constipation, fragmented sleep and REM-behavior disorder, and to modify disease progression.

Synthetic squalamine was recently shown to prevent the buildup and reduce the toxicity of alpha-synuclein, implicated in the pathogenesis and progression of Parkinson’s disease. The compound was shown to displace alpha-synuclein aggregates from the inner wall of nerve cells, and to prevent the stiffness which develops in C. Elegans worms engineered to produce alpha-synuclein in its muscles. The results were published online in the February 7th edition of the Proceedings of the National Academy of Sciences (Perni et al, PNAS Vol 114, no 6, 2017, doi: 10.1073/pnas.1610586114). Links to the article and to the press coverage can be found at the Enterin website.

Pineda and Burré have authored a Commentary in PNAS discussing Enterin’s paper published by Perni et al.

Read the abstract and learn more at PNAS

Abstract: The self-assembly of α-synuclein is closely associated with Parkinson’s disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of α-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing α-synuclein, observing a dramatic reduction of α-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson’s disease and related conditions.

See the article published at PNAS: Proceedings of the National Academy of Sciences of the United States of America