Events

On January 27, 2022 at 2:30 pm EST, top-line results from the Phase 2b (KARMET) study were presented on a conference call by Denise Barbut, MD, FRCP, Co-Founder, President and CMO of Enterin. Stuart Isaacson, MD, and Patrik Brundin, MD, Ph.D., shared their perspectives. A replay of the event is available here.

Press Releases

PHILADELPHIA, January 27, 2022 (Newswire.com) –​Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, announces the conclusion of a randomized, placebo-controlled, double-blind Phase 2b (KARMET) study involving 150 patients with Parkinson’s Disease (PD).

Enterin’s lead compound, ENT-01 targets alpha-synuclein, or αS, a protein known to play a key role in the pathophysiology of PD. αS accumulates in nerve cells of the gut (enteric nerves), preventing the nerve cells from functioning properly. Orally administered ENT-01 displaces αS aggregates from nerve cell membranes as well as preventing their formation. As a result, enteric nerve cell function is restored, as is communication between gut and brain.

The Phase 2b study was a randomized, placebo-controlled, double-blind study involving 150 patients with PD and constipation. Following a two-week baseline period, patients were stratified to start at high dose or low dose depending on baseline constipation severity and randomized to receive ENT-01 or placebo. Dosing was escalated every 2-3 days and “fixed” for the remainder of the 25-day treatment period. All patients were then placed on placebo for 2 weeks, followed by a 4-week wash-out.

There were no safety or tolerability concerns (n=150). There were no deaths or drug-related serious adverse events. Adverse events were largely confined to the GI tract and self-limiting. They included nausea and diarrhea.

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. These included spontaneous bowel movement (SBM; p=0.001), stool consistency (p=0.0001), ease of passage (p=0.004) and laxative use (p=0.03). Exploratory endpoints included psychosis (Scale of Positive Symptoms in PD, SAPS-PD) and dementia (Mini Mental State Examination, MMSE). 13 patients had psychotic symptoms at baseline (SAPS-PD score ≥4). In the ENT-01 group (n=6), SAPS-PD score improved by 73% by the end of the 3-week treatment period and by 82% 6-weeks after treatment discontinuation. Placebo patients (n=7) showed no improvement during treatment and worsened following treatment discontinuation. Twenty-four patients had dementia at baseline (MMSE≤26). In the ENT-01 group, MMSE score improved by 2 points during the 3-week treatment period, and by 3.5 points 6 weeks beyond the treatment period. Placebo patients improved during treatment but worsened following treatment discontinuation.

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. Results from small numbers of patients suggest that ENT-01 might also improve psychosis and dementia. According to Denise Barbut, MD, FRCP, Enterin’s Co-Founder, President and CMO, “The continued improvement of bowel and neurologic symptoms for weeks beyond the brief treatment period suggests a possible disease-modifying effect.”

Michael Zasloff, MD, Ph.D., Enterin’s Co-Founder and CSO, added, “Aging itself compounds the ongoing damage caused by the accumulation of alpha-synuclein. Our preclinical studies suggest that the persistence of benefit observed with ENT-01 are a consequence of the reversal of certain aspects of the aging process.”

The KARMET study was designed to replicate earlier findings of a preceding open-label RASMET study in a placebo-controlled trial. The RASMET study had established safety, tolerability and reversal of constipation following orally administered ENT-01, and signaled improvement in neurologic endpoints including memory, mood, sleep, REM-behavior disorder, psychosis, and circadian rhythm, with persistence of benefit for several weeks beyond the brief treatment period (https://doi.org/10.1016/j.prdoa.2019.06.001).

Top-line results will be presented on a conference call by Denise Barbut, MD, FRCP, Co-Founder, President and CMO of Enterin. Stuart Isaacson, MD, and Patrik Brundin, MD, Ph.D., will share their perspectives. Please join the call on Jan. 27 at 2:30 pm EST. A link to the invitation can be found on the Enterin website along with a replay of the event.

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 signaling between the gut and the brain. Enterin Inc. is now progressing ENT-01 through Phase 2 clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain and acutely normalizes blood sugar in diabetic mice. ENT-03 is being developed for the treatment of diabetes, obesity and Alzheimer’s disease. Studies in humans will begin in 2022.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, January 25, 2022 (Newswire.com) –​Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, 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, January 27th at 2:30pm EST. Key opinion leaders (KOLs) in Parkinson’s disease will discuss the findings in relation to the pathophysiology and to the implications for treatment.

The webinar will feature KOLs Patrik Brundin, MD, PhD (Van Andel Institute) and Stuart Isaacson, MD (Director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton). Dr. Brundin will discuss the pathophysiology of Parkinson’s disease, the role of alpha-synuclein, and the effect of ENT-01 on alpha-synuclein and disease progression. Dr. Isaacson will discuss the clinical context in which ENT-01 might be useful in the treatment of Parkinson’s disease, and what it might add to the existing armamentarium. ENT-01 prevents alpha synuclein (αS) – the culprit in Parkinson’s disease (PD) – from aggregating within enteric nerve cells and displaces existing aggregates from nerve cell membranes, restoring enteric neural function and communication between enteric neurons and the brain.

Denise Barbut, MD, FRCP. (Co-Founder, President, CMO, and Board Member of Enterin) will discuss the clinical trial data from the randomized, placebo-controlled Phase 2b (KARMET) study.

A live question and answer session will follow the formal presentations.

For those who are unable to listen at this time, a replay of the call will be available by clicking here and on the Enterin website.

To register for the event, please click here.

Patrik Brundin, MD, PhD joined the Van Andel Institute for Scientific Research in 2012, where he is Deputy Chief Scientific Officer and directs the Parkinson’s Disease Center. He earned his Ph.D. in 1988 and M.D. in 1992, both from Lund University, Sweden and is highly cited in neuroscience with more than 400 publications on Parkinson’s Disease and related movement disorders. His research focuses on pathogenic mechanisms of Parkinson’s Disease and development of therapies that slow or stop disease progression or that repair damaged brain circuits. He is a member of the World Parkinson Coalition Board of Directors and The Michael J. Fox Foundation for Parkinson’s Research Executive Scientific Advisory Board. He also serves as co-editor-in-chief of the Journal of Parkinson’s Disease and chair of the International Linked Clinical Trials scientific committee.

Stuart H. Isaacson, MD, FAAN is Director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton, where he directs a team of movement disorder neurologists and clinical coordinators combining a holistic approach to medical therapy with access to one of the largest Parkinson’s and Movement Disorder clinical trial centers in the US. Dr. Isaacson received his MD from Northwestern University School of Medicine in Chicago, and fellowships at the National Institutes of Health in Bethesda, Maryland, and in NYC at Mount Sinai Medical Center under Melvin Yahr, Warren Olanow, and Mitchell Brin. He has been involved in over 250 clinical trials and has served on national and international committees for many drug development programs, seeking to advance development of emerging symptomatic, nonmotor, and disease-modifying therapies. Dr. Isaacson has authored or co-authored over 300 abstracts, journal articles, and book chapters, and has presented research results at national and international scientific meetings. Dr. Isaacson is Board Certified in Neurology, a Fellow of the American Academy of Neurology, and a member of the International Association of Parkinson’s and Related Disorders, the Movement Disorders Society, the Section on Movement Disorders of the AAN, the Parkinson’s Study Group, the Huntington’s Study Group, and has been recognized in Best Doctors in America.

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. is now progressing ENT-01 through Phase 2 clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain and acutely normalizes blood sugar in diabetic mice. ENT-03 is being developed for the treatment of diabetes, obesity and Alzheimer’s disease. Studies in humans will begin in 2022.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, January 11, 2022 (Newswire.com) –​Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, announces the publication of a paper entitled “Alpha-synuclein, the culprit in Parkinson’s Disease, is required for normal immune function.”

Alpha-synuclein (αS), the pathologic protein associated with Parkinson’s Disease (PD), appears to be essential for the immune protection of the abdominal cavity. Furthermore, infections in the GI tract can cause accumulation of αS within the entire nervous system, potentially contributing to the development and/or progression of PD, according to scientists at the National Institutes of Health (NIH) and their colleagues, the founders of Enterin, Inc.

αS is causally involved in the development of PD as a consequence of its accumulation within the peripheral and central nervous system. Although the association between αS and PD was discovered almost 25 years ago, its role in normal vertebrate physiology has remained obscure. Recent studies have demonstrated that the presence of a functional αS gene confers survival benefit to mice infected with a neurotropic virus.

The Enterin and NIH teams had previously shown that αS is induced in the enteric nervous system of children who contract a norovirus infection and that it potently attracts components of the immune system such as macrophages and neutrophils and activates dendritic cells to alert the immune system of the specific pathogen encountered.

In this study, published today in the journal Cell Reports, the NIH team shows that αS is critical for the development of a normal immune response to bacterial components introduced into the peritoneal cavity. The authors show that the mice lacking the αS gene cannot recruit immune cells to the site of infection nor induce pathogen-specific immune responses. Remarkably, the animals fail to mount an effective immune response following vaccination. Conversely, when exogenous αS is introduced into the peritoneum, both the innate and adaptive immune response is enhanced. αS appears to enhance the immune response by activating macrophages and inducing the maturation of dendritic cells. Furthermore, they show that nerve cells are the sources of αS, and that infection in the GI tract “alerts” neurons in other locations, inducing widespread production of aS throughout the nervous system, with the highest concentrations produced closest to the site of infection. These findings suggest αS may provide a unique link between the nervous and immune systems. These data also establish that αS plays a critical role in the induction of the normal immune response and help explain the lack of an immune response to infection observed in the αS-/- mice. This study adds to the growing body of evidence that αS accumulates within the nervous system of individuals with PD as a result of an immune response.

“Until this federally-funded study, the importance of αS in mounting an effective immune response was poorly understood,” says the study’s senior author, Joost Oppenheim, M.D., Ph.D., Head, Cellular Immunology Section, National Cancer Institute. “My laboratory has described the importance of “alarmins” in innate and adaptive immunity. Alarmins are endogenous proteins that both alert and direct the immune system to effectively tackle an infectious insult. αS appears to be an alarmin. The connection between neuronally derived αS and the eventual development of PD remains to be resolved.”

“This study demonstrates beyond the shadow of a doubt that aS made by nerve cells is central to mounting a normal immune response to infection,” says the study’s co-senior investigator, Michael Zasloff, M.D., Ph.D., Scientific Director of MedStar Georgetown Transplant Institute and co-founder and CSO of Enterin, Inc. Enterin’s co-founder and CMO, and co-author, Denise Barbut M.D., FRCP., adds that “What’s remarkable is the rapid induction of aS in nerves at great distances from the site of the infectious stimulus. It is conceivable that aS production within the brain in Parkinson’s disease is triggered indirectly by a neural signal emanating from the site of a remote infection rather than being physically transported from the periphery.”

The study was funded by the National Institute of Health.

The full article can be found at Cell Reports.

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. is now progressing ENT-01 through Phase 2 clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain and acutely normalizes blood sugar in diabetic mice. ENT-03 is being developed for the treatment of diabetes, obesity and Alzheimer’s disease. Studies in humans will begin in 2022.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, January 10, 2022 (Newswire.com) –​Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, announces Patrik Brundin, M.D., Ph.D., has joined the Scientific Advisory Board.

Dr. Brundin joined the Van Andel Institute for Scientific Research in 2012, where he is Deputy Chief Scientific Officer and directs the Parkinson’s Disease Center. He earned his Ph.D. in 1988 and M.D. in 1992, both from Lund University, Sweden and is highly cited in neuroscience with more than 400 publications on Parkinson’s Disease and related movement disorders. His research focuses on pathogenic mechanisms of Parkinson’s Disease and development of therapies that slow or stop disease progression or that repair damaged brain circuits. He is a member of the World Parkinson Coalition Board of Directors and The Michael J. Fox Foundation for Parkinson’s Research Executive Scientific Advisory Board. He also serves as co-editor-in-chief of the Journal of Parkinson’s Disease and chair of the International Linked Clinical Trials scientific committee.

“We are very excited to welcome Patrik to Enterin’s Scientific Advisory Board,” said Denise Barbut, Enterin’s Co-founder, President and Chief Medical Officer. “Patrik is a thought leader in the field of Parkinson’s Disease and has pioneered an extensive body of research linking alpha-synuclein produced in the periphery to progression of the disease in the brain.”

“We’re absolutely delighted that Patrik is joining the Enterin Scientific Advisory Board. Patrik’s contribution to our understanding of the pathophysiology of Parkinson’s Disease, and of the role of alpha-synuclein in disease progression has been invaluable. He’s the perfect match to our current thinking,” added Michael Zasloff, Enterin’s Co-founder and Chief Scientific Officer.

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. is now progressing ENT-01 through Phase 2 clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain and acutely normalizes blood sugar in diabetic mice. ENT-03 is being developed for the treatment of diabetes, obesity and Alzheimer’s disease. Studies in humans will begin in 2022.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, November 19, 2021 (Newswire.com) –​Enterin Inc., a privately held Philadelphia-based clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, announces the publication in Scientific Reports of a paper entitled “Identification of SSRI‑evoked antidepressant sensory signals by decoding vagus nerve activity.”

The vagus nerve is the major neural connection between gut and brain. Vast numbers of sensory signals originating in the gut are captured by the enteric nervous system (ENS) and conveyed to the brain via the vagus nerve. As a consequence, damage either to the ENS or the vagus nerve can have significant GI as well as neuropsychiatric consequences.

Serotonin (5-hydroxytryptamine; 5-HT) is an important neurotransmitter both in the central nervous system (CNS) and the ENS. Furthermore, 95% of the body’s serotonin is produced in the GI tract. Serotonin is involved in GI-related functions such as neurogenesis, epithelial repair, GI secretions, and gut motility. Serotonin also has an excitatory effect on the vagus, regulating important CNS functions such as appetite, sleep, and mood.

Orally administered selective serotonin reuptake inhibitors (SSRIs) such as sertraline or fluoxetine exert their anti-depressant action by stimulating the vagus nerve (at least in mice) and severing the vagus nerve abolishes the anti-depressant effect. Unlike SSRIs, the anti-depressant effect of bupropion, a dopamine-norepinephrine reuptake inhibitor, is not mediated by the vagus nerve, nor is the effect abolished by vagotomy.

While vagal nerve fibers are known to be stimulated by SSRIs, how exactly they encode a specific “anti-depressant signal” (as opposed to say, a depressant signal) is unknown.

This study by West and colleagues at McMasters University’s Brain Body Institute and scientists at Enterin Inc., using recordings from single vagal fibers, demonstrated that SSRIs evoked unique firing patterns, consisting of increased spike frequency, burst duration, intra-burst spike interval and decreased gap duration between bursts. This pattern of firing was significantly different from the firing pattern produced by bupropion, which evoked an increase in all four firing parameters.

Pharmacological silencing of ENS cells abolished the “antidepressant code” induced by application of sertraline, indicating that sertraline’s effect on the vagus is mediated by the ENS.

“Our work demonstrates that electrical signals generated by the nervous system of the gut can influence complex behavioral states,” says Wolfgang Kunze, Ph.D., the senior author of the study. “Our discovery identifies, for the first time, a unique gut-brain signal carried by the vagus that can improve a specific neuropsychiatric symptom. We believe that our research will ultimately lead to the development of more effective treatments for neurologic diseases.”

Squalamine, a shark-derived aminosterol discovered by Enterin’s co-founder and CSO, Michael Zasloff, MD., Ph.D., produced an antidepressant code comparable to that evoked by sertraline. A synthetic version of this compound, ENT-01, is currently in Phase 2 clinical trials in patients with Parkinson’s Disease.

Dr. Zasloff commented, “We have recently shown that squalamine inhibits the monoamine reuptake transporter, inhibiting the reuptake of serotonin as well as dopamine and norepinephrine. Preventing the reuptake of serotonin in the GI tract would increase the amount of serotonin available to stimulate the ENS and vagus and would explain the serotonergic signal observed in the single fiber recordings.”

According to Enterin’s co-founder and CMO, Denise Barbut, MD., FRCP., “The serotonergic vagal signal observed following application of squalamine may explain the improvement in depression, dementia and psychosis we have observed in preliminary studies in patients with Parkinson’s Disease.” She added that Enterin is initiating further clinical studies specifically addressing PD-related dementia and PD-related psychosis.

The paper can be accessed at: https://www.nature.com/articles/s41598-021-00615-w

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 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. is now progressing ENT-01 through Phase 2 clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s Disease. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain and acutely normalizes blood sugar in diabetic mice. ENT-03 is being developed for the treatment of diabetes, obesity and Alzheimer’s disease. Studies in humans are expected to begin in H1 2022.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, September 13, 2021 (Newswire.com) –​Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, announces Dr. Roger Mills has joined the Board of Directors.

Dr. Mills is a highly accomplished and well-respected drug development expert and has held numerous senior level positions during his illustrious career ushering several blockbuster drugs through FDA approval. Most recently, Dr. Mills served as Chief Medical Officer for Acadia Pharmaceuticals where he led a highly successful Ph III program in Parkinson’s Disease Psychosis. This led to the approval of the first compound for the treatment of Parkinson’s Disease related Psychosis. Prior to joining Acadia, Dr. Mills served as Vice President, Pfizer Global Research and Development, where he was responsible for clinical development across a broad portfolio of therapeutic areas. Earlier in his career, Dr. Mills held senior positions within Clinical Development at Gilead Sciences and Abbott Laboratories. Dr. Mills is a Visiting Professor at the Centre for Age Related Diseases, Inst of Psychiatry, Psychology, and Neuroscience, King’s College London. He also serves as Professor of Medical Research in Practice at the University of Exeter Medical School, Exeter, UK. Additionally, he is Acting Chief Medical Officer and a member of the Board of Directors of Addex Theraputics. He received his medical degree from Imperial College, Charing Cross Hospital Medical School, London.

“We are extremely excited to welcome Roger to Enterin’s Board of Directors,” said David McCullough, Enterin’s Chief Executive Officer. “Roger brings a tremendous wealth of drug development experience and a solid track record of success. Given his presence in the field of Parkinson’s and other neurological diseases, Roger can instantly contribute to the strategic focus for Enterin as we begin two phase II programs in Parkinson’s Disease Psychosis and Parkinson’s Disease Dementia later this year.”

“We’re absolutely delighted that Roger is joining the Enterin team. Roger’s extensive experience in the fields of Parkinson’s Disease related psychosis and dementia as well as his background in pharmaceutical development is of tremendous value” said Denise Barbut, Enterin Co-founder and Chief Medical Officer.

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 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 aggregates from nerve cells in the ENS and improves neural signalling between the gut and brain. Enterin is now progressing ENT-01 through Phase 2 clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain and acutely normalizes blood sugar in diabetic mice. ENT-03 is being developed for the treatment of diabetes, obesity and Alzheimer’s disease. Studies in humans will begin in H1 2022.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, August 25, 2021 (Newswire.com) –​Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, announces that Hilde Williams has joined the organization as a Senior Regulatory Advisor. In this capacity, she will oversee and direct all regulatory activities for Enterin’s clinical development programs. Ms. Williams is an experienced regulatory strategist with over 30 years in biotech/pharma.

Ms. Williams has successfully led regulatory strategy from Pre-IND through NDA for neurologic, psychiatric, and other development programs and has served in executive leadership team positions. Most notably, Ms. Williams served as Sr. Vice President Regulatory Affairs and Development for Acadia Pharmaceuticals where she oversaw the largest-ever international Phase 3 clinical trial in Parkinson’s disease psychosis, including a successful pivotal study that met all study endpoints. Ms. Williams successfully garnered FDA agreement for an NDA submission based on a single Phase 3 study, gained strategic Breakthrough Designation (a first for the Psychiatry Division) and secured Priority Review leading to the only approved label for the treatment of Parkinson’s disease psychosis. Additionally, Ms. Williams has provided leadership on regulatory and development activities associated with the launch and conduct of multiple other development programs for CNS, psychiatric and other indications.

“We are extremely excited to have Hilde lead Regulatory Affairs at Enterin. Her extensive hands-on experience in the most difficult regulatory aspects of neurology and psychiatry and her exceptional leadership in the only FDA-approved drug for the treatment of Parkinson’s disease psychosis to date will be of great value to Enterin,” said Dr. Denise Barbut, Enterin’s co-founder and CMO.

“I am excited to serve as Senior Regulatory Advisor for Enterin and oversee regulatory strategy and operations for the company’s development programs,” said Ms. Williams. “I believe Enterin’s novel approach towards neurodegenerative diseases is truly groundbreaking, and I am looking forward to advancing the company’s regulatory and development strategies.”

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) 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 ENS and improves neural signaling between the gut and the brain in preclinical models of Parkinson’s disease. Enterin Inc. is now progressing ENT-01 through Phase 2 clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain and rapidly normalizes blood sugar in diabetic mice. ENT-03 is being developed for the treatment of diabetes, obesity and Alzheimer’s disease. Studies in humans will begin in H1 2022.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, August 10, 2021 (Newswire.com) –​Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, announces the appointment of Alan C. Moses, MD, to its Scientific Advisory Board. Dr. Moses is a former Professor of Medicine at Harvard University and Chief Medical Officer of the Joslin Diabetes Center. He subsequently served as Global Chief Medical Officer at Novo Nordisk.

Alan Moses was educated at Duke University (BS) and Washington University School of Medicine (MD) prior to training at Barnes Hospital in St. Louis, Missouri; the National Institutes of Health in Bethesda, Maryland; and Tufts-New England Medical Center in Boston. He is board certified by the ABIM with subspecialty certification in Endocrinology and Metabolism. He is a Fellow of the American College of Physicians. His academic career focused on basic and translational research at Harvard Medical School. Following his tenure at Harvard, Dr. Moses joined Novo Nordisk in 2004 and became Global Chief Medical Officer in 2008. As Global CMO, he was involved in the full spectrum of the diabetes focus of Novo Nordisk from drug discovery, through drug development, brand messaging, and the implications of diabetes for the company and for patients, healthcare professionals and for healthcare systems. He retired from Novo Nordisk in June 2018 and consults for multiple biotechnology companies focusing on developing treatments for diabetes.

“We are delighted Dr. Moses has agreed to join our Scientific Advisory Board. His clinical expertise in metabolic diseases coupled with his experience in developing diabetes drugs at a senior level is invaluable to us,” said Dr. Denise Barbut, Enterin’s Co-founder, President and CMO.

“I’m excited to join the Enterin team and to help in the development of ENT-03 and other compounds. ENT-03 is unique in that it targets central insulin resistance and can provide a new approach to effectively treat diabetes and obesity. It also has the potential to positively impact Alzheimer’s and Parkinson’s diseases, addressing major unmet medical needs,” said Alan Moses.

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) of the gut and the early onset and chronic progression of neurodegenerative disease. The lead compound, ENT-01, displaces membrane-bound alpha-synuclein aggregates from nerve cells in the ENS and improves neural signaling between the gut and the brain. Enterin is now progressing ENT-01 through Phase 2 clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain and rapidly normalizes blood sugar in diabetic mice. ENT-03 is being developed for the treatment of diabetes, obesity and Alzheimer’s disease. Studies in humans will begin in H1 2022.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, June 16, 2021 (Newswire.com) –​Enterin Inc., a clinical stage biopharmaceutical company pioneering novel treatments for neurodegenerative diseases, announces that the company will be presenting at JMP Securities Life Sciences Conference on Thursday, June 17 at 3:00 pm EDT.

Dr. Denise Barbut, Enterin’s co-founder, President and CMO, will give the company presentation.

About Enterin Inc.

Enterin, Inc. develops 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 early symptoms and progression of neurodegenerative disease. The lead compound, ENT-01, displaces membrane-bound alpha-synuclein (aS) aggregates from nerve cells in the ENS and improves neural signaling between the gut and the brain in preclinical models of Parkinson’s disease and in human studies. Enterin, Inc. is now progressing ENT-01 through clinical trials in an attempt to reverse the neurological symptoms of Parkinson’s disease. A second compound, ENT-03, reverses central insulin resistance, the central pathology in conditions ranging from obesity to diabetes to Alzheimer’s disease. In animal models of Alzheimer’s disease, ENT-03 normalizes memory and prolongs life. First-in-human studies will begin in 1H 2022.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, April 7, 2021 (Newswire.com) –​Enterin Inc., a clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative diseases, announces the appointment of Donald Munoz to its Board of Directors.

“We are thrilled to welcome Don to Enterin’s Board,” said David McCullough, Enterin’s Chief Executive Officer. “He brings significant biotechnology industry expertise and tremendous financial experience given his roles as a public-company CFO and healthcare investment banker. Don will be an ideal partner to the executive team as Enterin enters its next phase of growth.”

Enterin’s Board Chairman Jay Brammer added, “We look forward to working with Don and I am confident he will make strong contributions to the success of Enterin.”

“I am excited to join Enterin’s Board and work with the team to advance our compounds through clinical development,” said Don Munoz. “Enterin’s compounds represent a novel and highly promising approach toward the treatment of neurodegenerative diseases, and I look forward to contributing to the Company’s success.”

Mr. Munoz currently serves as Chief Financial Officer of NuCana plc, a Nasdaq-listed biotechnology company focused on significantly improving treatment outcomes for patients with cancer. NuCana completed a $114 million IPO in 2017 and an $80 million follow-on offering in 2020. Prior to joining NuCana in 2015, Don served as Group Chief Financial Officer of NOXXON Pharma. He has an extensive financial background with approximately 20 years as a healthcare investment banker at Alex. Brown & Sons, Deutsche Bank, Leerink Partners and Cowen. Don has completed over 100 financing and merger and acquisition transactions with an aggregate value of more than $30 billion. He received an MBA in Finance and Accounting from Columbia Business School, where he was elected to Beta Gamma Sigma, and an AB in Psychology from Dartmouth College.

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 early symptoms and progression of neurodegenerative disease. The 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 in preclinical models of Parkinson’s disease and in human studies. Enterin Inc. is now progressing ENT-01 through clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease. A second compound, ENT-03, reverses memory deficits in Alzheimer’s models and extends lifespan. First-in-human studies will begin in Q4 2021.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, March 1, 2021 (Newswire.com) –​Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative diseases, announces that the company will be presenting at Chardan’s virtual 3rd Annual Microbiome Medicines Summit on March 8, 2021, at 8:30 a.m. ET.

Dr. Denise Barbut, Enterin’s co-founder and CMO, will present the company’s latest updates relating to its lead compound, ENT-01, which is currently being developed for the treatment of Parkinson’s Disease (PD). ENT-01 displaces membrane-bound alpha-synuclein (αS) aggregates from enteric nerve cells, improving neural signaling from the gut to the brain. Enterin is currently completing a 150-patient randomized Phase 2b study and will be initiating studies in PD Psychosis and PD Dementia/Non-motor symptoms later this year.

Enterin also looks forward to one-on-one meetings with interested investors throughout the day.

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 early symptoms and progression of neurodegenerative disease. The 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 in preclinical models of Parkinson’s disease and in human studies. Enterin Inc. is now progressing ENT-01 through clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease. A second compound, ENT-03, reverses memory deficits in Alzheimer’s models and extends lifespan. First-in-human studies will begin in Q4 2021.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, February 24, 2021 (Newswire.com) –​Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative diseases, announces the appointment of Katherine Wolf as Chief Financial Officer. Ms. Wolf brings 30 years of health care industry experience in capital raising, business development, and strategy, during which she has executed financing, advisory, and M&A transactions worth approximately $24 billion.

“We are thrilled that Katherine is joining the Enterin team. She has deep experience as a healthcare CFO, advisor, and investment banker. Her background in capital markets, her reputation among the financial community, and her experience as a public company CFO will help Enterin as we position the company for the next phase of growth,” said David McCullough, Enterin’s CEO. Enterin’s Chairman, Jay Brammer, added “Katherine will make an excellent business partner to David as we move Enterin’s compounds through the clinic.”

“I am excited to join a company with such great potential,” said Ms. Wolf. “I believe Enterin’s novel approach toward neurodegenerative diseases is truly groundbreaking, and I am looking forward to advancing the company’s mission and strategy.”

Before joining Enterin, Ms. Wolf was Managing Member of health care consultancy KLW Advisors where she worked as an advisor and Acting CFO to various clients, prior to which she served as Partner and Senior Advisor at Ondra Partners, a boutique investment bank. Previously, her positions included CEO & Co-Founder of health care consultancy Rocket Science, and CFO & EVP of Vision-Sciences, a publicly-traded medical technology company. Additionally, Ms. Wolf has extensive prior health care investment banking experience at both global and boutique investment banks, including HSBC Securities, Bear Stearns and SG Cowen. Ms. Wolf received an MBA from Harvard Business School and a BA from Williams College.

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) 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 ENS and improves neural signaling between the gut and the brain in preclinical models of Parkinson’s disease. Enterin Inc. is now progressing ENT-01 through clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, October 16, 2020 (Newswire.com) –​Enterin Inc., a privately held, CNS-focused pharmaceutical company based in Philadelphia and developing novel compounds to treat neurodegenerative diseases, announces the appointment of David McCullough as Chief Executive Officer.

With over 30 years of pharma/biotech experience, Mr. McCullough is a demonstrated strategic, creative, and accomplished leader. With executive and board director experience in startup and established companies, David brings expertise in both the private and public sector. He has a deep understanding of drug development, clinical and regulatory strategy, commercial, finance, IP, manufacturing and operations. Mr. McCullough has a proven track record of building highly skilled, energetic, cross-functional teams both domestically and globally. He has strong experience moving products from early development to launch, including orphan drugs and billion-dollar brands. At Merck, he played a lead role in the $13.5B acquisition of Serono Biotech, and he was honored by the Merck family as a top contributor in corporate development. Additionally, Mr. McCullough has held leadership positions in Allergopharma/EMD Serono and BioCryst. He is interested in Enterin as he has a personal passion for the neurodegenerative therapeutic area and the patient population that can be served with better therapeutic outcomes. “I am thrilled to have the opportunity to join this team that is pioneering the science behind truly innovative approaches in the treatment of neurodegenerative diseases,” says McCullough.

Enterin’s founders and chairmen, Michael Zasloff, MD, PhD and Denise Barbut MD, FRCP reciprocated the sentiment. They said, “We are delighted that David has agreed to join Enterin. His extensive experience in the pharmaceutical industry will supplement the scientific and medical expertise of the existing management team.”

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) 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 ENS and improves neural signaling between the gut and the brain in preclinical models of Parkinson’s disease. Enterin Inc. is now progressing ENT-01 through clinical trials in an attempt to reverse the neurologic symptoms of Parkinson’s disease.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, April 17, 2020 (Newswire.com) –​Enterin Inc., a clinical stage company focused on neurodegenerative diseases, announced today that it has received feedback from the FDA laying out the path for a Phase 1/2a study in hospitalized patients with Covid-19 infection.

The study will involve 10 US sites and will enroll 80 hospitalized patients. Patients will have been diagnosed with SARS-CoV-2, have an SpO2 ≤94% or evidence of pneumonia by chest XR or CT scan. The first stage will involve 24 patients randomized in groups of 4 to escalating doses of COV-ENT-1 or placebo. The second stage will involve another 56 patients randomized to COV-ENT-1 or placebo at the highest tolerable doses. Patients will be followed for 28 days. The compound is administered by inhalation via standard nebulizer.

Once the dosing regimen has been established, a powdered, metered-dose, hand-held inhaler will be developed to treat patients with acute respiratory conditions including Covid-19 or other respiratory infections on an out-patient basis.

COV-ENT-1 has been shown to have broad-spectrum anti-viral activity against both RNA and DNA viruses, both in vitro and in vivo, in studies supported by the National Institutes of Allergy and Infectious Diseases (NIAID). It interferes with virus entry, protein synthesis, replication and egress, essentially rendering the cell resistant to virus. Additionally, in a recent lab study, it was shown to inhibit the replication of SARS-CoV-2 at low concentrations. COV-ENT-1 has also been shown to stimulate regenerative activity, and it could potentially promote tissue repair in lungs damaged by the SARS-CoV-2 virus.

Assuming Enterin is allowed to proceed with the study, it is anticipated that the study will begin within the next 3 months.

About Enterin Inc.

Enterin, Inc.  is a Philadelphia-based, privately held, clinical stage CNS company developing compounds for the treatment of neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. The company is currently conducting a large, randomized, placebo-controlled Phase 2b (KARMET) trial to further explore the effect of ENT-01 on constipation and neurologic symptoms in patients with Parkinson’s disease. The details of the study can be found on Clinicaltrials.gov (NCT#03781791). A second compound, ENT-03 is in advanced pre-clinical development for the treatment of Alzheimer’s disease.

For more information please visit www.enterininc.com. ​

PHILADELPHIA, September 10, 2019 (Newswire.com) –​Enterin Inc., a privately held, CNS-focused pharmaceutical company based in Philadelphia and developing novel compounds to treat neurodegenerative diseases, announces the publication of an article entitled “Colonic motility and jejunal vagal afferent firing rates are decreased in aged adult male mice and can be restored by an aminosterol.” The study was conducted at the Brain-Body Institute at McMaster University in Canada and published online in Frontiers in Neuroscience (DOI 10.3389/fnins.2019.00955).

The study demonstrated that colonic motility and neural signaling from the gut to the brain via the vagus nerve were significantly diminished in old mice compared to young mice. Importantly, the addition into the gut of squalamine, a compound originally discovered in the liver of the dogfish shark, restored colonic motility and vagal firing rates back to the levels in young mice. Similar findings from a pilot study were previously reported by the same authors in abstract form.

The nervous system of the gut is responsible not only for normal bowel function but also for healthy brain functioning. It coordinates the passage of food but also transmits vast amounts of information to the brain. As we age the gut’s nervous system “slows down,” resulting in constipation. Reduced activity of the gut’s nerve cells impairs gut-brain signaling via the vagus nerve and may account for depression and other neurologic symptoms. According to the lead author of the study, Dr. Christine West, the enteric nervous system appears to be particularly vulnerable to age-related degeneration and this, in turn, affects neural signals reaching the brain from the gut.

The senior author of the study, Dr. Wolfgang Kunze, a Professor at the Mind-Brain Institute said, “Our results show that vagal afferent firing is reduced in old age, but these changes are not permanent since the effects can be restored to within range of the young mice. This has profound implications for the treatment of neurodegenerative diseases in elderly individuals.”

ENT-01, a synthetic derivative of squalamine, is currently being tested in clinical trials involving patients with Parkinson’s Disease. The compound is given orally and acts locally on the enteric nerve cells of the gut. According to Dr. Michael Zasloff, the founder and Chairman of Enterin and discoverer of squalamine, the compound also displaces proteins that are electrostatically bound to intracellular membranes and, through this mechanism, suppresses aggregation of alpha-synuclein monomers into neurotoxic oligomers. He adds that “the pathology specific to neurodegenerative disorders such as Parkinson’s disease or Alzheimer’s disease is clearly superimposed on changes related to the aging process itself since these diseases occur in the elderly and not in the young.”

Enterin is currently conducting a randomized, double-blind, placebo-controlled trial (KARMET) to explore the effect of ENT-01 on constipation and neurologic symptoms in patients with Parkinson’s disease. The details of the study can be found on Clinicaltrials.gov (NCT#03781791). In an earlier Phase 2a study involving 50 patients with Parkinson’s disease and constipation, constipation was reversed in over 80% of patients. The study also found potential signals of clinical benefit for depression, cognition, hallucinations, sleep and circadian rhythm. The article is entitled “Targeting neurons in the gastrointestinal tract to treat Parkinson’s Disease” and was published online in Clinical Parkinsonism and Related Disorders (https://doi.org/10.1016/j.prdoa.2019.06.001).

About Enterin Inc.

Enterin Inc. is the first company 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, a synthetic derivative of squalamine, 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. The compound also has profound rejuvenative effects on the aging mouse gut. Enterin Inc. is now progressing ENT-01 through clinical trials in an attempt to reverse the constipation and neurologic symptoms of Parkinson’s disease.

For more information, please visit www.enterininc.com.

PHILADELPHIA, August 27, 2019 (Newswire.com) –​​​Enterin Inc., a privately held, CNS-focused pharmaceutical company based in Philadelphia developing novel compounds to treat neurodegenerative diseases, announces the publication of its Phase 2a RASMET study. The article entitled “Targeting neurons in the gastrointestinal tract to treat Parkinson’s Disease” was published online in Clinical Parkinsonism and Related Disorders.

RASMET was a Phase 2a multicenter, dose-escalating study to evaluate the safety, tolerability and efficacy of orally administered ENT-01 for the treatment of Parkinson’s Disease (PD)(NCT#03047629). ENT-01 is an orally administered, synthetic derivative of squalamine that acts locally on the enteric nerve cells of the gut, stimulating gut motility and altering afferent neural signaling from gut to brain. The compound displaces proteins that are electrostatically bound to intracellular membranes and, through this mechanism, suppresses aggregation of alpha-synuclein monomers into neurotoxic oligomers.

The trial enrolled 50 patients with Parkinson’s disease and constipation over a nine-month period. There were no safety issues and adverse events were largely confined to the GI tract. Systemic absorption was minimal, suggesting that the effect of the drug was local. The primary efficacy endpoint was the reversal of constipation. This was achieved in over 80% of patients, and the dose correlated positively with constipation severity at baseline, consistent with the hypothesis that constipation in PD results from the progressive accumulation of alpha-synuclein  in the enteric nervous system (ENS) and that the dose of ENT-01 required to restore neuronal activity is proportional to the load of alpha-synuclein in the enteric nerve cell.

The senior author of the study and Enterin Co-founder, President and CMO, Dr. Denise Barbut, said, “We demonstrate in this study that ENT-01 can restore gastrointestinal motility in patients with PD, suggesting that a major division of the nervous system and the largest sensory organ in the body (the GI tract) is not irreversibly damaged in patients with PD, despite the long-standing constipation that might suggest otherwise. We believe that this is the first demonstration of the reversal of a neurodegenerative process in humans.”

The study also found potential signals of clinical benefit for parkinsonism, cognition, hallucinations, sleep, REM-behavior disorder and circadian rhythm. According to the lead author, Dr. Robert Hauser, Professor of Neurology and Director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida, “While these results are intriguing, this was an open label trial and placebo effects cannot be excluded. These findings must undergo rigorous evaluation in future place-controlled trials.”

The company is currently conducting a larger, randomized, double-blind, placebo-controlled trial (KARMET) to further explore the effect of ENT-01 on constipation and neurologic symptoms in patients with Parkinson’s disease. The details of the study can be found on Clinicaltrials.gov (NCT#03781791).

About Enterin Inc.

Enterin Inc. is the first company 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, 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. Enterin Inc. is now progressing ENT-01 through clinical trials in an attempt to reverse the constipation and neurologic symptoms of Parkinson’s disease.

For more information, please visit www.enterininc.com.

PHILADELPHIA, January 9, 2019 (Newswire.com) – Enterin Inc., a privately held CNS-focused pharmaceutical company based in Philadelphia and developing novel compounds to treat neurodegenerative diseases, began screening patients for the KARMET study. Dr. Goldstein of Atlantis, Florida, and Dr. Kadimi of Fairfield, Connecticut, have both enrolled. The study is a Phase 2b 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. This clinical trial will enroll 72 patients over a six-month period. Details relating to the study can be found at ClinicalTrials.gov (NCT#03781791) and contact information is available on the Enterin website.

The study is a follow-up to a successful Phase 2a study (the RASMET study) completed last year. ENT-01 is an orally administered, synthetic derivative of squalamine that acts locally on the enteric nerve cells of the gut, stimulating gut motility and altering afferent neural signaling from gut to brain. Based on results from the RASMET study,  ENT-01 has the potential to ameliorate some or all of the non-motor and motor symptoms of Parkinson’s disease, including constipation, motor dysfunction, hallucinations, memory, depression, fragmented sleep and REM-behavior disorder.

About Enterin Inc.

Enterin Inc. is the first company 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, 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 and neurologic symptoms of Parkinson’s disease.

For more information, please visit www.enterininc.com.

Philadelphia, PA, March 26, 2018 (Newswire.com) – Enterin Inc., a CNS pharmaceutical company based in Philadelphia and developing novel compounds to treat Parkinson’s disease (PD), autism and schizophrenia, has completed enrollment of a two-stage Phase 2a study of ENT-01 in patients with PD.  The study was conducted at multiple US sites and 50 patients were enrolled over a 10-month period. In the first stage, single escalating doses of ENT-01 were administered to 10 patients and titrated to tolerability. In stage 2, daily escalating doses were administered to 40 patients and titrated to a clinically efficacious or maximum dose, followed by a randomized withdrawal period. Participating sites included Tampa Bay, Sarasota, Boca Raton, Port Charlotte, Georgetown, Los Angeles, New York, Philadelphia, Cleveland, Detroit, Michigan, Denver and others. Details relating to the study can be found at ClinicalTrials.gov. and on Enterin’s website, www.enterininc.com.

The study evaluated the safety, tolerability and efficacy of an orally administered synthetic derivative of squalamine (ENT-01), which is not absorbed into the bloodstream. 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 symptoms of Parkinson’s disease, including constipation, disturbed sleep and hallucinations, 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 paralysis that 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.

Enterin is planning to conduct a Phase 2b study in patients with PD and constipation in Q4 2018. Sites interested in participating should apply through Enterin’s website. The company is also planning to conduct studies in PD patients with hallucinations, in schizophrenia and in autism.

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 mobility. 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, 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