A Phase 1b/2a, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of APN1125 in Subjects With Schizophrenia

The purpose of this study in patients with schizophrenia is to evaluate the safety, tolerability, and pharmacokinetics of 3 doses (low, mid, high) of APN1125 compared with placebo when administered as repeated daily oral doses.

Start Date01 Apr 2016

Sponsor / Collaborator

CoMentis, Inc.

[+1]

NCT02331433 / CompletedPhase 1

A Phase 1 Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of APN1125 in Healthy Normal Subjects

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of APN1125 when administered as single doses to healthy adult subjects.

Start Date01 Dec 2014

Sponsor / Collaborator

CoMentis, Inc.

[+1]

NCT00783068 / CompletedNot ApplicableIIT

The Effect of the Alpha-7 Nicotinic AChR Agonist GTS-21 on Inflammation and End-organ Dysfunction During Human Endotoxemia

Rationale: The vagus nerve exerts an anti-inflammatory effect in in vitro and animal experiments. This 'vagal anti-inflammatory pathway' is mediated by the nicotinergic α7nACh receptor that can be selectively stimulated by GTS-21. Activation of the cholinergic anti-inflammatory pathway via vagus nerve stimulation or α7nAChR agonists improves outcome in animal models of endotoxemia, sepsis and experimental arthritis. Up to now, the anti-inflammatory effects of oral administration of GTS-21 in humans in vivo has not been investigated.
Objective: Primary aim: to investigate the anti-inflammatory effects of oral administration of GTS-21 on the inflammatory response in the human endotoxemia model and the subsequent inflammation-induced subclinical organ dysfunction. Secondary aim: to measure the effect of LPS administration in the absence or presence of GTS-21 in human volunteers on vagal nerve activity measured by heart rate variability analysis.
Study design: Double-blind placebo-controlled randomized cross-over intervention study in healthy human volunteers during experimental endotoxemia.
Study population: Non-smoking healthy male volunteers, age 18-35 yrs Intervention: Subjects will be tested in a cross-over design in 2 separate sequential sessions, 2-4 weeks apart. A total of 12 subjects will be randomly assigned to one of two dosing groups in a 1:1 ratio: GTS-21 followed by Placebo n=6, Placebo followed by GTS-21 n=6. Subjects will receive 150mg GTS-21 or placebo orally tid 3 days before LPS injection and an oral dose of 150 mg GTS-21 or placebo the morning of the day of LPS administration (07:00 AM). Subjects will then receive an oral dose of 150 mg GTS-21 or placebo at 08:00 AM and another oral dose of 150 mg GTS-21 or placebo at 1 hour before LPS administration (t=0). Before LPS injection, prehydration will be performed by infusion of 1.5 L 2.5% glucose/0.45% saline solution in 1 hour. One hour after the last dose of GTS-21 or placebo, LPS derived from E coli O:113 will be injected (2 ng/kg iv in 1 minute). There will be a 14 day washout period for patients in all groups. The last group of subjects will be subjected to an identical dose of LPS and placebo at two different moments 2-4 weeks apart to obtain time controls.
Main study parameters/endpoints: Main study endpoint is the concentration of circulating cytokines after LPS in the absence and presence of GTS-21.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: A medical interview and physical examination is part of this study. Approximately 350 ml blood will be withdrawn and urine will be collected. There will be mild discomfort associated with participation in this study, as LPS induces flu-like symptoms for approximately 4 hrs. GTS-21 was found to be well tolerated at a dose of 150 mg three times daily (450 mg/day).

Start Date01 Aug 2008

Sponsor / Collaborator

Radboud University Medical Center

[+1]

100 Clinical Results associated with CoMentis, Inc.

0 Patents (Medical) associated with CoMentis, Inc.

Literatures (Medical) associated with CoMentis, Inc.

01 Feb 2015·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand

Q4 · MEDICINE

Article

Author: Yen, Yu-Chen ; Bilcer, Geoffrey ; Brindisi, Margherita ; Xu, Xiaoming ; Koelsch, Gerald ; Mesecar, Andrew D ; Ghosh, Arun K ; Tang, Jordan ; Devasamudram, Thippeswamy ; Lei, Hui ; Huang, Xiangping

We describe structure-based design, synthesis, and biological evaluation of a series of novel inhibitors bearing a pyrazole (compounds 3a-h) or a thiazole moiety (compounds 4a-e) as the P3 ligand. We have also explored Boc-β-amino-l-alanine as a novel P2 ligand. A number of inhibitors have displayed β-secretase inhibitory potency. Inhibitor 4c has shown potent BACE1 inhibitory activity, Ki=0.25nM, cellular EC50 of 194nM, and displayed good selectivity over BACE2. A model of 4c was created based upon the X-ray structure of 2-bound β-secretase which revealed critical interactions in the active site.

01 Feb 2009·Journal of NeurotraumaQ2 · MEDICINE

Linking Binge Alcohol-Induced Neurodamage to Brain Edema and Potential Aquaporin-4 Upregulation: Evidence in Rat Organotypic Brain Slice Cultures andIn Vivo

Q2 · MEDICINE

Article

Author: Neafsey, Edward J. ; Brown, James ; Sripathirathan, Kumar ; Collins, Michael A.

Brain edema and derived oxidative stress potentially are critical events in the hippocampal-entorhinal cortical (HEC) neurodegeneration caused by binge alcohol (ethanol) intoxication and withdrawal in adult rats. Edema's role is based on findings that furosemide diuretic antagonizes binge alcohol-dependent brain overhydration and neurodamage in vivo and in rat organotypic HEC slice cultures. However, evidence that furosemide has significant antioxidant potential and knowledge that alcohol can cause oxidative stress through non-edemic pathways has placed edema's role in question. We therefore studied three other diuretics and a related non-diuretic that, according to our oxygen radical antioxidant capacity (ORAC) assays or the literature, possess minimal antioxidant potential. Acetazolamide (ATZ), a carbonic anhydrase inhibitor/diuretic with negligible ORAC effectiveness and, interestingly, an aquaporin-4 (AQP4) water channel inhibitor, prevented alcohol-dependent tissue edema and neurodegeneration in HEC slice cultures. Likewise, in binge alcohol-intoxicated rats, ATZ suppressed brain edema while inhibiting neurodegeneration. Torasemide, a loop diuretic lacking furosemide's ORAC capability, also prevented alcohol-induced neurodamage in HEC slice cultures. However, bumetanide (BUM), a diuretic blocker of Na(+)-K(+)-2Cl(-) channels, and L-644, 711, a nondiuretic anion channel inhibitor--both lacking antioxidant capabilities as well as reportedly ineffective against alcohol-dependent brain damage in vivo--reduced neither alcohol-induced neurotoxicity nor (with BUM) edema in HEC slices. Because an AQP4 blocker (ATZ) was neuroprotective, AQP4 expression in the HEC slices was examined and found to be elevated by binge alcohol. The results further indicate that binge ethanol-induced brain edema/swelling, potentially associated with AQP4 upregulation, may be important in consequent neurodegeneration that could derive from neuroinflammatory processes, for example, membrane arachidonic acid mobilization and associated oxidative stress.

01 Apr 2008·Investigative Opthalmology & Visual ScienceQ2 · MEDICINE

Mecamylamine Suppresses Basal and Nicotine-Stimulated Choroidal Neovascularization

Q2 · MEDICINE

ArticleOA

Author: Lima e Silva, Raquel ; Campochiaro, Peter A. ; Yokoi, Katsutoshi ; Matsuoka, Masato ; Ueno, Shinji ; Khu, Naw Htee ; Cooke, John P. ; Kengatharan, Muralitharan ; Verghese, Mary ; Wu, Jenny C. ; Kiuchi, Katsuji

PURPOSENicotinic acetylcholine receptors (nAChR) are best known for their role in neurotransmission, but they have recently been demonstrated on vascular endothelial cells. Acetylcholine is their endogenous ligand, but they are also stimulated by nicotine. By stimulating nAChR, nicotine promotes tumor angiogenesis as well as atherosclerotic plaque neovascularization. In this study, the authors investigated the role of nAChR in the pathogenesis of choroidal neovascularization (CNV).METHODSThe effect of the nonselective nAChR antagonist mecamylamine was tested on human retinal and choroidal endothelial cells in vitro and in a murine model of CNV.RESULTSSeveral nAChR isoforms were identified in retinal and choroidal microvascular endothelial cells, and the ability of these cells to form tubules when grown in growth factor-reduced basement membrane matrix and supplemented with VEGF was suppressed by the nAChR antagonist mecamylamine. Supplementation of the drinking water of mice with nicotine increased the size of CNV lesions at Bruch membrane rupture sites, an effect that was blocked by subcutaneous administration of mecamylamine (50 mg/kg/d) by an osmotic pump. In the absence of nicotine, CNV formation was suppressed by the infusion of 50 mg/kg/d mecamylamine or by topical application 0.1 or 1% mecamylamine to the cornea.CONCLUSIONSThese data suggest that endogenous activation of nAChR promotes CNV and that activation of nAChR by nicotine may contribute to the increased incidence of CNV seen in smokers with age-related macular degeneration (AMD). Topically administered mecamylamine could provide an appealing new treatment approach for CNV.

News (Medical) associated with CoMentis, Inc.

31 Jul 2023

·www.globenewswire.com

Neurona Therapeutics Appoints James Stutz as Chief Financial Officer and Chief Business Officer

SAN FRANCISCO, July 31, 2023 (GLOBE NEWSWIRE) -- Neurona Therapeutics, a clinical-stage biotherapeutics company advancing regenerative cell therapy candidates for the treatment of neurological disorders, today announced the appointment of James Stutz, a business and finance executive with over 20 years of experience in the biopharma industry, as chief financial officer (CFO) and chief business officer (CBO). “We are delighted to welcome James to the Neurona team and look forward to the value he will bring as we continue to advance our ongoing clinical studies of NRTX-1001 in adults with drug-resistant focal epilepsy and work to maximize the potential opportunities ahead for our novel cell therapy approach in other focal epilepsy conditions and Alzheimer’s disease,” said Cory R. Nicholas, Ph.D., Neurona’s chief executive officer. “James brings extensive business and operational experience in private and public companies as well as the venture capital world which makes him an excellent choice to lead our finance and business operations.” “I am excited to join Neurona at this important stage in the company’s development as it generates a growing body of positive clinical data supporting the development of NRTX-1001 as a potentially life-changing new therapy for focal epilepsy,” said Mr. Stutz. “Furthermore, it’s an honor to join this talented and dedicated team that is committed to developing new regenerative cell therapies to improve the lives of patients living with chronic neurological disorders.” Mr. Stutz has 20 years of experience in the biopharma industry across multiple operating roles in private and public biotech companies as well as in venture capital investment, and management consulting. Prior to joining Neurona, he served as CBO at Actym Therapeutics, a private company developing microbial cell therapies designed to overcome the tumor microenvironment, and prior to that as head of business development at Instil Bio, a global public, clinical stage, cell therapy company developing tumor infiltrating lymphocytes for the treatment of cancer. Before joining Instil Bio, Mr. Stutz was the CFO at Tolerion, and CBO at Tioma Therapeutics. Earlier in his career he held roles of increasing responsibility at InterMune, CoMentis, and Alios BioPharma (acquired by Janssen Pharmaceutical Companies of Johnson & Johnson). Prior to holding operating roles in biopharma companies, Mr. Stutz was a principal with Essex Woodlands Health Ventures where he focused on investments in the biopharma and life sciences tools space including ProteinSimple (acquired by BioTechne), Revance Therapeutics, IntegenX (acquired by Thermo Fisher Scientific) and Symphogen (acquired by Servier). He was also a senior consultant with Strategic Decisions Group and prior to his career in the life science industry was a commissioned officer in the United States Air Force. Mr. Stutz earned an MBA from the Tuck School of Business at Dartmouth and a B.A. in business economics, from the University of California at Santa Barbara. About NeuronaNeurona is focused on developing regenerative cell therapy candidates that have single-dose curative potential. Neurona is developing off-the-shelf, allogeneic neural cell therapy candidates that are designed to provide long-term repair of dysfunctional neural networks for multiple neurological disorders. For more information about Neurona, visit www.neuronatherapeutics.com Forward Looking StatementsThis press release includes forward-looking statements that are subject to risks and uncertainties, including risks and uncertainties inherent in clinical development of therapeutic candidates and obtaining data to support regulatory approval. NRTX-1001 is an investigational candidate and is being evaluated in ongoing clinical trials. NRTX-1001 has not been approved by any regulatory authority for commercial use or deemed to be safe or effective for any indication. Investor and Media Contacts: Sylvia WheelerWheelhouse LSAswheeler@wheelhouselsa.comElizabeth Wolffe, Ph.D.Wheelhouse LSAlwolffe@wheelhouselsa.com

Cell TherapyExecutive ChangeAcquisition

100 Deals associated with CoMentis, Inc.

100 Translational Medicine associated with CoMentis, Inc.

Corporation Tree

Boost your research with our corporation tree data.

view full example data

Pipeline

Pipeline Snapshot as of 27 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Other

Current Projects

Drug(Targets)	Indications	Global Highest Phase

APN-1125 ( CHRNA7 )	Schizophrenia More	Suspended
Mecamylamine Hydrochloride ( nAChRα1/β1/δ/γ )	Wet age-related macular degeneration More	Discontinued
ATG-002 ( Muscle-type nAChRs )	Diabetic foot ulcer More	Discontinued
DMXB-Anabaseine ( CHRNA7 )	Alzheimer Disease More	Discontinued
ATG-001 ( nAChRs )	Dystrophy, Macular More	Pending

Deal

Boost your decision using our deal data.

view full example data

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Profit

Explore the financial positions of over 360K organizations with Synapse.

view full example data

Grant & Funding(NIH)

Access more than 2 million grant and funding information to elevate your research journey.

view full example data

Investment

Gain insights on the latest company investments from start-ups to established corporations.

view full example data

Financing

Unearth financing trends to validate and advance investment opportunities.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

CoMentis, Inc.

Overview

Related

Corporation Tree

Pipeline

Pipeline Snapshot as of 27 Nov 2024

Current Projects

Deal

Translational Medicine

Profit

Grant & Funding(NIH)

Investment

Financing