A Single-Center, Randomized, Placebo-Controlled, Single Ascending Dose Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous Nts-104 Tris in Healthy Adults

NTS-104 TRIS will be administered as a single intravenous dose to healthy subjects at doses of 0.8, 4, 8 and 16 mg/kg in 4 Cohorts. Each cohort of 8 subjects will begin with dosing 2 sentinel subjects with one being given the investigational product and one the placebo. If no safety issues arise, dosing the remaining subjects in the cohort will begin. A Safety Review Committee will review the safety and pharmacokinetic data before approving escalation to the next dose level.

Start Date28 Apr 2023

Sponsor / Collaborator

NeuroTrauma Sciences LLC

[+1]

100 Clinical Results associated with NTS-104

100 Translational Medicine associated with NTS-104

100 Patents (Medical) associated with NTS-104

Literatures (Medical) associated with NTS-104

01 Oct 2024·Neurotherapeutics

Improvement in edema and cognitive recovery after moderate traumatic brain injury with the neurosteroid prodrug NTS-104

Article

Author: Dallera, Carlos A. ; Parry, Tom J. ; Balleste, Alyssa F. ; Alvarez, Jacqueline C ; Alvarez, Jacqueline C. ; Atkins, Coleen M. ; Buller, Benjamin ; Billing, Clare B. ; Torres, Maria Dominguez ; Mastromatteo-Alberga, Patrizzia ; Verdoorn, Todd A ; Billing, Clare B ; Dietrich, W Dalton ; Dallera, Carlos A ; Atkins, Coleen M ; Placeres-Uray, Fabiola ; Dietrich, W. Dalton ; Verdoorn, Todd A. ; Balleste, Alyssa F ; Parry, Tom J

Neuroactive steroids reduce mortality, decrease edema, and improve functional outcomes in preclinical and clinical traumatic brain injury (TBI) studies. In this study, we tested the efficacy of two related novel neuroactive steroids, NTS-104 and NTS-105, in a rat model of TBI. NTS-104 is a water-soluble prodrug of NTS-105, a partial progesterone receptor agonist. To investigate the effects of NTS-104 on TBI recovery, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion injury or sham surgery and were treated with vehicle or NTS-104 (10 mg/kg, intramuscularly) at 4, 10, 24, and 48 h post-TBI. The therapeutic time window was also assessed using the neuroactive steroid NTS-105 (3 mg/kg, intramuscularly). Edema in the parietal cortex and hippocampus, measured at 3 days post-injury (DPI), was reduced by NTS-104 and NTS-105. NTS-105 was effective in reducing edema when given at 4, 10, or 24 h post-injury. Sensorimotor deficits in the cylinder test at 3 DPI were ameliorated by NTS-104 and NTS-105 treatment. Cognitive recovery, assessed with cue and contextual fear conditioning and retention of the water maze task assessed subacutely 1-3 weeks post-injury, also improved with NTS-104 treatment. Cortical and hippocampal atrophy at 22 DPI did not improve, indicating that NTS-104/NTS-105 may promote post-TBI cognitive recovery by controlling edema and other processes. These results demonstrate that NTS-104/NTS-105 is a promising therapeutic approach to improve motor and cognitive recovery after moderate TBI.

01 Nov 2022·Stroke

Pharmacological Characterization of a Novel Neuroactive Steroid Prodrug, NTS-104, and Its Neuroprotective Activity in Experimental Stroke Models

Article

Author: Billing, Clare B. ; Woodhouse, Colleen ; Poulsen, David ; Lam, Leslie ; Zhang, Li ; Schwartz-Byrne, Robin ; Zhang, Zheng Gang ; Buller, Benjamin ; Li, Chao ; Verdoorn, Todd A. ; McGuire, Matthew ; Chopp, Michael ; Powell, Brianna ; Wei, Min ; Gertz, Steven ; Parry, Tom J.

Background::

Ischemic stroke affects about 700 000 patients per year in the United States, and to date, there are no effective pharmacological agents that promote recovery. Here, we studied the pharmacokinetics, pharmacodynamics, and efficacy of NTS-105, a novel neuroactive steroid, and NTS-104, a prodrug of NTS-105, in 2 models of ischemic stroke.

Methods::

The pharmacodynamics and pharmacokinetics of NTS-104/105 were investigated in naive and stroke rats, and models of embolic and transient middle cerebral artery occlusion were used to investigate the dose-related effects of NTS-104. All rats were randomly assigned into the experimental groups, and all outcome measurements were performed blindly.

Results::

Blood plasma and brain pharmacokinetic analysis revealed that NTS-104 rapidly converted to NTS-105, which reached peak concentration at ≈1 hour after dosing and distributed similarly to normal and ischemic brains. NTS-104 administration 4 hours after embolic middle cerebral artery occlusion led to a dose-dependent improvement of neurological outcomes and a dose-dependent reduction of infarct volumes relative to vehicle-treated animals. A single dose level study confirmed that NTS-104 administered 4 hours after transient middle cerebral artery occlusion was also neuroprotective. Quantitative ELISA revealed that NTS-104 treatment resulted in time- and dose-dependent changes in AKT activation and cytokine levels within the ischemic brain, which included reductions of IL-6, VEGF, ICAM-1, IL-1β, MCP-1, RAGE, and GM-CSF. Time- and dose-dependent reductions in IL-6 and GM-CSF were also observed in the plasma along with an elevation of galectin-1.

Conclusions::

NTS-104 is a novel prodrug that converts to a novel neuroactive steroid, NTS-105, which improves functional outcomes in experimental ischemic stroke models.

News (Medical) associated with NTS-104

09 Jan 2024

·www.biospace.com

NeuroTrauma Sciences Appoints William Fricker, CPA, MBA, as Chief Financial Officer

[09-January-2024] David Lawrence Departs as CFO; Appointed to Board of Directors ATLANTA, Jan. 9, 2024 /PRNewswire/ -- NeuroTrauma Sciences, LLC (NTS), a private biopharmaceutical company developing neuroprotective therapeutics for treating central nervous system (CNS) injuries including stroke and traumatic brain injury, today announced the appointment of William Fricker, CPA, MBA, to Chief Financial Officer, effective immediately. In this position, Mr. Fricker will assume responsibility for the oversight of NTS's financial strategy and operations. NeuroTrauma Sciences Appoints William Fricker, CPA, MBA, as Chief Financial Officer David Lawrence has stepped down from the full-time CFO position at NeuroTrauma Sciences. He will remain as a consultant and has been appointed to the Board of Directors. Mr. Fricker brings to NTS more than 25 years of financial expertise across industries, including pharmaceutical and biotechnology companies, most recently as Chief Financial Officer for Eleison Pharmaceuticals and NeuroRx. In addition, he served as Vice President, Finance & Principal Accounting Officer for Immunomedics, where he supported the transition from a clinical-stage organization to a fully commercial biopharmaceutical company through its acquisition by Gilead in 2020. There he also managed over $600 million in equity raises. Earlier in his career, he held finance and accounting positions at Johnson & Johnson Corporation and Bristol-Myers Squibb Company, as well as Coopers & Lybrand. Mr. Fricker holds a Bachelor of Science in Accounting from Penn State University and a Master of Business Administration from Villanova University. He is a Certified Public Accountant. "NTS is developing neuroprotective compounds in the critically underserved areas of stroke and traumatic brain injury, and I am honored to join the company and leverage my expertise to contribute to its success," said Mr. Fricker. "I look forward to partnering with the team to execute on its strategy and help realize the potential of investigational drug NTS-104." "Throughout Bill's significant industry tenure, he has improved financial discipline and supported the finance and operational functions of companies at all stages," said Carl Long, Chief Executive Officer. "We are pleased to welcome him to our executive leadership team at an important time in the company's growth." Mr. Long continued, "We also thank Dave Lawrence for his contributions to NTS, for his strategic leadership and integrity in the financial management of the company, and we look forward to continue working with him in another capacity." About NeuroTrauma Sciences NeuroTrauma Sciences is a biopharmaceutical company advancing its mission to develop neuroprotective therapies for treating CNS injuries, including ischemic stroke and traumatic brain injury (TBI). Acquired brain injuries remain areas of high unmet need with limited therapeutic options to alleviate the cognitive, functional, and neurobehavioral effects for millions of patients worldwide. By leveraging insights into the biology of acquired brain injury, NTS is advancing a pipeline of candidates targeting ischemic stroke and TBI. For additional information, please visit . Contacts: NeuroTrauma Sciences William Fricker, CPA, MBA Chief Financial Officer M: 215-622-7875 w.fricker@neurotraumasciences.com SMP Communications Susan Pietropaolo M: 201-923-2049 susan@smpcommunications.com

Executive ChangeAcquisition

31 Jul 2023

·www.prnewswire.com

NeuroTrauma Sciences Appoints Kevin Pong, PhD, MBA as Chief Business Officer

Accomplished Business Development and Licensing Executive to Drive NTS's Business Development and Partnering Activities ATLANTA, July 31, 2023 /PRNewswire/ -- NeuroTrauma Sciences, LLC (NTS), a private biopharmaceutical company developing neuroprotective therapeutics for treating central nervous system (CNS) injuries, including stroke and traumatic brain injury, today announced the appointment of Kevin Pong, PhD, MBA as Chief Business Officer. In this position, Dr. Pong is responsible for the strategic leadership of the company's global business development, licensing, and alliance management activities. "We are delighted to welcome Kevin to our executive leadership team," said Carl Long, Chief Executive Officer. "His deep experience in business development and partnering strategy and ability to foster strong business relationships, combined with a background in neuroscience, will be valuable as we progress our lead program NTS-104 in stroke through the clinic and advance our vital work in traumatic brain injury." Dr. Pong brings to NTS more than 20 years of industry experience with a successful track record of business development and licensing transactions in biotech and pharmaceutical companies. Most recently, he served as Chief Business Officer of Anima Biotech, where he drove multiple transformative transactions and helped evolve the company's partnering strategy. Prior to Anima, he served as vice president of business development, licensing, and alliance management at Summit Therapeutics and led the identification, evaluation, and negotiation of CNS business development opportunities at Sunovion Pharmaceuticals. He spent several years at Endo Pharmaceuticals in business development roles of increasing responsibility and held leadership roles in discovery neuroscience research at Wyeth. Dr. Pong holds a B.S. in Biological Sciences, a Ph.D. in Neuroscience from the University of Southern California, and an MBA from Rutgers University. "I am excited by the potential I see in NTS and the opportunity to be a part of the team advancing compounds in the critically underserved areas of stroke and traumatic brain injury," said Dr. Pong. "I am delighted to be working in the neuroscience field again and look forward to leveraging my expertise and network." About NeuroTrauma Sciences NeuroTrauma Sciences is a biopharmaceutical company advancing its mission to develop neuroprotective therapies for treating CNS injuries, including ischemic stroke and traumatic brain injury (TBI). Acquired brain injuries remain areas of high unmet need with limited therapeutic options to alleviate the cognitive, functional, and neurobehavioral effects for millions of patients worldwide. By leveraging insights into the biology of acquired brain injury, NTS is advancing a pipeline of candidates targeting ischemic stroke and TBI. For additional information, please visit . Contacts: NeuroTrauma Sciences David Lawrence Chief Financial Officer M: 845-548-6311 [email protected] SMP Communications Susan Pietropaolo M: 201-923-2049 [email protected] SOURCE NeuroTrauma Sciences, LLC

Executive Change

01 Jun 2023

·www.prnewswire.com

NeuroTrauma Sciences Commences First-in-Human Dosing in the US of Investigational Neuroprotective Drug NTS-104

Phase 1 safety study of NTS-104 is initiated in healthy volunteers Compound is being developed for stroke and other Central Nervous System (CNS) injuries ATLANTA, June 1, 2023 /PRNewswire/ -- NeuroTrauma Sciences, LLC (NTS), a private biopharmaceutical company developing neuroprotective therapeutics for treating patients with stroke and other CNS injuries, today announced that it has commenced dosing in a Phase 1 study of its investigational drug NTS-104, in healthy volunteers. The single-dose, randomized, double-blind, placebo-controlled, Phase 1 single-center dose-escalation study will assess the safety, tolerability, and pharmacokinetics of intravenous NTS-104 in healthy US participants. The study is expected to enroll a total of 32 participants across four cohorts. For more information, please visit . (NCT05547438) "First-in-human dosing of our novel drug, NTS-104, is an important achievement for NTS," said Carl Long, Chief Executive Officer. "NTS-104 represents a compelling approach to neuroprotection with the objective of improving neurologic recovery and function in millions of patients worldwide. Our principal developmental focus is in stroke, where there are few effective treatments and a tremendous unmet need. Additionally, NTS's extensive preclinical study program demonstrates NTS-104's potential to treat multiple forms of brain injury." About NTS-104 NTS-104 is a novel, water-soluble neurosteroid prodrug that, when delivered intravenously, is converted in the bloodstream to NTS-105, the active neurosteroid. NTS-105 rapidly enters the brain at concentrations sufficient to modulate key target receptors, protecting neurons from inflammation, edema, and programmed cell death. NTS-104 has demonstrated efficacy in multiple preclinical brain injury models validated at independent laboratories. NeuroTrauma Sciences plans to conduct a Phase 2 study of NTS-104 in acute ischemic stroke. About NeuroTrauma Sciences NeuroTrauma Sciences is a biopharmaceutical company advancing its mission to develop neuroprotective therapies for treating patients with stroke and other CNS injuries. By leveraging insights into the biology of CNS injury, NTS is advancing a pipeline of therapeutic candidates targeting ischemic stroke and CNS injuries. For additional information, please visit . Contacts: NeuroTrauma Sciences David Lawrence Chief Financial Officer M: 845-548-6311 [email protected] SMP Communications Susan Pietropaolo M: 201-923-2049 [email protected] SOURCE NeuroTrauma Sciences, LLC

Phase 1

100 Deals associated with NTS-104

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	Phase 1	United States	NeuroTrauma Sciences LLC	28 Apr 2023
Stroke	Phase 1	-	NeuroTrauma Sciences LLC	-
Brain Injuries, Traumatic	Preclinical	United States	NeuroTrauma Sciences LLC	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EANM2024	Not Applicable	-	-	Prodrug labeled in position 1	xngbrbfbvv(hiqavdiviz) = mwrmjaviym nzqsmoyjfc (ztgoigkjxw )	-	27 Sep 2024
				Prodrug labeled in position 2	xngbrbfbvv(hiqavdiviz) = oaaqqzvwui nzqsmoyjfc (ztgoigkjxw )

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