A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis

The primary purpose of this study is to determine if a single dose of nerinetide can reduce global disability in people who have had a stroke and are selected for endovascular therapy without the use of a tissue plasminogen activator (alteplase, tenecteplase, or equivalent).

Start Date06 Dec 2020

Sponsor / Collaborator

NoNO, Inc.

[+1]

NCT02930018

/ CompletedPhase 3

A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Intravenous NA-1 in Subjects With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy

The ESCAPE-NA-1 study is designed to determine the safety and efficacy of the neuroprotectant, Nerinetide (NA-1), in reducing global disability in subjects with major acute ischemic stroke (AIS) with a small established infarct core and with good collateral circulation who are selected for endovascular revascularization.

Start Date01 Mar 2017

Sponsor / Collaborator

NoNO, Inc.

[+1]

NCT02056574

/ WithdrawnPhase 2

Phase 2, Multicenter Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study Evaluating a Single Dose of Intravenous NA-1 in Patients With Subarachnoid Hemorrhage Undergoing Endovascular Repair of Ruptured Intracranial Aneurysms

This is a randomized, double-blind, placebo-controlled, single-dose study investigating the safety and efficacy of NA-1 in patients with subarachnoid hemorrhage (SAH) undergoing endovascular repair of ruptured intracranial aneurysms. Up to 300 male and female patients with SAH undergoing endovascular repair of a ruptured intracranial aneurysm will be dosed with 2.60 mg/kg of NA-1 or placebo as a 10 minute intravenous infusion after completion of the endovascular procedure on Day 1 of the study period. Subjects will undergo interim procedures at Day 2-4, Day 30-45, and end-of-study procedures on Day 90.

Start Date01 Nov 2015

Sponsor / Collaborator

NoNO, Inc.

100 Clinical Results associated with Nerinetide

100 Translational Medicine associated with Nerinetide

100 Patents (Medical) associated with Nerinetide

Literatures (Medical) associated with Nerinetide

01 Feb 2026·Canadian Journal of Emergency Medicine

Efficacy and safety of intravenous nerinetide initiated by paramedics in the field for acute cerebral ischaemia within 3 h of symptom onset (FRONTIER): a phase 2, multicentre, randomised, double-blind, placebo-controlled study

Author: Perry, Jeffrey J ; McKinnon, Mathieu ; Ferguson, Emma

14 Jan 2026·Science Translational Medicine

Brain-derived tau for monitoring brain injury in acute ischemic stroke

Article

A specific and accurate blood test for acute brain injury could help monitor infarct growth in ischemic stroke and serve as a surrogate end point in clinical trials. Using a single-molecule detection assay, we assessed plasma brain-derived tau (BD-tau), a marker selectively quantifying tau protein from the central nervous system, in a prospective cohort of 502 patients with acute ischemic stroke with serial blood sampling from admission to day 7. Higher BD-tau concentrations at admission were associated with more extensive early brain injury on computed tomography and predicted larger final infarct volumes. BD-tau increases from admission to day 2 were related to infarct growth. BD-tau concentrations rose until day 7 and were higher in patients with secondary events, including recurrent stroke. After thrombectomy, the rise of BD-tau was smaller in patients with complete versus incomplete recanalization. BD-tau outperformed other blood markers and imaging metrics in predicting 90-day functional outcome across infarct size strata and time points. In an independent multicenter prospective cohort ( N = 519), BD-tau showed higher performance than magnetic resonance imaging–derived final infarct volume in predicting functional outcomes at 3, 12, and 36 months. In the biomarker substudy of a phase 3 trial assessing nerinetide in patients with ischemic stroke ( N = 193), BD-tau showed predictive performance comparable to the other cohorts, mediated the relationship between recanalization and functional outcome, and showed a 49% smaller increase in the nerinetide group versus placebo. Overall, plasma BD-tau tracked ischemic brain injury over time, outperformed other biomarkers in predicting functional outcomes, and identified possible treatment responses.

01 Jan 2026·INTERNATIONAL JOURNAL OF PHARMACEUTICS

Modifying the PSD-95 inhibitor NA-1 for brain delivery through proteolytic stabilization and conjugation to the potentially brain homing peptide BR1

Article

Author: Gammelgaard, Bente ; Brodin, Birger ; Andresen, Amalie Kjær ; Øie Solbak, Sara Marie ; Kristensen, Mie ; Kolberg, Hannah Grønbech ; Jensen, Camilla ; Thaysen, Maria

Delivering peptide-based therapeutics to the brain through systemic administration is limited by poor blood-brain barrier permeation, rapid proteolytic degradation, and off-target accumulation. The peptide NA-1, targeting PSD-95 interactions, holds promise for stroke treatment but suffers from these limitations. With this study, we explored whether complete D-amino acid substitution of NA-1 and conjugation to the potentially brain-homing peptide BR1 would improve NA-1 plasma stability and brain delivery, while retaining receptor binding and limiting off-target organ accumulation. Four peptide constructs, L- and D-versions of NA-1 and BR1-NA-1, were synthesized and characterized using circular dichroism spectroscopy, surface plasmon resonance, mouse plasma stability assays, cellular uptake studies, and biodistribution analysis in mice. D-amino acid substitution significantly enhanced peptide stability in plasma but compromised receptor binding and to some extent cellular uptake. L-BR1-NA-1 showed improved accumulation in whole brain lysates as compared to L-NA-1, however parenchymal delivery did not differ between the two peptides, indicating vascular retention of the L-BR1-NA-1 form. The present study demonstrated that substitution of L-amino acids with their D-amino acid counterparts improved the proteolytic stability of the constructs. However, this came at the expense of target affinity. BR1 conjugation to L-NA-1 might increase vascular retention, but did not increase parenchymal delivery, indicating that BR1 does not mediate transendothelial passage of the construct.

News (Medical) associated with Nerinetide

22 Nov 2022

·www.nonoinc.ca

NoNO Inc. Announces First Patient Dosed with NoNO-42 in a First in Humans Phase 1 Study

TORONTO, Nov 22, 2022 – NoNO Inc. is pleased to announce the dosing of the first participant in its Phase 1 clinical trial evaluating NoNO-42. NoNO-42 is the next generation drug developed in NoNO’s PSD-95 inhibitor platform. It is intended for the treatment of all people experiencing an acute ischemic stroke. The first in human study with NoNO-42 will evaluate the safety, tolerability and pharmacokinetics of single ascending doses of NoNO-42 in consecutive cohorts of healthy volunteers. NoNO-42 builds on NoNO’s ground-breaking results for its first-generation PSD-95 inhibitor, nerinetide. In the Phase 3 ESCAPE-NA1 trial, participants who were treated with nerinetide but not with thrombolytics (“clot-busters”) exhibited improved functional independence, reduced stroke mortality, and reduced brain damage on medical imaging. ESCAPE-NA1 was conducted in stroke in patients who were selected to undergo endovascular thrombectomy, a treatment in which the blood clots causing the stroke are removed in order to restore blood flow to the brain. The study provided evidence that such patients may benefit from nerinetide if they are not previously treated with thrombolytics. However, in patients who had already received thrombolytic treatment nullified the efficacy of nerinetide. The results in the no-thrombolytic arm are currently under confirmatory testing in the ongoing Phase 3 ESCAPE-NEXT trial. NoNO-42 was developed to be administered with or without thrombolytic agents. It extends the potential benefits of PSD-95 inhibition to those patients who, in ESCAPE-NA1 were previously treated with thrombolytics and therefore could not benefit from nerinetide. “The Phase 1 trial of NoNO-42 is a key milestone in extending the benefits of PSD-95 inhibition all acute ischemic stroke patients. Given NoNO-42’s similarities to nerinetide in all material clinical aspects other than its expected efficacy with or without thrombolytics, success with current pivotal trials with nerinetide will de-risk NoNO-42 development substantially” said Dr. Michael Tymianski, President, CEO and founder of NoNO Inc. “The stroke neurology community is extremely excited about the prospects of both nerinetide and NoNO-42, and the academic community is eager to follow-up ESCAPE-NEXT with clinical trials to investigate the efficacy of NoNO-42 in stroke patients” said Dr. Michael Hill, MD, Global Principal Investigator and Professor of Neurology at the Cumming School of Medicine, University of Calgary. NoNO Inc. is a clinical stage, stroke-focused Ontario biotechnology company dedicated to offering people who experience stroke opportunities for a better life. NoNO’s therapeutic strategy is to inhibit key protein-protein interactions of PSD-95 that are involved selectively in cellular signals that cause stroke damage, but without interfering with normal cell functions. Our PSD-95 inhibitor platform consists of: Nerinetide, NoNO’s lead compound for people experiencing an ischemic stroke, currently completing its second global Phase 3 trail in people not previously treated with a clot dissolving drug. NoNO-42, in Phase 1 for use alongside clot dissolving drugs for all people experiencing ischemic stroke. NoNO-SC, administered subcutaneously to enable the treatment of people experiencing stroke outside of medical setting by anyone – anywhere. For more information, please visit www.nonoinc.ca.

Phase 1Phase 3Phase 2

22 Mar 2022

·www.nonoinc.ca

NoNO Inc. Announces the Start of the Global Phase 3 ESCAPE-NEXT Trial of the Peptide Nerinetide in Acute Ischemic Stroke Excluding Thrombolysis

TORONTO, Dec 6, 2020 – NoNO Inc. is pleased to announce the enrollment of the first patient in the ESCAPE-NEXT trial, NoNO’s second global phase 3 trial of its lead peptide, Nerinetide. ESCAPE-NEXT is a multicentre, randomized, double-blinded, placebo-controlled, parallel group, single-dose design to determine the efficacy and safety of nerinetide in participants with acute ischemic stroke undergoing endovascular thrombectomy (EVT). ESCAPE-NEXT is informed by the ESCAPE-NA1 trial which suggested that treatment with nerinetide may improve functional independence, reduce stroke mortality, and reduce brain damage due to stroke in patients who undergo EVT without the prior administration of thrombolytic (“clot busting”) agents. ESCAPE-NA1 results were presented at the 2020 International Stroke Conference in February. “Our prior trial showed us which stroke patients may benefit from nerinetide. ESCAPE-NEXT is a further pivotal study, focused on those patients, and is intended to confirm the promising findings of clinical benefits suggested by ESCAPE-NA1. ESCAPE-NEXT has a substantially similar design, but focuses on those patients who may experience the greatest benefit from nerinetide” said Dr. Michael Tymianski, President, CEO and founder of NoNO Inc. “We are exploring a novel mechanism of action for a new drug in a very common, but devasting disease. A new drug for acute ischemic stroke has the potential to further transform stroke therapeutics,” said Dr. Michael Hill, MD, Global Principal Investigator and Professor of Neurology at the Cumming School of Medicine, University of Calgary. ESCAPE-NEXT is designed to evaluate the clinical benefits of nerinetide in acute stroke patients who are selected for endovascular revascularization without prior treatment with intravenous thrombolytic therapy. The trial will enroll adult participants in the USA, Canada, Europe and Australia. It has an initial enrollment target of 680 participants, with an option to increase the sample to 1020 following an interim analysis. Pivotal outcomes will be evaluated at 90 days with a further analysis at one year after the stroke.

Phase 3

22 Mar 2022

·www.nonoinc.ca

Press Release - NoNO Inc. | Change Everything

Toronto, Canada, April 7, 2021, 2PM ET – NoNO Inc., an Ontario biotechnology company developing innovative neurotherapeutics for acute stroke and other central nervous system disorders, announced today the publication of prototypes for next generation protease-resistant PSD-95 inhibitors. Published in the journal Science Translational Medicine, the article entitled “Plasmin-resistant PSD-95 inhibitors resolve effect-modifying drug-drug interactions between alteplase and nerinetide in acute stroke” demonstrates the potential of novel next-generation protease-resistant compounds for the treatment of acute ischemic strokes. Such compounds may be practically integrated into current stroke care workflows without the need to modify existing medical practice. These next generation compounds are expected to extend the therapeutic utility of PSD-95 inhibition to all eligible stroke patients, including those that are treated with drugs such as alteplase. The next generation compounds build on nerinetide, NoNO Inc.’s clinical stage lead PSD-95 inhibitor compound. Nerinetide was recently tested in the Phase 3 ESCAPE-NA1 study which provided promising results for the clinical safety and efficacy of nerinetide in acute ischemic stroke, as published in the journal The Lancet. ESCAPE-NA1 showed that nerinetide is promising in stroke patients who do not receive prior treatment with the thrombolytic agent, alteplase, and this is currently being evaluated further in the ongoing global Phase 3 ESCAPE-NEXT study. If ESCAPE-NEXT is successful, both studies will provide support for PSD-95 inhibition as a platform therapy for stroke and related neurological disorders. NoNO Inc. CEO Dr. Michael Tymianski commented that, “Nerinetide and next generation PSD-95 inhibitors continue to grow as a strategy for treating a wide range of neurological disorders that implicate excitotoxicity and neuroplasticity. Neuroprotection for acute ischemic stroke is achievable, and with continued improvements in our PSD-95 inhibitor technology, providing a benefit to patients in additional indications such as stroke recovery, traumatic brain injury and Alzheimer’s disease should be achievable as well.” NoNO Inc. is an Ontario biotechnology company whose focus is on developing therapeutic drugs in areas of unmet medical needs. Its drug pipeline includes therapeutic agents in various stages of development ranging from cellular and molecular discovery to human clinical trials. Its lead projects relate to diseases of the nervous system whose mechanisms involve the protein PSD-95, including stroke, traumatic brain injury and neuropathic pain. NoNO Inc.’s strategy is to inhibit key protein-protein interactions of PSD-95 that are involved selectively in cellular signals that cause cell damage, but without interfering with normal cell functions. For more information, please visit www.nonoinc.ca.

Phase 3Clinical Result

100 Deals associated with Nerinetide

External Link

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D11729	-	-	DB12595

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	Phase 3	United States	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Australia	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Canada	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Germany	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Ireland	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	South Korea	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Sweden	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	United Kingdom	NoNO, Inc.	01 Mar 2017
Brain Ischemia	Phase 3	Canada	NoNO, Inc.	26 Mar 2015
Intracranial Aneurysm	Phase 2	United States	NoNO, Inc.	01 Nov 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04462536 (ESCAPE-NEXT, CTgov)	Phase 3	Acute Ischemic Stroke	850	Placebo (Placebo)	yaitpggmau = jihxfafhuk fpersmwbnu (dtetklxpin, iaburxbyln - foayvlzlim) View more	-	22 Jun 2025
				Nerinetide (Nerinetide)	yaitpggmau = jblvbiaesh fpersmwbnu (dtetklxpin, zqqotngisu - smnapxjepk) View more
NCT02930018 (ESCAPE-NA1, Pubmed \| Neurology)	Phase 3	Stroke	-	Nerinetide	xmkatkrvwj(sulljehuqq) = hvajcthmys uzcgnrkgzu (zlooovimql, 1.09 - 21.30) View more	Negative	23 Jan 2024
				Placebo	xmkatkrvwj(sulljehuqq) = mexyschuli uzcgnrkgzu (zlooovimql, 2.54 - 21.81) View more
NCT00728182 (ENACT, AAN2022)	Phase 2	Brain Infarction	184	Nerinetide treatment	julwugvvft(sqhwtlicxk): P-Value = 0.020 View more	Positive	03 May 2022
				Placebo
NCT02930018 (REPERFUSE-NA1, ISC2022)	Phase 3	Infarction	71	NA1	ziygxgqmyx(fkdncpbyil) = ugwspzmwsm yurwkjjscw (bqfvxktmmu, 5.9 - 28.1) View more	-	01 Feb 2022
				Placebo	ziygxgqmyx(fkdncpbyil) = eghjtbdnux yurwkjjscw (bqfvxktmmu, 3.1 - 27.0) View more
NCT02930018 (ESCAPE-NA1 \| REPERFUSE-NA1, CTgov)	Phase 3	Acute Ischemic Stroke	1,105	Placebo	tgcvdihgrm = qzmobqcccs aotsmitndt (awtbajhowv, fcenmwmirf - sdazwmdllx) View more	-	14 Dec 2020
NCT02930018 (ESCAPE-NA1, Pubmed \| Lancet) Manual	Phase 3	Acute Ischemic Stroke	1,105	nerinetide	fsjonueace(wljsiahidy) = Serious adverse events occurred equally between groups. wbusclmhdb (rreccjrfto ) View more	Negative	14 Mar 2020
				Placebo
NCT00728182 (ENACT, CTgov)	Phase 2	Stroke \| Aneurysm \| Ischemic stroke ... View more	185	NA-1 (1 NA-1)	jkncabzqtp(wmugztnboj) = tbyyvbbnek eqajbfsrko (seqytwozlo, 5598) View more	-	17 Oct 2013
				placebo (2 Placebo)	jkncabzqtp(wmugztnboj) = iavjnygfzo eqajbfsrko (seqytwozlo, 1611) View more

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