News and Media

Publications

PSD-95 Antagonist

Tymianski, M: Combining Neuroprotection with Endovascular Treatment of Acute Stroke: Is there hope? ,

Sattler R, Xiong Z, Lu WY, et al: Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein.  Science 284:1845-1848, 1999

Aarts M, Liu Y, Liu L, et al: Treatment of ischemic brain damage by perturbing NMDA receptor- PSD-95 protein interactions. Science 298:846-850, 2002

Cui H, Hayashi A, Sun H, et al: PDZ Protein Interactions Underlying NMDA-Receptor-Mediated Excitotoxicity and Neuroprotection by PSD-95 Inhibitors. J Neurosci29:9901-9915, 2007

Sun HS, Doucette TA, Liu Y, et al: Effectiveness of PSD95 inhibitors in permanent and transient focal ischemia in the rat. Stroke 39:2544-2553, 2008

F.X. Soriano, M. A. Martel, S. Papadia, A. Vaslin, P. Baxter, C. Rickman, J. Forder, M. Tymianski, R. Duncan, M. Aarts, P. Clarke, D. J. Wyllie, and G. E. Hardingham. Specific targeting of pro-death NMDA receptor signals with differing reliance on the NR2B PDZ ligand. J.Neurosci.  28 (42):10696-10710, 2008

T. Bratane, H. Cui, D. J. Cook, J. Bouley, M. Tymianski, and M. Fisher.  Neuroprotection by Freezing Ischemic Penumbra evolution Without Cerebral Blood Flow Augmentation With a Postsynaptic Density-95 Protein Inhibitor.  Stroke 42:3265-70, 2011

Cook, D.J., Teves, L., and Tymianski, M. Treatment of Stroke with a PSD-95 Inhibitor in the Gyrencephalic Primate Brain. Nature 483:213-217, 2012


TRPM7 Technology

Aarts M, Iihara K, Wei WL, et al: A key role for TRPM7 channels in anoxic neuronal death. Cell 115:863-877, 2003

Sun HS, Jackson MF, Martin LJ, et al: Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia. Nat Neurosci 12:1300-1307, 2009


Src:ND2 Inhibitors

Liu XJ, Gingrich JR, Vargas-Caballero M, et al: Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex. Nat Med 14:1325-1332, 2008


Clinical Trials

Hill MD, et al., Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 11(11):942-950, 2012

News & Media

Articles

The Promise of a Canadian Stroke Drug to Help the Brain. (IMS Magazine – Aug 2017)

The Stakes are High for an Acclaimed Cerebrovascular Surgeon Searching for a Stroke Drug. (Stroke Research – Krembil Neuro)

Order or Canada’s Newest Appointees Include Paralympian, Supreme Court Judge, and Astrophysicist. (CBC – Dec 2016)

Ondaatja, Kaspi, Ignatieff Among 100 Order of Canada Honorees. (Globe and Mail – Dec 2016)

Stroke-styming Effects of NA-1 Drug to be Studied in B.C. (CBC – Nov 2015)

Stroke Drug Approved for Pilot Program with Toronto Paramedics (Globe and Mail – May 2014)

One Toronto Neurosurgeons Crusade to Develop an Effective Stroke Drug (Globe and Mail – May 2014)

Promising Canadian Stroke Drug Receives Large Research Grant (Globe and Mail – May 2014)

NA-1 Stroke Drug A Victory for Basic Research, says UPEI Team (CBC – Mar 2015)

Canadian Drug Trial Could be Pivotal for Stroke Patients (Globe and Mail – Mar 2015)

Experimental Drug Could Mitigate Brain Damage Caused by Stroke (Globe and Mail – Mar 2012)

Stroke Drug Discovered at Toronto Western Hospital (The Toronto Star – Oct 2012)

Stroke Drug Looks Promising in Human Trial (CP24 – Oct 2012)

New Drug May Protect Brain from Stroke (CTV News – Oct 2012)

New Drug to ‘Stop stroke surgery damage’ (Britain National Health Service – Oct 2012)

Drug ‘may prevent stroke damage’ (BBC News – Oct 2012)

New Drug Lower Stroke Risk After Surgery (The Telegraph – Oct 2012)

Drug Holds Promise as Post-Stroke Therapy: Study (CTV News – Feb 2012)

Helping Brains to Help Themselves (Globe and Mail – Apr 2011)

Doctor Offers Picks for Top Medical Stories of 2009 (CTV News Dec – 2009)

Research Could Prevent the Effects of Stroke (Globe and Mail – Sept 2009)

Press Releases

NoNO Inc Initiates Phase III Study of NA-1 for Acute Ischemic Stroke

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 (ESCAPE-NA1 trial;  clinicaltrials.gov NCT02930018)

Toronto, Canada- 27 February 2017 – NoNO, Inc., a Canadian biotechnology company and the University of Calgary Stroke Unit announced today the initiation of its Phase III global clinical trial termed ESCAPE-NA-1 to evaluate the efficacy and safety of the investigational drug NA-1 for reducing functional disability in patients with Acute Ischemic Stroke (AIS) who are candidates for endovascular revascularization.  NoNO Inc. is conducting this trial in collaboration with the University of Calgary Stroke Unit, led by Drs. Michael D. Hill, and Mayank Goyal. The ESCAPE-NA-1 study is based on the successful global clinical trial ESCAPE, conducted by the University of Calgary team (Goyal, M., et al. (2015). “Randomized assessment of rapid endovascular treatment of ischemic stroke.” N Engl J Med 372(11): 1019-1030.)

Dr. Michael D. Hill, with the Department of Clinical Neurosciences in the Cumming School of Medicine and member of the Hotchkiss Brain Institute, who is the Coordinating Investigator of ESCAPE-NA-1 and a principal investigator of the ESCAPE trial, stated ““The ESCAPE-NA1 trial is bolstered by our past experience as the global coordinating centre for the successful predecessor study – ESCAPE. We have now set the stage for testing neuroprotection, for the first time, in the human ischemia-reperfusion paradigm. Our experience with ESCAPE will significantly de-risk the operational success of ESCAPE-NA-1.”

ESCAPE-NA-1 is a unique clinical trial. Michael Tymianski, M.D., Ph.D., President and CEO of NoNO, Inc., stated “For the first time, neuroprotection will be evaluated in a clinical setting of ischemia-reperfusion in which neuroprotection has the largest treatment effect. ESCAPE-NA-1 addresses the deficiencies of past neuroprotection trials as it is the first study to have a design grounded in- and consistent with- the preclinical science, to minimize subject heterogeneity, to ensure that the treatment effect size is maximized, and to enroll subjects in the correct therapeutic window.”

NA-1 belongs to a novel class of drugs termed PSD-95 inhibitors. NA-1 disrupts pro-death signalling pathways that involve postsynaptic density-95 (PSD-95) protein, a major protein found in neuronal synapses.  NA-1 has successfully advanced through Phase 1 and 2 clinical trials in the United States and Canada and currently is recruiting in another Phase 3 trial FRONTIER (clinicaltrials.gov NCT02315443). It has been extensively researched, has a clear mechanism of action, and its efficacy in preclinical studies has been reproduced in multiple indications by several leading laboratories. Preclinical results with NA-1 have been published in leading peer-review journals including Science, Science Translational Medicine and Nature. NoNO Inc. plans to continue developing NA-1, and wishes to thank their collaborators, scientists, investors and the academic stroke community for their continuing support of this important project.

About NoNO Inc.

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, including stroke, traumatic brain injury and neuropathic pain. NoNO Inc.’s strategy is to inhibit key protein-protein interactions involved selectively in cellular signals that cause cell damage, but without interfering with normal cell functions.

Media Contacts:

Dave Garman                dgarman@nonoinc.ca

Michael Tymianski      mtymianski@nonoinc.ca


Results of NoNO Inc.-Sponsored Phase 2 Clinical Trial in Procedurally-Induced Strokes to be Announced at the International Stroke Conference

Principal Investigator of NoNO Inc.-sponsored Trial Announces Promising Results of a Stroke Drug Study in Patients Subjected to Embolic Strokes at the International Stroke Conference, February 2, 2012

TORONTO, Jan. 30, 2012/PRNewswire-iReach/ — NoNO, Inc., a Canadian biotechnology company, announced that the final results of the ENACT Phase 2 clinical trial of their novel stroke drug, NA-1, will be presented by the trial principal investigator, Dr. Michael D. Hill, in Session IX:  Late Breaking Science Oral Abstracts, Room R03-05 at the International Stroke Conference in New Orleans on February 2, 2012 at 2:24 pm.  This trial executed a novel clinical trial protocol aimed at demonstrating safety and statistically significant reduction of stroke burden in human subjects.

The ENACT trial was a 185-patient, randomized, double-blind placebo-controlled study performed to assess the safety and efficacy of NA-1 in reducing small embolic strokes in patients that underwent an endovascular repair of intracranial aneurysms. Such subjects were demographically similar to patients that suffer from acute ischemic strokes. Patients enrolled in ENACT included individuals who had suffered a brain hemorrhage, in order to evaluate the safety of NA-1 in both ischemic and hemorrhagic strokes.  NA-1 belongs to a novel class of drugs termed PSD-95 inhibitors. NA-1 disrupts pro-death signaling pathways that involve postsynaptic density-95 (PSD-95) protein, a major protein found in neuronal synapses.  Based upon the results to be presented, NoNO intends to initiate later stage clinical trials in multiple stroke indications including acute ischemic stroke and subarachnoid hemorrhage.

Michael Hill, M.D., the principal investigator for the ENACT trial and Director of the Stroke Unit at Foothills Medical Center, Calgary, stated: “There is a huge unmet need for drugs to treat acute stroke and procedurally-induced strokes, which afflict millions of people worldwide.  NA-1 comprises one of the most advanced hopes for success with its novel mechanism and compelling research data.”

Michael Tymianski, M.D., Ph.D., Founder and President of NoNO, Inc., added, “I would like to extend my sincere thanks to the excellent teams of physicians, nurses and staff at the outstanding institutions that participated in the ENACT trial as well as to the patients who agreed to be involved.  The results of this trial have encouraged NoNO to proceed with the development of NA-1 and to expand the indications for this drug in further clinical trials.”

NA-1 has been granted Fast-Track Designation by the FDA for the reduction of procedurally induced strokes and cognitive impairment in patients undergoing endovascular repair of brain aneurysms.  This designation should facilitate the development of NA-1, as it is directed at the treatment of serious or life-threatening conditions and demonstrates the potential to address multiple unmet medical needs.

NA-1 has successfully advanced through Phase 1 and 2 clinical trials in the United States and Canada. It been extensively researched, has a clear mechanism of action, and its efficacy has been reproduced in multiple indications by several leading laboratories. Preclinical results with NA-1 have been published in leading peer-review journals. NoNO Inc. plans to continue developing NA-1, and thanks their collaborators, scientists, investors and the academic stroke community for their continuing support of this important project.

About NoNO Inc.

NoNO Inc. is an Ontario biotechnology company whose focus is on developing therapeutic drugs in areas of great unmet societal 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, including stroke, traumatic brain injury and neuropathic pain. NoNO Inc.’s strategy is to inhibit key protein-protein interactions involved selectively in cellular signals that cause cell damage, but without interfering with normal cell functions.

Media Contact:

Dave Garman                dgarman@nonoinc.ca

Michael Tymianski      mtymianski@nonoinc.ca