Acute Ischemic Stroke (AIS)

Acute stroke is defined as new-onset neurological dysfunction caused by confined necrosis or softening of brain tissue as a result of acute localized cerebral blood circulation disorders, ischemia, and hypoxia, with signs/symptoms lasting more than 24 hours and CT/MRI excluding cerebral hemorrhage.

Stroke is a major contributor to death and disability worldwide. According to the Journal of the American Medical Association, acute ischemic stroke is a leading cause of death and disability in the US and affects approximately 700,000 people each year. In China, AIS, the most common type of stroke, accounts for approximately 70% of strokes, with an annual case-fatality rate of 15% and a disability rate of 33.5%, imposing a significant socioeconomic burden on the country.

There are 7.6 million acute ischemic stroke incidents globally according to the World Stroke Organization 2022. Tissue-type plasminogen activator (t-PA; alteplase), is essentially the only available option for the thrombolytic therapy of acute ischemic stroke. As t-PA should be administered within 4.5 hours after the onset, only 5% to 10% of patients with ischemic stroke are said to receive t-PA even in developed countries.

JX10 (formerly BIIB131) is an investigational drug for AIS. Its proposed mechanism of action includes both thrombolytic and anti-inflammatory activities. By restoring critical blood flow following acute stroke, it may benefit more patients over current standard of care by extending the otherwise short treatment window.

JX10 is one of the SMTP compounds with (1) pro-thrombolytic, (2) anti-inflammatory, and (3) antioxidative activities.

A Phase 2a study including 90 participants in Japan established preliminary safety and efficacy in AIS patients with late presentations up to 12 hours from symptom onset. This study achieved the primary endpoints for both safety and efficacy as summarized below.

This was a multicenter, single-dose, double-blind, randomized, placebo-controlled, dose-escalation study conducted in Japan under the sponsorship of TMS Co. The study enrolled patients with acute ischemic stroke ineligible for the therapies with tissue-type plasminogen activator (t-PA) or thrombectomy. JX10 (at a dose of 1, 3, or 6 mg/kg) and placebo were administered within 12 hours of the symptom onset to 52 and 38 patients, respectively.

In January 2024, CORXEL acquired the global rights for JX10, excluding Japan, from Biogen. TMS regains Japan rights of JX10 and will join forces with CORXEL to expeditiously develop and launch JX10, facilitated by the formation of a Joint Development Committee. CORXEL is now initiating a global registrational study to further evaluate the Efficacy and Safety of JX10 in Acute Ischemic Stroke with Late Presentations.

Reference：

•    Overview of Acute Ischemic Stroke Evaluation and Management, Biomedicines. 2021 Oct; 9(10): 1486.
•    Chinese Expert Consensus on Assessment and Intervention of Collateral Circulation in Acute Ischemic Stroke in Emergency Medicine
•    Guidelines and Consensus | Expert Consensus on Anesthesia Management for Endovascular Treatment of Acute Ischemic Stroke (2020 Edition)
•    JAMA. 2022;327(9):885. doi:10.1001/jama.2022.1420 
•    Guidelines and Consensus | Expert Consensus on Anesthesia Management for Endovascular Treatment of Acute Ischemic Stroke (2020 Edition)