Pipeline & science

JX09 is a next-generation, highly selective aldosterone synthase inhibitor. Aldosterone plays an important role in the development of hypertension, heart failure and chronic kidney disease. Directly targeting the synthesis of aldosterone has been developed as a novel alternative strategy. Preclinical data suggest that JX09 offers strong potency inhibiting aldosterone synthase, with very little impact on the biological functions of a homologous enzyme that is key to cortisol synthesis. The high potency and selectivity make JX09 a potential best-in-class drug candidate. 

In February 2023, CORXEL obtained global rights to JX09 from PhaseBio Pharmaceuticals, Inc. In February 2024, CORXEL successfully dosed the first subject in the Phase I clinical trial of the cardiovascular investigational product JX09 in Australia.

JX10 (formerly BIIB131) is an investigational drug for acute ischemic stroke (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.

For further information please visit https://www.tms-japan.co.jp/

Aficamten is an investigational selective, small molecule cardiac myosin inhibitor from Cytokinetics, Incorporated (Nasdaq: CYTK), discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state.

In July 2020, CORXEL entered into a license and collaboration agreement with Cytokinetics, a late-stage biopharmaceutical company headquartered in California, pursuant to which Cytokinetics has granted to CORXEL an exclusive license to develop and commercialize aficamten (formerly known as CK-274) in the Greater China territory. In December 2023, CORXEL announced positive results from the China cohort of SEQUOIA-HCM, the pivotal phase 3 clinical trial of aficamten in patients with obstructive hypertrophic cardiomyopathy. In March 2024, CORXEL announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the PRC (NMPA) has approved the Clinical Trial Application (CTA) for the China cohort of ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM).

The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function. Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China. 

For further information about our partner, Cytokinetics, please visit cytokinetics.com

Etripamil, a new chemical entity, is the lead investigational product of Milestone® Pharmaceuticals Inc. (Nasdaq: MIST). It is a novel calcium channel blocker designed to be a rapid-response therapy for episodic cardiovascular conditions. As a nasal spray that is self-administered by the patient, etripamil has the potential to shift the current treatment experience for many patients from the emergency department to a medically unsupervised setting.

CORXEL acquired the Greater China right with etripamil in May 2021 from Milestone Pharmaceuticals. In October 2023, Milestone announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for etripamil for the treatment of paroxysmal supraventricular tachycardia (PSVT). In September 2024, JIXING announced positive results from Phase 3 JX02002 clinical trial of etripamil nasal spray in patients with paroxysmal supraventricular tachycardia.

For further information about our partner, Milestone Pharmaceuticals, please visit milestonepharma.com

LNZ100 (aceclidine) eye drops are being developed by LENZ Therapeutics. Aceclidine is a small molecule acetylcholine receptor agonist that causes pupil contraction, or miosis, creating a pinhole effect that improves near vision. Studies have shown that aceclidine’s mechanism of action (MOA) is well positioned to create a pinhole pupil effect while avoiding the impairment of distance vision called myopic shift. Aceclidine’s unique pupil selective MOA, in which miosis is decoupled from myopic shift, is expected to allow it to target a broad patient population.

CORXEL acquired the Greater China rights for the development and commercialization of the products in April 2022. In August 2024, CORXEL announced that the investigational ophthalmic products, LNZ100 (aceclidine) eye drops, have completed patient enrollment in a Phase 3 clinical study in China for the treatment of presbyopia.

For more information, visit: https://lenz-tx.com/

Varenicline solution nasal spray (US brand name TYRVAYA^®)  is a highly selective cholinergic agonist that is U.S. FDA approved to treat signs and symptoms of dry eye disease as a multidose nasal spray. The parasympathetic nervous system controls tear film homeostasis partially via the trigeminal nerve, which is accessible within the nose. The efficacy of varenicline solution nasal spray in dry eye disease is believed to be the result of varenicline's activity at heteromeric sub-type(s) of the nicotinic acetylcholine (nACh) receptor where its binding produces agonist activity and activates the trigeminal parasympathetic pathway resulting in increased production of basal tear film as a treatment for dry eye disease. Varenicline binds with high affinity and selectivity at human α4β2, α4α6β2, α3β4, α3α5β4 and α7 neuronal nicotinic acetylcholine receptors. 

CORXEL acquired the Greater China rights for Varenicline nasal spray in August 2021 from Oyster Point Pharma. In February 2023, Varenicline solution nasal spray was approved in Macao SAR, and since April 2023, it has been available in Boao Lecheng International Medical Tourism Pilot Zone as an imported drug for patients with urgent clinical needs.In July 2023, the new drug application was officially accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of the PRC.

TYRVAYA® is a registered trademark of Oyster Point Pharma, Inc., a Viatris company.