CORXEL Announces NMPA Acceptance of New Drug Application for Aficamten

SHANGHAI, China, October 18, 2024 – Corxel Pharmaceuticals (CORXEL), formerly named Ji Xing Pharmaceuticals, a leading biotech company committed to bringing innovative science and medicines to underserved patients with serious and life-threatening cardiometabolic diseases，today announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of the PRC has acceptedthe New Drug Application (NDA) for Aficamten tablets for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM) .

Aficamten is an investigational, next-in-class selective small molecule cardiac myosin inhibitor. It 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).

This new drug application is based on positive results from SEQUOIA-HCM, the global pivotal Phase 3 clinical trial of aficamten in patients with obstructive hypertrophic cardiomyopathy. SEQUOIA-HCM enrolled 282 patients with obstructive HCM. The results of SEQUOIA-HCM showed that treatment with aficamten significantly improved exercise capacity compared to placebo, The treatment effect with aficamten was consistent across all prespecified subgroups reflective of patient baseline characteristics and treatment strategies, including patients receiving or not receiving background beta-blocker therapy. Statistically significant and clinically meaningful improvements were also observed in all 10 prespecified secondary endpoints.

Sandy Mou, Board Executive Director and Chief Executive Officer of CORXEL, said that CORXEL was a biotechnology company fully focused on innovative treatment development in the field of cardiometabolic diseases，with the aim of bringing groundbreaking and innovative therapies to patients suffering from the diseases around the world. "This NDA for aficamten for the indication of symptomatic oHCM is an important milestone for CORXEL to achieve its corporate goal," according to Sandy Mou. " We look forward to engaging with CDE to bring this potential new medicine to patients in China.”

In July 2020, CORXEL entered into a license and collaboration agreement with Cytokinetics, a late-stage biopharmaceutical company headquartered in California,USA, 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, Cytokinetics announced positive results from the 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).

About Aficamten

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.

About Hypertrophic cardiomyopathy (HCM)

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, and the prevalence is likely to be underestimated due to the limitations of early screening. The prevalence is currently estimated to be at least 1/200, with obstructive (either at rest or with provocation) HCM accounting for approximately 2/3 of cases and non-obstructive HCM for approximately 1/3 of cases in clinical practice. HCM may result in exertional dyspnea, fatigue, chest pain, syncope/presyncope and limited exercise capacity. HCM is one of the main reasons of death in teenagers and athletes. Disease-related fatal and disabling events are most often attributable to sudden cardiac death, heart failure, and embolic stroke. Sudden cardiac death is the common mode of death in young patients between 10 to 35 years old. Heart failure is the common mode of death in middle-aged patients and stroke due to HCM related atrial fibrillation is common in old patients. The annual mortality rate for HCM patients in hospitals is 2% to 4%.

At present, patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) are generally offered pharmacotherapy with ??-blockers, verapamil, diltiazem and disopyramide based on experience; however, these medications often do not prevent progression of the disease, are associated with significant adverse effects, and do not target the underlying pathology (hypercontractility). Additionally, disopyramide is not available in China. For oHCM patients with a left ventricular outflow tract pressure gradient (LVOT-G) of ≥50 mm Hg either at rest or with provocation who also have severe symptoms refractory to medical therapy, septal reduction therapies (such as surgical myectomy or percutaneous alcohol septal ablation) can be effective, but these invasive procedures are not widely accessible in China and carry risk including death. Septal reduction therapies and their success depends on operator experience.

About CORXEL

CORXEL, formerly named Ji Xing Pharmaceuticals, is a leading biotech company headquartered in US and China committed to bringing innovative science and medicines to underserved patients with serious and life-threatening cardiometabolic?diseases. Backed by RTW Investments, CORXEL was founded in 2019 to develop and commercialize novel, innovative therapeutics to treat unmet medical needs in cardiometabolic?diseases. With a strong and further developing asset pipeline, industry leading talent, and patient-centric focus, CORXEL is dedicated to deliver a meaningful and lasting impact on patients.

The full portfolio of CORXEL consists of 2 assets with global rights and 4 assets with Greater China rights in late-stage clinical development. The portfolio with global rights are JX09 for hypertension and JX10 for acute ischemic stroke (AIS), while the portfolio with Greater China rights include aficamten, etripamil, varenicline solution nasal spray/US brand name TYRVAYA?,?and LNZ100.

For further information about CORXEL, please visit?www.jixing.com .???

About?Cytokinetics

Cytokinetics?is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing muscle biology-directed drug candidates as potential treatments for debilitating diseases in which cardiac muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact myocardial muscle function and contractility.?

Cytokinetics?is preparing for regulatory submissions for?aficamten, its next-in-class cardiac myosin inhibitor, following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in obstructive hypertrophic cardiomyopathy which were published in the?New England Journal of Medicine.?Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of?aficamten?as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of?aficamten?in patients with non-obstructive HCM, CEDAR-HCM, a clinical trial of?aficamten?in a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study of?aficamten?in patients with HCM.

?Cytokinetics?is also developing?omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure. Additionally,?Cytokinetics?is developing CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from?aficamten?for the potential treatment of HFpEF.

For additional information about?Cytokinetics, visit?www.cytokinetics.com ?and follow on ?X,?LinkedIn,?Facebook?and?YouTube.