Ji Xing Pharma Inks Up to $400M Deal with Cytokinetics to Bring Novel Heart Failure Therapy Omecamtiv Mecarbil to Greater China

Recently, Cytokinetics, Incorporated (NASDAQ: CYTK) and CORXEL Pharmaceuticals (“CORXEL”) announced an expansion of their collaboration, entering into an exclusive licensing agreement to jointly advance the development and commercialization of omecamtiv mecarbil for the proposed indication of heart failure with reduced ejection fraction (HFrEF) in the Greater China region.

Through the aforementioned transactions, Cytokinetics will secure $70 million in committed funding, comprising a $50 million upfront and short-term payment from CORXEL under the collaboration agreement, as well as $20 million in proceeds from the sale of common stock to RTW.In addition, Cytokinetics will be eligible to receive up to $330 million in additional milestone payments from CORXEL, plus sales-based royalties on net sales of omecamtiv mecarbil in the Greater China region, subject to certain percentage reductions.

In addition to the license and collaboration agreement reached with CORXEL, Cytokinetics also entered into a common stock purchase agreement to sell and issue 511,182 shares of Cytokinetics common stock to an affiliate of RTW at a price of $39.125 per share.

CORXEL is a biopharmaceutical company headquartered in Shanghai, dedicated to providing innovative scientific therapies and medicines to Chinese patients suffering from serious, life-threatening diseases, thereby addressing critical gaps in medical care. Established in 2019 with investment from RTW Investments, LP, CORXEL collaborates with multiple global biotechnology companies to develop and commercialize innovative therapeutic drugs, aiming to meet unmet medical needs in the fields of cardiovascular and ophthalmic diseases. Leveraging its robust and expanding product pipeline, experienced management team, and patient-centric service philosophy, CORXEL is poised to deliver lasting and profound benefits to patients across Greater China.

RTW Investments, LP (RTW), the founder of CORXEL, is a New York-headquartered global life-cycle investment firm dedicated to identifying transformative and breakthrough innovations in the biopharmaceutical and medical technology sectors. As a key partner to both industry and academia, RTW combines deep scientific expertise with a “solution-oriented investment approach” to support emerging therapies and the companies and/or scholars developing them.

Guided by its own business development strategy, CORXEL rapidly built a pipeline covering cardiovascular and ophthalmic diseases. In addition to the product licensed from Cytokinetics on this occasion,CORXEL’s pipeline also includes Aficamten, a cardiovascular drug licensed from Cytokinetics; Etripamil, a novel intranasal calcium channel blocker licensed from Milestone Pharmaceuticals, designed to provide rapid-response treatment for episodic cardiovascular conditions; and Tyrvaya and OC-02, two dry eye disease drugs licensed from Oyster Point Pharma.

Notably, in October 2021, the FDA approved Tyrvaya (varenicline) nasal spray for the treatment of dry eye disease. Tyrvaya is also the first nasal spray approved for the treatment of dry eye disease.

Omecamtiv mecarbil, the subject of this collaboration, is a selective small-molecule cardiac myosin activator. As a first-in-class investigational new drug, this sarcomere-targeting positive inotropic agent¹, can directly target the cardiac contraction mechanism; upon binding to its target, it increases the number of myosin head regions in cardiac myosin that interact with actin during cardiac systole.Omecamtiv mecarbil is designed to increase the number of active actin-myosin cross-bridges per cardiac cycle, thereby enhancing impaired myocardial contractility in patients with heart failure with reduced ejection fraction (HFrEF). Preclinical studies have shown that omecamtiv mecarbil enhances myocardial contractility without increasing intracellular calcium concentrations or myocardial oxygen consumption.^2-4。

Heart failure is a serious disease, with more than 64 million patients worldwide⁵(The number of patients in China is far higher than 10 million⁶), with approximately half of the patients exhibiting reduced left ventricular function^7,8. Heart failure is the leading cause of hospitalization and readmission among individuals aged 65 and older^{9, 10}. Despite the increasing prevalence of standard therapy and advances in medical care, the prognosis for patients with heart failure remains poor.¹¹. It is estimated that 20% of individuals aged over 40 are at risk of developing heart failure; among patients diagnosed with heart failure, approximately 50% die within five years of their initial hospitalization.^12,13. In the United States, it is estimated that more than 2 million people have an ejection fraction <30%, indicating the potential presence of severe heart failure.¹⁴。

Cytokinetics is currently evaluating the potential of omecamtiv mecarbil for the treatment of HFrEF in its development program, which includes two Phase III clinical trials: GALACTIC-HF and METEORIC-HF. The latter aims to assess the impact of omecamtiv mecarbil versus placebo on exercise capacity.

“We are pleased to expand our collaboration with CORXEL, building on our existing relationship, to jointly develop omecamtiv mecarbil. With CORXEL’s expertise in drug development and commercialization in China, we are confident that this partnership will help bring omecamtiv mecarbil to the large and strategically important cardiovascular patient market.”Cytokinetics President and Chief Executive Officer Robert I. Blumstated, “CORXEL will partner with us to realize our strategic vision of building a commercial platform through investments in science, people, and infrastructure, thereby facilitating the subsequent commercialization of omecamtiv mecarbil and Aficamten, the initial candidate from our collaboration. In summary, we believe that these two drug candidates have the potential to benefit more patients in China.”

CORXEL CEO Joseph Romanelli“We are impressed by the highly productive collaboration between both parties on the Aficamten project and are delighted to further expand our partnership on the omecamtiv mecarbil project. Although China has made certain progress in the field of heart failure treatment, patients still require new therapies to reduce disease risk. With the addition of omecamtiv mecarbil to our growing cardiovascular product pipeline, we will have the opportunity to bring much-needed novel heart failure treatments to patients in the Greater China region.”

Dr. Roderick Wong, Chairman of CORXEL and Managing Partner of RTW Investments, LPstated, “This expanded collaboration further pools the specialized expertise of both companies, thereby joining forces to safeguard the global commercialization of omecamtiv mecarbil. The partnership holds significant opportunities, signaling a major step forward in our mission to benefit more patients with heart failure. Given the strong performance demonstrated in our previous collaboration, we are pleased to provide further support aimed at improving patients’ cardiovascular health.”

Cytokinetics is a late-stage biopharmaceutical company dedicated to the discovery, development, and commercialization of first-in-class muscle activators and next-generation muscle inhibitors, providing potential therapeutic options for patients with progressive debilitating diseases characterized by impaired muscle function.Cytokinetics, a leader in the field of muscle biology and muscle mechanics, is currently developing small-molecule drug candidates specifically designed to modulate muscle function and contractility.

This collaboration is not the first between Cytokinetics and CORXEL; previouslyIn July 2020, CORXEL secured the rights to develop and commercialize Aficamten (CK-274), developed by Cytokinetics, in the Greater China region through an upfront payment, an additional $200 million in milestone payments, and sales royalties.

Aficamten is a next-generation cardiac myosin inhibitor developed by Cytokinetics, intended for the treatment of hypertrophic cardiomyopathy (HCM).Currently, the development of this drug is progressing smoothly. Cytokinetics recently announced that Cohorts 1 and 2 achieved positive results in the Phase II REDWOOD-HCM clinical trial evaluating aficamten for the treatment of patients with obstructive hypertrophic cardiomyopathy (HCM).

In terms of domestic progress,In December 2021, CORXEL announced the successful completion of the Phase I clinical study of Aficamten in China.In the study, a total of 28 subjects were randomized and all completed the study. Overall, aficamten demonstrated good tolerability similar to that of placebo and dose-proportional pharmacokinetic properties, consistent with the results observed in the prior Phase I clinical study conducted in the United States.

Cytokinetics plans to conduct the Phase III clinical trial of Aficamten, SEQUOIA-HCM, in patients with obstructive hypertrophic cardiomyopathy (oHCM), and is currently preparing for the study initiation. CORXEL will collaborate with Cytokinetics to conduct the Phase III clinical trial of Aficamten in patients with oHCM, SEQUOIA-HCM, and lead the China cohort study.

Building on the success of their previous collaboration, CORXEL and Cytokinetics are expanding their partnership to bring more global innovative products to Chinese patients, particularly offering new solutions for those with hard-to-treat heart failure.

References:

1. Psotka MA, Gottlieb SS, Francis GS et al. Cardiac Calcitropes, Myotropes, and Mitotropes. JACC. 2019; 73:2345-53.

2. Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J. et al. Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil. Nat Commun. 2017;8:190.

3. Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. 2010; 3: 522-27.

4. Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011 Mar 18;331(6023):1439-43.

5. James et al. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018; 392: 1789–858.

6. Groenewegen A, Rutten FH, Mosterd A, Hoes AW. Epidemiology of heart failure. European Journal of Heart Failure. 2020; 22: 1342–1356.

7. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240-e327. 

8. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–2200.

9. Roger VL. Epidemiology of Heart Failure. Circulation Research. 2013;113:646-659, originally published August 29, 2013. Doi: 10.1161/CIRCRESAHA.113.300268.

10. Kilgore M, Patel HK, Kielhorn A et al. Economic burden of hospitalizations of Medicare beneficiaries with heart failure. Risk Manag Healthc Policy. 2017; 10: 63-70. 

11. Jhund PS, MacIntyre K, Simpson CR, et al. Long-Term Trends in First Hospitalization for Heart Failure and Subsequent Survival Between 1986 and 2003. Circulation. 2009;119:515-523.

12. Benjamin EJ, Virani SS, Callaway CW et al. Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association. Circulation. 2018;137:e67-e492. 

13. Roger VL, Weston SA, Redfield MM, et al. Trends in Heart Failure Incidence and Survival in a Community-Based Population. JAMA. 2004;292:344-350.

14. Shannon M. Dunlay, Véronique L. Roger, Susan A. Weston, Ruoxiang Jiang, and Margaret M. Redfield (Circ Heart Fail. 2012;5:720-726.); Olmsted County community cohort of HF patients (1984 to 2009).