Xingxing Pharmaceuticals has partnered with Cytokinetics to develop myocardial myoglobulin inhibitors.

On July 14, 2020, RTW Investments announced that Xingxing Pharmaceuticals and Cytokinetics, a Shanghai-based biotech company, had signed an exclusive license agreement for the development and commercialization of CK-274, a new generation of myocardial myoglooprotein inhibitors, in Greater China.
the latter is a clinically late-stage biopharmaceutical company dedicated to the development and commercialization of "first-in-class" muscle activators and "next-in-class" muscle inhibitors.
agreement, Xingxing Pharmaceuticals has committed to pay the advance payment and an additional $200 million in milestone payments required in the research and development and commercialization process.
as part of the agreement, The Star will also pay Cytokinetics a double-digit sales commission for the product in the agreement area.
CK-274 is a new type of oral small molecule myoglobulin inhibitor developed independently by Cytokinetics scientists.
CK-274 is derived from a wide range of chemical optimization projects.
the project provides a detailed look at therapeutic index and pharmacokinetic properties that are expected to be translated into clinically developed "next-in-class" potential drugs.
CK-274 is designed to reduce the high constriction of hypertrophic cardiomyopathy (HCM).
in the preclinical model, CK-274 reduces myocardial contraction by binding directly with myocardial myoglobin at a unique and selective structural binding site, thereby preventing myoglobin from entering a contraction state.
CK-274 reduces the number of active actin-myoglobin crossbridges in each tachycardia cycle, thereby reducing myocardial contraction.
this mechanism of action may have therapeutic effects on diseases characterized by excessive contraction, such as HCM.
in preclinical models of cardiac function, whether in normal heart function models or in mouse HCM models, CK-274 reduced cardiac contraction in predictable dose and dose-dependent manners.
characterized, evaluated and optimized the preclinical pharmacokinetics of CK-274 to facilitate clinical dose adjustment.
a Phase 1 study showed that CK-274 performed safely and well tolerated in healthy subjects. The pharmacokinetics of
CK-274 were generally dose-linear, with significant steady state within 14 days of administration.
left ventricular blood fractions were reduced in a way that exposed dependence, and the calibrated protein binding differences were similar to those observed in human subjects in the pharmacokinetic/pharmacodynamic relationship of CK-274.
in general, the shallow exposure-reaction relationship observed before clinical use showed that it was applicable to humans and could make dose optimization flexible in humans.
overall research and development program will assess the potential of CK-274 to improve motor ability and alleviate symptoms in patients with alzheimered ventricles caused by HCM. "As a cardiology specialist, I have seen first-hand the pain of patients with unmet treatment needs in China with hypertrophic cardiomyopathy (HCM), and I am excited about the potential of innovative drugs such as CK-274," said Jianyong Li, chief medical officer at
.
" RTW is also understood to have signed a more in-depth strategic financing agreement and equity purchase agreement with Cytokinetics.
in addition to a $50 million direct equity investment in Cytokinetics at $25 per share of common stock, RTW has committed up to $90 million in research and development funds to CK-274.
the development of one or both indications of obstructive and non-obstructive hypertrophy of myocardial disease, with the start of each critical clinical trial by the required date.
RTW will receive a low-digit CK-274 sales commission in the United States, the European Union, the United Kingdom, Switzerland and some other European countries.
, RTW agreed to purchase a future sales commission for mavacamten from Cytokinetics for $85 million in cash under partial closing terms. "We believe molecularly targeted therapy is promising to treat cardiovascular disease, and are excited to have the opportunity to partner with Cytokinetics to assist CK-274," said Dr. Roderick Wong, Executive Partner and Chief Investment Officer, RTW Investments,
.
, RTW is also proud to assist Cytokinetic with its unique capabilities in achieving its strategic objectives, which support a variety of partnerships, including equity investments, non-diluted capital support and regional partnerships. Robert I. Blum, President and CEO of
Cytokinetics, said, "We are pleased to be able to enter into this transaction with RTW and Star as an opportunity to accelerate and expand the development of CK-274 in high-shrinkcardiotic diseases.
we share a common belief in the future of this highly promising "next-in-class" therapy. "CK-274 has a very good clinical future and is fully in line with Xingxing Pharmaceuticals' core strategy: to provide innovative drugs to Chinese patients to address unmet medical needs," said Peter Fong, CEO and head of RTW's business incubation division at the
.
we look forward to building a long-term relationship with Cytokinetics.
" References. Freddie Bray et. al., Global Cancer Statistics 2018: GLOBOCAN Estimates of the Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2018; 68: 394-424. [2] Wanqing Chen et. al., Cancer Statistics in China, 2015. CA Cancer J. Clin 2016; 66: 115-132 (China Cancer Association) Gastric Cancer Professional Committee, Gastric Cancer Peritoneal Metastasis Prevention Chinese Expert Consensus; Chin J Gastrointest Surg, May 2017, Vol. 20, No.