Tropomyosin

As Previously Announced, Reldesemtiv Had No Effect on the Primary Endpoint of Change from Baseline in ALSFRS-R or Key Secondary Endpoints Trial Discontinued in March 2023 Due to Futility Following Second Planned Interim Analysis Survey Reveals Site Personnel and Patients Have Favorable View of Trial Features to Reduce Burden of Participation SOUTH SAN FRANCISCO, Calif., Dec. 07, 2023 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that the full results of COURAGE-ALS (Clinical Outcomes Using Reldesemtiv on ALSFRS-R in a Global Evaluation in ALS), were presented at the 34th International Symposium on ALS/MND by Jeremy Shefner, M.D., Ph.D., Lead Investigator of COURAGE-ALS, Professor of Neurology, Barrow Neurological Institute, University of Arizona College of Medicine Phoenix. COURAGE-ALS was designed with two planned interim analyses of unblinded data by the Data Monitoring Committee. At the second interim analysis the Data Monitoring Committee recommended the discontinuation of the clinical trial due to futility. Subsequently, the Company concluded study conduct in March 2023 and discontinued treatment with reldesemtiv in all patients including those in the open-label extension study, COURAGE-ALS OLE. Development of reldesemtiv has been terminated. At the time of the discontinuation of COURAGE-ALS, 486 patients had started treatment with reldesemtiv or placebo and 276 had completed dosing through 24 weeks. Treatment with reldesemtiv for 24 weeks had no effect on the primary efficacy endpoint measure of change from baseline up to Week 24 in the ALS Functional Rating Scale Revised (ALSFRS-R) (joint rank test p=0.11). Patients treated with reldesemtiv declined 5.3 points per month (SD=5.3) while patients treated with placebo declined 4.8 points per month (SD=4.4). No pre-defined patient subgroup favored treatment with reldesemtiv. Patients with a faster disease progression rate did not experience a greater treatment effect from reldesemtiv, contrary to analyses conducted post hoc from FORTITUDE-ALS, the Phase 2 clinical trial of reldesemtiv, which had suggested that treatment effects were more evident in patients with a faster disease progression rate. Reldesemtiv also demonstrated no effect on key secondary endpoints including change from baseline to Week 24 in in-clinic percent predicted forced vital capacity (FVC), ALS Questionnaire 40 (ALSAQ-40) and handgrip strength. “ALS is a grievous, fatal disease for which there are few effective treatments, and we have been steadfastly pursuing a potential new treatment for patients with ALS for more than a decade,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “We are disappointed that reldesemtiv did not demonstrate an effect to slow the decline of the disease; however, we hope the design and conduct of COURAGE-ALS, a trial designed to reduce the burden of participation among site personnel and patients, will contribute to the design and conduct of future trials in ALS. We thank all the people with ALS, caregivers, investigators and site personnel who participated in this trial and hope that by engaging in high-quality, patient-centric clinical research we may continue to lead by example, not only in ALS but in other diseases of high unmet need.” The incidence of serious adverse events in COURAGE-ALS was similar between the placebo group and the reldesemtiv group. The most common treatment-emergent adverse events (TEAEs) were in system organ classes including respiratory, thoracic and mediastinal disorders, gastrointestinal disorders and infections and infestations. Overall, non-serious TEAEs also occurred at similar frequency between the placebo group and the reldesemtiv group. The only non-serious TEAE that differed between the placebo and reldesemtiv groups was abnormal laboratory investigations driven primarily by elevated transaminases, which occurred in 18.8% of patients treated with reldesemtiv and 11.8% of patients treated with placebo. The main cause of death for patients in COURAGE-ALS was respiratory failure/arrest, assisted suicide/euthanasia, ALS and infections. Mortality rates were similar between treatment groups; no deaths were assessed as related to treatment with reldesemtiv. Site and Patient Perspectives on Participating in an ALS Trial Designed to Reduce Burden COURAGE-ALS was designed with features intended to reduce the burden of participating in a clinical trial for both patients with ALS and site personnel including remote visits. All participants were provided with a mobile device to complete the ALSAQ-40 and portable home spirometer to measure FVC at home. Additionally, during in-clinic visits fewer muscles were tested with hand-held dynamometry (HHD) compared to previous trials. Upon the discontinuation of the clinical trial, a survey was conducted of site personnel and, as embedded in the original trial design, qualitative interviews were held with a subset of trial participants to assess their experience. Survey responses were received from 141 site personnel in North America, Europe and Australia, including study coordinators, investigators, ALSFRS-R trained evaluators, HHD/grip evaluators, and FVC trained evaluators. The survey results showed that site personnel viewed remote visits favorably when considering whether to participate as a site in COURAGE-ALS. Sites believed the remote visits favorably influenced a participant’s decision regarding the trial and the ability to convert an in-clinic visit to a remote visit resulted in patients being more willing or able to remain in the trial despite disease progression. Site personnel reported that 60% of their patients converted an in-clinic visit to a remote visit, citing reasons including disease progression, transportation limitations, caregiver availability, weather and COVID-19 restrictions. COURAGE-ALS was also deemed less time and labor intensive than a traditional clinic-based trial by 55% of site personnel. Patients with ALS responded positively to having labs collected at home, however, patients reported difficulty in conducting FVC remotely and challenges completing the ALSAQ-40 on the mobile device. There were more missed FVC assessments when conducted remotely than when done in-clinic, and approximately half of the time the ALSAQ-40 assessment was completed on paper rather than in the mobile app. Variability in technological skills and degree of weakness may have impacted use with the portable home spirometer and the mobile device. Despite certain limitations related to remote visits, implementing methods to reduce patient and site burden remains an important consideration in patient-centric clinical trial design. COURAGE-ALS & COURAGE-ALS OLE: Trial Design COURAGE-ALS was a Phase 3, multi-center, double-blind, randomized, placebo-controlled trial of reldesemtiv designed to enroll approximately 555 patients with ALS. Patients were randomized 2:1 to receive 300 mg of reldesemtiv or matching placebo dosed orally twice daily for 24 weeks, followed by a 24-week period in which all patients received 300 mg of reldesemtiv twice daily. Eligible patients were within the first two years of their first symptom of muscle weakness, had a vital capacity of ≥65% predicted, and a screening ALS Functional Rating Scale – Revised (ALSFRS-R) ≤44. Patients taking stable doses of edaravone and/or riluzole were permitted to enroll, and randomization was stratified accordingly. The primary efficacy endpoint was change from baseline to 24 weeks in ALSFRS-R. Secondary endpoints included combined assessment of ALSFRS-R total score, time to onset of respiratory insufficiency and survival time up to week 24 using a joint rank test; change from baseline to 24 weeks for vital capacity; ALSAQ-40; and bilateral handgrip strength. COURAGE-ALS was discontinued due to futility at the second planned interim analysis. About Reldesemtiv Skeletal muscle contractility is driven by the sarcomere, the fundamental unit of skeletal muscle contraction and a highly ordered cytoskeletal structure composed of several key proteins. Skeletal muscle myosin is the motor protein that converts chemical energy into mechanical force through its interaction with actin. A set of regulatory proteins, which includes tropomyosin and the troponin complex, make the actin-myosin interaction dependent on changes in intracellular calcium levels. Reldesemtiv is an investigational, selective, small molecule fast skeletal muscle troponin activator (FSTA) arising from Cytokinetics’ skeletal muscle contractility program. Reldesemtiv was designed to slow the rate of calcium release from the regulatory troponin complex of fast skeletal muscle fibers, which sensitizes the sarcomere to calcium, leading to an increase in skeletal muscle contractility. About ALS Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that afflicts approximately 27,000 people in the United States and a comparable number of patients in Europe. Approximately 6,300 new cases of ALS are diagnosed each year in the United States. The average life expectancy of a person with ALS is approximately two to four years and only approximately 10 percent of people with ALS survive for more than 10 years. Death is usually due to respiratory failure because of diminished strength in the skeletal muscles responsible for breathing. Few treatment options exist for these patients, resulting in a high unmet need for new therapies to address functional deficits and disease progression. About Cytokinetics Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors 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. Aficamten is a next-in-class cardiac myosin inhibitor, currently the subject of three Phase 3 clinical trials: SEQUOIA-HCM, evaluating aficamten in patients with obstructive hypertrophic cardiomyopathy (HCM), MAPLE-HCM, evaluating aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM and ACACIA-HCM, evaluating aficamten in patients with non-obstructive HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure. Additionally, Cytokinetics is developing CK-136, a cardiac troponin activator for the potential treatment HFrEF and other types of heart failure, such as right ventricular failure, resulting from impaired cardiac contractility, and CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten for the potential treatment of HFpEF. In 2023, Cytokinetics is celebrating its 25-year history of pioneering innovation in muscle biology and related pharmacology focused to diseases of muscle dysfunction and conditions of muscle weakness. For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). Cytokinetics disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act's Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements, express or implied, relating to our future plans for our neuromuscular development programs. Such statements are based on management's current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to, potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics' drug candidates that could slow or prevent clinical development or product approval; Cytokinetics' drug candidates may have adverse side effects or inadequate therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics' ability to conduct clinical trials; Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; standards of care may change, rendering Cytokinetics' drug candidates obsolete; and competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics' drug candidates and potential drug candidates may target. For further information regarding these and other risks related to Cytokinetics' business, investors should consult Cytokinetics' filings with the Securities and Exchange Commission. CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries. Contact:Cytokinetics Diane WeiserSenior Vice President, Corporate Communications, Investor Relations(415) 290-7757

在一项新的研究中，德国马克斯-普朗克分子生理学研究所主任Stefan Raunser领导的一个国际研究小组与英国伦敦国王学院的Mathias Gautel合作，利用一种名为低温电镜断层成像技术（electron cryo-tomography, cryo-ET）的前沿技术，在世界上成功获得了粗丝（thick protein filament，也称为粗蛋白丝，粗肌丝）在天然细胞环境中的首张高分辨率三维图像。这使人们得以一窥粗丝内部的分子分布和成分排列。这一新发现是理解肌肉在健康和疾病状态下如何运作的重要框架。相关研究结果于2023年11月1日在线发表在Nature期刊上，论文标题为“Structure of the native myosin filament in the relaxed cardiac sarcomere”。人类的心脏通常被描述为身体的发动机，它是一个非凡的器官，不知疲倦地跳动着，维持着我们的生命。在这个重要器官的核心部位，心脏收缩时会发生复杂的过程，在那里，粗丝和细丝（thick protein filament，也称为细蛋白丝，细肌丝）在肌节（sarcomere）内相互作用，而肌节是骨骼肌和心肌细胞的基本组成部分。粗丝蛋白的任何变化都会对我们的健康造成严重影响，导致肥厚型心肌病和其他多种心脏疾病和肌肉疾病。心房颤动、心力衰竭和中风-肥厚性心肌病可导致许多严重的健康问题，也是35岁以下人群心源性猝死的主要原因。Raunser 说，“心肌是人体的核心发动机。当然，如果了解了它的构造和功能，对出现故障的它进行修复就容易多了。在肌肉研究的初期，我们已成功地利用低温电镜观察到了这些肌肉基本组成成分的结构以及它们之间的相互作用。然而，这些都是从活细胞中提取的蛋白的静态图像。它们只能告诉我们肌肉成分的高度可变性和动态相互作用如何使肌肉在天然环境中运动。”骨骼肌和心肌的收缩是通过肌节中两种平行蛋白丝的相互作用实现的：细丝和粗丝。肌节被细分为几个称为区（zone）和带（band）的区域，在这些区域中，这些蛋白丝以不同的方式排列。细丝由 F-肌动蛋白（F-actin）、肌钙蛋白（troponin）、原肌球蛋白（tropomyosin）和伴肌动蛋白（nebulin）组成。粗丝由肌球蛋白（myosin）、肌联蛋白（titin）和肌球蛋白结合蛋白 C（myosin binding protein C, MyBP-C）组成。MyBP-C可在粗丝和细丝之间形成连接，而所谓的马达蛋白肌球蛋白则与细丝相互作用，产生力量和肌肉收缩。这些粗丝蛋白的变化与肌肉疾病有关。对粗丝的详细描述对于制定治疗这些疾病的策略极为重要，但迄今为止还没有这方面的研究。Raunser说，“如果想充分了解肌肉在分子水平上的工作原理，就需要描绘出肌肉的组成成分在天然环境中的情况---这是当今生物学研究中最大的挑战之一，传统的实验方法无法解决这个问题。”为了克服这一障碍，他的团队开发了一种cryo-ET工作流程，专门用于研究肌肉样本：他们将Mathias Gautel团队制作的哺乳动物心肌样本在极低的温度（- 175 °C）下进行速冻。这就保留了它们的水合作用和精细结构，从而保持了它们的天然状态。然后，使用聚焦离子束（FIB 铣削）将这些肌肉样本削薄至透射电子显微镜所需的理想厚度（约 100 纳米）。最后，通过计算方法重建高分辨率的三维图像。cMyBP-C在粗丝和细丝之间形成连接。图片来自Nature, 2023, doi:10.1038/s41586-023-06690-5。近年来，Raunser团队成功应用了这种定制的工作流程，最近发表了两篇突破性的论文：他们首次绘制了肌节的高分辨率图像，并绘制了一种迄今尚不清楚的肌肉蛋白---伴肌动蛋白---的高分辨率图像。这两项研究为我们提供了前所未有的关于肌节中肌肉蛋白三维组装的见解，例如肌球蛋白如何与肌动蛋白结合以控制肌肉收缩，以及伴肌动蛋白如何与肌动蛋白结合以稳定它并决定它的长度。完成图像绘制在这项新的研究中，这些作者首次绘制了横跨肌节多个区域的心脏粗丝的高分辨率图像。论文第一作者、马克斯-普朗克分子生理学研究所的Davide Tamborrini说，“500 纳米的长度是迄今为止通过cryo-ET解析的最长、最大的结构。”更令人印象深刻的是，他们对粗丝的分子结构及其功能有了新的认识。肌球蛋白分子的排列取决于它们在粗丝中的位置。他们猜测，这使得粗丝能够感知并处理众多肌肉调节信号，从而根据肌节区域调节肌肉收缩的强度。他们还揭示了肌联蛋白链是如何沿着粗丝运动的。肌联蛋白链与肌球蛋白交织在一起，作为肌球蛋白组装的支架，并可能协调肌节的长度依赖性激活。Raunser说，“我们的目标是有一天绘制出肌节的完整图像。在这项新的研究中，粗丝的图像只是肌肉放松状态下的快照。为了充分了解肌节的功能和调控机制，我们想分析不同状态下的肌节，例如收缩时的肌节。与肌肉疾病患者的肌肉样本进行比较，最终将有助于更好地了解肥厚性心肌病等疾病，并有助于开发创新疗法。”参考资料：Davide Tamborrini et al. Structure of the native myosin filament in the relaxed cardiac sarcomere. Nature, 2023, doi:10.1038/s41586-023-06690-5.First high-resolution image of thick filaments of muscle cellshttps://www.mpg.de/21017835/1030-moph-breakthrough-discovery-sheds-light-on-heart-and-muscle-health-151445-x本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

Analysis from FORTITUDE-ALS Shows Predicted Survival Risk Score Strongly Correlated with Decline in ALSFRS-R Findings Suggest Inclusion Criteria for COURAGE-ALS Will Enrich for the Enrollment of Faster Progressors SOUTH SAN FRANCISCO, Calif., Dec. 08, 2022 (GLOBE NEWSWIRE) -- Cytokinetics, Inc. (Nasdaq: CYTK) today announced that data were presented at the Virtual 33rd International Symposium on ALS/MND related to survival predictions from FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS), the Phase 2 clinical trial of reldesemtiv in ALS. “This analysis from FORTITUDE-ALS helps to build our understanding of disease progression in ALS, which is complex and heterogenous, and is an important element in the conduct of clinical research and the design of our clinical trials,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “Given the urgent need to deliver new therapies for people with ALS, it’s essential that clinical trials are designed with rigor to enhance the sensitivity of detecting a potential treatment effect. This analysis suggests the inclusion criteria we selected for the ongoing Phase 3 trial, COURAGE-ALS, may have the intended outcome of enrolling patients most likely to benefit from the investigational therapy. We look forward to continuing the conduct of COURAGE-ALS and completing patient enrollment in the first half of 2023.” Predicted Survival Risk Score for Participants in FORTITUDE-ALS Strongly Correlated with Decline in ALSFRS-R In a previously presented post-hoc analysis of disease progression in FORTITUDE-ALS, patients were grouped into tertiles according to their pre-study rate of decline in the ALS Functional Rating Scale Revised (ALSFRS-R) total score. The largest treatment effect from reldesemtiv was observed in the intermediate and fast progressing tertiles. Most patients in these two tertiles had experienced symptoms for ≤24 months and had a baseline ALSFRS-R total score ≤44 (referred to as the 24/44 criteria). In this analysis, the ENCALS survival model was used to calculate a predicted survival risk score for all participants in FORTITUDE-ALS. The ENCALS survival model calculates the risk score based on several factors, including age at onset, onset site, cognition, vital capacity, El Escorial classification, diagnostic delay, C9orf72 expansion repeat, and decline in ALSFRS-R total score. Based on their risk score, participants were assigned to one of five risk groups based on predicted survival: very short (G1), short (G2), intermediate (G3), long (G4), and very long (G5). Among participants in FORTITUDE-ALS, the mean ENCALS risk score at baseline was similar for patients receiving reldesemtiv and for those receiving placebo, and there was no statistically significant difference in the distribution of risk groups for those randomized to reldesemtiv compared to those randomized to placebo. When participants who met the 24/44 criteria (n=272) and those who did not (n=184) were categorized according to their ENCALS risk score, those who met the criteria were primarily in the G1, G2 or G3 groups associated with fast or intermediate progression and shorter predicted survival, whereas those who did not meet the criteria were primarily in the G4 and G5 risk groups associated with slow progression and longer survival. These findings suggest that ENCALS risk scores are strongly correlated with the rate of decline in the ALSFRS-R. In the ongoing Phase 3 trial of reldesemtiv, COURAGE-ALS (Clinical Outcomes Using Reldesemtiv on ALSFRS-R in a Global Evaluation in ALS), in order to enhance the ability to detect a treatment effect, participants must meet the 24/44 criteria to enroll in the trial. Findings from the current analysis of FORTITUDE-ALS suggest that implementing the 24/44 inclusion criteria will enrich for the enrollment of participants with more rapidly progressing disease, while minimizing, but not excluding, participants with more slowly progressing disease. COURAGE-ALS & COURAGE-ALS OLE: Trial Design COURAGE-ALS, a Phase 3, multi-center, double-blind, randomized, placebo-controlled trial of reldesemtiv is expected to enroll approximately 555 patients with ALS. Patients are randomized 2:1 to receive 300 mg of reldesemtiv or matching placebo dosed orally twice daily for 24 weeks, followed by a 24-week period in which all patients will receive 300 mg of reldesemtiv twice daily. Eligible patients are within the first two years of their first symptom of muscle weakness, have a vital capacity of ≥65% predicted, and a screening ALS Functional Rating Scale – Revised (ALSFRS-R) ≤44. Patients currently taking stable doses of Radicava® (edaravone) and/or Rilutek® (riluzole) are permitted to enroll, and randomization is stratified accordingly. In countries where the combination drug of sodium phenylbutyrate and taurursodiol is approved, Albrioza® (Canada) and Relyvrio® (US) are also permitted. The primary efficacy endpoint is change from baseline to 24 weeks in ALSFRS-R. Secondary endpoints include combined assessment of ALSFRS-R total score, time to onset of respiratory insufficiency and survival time up to week 24 using a joint rank test; change from baseline to 24 weeks for vital capacity; ALSAQ-40; and bilateral handgrip strength. Two unblinded interim analyses by the Data Monitoring Committee are planned. The first interim analysis assessing for futility occurred 12 weeks after approximately one-third or more of the planned sample size was randomized, and the Data Monitoring Committee recommended that the trial continue. A second interim analysis will also assess for futility and there will also be an option for a fixed increase in total enrollment, if deemed necessary, to augment the statistical power of the trial. An open-label extension trial, COURAGE-ALS OLE, is open to people who have completed participation in COURAGE-ALS. Following enrollment in COURAGE-ALS OLE, participants continue to receive 300 mg of reldesemtiv dosed orally twice daily for 48 weeks after which they may transition into the Managed Access Program. The primary endpoint is the incidence of adverse events. Secondary endpoints include the time to the first occurrence of respiratory insufficiency or death, time to the first hospitalization, combined assessment of change in ALSFRS-R total score, time to onset of respiratory insufficiency, and survival time, changes in ALSFRS-R total score, and the slope of changes in ALSFRS-R total score. Additional information on COURAGE-ALS OLE can be found at . About Reldesemtiv Skeletal muscle contractility is driven by the sarcomere, the fundamental unit of skeletal muscle contraction and a highly ordered cytoskeletal structure composed of several key proteins. Skeletal muscle myosin is the motor protein that converts chemical energy into mechanical force through its interaction with actin. A set of regulatory proteins, which includes tropomyosin and the troponin complex, make the actin-myosin interaction dependent on changes in intracellular calcium levels. Reldesemtiv is an investigational, selective, small molecule fast skeletal muscle troponin activator (FSTA) arising from Cytokinetics’ skeletal muscle contractility program. Reldesemtiv was designed to slow the rate of calcium release from the regulatory troponin complex of fast skeletal muscle fibers, which sensitizes the sarcomere to calcium, leading to an increase in skeletal muscle contractility. The development program for reldesemtiv is assessing its potential for the treatment of ALS and includes FORTITUDE-ALS, a completed Phase 2 trial, and COURAGE-ALS, the ongoing Phase 3 clinical trial designed to evaluate the effect of treatment with reldesemtiv compared to placebo on measures of disease progression, functional outcomes and survival. About ALS Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that afflicts approximately 27,000 people in the United States and a comparable number of patients in Europe. Approximately 6,300 new cases of ALS are diagnosed each year in the United States. The average life expectancy of a person with ALS is approximately three to five years after diagnosis and only approximately 10 percent of people with ALS survive for more than 10 years. Death is usually due to respiratory failure because of diminished strength in the skeletal muscles responsible for breathing. Few treatment options exist for these patients, resulting in a high unmet need for new therapies to address functional deficits and disease progression. About Cytokinetics Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors as potential treatments for debilitating diseases in which 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 muscle function and contractility. Cytokinetics is readying for the potential commercialization of omecamtiv mecarbil, its cardiac muscle activator, following positive results from GALACTIC-HF, a large, international Phase 3 clinical trial in patients with heart failure. Cytokinetics is also developing aficamten, a next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, the Phase 3 clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten is also being evaluated in non-obstructive HCM in Cohort 4 of the Phase 2 clinical trial, REDWOOD-HCM. Cytokinetics is also developing reldesemtiv, an investigational fast skeletal muscle troponin activator, currently the subject of COURAGE-ALS, a Phase 3 clinical trial in patients with amyotrophic lateral sclerosis (ALS). Cytokinetics continues its over 20-year history of pioneering innovation in muscle biology and related pharmacology focused to diseases of muscle dysfunction and conditions of muscle weakness. For additional information about Cytokinetics, visit and follow us on Twitter, LinkedIn, Facebook and YouTube. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). Cytokinetics disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act's Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements, express or implied, relating to the potential benefits of reldesemtiv for patients with ALS and statements relating to our ability to obtain marketing approval from FDA or any other regulatory body for reldesemtiv. Such statements are based on management's current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to, potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics' drug candidates that could slow or prevent clinical development or product approval; Cytokinetics' drug candidates may have adverse side effects or inadequate therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics' ability to conduct clinical trials; Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; standards of care may change, rendering Cytokinetics' drug candidates obsolete; and competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics' drug candidates and potential drug candidates may target. For further information regarding these and other risks related to Cytokinetics' business, investors should consult Cytokinetics' filings with the Securities and Exchange Commission. Contact: Cytokinetics Diane Weiser Senior Vice President, Corporate Communications, Investor Relations (415) 290-7757