THOUSAND OAKS, Calif.,?SOUTH SAN FRANCISCO, Calif., and?SURESNES--?Amgen?(NASDAQ: AMGN),?Cytokinetics, Incorporated?(NASDAQ: CYTK) and Servier today announced that METEORIC-HF (Multicenter?Exercise?Tolerance?Evaluation of?Omecamtiv Mecarbil?Related to?Increased?Contractility in?Heart?Failure), the second Phase 3 clinical trial of?omecamtiv mecarbil, a novel cardiac myosin activator, is open to enrollment.?Omecamtiv mecarbil?is being developed for the potential treatment of heart failure with reduced ejection fraction (HFrEF). METEORIC-HF is designed to evaluate the effect of treatment with?omecamtiv mecarbil?compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET) in patients with HFrEF.?Cytokinetics?is conducting METEORIC-HF in collaboration with?Amgen, with funding and strategic support from Servier. "The start of this second Phase 3 clinical trial marks an important milestone in the expansion of our clinical trials program for?omecamtiv mecarbil,?testing the hypothesis that improving cardiac function with a drug candidate that directly increases myocardial contractility may improve exercise capacity," said Fady I. Malik, M.D., Ph.D., executive vice president of Research & Development at?Cytokinetics. "Exercise intolerance, typically manifested by shortness of breath and fatigue on exertion, is a predominant symptom of chronic heart failure and often the first symptom that prompts patients to seek medical care. If positive, this clinical trial may provide key clinically relevant evidence." METEORIC-HF Clinical Trial Design METEORIC-HF is a Phase 3, randomized, placebo-controlled, double-blind, parallel group, multicenter clinical trial designed to evaluate the effect of treatment with?omecamtiv mecarbil?compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET) following 20 weeks of treatment. The trial is designed to enroll approximately 270 patients with HFrEF at sites throughout the U.S.,?Canada?and?Europe. In order to be eligible to participate in METEORIC-HF, patients must have a left ventricular ejection fraction (LVEF) =35 percent, be?New York Heart Association?(NYHA) heart failure class II or III and have reduced exercise capacity compared to age matched controls.?Patients will be randomized in a 2:1 fashion to?omecamtiv mecarbil, which will be started at 25 mg twice daily and titrated to 25, 37.5 or 50 mg twice daily based on the same PK-guided dosing regimen as is used in GALACTIC-HF, the ongoing Phase 3 cardiovascular outcomes trial of?omecamtiv mecarbil, or to placebo. The primary endpoint is the change in peak oxygen uptake (pVO₂) on CPET from baseline to Week 20. Secondary endpoints include the change in total workload during CPET from baseline to Week 20 and the change in the average daily activity units measured over a 2-week period from baseline (Week -2 to Day 1) to Week 18-20 as determined using accelerometry. Additional information about METEORIC-HF can be found on?https://clinicaltrials.gov/ct2/show/NCT03759392. About?Omecamtiv Mecarbil?and the Phase 3 Clinical Trials Program Omecamtiv mecarbil?is a novel, selective cardiac myosin activator that binds to the catalytic domain of myosin. Preclinical research has shown that cardiac myosin activators increase cardiac contractility without affecting intracellular myocyte calcium concentrations or myocardial oxygen consumption.^1,2,3?Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell that is directly responsible for converting chemical energy into the mechanical force resulting in cardiac contraction.?Omecamtiv mecarbil?is being developed for the potential treatment of heart failure with reduced ejection fraction (HFrEF) under a collaboration between?Amgen?and?Cytokinetics, with funding and strategic support from Servier. Omecamtiv mecarbil?is the subject of a comprehensive Phase 3 clinical trials program comprised of GALACTIC-HF?(Global?Approach to?Lowering?Adverse?Cardiac Outcomes?Through?Improving?Contractility in?Heart?Failure), a large, Phase 3 global cardiovascular outcomes study, and METEORIC-HF.?Amgen?is conducting GALACTIC-HF in collaboration with?Cytokinetics?and Servier. GALACTIC-HF is designed to enroll approximately 8,000 patients at over 900 sites in 35 countries who are either currently hospitalized for a primary reason of heart failure or have had a hospitalization or admission to an emergency room for heart failure within one year prior to screening. The trial is designed to evaluate whether treatment with?omecamtiv mecarbil, when added to standard of care, reduces the risk of heart failure events (heart failure hospitalization and other urgent treatment for heart failure) and cardiovascular (CV) death in patients with chronic heart failure with reduced ejection fraction. Enrollment in GALACTIC-HF is nearing 90 percent completion, with over 7,000 patients randomized to date from across the spectrum of the NYHA classification (class II to IV). Completion of patient enrollment in GALACTIC-HF is expected to occur during the first half of 2019. About Heart Failure Heart failure is a grievous condition that affects more than?26 million people worldwide,^4,5?about half of whom have reduced left ventricular function.^6,7?It is the leading cause of hospitalization and readmission in people age 65 and older.^8,9?Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor.¹⁰?An estimated one in five people over the age of 40 are at risk of developing heart failure, and approximately 50 percent of people diagnosed with heart failure will die within five years of initial hospitalization.^11,12 About?Cytokinetics?and Amgen Collaboration In 2006,?Cytokinetics?and?Amgen?entered into a strategic alliance to discover, develop and commercialize novel small molecule therapeutics designed to activate the cardiac sarcomere for the potential treatment of heart failure.?Omecamtiv mecarbil?is being developed by?Amgen?in collaboration with?Cytokinetics, with funding and strategic support from Servier.?Amgen?holds an exclusive, worldwide license to?omecamtiv mecarbil?and related compounds, subject to?Cytokinetics'?specified development and commercialization rights.?Cytokinetics?is eligible for pre-commercialization and commercialization milestone payments and royalties that escalate based on increasing levels of annual net sales of products commercialized under the agreement.?Cytokinetics?has co-invested with?Amgen?in the Phase 3 development program of?omecamtiv mecarbil?in exchange for increased royalties from?Amgen?on worldwide sales of?omecamtiv mecarbil?outside?Japan?and co-promotion rights in institutional care settings in North America.??Amgen?has also entered an alliance with Servier for exclusive commercialization rights in?Europe?as well as the Commonwealth of Independent States, including?Russia. Servier contributes funding for development and provides strategic support to the program. About?Amgen Amgen?is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgen?focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980,?Amgen?has grown to be the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. For more information, visit?www.amgen.com?and follow us on?www.twitter.com/amgen. About?Cytokinetics Cytokinetics?is a late-stage biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and best-in-class muscle inhibitors as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining. 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 collaborating with?Amgen Inc.?("Amgen") to develop?omecamtiv mecarbil, a novel cardiac muscle activator.?Omecamtiv mecarbil?is the subject of an international Phase 3 clinical trials program in patients with heart failure including GALACTIC-HF and METEORIC-HF. Amgen?holds an exclusive worldwide license to develop and commercialize?omecamtiv mecarbil?with a sublicense held by Servier for commercialization in?Europe?and certain other countries.?Cytokinetics?is also collaborating with?Amgen?to develop AMG 594, a first-in-class cardiac troponin activator, discovered under the companies' joint research program. Further development of AMG 594 is subject to the collaboration agreement between?Amgen?and?Cytokinetics. Cytokinetics?is collaborating with?Astellas Pharma Inc.?("Astellas") to develop?reldesemtiv, a fast skeletal muscle troponin activator (FSTA).?Reldesemtiv?has been granted orphan drug designation by the?FDA?for the potential treatment of spinal muscular atrophy.?Reldesemtiv?was the subject of a positive Phase 2 clinical study in patients with spinal muscular atrophy which showed increases in measures of endurance and stamina consistent with the mechanism of action.?Reldesemtiv?is currently the subject of a Phase 2 clinical trial in patients with amyotrophic lateral sclerosis.?Cytokinetics?is also advancing CK-601, a next-generation FSTA into IND-enabling studies under the collaboration with Astellas. Astellas holds an exclusive worldwide license to develop and commercialize?reldesemtiv. Licenses held by?Amgen?and Astellas are subject to specified co-development and co-commercialization rights of?Cytokinetics.?Cytokinetics?is also developing CK-274, a novel cardiac myosin inhibitor that company scientists discovered independent of its collaborations, for the potential treatment of hypertrophic cardiomyopathies. Cytokinetics?continues its 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?www.cytokinetics.com?and follow us on?Twitter,?LinkedIn,?Facebookand?YouTube. About Servier Servier is an international pharmaceutical company governed by a non-profit foundation and its headquarters in?France (Suresnes). With a strong international presence in 149 countries and a turnover of?4.152 billion euros in 2017, Servier employs over 21,700 people worldwide. Entirely independent, the Group reinvests 25% of its turnover (princeps drugs) in research and development and uses all its profits for development. Corporate growth is driven by Servier's constant search for innovation in five areas of excellence: cardiovascular, immune-inflammatory and neuropsychiatric diseases, cancer and diabetes, as well as by its activities in high-quality generic drugs. Servier also offers eHealth solutions beyond drug development. More information:?www.servier.com. Follow us on Social media:?LinkedIn,?Facebook,?Twitter Amgen Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of?Amgen. 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Cytokinetics 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 relating to?Cytokinetics'?and its partners' research and development activities; the timing of enrollment of patients in?Cytokinetics'?and its partners' clinical trials; the design, timing, results, significance and utility of preclinical and clinical results; and the properties and potential benefits of?Cytokinetics'?drug candidates.? 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, patient enrollment for or conduct of clinical trials may be difficult or delayed,?Cytokinetics'?drug candidates may have adverse side effects or inadequate therapeutic efficacy, the?FDA?or foreign regulatory agencies may delay or limit?Cytokinetics'?or its partners' ability to conduct clinical trials, and?Cytokinetics?may be unable to obtain or maintain patent or trade secret protection for its intellectual property; Astellas' decisions with respect to the design, initiation, conduct, timing and continuation of development activities for?reldesemtiv;?Amgen's?decisions with respect to the design, initiation, conduct, timing and continuation of development activities for?omecamtiv mecarbil; standards of care may change, rendering?Cytokinetics'drug candidates obsolete; competitive products or alternative therapies may be developed by others for the treatment of indications?Cytokinetics'?drug candidates and potential drug candidates may target; and risks and uncertainties relating to the timing and receipt of payments from its partners, including milestones and royalties on future potential product sales under?Cytokinetics'?collaboration agreements with such partners. For further information regarding these and other risks related to?Cytokinetics'?business, investors should consult?Cytokinetics'?filings with the?Securities and Exchange Commission. CONTACT:?Amgen,?Thousand Oaks Kristen Davis, 805-447-3008 (Media) Trish Hawkins, 805-447-5631 (Media) Arvind Sood, 805-447-1060 (Investors) CONTACT:?Cytokinetics Diane Weiser, Vice President, Corporate Communications, Investor Relations (415) 290-7757 CONTACT: Servier,?media@servier.com Sonia Marques, +33 (0)1 55 72 40 21 / + 33 (0) 7 84 28 76 13 Karine Bousseau, +33 (0)1 55 72 60 37 / + 33 (0)6 49 92 16 05 References ¹?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. ²?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. ³?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. ⁴?Savarese G and Lund LH. Global Public Health Burden of Heart Failure. Cardiac Failure Review 2017;3 (1): 7-11. ⁵?Ponikowski P, Anker SD, AlHabib KF, et al. Heart failure: preventing disease and death worldwide.?ESC Heart Failure?2014;1:4?25. ^6?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. ⁷?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. 8?Roger VL. Epidemiology of Heart Failure.?Circulation Research. 2013;113:646-659, originally published?August 29, 2013. Doi: 10.1161/CIRCRESAHA.113.300268. 9?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. ¹⁰?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. ¹¹?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. ^12?Rogers VL,?Weston SA, Redfield MM, et al. Trends in Heart Failure Incidence and Survival in a Community-Based Population.?JAMA. 2004;292:344-350.