# EDGAR Filing Document

**Accession Number:** 0001061983
**File Stem:** 0000950170-25-112564
**Filing Date:** 2025-9
**Character Count:** 21555
**Document Hash:** 371d6b6995da370aadc3d894fbd21598
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0000950170-25-112564.hdr.sgml**: 20250902

**ACCESSION NUMBER**: 0000950170-25-112564

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 14

**CONFORMED PERIOD OF REPORT**: 20250830

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20250902

**DATE AS OF CHANGE**: 20250902

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** CYTOKINETICS INC
- **CENTRAL INDEX KEY:** 0001061983
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 943291317
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 000-50633
- **FILM NUMBER:** 251286648

**BUSINESS ADDRESS:**
- **STREET 1:** 350 OYSTER POINT BOULEVARD
- **STREET 2:** .
- **CITY:** SOUTH SAN FRANCISCO
- **STATE:** CA
- **ZIP:** 94080
- **BUSINESS PHONE:** (650) 624-3000

**MAIL ADDRESS:**
- **STREET 1:** 350 OYSTER POINT BOULEVARD
- **CITY:** SOUTH SAN FRANCISCO
- **STATE:** CA
- **ZIP:** 94080

?xml version='1.0' encoding='ASCII'? 8-K

**UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549**

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## FORM 8-K

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**CURRENT REPORT**

**Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934**

**Date of Report (Date of earliest event reported):** August 30, 2025<br>

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Cytokinetics, Incorporated

**(Exact name of Registrant as Specified in Its Charter)**

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| | | |
|:---|:---|:---|
| Delaware | 000-50633 | 94-3291317 |
| **(State or Other Jurisdiction<br>of Incorporation)** | **(Commission File Number)** | **(IRS Employer<br>Identification No.)** |
| 350 Oyster Point Boulevard |  |  |
| South San Francisco**,** California |  | 94080 |
| **(Address of Principal Executive Offices)** |  | **(Zip Code)** |

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**Registrant's Telephone Number, Including Area Code:** (650) 624-3000<br>

n/a<br>

**(Former Name or Former Address, if Changed Since Last Report)**

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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

**Securities registered pursuant to Section 12(b) of the Act:**

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| | | |
|:---|:---|:---|
| **<br>Title of each class** | **Trading<br>Symbol(s)** | **<br>Name of each exchange on which registered** |
| Common Stock, $0.001 par value | CYTK | The Nasdaq Global Select Market |

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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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## Item 8.01 Other Events.
Cytokinetics, Incorporated announced that the primary results of MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM) were presented in a Hot Line Session at the European Society of Cardiology Congress 2025 in Madrid, Spain, and simultaneously published in The New England Journal of Medicine. The full text of the press release issued in connection with this announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

## Item 9.01 Financial Statements and Exhibits.
99.1 [<u>Press Release dated August 30, 2025</u>](cytk-ex99_1.htm)

104 The cover page of this report has been formatted in Inline XBRL

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**SIGNATURES**

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

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| | | | |
|:---|:---|:---|:---|
|  |  |  | CYTOKINETICS, INCORPORATED |
| Date: | September 2, 2025 | By:  | /s/ John Faurescu |
|  |  |  | SVP, Deputy General Counsel & Secretary |

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## Exhibit 99.1

![img114956760_0.jpg](img114956760_0.jpg)

**CYTOKINETICS ANNOUNCES PRIMARY RESULTS FROM MAPLE-HCM** 

**PRESENTED AT THE EUROPEAN SOCIETY OF CARDIOLOGY CONGRESS 2025**

**AND PUBLISHED IN THE *NEW ENGLAND JOURNAL OF MEDICINE*** 

*Positive Trial Demonstrates Superiority of Aficamten to Standard-of-Care Beta-Blocker Metoprolol* 

*Primary Endpoint Result Consistent Across All Prespecified Subgroups*

*Company to Host Investor Event and Webcast Tuesday September 2, 2025, at 8:00 AM Eastern Time*

**SOUTH SAN FRANCISCO, Calif., Aug. 30, 2025** – Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that primary results from MAPLE-HCM (***M****etoprolol* vs ***A****ficamten* in **P**atients with **L**VOT Obstruction on **E**xercise Capacity in **HCM**) were presented in a Hot Line Session at the European Society of Cardiology Congress 2025 in Madrid, Spain, and simultaneously published in *The New England Journal of Medicine.*<sup>1</sup>

MAPLE-HCM is a Phase 3 randomized, double-blind, active-comparator clinical trial of *aficamten* compared to *metoprolol* in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). MAPLE-HCM enrolled 175 patients, randomized on a 1:1 basis to receive *aficamten* or *metoprolol* as monotherapy. Compared to SEQUOIA-HCM, the pivotal Phase 3 clinical trial of *aficamten*, MAPLE-HCM was designed to include patients with less severe oHCM, enrolling patients without obstruction at rest and with higher predicted peak oxygen uptake (pVO2).

"This important study has the potential to inform our approach to treating obstructive HCM, as MAPLE-HCM provides the field its first look at a cardiac myosin inhibitor compared directly to a beta-blocker," said Pablo Garcia-Pavia, M.D., Ph.D., Head of the Inherited Cardiac Diseases and Heart Failure Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro and Full Professor, Centro Nacional de Investigaciones Cardiovasculares in Madrid, Spain. "In showing that *aficamten* is superior to *metoprolol* on all clinically relevant efficacy endpoints, these results call into question the reliance on beta-blockers as the initial treatment modality for obstructive HCM that has prevailed for over 60 years."

"These results demonstrate that *aficamten* meaningfully improves exercise capacity in patients with obstructive HCM while treatment with *metoprolol* resulted in a meaningful reduction in exercise capacity," said Fady I. Malik, M.D., Ph.D., Cytokinetics' Executive Vice President of Research & Development. "The clinical difference in the two treatments is reinforced by the effect of *aficamten* on the secondary endpoints. Compared to first-line standard-of-care *metoprolol*, treatment with *aficamten* had a larger effect on

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measures of symptoms, functional class, and LVOT gradients. Importantly, these effects were achieved in a broader patient population with oHCM than previously studied in SEQUOIA-HCM, inclusive of patients in MAPLE-HCM with less severe disease as measured by objective metrics of disease burden."

*Aficamten* is an investigational drug candidate currently under regulatory review in the U.S; the Food and Drug Administration (FDA) is reviewing a New Drug Application (NDA) for *aficamten* with a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2025.

**Results of MAPLE-HCM**

The primary endpoint in MAPLE-HCM was the mean change from baseline in pVO2 for *aficamten* compared to *metoprolol* after 24 weeks of treatment. For *aficamten*, the mean change in pVO2 from baseline to Week 24 was +1.1 mL/kg/min (95% CI 0.5 to 1.7) and for *metoprolol* was -1.2 mL/kg/min (95% CI -1.7 to -0.8). The primary endpoint was statistically significant with a least-squares mean (LSM) difference between groups of 2.3 mL/kg/min (95% CI 1.5 to 3.1; p<0.0001) (Figure 1). The effect of *aficamten* on pVO2 was consistent across all prespecified subgroups, including in patients who were newly diagnosed or treatment naïve (Figure 2).

![img114956760_1.jpg](img114956760_1.jpg)![img114956760_2.jpg](img114956760_2.jpg)

*Aficamten* also showed superiority to *metoprolol* in five of six secondary endpoints, all of which were evaluated at 24 weeks compared to baseline (Table 1). *Aficamten* substantially improved functional class and reduced patient symptom burden. For patients treated with *aficamten*, 51% had an improvement of one or more functional class in New York Heart Association (NYHA) Functional Class compared to 26% receiving *metoprolol* (p<0.001). There was also a significant improvement observed in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (LSM difference = 6.9 points; p<0.01).

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| | |
|:---|:---|
| &nbsp;&nbsp;**Table 1: Secondary Endpoints** | &nbsp;&nbsp;**Table 1: Secondary Endpoints** |
| &nbsp;&nbsp;**Endpoint** | &nbsp;&nbsp;**P-Value** |

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| | |
|:---|:---|
| &nbsp;&nbsp;Proportion of patients with ≥1 class improvement in NYHA functional class from baseline to week 24 | &nbsp;&nbsp;*P* <0.001 |
| &nbsp;&nbsp;Change in KCCQ-CSS from baseline to week 24 | &nbsp;&nbsp;*P* <0.010 |
| &nbsp;&nbsp;Change in NT-proBNP from baseline to week 12 | &nbsp;&nbsp;*P* <0.001 |
| &nbsp;&nbsp;Change in post-Valsalva LVOT-G from baseline to week 24 | &nbsp;&nbsp;*P* <0.001 |
| &nbsp;&nbsp;Change from baseline to week 24 in LAVI | &nbsp;&nbsp;*P* <0.001 |
| &nbsp;&nbsp;Change from baseline to week 24 in LVMI | &nbsp;&nbsp;*P* = 0.16 |

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Relative to *metoprolol, aficamten* significantly improved resting left ventricular outflow tract gradient (LVOT-G) (LSM difference = -30 mmHg; p<0.0001) and Valsalva LVOT-G (LSM difference = -35 mmHg; p<0.0001), with a modest reduction in left ventricular ejection fraction (LVEF) (LSM difference = -4%; p<0.0001), and only 1 (1.1%) patient experiencing LVEF <50% per core laboratory. Despite demonstrating on-target hemodynamic effects of lowering heart rate and systolic blood pressure, *metoprolol* did not improve LVOT-G.

Compared to *metoprolol, aficamten* was associated with an 81% reduction in NT-proBNP, a biomarker of cardiac wall stress (p<0.0001), and a significant improvement in left atrial volume index (LAVI) (LSM difference = 7.0 ml/m<sup>2</sup>; p<0.0001) consistent with an improvement in diastolic dysfunction and suggesting potentially favorable cardiac remodeling. There was no difference observed between *aficamten* and *metoprolol* on the secondary endpoint of left ventricular mass index (LVMI) (p=0.16).

Overall, the rate of adverse events (AEs) was similar between groups. *Aficamten* was down-titrated in four patients (4.5%), three due to site-read LVEF <50% and one due to an AE of dizziness, while *metoprolol* was down-titrated in 26 patients (29.9%) due to low systolic blood pressure, low heart rate or other AEs. One patient receiving *aficamten,* a 69-year-old woman with multiple co-morbidities, developed a viral illness and subsequently died. Three patients receiving *metoprolol* terminated treatment due to AEs. At least one treatment-emergent AE was reported by 65 (73.9%) and 66 (75.9%) patients treated with *aficamten* and *metoprolol*, respectively. The most common AE reported in excess (>5%) of the comparator was hypertension for *aficamten* (9 [10.2%] patients compared to 2 [2.3%] patients on *metoprolol*) and dizziness for *metoprolol* (15 [17.2%] patients compared to 5 [5.7%] patients on *aficamten*).

**Investor Webcast Information**

Cytokinetics will host an investor webcast on September 2, 2025, at 8:30 AM Eastern Time to discuss the primary results from MAPLE-HCM and other data presented at the European Society of Cardiology Congress 2025. Interested parties can register online at https://cytokinetics-esc-2025.open-exchange.net/. The live webcast will be available on the Investors & Media section of the Cytokinetics website at www.cytokinetics.com. A replay of the webcast will be archived on the Cytokinetics website for six months.

**About *Aficamten*** 

*Aficamten* is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index

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and pharmacokinetic properties.<sup>2</sup> *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 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.

The development program for *aficamten* is assessing its potential as a treatment that improves exercise capacity as measured by peak oxygen uptake (pVO2) and relieves symptoms in patients with HCM. *Aficamten* was evaluated in SEQUOIA-HCM, a positive pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). *Aficamten* received Breakthrough Therapy Designation for the treatment of symptomatic HCM from the U.S. Food & Drug Administration (FDA) and for the treatment of symptomatic obstructive HCM from the National Medical Products Administration (NMPA) in China.

*Aficamten* is also currently being evaluated in 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 oHCM; and FOREST-HCM, an open-label extension clinical study of *aficamten* in patients with HCM.

This communication contains a summary of new data related to the clinical development of *aficamten* presented at the European Society of Cardiology 2025 Congress. *Aficamten* is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. *Aficamten* is currently under regulatory review in the U.S, where the FDA is reviewing a New Drug Application (NDA) for *aficamten* with a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2025. Additionally, the European Medicines Agency (EMA) is reviewing a Marketing Authorization Application (MAA) for *aficamten*, and The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) is reviewing an NDA for *aficamten* with Priority Review.

**About Hypertrophic Cardiomyopathy**

Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart's pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed, however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed in the U.S.<sup>3,4,5</sup> Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn't impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.<sup>6</sup> People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes.<sup>7</sup> A subset of

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patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation.

**About Cytokinetics** 

Cytokinetics is a specialty cardiovascular biopharmaceutical company, building on its over 25 years of pioneering scientific innovations in muscle biology to advance a pipeline of potential new medicines for patients suffering from diseases of cardiac muscle dysfunction. Cytokinetics is readying for potential regulatory approvals and commercialization of *aficamten,* a cardiac myosin inhibitor following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy (HCM). *Aficamten* is also being evaluated in additional clinical trials enrolling patients with obstructive and non-obstructive HCM. Cytokinetics is also developing *omecamtiv mecarbil*, a cardiac myosin activator, in patients with heart failure with severely reduced ejection fraction (HFrEF), *ulacamten*, a cardiac myosin inhibitor with a mechanism of action distinct from *aficamten,* for the potential treatment of heart failure with preserved ejection fraction (HFpEF) and CK-089, a fast skeletal muscle troponin activator with potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired skeletal muscle function.

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 the properties, treatment effect or potential benefits of *aficamten* or any of our other drug candidates or our ability to obtain regulatory approval for *aficamten* for the treatment of obstructive hypertrophic cardiomyopathy or any other indication from FDA or any other regulatory body in the United States or abroad by any particular date, if ever. 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 the risks related to Cytokinetics' business outlines in Cytokinetics' filings with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and Cytokinetics' actual results of operations, financial condition and liquidity, and the development of the industry in which it operates, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that Cytokinetics makes in this press release speak only as of the date of this press release. Cytokinetics assumes no obligation to update its forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries.

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Contact:

Cytokinetics <br>Diane Weiser<br>Senior Vice President, Corporate Affairs

(415) 290-7757

References:

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;1.Garcia-Pavia, P, et al. *Aficamten* or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy. N Engl J Med. 2025

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;2.Chuang C, Collibee S, Ashcraft L, et al. Discovery of *Aficamten* (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. J Med Chem. 2021;64(19):14142–14152. https://doi.org/10.1021/acs.jmedchem.1c01290

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;3.CVrg: Heart Failure 2020-2029, p 44; Maron et al. 2013 DOI: 10.1016/S0140-6736(12)60397-3; Maron et al 2018 10.1056/NEJMra1710575

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;4.Symphony Health 2016-2021 Patient Claims Data DoF;

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;5.Maron MS, Hellawell JL, Lucove JC, Farzaneh-Far R, Olivotto I. Occurrence of Clinically Diagnosed Hypertrophic Cardiomyopathy in the United States. Am J Cardiol. 2016; 15;117(10):1651-1654.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;6.Gersh, B.J., Maron, B.J., Bonow, R.O., Dearani, J.A., Fifer, M.A., Link, M.S., et al. 2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Journal of the American College of Cardiology and Circulation, 58, e212-260.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;7.Hong Y, Su WW, Li X. Risk factors of sudden cardiac death in hypertrophic cardiomyopathy. Current Opinion in Cardiology. 2022 Jan 1;37(1):15-21

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