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What changed in CYTOKINETICS INC's 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of CYTOKINETICS INC's 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+549 added−413 removedSource: 10-K (2026-02-26) vs 10-K (2025-02-27)

Top changes in CYTOKINETICS INC's 2025 10-K

549 paragraphs added · 413 removed · 318 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

103 edited+125 added−44 removed45 unchanged
Biggest changeWe believe that our ability to successfully compete will depend on, among other things: • efficacy, safety and reliability of omecamtiv mecarbil, both alone and in combination with other therapies; • the ability to fund and successfully complete an additional confirmatory phase 3 clinical trial of omecamtiv mecarbil in HFrEF and resolve to the satisfaction of FDA the other deficiencies stipulated in the CRL we received in response to our initial NDA submission for omecamtiv mecarbil; • the timing and scope of regulatory approval by EMA and regulatory bodies in other countries; 16 Table of Contents • our ability to manufacture and sell commercial quantities of omecamtiv mecarbil product to the market; • our ability to gain market access and secure coverage and adequate reimbursement with affordable patient out of pocket cost in approved indications; • product acceptance by physicians and other health care providers; • if required in connection to regulatory approval by FDA, EMA and/or other regulatory authorities, the availability of an antibody-based immunoassay to measure omecamtiv mecarbil concentration levels in patients to whom omecamtiv mecarbil is administered; • price competition, particularly of generic products; • protection of our intellectual property, including our ability to enforce our intellectual property rights against potential generic competition; and • the availability of substantial capital resources to fund development and commercialization activities.
Biggest changeWe believe that our ability to successfully compete will depend on, among other things: • efficacy and safety of omecamtiv mecarbil, both alone and in combination with other therapies; • the ability to fund and successfully complete an additional confirmatory phase 3 clinical trial of omecamtiv mecarbil in HFrEF and resolve to the satisfaction of FDA the other deficiencies stipulated in the CRL we received in response to our initial NDA submission for omecamtiv mecarbil; • the timing and scope of regulatory approval by EMA and regulatory bodies in other countries, if at all; • our ability to manufacture and sell commercial quantities of omecamtiv mecarbil product to the market; • our ability to gain market access and secure coverage and adequate reimbursement with affordable patient out of pocket cost in approved indications; • product acceptance by physicians and other health care providers; • if required in connection to regulatory approval by FDA, EMA and/or other regulatory authorities, the commercial availability of an antibody-based immunoassay to measure omecamtiv mecarbil concentration levels in patients to whom omecamtiv mecarbil is administered • price competition, particularly of generic products; • protection of our intellectual property through enforcement of our intellectual property rights against any challengers, including potential generic competition, and the absence of any blocking intellectual property rights that limit our ability to market MYQORZO as we have planned; and • the availability of substantial capital resources to fund development and commercialization activities. 16 Table of Contents Competition for Ulacamten We believe the principal competition for ulacamten, if ultimately approved for sales and marketing by FDA and/or other regulatory agencies for the treatment of HFpEF will include both in-class cardiac myosin inhibitors as well as general heart failure drugs with HFpEF labels, many of which will be generic.
The first line HFrEF generic therapies, including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), Mineralocorticoid receptor antagonists (MRAs) as well the branded drugs such as Entresto ® (sacubitril/valsartan) and SGLT2 inhibitor class that have either expanded or are planning to expand their labels to include treatment of patients with heart failure, including Forxiga ® (dapagliflozin), Invokana ® (canagliflozin), and Jardiance ® (empagliflozin).
The first line HFrEF generic therapies, including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs) as well the branded drugs such as Entresto ® (sacubitril/valsartan) and the SGLT2 inhibitor class that have either expanded or are planning to expand their labels to include treatment of patients with heart failure, include Forxiga ® (dapagliflozin), Invokana ® (canagliflozin), and Jardiance ® (empagliflozin).
Omecamtiv mecarbil is designed to increase the number of active actin-myosin cross bridges during each cardiac cycle and consequently augment the impaired contractility that is associated with heart failure with reduced ejection fraction, or HFrEF. GALACTIC-HF GALACTIC-HF was a Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil which was conducted by Amgen in collaboration with Cytokinetics.
Omecamtiv mecarbil is designed to increase the number of active actin-myosin cross bridges during each cardiac cycle and consequently augment the impaired contractility that is associated with heart failure with reduced ejection fraction, or HFrEF. GALACTIC-HF GALACTIC-HF is a Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil that was conducted by Amgen in collaboration with Cytokinetics.
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. A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation.
People with HCM are at risk for potentially fatal ventricular arrhythmias, and HCM is one of the leading causes of sudden cardiac death in younger people or athletes. A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation.
These third parties must comply with applicable regulatory requirements, including FDA’s cGMP, the E.U.’s Guidelines on Good Distribution Practice, as well as other stringent regulatory requirements enforced by the FDA or foreign regulatory agencies, as applicable, and are subject to routine inspections by such regulatory agencies.
These third parties must comply with applicable regulatory requirements, including the FDA’s cGMP, the E.U.’s Guidelines on Good Distribution Practice, as well as other stringent regulatory requirements enforced by the FDA or foreign regulatory agencies, as applicable, and are subject to routine inspections.
Omecamtiv mecarbil could also compete against other novel drug candidates and therapies in development, such as those being developed by Novartis AG, Merck & Co., Inc., Bayer AG, AstraZeneca PLC and Bristol-Myers Squibb Company.
Omecamtiv mecarbil could also compete against other novel drug candidates and therapies in development, such as those being developed by Novartis AG, Merck & Co., Inc., Bayer AG, AstraZeneca PLC, Kardigan, Inc., and Bristol-Myers Squibb Company.
The treatement landscape for HFrEF is crowded and evolving rapidly, especially given the addition of SGLT2 inhibitors as AHA/ACC/HFSA guideline directed medical therapy for HFrEF. SGLT2 inhibitors have steadily gained market share. In addition, there are a number of medical devices both marketed and in development for the treatment of patients living with heart failure.
The treatment landscape for HFrEF is crowded and evolving, especially given the addition of SGLT2 inhibitors as AHA/ACC/HFSA guideline directed medical therapy for HFrEF. SGLT2 inhibitors have steadily gained market share. In addition, there are a number of medical devices both marketed and in development for the treatment of patients living with heart failure.
Central to our commercialization strategy is ensuring a clear understanding and expertise in navigating the regulatory and payer landscape in each geography along with market research and advanced analytics to inform positioning, messaging and value proposition development. IMPACT: Reach 100,000 patients globally with our medicines.
Central to our commercialization strategy is having a clear understanding and expertise in navigating the regulatory and payer landscape in each geography along with market research and advanced analytics to inform positioning, messaging and value proposition development IMPACT: Reach 100,000 patients globally with our medicines.
In preclinical models, aficamten reduces 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. Aficamten reduces the number of active actin-myosin cross bridges during each cardiac cycle and consequently reduces myocardial contractility.
In preclinical models, MYQORZO reduces 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. MYQORZO reduces the number of active actin-myosin cross bridges during each cardiac cycle and consequently reduces myocardial contractility.
At the highest single dose of 600 mg, the mean decrease in LVEF was AMBER-HFpEF In the fourth quarter of 2024, we announced the design of AMBER-HFpEF (Assessment of CK-586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF), a Phase 2 randomized, placebo-controlled, double-blind, multi-center, dose-finding clinical trial in patients with symptomatic HFpEF with left ventricular ejection fraction ≥ 60%.
At the highest single dose of 600 mg, the mean decrease in LVEF was AMBER-HFpEF In the fourth quarter of 2024, we announced the design of AMBER-HFpEF (Assessment of Ulacamten in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF), a Phase 2 randomized, placebo-controlled, double-blind, multi-center, dose-finding clinical trial in patients with symptomatic HFpEF with left ventricular ejection fraction ≥ 60%.
The results of GALACTIC-HF showed that after a median duration of follow-up of 21.8 months, the trial demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of CV death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care.
The results of GALACTIC-HF showed a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of CV death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care after a median duration of follow up of 21.8 months.
Pursuant to the RP OM RPA, as amended, RPFT has a revenue interest entitling it to up to 5.5% of our and our affiliates’ and licensees’ worldwide net sales of omecamtiv mecarbil. In the second quarter of 2024, we entered into the RP OM Loan Agreement with RPDF.
Pursuant to the RP OM RPA, as amended, RPFT has a revenue interest entitling it to up to 5.5% of our and our affiliates’ and licensees’ worldwide net sales of drug products containing omecamtiv mecarbil. In the second quarter of 2024, we entered into the RP OM Loan Agreement with RPDF.
Phase 1 Trial Results We conducted a Phase 1 double-blind randomized, placebo-controlled, multi-part single and multiple ascending dose clinical study with the goal of evaluating the safety, tolerability and PK of CK-586 when administered orally as single or multiple doses to healthy participants.
Phase 1 Trial Results We conducted a Phase 1 double-blind randomized, placebo-controlled, multi-part single and multiple ascending dose clinical study with the goal of evaluating the safety, tolerability and PK of ulacamten when administered orally as single or multiple doses to healthy participants.
Data from a Phase 2 clinical trial of aficamten in patients with non-obstructive HCM show that aficamten was well tolerated, improved patient reported outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Functional Class) and biomarkers, measures that are also relevant to HFpEF.
Data from a Phase 2 clinical trial of aficamten in patients with nHCM show that aficamten was well tolerated, improved patient reported outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Functional Class) and biomarkers, measures that are also relevant to HFpEF.
Our research and development activities relating to the biology of muscle function have evolved from our knowledge and expertise regarding the cytoskeleton, a complex biological infrastructure that plays a fundamental role within every human cell.
All our research and development activities relate to the biology of muscle function and have evolved from our knowledge and expertise regarding the cytoskeleton, a complex biological infrastructure that plays a fundamental role within every human cell.
In addition to patent exclusivity, the drug candidates may be protected by regulatory exclusivities upon approval in some countries. Aficamten The following table describes certain issued U.S. and European patents that relate to aficamten . In addition to the patents listed below, we continue to pursue additional patent applications.
In addition to patent exclusivity, the products and drug candidates may be protected by regulatory exclusivities upon approval in some countries. 17 Table of Contents Aficamten The following table describes certain issued U.S. and European patents that relate to aficamten. In addition to the patents listed below, we continue to pursue additional patent applications.
Our compensation and benefit programs are designed to enable us to attract and retain the best employees in a very competitive life science sector and regularly benchmark and survey the market to ensure we maintain competitive programs.
Our compensation and benefit programs are designed to enable us to attract and retain the best employees in a very competitive life science sector and we regularly benchmark and survey the market so that we maintain competitive programs.
The following tables list certain granted U.S. and European patents that relate to our most advanced drug candidates. Additional patent protection through granted patents in the U.S., Europe, or other foreign jurisdictions may be available, and additional patent applications in the U.S., Europe, or other foreign jurisdictions are being pursued.
The following tables list certain granted U.S. and European patents that relate to our commercialization product and our most advanced drug candidate. Additional patent protection through granted patents in the U.S., Europe, or other foreign jurisdictions may be available, and additional patent applications in the U.S., Europe, or other foreign jurisdictions are being pursued.
Based on these and other promising subgroup analyses from GALACTIC-HF and the high unmet need in patients with heart failure with severely reduced ejection fraction, we decided to continue the development program for omecamtiv mecarbil and to conduct a confirmatory study in a patient population similar to the approximately 4,000 prespecified subgroup of patients with an LVEF 28% in GALACTIC-HF.
Based on these and other promising subgroup analyses from GALACTIC-HF and the high unmet need in patients with heart failure with severely reduced ejection fraction, we are continuing the development program for omecamtiv mecarbil and conducting a confirmatory study in a patient population similar to the approximately 4,000 prespecified subgroup of patients with an LVEF 28% in GALACTIC-HF.
Royalty Pharma Revenue Interest We are party to a revenue interest agreement with RPI ICAV, the RP Aficamten RPA, pursuant to which RPI ICAV purchased rights to certain revenue streams from net sales of pharmaceutical products containing aficamten by us, our affiliates and our licensees.
Royalty Pharma Revenue Interest We are party to a revenue interest agreement with RPI ICAV, the RP Aficamten RPA, pursuant to which RPI ICAV purchased rights to certain revenue streams from net sales of MYQORZO and any other future potential pharmaceutical products containing aficamten by us, our affiliates and our licensees.
As we build our specialty cardiology franchise, we are committed to targeting disease areas of significant high unmet need in which there are either limited treatment options or in which the available treatments do not address the underlying disease.
As we build our specialty cardiology franchise, beginning with the commercialization of MYQORZO, we are committed to targeting disease areas of high unmet need in which there are either limited treatment options or in which the available treatments do not address the underlying disease.
This in turn could affect our ability to successfully commercialize our products and impact our profitability, results of operations, financial condition, and future success. Cytokinetics Human Capital As of December 31, 2024, we had 498 employees. We are committed to fostering and maintaining a culture that engenders collaboration and teamwork, inclusion, respect, transparency and candor.
This in turn could affect our ability to successfully commercialize our products and impact our profitability, results of operations, financial condition, and future success. 24 Table of Contents Cytokinetics Human Capital As of December 31, 2025, we had 673 employees. We are committed to fostering and maintaining a culture that engenders collaboration and teamwork, inclusion, respect, transparency and candor.
If approved, omecamtiv mecarbil is intended not to be competitive to guideline directed first line therapies but a complementary add-on therapy for the subset of heart failure patients with severely reduced ejection fraction.
If approved, omecamtiv mecarbil is not intended to compete with guideline directed first line therapies and instead is intended to be a complementary add-on therapy for the subset of heart failure patients with severely reduced ejection fraction.
We also expect to advance two earlier stage new chemical entities in clinical development programs: CK-586 for the potential treatment of a subgroup of patients with symptomatic HFpEF with hypercontractility and ventricular hypertrophy and CK-089 with potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired muscle function.
We also intend to advance two earlier stage new chemical entities in clinical development programs: (i) ulacamten for the potential treatment of a subgroup of patients with symptomatic HFpEF with hypercontractility and ventricular hypertrophy and (ii) CK-089, which has potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired muscle function.
ITEM 1. BUSINESS Overview We are 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 and/or declining.
ITEM 1. BUSINESS Overview We are a biopharmaceutical company focused on discovering, developing and commercializing novel muscle activators and muscle inhibitors as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining.
Building a Specialty Cardiology Franchise We believe we are well positioned to build a specialty cardiology franchise anchored by our later-stage development program for aficamten, complemented by earlier stage drug candidates that have arisen from our industry leading research and leadership in muscle biology and the mechanics of contractility.
Building a Specialty Cardiology Franchise We believe we are well positioned to build a specialty cardiology franchise anchored by MYQORZO and, later complemented by earlier stage drug candidates that have arisen from our research and leadership in muscle biology and the mechanics of contractility.
Under the RP CK-586 RPA, in consideration of an up-front $50 million payment, RPI ICAV purchased a revenue interest entitling it to 1.0% of our annual worldwide net sales of CK-586.
Under the RP Ulacamten RPA, in consideration of an up-front $50 million payment, RPI ICAV purchased a revenue interest entitling it to 1.0% of our annual worldwide net sales of drug products containing ulacamten.
Patent Type Patent Expiration* United States 10,836,755 Composition of matter 2039 Europe 3740481 Composition of matter 2039 Europe 3999180 Polymorphic forms 2040 Europe 3999038 Formulation 2040 *Stated expiration dates do not account for any patent term adjustment, patent term extension, supplementary protection certificates, or pediatric extensions that may be available.
Patent Type Patent Expiration* United States 10,836,755 Composition of matter 2039 United States 12,370,179 Method of treatment 2042 Europe 3740481 ^ Composition of matter 2039 Europe 3999180 ^^ Polymorphic forms 2040 Europe 3999038 Formulation 2040 Europe 4370116 ^^^ Compound for use 2042 *Stated expiration dates do not account for any patent term adjustment, patent term extension, supplementary protection certificates, or pediatric extensions that may be available.
Pursuant to the terms of the RP Aficamten RPA, as amended, RPI ICAV is entitled to receive 4.5% of our worldwide annual net sales of aficamten up to $5.0 billion and 1% of our annual net sales of aficamten above $5.0 billion.
Pursuant to the terms of the RP Aficamten RPA, as amended, RPI ICAV is entitled to receive 4.5% of our worldwide annual net sales of MYQORZO and any other future potential products containing aficamten up to $5.0 billion and 1% of our annual net sales above $5.0 billion.
As a leader in muscle biology and the mechanics of muscle performance, we are discovering and developing small molecule drug candidates specifically engineered to impact muscle function and contractility with objective to build a sustainable specialty biopharmaceutical business. Our research continues to drive innovation and leadership in muscle biology.
As a leader in muscle biology and the mechanics of muscle performance, we are discovering and developing small molecule drug candidates specifically engineered to impact muscle function and contractility with the objective of building a sustainable specialty biopharmaceutical business.
In addition to the patents listed below, we continue to pursue additional patent applications. At the appropriate time, the company will pursue available patent term extensions and supplementary protection certificates in the U.S. and Europe that may, if issued, extend exclusivity beyond the patent expirations listed in the table. Jurisdiction Patent No.
At the appropriate time, the Company will pursue available patent term extensions and supplementary protection certificates in the U.S. and Europe that may, if issued, extend exclusivity beyond the patent expirations listed in the table. Jurisdiction Patent No.
All of our drug candidates have arisen from our cytoskeletal research activities. Our focus on the biology of the cytoskeleton distinguishes us from other biopharmaceutical companies, and potentially positions us to identify or discover and develop and commercialize novel therapeutics that may be useful for the treatment of severe diseases and medical conditions.
Our specific focus on the biology of the cytoskeleton distinguishes us from other biopharmaceutical companies and potentially positions us to identify or discover and develop and commercialize novel therapeutics that may be useful for the treatment of severe diseases and medical conditions.
Patent Type Patent Expiration* United States 7,507,735 Composition of matter 2025 United States 9,988,354 Salt form 2034 United States 9,951,015 Formulation 2034 United States 11,576,910 Methods of treatment 2038 United States 12,194,093** Method of treatment 2041 Europe 1765327 Composition of matter 2025 Europe 2968173 Formulation 2034 Europe 2970123 Salt form 2034 *Stated expiration dates do not account for any patent term adjustment, patent term extension, supplementary protection certificates, or pediatric extensions that may be available.
Patent Type Patent Expiration* United States 9,988,354 Salt form 2034 United States 9,951,015 Formulation 2034 United States 11,576,910 Methods of treatment 2038 United States 12,194,039 Method of treatment 2041 Europe 2968173 Formulation 2034 Europe 2970123 Salt form 2034 Europe 3645002 Compound for use 2038 Europe 4243825 Compound for use 2041 *Stated expiration dates do not account for any patent term adjustment, patent term extension, supplementary protection certificates, or pediatric extensions that may be available.
Although we do not anticipate any immediate difficulties in procuring raw materials from China, we are actively seeking to establish alternative geographically diverse supply arrangements for this particular registered starting material and other raw materials and compounds.
For example, we currently source key registered starting materials for aficamten from manufacturers in China. Although we do not anticipate any immediate difficulties in procuring raw materials from China, we are actively seeking to establish alternative geographically diverse supply arrangements for these particular registered starting materials and other raw materials and compounds.
Pharmaceutical Product Development Process To establish a new product candidate’s safety and efficacy, the FDA requires companies seeking approval to market a pharmaceutical drug product to submit extensive preclinical and clinical data, along with other information, for each indication for which the product will be labeled.
The GCP requirements encompass both ethical and data integrity standards for clinical studies. To establish a new product candidate’s safety and efficacy, the FDA requires companies seeking approval to market a pharmaceutical drug product to submit extensive preclinical and clinical data, along with other information, for each indication for which the product will be labeled.
The primary objective is to evaluate the safety and tolerability profile of CK-586 compared to placebo. The secondary objectives include assessing the effect of CK-586 on LVEF and NT-proBNP, its pharmacokinetics, and its pharmacokinetic/pharmacodynamic relationship. AMBER-HFpEF is currently enrolling patients.
The primary objective is to evaluate the safety and tolerability profile of ulacamten compared to placebo. The secondary objectives include assessing the effect of ulacamten on LVEF and NT-proBNP, its pharmacokinetics, and its pharmacokinetic/pharmacodynamic relationship.
Our novel cardiac myosin activator works by a mechanism that directly stimulates the activity of the cardiac myosin motor protein, without increasing the intracellular calcium concentration. It accelerates the rate-limiting step of the myosin enzymatic cycle and shifts it in favor of the force-producing state.
Omecamtiv mecarbil is a novel cardiac myosin activator that works by directly stimulating the activity of the cardiac myosin motor protein, without increasing the intracellular calcium concentration. This drug candidate accelerates the rate-limiting step of the myosin enzymatic cycle and shifts it in favor of the force-producing state.
In addition, following the initiation of the first Phase 3 clinical trial (or the Phase 3 portion of the first Phase 2b/3 clinical trial) in heart failure with preserved ejection fraction in humans for CK-586, RPI ICAV, at its sole discretion, has the right to purchase an additional revenue interest which if exercised would entitle it to an additional 3.5% of our annual worldwide net sales of CK-586 in consideration of a payment equal to 50.0% of our future research and development costs of a Phase 3 trial of CK-586 up to a maximum of $150 million. 13 Table of Contents Neuromuscular Program Our neuromuscular program is focused on the activation of the skeletal sarcomere, the basic unit of skeletal muscle contraction.
In addition, following the initiation of the first Phase 3 clinical trial (or the Phase 3 portion of the first Phase 2b/3 clinical trial) in heart failure with preserved ejection fraction in humans for ulacamten, RPI ICAV, at its sole discretion, has the right to purchase an additional revenue interest which if exercised would entitle it to an additional 3.5% of our annual worldwide net sales of drug products containing ulacamten in consideration of a payment equal to 50.0% of our future research and development costs of a Phase 3 trial of ulacamten up to a maximum of $150 million.
In engineered human HCM heart tissues, CK-586 demonstrated a shallow force-concentration response and improved lusitropy. Lending support for investigating this mechanism of action in HFpEF, a subset of patients with HFpEF resemble patients with non-obstructive hypertrophic cardiomyopathy (HCM) in that those patients have higher ejection fractions, thickened walls of their heart, elevated biomarkers, and symptoms of heart failure.
Lending support for investigating this mechanism of action in HFpEF, a subset of patients with HFpEF resemble patients with non-obstructive hypertrophic cardiomyopathy (HCM) in that those patients have higher ejection fractions, thickened walls of their heart, elevated biomarkers, and symptoms of heart failure.
Pursuant to the RP OM Loan Agreement, RDPF has a revenue interest entitling it to quarterly payments in an amount equal to 2.0% of the annual worldwide net sales of omecamtiv mecarbil, subject to a minimum floor amount ranging from $5.0 million to $8.0 million during the first 18 calendar quarters commencing on the calendar quarter during which FDA approval for omecamtiv mecarbil is obtained, as further described in Note 3 to our consolidated financial statements included in this Annual Report on Form 10-K under the section "RP OM Loan Agreement," on condition that a new Phase 3 clinical trial of omecamtiv mecarbil is successful by June 30, 2028 and we receive the marketing approval from the FDA for omecamtiv mecarbil on or prior to December 31, 2029. 12 Table of Contents CK-586 CK-586 is a novel, selective, oral, small molecule cardiac myosin inhibitor designed to reduce the hypercontractility associated with heart failure with preserved ejection fraction, or HFpEF.
Pursuant to the RP OM Loan Agreement, RDPF has a revenue interest entitling it to quarterly payments in an amount equal to 2.0% of the annual worldwide net sales of drug products containing omecamtiv mecarbil, subject to a minimum floor amount ranging from $5.0 million to $8.0 million during the first 18 calendar quarters commencing on the calendar quarter during which FDA approval for any drug product containing omecamtiv mecarbil is obtained, as further described in Note 3 to our consolidated financial statements included in this Annual Report on Form 10-K under the section "Agreements with Royalty Pharma," on the condition that a new Phase 3 clinical trial of omecamtiv mecarbil is successful by June 30, 2028 and we receive the marketing approval from the FDA for omecamtiv mecarbil on or prior to December 31, 2029.
We aim to achieve higher commercial returns from our specialty franchise business strategies as would be enabled by experienced sales representatives who bring established rapport with their potential customers and appropriately coupling their selling activities with high touch customer support services designed to benefit prescribers and patients alike.
We aim to achieve commercial returns from our targeted specialty franchise business by deploying experienced sales representatives with established rapport with their potential customers and by coupling their selling activities with high-touch customer support services designed to support prescribers and patients alike.
If omecamtiv mecarbil is approved, an extension of the U.S. patent term may be available for one patent covering the approved drug, which could extend the term of the applicable patent by up to a maximum of five additional years but not to exceed a total of 14 years from the date of product approval.
If omecamtiv mecarbil is approved, an extension of the U.S. patent term may be available for one patent covering the approved drug, which could extend the term of the applicable patent by up to a maximum of five additional years but not to exceed a total of 14 years from the date of product approval. 18 Table of Contents In Japan, omecamtiv mecarbil is protected by issued patents covering the salt form and formulation of omecamtiv mecarbil that expire in 2034.
Statistically significant and clinically meaningful improvements were also observed in all 10 prespecified secondary endpoints, with functional and symptomatic improvements occurring within two weeks of initiating treatment with aficamten and sustained throughout the treatment period.
Statistically significant and clinically meaningful improvements were also observed in all 10 prespecified secondary endpoints, with functional and symptomatic improvements occurring within two weeks of initiating treatment with aficamten and sustained throughout the treatment period. There were no instances of worsening heart failure and no treatment interruptions due to low LVEF.
This mechanism of action may be therapeutically effective in conditions characterized by excessive hypercontractility, such as HCM. The preclinical pharmacokinetics of aficamten were characterized evaluated and optimized for potential rapid onset, ease of titration and rapid symptom relief.
Aficamten reduces the number of active actin-myosin cross bridges during each cardiac cycle and consequently reduces myocardial contractility. This mechanism of action may be therapeutically effective in conditions characterized by excessive hypercontractility, such as HCM. The preclinical pharmacokinetics of aficamten were characterized, evaluated and optimized for potential rapid onset, ease of titration and rapid symptom relief.
HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed in the U.S. However, there are an estimated 400,000-800,000 additional patients who remain undiagnosed, a rate that is growing at the same rate as the population.
HCM is the most common monogenic inherited cardiovascular disorder, with well over 300,000 patients diagnosed in the U.S. However, there are an estimated 400,000-800,000 additional patients who remain undiagnosed.
We further believe that our pioneering research directed to the same biology and emerging pharmacology could result in an expansion of our business franchise with the development and potential approval of CK-586 for the potential treatment of a subset of patients with HFpEF whose hypercontractility resembles that of patients with nHCM, as well as the development and potential approval of omecamtiv mecarbil, a cardiac myosin activator, for the potential treatment of patients with symptomatic heart failure with severely reduced ejection fraction. 9 Table of Contents Our planned specialty cardiology franchise is focused on the advancing of potential medicines that can address high unmet needs of patients primarily treated by a concentrated segment of cardiologists.
We further believe that our pioneering research directed to the same biology and emerging pharmacology could result in an expansion of our business franchise with the development and potential approval of ulacamten for the treatment of a subset of patients with HFpEF whose hypercontractility resembles that of patients with nHCM, as well as the development and potential approval of omecamtiv mecarbil, a cardiac myosin activator, for the treatment of patients with symptomatic heart failure with severely reduced ejection fraction.
FDA granted aficamten orphan drug designation for the treatment of symptomatic HCM. 10 Table of Contents The development program for aficamten assessed its potential as a treatment that improves exercise capacity and relieves symptoms in patients with oHCM, as well as its potential long-term effects on cardiac structure and function.
The FDA granted aficamten orphan drug designation for the treatment of symptomatic HCM in 2021. The development program for aficamten has assessed its potential as a treatment to improve exercise capacity and relieve symptoms in patients with oHCM. In addition, development work is ongoing to assess aficamten for its potential long-term effects on cardiac structure and function.
We intend to leverage our experience in muscle contractility to expand our current pipeline and expect to identify additional potential drug candidates that may be suitable for clinical development and commercialize. Corporate Strategy As a leader in muscle biology and the mechanics of muscle performance, we are developing small molecule drug candidates specifically engineered to impact muscle function and contractility.
We intend to leverage our experience in muscle contractility to expand our current pipeline and expect to identify additional potential drug candidates that may be suitable for clinical development and commercialization. Corporate Strategy We are discovering, developing and commercializing small molecule drugs and drug candidates specifically engineered to modulate muscle function to improve patient healthspan.
In addition, a Phase 1 study of aficamten in healthy Japanese patients is being conducted. Collaboration for Commercialization of Aficamten in Greater China We are party to a license and collaboration agreement, pursuant to which we granted to Corxel an exclusive license to develop and commercialize aficamten in China and Taiwan.
Collaboration for Commercialization of Aficamten in Greater China We are party to a license and collaboration agreement, pursuant to which we granted to Corxel an exclusive license to develop and commercialize drug products containing aficamten in China and Taiwan.
Specialty Cardiology Programs Our specialty cardiology program is focused on the cardiac sarcomere, the basic unit of muscle contraction in the heart. The cardiac sarcomere is a highly ordered cytoskeletal structure composed of cardiac myosin, actin and a set of regulatory proteins. Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell.
We also conduct research and development on novel treatments for disorders involving muscle function beyond muscle contractility. Specialty Cardiology Programs Our specialty cardiology program is focused on the cardiac sarcomere, the basic unit of muscle contraction in the heart. The cardiac sarcomere is a highly ordered cytoskeletal structure composed of cardiac myosin, actin and a set of regulatory proteins.
Intellectual Property Resources Our policy is to seek patent protection for the technologies, inventions and improvements that we develop that we consider important to the advancement of our business.
Intellectual Property Resources Our policy is to seek patent protection for the technologies, inventions and improvements that we develop and consider important to the advancement of our business. We also rely on trade secrets, technical know-how and continuing innovation to develop and maintain our competitive position.
Collaboration for Commercialization of Aficamten in Japan On November 19, 2024, we announced that we had entered into a collaboration and license agreement with Bayer Consumer Care AG, an affiliate of Bayer AG, for the exclusive development and commercialization of aficamten in Japan, subject to certain reserved development rights of Cytokinetics to continue conducting ACACIA-HCM and CEDAR-HCM in Japan.
Collaboration for Commercialization of Aficamten in Japan We are party to a collaboration and license agreement with Bayer Consumer Care AG, an affiliate of Bayer AG, for the exclusive development and commercialization of drug products containing aficamten in Japan, subject to certain reserved development rights of Cytokinetics to conduct ACACIA-HCM and CEDAR-HCM in Japan.
For our portfolio of small molecules, we continue to expand our network through well-established and reputable third-party contract manufacturers for our CMC and manufacturing needs that have good regulatory standing and suitable manufacturing capabilities and capacities.
For our portfolio of small molecules, we continue to expand our network through third-party contract manufacturers for our CMC and manufacturing needs.
We believe there are hundreds of thousands of patients who may benefit from clinically meaningful outcomes, as measured by improvements in clinical, social and psychological aspects, including patients overall quality of life within their community of family, friends and caregivers.
We believe there are hundreds of thousands of patients who may benefit from clinically meaningful outcomes delivered by our science focused on the biology of muscle function, as measured by improvements in clinical, social and psychological aspects, including patients' overall quality of life.
Two-thirds of patients with HCM have oHCM, in which the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have nHCM, in which blood flow is not impacted, but the heart muscle is still thickened.
Estimates vary but we believe approximately half of patients with HCM have oHCM, in which the thickening of the cardiac muscle leads to LVOT obstruction, while the remaining HCM patients have nHCM, in which blood flow is not impacted, but the heart muscle is still thickened.
Royalty Pharma Revenue Interest In the second quarter of 2024, we entered into a Revenue Participation Right Purchase agreement, which we refer to as the RP CK-586 RPA, with RPI ICAV, pursuant to which RPI ICAV purchased rights to certain revenue streams from worldwide net sales of CK-586 by us, our affiliates or licensees.
AMBER-HFpEF is currently enrolling patients, and we expect to complete enrollment in cohort 2 of the study by the end of 2026. 13 Table of Contents Royalty Pharma Revenue Interest In the second quarter of 2024, we entered into a Revenue Participation Right Purchase agreement, which we refer to as the RP Ulacamten RPA, with RPI ICAV, pursuant to which RPI ICAV purchased rights to certain revenue streams from worldwide net sales of drug products containing ulacamten by us, our affiliates or licensees.
Beyond Muscle Contractility We developed preclinical expertise in the mechanics of skeletal, cardiac and smooth muscle that extends from proteins to tissues to intact animal models.
We conducted a Phase 1 evaluation, and we are in ongoing discussions with regulatory authorities to inform next steps. Beyond Muscle Contractility We developed preclinical expertise in the mechanics of skeletal, cardiac and smooth muscle that extends from proteins to tissues to intact animal models.
These pressures can arise from rules and practices of managed care groups, judicial decisions and governmental laws and regulations related to Medicare, Medicaid and healthcare reform, pharmaceutical reimbursement policies and pricing in general.
These developments will put additional pressure on product pricing, reimbursement and utilization, which may adversely affect our future product sales and results of operations. These pressures can arise from rules and practices of managed care groups, judicial decisions and governmental laws and regulations related to Medicare, Medicaid and healthcare reform, pharmaceutical reimbursement policies and pricing in general.
Furthermore, we are working to bring additional new chemical entities into clinical development through both continuing internal activities and by also externalizing innovation through partnerships, seeking complementary potential therapies to support our late-stage cardiovascular franchise and emerging neuromuscular pipeline. 8 Table of Contents IGNITION: Achieve broad access and rapid use of our medicines in 15 countries throughout North America and Europe Given our focus on disease areas for which there are serious unmet medical needs, we direct our activities to potential commercial opportunities in concentrated and tractable customer segments, such as to disease-specific centers of excellence and cohorts of focused healthcare professionals, which may be addressed by smaller, targeted sales forces.
IGNITION: Achieve broad access and rapid use of our medicines in 15 countries throughout North America and Europe Given our focus on disease areas for which there are serious unmet medical needs, we direct our activities to potential commercial opportunities in concentrated and tractable customer segments, such as to disease-specific centers of excellence and cohorts of focused healthcare professionals, that may be addressed by targeted sales forces.
Omecamtiv mecarbil We are developing omecamtiv mecarbil as a potential treatment across the continuum of care in heart failure both for use in the hospital setting and for use in the outpatient setting. 11 Table of Contents Omecamtiv mecarbil is a selective, small molecule cardiac myosin activator, the first of a novel class of myotropes designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole.
Omecamtiv mecarbil is a selective, small molecule cardiac myosin activator, the first of a novel class of myotropes designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole.
In addition to Camzyos®, Edgewise Therapeutics is conducting clinical trials and could compete with aficamten if successful. Other companies may also be conducting clinical trials and pre-clinical activities in HCM, and if successful, there may other treatments approved for HCM, some of which may be complementary to aficamten and others of which may be competitive.
Other companies may also be conducting clinical trials and pre-clinical activities in HCM, and if successful, there may be other treatments approved for HCM, some of which may be complementary to MYQORZO and others of which may be competitive. Camzyos® was approved by the FDA in 2022 with a comprehensive and mandatory REMS.
Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM; 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 obstructive HCM; and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM.
Aficamten continues to be evaluated in ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with nHCM; 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.
FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon us and any third-party manufacturers that we may decide to use. 18 Table of Contents In addition, we are subject to other state and federal laws, including, among others, anti-kickback laws, fraud and abuse, false claims laws, Sunshine Act, patient protection and affordable care, data privacy and security laws and regulations, and transparency laws that restrict certain business practices in the pharmaceutical industry.
In addition, we are subject to other state and federal laws, including, among others, anti-kickback laws, fraud and abuse, false claims laws, Sunshine Act, patient protection and affordable care, data privacy and security laws and regulations, and transparency laws that restrict certain business practices in the pharmaceutical industry.
In Japan, aficamten is protected by an issued patent covering the composition of matter of aficamten that expires in 2039. In China, aficamten is protected by issued patents covering the composition of matter, polymorphic forms, and formulations of aficamten that expire between 2039 and 2040.
An oral hearing is anticipated in this proceeding at a time to be determined by the EPO. In Japan, aficamten is protected by issued patents covering the composition of matter, polymorphic forms, and formulations of aficamten that expire between 2039 and 2040.
At the appropriate time, the company will pursue available patent term extensions in Japan and China that may, if issued, extend exclusivity beyond the baseline patent expiration dates. 17 Table of Contents Omecamtiv Mecarbil The following table describes certain issued U.S. and European patents that relate to omecamtiv mecarbil.
In China, omecamtiv mecarbil is protected by issued patents covering the salt form and formulation of omecamtiv mecarbil that expire in 2034. At the appropriate time, the Company will pursue available patent term extensions in Japan and China that may, if issued, extend exclusivity beyond the baseline patent expiration dates.
We anticipate that aficamten, the first product in our potential franchise will help serve unmet needs in the growing HCM market. If aficamten is approved and indicated for the treatment of patients with oHCM, it could be followed by a subsequent regulatory approval and indication for the treatment of patients with nHCM (assuming positive results from ACACIA-HCM).
We anticipate that MYQORZO, the first approved product in our business franchise, will help serve unmet needs in the growing oHCM market. In addition to the oHCM market, if results from ACACIA-HCM are positive and support filing for registration, aficamten may receive regulatory approval for the treatment of adult patients with symptomatic nHCM.
The skeletal sarcomere is a highly ordered cytoskeletal structure composed of skeletal muscle myosin, actin, and a set of regulatory proteins, which include the troponins and tropomyosin. This program leverages our expertise developed in our ongoing discovery and development of cardiac sarcomere activator.
Neuromuscular Program Our neuromuscular program is focused on the activation of the skeletal sarcomere, the basic unit of skeletal muscle contraction. The skeletal sarcomere is a highly ordered cytoskeletal structure composed of skeletal muscle myosin, actin, and a set of regulatory proteins, which include the troponins and tropomyosin.
Royalty Pharma Revenue Interest In 2017, we entered into a Royalty Purchase Agreement, which we refer to as the RP OM RPA, with Royalty Pharma Development Funding, LLC, or RPFT, and amended the RP OM RPA on January 7, 2022.
COMET-HF is expected to enroll approximately 1,800 patients randomized on a 1:1 basis to receive omecamtiv mecarbil or placebo for up to 48 weeks. 12 Table of Contents Royalty Pharma Revenue Interest In 2017, we entered into a Royalty Purchase Agreement, which we refer to as the RP OM RPA, with Royalty Pharma Development Funding, LLC, or RPFT, and amended the RP OM RPA on January 7, 2022.
As we prepare for the potential regulatory approval and commercial launch of our first medicine, we aspire to provide equitable access for all patients regardless of gender, ethnicity or zip code. As such, we are developing programs for patients and healthcare providers to facilitate the accessibility of our products to those in need.
In commercializing our first medicine, we aspire to provide equitable access for all patients regardless of gender, ethnicity or location and we are developing programs for patients and healthcare providers to facilitate access accordingly.
In addition, through our third-party contract manufacturers and data service providers, we continue to provide serialized commercial products as required to comply with the Drug Supply Chain Security Act.
In addition, through our third-party contract manufacturers and data service providers, we continue to provide serialized commercial products as required to comply with the Drug Supply Chain Security Act. We are mindful of the increasing risks of relying on sole source raw materials from countries where global trade disputes or restrictive legislation are possible.
The study design included seven single ascending dose cohorts (10 mg to 600 mg) comprised of 10 participants each, and two multiple-dose cohorts (100 and 200 mg once daily) comprised of 10 participants each. This study data demonstrated that CK-586 was safe and well tolerated in healthy participants.
The primary objective of this clinical study was to evaluate the safety, tolerability and PK of ulacamten when administered orally to healthy participants. The study design included seven single ascending dose cohorts (10 mg to 600 mg) comprised of 10 participants each, and two multiple-dose cohorts (100 and 200 mg once daily) comprised of 10 participants each.
We believe that our ability to successfully compete will depend on, among other things: • efficacy, safety and reliability of aficamten, both alone and in combination with other therapies; • the timing and scope of regulatory approvals in the United States and other countries, if any; • the imposition by FDA or other regulatory authorities of a REMS program that is differentiated and less burdensome to healthcare providers, pharmacists and patients than the REMS program to which Camzyos® is subject; • our ability to manufacture and sell commercial quantities of aficamten product to the market; • our ability to gain market access and secure coverage and adequate reimbursement in approved indications; • product acceptance by physicians and other health care providers; • protection of our intellectual property, including our ability to enforce our intellectual property rights against potential generic competition; and • the availability of substantial capital resources to fund development and commercialization activities.
We believe that our ability to successfully compete will depend on, among other things: • the efficacy and safety of MYQORZO, both alone and in combination with other therapies; • the timing and scope of regulatory approvals in Europe, Japan and other countries in oHCM and potentially other indications, if at all; • our ability to manufacture quantities of MYQORZO to meet its market demand; • our ability to gain market access and secure coverage and adequate reimbursement in oHCM and potentially other indications, if any; • acceptance of MYQORZO by physicians and other health care providers; 15 Table of Contents • protection of our intellectual property, through enforcement of our intellectual property rights against any challengers, including potential generic competition and the absence of any blocking intellectual property rights that limit our ability to market MYQORZO as we have planned; and • the availability of substantial capital resources to fund development and commercialization activities.
We have discovered and are developing muscle-directed investigational medicines that may potentially improve the healthspan of people with devastating cardiovascular and neuromuscular diseases of impaired muscle function.
We have discovered and are developing muscle-directed investigational medicines that may potentially improve the healthspan of people with devastating cardiovascular and neuromuscular diseases of impaired muscle function. Our first commercial product is MYQORZO™ (aficamten), 5 mg, 10 mg, 15 mg, and 20 mg tablets, which the FDA approved in December 2025.
We keep patients at the heart of every phase of development — research, clinical development, commercial readiness and more. By prioritizing systematic patient engagement throughout the organization, we foster a culture of empathy and collaboration, ensuring that the voice of the patient remains central to our decision-making process.
INSPIRATION: Foster a patient-centric culture with an emphasis on equitable access We consider patients as we advance research, clinical development and commercialization. By prioritizing systematic patient engagement, we foster a culture of empathy and collaboration, ensuring that the voice of the patient remains central to our decision-making process.
In 2025, we articulated our five-year strategic plan, Vision 2030: “Empowering Muscle, Empowering Lives,” designed to enable Cytokinetics to become a leading muscle biology specialty biopharmaceutical company intent on meaningfully improving the lives of patients through global access to our innovative medicines.
In 2025, we articulated our five-year strategic plan, Vision 2030: “Empowering Muscle, Empowering Lives,” designed to enable Cytokinetics to become a leading muscle biology specialty biopharmaceutical company intent on meaningfully improving the lives of patients through global access to our innovative medicines. 7 Table of Contents The key components of our five-year corporate strategy are: INNOVATION: Advance 2 product approvals across 3 indications and 10 novel molecular entities into our pipeline Our myosin platform is the cornerstone of our innovation and the anchor of our portfolio of medicines and potential medicines is MYQORZO.
Competition There are many companies focused on the development of small molecules for the treatment HCM, HFrEF, HFpEF and other diseases that our drug candidates are intended to treat. Our competitors and potential competitors include major pharmaceutical and biotechnology companies, as well as academic research institutions, clinical reference laboratories and government agencies that are pursuing research activities similar to ours.
Our competitors and potential competitors include major pharmaceutical and biotechnology companies, as well as academic research institutions, clinical reference laboratories and government agencies that are pursuing research activities similar to ours.
It is directly responsible for converting chemical energy into the mechanical force, resulting in cardiac muscle contraction. Our most advanced cardiac program is based on the hypothesis that inhibitors of cardiac myosin may attenuate the hyperdynamic contraction resulting from pathologic mutations in the sarcomere that lead to hypertrophic cardiomyopathies.
Our most advanced cardiac program, MYQORZO (aficamten), is based on the hypothesis that inhibitors of cardiac myosin may attenuate the hyperdynamic contraction resulting from pathologic mutations in the sarcomere that lead to hypertrophic cardiomyopathies. MYQORZO was approved in the U.S., Europe and China for the treatment of adults with symptomatic oHCM.
As a result, coverage and adequate third-party reimbursement may not be available for our product candidates to enable us to realize an appropriate return on our investment in research and product development. 19 Table of Contents The market for our products and product candidates for which we may receive regulatory approval will depend significantly on access to third-party payors’ drug formularies, or lists of medications for which third-party payors provide coverage and reimbursement.
As a result, coverage and adequate third-party reimbursement may not be available for our product candidates to enable us to realize an appropriate return on our investment in research and product development.
These programs may include support to help understand and navigate insurance coverage and obtain financial assistance for eligible patients; comprehensive patient and office education and resources to help navigate the patient’s treatment journey; support to manage logistical challenges that prevent patients from starting and staying on therapy and behavioral and wellness tools and resources to support patient engagement and help manage adherence to treatment.
These programs may include support to help understand and navigate insurance coverage and obtain financial assistance for eligible patients; comprehensive patient and office education and resources to help navigate the patient’s treatment journey, support to manage logistical challenges that prevent patients from starting and staying on therapy and behavioral and wellness tools and resources to support patient engagement and help manage adherence to treatment. 8 Table of Contents INGENUITY: Extend leadership in muscle deploying multiple therapeutic modalities After expanding our discovery platform to include muscle mechanics, muscle metabolism, and muscle health and regeneration, we are seeking to expand our research modalities to better enable our programs to address more difficult-to-drug molecular targets.
Manufacturing Resources and Product Supply Our drug candidates require precise high-quality manufacturing that is compliant with good manufacturing processes (or foreign equivalent) and other applicable laws.
We are leveraging our current understandings of muscle biology to investigate new ways of modulating these other aspects of muscle function for other potential therapeutic applications. Manufacturing Resources and Product Supply Our drug candidates require precise high-quality manufacturing that is compliant with good manufacturing processes (or foreign equivalent) and other applicable laws.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeOur failure to comply with any of the covenants could result in a default under the RP Multi Tranche Loan Agreement, the RP OM Loan Agreement, the RP CK-586 RPA, the RP Aficamten RPA, the RP OM RPA, or the indentures related to the Convertible Notes, which could permit the counterparties to declare all or part of any outstanding borrowings or other payment obligations to be immediately due and payable and/or enforce any outstanding liens against our assets. 28 Table of Contents We have no rights to repurchase the revenue interests in aficamten, omecamtiv mecarbill, or CK-586 (other than, in respect of CK-586 only, in connection with a change of control of Cytokinetics) sold to affiliates of Royalty Pharma, thereby limiting our ability to eliminate future applicability of the covenants contained in the RP CK-586 RPA, the RP OM RPA and the RP Aficamten RPA, and although we have voluntary prepayment rights under the RP Multi Tranche Loan Agreement and the RP OM Loan Agreement, any voluntary prepayment rights under the RP Multi Tranche Loan Agreement require that we pay 190% of the principal amount of amounts disbursed to us as tranche 1, tranche 4, tranche 5, tranche 6, and tranche 7 loans and 200% for tranche 2 and tranche 3 loans, thereby making it potentially disadvantageous to voluntarily prepay RPDF prior to the final maturity date applicable to loans outstanding under the RP Multi Tranche Loan Agreement.
Biggest changeWe have no rights to repurchase the revenue interests in drug products containing aficamten, omecamtiv mecarbil, or ulacamten (other than, in respect of ulacamten only, in connection with a change of control of Cytokinetics) sold to affiliates of Royalty Pharma, thereby limiting our ability to eliminate future applicability of the covenants contained in the RP Ulacamten RPA, the RP OM RPA and the RP Aficamten RPA, and although we have voluntary prepayment rights under the RP Multi Tranche Loan Agreement and the RP OM Loan Agreement, any voluntary prepayment rights under the RP Multi Tranche Loan Agreement require that we pay 190% of the principal amount of amounts disbursed to us as tranche 1, tranche 4, tranche 5, tranche 6, and tranche 7 loans, thereby making it potentially disadvantageous to voluntarily prepay RPDF prior to the final maturity date applicable to loans outstanding under the RP Multi Tranche Loan Agreement.
The Convertible Notes may be converted into cash and shares of our common stock (subject to our right or obligation to pay cash in lieu of all or a portion of such shares).
The Convertible Notes may be converted into cash and/or shares of our common stock (subject to our right or obligation to pay cash in lieu of all or a portion of such shares).
The continuing efforts of governments, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare, including by imposing price controls, may adversely affect the demand and/or potential sales for our product candidates for which we obtain regulatory approval and our ability to set a price that we believe is fair for our products.
The continuing efforts of governments, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare, including by imposing price controls, may adversely affect the demand and/or potential sales for MYQORZO and our product candidates for which we obtain regulatory approval and our ability to set a price that we believe is fair for our products.
Factors that have caused and could cause in the future volatility in the market price of our common stock include, but are not limited to: announcements concerning any of the clinical trials for our drug candidates (including, but not limited to, the timing of initiation or completion of such trials and the results of such trials, and delays or discontinuations of such trials, including delays resulting from slower than expected or suspended patient enrollment or discontinuations resulting from a failure to meet pre-defined clinical end points); the commencement, settlement or adverse conclusion of litigation or a governmental investigation; failure or discontinuation of any of our research programs; issuance of new or changed securities analysts’ reports or recommendations; market conditions in the pharmaceutical, biotechnology and other healthcare-related sectors; actual or anticipated fluctuations in our quarterly financial and operating results; substantial sales of our common stock by our existing stockholders, whether or not related to our performance; and other factors described in this “Risk Factors” section.
Factors that have caused and could cause in the future volatility in the market price of our common stock include, but are not limited to: announcements concerning MYQORZO; any of the clinical trials for our drug candidates (including, but not limited to, the timing of initiation or completion of such trials and the results of such trials, and delays or discontinuations of such trials, including delays resulting from slower than expected or suspended patient enrollment or discontinuations resulting from a failure to meet pre-defined clinical end points); the commencement, settlement or adverse conclusion of litigation or a governmental investigation; failure or discontinuation of any of our research programs; issuance of new or changed securities analysts’ reports or recommendations; market conditions in the pharmaceutical, biotechnology and other healthcare-related sectors; actual or anticipated fluctuations in our financial and operating results; substantial sales of our common stock by our existing stockholders, whether or not related to our performance; and other factors described in this “Risk Factors” section.
Many of our employees were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although no legal proceedings against us are currently pending, we may be subject to claims that these employees or we have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers.
Additionally, many of our employees were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although no legal proceedings against us are currently pending, we may be subject to claims that these employees or we have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers.
The subsequent discovery of previously unknown problems with the drug, including adverse events of unanticipated severity or frequency, or the discovery that adverse events or toxicities observed in preclinical research or clinical trials that were believed to be minor constitute much more serious problems, may result in restrictions on the marketing of the drug or withdrawal of the drug from the market.
The subsequent discovery of previously unknown problems with a drug, including adverse events of unanticipated severity or frequency, or the discovery that adverse events or toxicities observed in preclinical research or clinical trials that were believed to be minor constitute much more serious problems, may result in restrictions on the marketing of the drug or withdrawal of the drug from the market.
If we are unable to obtain and maintain sufficient intellectual property protection for our technologies and drug candidates, or if the scope of the intellectual property protection obtained is not sufficiently broad, our competitors could develop and commercialize drug candidates similar or identical to ours, and our ability to successfully commercialize product candidates that we may pursue may be impaired.
If we are unable to obtain and maintain sufficient intellectual property protection for our technologies and drugs or drug candidates, or if the scope of the intellectual property protection obtained is not sufficiently broad, our competitors could develop and commercialize drugs similar or identical to ours, and our ability to successfully commercialize product candidates that we may pursue may be impaired.
If the market opportunities for any product candidates we develop are smaller than we believe they are, or if any approval that we obtain is based on a narrower definition of the patient population, our potential revenues may be adversely affected, and our business may suffer.
If the market opportunities for any products or product candidates we develop are smaller than we believe they are, or if any approval that we obtain is based on a narrower definition of the patient population, our potential revenues may be adversely affected, and our business may suffer.
In addition, under our license and collaboration agreements, we have committed to providing Sanofi and Bayer with supply of aficamten for development and commercialization of aficamten in China, Taiwan and Japan, which we will have to source from our contract manufacturers.
In addition, under our license and collaboration agreements, we have committed to providing Sanofi and Bayer with supply of aficamten for development and commercialization of MYQORZO in China, Taiwan and Japan, which we will have to source from our contract manufacturers.
It is difficult to predict at this time what third-party will decide with respect to coverage and reimbursement for our products. Coverage policies and third party reimbursement rates may change at any time.
It is difficult to predict at this time what third parties will decide with respect to coverage and reimbursement for our products. Coverage policies and third-party reimbursement rates may change at any time.
Given the amount of time required for the development, testing and regulatory review of new drug candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.
Given the amount of time required for the development, testing and regulatory review of new drugs and drug candidates, patents protecting such candidates might expire before or shortly after such drugs or drug candidates are commercialized.
Clinical trials may fail to demonstrate the desired safety and efficacy of our drug candidates, which could prevent or significantly delay completion of clinical development and regulatory approval.
Clinical trials could fail to demonstrate the desired safety and efficacy of our drug candidates, which could prevent or significantly delay completion of clinical development and regulatory approval.
Our ability to protect our drug candidates, compounds and technologies from unauthorized or infringing use by third parties depends substantially on our ability to obtain and enforce our patents.
Our ability to protect our drugs and drug candidates, and compounds and technologies from unauthorized or infringing use by third parties depends substantially on our ability to obtain and enforce our patents.
The RP Multi Tranche Loan Agreement, the RP OM Loan Agreement, the RP CK-586 RPA, the RP Aficamten RPA, the RP OM RPA, and the indentures related to the Convertible Notes require that we comply with certain covenants, including among other things, covenants restricting dispositions, changes in business, management, ownership or business locations, mergers or acquisitions, indebtedness, encumbrances, distributions, investments, transactions with affiliates and subordinated debt, any of which could restrict our business and operations, particularly our ability to respond to changes in our business or to take specified actions to take advantage of certain business opportunities that may be presented to us.
The RP Multi Tranche Loan Agreement, the RP OM Loan Agreement, the RP Ulacamten RPA, the RP Aficamten RPA, the RP OM RPA, and the indentures related to the Convertible Notes require that we comply with certain covenants, including among other things, covenants restricting dispositions, changes in business, management, ownership or business locations, mergers or acquisitions, indebtedness, encumbrances, distributions, investments, transactions with affiliates and subordinated debt, any of which could restrict our business and operations, particularly our ability to respond to changes in our business or to take specified actions to take advantage of certain business opportunities that may be presented to us.
Filing, prosecuting and defending patents on our product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States. Many companies have encountered significant difficulties in protecting and defending intellectual property rights in foreign jurisdictions.
Filing, prosecuting and defending patents on our products or product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States. Many companies have encountered significant difficulties in protecting and defending intellectual property rights in foreign jurisdictions.
We have contracted with Microgenics Corporation, a subsidiary of Thermo Fisher, to develop and eventually commercialize an antibody-based immunoassay for blood concentrations of omecamtiv mecarbil. The development, manufacture and regulatory approval of an antibody-based immunoassay, however, may be complex and/or time consuming.
We have contracted with Microgenics Corporation, a subsidiary of Thermo Fisher, to develop and eventually commercialize an antibody-based immunoassay for blood concentrations of omecamtiv mecarbil. The development, manufacture and regulatory approval of an antibody-based immunoassay, however, can be complex and/or time consuming.
We do not control the individual efforts of outlicense partners, and any failure by our partners to devote sufficient time and effort to the development and commercialization of aficamten or to meet their respective obligations to us, including for future milestone and royalty payments; or to satisfactorily resolve significant disagreements with us could each have an adverse impact on our financial results and operations.
We do not control the individual efforts of out-license partners, and any failure by our partners to devote sufficient time and effort to the development and commercialization of aficamten or to meet their respective obligations to us, including for future milestone and royalty payments; or to satisfactorily resolve significant disagreements with us could each have an adverse impact on our financial results and operations.
In addition, before a drug from any replacement manufacturer or manufacturing site can be commercialized, the FDA and, in some cases, foreign regulatory agencies, must approve that site. These approvals would require regulatory testing and compliance inspections.
In addition, before a drug from any replacement CMO or manufacturing site can be commercialized, the FDA and, in some cases, foreign regulatory agencies, must approve that site. These approvals would require regulatory testing and compliance inspections.
The timing and amount of any milestone and royalty payments we may receive under our license and collaboration agreements from Sanofi and Bayer will depend in part on the efforts and successful commercialization of aficamten by our outlicense partners.
The timing and amount of any milestone and royalty payments we may receive under our license and collaboration agreements from Sanofi and Bayer will depend in part on the efforts and successful commercialization of aficamten by our out-license partners.
In connection with the anticipation of filing of a new NDA and MAA for omecamtiv mecarbil at the conclusion of the COMET-HF trial, FDA and/or EMA may require that patients treated with omecamtiv mecarbil have their blood monitored during titration for concentrations of the drug in order to ensure optimized dosing that maximizes benefits without undue risk.
In connection with the anticipation of filing of a new NDA and MAA for omecamtiv mecarbil at the conclusion of COMET-HF, FDA and/or EMA may require that patients treated with omecamtiv mecarbil have their blood monitored during titration for concentrations of the drug in order to determine optimized dosing that maximizes benefits without undue risk.
We will also compete for market share against large pharmaceutical and biotechnology companies and smaller companies that are collaborating with larger pharmaceutical companies, new companies, academic institutions, government agencies and other public and private research organizations. Many of these competitors, either alone or together with their partners, may develop new drug candidates that will compete with ours.
We also compete for market share against large pharmaceutical and biotechnology companies and smaller companies that are collaborating with larger pharmaceutical companies, new companies, academic institutions, government agencies and other public and private research organizations. Many of these competitors, either alone or together with their partners, develop new drug candidates that can compete with ours.
ITEM 1A. R ISK FACTORS In evaluating our business, you should carefully consider the following risks in addition to the other information in this report. Any of the following risks could materially and adversely affect our business, results of operations, financial condition or your investment in our securities, and many are beyond our control.
ITEM 1A. R ISK FACTORS In evaluating our business, you should carefully consider the following risks in addition to the other information in this report. Any of the following risks could materially and adversely affect our business, results of operations, financial condition, cash flows, reputation or your investment in our securities, and many are beyond our control.
For example, the CRL we received on February 28, 2023 in connection to our NDA for omecamtiv mecarbil stated the results of GALACTIC-HF were not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death in adults with chronic heart failure with HFrEF, and on March 31, 2023, we announced the discontinuation of COURAGE-ALS, our Phase 3 clinical trial of reldesemtiv in patients with ALS, due to futility.
For example, the CRL we received in February 2023 in connection with our NDA for omecamtiv mecarbil stated that the results of GALACTIC-HF were not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death in adults with chronic heart failure with HFrEF, and in March 2023, we announced the discontinuation of COURAGE-ALS, our Phase 3 clinical trial of reldesemtiv in patients with ALS, due to futility.
Covenants in the RP Multi Tranche Loan Agreement, the RP OM Loan Agreement, the RP CK-586 RPA, the RP Aficamten RPA, the RP OM RPA, and the indentures related to our Convertible Notes restrict our business and operations in many ways and if we do not effectively manage our covenants, our financial conditions and results of operations could be adversely affected.
Covenants in the RP Multi Tranche Loan Agreement, the RP OM Loan Agreement, the RP Ulacamten RPA, the RP Aficamten RPA, the RP OM RPA, and the indentures related to our Convertible Notes restrict our business and operations in many ways and if we do not effectively manage our covenants, our financial conditions and results of operations could be adversely affected.
A new manufacturer or manufacturing site also would have to be educated in, or develop substantially equivalent processes for, production of our drugs and drug candidates.
A new CMO or manufacturing site also would have to be educated in, or develop substantially equivalent processes for, production of our drugs and drug candidates.
Our indebtedness and liabilities could limit the cash flow available for our operations, expose us to risks that could adversely affect our business, financial condition and results of operations and impair our ability to satisfy our obligations under the 2026 Notes, the 2027 Notes, the RP Multi Tranche Loan Agreement and the RP OM Loan Agreement.
Our indebtedness and liabilities could limit the cash flow available for our operations, expose us to risks that could adversely affect our business, financial condition and results of operations and impair our ability to satisfy our obligations under the Convertible Notes, the RP Multi Tranche Loan Agreement and the RP OM Loan Agreement.
The commercial success of our products depends on the availability and sufficiency of third‑party payor coverage and reimbursement. Patients in the United States and elsewhere generally rely on third‑party payors to reimburse part or all of the costs associated with their prescription drugs.
The commercial success of our products depends on the availability and sufficiency of third‑party payor and/or government for coverage and reimbursement. Patients in the United States and elsewhere generally rely on third‑party payors and/or governments to reimburse part or all of the costs associated with their prescription drugs.
Our estimated potential market opportunity for cardiac myosin inhibitors in HCM is based on the following assumptions: our understanding of the prevalence of HCM in the general population from published epidemiological studies and analysis of longitudinal claims data, the percentage split of diagnosed obstructive HCM and non-obstructive HCM patients derived from market research and patient transaction databases, the percentage of available symptomatic patients not adequately managed by the current standard of care among diagnosed HCM patients, rates of patient compliance and persistence, based on patient transaction database and/or third-party market research.
Our estimated potential market opportunity for cardiac myosin inhibitors in oHCM and nHCM is based on the following assumptions: our understanding of the prevalence of HCM in the general population from published epidemiological studies and analysis of longitudinal claims data, the percentage split of diagnosed oHCM and nHCM patients derived from publications, market research and patient transaction databases, the percentage of available symptomatic patients not adequately managed by the current standard of care among diagnosed HCM patients, rates of patient compliance and persistence, based on patient transaction database and/or third-party market research.
If our issued patents and patent applications, if granted, do not adequately describe, enable or otherwise provide coverage of our technologies and drug candidates, we, our licensors or our licensees would not be able to exclude others from developing or commercializing these drug candidates.
If our issued patents and patent applications, if granted, do not adequately describe, enable or otherwise provide coverage for our technologies and drugs and drug candidates, we, our licensors or our licensees would not be able to exclude others from developing or commercializing these drugs or drug candidates.
If any of our existing or future contract manufacturers fail to, or are unable to perform satisfactorily or if any of the raw materials or drug products are subject to restrictive import/export controls, it could delay development or regulatory approval of our drug candidates or commercialization of our drugs, producing additional losses and depriving us of potential product revenues, and also lead to our breach of one of our license and collaboration agreements, giving rise to the ability to terminate such agreements and other adverse consequences as stipulated in such agreements.
If our existing or future CMOs fail to, or are unable to perform satisfactorily or if any of the raw materials, drug substance, or drug products are subject to restrictive import/export controls or tariffs, it could impede commercialization or delay development or regulatory approval of our drug candidates or commercialization of our drugs, producing additional losses and depriving us of potential product revenues, and also lead to our breach of one of our license and collaboration agreements, giving rise to the ability to terminate such agreements and other adverse consequences as stipulated in such agreements.
Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations.
Activities to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that government authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations.
In addition, the RP CK-586 RPA, the RP Aficamten RPA and the RP OM RPA contain certain covenants applicable to us, including among other things, development and commercialization diligence obligations in connection to aficamten, omecamtiv mecarbil and CK-586 and reporting obligations, which could also restrict our business and operations, particularly in connection to our development and commercialization of aficamten, omecamtiv mecarbil and CK-586.
In addition, the RP Ulacamten RPA, the RP Aficamten RPA and the RP OM RPA contain certain covenants applicable to us, including among other things, development and commercialization diligence obligations in connection to MYQORZO, omecamtiv mecarbil and ulacamten and reporting obligations, which could also restrict our business and operations, particularly in connection to our development and commercialization of MYQORZO, omecamtiv mecarbil and ulacamten.
To achieve this adoption, our drugs will need to be widely reimbursed and listed in formularies of major pharmacy benefit managers and payors in the U.S. These major pharmacy benefit managers and payors include Medicare, Medicaid, VA, DoD, TriCare, and commercial payors.
To achieve this adoption, our drugs will need to be widely reimbursed via medical exception or listed in formularies of major pharmacy benefit managers and payors in the U.S. These major pharmacy benefit managers and payors include Medicare, Medicaid, VA, DoD, TriCare, and commercial payors.
We seek to ensure that we and our contract manufacturers comply fully with all applicable regulations, laws and standards. However, we do not have control over our contract manufacturers’ compliance with these regulations, laws and standards.
We seek, and require our contract manufacturers, to comply fully with all applicable regulations, laws and standards. However, we do not have control over our contract manufacturers’ compliance with these regulations, laws and standards.
We may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products.
We may need to conduct expensive pharmacoeconomic studies to demonstrate the cost-effectiveness of our products.
Although we rely, and will continue to rely, on these third parties to conduct our clinical trials, we remain responsible for ensuring that each of our studies and clinical trials is conducted in accordance with the applicable protocol, legal, regulatory and scientific standards and our reliance on third parties does not relieve us of our regulatory responsibilities.
Although we rely, and will continue to rely, on these third parties to conduct our clinical trials, we remain responsible for our studies and clinical trials being conducted in accordance with the applicable protocol, legal, regulatory and scientific standards and our reliance on third parties does not relieve us of our regulatory responsibilities.
These provisions may also prevent changes in our management or limit the price that investors are willing to pay for our stock. 33 Table of Contents ITEM 1B. UNRESOLV ED STAFF COMMENTS None.
These provisions may also prevent changes in our management or limit the price that investors are willing to pay for our stock. ITEM 1B. UNRESOLV ED STAFF COMMENTS None.
If we are unable to obtain and maintain sufficient third‑party coverage and adequate reimbursement for our products, the commercial success of our drug products may be greatly hindered and our financial condition and results of operations may be materially and adversely affected.
If we are unable to obtain and maintain sufficient third‑party coverage and adequate reimbursement for our products, the commercial success of MYQORZO, as well as any future marketed drug products may be greatly hindered and our financial condition and results of operations may be materially and adversely affected.
The number of patients with HCM, HFpEF or HFrEF in the United States and other major markets and elsewhere may turn out to be materially lower than expected, patients may not be otherwise amenable to treatment with our product candidates or new patients may become increasingly difficult to identify or gain access to, all of which would harm our results of operations and our business.
The number of patients within the United States and other major markets and elsewhere may turn out to be materially lower than expected, patients may not be otherwise amenable to treatment with our drugs or new patients may become increasingly difficult to identify or gain access to, all of which would harm our results of operations and our business.
We may not be able to successfully repeat or increase the manufacturing capacity for any of our drug candidates, whether in collaboration with third-party manufacturers or on our own, in a timely or cost-effective manner or at all. Significant changes or scale-up of manufacturing may require additional validation studies, which are costly and which regulatory authorities must review and approve.
We may not be able to successfully repeat or increase the manufacturing capacity for any of our drugs or drug candidates, in a timely or cost-effective manner or at all. Significant changes or scale-up of manufacturing may require additional validation studies, which are costly and which regulatory authorities must review and approve.
In addition, quality issues may arise during those changes or scale-up activities because of the inherent properties of a drug candidate itself or of a drug candidate in combination with other components added during the manufacturing and packaging process, or during shipping and storage of the finished product or active pharmaceutical ingredients. 24 Table of Contents Our drug candidates require precise high-quality manufacturing.
In addition, quality issues may arise during those changes or scale-up activities because of the inherent properties of a drug or drug candidate itself or of a drug or drug candidate in combination with other components added during the manufacturing and packaging process, or during shipping and storage of the finished product or active pharmaceutical ingredients.
Any regulatory approvals that we or our partners receive for our drug candidates may be subject to limitations on the indicated uses for which the drug may be marketed or require potentially costly post-marketing follow-up studies or compliance with a REMS program that includes FDA's elements of safe use.
Any regulatory approvals that we or our partners receive for our drugs or drug candidates are subject to limitations on the indicated uses for which the drug may be marketed or require potentially costly post-marketing follow-up studies or compliance with a REMS program that includes ETASU.
In order to conduct large scale clinical trials for a drug candidate and for commercialization of the resulting drug if that drug candidate is approved for sale, we will need to manufacture some drug candidates in larger quantities and validate the repeatability of those manufacturing processes.
In order to conduct large scale clinical trials for a drug candidate and for commercialization of the resulting drug if that drug candidate is approved for sale, such as for MYQORZO, we need to manufacture drugs in larger quantities and validate the repeatability of those manufacturing processes.
Our indebtedness could have significant negative consequences for our security holders and our business, results of operations and financial condition by, among other things: increasing our vulnerability to adverse economic and industry conditions; limiting our ability to obtain additional financing; requiring the dedication of a substantial portion of our cash flow from operations to service our indebtedness, which will reduce the amount of cash available for other purposes; limiting our flexibility to plan for, or react to, changes in our business; diluting the interests of our existing stockholders as a result of issuing shares of our common stock upon conversion of the Convertible Notes; and placing us at a possible competitive disadvantage with competitors that are less leveraged than us or have better access to capital.
Our indebtedness could have significant negative consequences for our security holders and our business, results of operations and financial condition by, among other things: increasing our vulnerability to adverse economic and industry conditions; limiting our ability to obtain additional financing; requiring the dedication of a substantial portion of our cash flow from operations to service our indebtedness, which will reduce the amount of cash available for other purposes; limiting our flexibility to plan for, or react to, changes in our business; diluting the interests of our existing stockholders as a result of issuing shares of our common stock upon conversion of the Convertible Notes; and placing us at a possible competitive disadvantage with competitors that are less leveraged than us or have better access to capital. 34 Table of Contents Our business may not generate sufficient funds, and we may otherwise be unable to maintain sufficient cash reserves, to pay amounts due under our indebtedness and our cash needs may increase in the future.
Even if we obtain coverage for a given drug product, the timeframe from approval to coverage could be lengthy, inadequate, and/or the associated reimbursement rate may not be adequate to cover our costs, including research, development, intellectual property, manufacture, sale and distribution expenses, or may require co‑payments that patients find unacceptably high.
Even if we obtain coverage for a given drug product, the timeframe from approval to coverage could be lengthy, inadequate, and/or the associated reimbursement rate may not be adequate to cover our costs, including research, development, intellectual property, manufacture, sale and distribution expenses, or may require co‑payments that patients find unacceptably high. 26 Table of Contents We historically have had limited interactions and relationships with payors.
Policing unauthorized use of our intellectual property is difficult, and we may not be able to prevent misappropriation of our proprietary rights, particularly in countries where the laws may not protect such rights as fully as in the United States. In addition, third parties may affirmatively challenge the scope or validity of our patent rights.
Policing unauthorized use of our intellectual property is difficult, and we may not be able to prevent misappropriation of our proprietary rights, particularly in countries where the laws may not protect such rights as fully as in the United States.
Legal and Compliance Risks Recently enacted laws, including the Inflation Reduction Act, or IRA, and potential future legislation may increase the difficulty and cost for us to obtain regulatory approval of, and to commercialize our products and to obtain Medicare coverage by 3rd party plans and affect the prices we may obtain upon commercialization.
Legal and Compliance Risks Legislation, such as the Inflation Reduction Act, or IRA, and the One Big Beautiful Bill Act, or OBBA, and potential future legislation may increase the difficulty and cost for us to obtain regulatory approval of, and to commercialize our products and to obtain Medicare coverage by 3rd party plans and affect the prices we may obtain upon commercialization.
Our potential market opportunity is based on a number of internal and third-party estimates and resources, including, without limitation, our estimates and research, as well as industry and general publications and research, surveys and studies conducted by third parties, which may be incorrect.
Our potential market opportunity for oHCM, nHCM, and other indications is based on internal and third-party estimates and resources, including, without limitation, our estimates and research, as well as industry and general publications and research, surveys and studies conducted by Cytokinetics and third parties, which may be incorrect.
If one of our contract manufacturers fails to pass its pre-approval inspection or maintain ongoing compliance at any time, the production of our drug candidates could be interrupted, resulting in delays or discontinuance of our clinical trials, additional costs and potentially lost revenues from delays or refusals of regulatory approvals for our drug candidates.
If one of our contract manufacturers fails to pass its pre-approval inspection or maintain ongoing compliance at any time, the production of our drugs or drug candidates could be interrupted, negatively impacting commercialization efforts for our approved drug products or resulting in delays or discontinuance of our clinical trials or refusal of regulatory approval for our drug candidates, leading to additional costs and potentially lost revenues.
In addition, if required by FDA and/or EMA as part of any approved label for omecamtiv mecarbil, we will be dependent on Microgenics Corporation to successfully manufacture and commercialize its immunoassay in sufficient quantities in all key markets in which we may seek to commercialize omecamtiv mecarbil, failing which, our potential sales of omecamtiv mecarbil could be materially adversely affected.
In addition, if required by FDA and/or EMA as part of any approved label for omecamtiv mecarbil, we will be dependent on Microgenics Corporation to successfully manufacture and commercialize its immunoassay in sufficient quantities in all key markets in which we may seek to commercialize omecamtiv mecarbil, failing which, our potential sales of omecamtiv mecarbil could be materially adversely affected. 31 Table of Contents We depend on CROs to conduct our clinical trials and we have limited control over their performance.
As an example of the NDA for omecamtiv mecarbil illustrates, while we have submitted an NDA to FDA and an MAA to EMA for aficamten, such marketing applications may not lead to any regulatory approvals, or may result in requirements to conduct additional clinical trials prior to any potential approvals, which would increase our development costs and delay or preclude any revenue from commercial sales of aficamten and/or our other drug candidates.
As our previously filed NDA for omecamtiv mecarbil illustrates, while we may submit marketing authorization applications for our drug candidates in the future, such applications may not lead to any regulatory approvals, or may result in requirements to conduct additional clinical trials prior to any potential approvals, which would increase our development costs and delay or preclude any revenue from commercial sales of our drug candidates.
If any of the physicians or other providers or entities with whom we expect to do business are found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.
If any of the physicians or other providers or entities with whom we expect to do business are found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs. 37 Table of Contents We may be subject to costly product liability or other liability claims and may not be able to obtain adequate insurance.
We have no manufacturing capabilities and depend on contract manufacturers to produce our clinical trial materials, including our drug candidates, and will have continued reliance on contract manufacturers for the development and commercialization of our potential drugs.
We have no manufacturing capabilities and depend on single source contract manufacturers to produce our commercial product and clinical trial materials, including our drug candidates, and will have continued reliance on contract manufacturers for the development and commercialization of our potential drugs. We do not operate manufacturing facilities for clinical or commercial production of our drugs and drug candidates.
In an infringement proceeding, a court may decide that one or more of our patents is invalid, unenforceable, or both. In such case third parties may be able to use our technology without paying licensing fees or royalties.
To prevent infringement or unauthorized use, we may need to file infringement suits, which are expensive and time-consuming. In an infringement proceeding, a court may decide that one or more of our patents is invalid, unenforceable, or both. In such case third parties may be able to use our technology without paying licensing fees or royalties.
The risks and uncertainties described below are not the only ones facing us. Additional risks and uncertainties not presently known to us, or that we currently see as immaterial, may also adversely affect our business.
The risks and uncertainties described below are not the only ones facing us. Additional risks and uncertainties not presently known to us, or that we currently see as immaterial, may also adversely affect our business. The disclosures in this section reflect our beliefs and opinions as to factors that could materially and adversely affect us in the future.
Our partners and other third parties on which we rely may also be subject to business interruptions from such events. In addition, California from time to time has experienced shortages of water, electric power and natural gas. Future shortages and conservation measures could disrupt our operations and cause expense, thus adversely affecting our business and financial results.
Our partners and other third parties on which we rely may also be subject to business interruptions from such events. In addition, California from time to time has experienced shortages of water, electric power and natural gas.
Should we fail to provide adequate privacy or data security protections or maintain compliance with these laws and regulations, including the CCPA, as amended by the CPRA, as well as the GDPR, we could be subject to sanctions or other penalties, litigation, an increase in our cost of doing business and questions concerning the validity of our data processing activities, including clinical trials. 31 Table of Contents Responding to any claims relating to improper handling, storage or disposal of the hazardous chemicals and radioactive and biological materials we use in our business could be time-consuming and costly.
Should we fail to provide adequate privacy or data security protections or maintain compliance with these laws and regulations, including the CCPA, as amended by the CPRA, as well as the GDPR, we could be subject to sanctions or other penalties, litigation, an increase in our cost of doing business and questions concerning the validity of our data processing activities, including clinical trials.
We have funded our operations and capital expenditures with proceeds primarily from private and public sales of our equity securities, royalty monetization agreements, revenue interest agreements, strategic alliances, long-term debt, other financings, interest on investments and grants.
We have historically funded our operations and capital expenditures with proceeds primarily from private and public sales of our equity securities, royalty monetization agreements, revenue interest agreements, strategic alliances, long-term debt, other financings, interest on investments and grants but will be increasingly relying on revenues generated from the commercial sales of MYQORZO to fund our operations and cash expenditures.
Therefore, we may be unable to acquire and protect intellectual property developed by these contractors to the same extent as if these development activities were being conducted in the United States. If we encounter difficulties in protecting our intellectual property rights in foreign jurisdictions, our business prospects could be substantially harmed.
Therefore, we may be unable to acquire and protect intellectual property developed by these contractors to the same extent as if these development activities were being conducted in the United States.
Various extensions may be available, but the life of a patent, and the protection it affords, is limited. Even if patents covering our technologies and drug candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including generics.
Even if patents covering our technologies, drugs and drug candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including generics.
Numerous U.S. and foreign issued patents and pending patent applications owned by third parties exist in the therapeutic areas in which we are developing drug candidates and seeking new potential drug candidates.
Numerous U.S. and foreign issued patents and pending patent applications owned by third parties exist in the therapeutic areas in which we are developing drug candidates or seeking new potential drug candidates, while others may exist that claim methods of use of our existing drugs.
The existence of the Convertible Notes and the obligations that we incurred by issuing them may restrict our ability to take advantage of certain future opportunities, such as engaging in future debt or equity financing activities.
The existence of the Convertible Notes and the obligations that we incurred by issuing them may restrict our ability to take advantage of certain future opportunities, such as engaging in future debt or equity financing activities. 35 Table of Contents We will depend on Sanofi for the development and commercialization of aficamten in China and Bayer for the development and commercialization of aficamten in Japan.
The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the trial until its conclusion.
If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected. The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the trial until its conclusion.
For example, in 2024, the closing price of our common stock on the Nasdaq Global Select Market ranged from $46.36 to $108.06.
Our stock price experiences significant volatility, which often does not directly relate to our operating performance. For example, in 2024, the closing price of our common stock on the Nasdaq Global Select Market ranged from $46.36 to $108.06.
The Camzyos® (mavacamten) REMS program requires, among other things, restrictions and qualifications on pharmacies that dispense the drug and certification, record-keeping, ongoing monitoring and patient counseling obligations on physicians who prescribe the drug.
For example, MYQORZO is subject to a comprehensive REMS program that includes, among other things, restrictions and qualifications on pharmacies that dispense the drug and certification, record-keeping, ongoing monitoring and patient counseling obligations on physicians who prescribe the drug.
Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. 30 Table of Contents We cannot predict the likelihood, nature, or extent of health reform initiatives that may arise from future legislation or administrative action and cannot predict the effect of any of such initiatives on our future financial results or the value of our common stock.
We cannot predict the likelihood, nature, or extent of health reform initiatives that may arise from future legislation or administrative action and cannot predict the effect of any of such initiatives on our future financial results or the value of our common stock.
We may not be able to protect our intellectual property rights throughout the world. Patent protection is afforded on a country-by-country basis.
We may not be able to protect our intellectual property rights throughout the world. Patent protection is afforded on a country-by-country basis. In addition, our patents in foreign jurisdictions may be subject to opposition proceedings that challenge the validity of our patents.
In December 2019, our IT systems were exposed to a ransomware attack, which partially impaired certain IT systems for a short period of time.
We have in the past and may in the future be subject to security breaches. In December 2019, our IT systems were exposed to a ransomware attack, which partially impaired certain IT systems for a short period of time.
We may be subject to costly product liability or other liability claims and may not be able to obtain adequate insurance. The use of our drug candidates in clinical trials or by commercial patients may result in adverse events. We cannot predict all the possible harms or adverse events that may result from our clinical trials.
The use of our drugs and drug candidates in clinical trials or by commercial patients may result in adverse events. We cannot predict all the possible harms or adverse events that may result from our clinical trials.
Any such breaches of security and inappropriate access could disrupt our operations, harm our reputation or otherwise have a material adverse effect on our business, financial condition and results of operations.
While we have implemented measures to protect our data security and information technology systems, such measures may not prevent these events. Any such breaches of security and inappropriate access could disrupt our operations, harm our reputation or otherwise have a material adverse effect on our business, financial condition and results of operations.
We have consumed substantial amounts of capital to date, and our operating expenditures will increase as we expand our research and development activities and expand our organization to commercialize aficamten, if approved.
We will need substantial additional capital in the future to sufficiently fund and maintain our operations. We have consumed substantial amounts of capital to date, and our operating expenditures will increase as we expand our research and development activities and expand our organization to commercialize MYQORZO.
We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties or that we or our employees have wrongfully used or disclosed trade secrets of their former employers.
If we are unable to protect the confidentiality of our trade secrets, the value of our technology could be materially adversely affected and our business would be harmed, and we may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties or that we or our employees have wrongfully used or disclosed trade secrets of their former employers.
If physicians and patients do not accept our drugs, we may be unable to generate significant revenue, if any. Even if our drug candidates obtain regulatory approval, the resulting drugs, if any, may not gain market acceptance among physicians, healthcare payors, patients and the medical community.
Risks Specific to our Company in connection with our Commercial Operations If physicians and patients do not accept our drugs, we may be unable to generate significant revenue, if any. MYQORZO may not gain market acceptance among physicians, healthcare payors, patients and the medical community, and our other drug candidates, if approved, may similarly fail to gain market acceptance.
We will depend on Sanofi for the development and commercialization of aficamten in China and Bayer for the development and commercialization of aficamten in Japan. Under the terms of our license and collaboration agreements, Sanofi and Bayer are responsible for the development and commercialization of aficamten in China and Japan, respectively.
Under the terms of our license and collaboration agreements, Sanofi is responsible for the development and commercialization of aficamten (to be commercialized as MYQORZO) in China and Bayer is responsible for the development and commercialization of aficamten in Japan.
Even if the clinical safety and efficacy of drugs developed from our drug candidates are established for purposes of approval, physicians may elect not to recommend these drugs for a variety of reasons including, but not limited to: the availability of competitive drugs to the market; cost-effectiveness; availability of insurance coverage and reimbursement; convenience and ease of administration; prevalence and severity of adverse events; HCP practice patterns and familiarity with earlier to market therapies. 25 Table of Contents Risks Specific to our Company in connection with our Intellectual Property Our success depends substantially upon our ability to obtain and maintain intellectual property protection relating to our drug candidates, compounds and research technologies.
Even if the clinical safety and efficacy of drugs developed from our drug candidates are established for purposes of approval, physicians may elect not to recommend these drugs for a variety of reasons including, but not limited to the availability of competitive drugs to the market, cost-effectiveness, availability of insurance coverage and reimbursement, convenience and ease of administration, prevalence and severity of adverse events, HCP practice patterns and familiarity with earlier to market therapies. 25 Table of Contents The size of the potential market for MYQORZO or our product candidates is difficult to estimate and, if any of our assumptions are inaccurate, the actual markets for our products or product candidates may be smaller than our estimates.
We may not be able to successfully manufacture our drug candidates in sufficient quality and quantity, which would delay or prevent us from developing our drug candidates and commercializing approved drug products, if any. To date, our drug candidates have been manufactured in quantities adequate for preclinical studies and early through late-stage clinical trials.
We may not be able to successfully manufacture our drugs or drug candidates in sufficient quality and quantity, which would delay or prevent us from developing our drug candidates and commercializing approved drug products.
As use of information technology systems has increased, deliberate attacks and attempts to gain unauthorized access to computer systems and networks have increased in frequency and sophistication.
As use of information technology systems has increased, deliberate attacks and attempts to gain unauthorized access to computer systems and networks have increased in frequency and sophistication. Furthermore, cybersecurity incidents increasingly involve the use of artificial intelligence and machine learning to launch more automated, targeted and coordinated attacks.
As a result, our owned, co-owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours or our partners. If we are unable to protect the confidentiality of our trade secrets, the value of our technology could be materially adversely affected and our business would be harmed.
As a result, our owned, co-owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours or our partners.
These sanctions could include fines, injunctions, civil penalties, failure of regulatory authorities to grant marketing approval of our products, delay, suspension or withdrawal of approvals, license revocation, product seizures or recalls, operational restrictions and criminal prosecutions, any of which could significantly and adversely affect our business.
These sanctions could include fines, injunctions, civil penalties, failure of regulatory authorities to grant marketing approval of our products, delay, suspension or withdrawal of approvals, license revocation, product seizures or recalls, operational restrictions and criminal prosecutions, any of which could significantly and adversely affect our business. 28 Table of Contents Approved drug products remain subject to ongoing obligations, including continued regulatory review by the FDA and foreign regulatory agencies and REMS, all of which may result in significant expense and limit commercialization efforts of our drugs.
Delays in patient enrollment may result in increased costs or may affect the timing or outcome of the planned clinical trials, which could prevent completion of these trials and adversely affect our and our partners’ ability to advance the development of product candidates. 21 Table of Contents The failure to successfully develop, manufacture and obtain regulatory clearance or approval of an immunoassay or companion diagnostics, if required by FDA as a condition to approval of our drugs, could harm our development and commercialization strategy for such drugs in key markets.
The failure to successfully develop, manufacture and obtain regulatory clearance or approval of an immunoassay or companion diagnostics, if required by FDA as a condition to approval of our drugs, could harm our development and commercialization strategy for such drugs in key markets.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeManaging Material Risks & Integrated Overall Risk Management Our cybersecurity team, led by our Chief Information Security Officer, identifies and assesses risks from cybersecurity threats by monitoring and evaluating our threat environment and the Company’s risk profile using various methods including, for example, through manual and automated tools, internal and external audits, third-party threat assessments and third-party conducted red/blue team testing and tabletop incident response exercises and by subscribing to reports and services that identify cybersecurity threats, analyzing reports of threats and actors, conducting scans of the threat environment, evaluating our and our industry’s risk profile, evaluating threats reported to us, conducting threat assessments for internal and external threats and conducting vulnerability assessments.
Biggest changeManaging Material Risks & Integrated Overall Risk Management Our cybersecurity team, led by our Chief Information Security Officer, identifies and assesses risks from cybersecurity threats by monitoring and evaluating our threat environment and the Company’s risk profile using various methods including, for example, through manual and automated tools, internal and external audits, third-party threat assessments and third-party conducted red/blue team testing and tabletop incident response exercises and by subscribing to reports and services that identify cybersecurity threats, analyzing reports of threats and actors, conducting scans of the threat environment, evaluating our and our industry’s risk profile, evaluating threats reported to us, conducting threat assessments for internal and external threats and conducting vulnerability assessments. 40 Table of Contents Depending on the environment, we implement and maintain various technical, physical, and organizational measures, processes, standards and policies designed to manage and mitigate material risks from cybersecurity threats to our Information Systems and Data, including, for example: maintaining an incident response plan, a vulnerability management policy, disaster recovery and business continuity plans and a vendor risk management program; conducting employee training, systems monitoring and penetration testing; implementing security standards, network security controls, access controls and physical security; encrypting and segregating data; though asset management, tracking and disposal; and maintaining cybersecurity insurance.
Mana gement’s Role Managing Risk Our Chief Information Security Officer, Chief Executive Officer and Chief Financial Officer play a pivotal role in informing the Audit Committee on cybersecurity risks. They provide cybersecurity briefings to the Audit Committee on a regular basis, with a minimum frequency of once per year.
Mana gement’s Role Managing Risk Our Chief Information Security Officer, Chief Executive Officer and Chief Financial Officer play a pivotal role in informing the Audit Committee on cybersecurity risks. They provide cybersecurity briefings to the Audit Committee on a regular basis, at least once per year.
With over 10 years of experience in the field of cybersecurity and over 20 years of experience in IT more broadly, Mr. Brown brings a wealth of expertise to his role. His background includes extensive experience as an enterprise Chief Information Security Officer. His in-depth knowledge and experience are instrumental in developing and executing our cybersecurity strategies.
Brown brings a wealth of expertise to his role. His background includes extensive experience as an enterprise Chief Information Security Officer. His in-depth knowledge and experience are instrumental in developing and executing our cybersecurity strategies.
Furthermore, significant cybersecurity matters, and strategic risk management decisions are escalated by any of our executive officers to the Audit Committee, so that the Audit Committee can oversee and provide guidance on critical cybersecurity issues. 35 Table of Contents
This is how executive management is kept abreast of our cybersecurity posture and potentially material cybersecurity risks facing Cytokinetics. Furthermore, significant cybersecurity matters, and strategic risk management decisions are escalated by any of our executive officers to the Audit Committee, so that the Audit Committee can oversee and provide guidance on critical cybersecurity issues.
Our Board has established oversight mechanisms designed to ensure effective governance in managing material risks associated with cybersecurity threats because we recognize the significance of these threats to our operational integrity and stakeholder confidence. 34 Table of Contents Board of Directors Oversight The Audit Committee is central to the Board’s oversight of cybersecurity risks and bears the primary responsibility for this domain.
Governance Cytokinetics’ Board of Directors is aware of the critical nature of managing risks associated with cybersecurity threats. Our Board has established oversight mechanisms designed to ensure effective governance in managing material risks associated with cybersecurity threats because we recognize the significance of these threats to our operational integrity and stakeholder confidence.
The Audit Committee is composed of board members with diverse expertise, including, risk management, technology, and finance. The Audit Committee reports to the Board of Directors periodically regarding cybersecurity topics presented to the Audit Committee, and all materials made available to the Audit Committee are available to rest of the Board of Directors.
The Audit Committee reports to the Board of Directors periodically regarding cybersecurity topics presented to the Audit Committee, and all materials made available to the Audit Committee are available to rest of the Board of Directors.
Our Chief Information Security Officer has overall responsibility for the Company’s IT department and operations, including oversight over the cybersecurity team to ensure efforts to contain and remediate security incidents are sufficient and effective.
Our Chief Information Security Officer has overall responsibility for the Company’s IT department and operations, including oversight over the cybersecurity team to ensure efforts to contain and remediate security incidents are sufficient and effective. Monitor Cybersecurity Incidents The CISO is responsible for staying apprised of the latest developments in cybersecurity, including potential threats and innovative risk management techniques.
These briefings encompass a broad range of topics, including as applicable: the current cybersecurity landscape and emerging threats, the status of ongoing cybersecurity initiatives and strategies, incident reports and learnings from any cybersecurity events, and compliance with regulatory requirements and industry practices.
These briefings encompass a broad range of topics, including as applicable: the current cybersecurity landscape and emerging threats, the status of ongoing cybersecurity initiatives and strategies, incident reports and learnings from any cybersecurity events, and compliance with regulatory requirements and industry practices. 41 Table of Contents In addition to our scheduled meetings, the Audit Committee, our Chief Information Security Officer, Chief Executive Officer and Chief Financial Officer maintain an ongoing dialogue regarding emerging or potential cybersecurity risks.
This review helps in identifying areas for improvement and ensuring the alignment of cybersecurity efforts with the overall risk management framework. Management Personnel in Cybersecurity Primary responsibility for assessing, monitoring and managing our risks from cybersecurity threats rests with our Chief Information Security Officer, Mr. Eric Brown, Vice President of Information Technology.
Management Personnel in Cybersecurity Primary responsibility for assessing, monitoring and managing our risks from cybersecurity threats rests with our Chief Information Security Officer, Mr. Eric Brown, Vice President of Information Technology. With over 10 years of experience in the field of cybersecurity and over 20 years of experience in IT more broadly, Mr.
Monitor Cybersecurity Incidents The CISO is responsible for informing himself from appropriate sources about the latest developments in cybersecurity, including potential threats and innovative risk management techniques. The CISO implements and oversees processes for the monitoring of our information systems. This includes the deployment of security measures and system audits to identify potential vulnerabilities.
The CISO implements and oversees processes for the monitoring of our information systems. This includes the deployment of security measures and system audits to identify potential vulnerabilities. In the event of a cybersecurity incident, the CISO is equipped with a well-defined incident response plan.
The Audit Committee actively participates in strategic decisions related to cybersecurity, offering guidance and approval for major initiatives. This involvement ensures that cybersecurity considerations are integrated into the broader strategic objectives of Cytokinetics. The Audit Committee conducts an annual review of the company’s cybersecurity posture and the effectiveness of its risk management strategies.
Together, they receive updates from one another, as appropriate, on any significant developments in the cybersecurity domain, ensuring the Board’s oversight is proactive and responsive. The Audit Committee actively participates in strategic decisions related to cybersecurity, offering guidance and approval for major initiatives. This involvement ensures that cybersecurity considerations are integrated into the broader strategic objectives of Cytokinetics.
In the event of a cybersecurity incident, the CISO is equipped with a well-defined incident response plan. This plan includes immediate actions designed to mitigate the impact and long-term strategies for remediation and prevention of future incidents.
This plan includes immediate actions designed to mitigate the impact and long-term strategies for remediation and prevention of future incidents. Reporting to Board of Directors Our Chief Information Security Officer regularly informs our executive management team of material cybersecurity risks and incidents.
This approach is designed to mitigate risks related to data breaches or other security incidents originating from third parties. Risks from Cybersecurity Threats For a description of the risks from cybersecurity threats that may materially affect the Company and how they may do so, see our risk factors under Part I. Item 1A.
This approach is designed to mitigate risks related to data breaches or other security incidents originating from third parties. Risks from Cybersecurity Threats Since the beginning of the last fiscal year, we have not identified risks from known cybersecurity threats, including as a result of any prior cybersecurity incidents, that have materially affected us.
Risk Factors in this Annual Report on Form 10-K, including the discussion under the headings “Our internal computer systems, or those of our CROs, CMOs, supply chain partners, collaboration partners or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our drug development programs” and “Significant disruptions of information technology systems or breaches of data security could adversely affect our business”.
However, we face ongoing risks from cybersecurity threats that may materially affect the Company in the future. For more information, see Part I. Item 1A. Risk Factors in this Annual Report on Form 10-K, including the discussion under the heading “Significant disruptions of information technology systems or breaches of data security could adversely affect our business”.
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Depending on the environment, we implement and maintain various technical, physical, and organizational measures, processes, standards and policies designed to manage and mitigate material risks from cybersecurity threats to our Information Systems and Data, including, for example: maintaining an incident response plan, a vulnerability management policy, disaster recovery and business continuity plans and a vendor risk management program; conducting employee training, systems monitoring and penetration testing; implementing security standards, network security controls, access controls and physical security; encrypting and segregating data; though asset management, tracking and disposal; and maintaining cybersecurity insurance.
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Board of Directors Oversight The Audit Committee is central to the Board’s oversight of cybersecurity risks and bears the primary responsibility for this domain. The Audit Committee is composed of Board members with diverse expertise, including, risk management, technology, and finance.
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Governance Cytokinetics’ Board of Directors is aware of the critical nature of managing risks associated with cybersecurity threats.
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The Audit Committee conducts an annual review of the company’s cybersecurity posture and the effectiveness of its risk management strategies. This review helps in identifying areas for improvement and ensuring the alignment of cybersecurity efforts with the overall risk management framework.
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In addition to our scheduled meetings, the Audit Committee, our Chief Information Security Officer, Chief Executive Officer and Chief Financial Officer maintain an ongoing dialogue regarding emerging or potential cybersecurity risks. Together, they receive updates from one another, as appropriate, on any significant developments in the cybersecurity domain, ensuring the Board’s oversight is proactive and responsive.
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Reporting to Board of Directors Our Chief Information Security Officer , in his capacity, regularly informs our executive management team of material cybersecurity risks and incidents. This is how executive management is kept abreast of our cybersecurity posture and potentially material cybersecurity risks facing Cytokinetics.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeITEM 2. PROPERTIES Our material facilities consist of 234,892 square feet of leased office and laboratory space at 350 Oyster Point, South San Francisco, California. Our lease over this property expires in 2033. We believe that these facilities are suitable and adequate for our current needs. ITEM 3. LEGAL PROCEEDINGS We are not currently subject to any material legal proceedings.
Biggest changeITEM 2. PROPERTIES Our material facilities consist of 234,892 square feet of leased office and laboratory space at 350 Oyster Point, South San Francisco, California. Our lease over this property expires in 2033. We believe that these facilities are suitable and adequate for our current needs.
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ITEM 4. MINE SAFETY DISCLOSURES Not applicable. 36 Table of Contents PART II

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

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Biggest changeItem 4. Mine Safety Disclosures 36 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 37 Item 6. [Reserved] 38 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 39 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 50 Item 8.
Biggest changeItem 4. Mine Safety Disclosures 43 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 44 Item 6. [Reserved] 45 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 46 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 58 Item 8.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeThe graph assumes (a) $100 was invested on December 31, 2019 in each of our common stock, the stocks comprising the Nasdaq Composite Index and the stocks comprising the Nasdaq Biotechnology Index, and (b) the reinvestment of dividends into shares of common stock; however, no dividends have been declared on our common stock to date. $100 investment in stock or index 12/31/2019 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 Cytokinetics, Inc. $ 100.00 $ 195.85 $ 429.59 $ 431.86 $ 786.90 $ 443.36 Nasdaq Composite Index 100.00 143.64 174.36 116.65 167.30 215.22 Nasdaq Biotechnology Index 100.00 125.69 124.89 111.27 115.42 113.84 Holders of Record As of February 26, 2025, we had 41 holders of record of common stock.
Biggest changeThe graph assumes (a) $100 was invested on December 30, 2020 in each of our common stock, the stocks comprising the Nasdaq Composite Index and the stocks comprising the Nasdaq Biotechnology Index, and (b) the reinvestment of dividends into shares of common stock; however, no dividends have been declared on our common stock to date. $100 investment in stock or index 12/30/2020 12/31/2021 12/31/2022 12/31/2023 12/30/2024 12/31/2025 Cytokinetics, Inc. $ 100.00 $ 219.35 $ 220.50 $ 401.78 $ 226.37 $ 305.77 Nasdaq Composite Index 100.00 121.39 81.21 116.47 149.83 180.33 Nasdaq Biotechnology Index 100.00 99.37 88.53 91.84 90.58 119.92 Holders of Record As of February 23, 2026, we had 38 holders of record of common stock.
The number of holders of record is based upon the actual number of holders registered as of such date and does not include holders of shares in “street name” or persons, partnerships, associates, corporations or other entities in security position listings maintained by depositories. 37 Table of Contents Dividends We have never declared or paid, and do not anticipate declaring or paying in the foreseeable future, any cash dividends on our capital stock.
The number of holders of record is based upon the actual number of holders registered as of such date and does not include holders of shares in “street name” or persons, partnerships, associates, corporations or other entities in security position listings maintained by depositories. 44 Table of Contents Dividends We have never declared or paid, and do not anticipate declaring or paying in the foreseeable future, any cash dividends on our capital stock.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeResearch and development expenses for 2024, 2023, and 2022 were as follows (in millions): Years Ended December 31, Change 2024 2023 2022 2024-2023 2023-2022 (In millions) Total research and development expenses $ 339.4 $ 330.1 $ 240.8 $ 9.3 $ 89.3 Research and development expenses increased to $339.4 million in 2024 from $330.1 million in 2023, primarily due to advancing our clinical trials and higher personnel related costs.
Biggest changeResearch and development expenses for 2025, 2024, and 2023 were as follows (in millions): Years Ended December 31, Change 2025 2024 2023 2025-2024 2024-2023 External costs: (In millions) Aficamten $ 104.5 $ 90.8 $ 91.3 $ 13.7 $ (0.5 ) Omecamtiv Mecarbil 20.0 11.0 6.8 9.0 4.2 Other programs 13.3 15.2 40.8 (1.9 ) (25.6 ) Unallocated 48.9 35.2 30.3 13.7 4.9 Total external costs 186.7 152.2 169.2 34.5 (17.0 ) Internal costs: Employee related 171.5 136.5 110.2 35.0 26.3 Facilities, lab supplies and other 57.8 50.7 50.7 7.1 — Total internal costs 229.3 187.2 160.9 42.1 26.3 Total research and development expenses $ 416.0 $ 339.4 $ 330.1 $ 76.6 $ 9.3 Research and development expenses increased to $416.0 million in 2025 from $339.4 million in 2024, primarily due to advancing our clinical trials, higher personnel related costs including stock based compensation and medical affairs related activities.
Additionally, we have FOREST-HCM which is an open label extension study designed to assess the long term safety and tolerability of aficamten in patients with symptomatic oHCM. We continue to develop omecamtiv mecarbil in COMET-HF, a Phase 3 clinical trial of omecamtiv mecarbil in patients with symptomatic HFrEF with severely reduced ejection fraction.
Additionally, we have FOREST-HCM which is an open label extension study designed to assess the long-term safety and tolerability of aficamten in patients with HCM. We continue to develop omecamtiv mecarbil in COMET-HF, a Phase 3 clinical trial of omecamtiv mecarbil in patients with symptomatic HFrEF with severely reduced ejection fraction.
We issued 5,016,170 and 1,237,460 shares of our common stock for net proceeds of $164.2 million and $93.6 million in 2023 and 2024, respectively, under the Amended ATM Facility. We exercised our rights to terminate the Amended ATM Facility with Cantor in February 2024.
In 2023 and 2024, we issued 5,016,170 shares of our common stock for net proceeds of $164.2 million and 1,237,460 shares of our common stock for net proceeds of $93.6 million, respectively, under the Amended ATM Facility. We exercised our rights to terminate the Amended ATM Facility with Cantor in February 2025.
Accordingly, all rights to develop and commercialize omecamtiv mecarbil have reverted to us. China Out-license for Aficamten In July 2020, we entered into a license and collaboration agreement with Corxel, pursuant to which we granted to Corxel an exclusive license to develop and commercialize aficamten in China and Taiwan.
Accordingly, all rights to develop and commercialize omecamtiv mecarbil have reverted to us. Greater China Out-license for Aficamten In July 2020, we entered into a license and collaboration agreement with Corxel, pursuant to which we granted to Corxel an exclusive license to develop and commercialize aficamten in China and Taiwan.
If, at any time, our prospects for internally financing programs and activities decline, we may decide to reduce expenses across the business. Alternatively, we might raise funds through strategic relationships, public or private financings or other arrangements.
If, at any time, our prospects for internally financing programs and activities decline, we may decide to reduce expenses across the business. Alternatively, we may raise funds through strategic relationships, public or private financings or other arrangements.
China Out-license for Omecamtiv Mecarbil In December 2021, we entered into the Corxel OM License Agreement, pursuant to which we granted to Corxel an exclusive license to develop and commercialize omecamtiv mecarbil in China and Taiwan. In December 2024, we entered into a mutual termination agreement with Corxel to terminate the Corxel OM License Agreement.
Greater China Out-license for Omecamtiv Mecarbil In December 2021, we entered into the Corxel OM License Agreement, pursuant to which we granted to Corxel an exclusive license to develop and commercialize omecamtiv mecarbil in China and Taiwan. In December 2024, we entered into a mutual termination agreement with Corxel to terminate the Corxel OM License Agreement.
If and when aficamten is commercialized and royalties become due, we will recognize the portion of royalties paid to RPI ICAV as a decrease to the RP Aficamten Liability and a corresponding reduction in cash.
When aficamten is commercialized and royalties become due, we will recognize the portion of royalties paid to RPI ICAV as a decrease to the RP Aficamten Liability and a corresponding reduction in cash.
These factors could have a material adverse effect on our future financial results, financial position and cash flows. 44 Table of Contents Based on the current planning assumptions, we believe that our existing cash and cash equivalents, investments and interest earned on investments will be sufficient to meet our projected operating requirements for at least the next 12 months.
These factors could have a material adverse effect on our future financial results, financial position and cash flows. 52 Table of Contents Based on the current planning assumptions, we believe that our existing cash and cash equivalents, investments and interest earned on investments will be sufficient to meet our projected operating requirements for at least the next 12 months.
Our obligation to pay the Royalty Payment will continue after maturity of the Loan; 40 Table of Contents • Scenario 2: If the Phase 3 clinical trial of omecamtiv mecarbil is successful by June 30, 2028 but we have not received the marketing approval from the FDA for omecamtiv mecarbil on or prior to December 31, 2029, we are required to pay RPDF 18 equal quarterly cash payments totaling 237.5% of the principal amount of the loan commencing on March 31, 2030; and • Scenario 3: If the Phase 3 clinical trial of omecamtiv mecarbil is not successful by June 30, 2028, we are required to pay RPDF 22 equal quarterly cash payments totaling 227.5% of the principal amount of the loan commencing on September 30, 2028.
Our obligation to pay the Royalty Payment will continue after maturity of the Loan; • Scenario 2: If the Phase 3 clinical trial of omecamtiv mecarbil is successful by June 30, 2028 but we have not received the marketing approval from the FDA for omecamtiv mecarbil on or prior to December 31, 2029, we are required to pay RPDF 18 equal quarterly cash payments totaling 237.5% of the principal amount of the loan commencing on March 31, 2030; and • Scenario 3: If the Phase 3 clinical trial of omecamtiv mecarbil is not successful by June 30, 2028, we are required to pay RPDF 22 equal quarterly cash payments totaling 227.5% of the principal amount of the loan commencing on September 30, 2028.
In addition, Sanofi will pay us tiered royalties in the low-to-high teens range on the net sales of pharmaceutical products containing aficamten in China and Taiwan, subject to certain reductions for generic competition, patent expiration and payments for licenses to third party patents.
In addition, Sanofi will pay us tiered royalties in the low-to-high teens range on the net sales of pharmaceutical products containing aficamten, including MYQORZO, in China and Taiwan, subject to certain reductions for generic competition, patent expiration and payments for licenses to third party patents.
See Note 3 — Agreements with Royalty Pharma for further detail. Derivative Liabilities We recognize liabilities of our embedded derivative instruments related to the RP Multi Tranche Loan at fair value in the consolidated balance sheets.
See Note 3 — "Agreements with Royalty Pharma," to our Consolidated Financial Statements for further detail. Derivative Liabilities We recognize liabilities of our embedded derivative instruments related to the RP Multi Tranche Loan at fair value in the consolidated balance sheets.
At-the-Market Sales of Common Stock In March 2023, we entered into the Amended ATM Facility, with Cantor, under which we may offer and sell, from time to time at our sole discretion, shares of our common stock having an aggregate offering price of up to $300.0 million through Cantor, as sales agent.
At-the-Market Sales of Common Stock On March 1, 2023, we entered into the Amended ATM Facility, with Cantor, under which we may offer and sell, from time to time at our sole discretion, shares of Common Stock having an aggregate offering price of up to $300.0 million through Cantor, as sales agent.
General and Administrative Expenses General and administrative expenses consist primarily of compensation for employees in executive and administrative functions, including, but not limited to, finance, human resources, legal, business and commercial development and strategic planning.
General and Administrative Expenses General and administrative expenses consist primarily of compensation for employees in executive and administrative functions, including, but not limited to, finance, human resources, legal, business and corporate development and strategic planning.
We may also be eligible to receive up to an additional €490 million in commercial milestone payments upon the achievement by Bayer of certain sales milestones and tiered royalties on the net sales of pharmaceutical products containing aficamten in Japan ranging from the high teens to the low thirty percents, subject to certain reductions for generic competition, expiration of certain patents and payments for licenses to third-party patents, until the latest of the expiration of certain patents, the expiration of regulatory exclusivity for the Product in Japan, and the end of a minimum specified term.
We are also eligible for an additional €490 million in commercial milestone payments upon the achievement by Bayer of certain sales milestones and tiered royalties on the net sales of pharmaceutical products containing aficamten in Japan ranging from the high teens to the low thirty percents, subject to certain reductions for generic competition, expiration of certain patents and payments for licenses to third-party patents, until the latest of the expiration of certain patents, the expiration of regulatory exclusivity for the Product in Japan, and the end of a minimum specified term.
Results of Operations A discussion of our results of operations for the year ended December 31, 2022 and year-to-year comparisons between 2023 and 2022 can be found in Item 7.
Results of Operations A discussion of our results of operations for the year ended December 31, 2023 and year-to-year comparisons between 2024 and 2023 can be found in Item 7.
Other significant costs include facilities costs, consulting costs and professional fees for accounting and legal services, including legal services associated with obtaining and maintaining patents and regulatory compliance.
Other significant costs include commercial readiness costs, facilities costs, consulting costs and professional fees for accounting and legal services, including legal services associated with obtaining and maintaining patents and regulatory compliance.
As products containing omecamtiv mecarbil and CK-586 have not yet been commercialized, the estimates are highly subjective. For example, assumed increases in the probability of the clinical success for the omecamtiv mecarbil or CK-586 programs could increase the value of the liabilities.
As products containing omecamtiv mecarbil and ulacamten have not yet been commercialized, the estimates are highly subjective. For example, assumed increases in the probability of the clinical success for the programs for omecamtiv mecarbil or ulacamten could increase the value of the liabilities.
We will not know for certain whether any additional funding under the RP CK-586 RPA will be available to us until the conclusion of AMBER-HFpEF, the results of the trial are known, and RPI ICAV has decided to exercise its option to purchase an incremental 3.5% revenue interest on our future annual worldwide net sales of CK-586 or not. 2022 Royalty Pharma Transactions In January 2022, we entered into a series of financing agreements with affiliates of Royalty Pharma, including the RP Multi Tranche Loan Agreement, and the RP Aficamten RPA.
We will not know for certain whether any additional funding under the RP Ulacamten RPA may be available to us until the conclusion of AMBER-HFpEF, the results of the trial are known, and RPI ICAV has decided to exercise its option to purchase an incremental 3.5% revenue interest on our future annual worldwide net sales of drug products containing ulacamten or not. 2022 Royalty Pharma Transactions In January 2022, we entered into a series of financing agreements with affiliates of Royalty Pharma, including the RP Multi Tranche Loan Agreement, and the RP Aficamten RPA.
Pursuant to the RP CK-586 RPA, RPI ICAV purchased rights to up to 4.5% of worldwide net sales of CK-586 by us, our affiliates or licensees, in exchange for up to $200 million in consideration, $50 million of which was paid upfront and, following the initiation of the first Phase 3 clinical trial (or the Phase 3 portion of the first Phase 2b/3 clinical trial) in HFpEF for CK-586, at RPI ICAV’s sole discretion, up to in aggregate $150 million to fund 50.0% of the research and development cost of CK-586.
Pursuant to the RP Ulacamten RPA, RPI ICAV purchased rights to up to 4.5% of worldwide net sales of drug products containing ulacamten by us, our affiliates or licensees, in exchange for up to $200 million in consideration, $50 million of which was paid upfront and, following the initiation of the first Phase 3 clinical trial (or the Phase 3 portion of the first Phase 2b/3 clinical trial) in HFpEF for ulacamten, at RPI ICAV’s sole discretion, up to in aggregate $150 million to fund 50.0% of the research and development cost of ulacamten.
These factors include, but are not limited to, the following: • the initiation, progress, timing, scope and completion of preclinical research, non-clinical development, CMC, and clinical trials for our drug candidates and other compounds; • the time, costs and outcomes of regulatory reviews or other regulatory actions related to our drug candidates, including with respect to our NDA submission for aficamten for the treatment of oHCM to FDA and our related MAA submission to EMA; • the jurisdictions in which we are granted regulatory approvals and thus are able to successfully launch our products for commercial sale; • delays that may be caused by requirements of regulatory agencies; • our level of funding for the development of current or future drug candidates; • the number of drug candidates we pursue and the stage of development that they are in; • the costs involved in filing and prosecuting patent applications and enforcing or defending patent claims; • our ability to establish and maintain selected strategic alliances required for the development of drug candidates and commercialization of our potential drugs; • our plans or ability to expand our drug development capabilities, including our capabilities to conduct clinical trials for our drug candidates; • our plans or ability to engage third-party manufacturers for our drug candidates and potential drugs; • our plans or ability to build or access sales and marketing capabilities and to achieve market acceptance for potential drugs; • the expansion and advancement of our research programs; • the hiring of additional employees and consultants; • the acquisition of technologies, products and other business opportunities that require financial commitments; • our revenues, if any, from successful development of our drug candidates and commercialization of potential drugs; • the cost of additional construction to expand our headquarters in South San Francisco and the cost in relation to expanding our leased office facilities in Radnor, Pennsylvania or other leased office spaces in Europe; and • the payments due for interest on the term loan and convertible debt; We have incurred an accumulated deficit of approximately $2.7 billion since inception and there can be no assurance that we will attain profitability.
These factors include, but are not limited to, the following: • the initiation, progress, timing, scope and completion of preclinical research, non-clinical development, CMC, and clinical trials for our drug candidates and other compounds; • the time, costs and outcomes of regulatory reviews or other regulatory actions related to our drugs and drug candidates, • the jurisdictions in which we are granted regulatory approvals and thus are able to successfully launch our products for commercial sale; • delays that may be caused by requirements of regulatory agencies; • our level of funding for the development of current or future drugs and drug candidates; • the number of drug candidates we pursue and the stage of development that they are in; • the costs involved in filing and prosecuting patent applications and attacking, enforcing or defending patent claims; • our ability to establish and maintain selected strategic alliances required for the development of drug candidates and commercialization of our drugs and future drugs, if any; • our plans or ability to expand our drug development capabilities, including our capabilities to conduct clinical trials for our drug candidates; • our plans or ability to engage third-party manufacturers for our drugs or drug candidates; • our plans or ability to build or access sales and marketing capabilities, including commercial infrastructure and distribution capabilities, and to achieve market acceptance for MYQORZO and potential future drugs; • the expansion and advancement of our research programs; • the hiring of additional employees and consultants; • the acquisition of technologies, products and other business opportunities that require financial commitments; • our revenues from commercialization of MYQORZO and successful development and commercialization of any other drug candidates; • the cost of additional construction to expand our headquarters in South San Francisco and the cost in relation to expanding our leased office facilities in Radnor, Pennsylvania or other leased office spaces in Europe; and • the payments due for interest on the term loan and convertible debt; We have incurred an accumulated deficit of approximately $3.5 billion since inception and there can be no assurance that we will attain profitability.
In the second quarter of 2024, we recorded an additional $33.3 million to the carrying value related to the RP Aficamten RPA Amendment entered into May 22, 2024. The imputed rate of interest on the carrying value of the RP Aficamten Liability was approximately 23.5% as of December 31, 2024 and 24.8% as of December 31, 2023.
In the second quarter of 2024, we recorded an additional $33.3 million to the carrying value related to the RP Aficamten RPA Amendment entered into May 22, 2024. The imputed rate of interest on the carrying value of the RP Aficamten Liability was approximately 22.6% as of December 31, 2025 and 23.5% as of December 31, 2024.
The fair values are based on significant unobservable inputs, including the probability of change of control, the probability of default (less than 10%), discount rates (ranging from 10% to 16% as of December 31, 2024) and other factors.
The fair values are based on significant unobservable inputs, including the probability of change of control, the probability of default (less than 10%), discount rates (ranging from 10% to 15% as of December 31, 2025) and other factors.
The 2026 Notes and the 2027 Notes are redeemable, at our option at any time in the case of the 2026 Notes and at any time after July 7, 2025 in the case of the 2027 Notes and, in the case of any partial redemption, on or before the 60th scheduled trading day before the maturity date for the relevant notes, at a cash redemption price equal to the principal amount of the relevant notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date but only if the last reported sale price per share of our common stock exceeds 130% of the conversion price for the relevant notes on (1) each of at least 20 trading days, whether or not consecutive, during the 30 consecutive trading days ending on, and including, the trading day immediately before the date we may send the related redemption notice; and (2) the trading day immediately before the date we may send such notice.
The 2026 Notes and the 2027 Notes are redeemable, in whole or in part (subject to the Partial Redemption Limitation, in the case of the 2027 Notes), at our option at any time, and from time to time, and, in the case of any partial redemption, on or before the 60th scheduled trading day before the applicable maturity date, at a cash redemption price equal to the principal amount of the relevant Convertible Notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date but only if the last reported sale price per share of our common stock exceeds 130% of the conversion price for the relevant notes on (1) each of at least 20 trading days, whether or not consecutive, during the 30 consecutive trading days ending on, and including, the trading day immediately before the date we may send the related redemption notice; and (2) the trading day immediately before the date we may send such notice.
Under the terms of the Bayer License Agreement, we received an up-front payment of €50.0 million (equivalent to $52.4 million at the time of payment) which was recorded as deferred revenue at December 31, 2024 and will be recognized upon the completion of certain performance obligations.
Under the terms of the Bayer License Agreement, we received an up-front payment of €50.0 million (equivalent to $52.4 million at the time of payment) which was recorded as deferred revenue at December 31, 2024 and was recognized in 2025 upon completion of certain performance technology transfer obligations.
We continue to develop aficamten to treat both oHCM and nHCM in three additional clinical trials, as follows: (i) MAPLE-HCM is our Phase 3 clinical trial of aficamten as a monotherapy for patients with oHCM, (ii) ACACIA-HCM is a Phase 3 clinical trial for patients with symptomatic nHCM, and (iii) CEDAR-HCM, our placebo-controlled and open-label extension clinical trial to evaluate the efficacy, pharmacokinetics (PK) and safety of aficamten in a pediatric population with symptomatic oHCM.
We continue to develop aficamten to treat both oHCM and nHCM in two additional clinical trials: (i) ACACIA-HCM is a Phase 3 clinical trial for patients with symptomatic nHCM, and (ii) CEDAR-HCM, our placebo-controlled and open-label extension clinical trial to evaluate the efficacy, pharmacokinetics (PK) and safety of aficamten in a pediatric population with symptomatic oHCM.
The $50 million in proceeds from the RP CK-586 RPA are intended to offset expenses related to the conduct of AMBER-HFpEF.
The $50 million in proceeds from the RP Ulacamten RPA are intended to offset expenses related to the conduct of AMBER-HFpEF.
The carrying amount of the RP Aficamten Liability is based on our estimate of the future royalties to be paid pursuant to RP Aficamten RPA over the life of the arrangement as discounted using an imputed rate of interest.
The carrying amount of the RP OM Liability is based on our estimate of the future royalties to be paid to RPFT over the life of the arrangement as discounted using an imputed rate of interest.
Therefore, our success is dependent on our ability to obtain additional capital by entering into new strategic collaborations and/or through financings, and ultimately on our and our collaborators’ ability to successfully develop and market one or more of our drug candidates.
Therefore, our success is dependent on our ability to generate substantial revenues from MYQORZO or potentially obtain additional capital by entering into new strategic collaborations and/or through financings, and ultimately on our and our collaborators’ ability to successfully develop and market one or more of our drug candidates.
We recognized $15.0 million dollars from Corxel in connection with a modification of the original license prior to the assignment of Corxel's rights under our license and collaboration agreement for the development and commercialization of aficamten to Sanofi and we may be eligible for another $10.0 million milestone from Corxel under certain commercial circumstances.
In 2024, we recognized $15.0 million dollars from Corxel in connection with a modification of the original license prior to the assignment of Corxel's rights under our license and collaboration agreement for the development and commercialization of aficamten to Sanofi, and we may be eligible for another $10.0 million milestone payment from Corxel if certain conditions are met.
We may be eligible to receive from Sanofi future milestone payments totaling up to $150.0 million for the achievement of certain development and commercial milestone events in connection to aficamten in oHCM and/or nHCM.
We may be eligible to receive future milestone payments from Sanofi totaling up to $135.0 million for the achievement of certain development and commercial milestone events in connection to sales of MYQORZO and development of aficamten in nHCM.
If the results of AMBER-HFpEF are supportive of continuing the development of CK-586 and commencing a Phase 3 clinical trial, we expect to Royalty Pharma to cover potentially 50% of the continued development of CK-586 up to $150 million, subject to Royalty Pharma’s opt-in right to acquire an additional 3.5% revenue interest in our or our licensee’s future worldwide net sales of CK-586.
If the results of AMBER-HFpEF are supportive of continuing the development of ulacamten and commencing a Phase 3 clinical trial, Royalty Pharma has the option to cover potentially 50% of the continued development of ulacamten up to $150 million, subject to Royalty Pharma’s opt-in right to acquire an additional 3.5% revenue interest in our or our licensee’s future worldwide net sales of drug products containing ulacamten.
In accordance with ASC 825, the Company records the liabilities at fair value and remeasures the liabilities at fair value each reporting period with changes in fair value associated with non-credit components are recognized in Other income (expense), net, while the change in fair value associated with credit components is recognized in accumulated other comprehensive loss.
In accordance with ASC 825, the Company records the liabilities at fair value and remeasures the liabilities at fair value each reporting period with changes in fair value associated with non-credit components are recognized in the consolidated statement of operations and comprehensive loss while the change in fair value associated with credit components is recognized in accumulated other comprehensive loss.
However, in May 2024, we entered into the RP Aficamten RPA Amendment to restructure the royalty so that RPI will now receive 4.5% up to $5.0 billion of worldwide annual net sales of aficamten and 1% above $5.0 billion of worldwide annual net sales.
However, in May 2024, we entered into the RP Aficamten RPA Amendment to restructure the royalty so that RPI will now receive 4.5% up to $5.0 billion of worldwide annual net sales of aficamten and 1% above $5.0 billion of worldwide annual net sales. Our liability to RPI ICAV is referred to as the “RP Aficamten Liability”.
The intention of the $100 million RP OM Loan Agreement was to partially cover the costs of the COMET-HF clinical trial. We recently announced our commencement of AMBER-HFpEF, a Phase 2 clinical trial of CK-586 in patients with symptomatic HFpEF, in which patient enrollment commenced in the first quarter of 2025.
The intention of the $100 million RP OM Loan Agreement was to partially cover the costs of COMET-HF. We continue to develop ulacamten in AMBER-HFpEF, a Phase 2 clinical trial of ulacamten in patients with symptomatic HFpEF, in which patient enrollment commenced in the first quarter of 2025.
Change in fair value liabilities related to RPI transactions and derivative liabilities reflected on the Consolidated Statement of Operations The change in fair value liabilities related to the RPI transactions (RP OM Loan Agreement and CK-586 RPA) and the derivative liabilities for the RP Multi Tranche Loan Agreement for 2024 were as follows (in millions): Year Ended December 31 2024 (In millions) CK-586 RPA $ (1.3 ) RP OM Loan (18.3 ) RP Multi Tranche Loan Agreement Derivatives 1.3 Total change in fair value liabilities $ (18.3 ) The fair values of the liabilities related to RPI transactions (RP OM Loan Agreement and CK-586 RPA) are based on significant unobservable inputs, including the probability of clinical success and regulatory approval based on historical industry success rates for product development specific to cardiovascular products, the estimated date of a product launch, estimates of pricing, sales ramp, variables for the timing of the related events, probability of change of control, and discount rates (which range from 10% to 18% as of December 31, 2024), which are deemed to be Level 3 inputs in the fair value hierarchy.
The change in fair value liabilities related to the RPI transactions (RP OM Loan Agreement and RP Ulacamten RPA) and the derivative liabilities for the RP Multi Tranche Loan Agreement for the 2025 were as follows (in millions): Year Ended December 31 Change 2025 2024 2025-2024 (In millions) RP Ulacamten RPA $ 0.3 $ (1.3 ) $ 1.6 RP OM Loan (0.5 ) (18.3 ) 17.8 RP Multi Tranche Loan Agreement Derivatives 4.2 1.3 2.9 Total change in fair value liabilities $ 4.0 $ (18.3 ) $ 22.3 56 Table of Contents The fair values of the liabilities related to RPI transactions (RP OM Loan Agreement and RP Ulacamten RPA) are based on significant unobservable inputs, including the probability of clinical success and regulatory approval based on historical industry success rates for product development specific to cardiovascular products, the estimated date of a product launch, estimates of pricing, sales ramp, variables for the timing of the related events, probability of change of control, and discount rates (which range from 10% to 18% as of December 31, 2025), which are deemed to be Level 3 inputs in the fair value hierarchy.
The imputed rate of interest on the carrying value of the RP Aficamten Liability was approximately 23.5% and 24.8% as of December 31, 2024 and 2023, respectively. Convertible Notes On November 13, 2019, we issued $138.0 million aggregate principal amount of 2026 Notes.
The imputed rate of interest on the carrying value of the RP OM Liability was 0.0% and approximately 0.1% as of December 31, 2025 and 2024, respectively. Convertible Notes On November 13, 2019, we issued $138.0 million aggregate principal amount of 2026 Notes.
We have generated significant operating losses since our inception. Our expenditures have historically primarily related to research and development activities, but have recently and will increasingly also relate to our commercial readiness activities and general commercialization activities upon regulatory approval of aficamten.
We have generated significant operating losses since our inception. Our expenditures have historically been primarily related to research and development activities but have recently and will increasingly relate to our commercial readiness activities and general commercialization activities of our drug products.
As of December 31, 2024, we have a total carrying value of approximately $462.2 million of liabilities related to revenue participation right purchase agreements. 49 Table of Contents Accrued Research and Development Expenditures Clinical trial costs are a component of research and development expense.
As of December 31, 2025, we have a total carrying value of approximately $520.6 million of liabilities related to revenue participation right purchase agreements. Accrued Research and Development Expenditures Clinical trial costs are a component of research and development expense.
The initial $50 million paid to us entitles RPI ICAV to 1% of worldwide net sales of CK-586 by us, our affiliates, or licenses.
The initial $50 million paid to us entitles RPI ICAV to 1% of worldwide net sales of drug products containing ulacamten by us, our affiliates, or licenses.
As products containing aficamten, omecamtiv mecarbil and CK-586 have not yet been commercialized, the estimates are highly subjective. The carrying amount of the liabilities are based on our estimate of the future royalties to be paid over the life of the arrangements as discounted using an imputed rate of interest.
As MYQORZO sales have not commenced and products containing omecamtiv mecarbil and ulacamten have not yet been approved as of December 31, 2025, the estimates are highly subjective. The carrying amount of the liabilities are based on our estimate of the future royalties to be paid over the life of the arrangements as discounted using an imputed rate of interest.
The excess of future estimated royalty payments over the $92.3 million of allocated proceeds, less issuance costs, is recognized as non-cash interest expense using the effective interest method. The imputed rate of interest on the carrying value of the RP OM Liability was approximately 0.1% as of December 31, 2024 and 0.1% as of December 31, 2023.
The excess of future estimated royalty payments over the $92.3 million of allocated proceeds, less issuance costs, is recognized as non-cash interest expense using the effective interest method. The imputed rate of interest on the carrying value of the RP OM Liability is reassessed periodically and is not reduced below 0%.
Net loss for 2024 and 2023 included, among other items: non-cash stock-based compensation, non-cash interest expense on liabilities related to revenue participation right purchase agreements, non-cash interest expense related to debt and non-cash changes in fair values related to derivative liabilities and liabilities related to RPI Transactions.
Net loss for 2025 and 2024 included, among other items: stock-based compensation, interest expense on liabilities related to revenue participation right purchase agreements and debt, and/or changes in fair values related to derivative liabilities and liabilities related to RPI Transactions and the debt conversion expense due to 2027 Note repurchase.
RP Aficamten Royalty Purchase Agreement Under the RP Aficamten RPA, RPI ICAV purchased rights to certain revenue streams from net sales of pharmaceutical products containing aficamten by us, our affiliates and our licensees in exchange for up to $150.0 million in consideration, $50.0 million of which was paid on the closing date, $50.0 million of which was paid to us in March 2022 following the initiation of the first pivotal trial in oHCM for aficamten, and $50.0 million of which was paid to us in September 2023 following the initiation of the first pivotal clinical trial in nHCM for aficamten.
We commenced repayment of the RP Multi Tranche Loans in the fourth quarter of 2023 and will pay approximately $20.2 million in interest and principal on the term loans in 2026. 48 Table of Contents RP Aficamten Royalty Purchase Agreement Under the RP Aficamten RPA, RPI ICAV purchased rights to certain revenue streams from net sales of pharmaceutical products containing aficamten by us, our affiliates and our licensees in exchange for up to $150.0 million in consideration, $50.0 million of which was paid on the closing date, $50.0 million of which was paid to us in March 2022 following the initiation of the first pivotal trial in oHCM for aficamten, and $50.0 million of which was paid to us in September 2023 following the initiation of the first pivotal clinical trial in nHCM for aficamten.
Management’s Discussion and Analysis of Financial Condition and Results of Operations in our 2023 Annual Report on Form 10-K under the heading "Results of Operations." Revenues Our revenues since inception were primarily from our strategic alliances. We have not generated any revenue from commercial product sales to date.
Management’s Discussion and Analysis of Financial Condition and Results of Operations in our 2024 Annual Report on Form 10-K under the heading "Results of Operations." Revenues Our revenues since inception were primarily from our strategic alliances. We did not generate any revenue from commercial product sales prior to the year ended December 31, 2025.
Cash Flows Used in Operating Activities Net cash used in operating activities of $395.9 million and $414.3 million for 2024 and 2023, respectively, was largely due to ongoing research and development activities and general and administrative expenses to support those activities.
Cash Flows Used in Operating Activities Net cash used in operating activities of $510.0 million and $395.9 million for 2025 and 2024, respectively, was largely due to ongoing research and development activities and general and administrative expenses to support research and development as well as commercial readiness.
Cash Flows Used in Investing Activities Net cash used in investing activities of $553.1 million for 2024 was primarily due to purchases of investments offset by maturities of investments. Net cash used in investing activities of $239.3 million for 2023 was primarily due to sales and maturities of investments offset by purchases of investments.
Cash Flows Used in Investing Activities Net cash used in investing activities of $16.7 million for 2025 was primarily due to maturities of investments, offset by purchases of investments and property, plant and equipment. Net cash used in investing activities of $553.1 million for 2024 was primarily due to purchases of investments, offset by maturities of investments.
Our liability to RPI ICAV is referred to as the “RP Aficamten Liability”. 41 Table of Contents We account for the RP Aficamten Liability as a liability primarily because we have significant continuing involvement in generating the related revenue stream from which the liability will be repaid.
We account for the RP Aficamten Liability as a liability primarily because we have significant continuing involvement in generating the related revenue stream from which the liability will be repaid.
Under the terms of the Bayer License Agreement, we received an up-front payment of €50.0 million (equivalent to $52.4 million at the time of payment) which was recorded as deferred revenue at December 31, 2024 and will be recognized upon the completion of certain performance obligations.
Under the terms of the Bayer License Agreement, we received an up-front payment of €50.0 million which was initially deferred at December 31, 2024 and was recognized in 2025 upon completion of certain technology transfer performance obligations, as discussed above.
General and administrative expenses by program for 2024, 2023, and 2022 were as follows (in millions): Years Ended December 31, Change 2024 2023 2022 2024-2023 2023-2022 (In millions) Total general and administrative expenses $ 215.3 $ 173.6 $ 178.0 $ 41.7 $ (4.4 ) 46 Table of Contents General and administrative expenses increased to $215.3 million in 2024 from $173.6 million in 2023, primarily due to investments in commercial readiness and higher personnel related costs, including stock based compensation.
General and administrative expenses by program for 2025, 2024, and 2023 were as follows (in millions): Years Ended December 31, Change 2025 2024 2023 2025-2024 2024-2023 (In millions) Total general and administrative expenses $ 284.3 $ 215.3 $ 173.6 $ 69.0 $ 41.7 General and administrative expenses increased to $284.3 million in 2025 from $215.3 million in 2024, primarily due to investments toward commercial readiness including the hiring of our U.S. sales force primarily in the fourth quarter of 2025 and higher non-sales personnel related costs.
Liquidity and Capital Resources Our cash, cash equivalents, and investments and a summary of our borrowings and working capital as of December 31, 2024 and 2023 are summarized as follows (in millions): December 31, 2024 December 31, 2023 (In millions) Financial assets: Cash and cash equivalents $ 94.9 $ 113.0 Short-term investments 981.2 501.8 Long-term investments 145.1 40.5 Total cash, cash equivalents, and marketable securities $ 1,221.2 $ 655.3 Borrowings: Term loans, net $ 104.7 $ 68.5 RP OM Loan 123.0 — 2026 Notes, net 20.9 20.8 2027 Notes, net 531.5 528.2 Total borrowings $ 780.1 $ 617.5 Working capital: Current assets $ 1,107.9 $ 628.1 Current liabilities 179.7 102.7 Working capital $ 928.2 $ 525.4 The following table shows a summary of our cash flows for the periods set forth below (in millions): Years Ended December 31, 2024 2023 2022 (In millions) Net cash used in operating activities $ (395.9 ) $ (414.3 ) $ (299.5 ) Net cash (used in) provided by investing activities (553.1 ) 239.3 (262.1 ) Net cash provided by financing activities 930.6 221.3 516.2 Net (decrease) increase in cash, cash equivalents, and restricted cash $ (18.4 ) $ 46.3 $ (45.4 ) 39 Table of Contents Sources and Uses of Cash To date we have funded our operations and capital expenditures with proceeds primarily from private and public sales of our equity securities, royalty monetization agreement, and revenue interest agreements, strategic alliances, long-term debt, other financings and interest on investments.
Liquidity and Capital Resources Our cash, cash equivalents, and investments and a summary of our borrowings and working capital as of December 31, 2025 and 2024 are summarized as follows (in millions): December 31, 2025 December 31, 2024 (In millions) Financial assets: Cash and cash equivalents $ 122.5 $ 94.9 Short-term investments 759.7 981.2 Long-term investments 335.0 145.1 Total cash, cash equivalents, and marketable securities $ 1,217.2 $ 1,221.2 Borrowings: Term loans (including related derivative liabilities measured at fair value) $ 297.6 $ 116.0 Convertible notes, net 890.6 552.4 Liabilities related to RPI transactions measured at fair value 137.2 137.0 Total borrowings $ 1,325.4 $ 805.4 Working capital: Current assets $ 917.0 $ 1,107.9 Current liabilities 202.5 179.7 Working capital $ 714.5 $ 928.2 46 Table of Contents The following table shows a summary of our cash flows for the periods set forth below (in millions): Years Ended December 31, 2025 2024 2023 (In millions) Net cash used in operating activities $ (510.0 ) $ (395.9 ) $ (414.3 ) Net cash (used in) provided by investing activities 16.7 (553.1 ) 239.3 Net cash provided by financing activities 524.5 930.6 221.3 Total $ 31.2 $ (18.4 ) $ 46.3 Sources and Uses of Cash We funded our operations and capital expenditures with proceeds primarily from private and public sales of our equity securities, royalty monetization agreements, and revenue interest agreements, strategic alliances, long-term debt, other financings and interest on investments.
We expect to draw all available loans under the RP Multi Tranche Loan Agreement unless we are able to meet our financing requirements through more favorable funding sources.
We expect to draw Tranche 7 unless we are able to meet our financing requirements through more favorable funding sources.
Net cash provided by financing activities of $221.3 million in 2023 was due to proceeds from public offerings of common stock of $164.2 million under the Controlled Equity Offering Sales Agreement with Cantor Fitzgerald & Co discussed below and $50.0 million of additional consideration associated with the 2022 RP Aficamten Royalty Purchase Agreement which was paid to us in September 2023 and stock-based award activities. 2024 Royalty Pharma Transactions In May 2024, we entered into a series of financing agreements with affiliates of Royalty Pharma, including the RP OM Loan Agreement, the RP CK-586 RPA, the 2022 RP Multi Tranche Loan Agreement Amendment, the RP Aficamten RPA Amendment, and the RP Stock Purchase Agreement for a private placement of common stock concurrent with our underwritten public offering of common stock.
Net cash provided by financing activities of $930.6 million in 2024 was due to $250.0 million in proceeds from the 2024 RPI Transactions, $563.2 million of net proceeds from a public offering of common stock and issuances of common stock of $93.6 million under the Controlled Equity Offering Sales Agreement with Cantor Fitzgerald & Co, discussed below, and stock-based award activities. 2024 Royalty Pharma Transactions In May 2024, we entered into a series of financing agreements with affiliates of Royalty Pharma, including the RP OM Loan Agreement, the RP Ulacamten RPA, the 2022 RP Multi Tranche Loan Agreement Amendment, the RP Aficamten RPA Amendment, and the RP Stock Purchase Agreement for a private placement of common stock concurrent with our underwritten public offering of common stock. 47 Table of Contents The RP OM Loan Agreement provides for a loan in the principal amount of $100.0 million that was drawn at the closing with no remaining amounts available for disbursement.
We cannot be certain that sufficient funds will be available from such collaborators or financings when needed or on satisfactory terms. Additionally, there can be no assurance that any of our drug candidates will be accepted in the marketplace or that any future products can be developed or manufactured at an acceptable cost.
Additionally, there can be no assurance that MYQORZO or any of our drug candidates will be accepted in the marketplace or that any future products can be developed or manufactured at an acceptable cost.
We are subject to risks common to clinical-stage companies including, but not limited to, development of new drug candidates, dependence on key personnel, and the ability to obtain additional capital as needed to fund our future plans. Our liquidity will be impaired if sufficient additional capital is not available on terms acceptable to us, if at all.
Although we have one approved product at this time, we remain subject to risks common to clinical-stage companies including, but not limited to, development of new drug candidates, dependence on key personnel, and the ability to obtain additional capital as needed to fund our future plans.
Revenues in 2024, 2023, and 2022 were as follows (in millions): Years Ended December 31, Change 2024 2023 2022 2024-2023 2023-2022 (In millions) License and milestone revenues $ 15.0 $ 3.5 $ 1.0 $ 11.5 $ 2.5 Collaboration revenues 3.5 4.0 6.6 (0.5 ) (2.6 ) Realization of revenue participation right purchase agreement — — 87.0 — (87.0 ) Total revenues $ 18.5 $ 7.5 $ 94.6 $ 11.0 $ (87.1 ) License and milestone revenues recognized in 2024 were attributable to a $15.0 million non-refundable upfront payment from Corxel in the fourth quarter of 2024 in connection with a modification of the original license prior to the assignment of Corxel’s rights under our license and collaboration agreement for the development and commercialization of aficamten in China and Taiwan to Sanofi.
License and milestone revenues recognized in 2024 were attributable to a $15.0 million non-refundable upfront payment from Corxel in the fourth quarter of 2024 in connection with a modification of the original license prior to the assignment of Corxel’s rights under our license and collaboration agreement for the development and commercialization of aficamten in China and Taiwan to Sanofi.
Interest Expense Interest expense for 2024, 2023, and 2022 were as follows (in millions): Years Ended December 31, Change 2024 2023 2022 2024-2023 2023-2022 (In millions) Term loan $ 9.7 $ 5.1 $ 4.8 $ 4.6 $ 0.3 2026 Notes 1.0 1.0 3.6 — (2.6 ) 2027 Notes 22.1 22.0 10.7 0.1 11.3 Other 4.9 0.2 0.3 4.7 (0.1 ) Total interest expense $ 37.7 $ 28.3 $ 19.4 $ 9.4 $ 8.9 The components of interest expense were fairly consistent period over period in 2024 and 2023.
Interest Expense Interest expense for 2025, 2024, and 2023 were as follows (in millions): Years Ended December 31, Change 2025 2024 2023 2025-2024 2024-2023 (In millions) Term loans $ 22.3 $ 9.7 $ 5.1 $ 12.6 $ 4.6 2026 Notes 1.0 1.0 1.0 — — 2027 Notes 17.5 22.1 22.0 (4.6 ) 0.1 2031 Notes 4.7 — — 4.7 — Other 0.1 4.9 0.2 (4.8 ) 4.7 Total interest expense $ 45.6 $ 37.7 $ 28.3 $ 7.9 $ 9.4 Term loan interest increased year over year due to drawing on Tranche 4 and Tranche 5 in 2025 and incurring a full year of interest on Tranche 6 of the RP Multi Tranche Loan.
We periodically assess the amount and timing of expected royalty payments and account for any changes in such estimates on a prospective basis.
The imputed rate of interest on the RP OM Liability was 0.0% as of December 31, 2025 and approximately 0.1% as of December 31, 2024. We periodically assess the amount and timing of expected royalty payments and account for any changes in such estimates on a prospective basis.
The Sanofi Aficamten License Agreement, unless terminated earlier, will continue on a market-by-market basis until expiration of the relevant royalty term. 42 Table of Contents Japan Out-license for Aficamten In November 2024, we entered into a license and collaboration agreement with Bayer Consumer Care AG, an affiliate of Bayer AG, pursuant to which we granted to Bayer an exclusive license to develop and commercialize aficamten in Japan, subject to certain reserved development rights.
We expect royalty revenues in 2026 to be immaterial as Sanofi begins initial commercialization activities in China. 50 Table of Contents Japan Out-license for Aficamten In November 2024, we entered into a license and collaboration agreement with Bayer Consumer Care AG, an affiliate of Bayer AG, pursuant to which we granted to Bayer an exclusive license to develop and commercialize aficamten in Japan, subject to certain reserved development rights.
As of December 31, 2024, there remains $21.1 million aggregate principal amount of 2026 Notes outstanding and $540.0 million of aggregate principal amount of 2027 Notes outstanding.
As of December 31, 2025, there remains $21.1 million aggregate principal amount of 2026 Notes outstanding reflected in current liabilities, $140.5 million of aggregate principal amount of 2027 Notes outstanding reflected in long term liabilities, and $750.0 million of aggregate principal amount of 2031 Notes outstanding in long term liabilities.
Finally, we also recently announced commencement of our Phase 1 single and multiple ascending dose clinical study of CK-089, a fast skeletal muscle troponin activator with the potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired muscle function.
CK-089 is a fast skeletal muscle troponin activator with potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired muscle function.
While our significant accounting policies are described in more detail in the notes to our financial statements included in this Annual Report on Form 10-K, we believe the following accounting policies to be critical to the judgments and estimates used in the preparation of our financial statements 48 Table of Contents Fair Value of 2024 RPI transactions In May 2024, the Company entered into 2024 RPI transactions including the 2024 RP OM Loan Agreement, the RP CK-586 RPA, the RP Stock Purchase Agreement, the 2022 RP Multi Tranche Loan Agreement Amendment and the RP Aficamten RPA Amendment.
While our significant accounting policies are described in more detail in the notes to our financial statements included in this Annual Report on Form 10-K, we believe the following accounting policies to be critical to the judgments and estimates used in the preparation of our financial statements Fair Value Liabilities As permitted under Accounting Standards Codification 825, Financial Instruments, or ASC 825, the Company elected the fair value option for recognition of the liabilities related to 2024 RP OM Loan Agreement and the RP Ulacamten RPA.
Revenue Participation Right Purchase Agreements We have entered into certain revenue participation right purchase agreements for omecamtiv mecarbil, aficamten, and CK-586 with affiliates of Royalty Pharma, pursuant to which such affiliates purchased rights to royalties from certain revenue streams.
We recognized a gain on the change in the estimated fair value of the derivative liabilities of approximately $4.2 million in 2025, 57 Table of Contents Revenue Participation Right Purchase Agreements We have entered into certain revenue participation right purchase agreements for omecamtiv mecarbil, aficamten, and ulacamten with affiliates of Royalty Pharma, pursuant to which such affiliates purchased rights to royalties from certain revenue streams.
Collaboration revenues in 2024 were primarily from Corxel under our collaboration and license agreement with Corxel (now assigned to Genzyme Corporation, an affiliate of Sanofi). As of December 31, 2024 receivables of $1.5 million were recorded related to Corxel. In 2023, Collaboration revenues were primarily from Astellas for reimbursements under the Astellas FSRA Agreement.
The $15.0 million was reflected as a receivable at December 31, 2024. 53 Table of Contents Collaboration revenues in 2024 were primarily from Corxel under our collaboration and license agreement with Corxel. As of December 31, 2024 receivables of $1.5 million were recorded related to Corxel.
Overview We are 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 and/or declining.
Overview We are a biopharmaceutical company focused on discovering, developing and commercializing novel muscle activators and muscle inhibitors as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining. We have discovered and are developing muscle-directed investigational medicines that may potentially improve the healthspan of people with devastating cardiovascular and neuromuscular diseases of impaired muscle function.
Until we achieve profitable operations, we intend to continue to fund operations through payments from strategic collaborations, additional sales of equity securities, grants and other financings. We have never generated revenues from commercial sales of our drugs.
Our liquidity will be impaired if sufficient additional capital is not available on terms acceptable to us, if at all. Until we achieve profitable operations, we intend to continue to fund operations through payments from strategic collaborations, additional sales of equity securities, grants and other financings.
We review our assumptions on a regular basis and our estimates may change in the future as we refine and reassess our assumptions. 47 Table of Contents Non-cash interest expense on the liabilities related to the RP OM RPA and the RP Aficamten RPA for 2024, 2023, and 2022 was as follows (in millions): Years Ended December 31, Change 2024 2023 2022 2024-2023 2023-2022 (In millions) RP OM Liability $ 0.1 $ 3.9 $ 31.7 $ (3.8 ) $ (27.8 ) RP Aficamten Liability 48.7 25.5 — 23.2 25.5 Total non-cash interest expense recognized $ 48.8 $ 29.4 $ 31.7 $ 19.4 $ (2.3 ) Interest and Other Income, net Interest and other income, net for 2024, 2023, and 2022 consisted primarily of interest income generated from our cash, cash equivalents and investments.
Non-cash interest expense on liability related to the RP OM RPA and the RP Aficamten RPA in 2025, 2024, and 2023 were as follows (in millions): Years Ended December 31, Change 2025 2024 2023 2025-2024 2024-2023 (In millions) RP OM Liability $ 0.1 $ 0.1 $ 3.9 $ — $ (3.8 ) RP Aficamten Liability 58.2 48.7 25.5 9.5 23.2 Total non-cash interest expense recognized $ 58.3 $ 48.8 $ 29.4 $ 9.5 $ 19.4 The carrying amount of the RP Aficamten Liability is based on our estimate of the future royalties to be paid pursuant to RP Aficamten RPA over the life of the arrangement as discounted using an imputed rate of interest.
Non-cash interest expense on liabilities related to revenue participation right purchase agreements Non-cash interest expense results from the accretion of our liabilities to RPFT and RP ICAV related to the sale of future royalties under the RP OM RPA and the RP Aficamten RPA, respectively.
Debt conversion expense As a result of the partial repurchase of the 2027 Notes in the third quarter of 2025, we recorded $121.2 million in debt conversion expense, consisting of the difference between the consideration paid to the holders pursuant to the exchange agreements and the if-converted value of the 2027 Notes under the original terms. 55 Table of Contents Non-cash interest expense on liabilities related to revenue participation right purchase agreements Non-cash interest expense results from the accretion of our liabilities to RPFT and RP ICAV related to the sale of future royalties under the RP OM RPA and the RP Aficamten RPA, respectively.
The imputed rate of interest on the RP Aficamten Liability was approximately 23.5% as of December 31, 2024 and 24.8% as of December 31, 2023. The imputed rate of interest on the RP OM Liability was approximately 0.1% as of December 31, 2024 and 0.1% as of December 31, 2023.
The imputed rate of interest on the RP Aficamten Liability was approximately 22.6% as of December 31, 2025 and 23.5% as of December 31, 2024. The imputed rate of interest on the RP OM Liability is reassessed periodically, and we have adopted an accounting policy to not reduce the effective borrowing rate below 0%.
As a result of the partial repurchase of the 2026 Notes, we recorded an inducement loss of $22.2 million, consisting of the difference between the consideration to the holders pursuant to the exchange agreements and the if-converted value of the 2026 Notes under the original terms.
This resulted in recording debt conversion expense in the third quarter of 2025 of $121.2 million, consisting of the difference between the consideration to the holders pursuant to the exchange agreements and the if-converted value of the 2027 Notes under the original terms.
The total change in the estimated fair value liabilities for 2024, was primarily due to a decrease in the discount rates used in the measurement of the 2024 RP OM Loan Agreement and the RP CK-586 RPA as of December 31, 2024, compared to June 30, 2024.
The total change in the estimated fair value liabilities for 2025, was primarily driven by changes in the discount rates used in the valuation of the 2024 RP OM Loan and the derivatives associated with the RP Multi Tranche Loan Agreement.
We are obliged to draw at least $50 million of either the tranche 4 or tranche 5 facility by November 24, 2025. The remaining $175 million tranche 7 loan is subject to conditions related to the approval of our NDA for aficamten in patients with oHCM on or prior to December 31, 2025.
Under the RP Multi Tranche Loan Agreement, we have drawn $275 million as of December 31, 2025. The remaining $175 million tranche 7 loan is also available to us now that the conditions for reimbursement, namely approval of our NDA for aficamten in patients with oHCM on or prior to December 31, 2025, have been met.
We expect to fulfill and satisfy the associated performance obligation in the first half of 2025. 45 Table of Contents Research and Development Expenses We incur research and development expenses associated with both partnered and our own research activities, which we finance from our own cash-on-hand, financing arrangements with third parties, and reimbursement from our collaboration partners Research and development expenses related to any development activities we elect to fund consist primarily of employee compensation, supplies and materials, costs for consultants and contract research and manufacturing, facilities costs and depreciation of equipment.
Research and Development Expenses We incur research and development expenses associated with both partnered and our own research activities, which we finance from our own cash-on-hand, financing arrangements with third parties, and reimbursement from our collaboration partners.
We expect that general and administrative expenses will increase in 2025. We have submitted an NDA to FDA for aficamten for the treatment of oHCM. Accordingly, we will be incurring additional expenses for commercial readiness activities, included, but not limited to, the hiring and training of a field sales force, the implementation of compliance systems, sales and marketing expenses.
We expect sales, general and administrative expenses to increase significantly in 2026. With the approval of MYQORZO in the United States, we expect to incur additional expenses for commercial activities, included, but not limited to, the full year impact of the U.S. sales force, training and education, the implementation of compliance systems, patient support programs, sales and marketing expenses.
In addition. we submitted an MAA to EMA for aficamten for the treatment of oHCM in the fourth quarter of 2024, and therefore, we will be incurring similar expenses for commercial readiness activities in Europe but with additional expenses for the establishment of a corporate infrastructure to enable commercialization activities in key European markets.
In addition, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion recommending marketing authorization in the European Union for MYQORZO for the treatment of adults with symptomatic oHCM, (New York Heart Association class II-III), and therefore, we expect to incur similar expenses for commercial readiness activities in Europe but with additional expenses for the establishment of a corporate infrastructure to enable commercialization activities in key European markets, beginning in Germany with other major European markets to follow.
A significant portion of these anticipated commercial readiness expenses in the United States and Europe are not expenses that have been reflected in our financial statements for previous periods. 43 Table of Contents In future periods, we also expect to incur substantial costs as we continue to expand our research programs and related research and development activities, including for the conduct of our on-going clinical trials for aficamten, omecamtiv mecarbil, CK-586 and CK-089.
In February 2026, the European Commission approved MYQORZO® (aficamten), 5 mg, 10 mg, 15 mg and 20 mg tablets for the treatment of symptomatic (New York Heart Association, NYHA, class II-III) obstructive hypertrophic cardiomyopathy in adult patients, which means that we will significantly increase commercial readiness activities in Europe, initially in Germany, with commercial readiness activities in other major European countries to follow, 51 Table of Contents In future periods, we also expect to incur substantial costs as we expand our research programs and continue development activities, including for the conduct of our on-going clinical trials for aficamten, omecamtiv mecarbil, ulacamten and CK-089.
As of December 31, 2024, the discount rates that we used in the measurement of the 2024 RP OM Loan Agreement and the RP CK-586 RPA decreased compared to June 30, 2024, which resulted in an increase in the estimated fair value of the liabilities and the recognition of a loss on the change in the fair value of liabilities related to RPI transactions in our consolidated statement of operations of approximately $19.6 million in 2024.
As products containing omecamtiv mecarbil and ulacamten have not yet been commercialized, the estimates are highly subjective. We recognized a loss on the change in the estimated fair value of liabilities of approximately $0.2 million in 2025, primarily due to changes in the discount rates used to measure the 2024 RP OM Loan Agreement and the RP Ulacamten RPA.
Future Uses of Cash We expect that general and administrative expenses will significantly increase in 2025. We have submitted an NDA to FDA for aficamten for the treatment of oHCM, which was accepted for filing with a PDUFA target action date of September 26, 2025.
Future Uses of Cash We expect that general and administrative expenses will significantly increase in 2026. In December 2025, MYQORZO was approved by the FDA, and accordingly, our sales and marketing expenses will increase significantly as we engage in commercialization activities in the United States.
Removed
We have discovered and are developing muscle-directed investigational medicines that may potentially improve the healthspan of people with devastating cardiovascular and neuromuscular diseases of impaired muscle function.
Added
Our first commercial product is MYQORZO™ (aficamten), 5 mg, 10 mg, 15 mg, and 20 mg tablets which the FDA approved in December 2025. MYQORZO has since been approved in both the European Union and China. MYQORZO is an allosteric and reversible inhibitor of cardiac myosin motor activity.
Removed
Our clinical-stage drug candidates are: (i) aficamten, a next-in-class cardiac myosin inhibitor, (ii) omecamtiv mecarbil, a novel cardiac myosin activator, (iii) CK-586, an additional cardiac myosin inhibitor, and (iv) CK-089, a novel fast skeletal troponin activator. For further information regarding our business, refer to Part I, Item 1 (Business) of this Annual Report on Form 10-K.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

9 edited+1 added−0 removed1 unchanged
Biggest changeWe do not record our convertible debt at fair value but present the fair value for disclosure purposes (see Note 7 to our Consolidated Financial Statements). As of December 31, 2024, the fair value of the 2026 Notes and 2027 Notes was estimated at $95.1 million and $651.7 million using quoted market prices. 50 Table of Contents
Biggest changeThe convertible notes issued at fixed interest rates are exposed to fluctuations in fair value resulting from changes in market price and interest rates. We do not record our convertible debt at fair value but present the fair value for disclosure purposes (See Note 7, "Debt," to our Consolidated Financial Statements for further information).
In addition, we have elected the fair value option for certain liabilities. The fair value of the liabilities related to 2024 RP OM Loan Agreement, the RP CK-586 RPA, and the derivatives of the RP Multi Tranche Loan Agreement will increase as market interest rates decrease.
In addition, we have elected the fair value option for certain liabilities. The fair value of the liabilities related to 2024 RP OM Loan Agreement, the RP Ulacamten RPA, and the derivatives of the RP Multi Tranche Loan Agreement will increase as market interest rates decrease.
We have not been exposed to, nor do we anticipate being exposed to, material risks due to changes in interest rates. A hypothetical 1% increase in market interest rates would result in a decline in the value of our investments of approximately $6.1 million and $2.4 million as of December 31, 2024 and December 31, 2023, respectively.
We have not been exposed to, nor do we anticipate being exposed to, material risks due to changes in interest rates. A hypothetical 1% increase in market interest rates would result in a decline in the value of our investments of approximately $6.0 million and $6.1 million as of December 31, 2025 and December 31, 2024, respectively.
For example, a hypothetical 1% decrease in the discount rates used to measure the 2024 RP OM Loan Agreement, the RP CK-586 RPA, and the derivatives of the RP Multi Tranche Loan Agreement would result an increase in the fair value, and the recognition of a loss, of approximately $5.4 million as of December 31, 2024.
For example, a hypothetical 1% decrease in the discount rates used to measure the 2024 RP OM Loan Agreement, the RP Ulacamten RPA, and the derivatives of the RP Multi Tranche Loan Agreement would result in an increase in the fair value, and the recognition of a loss, of approximately $4.3 million as of December 31, 2025.
In 2024, we recognized a loss on the change in the estimated fair value of liabilities of approximately $19.6 million, primarily due to changes in the discount rates used to measure the 2024 RP OM Loan Agreement and the RP CK-586 RPA.
In 2025 and 2024, we recognized a loss on the change in the estimated fair value of liabilities of approximately $0.2 million and $19.6 million, respectively, primarily due to changes in the discount rates used to measure the 2024 RP OM Loan Agreement and the RP Ulacamten RPA.
As of December 31, 2024, our cash and investments totaled $1221.1 million, comprising U.S. Treasury securities, U.S. and non-U.S. government agency bonds, commercial paper, a global portfolio of corporate debt, money market funds, and repurchase agreements backed by U.S. Treasury securities. Our investments are subject to interest rate risk and could fall in value if market interest rates increase.
Treasury securities, U.S. and non-U.S. government agency bonds, commercial paper, a global portfolio of corporate debt, money market funds, and repurchase agreements backed by U.S. Treasury securities. 58 Table of Contents Our investments are subject to interest rate risk and could fall in value if market interest rates increase.
ITEM 7A. QUANTITATIVE AND QUALITA TIVE DISCLOSURES ABOUT MARKET RISK We are exposed to market risks in the ordinary course of our business. These risks primarily include risk related to interest rate sensitivities. Interest Rate Risk We are exposed to market risk related to changes in interest rates.
ITEM 7A. QUANTITATIVE AND QUALITA TIVE DISCLOSURES ABOUT MARKET RISK We are exposed to market risks in the ordinary course of our business. These risks primarily include risk related to interest rate sensitivities. We are exposed to market risk related to changes in interest rates. As of December 31, 2025, our cash and investments totaled $1,217.3 million comprising U.S.
The discount rates ranged from 10% to 18% as of December 31, 2024, compared to 14% to 18% as of June 30, 2024, resulting in an increase in the estimated fair value of the liabilities.
The discount rates ranged from 10% to 18% as of December 31, 2025 and 10% to 18% as of December 31, 2024.
We had $21.1 million under 2026 Notes with a fixed rate of 4.0% and $540.0 million under 2027 Notes with a fixed rate of 3.5% outstanding as of December 31, 2024. The convertible notes issued at fixed interest rates are exposed to fluctuations in fair value resulting from changes in market price and interest rates.
We had $21.1 million under 2026 Notes with a fixed rate of 4.0%, $140.5 million under 2027 Notes with a fixed rate of 3.5% and $750.0 million under 2031 Notes with a fixed rate of 1.8% outstanding as of December 31, 2025.
Added
As of December 31, 2025, the fair value of the 2026 Notes, 2027 Notes and 2031 Notes was estimated at $127.8 million, $200.0 million and $919.7 million using quoted market prices. 59 Table of Contents

Other CYTK 10-K year-over-year comparisons