Full Press Release Details
Forward-Looking Statements This presentation contains forward-looking
statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). Cytokinetics, Incorporated ("Cytokinetics" or the "Company") disclaims any intent or obligation to update these
forward-looking statements and claims the protection of the Act's Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements express or implied related to Cytokinetics' research and
development and commercial readiness activities, including the initiation, conduct, design, enrollment, progress, continuation, completion, timing and results of clinical trials, projections regarding growing prevalence, low survival rates and
market opportunity in heart failure, hypertrophic cardiomyopathy (HCM) or heart failure with preserved ejection fraction (HFpEF); projections regarding the size of the addressable patient population for aficamten, omecamtiv mecarbil, CK-136, CK-586
or any of our other drug candidates; Cytokinetics' commercial readiness for aficamten or omecamtiv mecarbil; our ability to submit a new drug application for aficamten with FDA in the third quarter 2024 or a marketing authorization application
with EMA in the fourth quarter 2024, the likelihood and/or timing of regulatory approval for our planned new drug application for aficamten, omecamtiv mecarbil or any future new drug application for any of our other drug candidates or the
anticipated timing of any interactions with FDA, EMA or any other regulatory authorities in connection thereto; the timing of completion of MAPLE-HCM, ACACIA-HCM, CEDAR-HCM or any of our other clinical trials, the efficacy or safety of aficamten,
omecamtiv mecarbil, CK-136, CK-586 or any of our other drug candidates, our ability to fully enroll or to announce the results of any of our clinical trials by any particular date; the properties, potential benefits and commercial potential of
aficamten, omecamtiv mecarbil, CK-136, CK-586 or any of Cytokinetics' other drug candidates. Such statements are based on management's current expectations; but actual results may differ materially due to various risks and uncertainties,
including, but not limited to, potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics' drug candidates that could
slow or prevent clinical development or product approval, including risks that current and past results of clinical trials or preclinical studies may not be indicative of future clinical trial results, patient enrollment for or conduct of clinical
trials may be difficult or delayed, Cytokinetics' drug candidates may have adverse side effects or inadequate therapeutic efficacy, the FDA or foreign regulatory agencies may delay or limit Cytokinetics' ability to conduct clinical
trials, and Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; Cytokinetics may incur unanticipated research, development and other costs or be unable to obtain financing necessary to
conduct development of its products; standards of care may change, rendering Cytokinetics' drug candidates obsolete; and competitive products or alternative therapies may be developed by others for the treatment of indications
Cytokinetics' drug candidates and potential drug candidates may target. These forward-looking statements speak only as of the date they are made, and Cytokinetics undertakes no obligation to subsequently update any such statement, except as
required by law. For further information regarding these and other risks related to Cytokinetics' business, investors should consult Cytokinetics' filings with the Securities and Exchange Commission (the "SEC"). Disclaimer
This presentation concerns drug candidates that are under clinical investigation, and which have not yet been approved by the U.S. Food and Drug Administration. These are currently limited by federal law to investigational use, and no representation
is made as to their safety or effectiveness for the purposes for which they are being investigated. The assumptions used in the preparation of this presentation, although considered reasonable by us at the time of preparation, may prove to be
incorrect. You are cautioned that the information is based on assumptions as to many factors and that actual results may vary from the results projected and such variations may be material. Accordingly, you should not place undue reliance on any
forward-looking statements contained herein or rely on them as predictions of future events. The trademarks, trade names and service marks appearing in this presentation are the property of their respective owners. Certain information contained in
this presentation relate to or are based on studies, publications and other data obtained from third-party sources as well as our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this
presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. 2
Structured Financing Transaction with Royalty Pharma Four Separate
Components Providing $250M upon Closing; up to $575M Total Royalty Pharma R&D Partnership, Royalty Monetization, Long-term Debt and Equity Investment Diversifies access to capital to support potential commercial launch and monetize/advance
myosin focused pipeline CK-586: R&D Funding Aficamten: Potential Commercial Launch Omecamtiv Mecarbil: R&D Funding Capital Cytokinetics to receive $50M upfront in exchange Cytokinetics to receive $100M in upfront capital for 1.0% royalty on
net sales of CK-586 to fund confirmatory Phase 3 clinical trial Cytokinetics to receive $50M upfront capital Royalty Pharma will have option to invest up to If new Phase 3 clinical trial is positive and FDA Cytokinetics eligible to draw additional
$175M additional $150M for Phase 3 development approval is received within specified time frames, within 12 months of FDA approval for oHCM Royalty Pharma will receive 1.0x milestone If Royalty Pharma opts in to Phase 3 funding, it will Capital
repayable over 10 years in quarterly payment and incremental 2.0% royalty on global be eligible to receive up to 0.75x milestone upon installments (totaling 1.9x) net sales and/or fixed quarterly payments certain regulatory approvals and 4.5%
royalty on global net sales Otherwise Cytokinetics required to repay loan in fixed quarterly payments (totaling 2.275x - If Royalty Pharma does not opt in to Phase 3 2.375x) over either 18 or 22 quarters funding, eligible for 1% royalty on
global net sales Royalty Pharma's royalty on aficamten was restructured so that Royalty Pharma will now receive 4.5% up to $5.0 billion of annual net sales of aficamten and 1% above $5.0 billion of annual net sales compared to the prior 4.5%
up to $1.0 billion of annual net sales and 3.5% above $1.0 billion of annual net sales Royalty Pharma to purchase $50M of Cytokinetics' common stock, at Cytokinetics' option, subject to certain conditions 3
Achieve regulatory approvals for drugs arising from our pipeline Build
commercial capabilities to market and sell our medicines reflective of their innovation and value Generate sustainable and growing Our vision is to be the revenues from product sales leading muscle biology biopharma company that meaningfully
improves the lives of patients with diseases of impaired muscle function through access to our pioneering medicines Leading with Science, Expand our development programs As always, we will support disease advocacy groups elevating the patient voice
and live by our values of Expand our discovery platform to muscle integrity, fairness and compassion in all that we do. energetics, growth and metabolism Be the science-driven company people want to join and partner with 4
Sarcomere Directed Drug Development The sarcomere is a molecular
structure found in skeletal and cardiac muscle that enables myocytes to contract and generate force ACTIVATE INHIBIT INHIBIT ACTIVATE Troponin Omecamtiv CK-136 Aficamten CK-586 Mecarbil (Cardiac) (Cardiac) (Cardiac) Myosin (Cardiac) Tropomyosin
Actin Calcium Thin filament Myosin ATP head Myosin lever arm Thick filament 5 5
A Commitment to Muscle-Directed Cardiac Medicines Building a specialty
cardiology franchise anchored by aficamten Protein Target Therapeutic Area Drug Candidate Research Pre-Clinical Phase 1 Phase 2 Phase 3 Approval Preparing for regulatory oHCM Aficamten submissions in 2H 2024 Myosin oHCM Aficamten (First-line*)
Pediatric oHCM Aficamten Myosin-Targeted Therapy nHCM Aficamten HFpEF CK-586 Omecamtiv HFrEF Mecarbil Troponin Troponin- Heart Failure, CK-136 Targeted Therapy other Muscle Biology Other Biology Research Directed *Pending results from MAPLE-HCM, an
ongoing Phase 3 clinical trial evaluating for the potential superiority of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM. All drug candidates above are investigational products and are not approved
as safe or effective for any indication. 6
Building a Specialty Cardiology Franchise Anchored by Aficamten
Potential patient market for specialty cardiology franchise strategy Myosin-Targeted Therapies Myosin Troponin CK-136 Troponin-Targeted Therapies Heart failure 3 800K Potential to HFpEF + EF 65% expand to in 2030 subsets of heart Omecamtiv
failure Mecarbil HFrEF 1,2 250-400K Potential in nHCM patients HFrEF in Europe in 2027 CK-586 1,2 450-700K HFpEF oHCM patients With nHCM as a in 2025-2026 proxy, potential to expand into Aficamten HFpEF nHCM All drug candidates above are
investigational products and are not ACACIA-HCM approved as safe or effective for any indication. Aficamten Potential to 1. Cardiovascular Research Group: CVrg Market Strategies: Heart Failure, p 48, Q4 2022; Maron BJ: et al: Prevalence of
Hypertrophic Cardiomyopathy In Aficamten expand into A General Population of Young Adults, Circulation 1995;92;785-789; oHCM Estimated nHCM Semsarian C. et al: New Perspectives on the Prevalence of Hypertrophic oHCM MAPLE-HCM Cardiomyopathy, J. Am,
Coll. Cardiol. 2015; 65: 1249-1254; prevalence in 2. Lu DY et al: Clinical Outcomes in Patients With Nonobstructive, Labile, and SEQUOIA-HCM Potential to US only Obstructive Hypertrophic Cardiomyopathy. J. Am. Heart Assoc. 2018;7:1-11 First
potential expand to 3. Dunlay et al (2012) Circ Heart Fail. 2012 Nov;5(6):720-6. doi: 10.1161/CIRCHEARTFAILURE.111.966366. Epub 2012 Aug 30. indication first-line treatment 7
Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients 1 Prevalence
of HCM 700K to 1.1M ~65% ~35% 1,3 1,3 Diagnosed HCM oHCM nHCM US US 2 ~300K oHCM Prevalence nHCM Prevalence 1,3 1,3 450-700K 250-400K Diagnosed oHCM Diagnosed nHCM 2,3 2,3 ~200K ~100K Sympt. Sympt. 4,5 4,5 >130K >40K Projections and forecasts
for illustration. 1. Cardiovascular Research Group: CVrg Market Strategies: Heart Failure, p 48, Q4 2022; Maron BJ: et al:: Prevalence of Hypertrophic Cardiomyopathy In A General Population of Young Adults, Circulation 1995;92;785-789; Semsarian C.
et al: New Perspectives on the Prevalence of Hypertrophic Cardiomyopathy, J. Am, Coll. Cardiol. 2015; 65: 1249-1254; 2. DoF: SHA; Symphony PTD (Patient Transaction Data): Includes patients diagnosed since 2016 and having any HC transaction in the
claims data universe in the last year June 2022-May 2023); 3. Lu DY et al: Clinical Outcomes in Patients With Nonobstructive, Labile, and Obstructive Hypertrophic Cardiomyopathy. J. Am. Heart Assoc.2018;7:1-11 4. DoF: SHA Symphony PTD (Patient
Transaction Data) includes any patients with symptoms in the last 2 years: angina, dyspnea, fatigue, palpitations, syncope, tachycardia; and/or treatments in the past 2 years: bb, ccb, dyso, ralo, Camzyos; 5. DoF Primary market research: 443 HCPs
treating HCM - % of nHCM patients not considered under control with current SOC. 9
Aficamten: Mechanism of Action Aficamten stabilized myosin in the
released post-powerstroke state unable to hydrolyze ATP "Fewer hands pulling on the rope" Before Aficamten After Aficamten Mechanochemical domain ATP AF Post-Powerstroke State Actin sliding Actin sliding Aficamten is an investigational
drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. 10
Aficamten: Aspirational Target Profile Potential next-in-class cardiac
myosin inhibitor No clinically Rapid Rapid Speed to Predictable No meaningful onset reversibility optimal dose dose response teratogenicity P450 liabilities Aspirational information. Aficamten is an investigational drug and is not approved by any
regulatory agency. Its safety and efficacy have not been established. 11
Aficamten: Clinical Development Plan for HCM Phase 2 Phase 1 Phase 3
SAD & MAD REDWOOD-HCM Cohorts 1-3 SEQUOIA-HCM Healthy obstructive HCM obstructive HCM Target Volunteers Placebo controlled; echocardiography endpoints Pivotal trial with exercise endpoint (peak VO2) IND Filed NDA Potential for Well tolerated
dose Improved LVOT gradient approval based with desired PD effects on results from MAPLE-HCM SEQUOIA-HCM obstructive HCM Phase 1 Aficamten monotherapy vs. Metoprolol monotherapy Study in healthy Japanese REDWOOD-HCM Cohort 4 ACACIA-HCM volunteers
non-obstructive HCM non-obstructive HCM Proof of activity Pivotal trial in patients with symptomatic nHCM KEY Complete CEDAR-HCM Pediatric obstructive HCM Ongoing Trial in a pediatric population with symptomatic oHCM Not Yet Started FOREST-HCM
obstructive & non-obstructive HCM Extension study for long-term safety & efficacy Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. 12
SEQUOIA-HCM: Phase 3 Trial Primary endpoint: Change in pVO by 2 CPET
from baseline to Week 24 Patients with Aficamten + SoC oHCM treated 1 with SOC with Secondary objectives include measuring post-Valsalva peak LVOT-G change in KCCQ & improvement in 1 50 mmHg & NYHA class II/III Placebo + SoC NYHA
class at week 12 and 24 Enrolled 282 patients treated with Study Visits standard of care with: Screen D1 W2 W4 W6 W8 W12 W16 W20 W24 W28 - resting LVOT-G 30 mmHg, * * * * Echocardiogram - post-Valsalva LVOT-G 50 mmHg, CPET - NYHA Class
II or III, KCCQ - exercise performance <80% predicted NYHA Echocardiogram Individualized dose up-titration based on Dose Options (Dose optimization completed by Week 8) echocardiography: LVEF 55%, post-Valsalva LVOT-G 30 mmHg 5 mg
QD 10 mg QD 15 mg QD 20 mg QD SOC: standard of care * Focused echocardiogram 13 Screening Randomization End of Study
SEQUOIA-HCM: Baseline Characteristics Baseline characteristics reflect
highly symptomatic patient population with reduced exercise capacity Aficamten Placebo Aficamten Placebo n=142 n=140 n=142 n=140 Background HCM therapy, n (%) Age, y 59.2 12.6 59.0 13.4 Beta-blocker 86 (60.6) 87 (62.1) Female sex, n
(%) 56 (39.4) 59 (42.1) Significant symptom Calcium channel blocker 45 (31.7) 36 (25.7) Race, n (%) burden despite Disopyramide 16 (11.3) 20 (14.3) background therapy White 108 (76.1) 115 (82.1) None 19 (13.4) 22 (15.7) Geographic region, n
(%) KCCQ-CSS 76 18 74 18 61% of patients on North America 49 (34.5) 45 (32.1) NYHA FC, n (%) beta-blockers China 24 (16.9) 22 (15.7) II 108 (76.1) 106 (75.7) Europe and Israel 69 (48.6) 73 (52.1) III/IV 34 (23.9) 34 (24.3)
Baseline pVO 2 Medical history, n (%) Median NT-proBNP (IQR), pg/mL 818 (377-1630) 692 (335-1795) reflects patient Hypertension 75 (52.8) 70 (50.0) population with Median hs-cTnl (IQR), ng/L 12.9 (7.6-33.6) 11.5
(7.7-25.0) Paroxysmal atrial fibrillation 21 (14.8) 20 (14.3) reduced exercise Echocardiographic parameters Permanent atrial fibrillation 2 (1.4) 1 (0.7) capacity Valsalva LVOT-G, mmHg 82.9 32 83.3 33 CPET Resting LVOT-G, mmHg
54.8 27 55.3 32 pVO (mL/kg/min) 18.5 (4.5) 18.6 (4.5) 2 LVEF, % 74.8 5.5 74.8 6.3 Percent of predicted pVO (%) 58 (13) 57 (12) Maximal LV wall thickness, mm 20.7 3.0 21.0 3.0 2 Values are the mean SD
unless otherwise indicated. Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. Maron M. "Aficamten for the Treatment of Symptomatic Obstructive Hypertrophic
Cardiomyopathy". ESC Heart Failure 2024. 14
SEQUOIA-HCM: Dosing Mean SD, n (%), or median Placebo 5 mg 10 mg
15 mg 20 mg (IQR) n=140 n=5 n=18 n=49 n=68 Aficamten dose at Week 8 % per treatment group 100% 3.5% 12.7% 34.5% 47.9% (end of titration) Background HCM therapy Beta-blocker 87 (62.1) 5 (100.0) 10 (55.6) 31 (63.3) 40 (58.8) 3% Calcium channel blocker
36 (25.7) 1 (20.0) 3 (16.7) 17 (34.7) 24 (35.3) 13% Disopyramide 20 (14.3) 1 (20.0) 5 (27.8) 3 (6.1) 7 (10.3) Baseline study assessments KCCQ-CSS 74 18 68 26 75 19 77 20 75 17 NYHA class II 106 (75.7) 3 (60.0) 16
(88.9) 33 (67.3) 54 (79.4) 49% 5 mg 692 1133 338 871 962 NT-proBNP, pg/mL (335, 1795) (992, 1475) (283, 674) (428, 1505) (511, 2085) 10 mg hs-cTnI, ng/L 12 (8, 25) 12 (6, 234) 10 (5, 17) 13 (7, 24) 16 (8, 38) 35% 15 mg pVO , mL/kg/min 18.6
4.5 18.7 2.9 18.6 3.9 18.2 4.1 18.3 4.9 2 20 mg Echocardiographic parameters (core laboratory) LVEF at baseline, % 75 6 71 12 76 5 75 5 75 5 Peak LVOT-G at rest 55 32 29 13
45 21 56 24 58 30 There were no differences in age, sex, ethnicity, body mass index, or Peak LVOT-G post-Valsalva 83 33 51 24 71 29 84 26 88 35 comorbidities (diabetes, hypertension or AF)
between dose groups Left ventricular MWT, cm 2.10 0.30 2.42 0.74 1.94 0.22 2.04 0.26 2.11 0.28 Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not
been established. hs-cTnl, high-sensitive cardiac troponin; IQR, interquartile range; KCCQ-CSS, Kansas City Cardiomyopathy Questionnaire-Clinical Summary score; MWT, maximal wall thickness; NT-proBNP, N-terminal pro b-type natriuretic peptide; NYHA,
New York Heart Association. Coats CJ. "Dosing and Safety Profile of Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy". ESC Heart Failure 2024. 15
SEQUOIA-HCM: Primary Endpoint Significant improvement in exercise
capacity compared to placebo Results presented at Heart Failure 2024 and published in NEJM Absolute Change from Baseline to Week 24 LS mean Change from Baseline to Week 24 P=0.000002 Aficamten 2.5 Placebo 21 2.0 1.5 Data are mean and 95% CI 20 1.0
LS mean difference (SE) vs placebo: 1.74 mL/kg/min (0.36) 19 0.5 pVO = 0.0 ml/kg/min 2 pVO = 0.0 ml/kg/min 2 0.0 18 0.5 Placebo Aficamten Baseline Week 24 Aficamten is an investigational drug and is not approved by any regulatory
agency. Its safety and efficacy have not been established. Maron M. "Aficamten for the Treatment of Symptomatic Obstructive Hypertrophic Cardiomyopathy". ESC Heart Failure 2024. 16 pVO (mL/kg/min) 2 pVO (mL/kg/min) 2
SEQUOIA-HCM: Subgroup Analysis Results consistent across all
prespecified subgroups including patients receiving or not receiving background beta-blockers Mean difference Mean difference n Aficamten Placebo n Aficamten Placebo (95% CI) (95% CI) (Afi/Plb) LS mean LS mean LS mean LS mean (Afi/Plb) Age Baseline
NT-proBNP (median) <65 y 85/84 2.4 0.4 2.0 (1.1, 2.8) 788 pg/mL 66/73 2.2 0.6 1.7 (0.7, 2.7) 65 y 57/56 0.9 0.5 1.4 (0.3, 2.5) > 788 pg/mL 73/65 1.4 0.6 2.0 (1.0, 2.9) Sex CPET Modality Male 86/81 2.5 0.7 1.8 (0.9,
2.7) Treadmill 78/77 2.5 0.2 2.3 (1.4, 3.2) Female 56/59 Bicycle 0.6 0.8 1.4 (0.4, 2.5) 64/63 0.9 0.1 1.0 ( 0.0, 2.1) Baseline BMI Baseline Median pVO 2 2 <30 kg/m 97/94 1.9 0.1 1.8 (1.0, 2.7) 18.4 mL/kg/min 1.5