Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (December 2024)
60 slides from Cytokinetics's investor presentation, December 2024
Slide 1: Empowering muscle, empowering lives
EMPOWERING muscle EMPOWERING lives
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act's Safe Ha
Slide 3: Our Mission
Our Mission To bring forward new medicines to improve the healthspan of people with devastating cardiovascular and neuromuscular diseases of impaired muscle function. 3
Slide 4: Leading with Science, Pioneering Medicines
Achieve regulatory approvals for drugs arising from our pipeline Build commercial capabilities to market and sell our medicines reflective of their innovation and value Our vision is to be the Generate sustainable and growing revenues from product sales leading muscle biology biopharma company that
Slide 5: A Commitment to Muscle-Directed Cardiac Medicines
A Commitment to Muscle-Directed Cardiac Medicines Protein Target Therapeutic Area Drug Candidate Research Pre-Clinical Phase 1 Phase 2 Phase 3 Approval U.S. PDUFA date of 9/26/25 oHCM Aficamten China NDA & EU MAA submitted Myosin oHCM Aficamten (First-line*) Pediatric oHCM Aficamten Myosin-Targeted
Slide 6: Strong Financial Position
Strong Financial Position Strengthened balance sheet & access to capital to execute launch & advance R&D pipeline September 30, 2024 ~$1.3B in cash, cash equivalents and investments Further access to capital through term loans with Access up to $350M in term loans* Royalty Pharma (RP) Add’l $500M RP
Slide 7: Myosin Platform Fuels Multiple Milestones and Increased Value
Myosin Platform Fuels Multiple Milestones and Increased Value Potential Results FDA Approval Aficamten For illustrative purposes only Aficamten SEQUOIA-HCM oHCM Enhancing Potential Results Approval shareholder Emerging Aficamten value Monotherapy U.S. PDUFA date of September 26, 2025, Pipeline MAPLE
Slide 8: Cytokinetics Poised to Compete in the Specialty Cardiology Business
Cytokinetics Poised to Compete in the Specialty Cardiology Business Potential for high return on investment Broad Cardiology Specialty Cardiology Example Therapies Heart failure, cholesterol, blood thinner HCM, TTR amyloidosis Prescribers Broad: Cardiologists, PCPs (50K+) Concentrated: Subset of car
Slide 9: Addressing Difficult to Treat Populations Within Heart Failure
Addressing Difficult to Treat Populations Within Heart Failure Specialty cardiology franchise strategy applies to markets with similar characteristics HFrEF HFpEF HCM Severely Supranormal EF reduced EF Opportunity for aficamten as Addressing underserved segment of HF Expanding into adjacent populati
Slide 10: Building a Specialty Cardiology Franchise Anchored by Aficamten
Building a Specialty Cardiology Franchise Anchored by Aficamten Potential patient market for specialty cardiology franchise strategy Myosin Myosin-Targeted Therapies 800K4 HFpEF + EF ≥ 65% in 2030 ~840K3 HFrEF + EF <30% in 2029 CK-586 HFpEF With nHCM as a 250-400K1,2 proxy, potential to nHCM patient
Slide 11: Aficamten
Aficamten G Aficamten is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) Cytokinetics’ or any regulatory agency. The safety and effectiveness of this product has not been established. W
Slide 12: Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients
Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients US Prevalence of HCM1 700K to 1.1M ~65% ~35% US oHCM1,3 nHCM1,3 USDiagnosed HCM oHCM Prevalence ~300K2 nHCM Prevalence 450-700K1,3 250-400K1,3 Diagnosed oHCM Diagnosed nHCM ~200K2,3 ~100K2,3 Sympt. Sympt. >130K4,5 >40K4,5 Projections and fo
Slide 13: Aficamten: Aspirational Target Profile
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 no
Slide 14: SEQUOIA-HCM: Phase 3 Trial
SEQUOIA-HCM: Phase 3 Trial Primary endpoint: Change in pVO2 by CPET from baseline to Week 24 Randomization Aficamten + SoC End of Study Patients with Screening oHCM treated Secondary objectives include measuring with SOC with post-Valsalva 1 change in KCCQ & improvement in peak LVOT-G ≥50 mmHg & 1 N
Slide 15: SEQUOIA-HCM: Baseline Characteristics
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 Age, y 59.2 ± 12.6 59.0 ± 13.4 Background HCM therapy, n (%) Beta-blocker 86 (60.6) 87 (62.1) • Sign
Slide 16: SEQUOIA-HCM: Primary Endpoint
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 Aficamten 2.5 P=0.000002 Placebo 21 2.0 ΔpVO2 (mL/kg/min) pVO2
Slide 17: SEQUOIA-HCM: Subgroup Analysis
SEQUOIA-HCM: Subgroup Analysis Results consistent across all prespecified subgroups including patients receiving or not receiving background beta-blockers n Aficamten Placebo Mean difference n Aficamten Placebo Mean difference (Afi/Plb) LS mean LS mean (95% CI) (Afi/Plb) LS mean LS mean (95% CI) Age
Slide 18: SEQUOIA-HCM: Secondary Endpoints
SEQUOIA-HCM: Secondary Endpoints Statistically significant improvements in all 10 pre-specified secondary endpoints Endpoints P value Primary Endpoint pVO2 change from baseline to Week 24 <0.0001 Secondary Endpoints 1. KCCQ-CSS change from baseline to Week 24 <0.0001 2. NYHA Class Improvement by at
Slide 19: SEQUOIA-HCM: Secondary & Exploratory Endpoints
SEQUOIA-HCM: Secondary & Exploratory Endpoints Significant improvement in gradients by ~60% with no significant adverse change in LVEF LS mean difference: Resting LVOT-G Valsalva LVOT-G - 50 mmHg P<0.001 P<0.001 100 100 90 90 Resting LVOT-G (mmHg) Valsalva LVOT-G (mmHg) 80 80 70 70 60 60 50 50 40 40
Slide 20: SEQUOIA-HCM: Secondary & Exploratory Endpoints
SEQUOIA-HCM: Secondary & Exploratory Endpoints Significant improvement in patient symptom burden and quality of life KCCQ-OSS2 ≥1 NYHA FC Improvement1 P<0.001 SAQ7-SS2 P<0.001 Proportion of patients with ≥1 100 NYHA FC improvement (%) 90 80 58% 70 60 50 40 30 20 10 0 2 4 6 8 12 16 20 24 Weeks Mean d
Slide 21: SEQUOIA-HCM: Improvement in Biomarkers
SEQUOIA-HCM: Improvement in Biomarkers Significant improvement in cardiac biomarkers indicative of cardiac wall stress & myocardial injury Treatment with aficamten Treatment with aficamten led to 80% reduction led to 43% reduction from baseline to week 24 from baseline to week 24 NT-proBNP hs-CTnI P
Slide 22: SEQUOIA-HCM: Responder Analysis
SEQUOIA-HCM: Responder Analysis Significant improvement in exercise capacity and symptoms in composite responder endpoint Aficamten Placebo n=142 n=140 ≥1.5 mL/kg/min increase in pVO2 and ≥1 NYHA FC improvement or 60 (42) 19 (14) ≥3.0 mL/kg/min increase in pVO2 and no worsening of NYHA FC, n (%) ≥1.
Slide 23: Clinically Relevant Improvements
Clinically Relevant Improvements 2/3 patients achieved complete hemodynamic response in prespecified analyses Responder Analysis: Complete Hemodynamic Response Achievement of 4 Clinically Relevant Assessments Resting LVOT-G <30 mmHg & Valsalva LVOT-G <50 mmHg 100 Limiting Exercise 90 Outcome LVOT-G
Slide 24: SEQUOIA-HCM: CMR Sub-Study
SEQUOIA-HCM: CMR Sub-Study Aficamten associated with favorable cardiac remodeling Among 50 of the 284 eligible patients who opted to complete the CMR sub-study there was: Left Ventricular Mass Index (LVMI) (g/m2) -15.4 (-24.5,-6.3); P=0.001 • Significant improvement in LVMI • Favorable cardiac remod
Slide 25: SEQUOIA-HCM: Safety Data
SEQUOIA-HCM: Safety Data Placebo Aficamten Event, n (%) (n=140) (n=142) Overall AEs 99 (70.7) 105 (73.9) Headache 10 (7.1) 11 (7.7) Hypertension 3 (2.1) 11 (7.7) Palpitations 4 (2.9) 10 (7.0) AEs with ≥5% incidence Upper respiratory infection 12 (8.6) 9 (6.3) COVID-19 9 (6.4) 8 (5.6) Dyspnea 8 (5.7)
Slide 26: Integrated Safety Analysis
Integrated Safety Analysis Analysis represents 206 patient-years* of exposure to aficamten a Cumulative Placebo-controlled aficamten-treated b pool pool Aficamten Aficamten Placebo • <4% of patients experienced LVEF <50% Number of participants 283 170 153 c LVEF <50% , n (%) 11 (3.9) 9 (5.3) 1 (0.7)
Slide 27: Implementation of Dosing in Real-World Setting (FOREST-HCM)
Implementation of Dosing in Real-World Setting (FOREST-HCM) Low incidence of LVEF <50% in patients with oHCM treated with aficamten 5% N = 282 5% N = 267 4% 4.2% 4% Incidence LVEF <50% Incidence LVEF <50% Placebo-corrected 3% 3% 3.0% 2.8% 2% 2% 1% 1% 1 patient in common 0% 0% Core Lab Site Site ✓ No
Slide 28: US NDA Accepted; Progressing Ex-US Regulatory Submissions
US NDA Accepted; Progressing Ex-US Regulatory Submissions • U.S. PDUFA target action date of September 26, 2025 • Corxel (formerly Ji Xing Pharmaceuticals) 2024 submitted NDA to the CDE of the NMPA in China; NDA was accepted Positive Results from SEQUOIA-HCM • MAA submitted to EMA Aficamten is an in
Slide 29: Aspirational Profile of Aficamten & Potential Distinct Risk Mitigation
Aspirational Profile of Aficamten & Results from SEQUOIA-HCM Inform Potential Distinct Risk Mitigation REMS Existing Potential Distinct Aficamten Aspirational Profile Challenges Risk Mitigation Approach • Rapid onset • Rapid reversibility • Speed to optimal dose Potential for: Echo frequency • SEQUO
Slide 30: Ongoing Clinical Trials of Aficamten
Ongoing Clinical Trials of Aficamten Pivotal Phase 3 clinical Pivotal Phase 3 clinical Clinical trial in a pediatric Open-label extension trial of aficamten as trial in nHCM population with oHCM clinical study in HCM monotherapy vs. metoprolol in oHCM Enrollment Complete Aficamten is an investigatio
Slide 31: Market Research Shows Aficamten May Achieve High Share & Grow Category
Market Research Shows Aficamten May Achieve High Share & Grow Category oHCM CMI Preference Shares in • Potential target product profile for aficamten Eligible Patient Population* interest creates share opportunity in newly treated CMI patients • Aficamten could also be expected to expand the total C
Slide 32: $10B Potential Market of CMI-Eligible Patients
$10B Potential Market of CMI-Eligible Patients, Majority Expected to be Available at Launch, if Aficamten is Approved Diagnosis of HCM anticipated to grow 5x the rate of the general U.S. population US and EU HCM Patients in 2035 Illustrative 880K1,2 2035 Projected Diagnosed HCM Patients (5x the grow
Slide 33: Cardiologists Located in Concentrated Geographic Clusters Across the US
Cardiologists Located in Concentrated Geographic Clusters Across the US ~75% of the HCM patient volume is treated by ~10,000 cardiologists HCM Patient Concentration by Cardiologist Geographic Distribution of HCM Patients 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 7,000 10,000 … 30,000 Note: include
Slide 34: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Sales representative hiring to occur in proximity to approval 2/3 of hiring to occur at-approval Activities initiated upon key de-risking events Underway before SEQUOIA-HCM readout Market access strategy Commercial leadership Pricing strategy Marketing Distri
Slide 35: Omecamtiv Mecarbil
Omecamtiv Mecarbil G Omecamtiv mecarbil is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) Cytokinetics" or any regulatory agency. The safety and effectiveness of this product has not been established. 35
Slide 36: Omecamtiv Mecarbil: Potential for High-Risk Severe HF Patients Despite GDMT
Omecamtiv Mecarbil: Potential for High-Risk Severe HF Patients Despite GDMT Advancing efficient, pragmatic Phase 3 clinical trial High Unmet Need Ph 3 clinical trial results in 8,000 patients point to important treatment benefit The large and growing heart failure population faces frequent Planning
Slide 37: GALACTIC-HF: Clinical Trial Overview
GALACTIC-HF: Clinical Trial Overview Phase 3 clinical trial Event-driven clinical trial; 8,256 patients randomized in 35 countries at 944 clinical trial sites Chronic HFrEF Patients Randomization 1:1 Currently hospitalized for Omecamtiv mecarbil + Standard HF Therapy End of Study primary reason of H
Slide 38: Primary Composite Endpoint
Primary Composite Endpoint 50 Placebo HR = 0.92 45 (95% CI, 0.86–0.99) 40 Omecamtiv Cumulative incidence, % P = 0.025 mecarbil 35 30 CV Death 25 HR = 1.01 (95% CI, 0.92–1.11) P = 0.86 20 Omecamtiv 15 mecarbil 10 5 0 0 6 12 18 24 30 36 Patients Months (30 days) since randomization at risk, n Placebo
Slide 39: Benefit Observed to Increase as Baseline LVEF Decreased
Benefit Observed to Increase as Baseline LVEF Decreased Incidence of Primary Composite Endpoint Relative Treatment Effect on Primary Endpoint 60 50 Placebo 1.2 Incidence Rate (per 100 py) 40 Treatment Effect (Ratio) Treatment 1.0 Effect 30 Omecamtiv 0.8 mecarbil 20 0.6 4,456 patients 3,776 patients
Slide 40: Large Treatment Effect in Easily Defined HF Population
Large Treatment Effect in Easily Defined HF Population Nom N Hazard Ratio (95% CI) ARR p-value All Patients 8232 0.025 2.1 LVEF <30% 4704 <0.001 4.9 + Hosp <3 mos 2836 <0.001 6.2 + SBP <110 1881 0.004 7.2 + Class III/IV 2249 <0.001 8.9 + NT-proBNP ≥1000 pg/mL 2852 <0.001 8.8 0.6 0.7 0.8 0.9 1 1.1 1.
Slide 41: Residual Risk is High Despite Best Therapy
Residual Risk is High Despite Best Therapy DAPA-HF Trial: Patients on GDMT including SGLT2-i DAPA-HF Trial Residual Risk DAPA-HF trial (dapagliflozin group) • Primary endpoint: CV Death/HF hospitalization/urgent HF visit • 4744 patients • Renin-angiotensin system blocker 94% • Dapagliflozin 96% • Mi
Slide 42: Phase 3 Confirmatory Clinical Trial Design (COMET-HF)
Phase 3 Confirmatory Clinical Trial Design Currently enrolling COMET-HF: Confirmation of Omecamtiv Mecarbil Efficacy Trial in Heart Failure 2-week washout period LVEF < 30% 2-week run-in period • Primary endpoint: time to within 6 mo Omecamtiv Mecarbil + Standard of Care CV death, HF events, Direct
Slide 43: Large and Growing Target Patient Population in US
Large and Growing Target Patient Population in US Prevalence in Adults (18+, USA) 2020 Estimates 2029 Estimates 7.1M1 8.6M3 Heart Failure Including HFpEF 3.5M2 4.3M3 HFrEF Population 2.4M2 2.8M3 HFrEF Patients with EF<30% ~720K4 ~840K4 High risk HF patients with EF<30% Proposed Cardiac Function Mark
Slide 44: Higher Event Rate & Costs in Patients with Severely Reduced EF
Higher Event Rate & Costs in Patients with Severely Reduced EF Accounts for ~60% of HFrEF hospitalizations5 35% of patients with severely reduced EF re-hospitalized within 1 year6 $15,493 per HF re-hospitalization7 Direct costs from HF re-hospitalizations projected to increase from $3.9 billion in 2
Slide 45: The Business Case for Omecamtiv Mecarbil
The Business Case for Omecamtiv Mecarbil Significant clinical need, lack of treatments drives higher price potential in HF with severely reduced EF “Severely Reduced EF” US Price Potential Premium to market Disease Severely Reduced EF Market Insights Severity LVEF <30 Payer ~1M patients Positioning
Slide 46: CK-586
CK-586 G CK-586 is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) or any Cytokinetics’ regulatory agency. The safety and effectiveness of this product has not been established. AG
Slide 47: CK-586: Distinct Mechanism of Action from Aficamten
CK-586: Distinct Mechanism of Action from Aficamten “Fewer hands pulling on the rope” Before CK-586 After CK-586 CK- Mechanochemical 586 domain ATP Post-Powerstroke State Actin sliding Actin sliding CK-586 is an investigational drug and is not approved by any regulatory agency. Its safety and effica
Slide 48: CK-586: Shallow In Vivo Concentration-Response
CK-586: Shallow In Vivo Concentration-Response CK-586 has a shorter half-life than aficamten Pharmacodynamic window Fractional shortening IC50 /IC10 ratio mavacamten 2.8x aficamten 9.9x CK-586 9.3x IC10: plasma concentration at 10% relative reduction in fractional shortening IC50: plasma concentrati
Slide 49: Phase 1 Data Support Advancement to Phase 2 Clinical Trial
Phase 1 Data Support Advancement to Phase 2 Clinical Trial Phase 2 dose-finding trial in HFpEF expected to start in Q4 2024 Phase 1 study design: 7 SAD cohorts (10 mg to 600 mg) & 2 MAD cohorts (100 & Plasma Concentration Change in LVEF vs. 200 mg once daily), 10 participants each (mean [SD]) over t
Slide 50: Phase 2 Study Schema (AMBER-HFpEF)
Phase 2 Study Schema AMBER-HFpEF expected to start in Q4 2024 AMBER-HFpEF: Assessment of CK-586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF 6 WEEKS 6 WEEKS 2 weeks 1 Enrolling HFpEF SoC + Placebo Cohort 1 patients with: n=12 Washout SoC + 150 mg CK-586 SoC + 300
Slide 51: Heart Failure with Preserved Ejection Fraction (HFpEF)
Heart Failure with Preserved Ejection Fraction (HFpEF) Despite broad use of standard treatments & advances in care, the prognosis for patients with HF is poor1 ~75% ~84% HFpEF patients will HFpEF patients will Subset of HFpEF patients Significant increase Lifetime healthcare costs die within five ye
Slide 52: CK-586: Focusing on Patients with HFpEF and EF ≥60%
CK-586: Focusing on Patients with HFpEF and EF ≥ 60 7.9M 4.0M (2024) 1.0M (EF>65) to 2.0M (EF > 60) Heart Failure Prevalence in 2024, US 50% of HF with HFpEF (EF ≥ 50%) ~20% of HF with EF ≥ 60% 2024 prevalence calculated using published, historic estimate and projected to 2024 using age adjusted US
Slide 53: CK-586 May Address Unmet Needs of HFpEF Patients
CK-586 May Address Unmet Needs of HFpEF Patients Proposed Mechanistic Benefits Target Product Profile • Statistically significant reduction in composite of mortality and • CK-586 may benefit cardiac relaxation hospitalization outcomes during diastole • Oral QD tablet • CK-586 may reduce symptoms and
Slide 54: Financials & Milestones
Financials & Milestones G Cytokinetics’ 54
Slide 55: Strong Financial Position
Strong Financial Position Strengthened balance sheet & access to capital to execute launch & advance R&D pipeline September 30, 2024 ~$1.3B in cash, cash equivalents and investments Further access to capital through term loans with Access up to $350M in term loans* Royalty Pharma (RP) Add’l $500M RP
Slide 56: 2024 Financial Guidance
2024 Financial Guidance Current Guidance Issued on Aug. 8, 2024 GAAP Operating Expense[1] $555m to $575m Non-cash Expense[2] Included in GAAP Operating Expense $110m to $105m Non-GAAP Operating Expense[3] $445m to $470m Net Cash Utilization[4] $400m to $420m The financial guidance does not include t
Slide 57: Exclusive Licensing Collaboration with Bayer for Aficamten in Japan
Exclusive Licensing Collaboration with Bayer for Aficamten in Japan Upfront payment, development & commercial milestone payments & tiered royalties Collaboration leverages Bayer’s regional capabilities & expertise in development & commercialization Collaboration Financials: Joint Development Program
Slide 58: Robust Pipeline, Upcoming Commercial Launch & Solid Financial Position
Robust Pipeline, Upcoming Commercial Launch & Solid Financial Position U.S. PDUFA date of September 26, 2025 China NDA and Commercial for aficamten EU MAA submitted U.S go-to-market strategies anchored in differentiated European commercial readiness activities market access & patient experience unde
Slide 59: Upcoming Milestones
Upcoming Milestones Aficamten Aficamten Omecamtiv Mecarbil Continue enrollment of COMET-HF Complete enrollment of ACACIA-HCM in 2024 Report topline results from MAPLE-HCM in 1H 2025 in 2025 CK-586 Continue Phase 1 study of aficamten Continue enrollment of CEDAR-HCM in healthy Japanese volunteers in
Slide 60: Thank you
CG Cytokinetics’ thank you