Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (September 2024)
51 slides from Cytokinetics's investor presentation, September 2024
Slide 1: Empowering muscle, empowering lives
muscle EMPOWERING 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 Building a specialty cardiology franchise anchored by aficamten Protein Target Therapeutic Area Drug Candidate Research Pre-Clinical Phase 1 Phase 2 Phase 3 Approval Expect regulatory oHCM Aficamten submissions in 2H 2024 Myosin oHCM Aficamten (First
Slide 6: Myosin Platform Fuels Multiple Milestones and Increased Value
Myosin Platform Fuels Multiple Milestones and Increased Value Potential Results Aficamten FDA Approval Aficamten oHCM SEQUOIA-HCM For illustrative purposes only Potential Results Approval Enhancing shareholder Emerging Aficamten Pipeline MAPLE-HCM value Results Aficamten Aficamten oHCM SEQUOIA-HCM P
Slide 7: Strong Financial Position
Strong Financial Position Strengthened balance sheet & access to capital to execute launch & advance R&D pipeline June 30, 2024 ~$1.4B in cash, cash equivalents and investments Secured access to additional $175M* in term loan on top of Further access to capital through term loans with RP $175M** alr
Slide 8: 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 9: 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 10: 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. 10
Slide 11: 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 12: 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 13: 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 14: 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 15: 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 16: 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 17: 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 18: SEQUOIA-HCM: Secondary & Exploratory Endpoints
SEQUOIA-HCM: Secondary & Exploratory Endpoints Significant improvement in post-Valsalva left ventricular outflow tract gradient (LVOT-G) LS mean difference: Resting LVOT-G Valsalva LVOT-G - 50 mmHg 100 100 90 90 Resting LVOT-G (mmHg) Valsalva LVOT-G (mmHg) 80 80 70 70 60 60 50 50 40 40 30 30 20 20 0
Slide 19: SEQUOIA-HCM: Secondary & Exploratory Endpoints
SEQUOIA-HCM: Secondary & Exploratory Endpoints LS mean difference: ≥1 NYHA FC Improvement KCCQ-CSS 7 points Proportion of patients with ≥1 100 100 NYHA FC improvement (%) 90 80 58% 90 KCCQ–CSS 70 60 50 80 40 30 70 20 10 60 0 0 2 4 6 8 12 16 20 24 28 2 4 6 8 12 16 20 24 Weeks Weeks 78 fewer days 80%
Slide 20: 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 21: 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 22: 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 23: Preparing for Regulatory Submissions to FDA, EMA
Preparing for Regulatory Submissions to FDA, EMA • Participated in • Two meetings with FDA in Q1 2024 • Type B meeting with FDA in Q2 2024 • Meetings with EMA in Q2 2024 2024 • Expect to submit NDA to FDA in Q3 2024, MAA to Positive Results from EMA in Q4 2024 and coordinate with Ji Xing to SEQUOIA-
Slide 24: Aspirational Profile of Aficamten & Results Inform 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 25: 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 Aficamten is an investigational drug and is not
Slide 26: 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 27: Expect Majority of CMI-Eligible Patients Available at Launch
If Aficamten is Approved, Expect Majority of CMI-Eligible Patients Available at Launch Diagnosis of HCM anticipated to grow 5x the rate of the general U.S. population US + EU5 HCM Patients (in 000s) Illustrative nHCM ACACIA-HCM 880K1,2 oHCM Q4 2028 SEQUOIA-HCM Q4 2025 570K1 Projected Diagnosed HCM P
Slide 28: 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 29: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Majority of spending to occur closer to potential approval in 2025 Key activities after SEQUOIA-HCM readout 2/3 of hiring to occur at-approval Continued insight generation Market access strategy validation Pricing strategy finalization Commercial leadership D
Slide 30: 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. 30
Slide 31: 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 32: 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 33: 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 34: 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 35: 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 36: 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 37: Omecamtiv Mecarbil: Regulatory Feedback
Omecamtiv Mecarbil: Regulatory Feedback Preparing to Start Received CRL from FDA Engagements with FDA Feb 28, 2023 2023 - 2024 Additional Phase 3 Trial 2024 GALACTIC-HF not sufficiently persuasive to establish substantial evidence of Discussions with FDA about effectiveness for reducing the potentia
Slide 38: Anticipated Phase 3 Confirmatory Clinical Trial Design
Anticipated Phase 3 Confirmatory Clinical Trial Design Trial design to be finalized • Primary endpoint: time to 2-week washout period 2-week run-in period a LVEF < 30% CV death, HF events, Omecamtiv Mecarbil + Standard of Care NT-proBNP transplant/LVAD, or stroke direct randomization to final dose b
Slide 39: 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% 1.3M2 1.5M3 EF <30% and consistent with clinical trial ~720K4 ~840K4 Severe H
Slide 40: Patients with Severe HF at Excess Risk of Hospitalization
Patients with Severe HF at Excess Risk of Hospitalization HF is #1 cause of 30-day readmission among Medicare beneficiaries1 All HF Patients HF Hospitalizations LVEF ≤30% + WHF* 36% 516% Excess risk of HF hospitalization vs all HF LVEF 31%‒40% & HFrEF LVEF ≤ 30% excluding WHF 24% HF LVEF >40% 40% *P
Slide 41: Higher Price Potential in a Narrow, Sicker Patient Population
Higher Price Potential in a Narrow, Sicker Patient Population Significant clinical need and lack of treatments drives higher price potential “Original Potential Label” “Severely Reduced EF” (GALACTIC-HF) US Price Potential Parity to market Premium to market Worsening HF Severe HF Disease Severity LV
Slide 42: 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. 42
Slide 43: 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 44: Heart Failure with Preserved Ejection Fraction (HFpEF)
Heart Failure with Preserved Ejection Fraction (HFpEF) Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor1 8.5 million ~50% ~75% ~84% Americans will have HF patients have HFpEF patients will HFpEF patients will Subset of HFpEF patient
Slide 45: 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 46: Phase 1 Data Support Advancement to Phase 2 Clinical Trial
Phase 1 Data Support Advancement to Phase 2 Clinical Trial Phase 2a dose-finding trial in HFpEF expected to start in Q4 2024 Plasma Concentration (mean [SD]) over time after single ascending doses of CK-586 Phase 1 study design: 7 SAD cohorts (10 mg to 600 mg) & 2 MAD cohorts (100 & 200 mg once dail
Slide 47: Financials & Milestones
Financials & Milestones G Cytokinetics” 47
Slide 48: Strong Financial Position
Strong Financial Position Strengthened balance sheet & access to capital to execute launch & advance R&D pipeline June 30, 2024 ~$1.4B in cash, cash equivalents and investments Secured access to additional $175M* in term loan on top of Further access to capital through term loans with RP $175M** alr
Slide 49: 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 50: Planned 2024 Milestones
Planned 2024 Milestones Aficamten Aficamten Omecamtiv Mecarbil Submit NDA to FDA in Q3 2024, MAA to EMA in Q4 2024, and Complete enrollment of MAPLE-HCM Start Phase 3 clinical trial of coordinate with Ji Xing to submit in Q3 2024 omecamtiv mecarbil in HFrEF NDA in China in 2H 2024 in Q4 2024 Continu
Slide 51: Thank you
G Cytokinetics’ thank you
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