Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (November 2023)
54 slides from Cytokinetics's investor presentation, November 2023
Slide 1: Empowering muscle, empowering lives
empowering muscle empowering lives Sarcomere directed therapies
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
Sarcomere Directed Therapies 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: Vision
Achieve regulatory approvals for at least two drugs arising from our pipeline Build commercial capabilities to market and sell our medicines reflective of their innovation and value VISION Our vision is to be the leading muscle biology biopharma company that Generate sustainable and growing revenues
Slide 5: A Great Place to Work; Uncommon Continuity of Team
A Great Place to Work; Uncommon Continuity of Team VALUES RETENTION patients are our North Star science is in our soul we > me make it happen <5% Turnover rate of leadership; low attrition AWARDS Winner in >10 yrs Wellness 3rd San Francisco Business Times Out of 25 Large Companies Average tenure of
Slide 6: Sarcomere Directed Drug Development
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 ACTIVATE Troponin Omecamtiv Reldesemtiv CK-136 Aficamten CK-586 Mecarbil (Cardiac) (Cardiac) (Skeleta
Slide 7: Contractile Dysfunction Underlies Cardiac Diseases
Contractile Dysfunction Underlies Cardiac Diseases Decreased Increased / Preserved Cardiac Contractility Cardiac Contractility • Heart Failure with Reduced • Non-obstructive Hypertrophic Ejection Fraction (HFrEF) Cardiomyopathy (nHCM) • Genetic Dilated • Obstructive Hypertrophic Cardiomyopathy Cardi
Slide 8: Pipeline of Novel Muscle-Directed Drug Candidates
Pipeline of Novel Muscle-Directed Drug Candidates Research Pre-Clinical Phase 1 Phase 2 Phase 3 CARDIAC MUSCLE Omecamtiv Mecarbil (HFrEF)* Aficamten (oHCM) Aficamten (nHCM) CK-136 (Heart Failure, other) CK-586 (HFpEF) SKELETAL MUSCLE Reldesemtiv (ALS)** Additional Skeletal Muscle Activators OTHER Mu
Slide 9: Building a Specialty Cardiology Franchise Anchored by Aficamten
Building a Specialty Cardiology Franchise Anchored by Aficamten Addressing severely ill and underserved populations in need of new therapies Strategic expansion of clinical development program to various patient populations fuels leadership in cardiology Omecamtiv Aficamten Aficamten Aficamten CK-58
Slide 10: Specialty Cardiovascular Portfolio
Sarcomere Directed Drug Development Specialty Cardiovascular Portfolio Aficamten Omecamtiv Mecarbil Emerging Pipeline – CK-136 & CK-586 10
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) or any Cytokinetics regulatory agency. The safety and effectiveness of this product has not been established.
Slide 12: HCM Prevalence: Significant and Growing Globally
HCM Prevalence: Significant and Growing Globally HCM prevalence estimates vary across geography and over time Estimated HCM Prevalence Rates HCM True Patient Prevalence (Est. 2021) China 1,100 Europe GER: 0.07% (1) USA IT: 0.05-0.07% (5, 7) 0.02% (3), 0.08% (12), EU: 0.2% (13) EU 1,000 Asia 0.17% (6
Slide 13: Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients
Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients Potential for nearly 200K patients eligible for CMIs in 2025 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
Slide 14: Aficamten: Proposed Mechanism of Action
Aficamten: Proposed Mechanism of Action Aficamten stabilizes myosin in the released post-powerstroke state unable to hydrolyze ATP “Fewer hands pulling on the rope” Before Aficamten After Aficamten Mechanochemical domain AF Post-Powerstroke State Actin sliding Actin sliding Aficamten is an investiga
Slide 15: 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 16: REDWOOD-HCM: Cohorts 1 & 2 Design
REDWOOD-HCM: Cohorts 1 & 2 Patients with symptomatic oHCM on background therapy excluding disopyramide Two sequential dose-finding cohorts Randomization Patients with Aficamten + SoC End of Study Screening symptomatic oHCM, 2 and resting or provoked LVOT 1 gradient ≥ 50 mmHg Placebo + SoC Study Visi
Slide 17: REDWOOD-HCM: Robust Reduction of LVOT Gradients
REDWOOD-HCM: Robust Reduction of LVOT Gradients Cohorts 1 & 2 Consistent, clinically meaningful reductions in LVOT gradients within two weeks No treatment interruptions or discontinuations Reversibility of drug effect demonstrated Resting LVOT-G Valsalva LVOT-G 80 100 Combined Placebo 80 60 Aficamte
Slide 18: Change from Baseline in NT-proBNP & NYHA Class
Change from Baseline in NT-proBNP & NYHA Class Cohorts 1 & 2 Change from Baseline NT-proBNP to Week 10 Improvement in Heart Failure Symptoms (NYHA Class) Week 10 Responder Definition: Improvement in NYHA Class ≥1 0 100 31% -200 80 (n=4) 43% (n=6) 64% NT-proBNP (pg/mL) (n=9) -400 60 % Total -600 40 6
Slide 19: Improved Cardiac Structure and Diastolic Function
Improved Cardiac Structure and Diastolic Function Cohorts 1 & 2: Early signs of improvement in cardiac structure and myocardial relaxation Cardiac Structure Treatment with aficamten for 10 weeks resulted in: • Significant reduction in left atrial volume index • Trend towards a reduction in LV mass i
Slide 20: Response Rates on Treatment with Aficamten
Response Rates on Treatment with Aficamten Cohorts 1 & 2 1/13 11/14 13/14 100 Responder # / Total # 7.7% 78.6% 92.9% Not Responder • Consistent, clinically Responder 80 meaningful reductions in LVOT Responder Definition: Resting LVOT-G <30 gradients within two weeks mmHg and post- 60 Valsalva LVOT-G
Slide 21: REDWOOD-HCM: Cohort 4 Design
REDWOOD-HCM: Cohort 4 Patients with symptomatic nHCM on background therapy Results presented at ESC Heart Failure 2023 End of Study Screening Patients with symptomatic nHCM on background Aficamten + SoC therapy Study Visits Screen W-1* D1 W2 W4 W6** W8* W9* W10 W12 W14* Ambulatory Cardiac Monitoring
Slide 22: Significant Improvements in KCCQ & NYHA Class
Significant Improvements in KCCQ & NYHA Class Cohort 4 85% of patients achieved 15 mg dose; no discontinuations due to adverse events Kansas City Cardiomyopathy Questionnaire Categorical Changes at Week 10 in KCCQ-CSS NYHA Functional Class Mean improvement in KCCQ of 10.6 points 56% of patients impr
Slide 23: Change in Baseline in Biomarkers & Angina Frequency
Change in Baseline in Biomarkers & Angina Frequency Cohort 4 Proportional Change from Baseline in Cardiac Seattle Angina Questionnaire Angina Biomarkers Frequency (SAQ-AF) Mean reduction in high-sensitivity cardiac troponin of 21% Reduction in frequency of angina from daily or weekly, to weekly or m
Slide 24: FOREST-HCM: Baseline Characteristics
FOREST-HCM: Baseline Characteristics Baseline characteristics indicate substantial disease burden; ~2/3 patients achieving 15 or 20 mg FOREST-HCM oHCM Dose of Aficamten * Data cut Sept 15, 2023 N=143* Age (Years), Mean (SD) 60.4 (13.2) Female, n (%) 65 (45.5) BMI (kg/m2), Mean (SD) [Range] 29.2 (4.5
Slide 25: No Dose Interruptions During Titration; Few Dose Reductions
No Dose Interruptions During Titration; Few Dose Reductions During Maintenance Dose Titration Phase Maintenance Phase Down-titration triggered 0.5% • No treatment-related LVEF • 579 monitoring echocardiograms <50% during the titration completed* in oHCM patients period • None with LVEF <40% requirin
Slide 26: Durable Effects of Aficamten on LVOT-G & LVEF
Durable Effects of Aficamten on LVOT-G & LVEF Resting & provoked gradients remain below diagnostic threshold for >2 years, LVEF remains flat after titration Resting LVOT Gradient Valsalva LVOT Gradient LVEF = Diagnostic threshold = Diagnostic threshold = Safety threshold Aficamten is an investigatio
Slide 27: Durable Effects of Aficamten on Biomarkers
Durable Effects of Aficamten on Biomarkers Sustained relative reductions in high-sensitivity Troponin I (~30%) & NT-proBNP (~70%) observed High-Sensitivity Cardiac Troponin I NT-proBNP Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not
Slide 28: Durable Effects of Aficamten on Clinical Endpoints
Durable Effects of Aficamten on Clinical Endpoints KCCQ-CSS NYHA Class Guideline-Eligible for SRT 71% of patients had ≥ 5-point KCCQ-CSS increase ~50% of patients were asymptomatic at 1 year 90% of SRT-eligible patients at baseline are no longer SRT-eligible 30% of patients had ≥ 10-point KCCQ-CSS i
Slide 29: Safety Data: Phase 2 & OLE
Safety Data: Phase 2 & OLE • oHCM → Cohorts 1, 2, & 3: After 10-weeks of treatment • Almost all eligible patients choose to participate in the OLE • 2 SAEs reported in 41 aficamten-treated → none were • Echocardiography-guided dose titration of aficamten is managed entirely by the treating physician
Slide 30: SEQUOIA-HCM: Phase 3 Trial
SEQUOIA-HCM: Phase 3 Trial Completed enrollment; expect topline results in late December 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-Valsalv
Slide 31: SEQUOIA-HCM: Baseline Characteristics
SEQUOIA-HCM: Baseline Characteristics Baseline characteristics reflect highly symptomatic patient population with reduced exercise capacity Baseline Characteristics (N=282) n (%) or Mean (SD)a Baseline Characteristics (N=282) n (%) or Mean (SD)a Demographics HCM Medical Therapies Age, years 59.1 (12
Slide 32: MAPLE-HCM: Phase 3 Monotherapy Trial
MAPLE-HCM: Phase 3 Monotherapy Trial Open to enrollment Active-comparator trial of aficamten as monotherapy vs. metoprolol in patients with oHCM (if applicable) Recently diagnosed 2 Week SOC LVOT-G (mmHg) • Trial to enroll Washout or treatment naïve Resting ≥ 30 Randomization with symptomatic Aficam
Slide 33: ACACIA-HCM: Pivotal Phase 3 Trial in nHCM
ACACIA-HCM: Pivotal Phase 3 Trial in nHCM Open to enrollment Patients with: Randomization • Trial to enroll approximately Aficamten End of Study Symptomatic 420 symptomatic nHCM N = 420 Screening (1:1) (NYHA Class (EOS) patients II/III) nHCM, KCCQ-CSS Placebo • Primary endpoint: change in ≥ 30 and ≤
Slide 34: Aficamten: Clinical Development Plan for HCM
Aficamten: Clinical Development Plan for HCM Phase 1 Phase 2 Phase 3 SAD & MAD REDWOOD-HCM Cohorts 1-3 SEQUOIA-HCM Healthy obstructive HCM obstructive HCM Target IND Filed Volunteers Placebo controlled; echocardiography endpoints Pivotal trial with exercise endpoint (peak VO2) NDA Potential for Well
Slide 35: Aficamten: Planned Commercial Approach
Aficamten: Planned Commercial Approach Driven by a relentless focus on our North Star: the HCM patient Learn Design Build Leverage deep Engage with all Tap into deep functional understanding of stakeholders to design experience to build patients, HCPs, payers, an optimal customer operational excelle
Slide 36: 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 is also expected to expand the total CMI mar
Slide 37: 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 population US HCM Patients (in ‘000) Illustrative Potential Potential nHCM Launch 500K1,2 oHCM Launch >80% CMI-Eligible >90% patients available 300K1
Slide 38: 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 Aficamten is an
Slide 39: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Majority of spending to occur closer to approval in 2025 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 Distributio
Slide 40: Omecamtiv Mecarbil
mecamtiv ecarbil 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.
Slide 41: Omecamtiv Mecarbil: Current Status
Omecamtiv Mecarbil: Current Status No current plans to conduct additional clinical trial of omecamtiv mecarbil Received CRL from FDA Feb 28, 2023 • Submitted Formal Dispute Resolution Request to the FDA GALACTIC-HF not sufficiently 2023 persuasive to establish substantial evidence of • Continue to p
Slide 42: Emerging Cardiovascular Pipeline CK-136 & CK-586
Emerging Cardiovascular Pipeline CK-136 & CK-586 42
Slide 43: Novel Approach May Address Multiple Unmet Patient Needs
Novel Approach May Address Multiple Unmet Patient Needs oHCM Obstructive HCM aficamten Cardiac myosin Inhibitors aficamten CK-586 nHCM HFpEF Non-Obstructive HCM Heart Failure with Preserved Ejection Fraction Not for Promotional Use, For Investors Only OVERVIEW AFICAMTEN OMECAMTIV MECARBIL EMERGING P
Slide 44: CK-586: Distinct Mechanism of Action from Aficamten
CK-586: Distinct Mechanism of Action from Aficamten CK-586 inhibits actin-activated ATPase of HMM only; aficamten inhibits both S1 and HMM Single-headed Two-headed Myosin (S1) Myosin (HMM) CK-586 is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have no
Slide 45: CK-586: Shallow In Vivo Concentration-Response
CK-586: Shallow In Vivo Concentration-Response CK-586 is predicted to have a shorter half-life in humans 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 shorteni
Slide 46: CK-586 is Efficacious in ZSF1 Obese Rat Model of HFpEF
CK-586 is Efficacious in ZSF1 Obese Rat Model of HFpEF Model is representative of hypertensive, diabetic, metabolic aspects of HFpEF 10 weeks of treatment improved diastolic function and reduced cardiac fibrosis Reduced Fractional Shortening Improved Diastolic Function Reduced Fibrosis CK-586 is an
Slide 47: CK-136: Mechanism of Action
CK-136: Mechanism of Action Key biochemical and cellular features The first selective cardiac troponin activator Contractability Strongly Calcium Transients Unchanged Greater ATPase Activity Greater ATPase Activity Activated After Treatment After Treatment 1PD Window = Maximum Tolerated Concentratio
Slide 48: CK-136: Exposure Response Relationship
CK-136: Exposure Response Relationship Exposure-response of troponin activator is shallower than myosin activator Analyzing single ascending dose data from Phase 1 study Animal Models of Cardiac Function Healthy Rats PD Window1 MI Rats PD Window1 Healthy Dogs PD Window1 ≥15X ≥15X ≥15X 1PD Window = M
Slide 49: Corporate Profile
Sarcomere Directed Therapies Corporate Profile 49
Slide 50: Robust Pipeline, Solid Financial Position
Robust Pipeline, Solid Financial Position Pipeline 1-2 Potential commercial launches in 2025 5 Clinical stage programs 10 Development programs by 2025 HCM Heart Failure Ongoing Aficamten o SEQUOIA-HCM ongoing (Phase 3 trial in oHCM) Omecamtiv mecarbil CK-586 R&D Programs o Engaging with FDA o Procee
Slide 51: Cytokinetics: Uniquely Positioned for Success
Cytokinetics: Uniquely Positioned for Success Leadership Depth Relationships Access in muscle biology in cardiology with stakeholders to capital Pioneer in CMI space Late-stage HCM program Seasoned commercial team Strong cash runway of over 18 months based on 2023 Multiple drug candidates arising HF
Slide 52: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance Over 18 months of cash runway based on 2023 guidance 2023 Condensed Balance Sheet 2023 Financial Guidance As of 9/30/2023 in millions in millions Total Total Cash and investments $554.7 Cash Revenue $5 Accounts receivable $2.5 Cash Operating Expenses $390-410 PPE $
Slide 53: Expected 2023 Milestones
Expected 2023 Milestones Aficamten Aficamten Omecamtiv Mecarbil Expect topline results from Continue to pursue approval for SEQUOIA-HCM in late December omecamtiv mecarbil in Europe Emerging Pipeline Continue enrollment of MAPLE-HCM, second Phase 3 trial of aficamten in oHCM Proceed to MAD Cohorts o
Slide 54: Thank You
Thank You Sarcomere directed therapies