Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (July 2020)
59 slides from Cytokinetics's investor presentation, Jul 15, 2020
Slide 1: Sarcomere Directed Therapies: Empowering Muscle, Empowering Lives
Exhibit 99.1 Sarcomere Directed Therapies EMPOWERING MUSCLE EMPOWERING LIVES John, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALSExhibit 99.1 Sarcomere Directed Therapies EMPOWERING MUSCLE EMPOWERING LIVES John, diagnosed with heart failure Jillian, diagnosed with
Slide 2: Disclaimer
Disclaimer 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 Harbor for forwar
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. 3Sarcomere Directed Therapies OUR MISSION To bring forward new medicines to improve the healthspan of pe
Slide 4: Vision and Strategic Goals
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 Generate sustainable and growing Our vision is to be the revenues from product sales leading muscle biology bio
Slide 5: How Do We Get There?
How Do We Get There? Conduct rigorous, step-wise clinical research Exploit muscle biology roots De-risk development programs Measure pharmacodynamics of to increase POS muscle function Optimize PK/PD relationships Develop first-in-class, next-in class, best-in-class compounds Maintain continuity of
Slide 6: 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 (Heart Failure) AMGEN COLLABORATION CK-274 (oHCM, nHCM, HFpEF) RTW / JI XING COLLABORATION CK-271 AMG 594 (Heart Failure, other) AMGEN COLLABORATION SKELETAL MUSCLE Relde
Slide 7: Corporate Development Strategy
Corporate Development Strategy Multiple product launches catalyze revenue growth Organizational capacity Diversified commercial cash flows sustain profitability Commercial infrastructure Propriety research & development 2020 2021 2022 2023 2024 2025 • Potential for $100M • Potential for $300M • Esca
Slide 8: Omecamtiv Mecarbil: Collaborations & Agreements
Omecamtiv Mecarbil: Collaborations & Agreements Amgen & Royalty Pharma Amgen Collaboration Royalty Monetization Purchase Option: 2006 Exercise Option Ex-Japan: 2009 Royalty Pharma paid $100M** for 4.5% royalty on worldwide sales of omecamtiv mecarbil: 2017 Expanded to Include Japan/Purchase Equity:
Slide 9: CK-274: Collaborations & Agreements
CK-3773274: Collaborations & Agreements RTW Investments, LP & Ji Xing Pharmaceuticals Limited RTW & Ji Xing Pharma Licensing Collaboration, Funding Commitments & Royalty Monetization RTW Investments committed capital, funding and sale proceeds of $250M to Cytokinetics Ji Xing Pharma to develop & com
Slide 10: Reldesemtiv: Collaborations & Agreements
Reldesemtiv: Collaborations & Agreements Astellas Collaboration Cytokinetics has exclusive rights to reldesemtiv, CK-601 and other FSRAs Cytokinetics has exclusive control and responsibility for development and commercialization of reldesemtiv, CK-601 and other fast skeletal regulatory activators As
Slide 11: Commercialization Strategy
Commercialization Strategy Leveraging partnership with Amgen to finance the build of our commercial business Amgen to reimburse Cytokinetics’ commercialization Focus to Concentrated Customer Segments costs in North America (e.g. Centers of Excellence) Potential royalties and milestone payments from
Slide 12: Sarcomere Directed Drug Development: Cardiac Muscle
Sarcomere Directed Drug Development CARDIAC MUSCLE Omecamtiv Mecarbil AMG 594 CK-274, CK-271 12Sarcomere Directed Drug Development CARDIAC MUSCLE Omecamtiv Mecarbil AMG 594 CK-274, CK-271 12
Slide 13: Tremendous Need Exists to Improve CV Care
Tremendous Need Exists to Improve CV Care Novel CV drugs are desperately needed to improve patient healthspan Heart Disease the Leading CV Disease the Leading Lack of innovation Exists Cause of Death in the US Category in Healthcare Spend Across CV Conditions #1 Rare diseases #1 Heart disease #1 Car
Slide 14: Heart Failure: Growing Prevalence and Low Survival Rates
Heart Failure: Growing Prevalence and Low Survival Rates 6 million people have heart failure in the United States Prevalence Expected to HF Survival Rates Worse than Some Increase by 46% from 2012 – 2030 Prevalent Cancers Men Women 10 9 8 7 6 +46% 5 8.3 4 3 5.7 2 1 0 2012 2030 Mozzafarian, et al. Ci
Slide 15: High Mortality and Hospital Readmission Rates
High Mortality and Hospital Readmission Rates 1,2 Acute heart failure is the most frequent cause of hospitalization in people > 65 5 years 3,7,8 post-discharge 1 year 7,9 post-discharge ~ 40-50% 60 days mortality 7 post-discharge ~ 20-30% after 5 years Initial mortality Hospitalization ~ 25-50% 1 of
Slide 16: High Economic Burden of Heart Failure
High Economic Burden of Heart Failure 1,2 Heart failure costs ~$123 billion annually, representing 33% of total Medicare budget Inpatient Admission Rates for HF Patients 1 6X Higher than Non-HF Patients 1800 1600 1400 1200 Heart failure is the most 1000 frequent diagnosis for 1,664 800 hospitalized
Slide 17: Significant Unmet Need in HFrEF
Significant Unmet Need in HFrEF Proprietary market research suggests need for novel therapy Market research Drugs that Drugs that Disease Drugs that do Drugs that suggests need do not affect enhance cardiac modifying not affect BP increase QoL for novel therapy renal function performance therapies P
Slide 18: Significant Unmet Need in HCM
Significant Unmet Need in HCM Current therapies do not target underlying disease Current medical HCM is an inherited Surgical intervention therapy does not target cardiovascular disease not permanent solution underlying disease 1 in 500 have genetic mutation Invasive therapy to reduce Indirect mecha
Slide 19: Sarcomere Directed Drug Development: Cardiac Muscle
Sarcomere Directed Drug Development Cardiac muscle The sarcomere is a molecular structure found in skeletal and cardiac muscle that enables cardiac myocytes to contract and generate force Troponin Activate Activate Inhibit Inhibit AMG 594 Omecamtiv CK-274 CK-271 (Cardiac) Mecarbil (Cardiac) (Cardiac
Slide 20: Omecamtiv Mecarbil: Novel Mechanism Approach
Omecamtiv Mecarbil: Novel Mechanism Approach O V E R V I E W C A R D I A C C A N D I D A T E S S K E L E T A L C A N D I D A TE S C O R P O R A TE P R OF I L E 20Omecamtiv Mecarbil: Novel Mechanism Approach O V E R V I E W C A R D I A C C A N D I D A T E S S K E L E T A L C A N D I D A TE S C O R P
Slide 21: Omecamtiv Mecarbil: Pivotal Phase Results Q4 2020
Omecamtiv Mecarbil: Pivotal Phase 3 Results Q4 2020 11 Phase 1 studies with over 300 patients, 7 Phase 2 trials with over 1,400 patients Initiate Initiate Initiate Initiate METEORIC-HF Amgen Amgen Option First Cardiac First CTA/ CK-1827452 GALACTIC-HF COSMIC-HF ATOMIC-AHF Exercises Agreement Sarcome
Slide 22: What Did We Learn from COSMIC-HF?
What Did We Learn from COSMIC-HF? Phase 2 clinical trial of omecamtiv mecarbil • First demonstration of the effectiveness of PK- guided dose titration to prevent excessive exposures to omecamtiv mecarbil • Demonstrated improvement in several different measures that predict improved prognosis • Decre
Slide 23: Dose-Dependent Increases in Cardiac Performance
Dose-Dependent Increases in Cardiac Performance Pharmacodynamic results from COSMIC-HF SET Stroke Volume 8 40 p = 0.004 p = 0.022 p = 0.001 p < 0.001 35 6 30 4 25 2 20 15 0 10 -2 5 -4 0 Placebo 25 mg All PK Titration Placebo 25 mg All PK Titration LVFS LVEF 7.0 5 p = 0.025 p = 0.063 p = 0.017 p = 0.
Slide 24: Decreases in Physiology & Cardiac Risk
Decreases in Physiology & Cardiac Risk Reductions in heart volume, oxygen demand & wall stress in COSMIC-HF LVEDV LVESV 10 0 5 -5 0 -10 -5 -10 -15 p = 0.062 p = 0.021 -15 -20 p = 0.019 p = 0.005 -20 -25 Placebo 25 mg All PK Titration Placebo 25 mg All PK Titration Heart Rate NT-proBNP 0 0 -1 P = 0.1
Slide 25: Neutral or Improved Measures of Diastolic Function
Neutral or Improved Measures of Diastolic Function Improved systolic function with no negative impact on diastolic function E/e’ IVRT 1 10 p<0.0001 p<0.0001 0 5 p=0.6718 0 -1 p=0.1355 -5 -2 Placebo 25 mg Fixed Dose PK Titration Placebo 25 mg Fixed Dose PK Titration TR Velocity Diastolic Filling Time
Slide 26: Improvements in Symptoms
Improvements in Symptoms Change from Baseline in KCCQ Total Symptoms Score at Week 20 4.9-point improvement p= 0.03 14 12 10 8 6 4 2 0 Placebo OM 25 mg BID PK-titration Change from Baseline in KCCQ Subdomain Scores at Week 20 Symptom Frequency Symptom Burden 12 18 16 10 14 8 12 10 6 8 4 6 4 2 2 0 0
Slide 27: Troponins: Small Increases, Unrelated to Exposures
Troponins: Small Increases, Unrelated to Exposures to Omecamtiv Mecarbil COSMIC-HF • Baseline troponin I levels were above the diagnostic limit for myocardial infarction (0.04 ng/mL) for ~25% in COSMIC-HF • Events of increased troponin I (n=278 across all treatment groups) were independently adjudic
Slide 28: Prognostic Implications: NT-proBNP and Remodeling
Prognostic Implications: NT-proBNP and Remodeling Studies demonstrate correlation with cardiovascular outcomes Patients in PARADIGM-HF who had significant reductions in NT-proBNP had lower rates of CV death or heart 1 failure hospitalization Meta-analysis of drug/device therapies demonstrated associ
Slide 29: Pivotal Phase 3 Trial Completed Enrollment
Pivotal Phase 3 Trial Completed Enrollment GALACTIC-HF continuing following second planned interim analysis Topline results expected in Q4 2020 Overview Key Design Points Enrolled 8,256 patients at ~1,000 sites in 35 countries • Dose optimization based on trough concentration of omecamtiv mecarbil a
Slide 30: Clinical Trial Overview
Clinical Trial Overview Chronic HFrEF patients Omecamtiv mecarbil + SoC Starting dose: 25mg PO BID currently hospitalized for a primary reason of HF or with history of hospitalization or ER/ED admission for a primary Placebo + SoC reason of HF within 1 year Follow the same study procedures as OM gro
Slide 31: GALACTIC-HF: Design Paper & Interim Analyses
GALACTIC-HF: Design Paper & Interim Analyses • Passed first interim analysis: Q1 2019 • Assessed futility only (HR>1.0) • Triggered at 1/3 of target 1,590 deaths • Passed second interim analysis: Q1 2020 • Assessed futility & superiority • Triggered at 2/3 of target 1,590 deaths • Superiority: p-val
Slide 32: Baseline Characteristics: High Risk Population
Baseline Characteristics: High Risk Population Overall Inpatient Outpatient (N=8,256) (N=2,083) (N=6,173) • 8,256 patients enrolled in 35 Time from most recent HF hospitalization/ 2 (1-5) - 3 (2-6) ED visit (months), median (Q1-Q3) countries Age (years), mean (SD) 65 (11) 65 (11) 64 (11) • Populatio
Slide 33: Comparing Patients in Large Heart Failure Trials
Comparing Patients in Large Heart Failure Trials Highest risk patients in VICTORIA; lower risk in PARADIGM-HF, DAPA-HF GALACTIC-HF VICTORIA PARADIGM-HF DAPA-HF (N=8,256) (N=5,050) (N=8,339) (N=4,744) Age (y, mean (SD)) 65 (11) 67.3 (12.2) 63.8 (11.4) 66 (11) Race White 6,358 (77.0%) 3,239 (64.1%) 5,
Slide 34: Second Phase 3 Clinical Trial Underway
Second Phase 3 Clinical Trial Underway Investigating effect of omecamtiv mecarbil on exercise tolerance Trial enrolling patients in 9 countries in North America and Europe Primary Endpoint Study Plan Key Design Points Change in peak VO2 on CPET from baseline to • Designed to enroll approximately Tot
Slide 35: Clinical Trial Overview
Clinical Trial Overview Omecamtiv mecarbil + SoC Starting dose 25mg BID; titrated by PK to 25, 37.5 or 50 mg BID Subjects with chronic HFrEF and reduced exercise capacity Placebo + SoC “Titrated” to maintain study blind Study Visits Screen W-2 D1 W2 W4 W6 W8 W14 W20 W24 OM Concentration Dose Adjustm
Slide 36: Commercial Opportunity for New Heart Failure Therapy
Commercial Opportunity for New Heart Failure Therapy $1.7B sold in 2019; Q1 2020 sales increased 62% year over year ® Entresto Global Product Sales (M) 1.7bn US Ex-US 569 518 1.0bn 430 421 357 318 507m 271 239 200 185 128 110 84 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 2017 2018 2019 2020 *As with all
Slide 37: Commercial Readiness for Omecamtiv Mecarbil
Commercial Readiness for Omecamtiv Mecarbil Multiple workstreams in progress to prepare for successful commercial launch Determine areas of Cultivate advocacy Educate heart failure Assess impact for differentiation for heart failure market value proposition for HCPs patients O V E R V I E W C A R D
Slide 38: CK-274: Next-In-Class Cardiac Myosin Inhibitor
CK-274: Next-In-Class Cardiac Myosin Inhibitor Potential treatments for patients with HCM • Discovered by company scientists independent of collaborations • Selective allosteric inhibitor of cardiac myosin • No inhibition of smooth muscle myosin observed • Potential in vivo pharmacodynamic advantage
Slide 39: SAD & MAD Results Support Progression to Phase 2
SAD & MAD Results Support Progression to Phase 2 Phase 1: CK-274 was well tolerated in healthy participants, no SAEs* MAD PK: Steady-State Achieved After 14 SAD PK: Absorption and Elimination Generally Dose Days of Dosing Proportional Steady-state 600 150 attained 5 mg qd x 14d 10 mg qy x 14d 3,000
Slide 40: MAD Pharmacokinetic Parameters
CY 6011: MAD Pharmacokinetic Parameters Shallow Exposure-Response Relationship Observed Half-Life of CK-274 at Steady-State Preclinically Appears to Have Translated to Humans, was ~81 hours (3.4 days) On Average May Enable Flexible Dose Optimization in Humans PK/PD Relationship of CK-274 for Ejectio
Slide 41: Phase 2 Clinical Trial Design
Phase 2 Clinical Trial Design Two sequential dose-finding cohorts (optional 3rd cohort) CK-3773274 + SoC Patients with 2 symptomatic oHCM, and resting or provoked LVOT 1 gradient ≥ 50 mmHg Placebo + SoC Study Visits Screen W-1 D1 W2 W4 W6 W9 W10 W12 W14 Dose 1 Dose 3 Dose 2 IP Dosing PK Echocardiogr
Slide 42: CK-274: Clinical Development Plan for HCM
CK-274: Clinical Development Plan for HCM Phase 1 Phase 2 Phase 3 Safety, PK & PD Proof of Concept, Dose Finding Pivotal Studies SAD & MAD oHCM patients oHCMpatients Healthy Placebo Controlled Exercise Endpoint (peak VO2) Volunteers Echocardiography Endpoints IND Filed NDA Safe & tolerated dose NDA:
Slide 43: Obstructive HCM: Potential Phase 3 Trial Endpoints
Obstructive HCM: Potential Phase 3 Trial Endpoints • CPET – Cardiopulmonary exercise testing • Peak VO (oxygen uptake) 2 • V /VCO (ventilatory efficiency) E 2 • OUES (oxygen uptake efficiency slope) • NYHA class • Echocardiographic parameters – LVOT gradient, LVEF, LVFS, GLS • Biomarkers – NT-proBNP
Slide 44: Non-Obstructive HCM: Human Model of HFpEF Subgroup
Non-Obstructive HCM: Human Model of HFpEF Subgroup nHCM patients with similarities to subgroups of HFpEF patients with hypercontractility Symptoms and Pathophysiology are Similar in Both Conditions Symptoms Pathophysiology nHCM Dyspnea Increased Contractility Exercise Capacity Left Ventricular Hyper
Slide 45: Novel Approach Addresses Multiple Unmet Patient Needs
Novel Approach Addresses Multiple Unmet Patient Needs No FDA Approved Therapies Obstructive HCM oHCM CK-274 (Cardiac myosin Inhibitor) nHCM HFpEF Non-Obstructive HCM Heart Failure with Preserved Ejection Fraction O V E R V I E W C A R D I A C C A N D I D A T E S S K E L E T A L C A N D I D A TE S C
Slide 46: CV Franchise: Building to Improve Patient Healthspan
CV Franchise: Building to Improve Patient Healthspan Build leading CV Leverage Successfully launch, Expand CV pipeline commercial commercial omecamtiv mecarbil, internally and Improve CV patient organization organization to bring for patients with through novel healthspan supported by CK-274 & other
Slide 47: Building Synergistic Commercial Capabilities
Building Synergistic Commercial Capabilities Building Today… To Lead Tomorrow BUILDING TODAY… Building commercial organization focused Establish Cytokinetics as a CV leader by on hospitalized CV patients and HCPs to leveraging commercial capabilities for optimize opportunity for omecamtiv mecarbil f
Slide 48: Sarcomere Directed Drug Development: Skeletal Muscle
Sarcomere Directed Drug Development SKELETAL MUSCLE Reldesemtiv CK-601 48Sarcomere Directed Drug Development SKELETAL MUSCLE Reldesemtiv CK-601 48
Slide 49: Sarcomere Directed Drug Development: Skeletal Muscle
Sarcomere Directed Drug Development Skeletal muscle The sarcomere is a molecular structure found in skeletal and cardiac muscle that enables skeletal myocytes to contract and generate force Troponin Activate Activate Reldesemtiv CK-601 (Skeletal) (Skeletal) Tropomyosin Actin Calcium Thin filament AT
Slide 50: Phase 2 Clinical Trial in ALS
Phase 2 Clinical Trial in ALS Results presented at American Academy of Neurology 2019 Double-Blind, Placebo-Controlled: 12 weeks Placebo (n = 110) Parallel group, dose ranging study enrolled 458 patients with ALS in the US, Canada, 150 mg BID (n = 110) Australia and Europe evaluating change from Scr
Slide 51: Primary Endpoint: SVC
Primary Endpoint: SVC Change from baseline in percent predicted SVC at week 12 -6.46 -4.97 -4.62 -4.58 0 -1 -2 -3 Primary Analysis* P = 0.11 -4 for weighted -5 dose-response relationship -6 -7 * -8 -9 Placebo 150 mg BID 300 mg BID 450 mg BID *Based on Mixed Model for Repeated Measures (MMRM) with th
Slide 52: Change From Baseline: All Active vs Placebo
Change From Baseline: All Active vs Placebo* Results support progression to potential Phase 3 clinical trial SVC Change From Baseline ALSFRS-R Change From Baseline (All Active vs Placebo) (All Active vs Placebo) 0.0 0.0 *P = 0.10 *P = 0.01 LS Mean (SE) Difference LS Mean (SE) in Change of % Differen
Slide 53: Subgroup Analyses
Subgroup Analyses* ALSFRS-R Total Score Percent Predicted SVC No. of Patients LSM Difference No. of Patients LSM Difference (pbo/reldesemtiv) (95% Cl) Estimate P value (pbo/reldesemtiv) (95% Cl) Estimate P value Percent predicted SVC at baseline Percent predicted SVC at baseline <80 38/102 1.037 0.5
Slide 54: Post-Hoc Analyses Inform Potential Path Forward
Post-Hoc Analyses Inform Potential Path Forward Change From Baseline in ALSFRS-R Probability of No New DME* Over Time by Progressor Tertiles With Treatment With Reldesemtiv DME (Durable Medical Equipment): Manual wheelchair, power wheelchair, NIV, Augmentative Language Device, PEG Time (weeks) 0 1.0
Slide 55: Convergence of Verticals Addresses CV Conditions & Co-Morbidities
Convergence of Verticals Addresses CV Conditions & Co-Morbidities • HFrEF þ Enhanced Cardiac • HCM þ Muscle Performance • HFpEF Applicable Across • Other Cardiomyopathies Additional • Right Ventricle (RV) CV Conditions Dysfunction Enhanced Skeletal • Frailty Muscle Performance • Reduced Work Capacit
Slide 56: Sarcomere Directed Therapies Corporate Profile
Sarcomere Directed Therapies CORPORATE PROFILE 56Sarcomere Directed Therapies CORPORATE PROFILE 56
Slide 57: We're Up To The Challenge
We’re Up To The Challenge Pivotal trial Development Pivotal trials Potential FDA Clinical stage readout in programs by Pipeline* in 2021 approvals by 2025 programs 1 2 3 5 10 Q4 2020 2025 Heart Failure HCM ALS Ongoing Omecamtiv mecarbil CK-274 Reldesemtiv R&D o Phase 3 CV outcomes Programs* o Phase
Slide 58: Upcoming 2020 Milestones
Upcoming 2020 Milestones Expect Topline Results from Expect Data from Cohort 1 of Expect to Complete Enrollment GALACTIC-HF in Q4 REDWOOD-HCM in 2H in METEORIC-HF Conduct Commercial Readiness Prepare for Potential Phase 3 & Develop Co-Promotion Plan Clinical Trial of Reldesemtiv in for Omecamtiv Mec
Slide 59: Thank You
Sarcomere Directed Therapies THANK YOU John, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALSSarcomere Directed Therapies THANK YOU John, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALS