Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (June 2021)
56 slides from Cytokinetics's investor presentation, Jun 1, 2021
Slide 1: Empowering Muscle, Empowering Lives
Sarcomere Directed Therapies EMPOWERING MUSCLE EMPOWERING LIVES John, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALS
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: 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) CK-274 (oHCM, nHCM, HFpEF) CK-271 CK-136 (AMG 594) (Heart Failure, other) SKELETAL MUSCLE Reldesemtiv (ALS)* CK-601 Additional Skeletal Muscle Activators
Slide 6: Cardiac Muscle: Sarcomere Directed Drug Development
Sarcomere Directed Drug Development CARDIAC MUSCLE Omecamtiv Mecarbil CK-136 (AMG 594) CK-274, CK-271 6
Slide 7: 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 10 Men Women 9 8 7 Number of cases (M) 6 +46% 5 4 8.3 3 5.7 2 1 0 2012 2030 Mo
Slide 8: High Hospital Readmission Rates
High Hospital Readmission Rates Heart failure is one of the most frequent causes of hospitalization in people > 65 1,2 Initial <1 month 60 days <6 months <12 months Hospitalization post-discharge4,6 post-discharge7 post-discharge5 post-discharge3,8 1 of 2 24% ~ 25-50% 44% 66% hospitalized readmitted
Slide 9: High Economic Burden of Heart Failure
High Economic Burden of Heart Failure Heart failure costs ~$123 billion annually, representing 33% of total Medicare budget 1,2 Inpatient Admission Rates for HF Patients 6X Higher than Non-HF Patients1 1800 1600 Annual Inpatient Admits per 1,000 1400 Heart failure is the most 1200 frequent diagnosis
Slide 10: 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 11: 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 Inhibit Inhibit Omecamtiv CK-274 CK-271 Activate Mecarbil (Cardiac) (Cardiac) CK-136 Myosin (C
Slide 12: Omecamtiv Mecarbil: Novel Mechanism Approach
Omecamtiv Mecarbil: Novel Mechanism Approach OV ER V IEW C A RD IAC C AND ID ATES 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 O F I L E 12
Slide 13: Omecamtiv Mecarbil: Positive Phase 3 Trial Results
Omecamtiv Mecarbil: Positive Phase 3 Trial Results >30 trials: 23 Phase 1 studies with 600+ participants, 7 Phase 2 trials with 1,400+ patients, 2 Phase 3 trials with 8,000+ patients Phase 2 Amgen Initiate Initiate Initiate Initiate First Cardiac First POC CK-1827452 CY 1121 Exercises Phase 2b Phase
Slide 14: Pivotal Phase 3 Trial Design
Pivotal Phase 3 Trial Design Landmark clinical trial results published in NEJM Overview Key Design Points Enrolled 8,256 patients at ~1,000 sites in 35 countries • Dose optimization based on trough concentration of omecamtiv mecarbil at 2 weeks and 6 weeks Primary Endpoint • High risk patients enrol
Slide 15: Clinical Trial Overview
Clinical Trial Overview Overall median study exposure was 21.8 months Clinical Trial Schema Patient Disposition 11121 Screened 2865 Excluded Chronic HFrEF patients currently hospitalized for a 1831 Did not meet inclusion criteria primary reason of HF or with history of hospitalization or 723 Did not
Slide 16: Baseline Characteristics
Baseline Characteristics OM Placebo OM Placebo Characteristic Characteristic (N=4120) (N=4112) (N=4120) (N=4112) Demographics Vitals and Laboratory Parameters 1977 2025 NT-proBNP (pg/mL), median (Q1, Q3) Age (years), median (Q1, Q3) 66 (58, 73) 66 (58, 73) (980, 4061) (1000, 4105) SBP (mmHg), mean (
Slide 17: Primary Composite Endpoint
Primary Composite Endpoint Time to first HF event or CV death 50 Placebo 45 40 Omecamtiv Cumulative incidence, % mecarbil 35 30 25 20 HR = 0.92 (95% CI, 0.86–0.99) 15 10 P = 0.025 5 0 0 6 12 18 24 30 36 Patients Months (30 days) since randomization at risk, n Placebo 4112 3310 2889 2102 1349 647 141
Slide 18: Primary Composite Components and KCCQ TSS
Primary Composite Components and KCCQ TSS CV Death Change in KCCQ TSS from Baseline to Week 24 HR = 1.01 (95% CI, 0.92–1.11) P = 0.86 50 Joint test P = 0.028 Cumulative incidence, % 40 30 Placebo 25 +2.5 (95% CI, 0.54–4.46) OM Placebo 20 Omecamtiv 23.7 mecarbil 10 20 21.2 LS mean change 0 0 6 12 18
Slide 19: Laboratory and Safety Events
Laboratory and Safety Events Omecamtiv Mecarbil Placebo Relative Risk or Difference Variable (N=4110) (N=4101) (95% CI) Laboratory value change from baseline to Week 24 Systolic blood pressure – mmHg, mean (SD) 1.4 (15.3) 1.5 (15.6) -0.1 (-0.9, 0.6) Heart rate, bpm, mean (SD) -2.1 (12.6) -0.5 (12.8)
Slide 20: Greater Treatment Effect in More Severe HF
Greater Treatment Effect in More Severe HF No. of Events/ Hazard Ratio Norm Subgroup ARR No. of Patients (95% Cl) p-value 0.92 (0.86, All Patients 3103/8232 0.025 2.1% 0.99) 0.84 (0.77, LVEF ≤28% 1821/4456 <0.001 4.9% 0.92) Results of the primary outcome in Outpatients 1255/3304 0.83 (0.75, 0.93) 0.
Slide 21: Baseline Characteristics by EF Quartile (1)
Baseline Characteristics by EF Quartile (1) Q1: EF ≤22% Q4: EF ≥33% Q1: EF ≤22% Q4: EF ≥33% Demographics P-Value Medical Conditions, n (%) P-Value (N=2246) (N=1750) (N=2246) (N=1750) Age (years), mean±SD 62.5 ± 12 66.4 ± 11 <0.001 Coronary artery disease 1267 (56) 1218 (70) <0.001 Sex, female, n (%)
Slide 22: Baseline Characteristics by EF Quartile (2)
Baseline Characteristics by EF Quartile (2) Vitals and Q1: EF ≤22% Q4: EF ≥33% Medications and Q1: EF ≤22% Q4: EF ≥33% Laboratory P-Value P-Value (N=2246) (N=1750) Cardiac Devices, n (%) (N=2246) (N=1750) Parameters ACEi, ARB or ARNi 1900 (85) 1539 (88) <0.001 Body mass index 27.9 (6.3) 29.1 (6.1) <
Slide 23: Treatment Effect Increased Progressively As Baseline EF Decreased
Treatment Effect Increased Progressively As Baseline EF Decreased In EF ≤22%, 11.8 needed-to-treat to prevent 1 event over 3 years Relative Treatment Effect on Primary Incidence of Primary Composite Endpoint Composite Endpoint 60 Interaction 50 Placebo p = 0.013 1.2 by EF quartile 40 Incidence Rate
Slide 24: Large, Well-Identified Severe HF Patient Population
Large, Well-Identified Severe HF Patient Population Adult (18+ yrs, USA) 2020 Estimates 2032 Estimates 7.1M 9.2M Heart failure prevalence including HFpEF 3.6M 4.6M HFrEF population (i.e. Entresto target population) Omecamtiv mecarbil Target Population 2.3M 3.0M Patient with HFrEF & EF ≤30% Patient w
Slide 25: Potential to Offset Medicare Hospitalization Costs
Potential to Offset Medicare Hospitalization Costs Hospitalization drives cost Patients on omecamtiv mecarbil showed reductions in both hospital for Medicare patients1 admissions and re-admissions2 • Mean cost per HFrEF hospitalization: $10,735 20% 23% • Mean cost for 30-day post- 18% Yr 3 18% Yr 1
Slide 26: Fit-for-Purpose Sales Team: Face-to-Face & Virtual Visits
Fit-for-Purpose Sales Team: Face-to-Face & Virtual Visits Illustration Cytokinetics Rep Field Heavy Targets Balanced Targets Remote Heavy Targets % of Face-to-Face Visits Heavy face-to-face Mix of face-to-face and remote Minimum face-to-face Engagement Description Similar to traditional engagement –
Slide 27: Applied Analytics Will Inform Channel Mix and Deployment
Applied Analytics Will Inform Channel Mix and Deployment Patient and HCP Heat Map in HFrEF Physician Engagement Type by Geography Illustrative Example Cities High PFF Miami, FL High DP High DP Wichita, KS Engagement High PFF Montgomery, AL Low DP Las Vegas, NV Low PFF Boston, MA Deploy to Hot Spots
Slide 28: Second Phase 3 Clinical Trial Underway
Second Phase 3 Clinical Trial Underway Investigating effect of omecamtiv mecarbil on exercise tolerance Expect enrollment to complete in 1H 2021 Primary Endpoint Study Plan Key Design Points Change in peak VO2 on CPET from baseline to Total Countries • Designed to enroll approximately 9 Week 20 Plan
Slide 29: Clinical Trial Overview
Clinical Trial Overview (omecamtiv mecarbil: Omecamtiv mecarbil + SoC Randomized 2:1 Subjects with Starting dose 25mg BID; titrated by PK to 25, 37.5 or 50 mg BID End of Study Screening placebo) chronic HFrEF and reduced exercise capacity Placebo + SoC “Titrated” to maintain study blind Study Visits
Slide 30: 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 31: 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 32: 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* SAD PK: Absorption and Elimination Generally Dose MAD PK: Steady-State Achieved After 14 Proportional Days of Dosing 600 Steady-state 150 attained 5 mg qd x 14d 3,000 10 mg qy x 14d
Slide 33: CY 6011: MAD Pharmacokinetic Parameters
CY 6011: MAD Pharmacokinetic Parameters Half-Life of CK-274 at Steady-State Shallow Exposure-Response Relationship Observed was ~81 hours (3.4 days) On Average Pre-clinically Appears to Have Translated to Humans, May Enable Flexible Dose Optimization in Humans PK/PD Relationship of CK-274 for Ejecti
Slide 34: Phase 2 Clinical Trial Design
Phase 2 Clinical Trial Design Two sequential dose-finding cohorts (optional 3rd cohort) CK-3773274 + SoC Randomization Patients with End of Study 2 Screening 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 Do
Slide 35: Interim Analysis Informed Progression to Cohort 2
Interim Analysis Informed Progression to Cohort 2 Cohort 2 enrollment complete; Cohort 3 enrolling patients on disopyramide Topline results for Cohort 1 and 2 expected mid-year 2021 Cohort 1: Escalating doses of • Interim analysis of data from Cohort 1 demonstrated: 5, 10, 15 mg once daily • Substan
Slide 36: Open Label Extension Trial
Open Label Extension Trial REDWOOD-HCM OLE open for eligible patients who completed REDWOOD-HCM • Primary endpoint: incidence of AEs & LVEF <50 • Secondary endpoints: measures of long-term effects of CK-274 on LVOT-G; assessments of steady-state pharmacokinetics. • Cardiac MRI sub-study to assess ch
Slide 37: 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 oHCM patients Healthy Placebo Controlled Exercise Endpoint (peak VO2) IND Filed Volunteers Echocardiography Endpoints NDA Well tolerated dose Impro
Slide 38: Novel Approach May Address Multiple Unmet Patient Needs
Novel Approach May Address 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 OV ER V IEW C A RD IAC C AND ID ATES S K E L E T A L C A N D I D A TE S C O R P O R A
Slide 39: CK-274: Collaborations & Agreements
CK-274: 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 & commerc
Slide 40: CV Franchise: Building to Improve Patient Healthspan
CV Franchise: Building to Improve Patient Healthspan Successfully launch, Leverage Build leading CV commercial Expand CV pipeline omecamtiv mecarbil, internally and Improve CV patient commercial organization to bring for patients with through novel healthspan organization CK-274 & other HFrEF partne
Slide 41: Building Synergistic Commercial Capabilities
Building Synergistic Commercial Capabilities Building BUILDING Today… TODAY… To Lead Tomorrow 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 42: Skeletal Muscle: Sarcomere Directed Drug Development
Sarcomere Directed Drug Development SKELETAL MUSCLE Reldesemtiv CK-601 42
Slide 43: 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 44: 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, Australia and 150 mg BID (n = 110) Europe evaluating change Screenin
Slide 45: 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 Percent Predicted SVC Change From -1 Baseline at Week 12 (95% CI) -2 -3 Primary Analysis* -4 P = 0.11 for weighted -5 dose-response relationship -6 -7 -8 * -9 Placebo 150 mg BID 300 mg BID 450 mg
Slide 46: 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 LS Mean (±SE) of Change in Functional Rating *P = 0.10 *P = 0.01 Scale – Revised
Slide 47: Subgroup Analyses
Subgroup Analyses* Percent Predicted SVC ALSFRS-R Total Score 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
Slide 48: 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, Time (weeks) Augmentative Language Device, PEG 0 LS
Slide 49: Planned Phase 3 Clinical Trial Design
Planned Phase 3 Clinical Trial Design Trial to open for enrollment in 2021 Enrolling 555 patients with ALS in the US, Canada, Reldesemtiv Australia and (N= 555) 300 mg BID End of Study Screening Randomization Europe evaluating 2:1 change from baseline ALSFRS-R Stratification: Riluzole & at 24 weeks
Slide 50: 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 51: Corporate Profile
Sarcomere Directed Therapies CORPORATE PROFILE 51
Slide 52: Robust Pipeline, Solid Financial Position
Robust Pipeline, Solid Financial Position Pipeline* 1 Positive trial readout in Q4 2020 2 Pivotal trials in 2021 3 Potential FDA approvals by 2025 5 Clinical stage programs 10 Development programs by 2025 Heart Failure HCM ALS Ongoing Omecamtiv mecarbil o Positive outcomes CK-274 o Phase 2 trial Rel
Slide 53: Cytokinetics Financing History
Cytokinetics Financing History in millions Upfront Cash, Option, R&D As of 3/31/2021 Financing Equity & Milestones Reimbursement Total Private Investors (VCs) $116 $116 IPO $94 $94 Public Post-IPO/Other $609 $609 Investors Term Loan $45 $45 Convertible Debt (net)* $120.5 $120.5 $165.5 $819 $984.5 Ca
Slide 54: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance Ended Q1 with 2+ years cash runway based on 2021 guidance 2021 Condensed Balance Sheet 2021 Financial Guidance As of 3/31/2021 in millions in millions Total Total Cash and investments $460.2 Cash Revenue $23 – 28 Leased assets $86.1 Cash Operating Expenses* $195 –
Slide 55: Upcoming 2021 Milestones
Upcoming 2021 Milestones Continue to Engage Regulatory Develop Go-To-Market Strategy Authorities for Omecamtiv Expect to Complete Enrollment and Launch Plan for Omecamtiv Mecarbil in Q2 2021; Submit in METEORIC-HF in 1H 2021 Mecarbil in 1H 2021 US NDA in 2H 2021 Conduct Start-Up Activities for Expec
Slide 56: Thank You
Sarcomere Directed Therapies THANK YOU John, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALS