Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (July 2021)
54 slides from Cytokinetics's investor presentation, Jul 19, 2021
Slide 1: Sarcomere Directed Therapies
Sarcomere Directed Therapies Exhibit 99.1
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
To bring forward new medicines to improve the healthspan of people with devastating cardiovascular and neuromuscular diseases of impaired muscle function. Sarcomere Directed Therapies OUR MISSION
Slide 4: Our Vision: Leading with Science
Our vision is to be the leading muscle biology biopharma company that meaningfully improves the lives of patients with diseases of impaired muscle function through access to our pioneering medicines Achieve regulatory approvals for at least two drugs arising from our pipeline Build commercial capabi
Slide 5: Executing On Our Vision
Executing On Our Vision Scientific innovation driven by modulating cardiac myosin First-in-class myosin activator Next-in-class myosin inhibitor Expansion beyond contractility to muscle energetics, metabolism Regular input, collaboration and guidance Elevate patient voice Improve function, performan
Slide 6: Pipeline of Novel Muscle-Directed Drug Candidates
Pipeline of Novel Muscle-Directed Drug Candidates * Astellas to provide co-funding in exchange for low single-digit royalty All drug candidates above are investigational products and are not approved as safe or effective for any indication. CARDIAC MUSCLE Omecamtiv Mecarbil (Heart Failure) CK-274 (o
Slide 7: Sarcomere Directed Drug Development: Cardiac Muscle
CK-274, CK-271 Omecamtiv Mecarbil CK-136 (AMG 594) Sarcomere Directed Drug Development Cardiac MUSCLE
Slide 8: Contractile Dysfunction Underlies Heart Failure
Contractile Dysfunction Underlies Heart Failure Increased / Preserved Cardiac Contractility Non-obstructive Hypertrophic Cardiomyopathy (nHCM) Obstructive Hypertrophic Cardiomyopathy (oHCM) Heart Failure with Preserved Ejection Fraction (certain HFpEF subsets) Decreased Cardiac Contractility Heart F
Slide 9: 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 Actin Tropomyosin Myosin head Myosin lever arm Calcium ATP Thin filament Thick filament Activate CK-136 (Cardiac
Slide 10: Sarcomere Directed Drug Development: CK-274
Sarcomere Directed Drug Development CK-274
Slide 11: Symptomatic HCM: Orphan Indication
Symptomatic HCM: Orphan Indication Source: #26 SHA 2016-2021 Patient Claims Data; #20 Cogent HC 2020 DoF US HCM Prevalence
Slide 12: CK-274: Next-In-Class Cardiac Myosin Inhibitor
CK-274: Next-In-Class Cardiac Myosin Inhibitor Potential treatment for patients with HCM Myosin Selective allosteric inhibitor of cardiac myosin discovered by company scientists independent of collaborations Potential in vivo pharmacodynamic advantages related to distinctive binding site Optimized f
Slide 13: SAD & MAD Results Support Progression to Phase 2
Preclinical data translated to healthy participants SAD & MAD Results Support Progression to Phase 2 MAD PK: Steady-State Achieved After 14 Days of Dosing Nominal Day 0 2 4 6 8 10 12 14 16 18 20 150 100 50 0 CK-274 (ng/mL) 10 mg qy x 14d 5 mg qd x 14d Steady-state attained Last dose Trough samples o
Slide 14: Phase 2 Clinical Trial Design
Phase 2 Clinical Trial Design Two sequential dose-finding cohorts (with third cohort assessing patients on disopyramide) PK Echocardiogram Dose 1 Dose 2 Dose 3 Patients with symptomatic oHCM, and resting or provoked LVOT gradient ≥ 50 mmHg Study Visits Screen W-1 D1 W2 W4 W6 W9 W10 W12 W14 Screening
Slide 15: Patient Enrollment and Dosing
Patient Enrollment and Dosing 41 Total Enrolled Patients Final Dose Achieved (N) Cohort 1 Cohort 2 Placebo 5mg 10mg 15mg 10mg 20mg 30mg 13 4 5 5 9 4 1
Slide 16: Baseline Echocardiographic Data
Baseline Echocardiographic Data Characteristic, mean Baseline (Day 1 Pre-dose) Placebo C1 + C2 Combined (N = 13) CK-274 Cohort 1 (N = 14) Cohort 2 (N = 14) LVEF (%) 74.5 73.2 75.4 LVOT-G, Rest (mmHg) 52.1 53.8 58.2 LVOT-G, Valsalva (mmHg) 84.6 74.4 82.3
Slide 17: High Response Rates on Treatment with CK-274
High Response Rates on Treatment with CK-274 1/13 11/14 13/14 Responder # / Total # Responder Definition: Resting LVOT-G <30 mmHg and post-Valsalva LVOT-G <50 mmHg at Week 10
Slide 18: Resting Left Ventricular Outflow Tract Gradient
Resting Left Ventricular Outflow Tract Gradient Mean ± SEM Resting LVOT-G (mmHg) Baseline Week 2 Week 4 Week 6 Week 10 Placebo (n=13) 52.1 45.0 47.1 49.0 44.0 Cohort 1 (n = 14) 53.8 24.3 27.3 13.9 13.4 p-value vs placebo - 0.007 0.025 <0.0001 0.0003 Cohort 2 (n = 14) 58.2 15.5 16.1 10.9 15.1 p-value
Slide 19: Post-Valsalva Left Ventricular Outflow Tract Gradient
Post-Valsalva Left Ventricular Outflow Tract Gradient Mean ± SEM Valsalva LVOT-G (mmHg) Baseline Week 2 Week 4 Week 6 Week 10 Placebo (n=13) 84.6 71.3 71.3 73.4 76 Cohort 1 (n = 14) 74.4 51.3 46.1 37.1 38.1 p-value vs placebo - 0.097 0.038 0.0003 0.001 Cohort 2 (n = 14) 82.3 32.3 31.5 30.3 29.8 p-va
Slide 20: Safety Data
Safety Data Incidence of adverse events on CK-274 similar to placebo and mild or moderate There were no treatment related serious adverse events reported by investigators No patients who received CK-274 in Cohort 1 had an LVEF <50% In Cohort 2, one patient with LVEF at baseline of 58% was up titrate
Slide 21: 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 changes
Slide 22: Engaging Regulatory Authorities to Inform Phase 3
Engaging Regulatory Authorities to Inform Phase 3 Type C meeting with FDA to review Phase 3 clinical trial design End of Phase 2 meeting to review final dose selection rationale for Phase 3
Slide 23: CK-274: Clinical Development Plan for HCM
Well tolerated dose with desired PD effects oHCM patients Placebo Controlled Echocardiography Endpoints oHCM patients Exercise Endpoint (peak VO2) Extension study Long-term safety & efficacy SAD & MAD Healthy Volunteers Proof of activity in nHCM pts Pivotal study in nHCM IND Filed NDA CK-274: Clinic
Slide 24: Novel Approach May Address Multiple Unmet Patient Needs
Novel Approach May Address Multiple Unmet Patient Needs No FDA-approved therapies nHCM Non-Obstructive HCM HFpEF Heart Failure with Preserved Ejection Fraction Obstructive HCM oHCM CK-274 (Cardiac myosin Inhibitor)
Slide 25: 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: Funding for Development of CK-274 Cytokinetics receives options for additional funding for further development of CK
Slide 26: Sarcomere Directed Drug Development: Omecamtiv Mecarbil
Sarcomere Directed Drug Development Omecamtiv Mecarbil
Slide 27: Heart Failure: Growing Prevalence and High Readmission Rates
Mozzafarian, et al. Circulation 2016; 133: e38-360 Number of cases (M) 2012 2030 +46% Heart Failure: Growing Prevalence and High Readmission Rates 6 million people have heart failure in the United States Prevalence Expected to Increase by 46% from 2012 – 2030 Initial Hospitalization 24% readmitted <
Slide 28: Pivotal Phase 3 Trial Design
Pivotal Phase 3 Trial Design *An HF event defined as the presentation of the subject for an urgent, unscheduled clinic/office/ED visit, or hospital admission, with a primary diagnosis of HF, where the patient exhibits new or worsening symptoms of HF on presentation, has objective evidence of new or
Slide 29: Baseline Characteristics
Baseline Characteristics Characteristic OM (N=4120) Placebo (N=4112) Demographics Age (years), median (Q1, Q3) 66 (58, 73) 66 (58, 73) Sex, female, n (%) 875 (21.2) 874 (21.3) White/Asian/Black/other, % 78/9/7/7 78/9/7/7 Heart Failure History and Medical Conditions LVEF (%), mean (SD) 26.6 (6.3) 26.
Slide 30: Primary Composite Endpoint
Primary Composite Endpoint Time to first HF event or CV death Placebo 4112 3310 2889 2102 1349 647 141 OM 4120 3391 2953 2158 1430 700 164 Patients at risk, n Cumulative incidence, % 0 6 12 18 24 30 36 50 40 30 20 10 0 45 35 25 15 5 Months (30 days) since randomization Placebo Omecamtiv mecarbil HR
Slide 31: Primary Composite Components and KCCQ TSS
Change in KCCQ TSS from Baseline to Week 24 Primary Composite Components and KCCQ TSS LS mean change Status at randomization CV Death HR = 1.01 (95% CI, 0.92–1.11) P = 0.86 Heart Failure Event HR = 0.93 (95% CI, 0.86–1.00) P = 0.063 +2.5 (95% CI, 0.54–4.46) -0.5 (95% CI, -1.40–0.48) Joint test P = 0
Slide 32: Laboratory and Safety Events
Laboratory and Safety Events Variable Omecamtiv Mecarbil (N=4110) Placebo (N=4101) Relative Risk or Difference (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 33: Treatment Effect Increased 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 Interaction p = 0.013 by EF quartile 25 20 15 10 30 35 10 20 30 40 50 60 Ejection fraction (%) Incidence Rate (per 100 py) Placebo Omecamtiv mecarbil Treatment Effect Tr
Slide 34: Greater Treatment Effect in More Severe HF
Greater Treatment Effect in More Severe HF Results of the primary outcome in pre-specified subgroups showed greater treatment effect in patients with markers of more severe heart failure, including patients with LVEF ≤28%: (n=4,456) HR 0.84; 95% CI 0.77, 0.92 Subgroup No. of Events/ No. of Patients
Slide 35: Increased Treatment Effect with Severe HF
Increased Treatment Effect with Severe HF Severe HF defined as NYHA III-IV, EF ≤ 30%, HF hospitalization in last 6 months Treatment effect for primary endpoint in severe HF HR = 0.80 (0.71, 0.90) Absolute risk reduction 8.3 events/100 pt-years NNT = 12 Source: Felker GM, Omecamtiv Mecarbil in Patien
Slide 36: Increased Treatment Effect with Higher NT-proBNP
Increased Treatment Effect with Higher NT-proBNP Source: McMurray JM, Efficacy of omecamtiv mecarbil in HFrEF according to NT-proBNP level: Insights from the GALACTIC-HF trial, ESC Heart Failure 2021, June 2021 Continuous HR 95%CI HR=1 (unity) Placebo better OM better HR=1 (unity) Primary Composite
Slide 37: On Track to Submit NDA in Second Half 2021
On Track to Submit NDA in Second Half 2021 Three interactions with FDA in 2021 inform submission based on GALACTIC-HF Topline meeting to review results of GALACTIC-HF Type C meeting to discuss questions about GALACTIC-HF, approach to NDA submission Pre-NDA meeting to review administrative details of
Slide 38: Large Number of Patients At Potential US Launch
Large Number of Patients At Potential US Launch Of Omecamtiv Mecarbil Patient with HFrEF & EF ≤30% HFrEF Population Heart Failure Prevalence including HFpEF 1.2 – 2.0M patients at potential launch Omecamtiv mecarbil Target Population Patient with HFrEF & EF ≤30% and NYHA III/IV 2032 Estimates 2020 E
Slide 39: Potential to Offset Medicare Hospitalization Costs
Patients on omecamtiv mecarbil showed reductions in both hospital admissions and re-admissions2 Potential to Offset Medicare Hospitalization Costs 18% Yr 1 20% Yr 2 23% Yr 3 Reduction in 30-day re-admissions Decrease in number of hospital admissions per year Desai et al, Yale University School of Me
Slide 40: Fit-for-Purpose Sales Team: Face-to-Face & Virtual Visits
Remote Heavy Targets Field Heavy Targets Balanced Targets Cytokinetics Rep % 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 – rep spends most of the time in face-to-face interaction Hybrid engagem
Slide 41: Applied Analytics Will Inform Channel Mix and Deployment
Applied Analytics Will Inform Channel Mix and Deployment Deploy to Hot Spots Example Cities High PFF High DP Miami, FL Wichita, KS High PFF Low DP Montgomery, AL Las Vegas, NV Low PFF High DP Boston, MA Minneapolis, MN Low PFF Low DP Austin, TX Grand Rapids, MI Illustrative High DP Engagement High P
Slide 42: Building Synergistic Commercial Capabilities
Building commercial organization focused on hospitalized CV patients and HCPs to optimize opportunity for omecamtiv mecarbil Cultivate advocacy with CV patients and HCPs Establish Cytokinetics as a CV leader by leveraging commercial capabilities for future product launches Significant overlap betwee
Slide 43: Sarcomere Directed Drug Development: Skeletal Muscle
Reldesemtiv CK-601 Sarcomere Directed Drug Development Skeletal MUSCLE
Slide 44: 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 Actin Tropomyosin Thin filament Thick filament Myosin head Myosin lever arm Calcium ATP Activate Reldesemtiv (
Slide 45: Planned Phase 3 Clinical Trial Design
Planned Phase 3 Clinical Trial Design Trial to open for enrollment in 2021 (N= 555) Randomization 2:1 Stratification: Riluzole & Edaravone Placebo Reldesemtiv 300 mg BID End of Study 14 days Reldesemtiv 300 mg BID Screening Enrolling 555 patients with ALS in the US, Canada, Australia and Europe eval
Slide 46: Corporate Profile
Sarcomere Directed Therapies Corporate profile
Slide 47: Robust Pipeline, Solid Financial Position
Programs* Heart Failure Omecamtiv mecarbil HCM CK-274 Positive results from REDWOOD-HCM Expect to begin Phase 3 trial by year end ALS Reldesemtiv Expect to begin COURAGE-ALS, Phase 3 trial, in Q3 2021 Ongoing R&D Additional research in muscle biology, energetics & metabolism Robust Pipeline, Solid F
Slide 48: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance in millions Total Cash and investments $460.2 Leased assets $86.1 Other assets $30.8 Total Assets $577.1 Debt $134.0 Liability related to sale of future royalties $168.9 Deferred Revenue $87.0 Lease liability $85.6 Other liabilities $33.7 Total Liabilities $509.2 W
Slide 49: Expected Upcoming 2021 Milestones
Submit US NDA for omecamtiv mecarbil in 2H 2021 Expected Upcoming 2021 Milestones Expect results from METEORIC-HF in early 2022 Expect to Begin Phase 3 Trial of CK-274 by Year End Start COURAGE-ALS, Phase 3 Clinical Trial of Reldesemtiv in Patients with ALS, in Q3
Slide 50: Thank You
y G Cytokinetics THANK YOU
Slide 51: Appendix
Sarcomere Directed Therapies APPENDIX
Slide 52: Significant Unmet Need in HCM
Significant Unmet Need in HCM Current therapies do not target underlying disease Surgical intervention not permanent solution Current medical therapy does not target underlying disease 1 in 500 have genetic mutation 1 in 3200 have HCM Subset of patients have progressive symptoms, atrial fibrillation
Slide 53: Under-Treatment Due To Concerns Over Tolerability, Co-Morbidities
Under-Treatment Due To Concerns Over Tolerability, Co-Morbidities Initiation of therapy limited due to concerns over patient tolerability and co-morbidities… “Obviously [goal is to] help increase their longevity, reduce their morbidity and mortality with [being] able to tolerate the side effects of
Slide 54: Omecamtiv Mecarbil: Positive Phase 3 Trial Results
Omecamtiv Mecarbil: Positive Phase 3 Trial Results First Cardiac Sarcomere Screen First POC Isolated Hearts and in vivo CK-1827452 First Synthesized First CTA/ Regulatory Filing Phase 1 CY 1111 Amgen Option Agreement Phase 2 CY 1121 Amgen Exercises Option Initiate Phase 2 COSMIC-HF Initiate Phase 3