Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (July 2021)
60 slides from Cytokinetics's investor presentation, July 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: Executing On Our Vision
Executing On Our Vision • Positive Phase 3 results from • Scientific innovation driven by GALACTIC-HF; NDA submission modulating cardiac myosin expected in 2H 2021 • First-in-class myosin activator • Positive Phase 2 results from • Next-in-class myosin inhibitor REDWOOD-HCM; Phase 3 clinical • Expan
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) 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 7: Cardiac Muscle
Sarcomere Directed Drug Development CARDIAC MUSCLE Omecamtiv Mecarbil CK-136 (AMG 594) CK-274, CK-271 7
Slide 8: Omecamtiv Mecarbil
Omecamtiv Mecarbil 8
Slide 9: Contractile Dysfunction Underlies Heart Failure
Contractile Dysfunction Underlies Heart Failure Increased / Preserved Decreased Cardiac Cardiac Contractility Contractility • Non-obstructive • Heart Failure with Hypertrophic Reduced Ejection Cardiomyopathy (nHCM) Fraction (HFrEF) • Obstructive Hypertrophic • Genetic Dilated Cardiomyopathy (oHCM) C
Slide 10: Heart Failure: Growing Prevalence and High Readmission Rates
Heart Failure: Growing Prevalence and High Readmission Rates 6 million people have heart failure in the United States Prevalence Expected to Initial 1 of 2 hospitalized HF patients are Increase by 46% from 2012 – 2030 Hospitalization readmitted within 6 months5 <1 month 10 post-discharge4,6 9 24% re
Slide 11: 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 12: 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 13: Sarcomere Directed Drug Development
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 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: 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 16: 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 17: 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 18: 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 19: 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 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: 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 22: Increased Treatment Effect with Higher NT-proBNP
Increased Treatment Effect with Higher NT-proBNP Primary Composite Outcome HF Hospitalization Placebo better 1.8 1.8 1.6 1.6 1.4 1.4 1.2 1.2 Treatment Effect Treatment Effect HR=1 (unity) 1 1 HR=1 (unity) .8 .8 95%CI .6 .6 Continuous HR OM better .4 .4 200 500 1000 2000 5000 10000 20000 200 500 1000
Slide 23: Large Number of Patients At Potential US Launch
Large Number of Patients At Potential US Launch Of Omecamtiv Mecarbil Adult (18+ yrs, USA) 2020 Estimates 2032 Estimates 6.2M1 8.0M3 Heart Failure Prevalence including HFpEF 3.1M2 4.0M3 HFrEF Population Omecamtiv mecarbil Target Population 2.0M2 2.6M3 Patient with HFrEF & EF ≤30% Patient with HFrEF
Slide 24: Potential to Offset Medicare Hospitalization Costs
Potential to Offset Medicare Hospitalization Costs Outcomes from GALACTIC-HF may translate into economic benefits to payers and IDNs Hospitalization drives cost Patients on omecamtiv mecarbil showed reductions in both hospital for Medicare patients1 admissions and re-admissions2 • Mean cost per HFrE
Slide 25: 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 26: 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 27: Second Phase 3 Clinical Trial Underway
Second Phase 3 Clinical Trial Underway Investigating effect of omecamtiv mecarbil on exercise tolerance Enrollment complete; results expected in 2H 2022 Primary Endpoint Study Plan Key Design Points Change in peak VO2 on CPET from baseline to Total Countries • Designed to enroll approximately 9 Week
Slide 28: 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 29: CK-274
CK-274 29
Slide 30: Symptomatic HCM: Orphan Indication
Symptomatic HCM: Orphan Indication US HCM Prevalence 1,081 High end est. (CVrg 2020) 1000 421 800 Diagnosis gap Low end est. (560-805K patients) 600 (Maron 2013) 400 High end (SHA 280 660 diagnosed HCM 200 pts. 2016-2021) 180 Low end (Maron 2013) 100 0 Diagnosed Patients Patient Prevalence Source: #
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: CK-274: Next-In-Class Cardiac Myosin Inhibitor
CK-274: Next-In-Class Cardiac Myosin Inhibitor Potential treatment for patients with HCM • Selective allosteric inhibitor of cardiac myosin discovered by company scientists independent of collaborations • Potential in vivo pharmacodynamic advantages related to distinctive binding site • Optimized fo
Slide 33: SAD & MAD Results Support Progression to Phase 2
SAD & MAD Results Support Progression to Phase 2 Preclinical data translated to healthy participants Shallow Exposure-Response Relationship Observed MAD PK: Steady-State Achieved After 14 Pre-clinically Appears to Have Translated to Humans, Days of Dosing May Enable Flexible Dose Optimization in Hum
Slide 34: Phase 2 Clinical Trial Design
Phase 2 Clinical Trial Design Two sequential dose-finding cohorts (with third cohort assessing patients on disopyramide) Randomization Patients with CK-3773274 + SoC End of Study Screening symptomatic oHCM, 2 and resting or provoked LVOT 1 gradient ≥ 50 mmHg Placebo + SoC Study Visits Screen W-1 D1
Slide 35: Patient Enrollment and Dosing
Patient Enrollment and Dosing 41 Total Enrolled Patients Final Dose Achieved (N) Cohort 1 Cohort 2 Placebo 5 mg 10 mg 15 mg 10 mg 20 mg 30 mg 13 4 5 5 9 4 1 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 35
Slide 36: Baseline Echocardiographic Data
Baseline Echocardiographic Data Baseline (Day 1 Pre-dose) Characteristic, mean Placebo CK-274 C1 + C2 Combined (N = 13) 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 OV ER V IEW C A RD IAC C AND ID ATES S K E L E
Slide 37: High Response Rates on Treatment with CK-274
High Response Rates on Treatment with CK-274 1/13 11/14 13/14 Responder # / Total # 100 7.7% 78.6% 92.9% Not Responder Responder 80 Responder Definition: 60 Resting LVOT-G <30 mmHg % Total and post-Valsalva LVOT-G <50 mmHg at Week 10 40 20 92.3% 21.4% 7.1% 0 Placebo CK-274: C1 CK-274: C2 OV ER V IEW
Slide 38: Resting Left Ventricular Outflow Tract Gradient
Resting Left Ventricular Outflow Tract Gradient Resting LVOT-G 80 Combined Placebo CK-274: Cohort 1 60 CK-274: Cohort 2 mmHg 40 20 mean ± SEM 0 0 2 4 6 8 10 Weeks Mean ± SEM Valsalva 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
Slide 39: Post-Valsalva Left Ventricular Outflow Tract Gradient
Post-Valsalva Left Ventricular Outflow Tract Gradient Valsalva LVOT-G 100 Combined Placebo CK-274: Cohort 1 80 60 CK-274: Cohort 2 mmHg 40 20 mean ± SEM 0 0 2 4 6 8 10 Weeks 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
Slide 40: 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
Slide 41: 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 42: CK-274: Clinical Development Plan for HCM
CK-274: Clinical Development Plan for HCM Engaging regulatory authorities to inform Phase 3 Type C meeting with FDA to review Phase 3 design; End-of-Phase 2 meeting to review dose selection rationale for Phase 3 Phase 1 Phase 2 Phase 3 Safety, PK & PD Proof of Concept, Dose Finding Pivotal Studies S
Slide 43: 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 44: 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 45: 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 46: Skeletal Muscle
Sarcomere Directed Drug Development SKELETAL MUSCLE Reldesemtiv CK-601 46
Slide 47: 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 48: Reldesemtiv
Reldesemtiv 48
Slide 49: 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 50: 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 51: 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 52: 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 53: 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 54: 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 55: Corporate Profile
Sarcomere Directed Therapies CORPORATE PROFILE 55
Slide 56: Robust Pipeline, Solid Financial Position
Robust Pipeline, Solid Financial Position Pipeline* 1 Positive trial readout in 2021 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 CK-274 Reldesemtiv R&D Programs* o Positive trial
Slide 57: Cytokinetics Financing History
Cytokinetics Financing History As of 3/31/2021, with estimated proceeds from 7/23/21 offering 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 $906 $906 Investors Term Loan $45
Slide 58: 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* $230 –
Slide 59: Expected Upcoming 2021 Milestones
Expected Upcoming 2021 Milestones Expect to Begin Phase 3 Trial of Submit US NDA for omecamtiv CK-274 by Year End mecarbil in 2H 2021 Start COURAGE-ALS, Phase 3 Expect results from Clinical Trial of Reldesemtiv in METEORIC-HF in early 2022 Patients with ALS, in Q3 OV ER V IEW C A R D I A C C A N D I
Slide 60: Thank You
Sarcomere Directed Therapies THANK YOU John, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALS