Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Corporate Update (January 2020)
45 slides from Cytokinetics's corporate update, Jan 13, 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: 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 H
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: 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 5: 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 6: 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 7: 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 8: 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 9: 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 (HCM) CK-271 AMG 594 (Heart Failure, other) AMGEN COLLABORATION SKELETAL MUSCLE Reldesemtiv CK-601 Additional Skeletal Muscle A
Slide 10: Sarcomere Directed Drug Development: Cardiac Muscle
Sarcomere Directed Drug Development CARDIAC MUSCLE Omecamtiv Mecarbil AMG 594 CK-274, CK-271 10Sarcomere Directed Drug Development CARDIAC MUSCLE Omecamtiv Mecarbil AMG 594 CK-274, CK-271 10
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 Activate Inhibit Inhibit AMG 594 Omecamtiv CK-274 CK-271 (Cardiac) Mecarbil (Cardiac) (Cardiac
Slide 12: 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 T E S C O R P O R A T E P R O F I L E 12Omecamtiv 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 T E S C O
Slide 13: Omecamtiv Mecarbil: Robust Clinical Trials Program
Omecamtiv Mecarbil: Robust Clinical Trials Program Over 10,000 patient-years of exposure to omecamtiv mecarbil 11 7 Phase 1 Studies Phase 2 Studies 324 1,414 Subjects Enrolled Subjects Enrolled Well characterized safety, COSMIC-HF showed statistically tolerability and PK/PD data significant improvem
Slide 14: 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 15: 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 16: 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 PK Titration 25 mg Fixed Dose Placebo PK Titration 25 mg Fixed Dose TR Velocity Diastolic Filling Time
Slide 17: 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 failure 1 hospitalization Meta-analysis of drug/device therapies demonstrated associ
Slide 18: Pivotal Phase Trial Completed Enrollment
Pivotal Phase 3 Trial Completed Enrollment GALACTIC-HF continuing following first planned interim analysis Second interim analyses expected in Q1 2020 Overview Key Design Points • Dose optimization based on trough concentration of omecamtiv mecarbil Enrolled over 8,200 patients at ~1,000 sites in 35
Slide 19: Clinical Trial Overview
Clinical Trial Overview Chronic HFrEF patients Omecamtiv mecarbil + SoC currently hospitalized Starting dose: 25mg PO BID 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 20: Second Phase Clinical Trial Underway
Second Phase 3 Clinical Trial Underway Investigating effect of omecamtiv mecarbil on exercise tolerance Trial will enroll patients in 9 countries in North America and Europe Overview Key Design Points • Designed to enroll approximately 270 patients Change in peak VO2 on CPET from baseline to Week 20
Slide 21: 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 22: Commercial Opportunity for New Heart Failure Therapy
Commercial Opportunity for New Heart Failure Therapy Projected to reach between $1.5-2B in sales in 2019; Analysts expect $3-5B in peak annual sales ® Entresto Global Product Sales (M) US Ex-US 1,208m 430 421 1,028m 357 318 507m 271 239 200 185 128 110 84 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 2017 2018 2
Slide 23: 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 24: Collaborations & Agreements
Collaborations & Agreements 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: 2013 Received >$220M over 13 Years Commercial
Slide 25: AMG 594: Cardiac Troponin Activator
AMG 594: Cardiac Troponin Activator Advancing through Phase 1: Potential for HFrEF and other indications Troponin • Intended to improve ventricular systolic function in patients with heart failure • Preclinical results support the potential for best-in-class safety and efficacy • Projected once dail
Slide 26: AMG 594: Nested SAD and MAD in Healthy Subjects
AMG 594: Nested SAD and MAD in Healthy Subjects Randomized, placebo-controlled, double-blind, Objectives Endpoints multi-part, single center study Safety and tolerability AEs, laboratories, cardiac markers, ECGs • Part 1: 5 ascending single oral doses (SAD) Pharmacokinetics C , T , AUC max max • Par
Slide 27: 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 • Potential in vivo pharmacodynamic advantages related to distinctive binding site • No inhibi
Slide 28: SAD & MAD Results Support Progression to Phase 2
SAD & MAD Results Support Progression to Phase 2 CK-274 was well tolerated in healthy participants: no SAEs* SAD Pharmacokinetics Appeared Steady-State Appeared Evident After Generally Dose Proportional 14 Days of Dosing Steady-state 600 150 attained 5 mg qd x 14d 10 mg qy x 14d 3,000 400 100 2,000
Slide 29: CK-274: 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 30: Phase 2 Clinical Trial Design
Phase 2 Clinical Trial Design Phase 2 clinical trial open to enrollment 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 Ambulatory Cardiac Monitoring PK Echocardiogram Dose Titration
Slide 31: 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) Volunteers Echocardiography Endpoints IND Filed NDA Safe & tolerated dose NDA
Slide 32: Sarcomere Directed Drug Development: Skeletal Muscle
Sarcomere Directed Drug Development SKELETAL MUSCLE Reldesemtiv CK-601 32Sarcomere Directed Drug Development SKELETAL MUSCLE Reldesemtiv CK-601 32
Slide 33: 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 cardiac myocytes to contract and generate force Troponin Activate Activate Reldesemtiv CK-601 (Skeletal) (Skeletal) Tropomyosin Actin Calcium Thin filament ATP
Slide 34: Significant Unmet Need in ALS
Significant Unmet Need in ALS No approved muscle directed therapies Prevalence* Incidence* • Average 3-5 year mortality U.K. U.K. • Current therapies provide modest benefit 4,300 1,200 France • Initial symptoms include: limb weakness, France 4,300 slurred speech, swallowing issues 1,200 • Average ag
Slide 35: 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 and 150 mg BID (n = 110) Canada, evaluating change Screening Follow-up from b
Slide 36: 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 37: 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 38: 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 39: 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 40: Corporate Profile
Sarcomere Directed Therapies CORPORATE PROFILE 40Sarcomere Directed Therapies CORPORATE PROFILE 40
Slide 41: 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 42: Cytokinetics Financing History
Cytokinetics Financing History in millions Upfront Cash, Option, R&D Financing Equity & Milestones Reimbursement Total Private Investors (VCs) $116 $116 IPO $94 $94 Public Post-IPO/Other $420 $420 Investors Term Loan $45 $45 Convertible Debt (net)* $120.5 $120.5 Capital raised: $165.5 $630 $795.5 co
Slide 43: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance Ended 2019 with 2-3 years of cash based on 2019 guidance* Q3 2019 Condensed Balance Sheet 2019 Financial Guidance As of 9/30/19 in millions in millions Total Total $28 – 32 Cash and investments $166.0 Cash Revenue $110 – 115 Cash Operating Expenses Other assets $21
Slide 44: Upcoming 2020 Milestones
Upcoming 2020 Milestones Expect Second Interim Analyses from Conduct Commercial File IND and Initiate GALACTIC-HF in Q1 Complete Enrollment in Readiness & Develop Conduct Phase 1 Study of METEORIC-HF Co-Promotion Plan for REDWOOD-HCM CK-271 in 1H Expect Topline Results Omecamtiv Mecarbil from GALACT
Slide 45: 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