Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (March 2020)
48 slides from Cytokinetics's investor presentation, March 2020
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 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. 3
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 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 5: High Mortality and Hospital Readmission Rates
High Mortality and Hospital Readmission Rates Acute heart failure is the most frequent cause of hospitalization in people > 651,2 5 years post-discharge3,7,8 1 year post-discharge7,9 ~ 40-50% 60 days mortality post-discharge7 ~ 20-30% Initial after 5 years mortality 1 of 2 Hospitalization ~ 25-50% a
Slide 6: High Economic Burden of Heart Failure
High Economic Burden of Heart Failure Heart failure costs ~$123 billion annually, representing 33% of total Medicare budget1,2 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 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 10
Slide 11: 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 Activate Omecamtiv CK-274 CK-271 AMG 594 (Cardiac) Myosin Mecarbil (Cardiac) (
Slide 12: Omecamtiv Mecarbil: Novel Mechanism Approach
Omecamtiv Mecarbil: Novel Mechanism Approach OVERVIEW CARDIAC CANDIDATES SKELETAL CANDIDATES CORPORATE PROFILE 12
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 LS Mean (SE) Change (msec) 40 8 LS Mean (SE) Change (mL) p = 0.001 p < 0.001 p = 0.004 p = 0.022 35 6 30 4 25 20 2 15 0 10 -2 5 0 -4 Placebo 25 mg All PK Titration Placebo 25 mg All PK Titration
Slide 15: Decreases in Physiology & Cardiac Risk
Decreases in Physiology & Cardiac Risk Reductions in heart volume, oxygen demand & wall stress in COSMIC-HF LVESV LVEDV 10 LS Mean (SE) Change (mL) LS Mean (SE) Change (mL) 0 5 -5 0 -10 -5 -15 -10 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 Al
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 Change in E/e' ratio Change in IVRT (ms) p<0.0001 p<0.0001 0 5 p=0.6718 -1 0 p=0.1355 -5 -2 Placebo 25 mg Fixed Dose PK Titration Placebo 25 mg Fixed Dose PK Tit
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 hospitalization1 Meta-analysis of drug/device therapies demonstrated associa
Slide 18: Troponins: Small Increases, Unrelated to Exposures
Troponins: Small Increases, Unrelated to Exposures of Omecamtiv Mecarbil Baseline troponin levels were above the diagnostic limit for myocardial infarction (0.04 ng/mL) for >50% of patients in ATOMIC-AHF and ~25% in COSMIC-HF ATOMIC-AHF COSMIC-HF Change from Baseline (ng/mL) Events of increased trop
Slide 19: Pivotal Phase 3 Trial Completed Enrollment
Pivotal Phase 3 Trial Completed Enrollment GALACTIC-HF continuing following first planned interim analysis Second interim analyses expected in Q1 2020, following accrual of 2/3 of targeted 1,590 CV deaths Overview Key Design Points • Dose optimization based on trough concentration of omecamtiv mecar
Slide 20: Clinical Trial Overview
Clinical Trial Overview Chronic HFrEF patients Omecamtiv mecarbil + SoC Randomization 1:1 Stratified by Patient Subsets and Region currently hospitalized Starting dose: 25mg PO BID for a primary reason of Screening HF or with history of EOS hospitalization or ER/ED admission for a primary Placebo +
Slide 21: Second Phase 3 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 Primary Endpoint Key Design Points • Designed to enroll approximately 270 patients Change in peak VO2 on CPET from baseline to
Slide 22: 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 23: Omecamtiv Mecarbil: Pivotal Phase 3 Results Q4 2020
Omecamtiv Mecarbil: Pivotal Phase 3 Results Q4 2020 July 1999 Aug 2004 July 2005 Dec 2006 May 2009 May 2011 Jan 2013 Dec 2016- Feb 2019 First Cardiac CK-1827452 First CTA/ Amgen Option Amgen Initiate Initiate Initiate Initiate Sarcomere Screen First Synthesized Regulatory Filing Agreement Exercises
Slide 24: Commercial Opportunity for New Heart Failure Therapy
Commercial Opportunity for New Heart Failure Therapy 2019 sales exceeded $1.5B; Analysts expect $3-5B in peak annual sales Entresto® Global Product Sales (M) US Ex-US 1.7bn 518 1.0bn 430 421 357 318 507m 271 239 185 200 128 110 84 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2017 2018 2019 *As with all produ
Slide 25: 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 OVERVIEW CARDIAC CANDIDA
Slide 26: 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 Expanded to Include Japan/Purchase Equity: 2013 worldwide sales of omecamtiv mecarbil: 2017 Received >$220M over 13 Years Amgen resp
Slide 27: 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 28: 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) • Part 2: 3 ascending multiple oral doses
Slide 29: 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 30: 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 600 Steady-state 150 attained 5 mg qd x 14d 3,000 10 mg qy x 14d 400 100 CK-274
Slide 31: 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 Preclinically Appears to Have Translated to Humans, May Enable Flexible Dose Optimization in Humans PK/PD Relationship of CK-274 for Ejectio
Slide 32: Phase 2 Clinical Trial Design
Phase 2 Clinical Trial Design Phase 2 clinical trial open to enrollment Patients with CK-3773274 + SoC Randomization End of Study symptomatic oHCM, 2 Screening 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 Monito
Slide 33: 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 Safe & tolerated dose Imp
Slide 34: Opportunity to Tap Intersection of HF & HCM Centers
Opportunity to Tap Intersection of HF & HCM Centers • 49% account overlap between HF & HCM treatment centers represents: Situation • 94% of total claim volume (923K of 980K claims)1 • Total of 2,000 treatment centers represent key targets for cross selling sales force Opportunity • ~50% of addressab
Slide 35: Sarcomere Directed Drug Development: Skeletal Muscle
Sarcomere Directed Drug Development SKELETAL MUSCLE Reldesemtiv CK-601 35
Slide 36: Sarcomere Directed Drug Development
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 37: 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. 4,300 1,200 • Current therapies provide modest benefit France • Initial symptoms include: limb weakness, France 4,300 1,200 slurred speech, swallowing issues U.S. • Avera
Slide 38: 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 39: 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 40: 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 41: 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 0.5
Slide 42: 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 1.0
Slide 43: Corporate Profile
Sarcomere Directed Therapies CORPORATE PROFILE 43
Slide 44: 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 45: 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 $165.5 $630 $795.5 Capital raised: co
Slide 46: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance Ended 2019 with more than 2 years of cash based on 2020 guidance Q4 2019 Condensed Balance Sheet 2020 Financial Guidance As of 12/31/19 in millions in millions Total Total Cash and investments $267.8 Cash Revenue $18 – 22 Other assets $22.1 Cash Operating Expenses
Slide 47: Upcoming 2020 Milestones
Upcoming 2020 Milestones Conduct Commercial File IND and Initiate Expect Topline Results Complete Enrollment in Readiness & Develop Conduct Phase 1 Study of from GALACTIC-HF in Q4 METEORIC-HF Co-Promotion Plan for REDWOOD-HCM CK-271 in 1H Omecamtiv Mecarbil Prepare for Potential Complete Phase 1 Pha
Slide 48: Thank You
Sarcomere Directed Therapies THANK YOU John, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALS