Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (April 2022)
63 slides from Cytokinetics's investor presentation, April 2022
Slide 1: Empowering Muscle, Empowering Lives
Sarcomere Directed Therapies EMPOWERING MUSCLE EMPOWERING LIVES Nefertari, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALS CYTOKINETICS® and the C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries Copyright©2022 CYTOKINET
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 modulating cardiac myosin • Phase 3 trial, SEQUOIA-HCM, • First-in-class myosin activator enrolling patients with oHCM • Next-in-class myosin inhibitor • Cohort 4 of Phase 2 trial, • Expansion beyon
Slide 6: Sarcomere Directed Drug Development
Sarcomere Directed Drug Development The sarcomere is a molecular structure found in skeletal and cardiac muscle that enables cardiac myocytes to contract and generate force ACTIVATE INHIBIT INHIBIT ACTIVATE ACTIVATE ACTIVATE Troponin Omecamtiv Reldesemtiv CK-136 CK-601 Aficamten CK-271 Mecarbil (Car
Slide 7: 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) NDA Filed PDUFA: 11/30/22 Aficamten (oHCM, nHCM, HFpEF) CK-271 CK-136 (Heart Failure, other) SKELETAL MUSCLE Reldesemtiv (ALS)* CK-601 Additional Skeletal
Slide 8: Cardiac Muscle
Sarcomere Directed Drug Development CARDIAC MUSCLE Omecamtiv Mecarbil Aficamten 8
Slide 9: Contractile Dysfunction Underlies Cardiac Diseases
Contractile Dysfunction Underlies Cardiac Diseases 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
Slide 10: Omecamtiv Mecarbil
Omecamtiv Mecarbil Omecamtiv mecarbil is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) or any regulatory agency. The safety and effectiveness of this product has not been established. 10
Slide 11: Heart Failure Is a Public Health Epidemic
Heart Failure Is a Public Health Epidemic ~6.5M Americans ≥20 years of age have HF; 1M new HF cases occur annually 1 High cost burden driven by hospitalizations; mean cost for each hospital stay ~$17K2 46% 127% 50% ~900,000 24% 49% Increase in Cost increase of HF patients who will Annual HF Patients
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: Pivotal Phase 3 Trial Design
Pivotal Phase 3 Trial Design Second largest clinical trial ever conducted in heart failure Overview Enrolled 8,256 patients at ~1,000 sites in 35 countries Primary Endpoint Composite of time to cardiovascular (CV) death or first HF event*, whichever occurs first Secondary Endpoints • Time to CV deat
Slide 14: 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 15: Positive Primary Composite Endpoint
Positive Primary Composite Endpoint Treatment effect increased in more advanced patients 8% Relative Risk Reduction in Primary Composite Endpoint Treatment Effect Increased Progressively As (Time to First Heart Failure Event or CV Death)1 Baseline LVEF Decreased2 1.2 Treatment Effect (Ratio) 1.0 0.8
Slide 16: Greater Treatment Effect in Worsening HF
Greater Treatment Effect in Worsening HF Primary Outcome in Severe HF: HR = 0.80 (0.71, 0.90) Primary Outcome in Patients with LVEF ≤28%: (Severe HF defined as NYHA III-IV, EF ≤30%, HF hosp <6 mos)1,2 HR 0.84; 95% CI 0.77, 0.92 Severe HF-Placebo Not severe HF-Placebo Severe HF-Omecamtiv Not severe H
Slide 17: Similar Risk Reduction in Hospitalized Patients vs. Outpatients
Similar Risk Reduction in Hospitalized Patients vs. Outpatients Initiating omecamtiv mecarbil in hospitalized patients safe, well-tolerated • Rate of primary outcome higher in hospitalized patients in the placebo group than in outpatients • Effect of omecamtiv mecarbil versus placebo on the primary
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: Large and Growing Heart Failure Patient Population
Large and Growing Heart Failure Patient Population Prevalence in Adults (18+, USA) 2020 Estimates 2032 Estimates 6.2M1 8.0M3 Heart Failure Including HFpEF 3.1M2 4.0M3 HFrEF Population 2.0M2 2.6M3 HFrEF & EF ≤30% Proposed Cardiac Function Recent Event GDMT Limitations Omecamtiv Mecarbil Target Patien
Slide 20: High Cost Burden Primarily Due to Hospitalizations
High Cost Burden Primarily Due to Hospitalizations Omecamtiv mecarbil reduced clinical events, resource utilization & costs related to HF events Omecamtiv mecarbil reduced costs Over next decade, HF cost burden Mostly due to cycle of hospitalizations related to HF events in is expected to increase o
Slide 21: Omecamtiv Mecarbil: Value Proposition
Omecamtiv Mecarbil: Value Proposition In HFrEF, patients with lower ejection Hospitalization reductions seen in fractions are hospitalized more often clinical trial of omecamtiv mecarbil In HFrEF, every 10 points lower EF, is proven to drive Clinically meaningful and statistically significant higher
Slide 22: Small Subset of Cardiologists Manage Majority of Patients
Small Subset of Cardiologists Manage Majority of Patients HFrEF Patient Concentration in Cardiologists Distribution of High-Volume Cardiologists 100% % of Patients 50% 0% 0% 50% 100% % of Cardiologists Allows for more targeted field team approach, focusing on <10,000 HCPs Symphony APLD (1/1/2019 – 1
Slide 23: Engagement Approach Allows Customizing and Broadening
Engagement Approach Allows Customizing and Broadening Customizing engagement by different types of customers Digital allows broader reach ~~ illustrative ~~ ~~ illustrative ~~ Targeted Broadening Targeted Community Reach Beyond HF Specialist Cardiologist Initial Target Field & Inside Digital Reimbur
Slide 24: Medicare Is Major Payer with Select Key Players
Medicare Is Major Payer with Select Key Players Medicare is largest payer; enrollment highly concentrated with nearly 3 of 4 patients in only 5 plans Medicare Part D Enrollment (2019) Estimated Payer Mix Entresto Based Payer Mix on Entresto® (2018) 2018 Data Managed Medicaid 8% Top 5 plans have 75%
Slide 25: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Majority of spending to occur post-approval 2/3 of hiring to occur post-approval Activities initiated upon key de-risking events Underway Pre-NDA filing Market access Commercial leadership Pricing strategy Marketing Distribution approach HEOR Payer engagement
Slide 26: Commercial Supply Chain Operating Model
Commercial Supply Chain Operating Model Planning, Analytics & Master Data 2021-2022 Manufacturing, Finance Science & Quality Technology 2021-2022 External Commercial Manufacturing 2021-2022 Supply Chain Logistics 2021-2022 Commercial R&D Sales & Marketing Product Strategy 2023+ Not for Promotional U
Slide 27: Aficamten
Aficamten Aficamten is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) or any regulatory agency. The safety and effectiveness of this product has not been established. 27
Slide 28: In US, Large HCM Population With Many Undiagnosed
In US, Large HCM Population With Many Undiagnosed HCM Prevalence Potential Undiagnosed Patients Currently ~400-800K ~280K diagnosed, 700 – ~190K oHCM 1,100K symptomatic patients Estimated ~400-800K nHCM* 280K Diagnosed Patients un-diagnosed patients oHCM* ~280K Mava success 190K Now Future nHCM: non
Slide 29: 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 30: Aficamten: Aspirational Target Profile
Aficamten: Aspirational Target Profile Potential next-in-class cardiac myosin inhibitor Functional Improvement: Improved exercise capacity Efficacy Symptom Improvement: One or two class improvement in NYHA class Quality of Life: KCCQ improvement Minimal drug-drug interactions Safety and Maintain LVE
Slide 31: 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 32: REDWOOD-HCM: Cohorts 1 & 2
REDWOOD-HCM: Cohorts 1 & 2 Patients with symptomatic oHCM on background therapy excluding disopyramide Two sequential dose-finding cohorts Randomization Patients with Aficamten + SoC End of Study Screening symptomatic oHCM, 2 and resting or provoked LVOT 1 gradient ≥ 50 mmHg Placebo + SoC Study Visi
Slide 33: Patient Enrollment and Dosing
Patient Enrollment and Dosing Cohorts 1 & 2 41 Total Enrolled Patients Final Dose Achieved (N) 5 mg 10 mg 15 mg 20 mg 30 mg N = 14 Cohort 1 4 5 5 N = 14 Cohort 2 9 4 1 Not for Promotional Use, For Investors Only OV ER V IEW C A RD IAC C AND ID ATES F R A N C H I S E S T R A T EG Y S K E L E T A L C
Slide 34: Baseline Characteristics
Baseline Characteristics Cohorts 1 & 2 Placebo Aficamten Characteristic (n = 13) (n = 28) Age (Years), Mean (SD) [Range] 57.2 (9.6) [36,69] 56.6 (13.6) [33,78] < 65 Years 10 (77%) 17 (61%) Sex, n (%) Female 8 (62%) 15 (54%) Race = White, n (%) 12 (92%) 28 (100%) NYHA Class, n (%) Class II 11 (85%) 1
Slide 35: Response Rates on Treatment with Aficamten
Response Rates on Treatment with Aficamten Cohorts 1 & 2 1/13 11/14 13/14 100 Responder # / Total # 7.7% 78.6% 92.9% Not Responder • Consistent, clinically Responder 80 meaningful reductions in LVOT Responder Definition: Resting LVOT-G <30 gradients within two weeks mmHg and post- 60 Valsalva LVOT-G
Slide 36: REDWOOD-HCM: Efficacy
REDWOOD-HCM: Efficacy Cohorts 1 & 2 Reductions in LVOT gradients Resting LVOT-G Valsalva LVOT-G 80 100 80 Combined Placebo 60 Aficamten: Cohort 1 60 Aficamten: Cohort 2 mmHg mmHg 40 LVOT-G ≥50 mmHg 40 * ** ** ** * 20 ** ** *** *** * P < 0.05 *** ** 20 ** ** ** ** P < 0.001 mean ± SEM *** mean ± SEM
Slide 37: Change from Baseline in NT-proBNP & NYHA Class
Change from Baseline in NT-proBNP & NYHA Class Cohorts 1 & 2 Change from Baseline NT-proBNPto Week 10 Improvement in Heart Failure Symptoms (NYHA Class) Week 10 Responder Definition: Improvement in NYHA Class ≥1 0 100 31% -200 80 (n=4) 43% (n=6) 64% (n=9) NTproBNP (pg/mL) -400 60 % Total -600 40 69%
Slide 38: REDWOOD-HCM: Cohort 3
REDWOOD-HCM: Cohort 3 Patients with symptomatic oHCM on background therapy of disopyramide Same doses used in Cohort 3 as in Cohort 1 Patients with End of Study symptomatic Screening oHCM, and resting or provoked LVOT Aficamten + SoC AND disopyramide gradient ≥ 50 mmHg Study Visits Screen W-1* D1 W2
Slide 39: REDWOOD-HCM: Efficacy in Patients on Disopyramide
REDWOOD-HCM: Efficacy in Patients on Disopyramide Cohort 3 Reductions in LVOT gradients; no patients whose LVEF dropped below safety threshold LVOT Gradients Response Rates Treatment Washout For 53.8% with incomplete response, opportunity for dose escalation in SEQUOIA-HCM Complete Response: Resting
Slide 40: REDWOOD-HCM: Efficacy in Patients on Disopyramide
REDWOOD-HCM: Efficacy in Patients on Disopyramide Cohort 3 Improvement in functional class and cardiac biomarkers NYHA Response NT-proBNP Hs-Troponin I Geometric mean change from baseline to Week 10 Mean change from baseline to Week 10 Not for Promotional Use, For Investors Only OV ER V IEW C A RD I
Slide 41: REDWOOD-HCM: Cohort 4
REDWOOD-HCM: Cohort 4 Patients with symptomatic nHCM on background therapy Opened to enrollment in Q1 2022 End of Study Patients with Screening symptomatic nHCM, and resting or Aficamten + SoC provoked LVOT gradient ≥ 50 mmHg Study Visits Screen W-1* D1 W2 W4 W6** W8* W9* W10 W12 W14* Ambulatory Car
Slide 42: SEQUOIA-HCM: Phase 3 Trial
SEQUOIA-HCM: Phase 3 Trial Plan to enroll at 115 sites in US, Europe and Asia** Primary endpoint: Change in pVO2 by CPET from baseline to Week 24 Randomization Aficamten + SoC End of Study Patients with Screening Secondary objectives include measuring oHCM treated with SOC with 1 post-Valsalva chang
Slide 43: REDWOOD-HCM: Open Label Extension
REDWOOD-HCM: Open Label Extension Open for eligible patients who completed REDWOOD-HCM & SEQUOIA-HCM Expect to share data from REDWOOD-HCM OLE in 2022 • Primary endpoint: incidence of AEs & LVEF <50 • Secondary endpoints: measures of long-term effects of aficamten on LVOT-G; assessments of steady-st
Slide 44: Aficamten: Clinical Development Plan for HCM
Aficamten: Clinical Development Plan for HCM SEQUOIA-HCM enrolling patients with oHCM; REDWOOD-HCM Cohort 4 enrolling patients with nHCM Phase 1 Phase 2 Phase 3 Safety, PK & PD Proof of Concept, Dose Finding Pivotal Studies SAD & MAD REDWOOD-HCM Cohorts 1-3 SEQUOIA-HCM Healthy obstructive HCM obstru
Slide 45: Novel Approach May Address Multiple Unmet Patient Needs
Novel Approach May Address Multiple Unmet Patient Needs No FDA-approved therapies Obstructive HCM oHCM Aficamten (Cardiac myosin Inhibitor) nHCM HFpEF Non-Obstructive HCM Heart Failure with Preserved Ejection Fraction Not for Promotional Use, For Investors Only OV ER V IEW C A RD IAC C AND ID ATES F
Slide 46: Franchise Strategy
Sarcomere Directed Drug Commercialization FRANCHISE STRATEGY 46
Slide 47: Launch Guiding Principles Strengthen Franchise Build
Launch Guiding Principles Strengthen Franchise Build Patient and Creating broad value for cardiac patients and build long-term, deep relationships customer centric with cardiologists with multiple CV medicines Leverage Go-to-Market synergies between multiple CV medicines, enabling Cost-efficient eff
Slide 48: Limited Incremental Cost For Future U.S. CV Launches
Limited Incremental Cost For Future U.S. CV Launches Building Today … … To Lead Tomorrow To optimize value capture for potential To support future launches and establish launch of omecamtiv mecarbil Cytokinetics as a CV leader • Building deep, long-term relationships • Significant overlap between HF
Slide 49: Go-to-Market Synergies for Omecamtiv Mecarbil & Aficamten
Go-to-Market Synergies for Omecamtiv Mecarbil & Aficamten Sales Given target overlap, leveraging same sales team Team Commercial Support Utilize resources across brands (e.g., access, analytics, …) Functions Synergy PV of ~ $500M Medical MSLs qualified to cover both HFrEF and HCM Affairs Corporate S
Slide 50: Skeletal Muscle
Sarcomere Directed Drug Development SKELETAL MUSCLE Reldesemtiv 50
Slide 51: Reldesemtiv
Reldesemtiv Reldesemtiv is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) or any regulatory agency. The safety and effectiveness of this product has not been established. 51
Slide 52: Phase 2 Clinical Trial in ALS
Phase 2 Clinical Trial in ALS Results presented at American Academy of Neurology 2019 Annual Meeting 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
Slide 53: 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 54: Phase 2 Clinical Trial in ALS Results
Phase 2 Clinical Trial Primary analysis not statistically significant; patients on all doses of reldesemtiv declined less than patients on placebo* 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 Rat
Slide 55: 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 56: Post-Hoc Analyses Inform Potential Path Forward
Post-Hoc Analyses Inform Potential Path Forward Probability of No New DME Over Time Change From Baseline in ALSFRS-R With Treatment With Reldesemtiv by Progressor Tertiles DME (Durable Medical Equipment): Manual wheelchair, power wheelchair, NIV, Time (weeks) Augmentative Language Device, PEG 0 LS m
Slide 57: COURAGE-ALS Phase 3 Clinical Trial Design
Phase 3 Clinical Trial Design Plan to enroll 555 patients; interim analysis for futility in 2H 2022 Enrolling 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: Ri
Slide 58: Corporate Profile
Sarcomere Directed Therapies CORPORATE PROFILE 58
Slide 59: Robust Pipeline, Solid Financial Position
Robust Pipeline, Solid Financial Position Pipeline 1 Potential commercial launch in 2022 2 Programs in Phase 3 trials 3 Potential FDA approvals by 2025 5 Clinical stage programs 10 Development programs by 2025 Heart Failure HCM ALS Ongoing Omecamtiv mecarbil Aficamten Reldesemtiv R&D Programs o Posi
Slide 60: Monetizing Our Pipeline to Bolster Balance Sheet
Monetizing Our Pipeline to Bolster Balance Sheet Symmetry of deals for omecamtiv mecarbil and aficamten affords synergies for development and potential launches and supports franchise strategies Sold 4.5% royalty Sold 3.5-4.5% royalty Transactions on worldwide net sales of on worldwide net sales of
Slide 61: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance 2021 Condensed Balance Sheet 2022 Financial Guidance As of 12/31/2021 in millions in millions Total Total Cash and investments $623.7* Cash Revenue $20 – 25 Accounts receivable $51.8 Cash Operating Expenses $380 – 400 PPE $73.3 Net ~ $365 - 385 Leased assets $73.1
Slide 62: Expected Milestones in 2022
Expected Milestones in 2022 Launch omecamtiv mecarbil in the U.S. pending FDA approval in Q4 2022 Continue enrollment in Begin second Phase 3 Expect to share data from Continue enrollment SEQUOIA-HCM trial of aficamten in REDWOOD-HCM OLE in Cohort 4 of through 2022 oHCM in 2H 2022 in 2022 REDWOOD-HC
Slide 63: Thank You
Sarcomere Directed Therapies THANK YOU Nefertari, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALS Copyright©2022 CYTOKINETICS, All Rights Reserved Actual patients who consented to use of their name, image, and condition.