Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Day (October 2023)
125 slides from Cytokinetics's investor day presentation, Oct 19, 2023
Slide 1: Cytokinetics
©2023 CYTOKINETICS, All Rights Reserved. CYTOKINETICS® and the C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries.
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: Company Speakers
Company Speakers Robert Blum President & CEO Fady Malik, M.D., Ph.D. EVP, Research & Development Andrew Callos EVP, Chief Commercial Officer Stuart Kupfer, M.D. SVP, Chief Medical Officer Steve Heitner, M.D. VP, Clinical Research & Therapeutic Area Lead, Cardiovascular Diane Weiser SVP, Corporate Co
Slide 4: Expert Speakers
Expert Speakers Theodore Abraham, M.D., FACC, FASE Meyer Friedman Distinguished Professor of Medicine, Division of Cardiology, University of California, San Francisco; Co-director, UCSF HCM Center of Excellence; Director, UCSF Adult Cardiac Echocardiography Laboratory Caroline Coats, Ph.D. Clinical
Slide 5: Today's Agenda
Today’s Agenda Topic Presenter Welcome Diane Weiser, SVP, Corporate Communications & Investor Relations Building a Specialty Cardiology Franchise Robert Blum, President & CEO Cardiac Myosin Inhibition Fady Malik, M.D., Ph.D., EVP, Research & Development HCM Landscape Andrew Callos, EVP, Chief Commer
Slide 6: Building a Specialty Cardiology Franchise
Building a Specialty Cardiology Franchise Robert Blum President & CEO
Slide 7: Building a Specialty Cardiology Franchise Anchored by Aficamten
Addressing severely ill and underserved populations in need of new therapies Building a Specialty Cardiology Franchise Anchored by Aficamten oHCM MAPLE-HCM Potential to expand to first-line treatment nHCM ACACIA-HCM Potential to expand into nHCM Strategic expansion of clinical development program to
Slide 8: 75% of HCM patient volume is treated by 10,000 cardiologists
75% of the HCM patient volume is treated by 10,000 cardiologists Cardiologists Located in Concentrated Geographic Clusters Across the US Note: includes only patients who are treated by a cardiologist - not all patients see a cardiologist; sample of 67K HCM patients Source: Symphony PTD (Patient Tran
Slide 9: Investing in Aficamten to Achieve Sustainable, Growing Revenue
Investing in Aficamten to Achieve Sustainable, Growing Revenue Investment in R&D for aficamten oHCM revenue nHCM revenue Potential approval in oHCM Potential approval in nHCM Potential to be first-line treatment Projected forecast for illustration
Slide 10: Aficamten Supports Potential Go-To-Market in Europe
Aficamten Supports Potential Go-To-Market in Europe Opportunity is of sufficient scale for standalone launch of aficamten and can support portfolio Plan is to launch across 6 country clusters representing >95% of forecasted EU/UK revenue Minimal FTEs in 2024-2025, with gradual build by country gated
Slide 11: Unique Attributes of a Specialty Cardiology Company
Unique Attributes of a Specialty Cardiology Company Broad Cardiology Specialty Cardiology Example Therapies Heart failure, cholesterol, blood thinner HCM, TTR amyloidosis Prescribers Broad: Cardiologists, PCPs (50K+) Concentrated: Subset of cardiologists (~10K) ROI / Prescriber Limited High Distribu
Slide 12: Cytokinetics: Uniquely Positioned for Success
Strong cash runway Access to capital through Royalty Pharma transaction Pioneer in CMI space Multiple drug candidates arising from our research Core research engine Cytokinetics: Uniquely Positioned for Success Late-stage HCM program HFrEF opportunity in Europe Early-stage HFpEF research Early-stage
Slide 13: Cardiac Myosin Inhibition
Cardiac Myosin Inhibition Fady Malik, M.D., Ph.D. EVP, Research & Development
Slide 14: Pioneers in the Pharmacology of Muscle Contractility
Pioneers in the Pharmacology of Muscle Contractility Reconstituted Sarcomere Flexible Biochemical Assay Muscle Fiber Assay in Native Context Organ and In Vivo Functional Outcome Novel molecular targets require novel assays Faithful representation of biological function from in vitro to in vivo setti
Slide 15: Sarcomere Directed Drug Development
Sarcomere Directed Drug Development HCM = Hypercontraction HFrEF = Hypocontraction Impaired cardiac muscle function Sarcomere Modulation Activators CK-136 (Cardiac Troponin Activator) Omecamtiv mecarbil (Cardiac Myosin Activator) PII PC CK-586 (Cardiac Myosin Inhibitor) Aficamten (Cardiac Myosin Inh
Slide 16: Hypertrophic Cardiomyopathy
Hypertrophic Cardiomyopathy Phenotypically Defined Cardiac hypertrophy (increased wall thickness >15 mm) of left ventricle in the absence of another cardiac or systemic disease that could produce a similar magnitude of hypertrophy Genetic Etiology Both monogenetic (30%) and polygenetic (70%) etiolog
Slide 17: Hypertrophic Cardiomyopathy
Hypertrophic Cardiomyopathy Mutations in the sarcomere can cause hypercontraction, leading to abnormal growth (pathological hypertrophy) of the heart Sarcomere: The basic contractile unit of muscle HCM: A Disease of the Sarcomere Normal HCM Disarray Normal
Slide 18: Obstructive HCM is the Most Common Form of HCM
Obstructive HCM is the Most Common Form of HCM Obstructive (~65%) Non-Obstructive (~35%) Hypertrophic Cardiomyopathy
Slide 19: HCM: A Disease of the Sarcomere
Therapeutic hypothesis HCM: A Disease of the Sarcomere Normalization of excessive crossbridge formation (2D-echo) Relief of obstruction of blood flow out of the LV (Doppler echo) Improvements in relaxation & high LV filling pressures (NT-proBNP) Positive remodeling of the heart (Cardiac MRI) Teekaki
Slide 20: Cardiac Myosin Inhibitors: Aspirational Target Profile
Cardiac Myosin Inhibitors: Aspirational Target Profile Precise Dosing Simplicity of Use Rapid Reversibility Symptom relief as early as within 2 weeks initiation and dose adjustment possible biweekly if indicated Echo guided dose titration allows both dose increases and decreases at the patient visit
Slide 21: Aficamten: Mechanism of Action
Aficamten: Mechanism of Action Post-Powerstroke State Before Aficamten After Aficamten Mechanochemical domain AF Actin sliding Actin sliding “Fewer hands pulling on the rope” Aficamten stabilizes myosin in the released post-powerstroke state unable to hydrolyze ATP Aficamten is an investigational dr
Slide 22: Aficamten: Binds to a Distinct Allosteric Site on Myosin
Aficamten: Binds to a Distinct Allosteric Site on Myosin Blebbistatin chemical structure and binding site on MgADP-vanadate myosin II (Allingham, NSMB (2005)) Blebbistatin fluorescence increases when bound to cardiac S1 Fluorescence of blebbistatin/S1 decreases in the presence of increasing concentr
Slide 23: Aficamten: Shallow Concentration-Response
Aficamten: Shallow Concentration-Response Pharmacodynamic window Fractional shortening IC50 /IC10 ratio mavacamten 2.8x aficamten 9.9x IC10: plasma concentration at 10% relative reduction in fractional shortening IC50: plasma concentration at 50% relative reduction in fractional shortening Compound
Slide 24: Aficamten: Concentration-Response Relationship
p=0.6 Log transformed PK concentration 0 2 4 6 0 2 4 6 -10 0 10 Linear Predictor Cohort 4 Cohorts 1-3 Shallow exposure response relationship appears to translate from animal to humans with HCM Aficamten: Concentration-Response Relationship PK:PD Dog + Human (Ph1 and Ph2 oHCM) PK:PD Slope Human (P1 a
Slide 25: HCM Landscape
HCM Landscape Andrew Callos EVP, Chief Commercial Officer
Slide 26: CMIs May Offer Treatment Option for HCM & Heart Failure
CMIs May Offer Treatment Option for HCM & Heart Failure HCM Up to 1.1M patients Heart Failure >7M patients Potential Applications for Cardiac Myosin Inhibitors (CMIs) oHCM 65-75% of diagnosed patients nHCM 25-35% of diagnosed patients (EF>65%) ~10% of diagnosed patients Projections and forecasts for
Slide 27: Potential for nearly 200K patients eligible for CMIs in 2025
Potential for nearly 200K patients eligible for CMIs in 2025 Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients Projections and forecasts for illustration. 1. Cardiovascular Research Group: CVrg Market Strategies: Heart Failure, p 48, Q4 2022; Maron BJ: et al:: Prevalence of Hypertrophic Ca
Slide 28: Diagnosis of HCM Anticipated to Grow 5x the General Population
Diagnosis of HCM Anticipated to Grow 5x the Rate of the General Population Disease Awareness Inclusion in Guidelines Earlier Detection 1% Prevalence Growth1 5% Diagnosis Growth2 Improved Therapeutics 2023: ~300K Diagnosed HCM Patients 2033: ~500K Diagnosed HCM Patients Source: 1) UN Population Proje
Slide 29: oHCM: High Unmet Need
oHCM patients tend to be older, NYHA Class II-III and symptomatic oHCM: High Unmet Need 1. SHA 2015-2023 DoF for patients ever diagnosed with I42.1 2. DoF Cogent MR October 2022; US data representative for 19,281 patients ~65% NYHA II-III Patient Demographics Symptom Status
Slide 30: oHCM: 90% of Diagnosed Patients are Treated
oHCM: 90% of Diagnosed Patients are Treated, Many Not Well-Controlled1 Camzyos patient share >1% Under-reported due to data blockage of select SPs and patients on free goods Patients can be on more than one drug therapy 90% Treated 10% Not Treated Any oHCM Patient (past 2 years) Note: Over a 2-year
Slide 31: nHCM: High Unmet Need
35-50% of patients are NYHA II-III, symptomatic nHCM: High Unmet Need Note: Due to ICD-10 coding, claims analyses focusing on I42.2 includes both o/nHCM patients 1. Lu D. et al: “Clinical Outcomes in Patients With Nonobstructive, Labile, and Obstructive Hypertrophic Cardiomyopathy”, JAHAVolume 7, Is
Slide 32: nHCM: 68%+ of Diagnosed Patients are Treated
nHCM: 68%+ of Diagnosed Patients are Treated 1. Lu D. et al: “Clinical Outcomes in Patients With Nonobstructive, Labile, and Obstructive Hypertrophic Cardiomyopathy”, JAHA Volume 7, Issue 5, March 2018 >68%+ Treated <32% Not Treated Any nHCM Patient (past 2 years) % Treated nHCM Patients1 N=214 Pati
Slide 33: Symptoms Limiting Function Are Burdensome
Symptoms Limiting Function Are Burdensome Hypertrophic Cardiomyopathy Association. The Voice of the Patient report for hypertrophic cardiomyopathy (HCM). Proceedings from an externally led public Patient-Focused Drug Development meeting corresponding to the FDA’s Patient-Focused Drug Development mee
Slide 34: Majority of CMI-Eligible Patients Available at Launch
If Aficamten is Approved, Expect Majority of CMI-Eligible Patients Available at Launch Projections and forecasts for illustration Source: 1) DoF: SHA; Symphony PTD (Patient Transaction Data): Includes patients diagnosed since 2016 and having any HC transaction in the claims data universe in the last
Slide 35: Aficamten: Development Program
Aficamten: Development Program Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 36: REDWOOD-HCM: oHCM
REDWOOD-HCM: oHCM Stuart Kupfer, M.D. SVP, Chief Medical Officer Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 37: Aficamten: Clinical Development Plan for HCM
Aficamten: Clinical Development Plan for HCM Well tolerated dose with desired PD effects REDWOOD-HCM Cohorts 1-3 obstructive HCM Placebo controlled; echocardiography endpoints SEQUOIA-HCM obstructive HCM Pivotal trial with exercise endpoint (peak VO2) FOREST-HCM obstructive & non-obstructive HCM Ext
Slide 38: REDWOOD-HCM: Cohorts 1 & 2
Patients with symptomatic oHCM on background therapy excluding disopyramide REDWOOD-HCM: Cohorts 1 & 2 Two sequential dose-finding cohorts NT-proBNP 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
Slide 39: REDWOOD-HCM: Robust Reduction of LVOT Gradients
Cohorts 1 & 2 REDWOOD-HCM: Robust Reduction of LVOT Gradients Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. Maron M, et. al. Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy. JA
Slide 40: High Proportion of Responders with Aficamten
Cohorts 1 & 2 High Proportion of Responders with Aficamten Responder Definition: Resting LVOT-G <30 mmHg and post-Valsalva LVOT-G <50 mmHg at Week 10 1/13 11/14 13/14 Responder # / Total # Placebo Aficamten: Cohort 1 0 20 40 60 80 100 % Total Not Responder Responder 21.4% 7.1% 7.7% 78.6% 92.9% 92.3%
Slide 41: Improvements in NT-proBNP and NYHA Class
Cohorts 1 & 2 Improvements in NT-proBNP and NYHA Class Change from Baseline NT-proBNP to Week 10 * p = 0.003 for Pooled Cohort 1 & 2 vs. Placebo 0 -200 -400 -600 -800 -1000 NT-proBNP (pg/mL) * Placebo Aficamten: Cohort 1 Aficamten: Cohort 2 Combined Placebo (N=13) Aficamten: Cohort 1 (N=14) Aficamte
Slide 42: Early signs of improvement in cardiac structure and relaxation
Cohorts 1 & 2: Early signs of improvement in cardiac structure and myocardial relaxation Improved Cardiac Structure and Diastolic Function Treatment with aficamten for 10 weeks resulted in: Significant reduction in left atrial volume index Trend towards a reduction in LV mass index Improved diastoli
Slide 43: REDWOOD-HCM: Selected Safety Observations
Cohorts 1 – 3 REDWOOD-HCM: Selected Safety Observations No treatment interruptions or discontinuations No patients met the “stopping criteria” of LVEF < 40% Transient and asymptomatic decrease in LVEF < 50% in 2 of 41 aficamten-treated patients in Cohort 2 2 SAEs in 41 aficamten-treated patients, ne
Slide 44: FOREST-HCM
FOREST-HCM Steve Heitner, M.D. VP, Clinical Research & Therapeutic Area Lead, Cardiovascular Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 45: FOREST-HCM: Sustained Efficacy with Aficamten
FOREST-HCM: Sustained Efficacy with Aficamten Aficamten appears to result in sustained treatment effect in oHCM patients More than 200 patients are currently enrolled in FOREST-HCM 143 patients were available for this analysis (data cut Sept 15, 2023) Almost all those eligible have chosen to partici
Slide 46: FOREST-HCM: Baseline Characteristics
FOREST-HCM: Baseline Characteristics Baseline characteristics indicate substantial disease burden; ~2/3 patients achieving 15 or 20 mg FOREST-HCM oHCM N=143* Age (Years), Mean (SD) 60.4 (13.2) Female, n (%) 65 (45.5) BMI (kg/m2), Mean (SD) [Range] 29.2 (4.5) NYHA Class, n (%) Class II 82 (58) Class
Slide 47: No Treatment Interruptions During Dose Titration
No Treatment Interruptions During Dose Titration No patients had a treatment-related LVEF <50% during the titration period Of the 94 patients having completed the titration period, ~2/3 are receiving 15 and 20 mg qd Approximately 30% of patients have reduced doses or discontinued background therapy
Slide 48: Dose Reduction During Maintenance Phase is Rare
Dose Reduction During Maintenance Phase is Rare Target dose defined as achieved if Valsalva LVOT-G ≤ 30 mmHg or no dose change for 2 consecutive visits 579 monitoring echocardiograms have been completed* in oHCM patients None with LVEF <40% requiring treatment interruption 3 patients (0.5%) with LVE
Slide 49: Durable Effects of Aficamten on LVOT-G & LVEF
Durable Effects of Aficamten on LVOT-G & LVEF Resting & provoked gradients remain below diagnostic threshold for >2 years, LVEF remains flat after titration Resting LVOT Gradient Valsalva LVOT Gradient LVEF = Diagnostic threshold = Diagnostic threshold = Safety threshold Aficamten is an investigatio
Slide 50: Durable Effects of Aficamten on Biomarkers
Sustained relative reductions in high-sensitivity Troponin I (~30%) & NT-proBNP (~70%) observed Durable Effects of Aficamten on Biomarkers High-Sensitivity Cardiac Troponin I NT-proBNP Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not
Slide 51: Durable Effects of Aficamten on Clinical Endpoints
Durable Effects of Aficamten on Clinical Endpoints 90% of SRT-eligible patients at baseline are no longer SRT-eligible KCCQ-CSS NYHA Class Guideline-Eligible for SRT ~50% of patients were asymptomatic at 1 year >80% of patients improved ≥1 NYHA Class at every visit after initiation of aficamten 71%
Slide 52: 64-year-old Man with a Family History of oHCM
10 mmHg 74 mmHg 64-year-old Man with a Family History of oHCM Week 2 Baseline NYHA Class Class IV Class III Class II Class I 0 10 20 30 40 50 60 70 80 90 100 110 120 NT-proBNP 0 10 20 30 40 50 60 70 80 90 100 110 120 1160 780 390 0 = ≤50 pg/mL Weeks Weeks
Slide 53: Summary of Observations to Date
Summary of Observations to Date Almost all eligible patients choose to participate in the OLE Echocardiography-guided dose titration of aficamten is managed entirely by the treating physicians 2/3 of patients achieve higher doses; no low LVEF events requiring treatment interruption 94 patients have
Slide 54: SEQUOIA-HCM
SEQUOIA-HCM Daniel Jacoby, M.D. Senior Medical Director, Clinical Research Cardiovascular Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 55: SEQUOIA-HCM: Phase 3 Trial
Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. SOC: standard of care * Focused echocardiogram SEQUOIA-HCM: Phase 3 Trial Completed enrollment; expect topline results by end of year Dose Options (Dose optimization
Slide 56: SEQUOIA-HCM: Enrollment Summary
SEQUOIA-HCM: Enrollment Summary Europe + Israel 142 Enrolled China 46 Enrolled North America 94 Enrolled Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 57: SEQUOIA-HCM: Baseline Characteristics
SEQUOIA-HCM: Baseline Characteristics Significant symptom burden despite background therapy 61% of patients on beta-blockers Baseline pVO2 reflects patient population with reduced exercise capacity Baseline Characteristics (N=282) n (%) or Mean (SD)a Demographics Age, years 59.1 (12.9) Female 114 (4
Slide 58: SEQUOIA-HCM: Baseline Characteristics
SEQUOIA-HCM: Baseline Characteristics Baseline Characteristics Target population was successfully enrolled and representative of a broad group of oHCM patients seen in the clinic Diverse by race and sex Objective physical limitation demonstrated and a high degree of symptom burden Approximately equa
Slide 59: Expected 2023 Milestones
Continue enrollment of ACACIA-HCM, pivotal Phase 3 trial of aficamten in nHCM Expected 2023 Milestones Aficamten Aficamten Continue enrollment of MAPLE-HCM, second Phase 3 trial of aficamten in oHCM Omecamtiv Mecarbil Pursue international approvals for omecamtiv mecarbil Emerging Pipeline Expect dat
Slide 60: MAPLE-HCM
MAPLE-HCM Daniel Jacoby, M.D. Senior Medical Director, Clinical Research Cardiovascular Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 61: MAPLE-HCM: Rationale
Filling Pressure Gradients Symptom Burden Exercise Capacity Exercise Capacity MAPLE-HCM: Rationale Beta-blocker withdrawal in HFpEF improves exercise capacity & symptoms1 Beta blockers in oHCM improve symptoms & LVOT obstruction BUT do not improve exercise capacity, filling pressures or NT-proBNP2,3
Slide 62: MAPLE-HCM: Phase 3 Monotherapy Trial
Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. SOC: standard of care * Focused echocardiogram MAPLE-HCM: Phase 3 Monotherapy Trial Trial to enroll approximately 170 patients Primary endpoint: change in peak VO2, a
Slide 63: MAPLE-HCM: Evolving the Treatment Paradigm
MAPLE-HCM: Evolving the Treatment Paradigm Pending favorable results, MAPLE-HCM has the potential to evolve the treatment paradigm by potentially: Supporting the rationale for first-line use in HCM treatment guidelines Demonstrating efficacy in an earlier diagnosed patient population Demonstrating m
Slide 64: Expected 2023 Milestones
Continue enrollment of ACACIA-HCM, pivotal Phase 3 trial of aficamten in nHCM Expected 2023 Milestones Aficamten Aficamten Continue enrollment of MAPLE-HCM, second Phase 3 trial of aficamten in oHCM Omecamtiv Mecarbil Pursue international approvals for omecamtiv mecarbil Emerging Pipeline Expect dat
Slide 65: REDWOOD-HCM: nHCM ACACIA-HCM
REDWOOD-HCM: nHCM ACACIA-HCM Steve Heitner, M.D. VP, Clinical Research & Therapeutic Area Lead, Cardiovascular Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 66: REDWOOD-HCM: Cohort 4
Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. *Telephone visits **Patient can only be down-titrated at Week 6 Patients with symptomatic nHCM on background therapy REDWOOD-HCM: Cohort 4 Dose 1 Dose 2 Dose 3 Cohort
Slide 67: Cohort 4: Significant Improvements in KCCQ & NYHA Class
Cohort 4 Significant Improvements in KCCQ & NYHA Class Kansas City Cardiomyopathy Questionnaire Categorical Changes at Week 10 in KCCQ-CSS NYHA Functional Class 56% of patients improved by ≥1 NYHA class Mean improvement in KCCQ of 10.6 points 85% of patients achieved 15 mg dose; no discontinuations
Slide 68: Cohort 4: Change in Biomarkers & Angina Frequency
Cohort 4 Change in Baseline in Biomarkers & Angina Frequency Proportional Change from Baseline in Cardiac Biomarkers Mean reduction in high-sensitivity cardiac troponin of 21% Mean reduction in NT-proBNP of 55% Seattle Angina Questionnaire Angina Frequency (SAQ-AF) Reduction in frequency of angina f
Slide 69: ACACIA-HCM Trial Design
Patients with: Symptomatic (NYHA Class II/III) nHCM, KCCQ-CSS ≥ 30 and ≤ 85 LVEF ≥ 60% NT-proBNP ≥ 300 ng/mL Study Visits CPET KCCQ Echocardiogramc Dose Titration Biomarkers NYHA Placebo Aficamten End of Study (EOS) Week 36 Primary Analysis KCCQ plus Secondary Week 72 End of Treatment (EOT) Screenin
Slide 70: Expected 2023 Milestones
Continue enrollment of ACACIA-HCM, pivotal Phase 3 trial of aficamten in nHCM Expected 2023 Milestones Aficamten Aficamten Continue enrollment of MAPLE-HCM, second Phase 3 trial of aficamten in oHCM Omecamtiv Mecarbil Pursue international approvals for omecamtiv mecarbil Emerging Pipeline Expect dat
Slide 71: Minute Break
5 Minute Break The program will return shortly.
Slide 72: HCM Patient Perspective
HCM Patient Perspective Megan Link, Person Living with HCM Actual patient who consents and agrees to appear.
Slide 73: Aficamten: Commercial Readiness
Aficamten: Commercial Readiness Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 74: New Market Research & Preliminary Positioning
New Market Research & Preliminary Positioning John Jacoppi VP, US Marketing for Aficamten
Slide 75: Patients Are Our North Star: Significant Impact of HCM
Patients Are Our North Star: Significant Impact of HCM The most commonly reported impacts of HCM symptoms on patients’ lives included limitations to physical activities (78%), emotional impacts, including feeling anxious or depressed (78%), and impacts on work (63%). My life was always unraveling, a
Slide 76: Our Planned Commercial Approach to Aficamten
Driven by a relentless focus on our North Star: the HCM patient Our Planned Commercial Approach to Aficamten Leverage deep understanding of patients, HCPs, payers, and community Tap into deep functional experience to build operational excellence across launch functions Engage with all stakeholders t
Slide 77: Deep Understanding & Insights Gathered
Deep Understanding & Insights Gathered Over Last 18 Months Cytokinetics has completed 14 primary market research projects with >831 HCPs, including cardiologists, NP/PAs, and others Cytokinetics has completed 5 primary market research projects with >163 HCM patients & their loved ones
Slide 78: oHCM Patient Journey Includes Complex Diagnosis & Progression
oHCM Patient Journey Includes Complex Diagnosis & Progression Symptomatic Presentation to PCP PCP Orders EKG PCP Refers to Cardiologist Genetic Test (not standard practice) Symptomatic HCM Diagnosis Abnormal EKG or Heart Murmur Detected Family History of HCM Cardiologist Conducts Diagnostic Workup (
Slide 79: HCM Patients Suffer Serious Complications & Debilitating Symptoms
HCM Patients Suffer Serious Complications & Debilitating Symptoms Sources: ACC, AHA, Elliott 2006, Harris 2016, Ommen 2009, Hamada 2014, Spirito 2017, Mayo Clinic, Bionest Partners Sudden Cardiac Death Atrial Fibrillation Heart Failure Emotional & Psychological Impact 80% of Patients Experience Limi
Slide 80: Cardiac Myosin Inhibitors are Entering Treatment Guidelines
Cardiac Myosin Inhibitors are Entering Treatment Guidelines
Slide 81: CMIs Have Transformed Patients' Lives
CMIs Have Transformed Patients’ Lives Selected example for illustration There was an incredible moment in clinic yesterday when I was able to tell a patient that her disease appeared to be “reversing”. This is the first time in my life I have used those words. Cardiac myosin inhibitors for hypertrop
Slide 82: However, Opportunities Exist…
However, Opportunities Exist… Key Benefits First non-interventional way to address underlying cause of oHCM Strong efficacy with few tolerability issues Few, if any, long-term concerns Key Challenges Burden of required monitoring/echo frequency Concerns about drug-drug interactions Down titration ch
Slide 83: Elements of ETASU REMS
Elements of ETASU REMS Certification or specialized training of HCPs who prescribe the drug A Certification of pharmacies or other dispensers of the drug B Dispensing/ administration of drug in limited settings C Dispensing/ administration only with evidence of safe-use conditions D Each patient usi
Slide 84: Class May Not Necessarily Define Scope of REMS
Class May Not Necessarily Define Scope of REMS REMS requirements impact all stakeholders, but greatest pain points include: Frequency & rigidity of required echo monitoring Stringency of pharmacy certification and dispensing requirements Significant process complexity and can lead to confusion for H
Slide 85: Potential Profile for Aficamten
Possible key attributes Potential Profile for Aficamten Predictable dose response Rapid reversibility Speed to optimal dose No clinically meaningful P450 liabilities Rapid onset No teratogenicity Aspirational information. Aficamten is an investigational drug and is not approved by any regulatory age
Slide 86: Potential Target Patient for Aficamten
Potential Target Patient for Aficamten Consistent with Anticipated Label Symptomatic oHCM1 NYHA Class II-III, LVEF ≥60%1 Not well-controlled, contraindicated to, or cannot tolerate BB / CCB2 We expect CMI penetration to be <20% of total addressable patient population at expected launch of aficamten
Slide 87: Market Research Shows Aficamten May Achieve High Share
Market Research Shows Aficamten May Achieve High Share & Grow Category Aficamten >60% Potential target product profile for aficamten interest creates share opportunity in newly treated CMI patients Aficamten is also expected to expand the total CMI market Key attributes that may drive preference inc
Slide 88: Our Brand Vision for Aficamten
Our Brand Vision for Aficamten Aficamten exists to… elevate the standard of care in HCM Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 89: Our Commercial Path Forward
Our Commercial Path Forward Leverage deep understanding of patients, HCPs, payers, and community Tap into deep functional experience to build operational excellence across launch functions Engage with all stakeholders to design an optimal customer experience Learn Design Build Our 2024 Focus Our Foc
Slide 90: Payer Landscape
Payer Landscape Andrew Callos EVP, Chief Commercial Officer
Slide 91: Most Patients Covered by Commercial or Medicare
Most Patients Covered by Commercial or Medicare 1. Symphony Metys Data Jan 2023 to End of April 2023. Symphony does NOT provide full Camzyos data capture. A significant PBM has blocked their reporting 2. SHA Patient Level Claims Data 12/20-11/21; includes BB, ACE, CCB, Disopyramide. 3. MMIT enrollme
Slide 92: Payer Research Points to Broad Access
Payer Research Covering >60% of Enrolled Lives Points to Broad Access Source: 4 waves of US payer research 2019 through 2023 covering 190M to 250M lives. Most recent: Clearview HealthPartners qualitative interviews completed Mar 2023, n=15, Med-D lives = 41M, Comm Lives = 149M, Total lives ~190M; Ma
Slide 93: Medicare & Commercial Coverage Expectations
Medicare & Commercial Coverage Expectations 2025 2026 2027 Coverage Broad Limited 2027 Medicare Bids Due Q4 2025 Building Coverage Broad Coverage Launch Access Estimates Initial Coverage Target PDUFA Medicare Bid 2027 Medicare Formulary Medicare bid timing is a key driver of Medicare access; commerc
Slide 94: Experienced Market Access Team to Accelerate Access
Experienced Market Access Team to Accelerate Access Collectively, ~300 years of payer/PBM relationship experience ~250 product launches, including ~100 CV products Average of 30+ Years of experience per Account Director Strong & extensive customer relationship experience
Slide 95: Health Economics Data to Support Value Proposition
Improvement in exercise capacity (pVO2), improvement in NYHA functional class and improvement in KCCQ-CSS lead to better health outcomes and cost savings Sustained efficacy could delay cost and complication of SRTs Minimal drug-drug interactions & rapid reversibility could result in broad usage of a
Slide 96: IRA Potentially Reduces Patient OOP Cost Burden
IRA Potentially Reduces Patient OOP Cost Burden $7,420 $2,000 Initial Coverage 25% Coverage Gap 25% Catastrophic 5% (uncapped) IRA Shift Initial Coverage 25% up to OOP Cap 73% reduction 2 2 1. Illustration assumes a specialty drug with a WAC price of $96,000 per year. 2. OOP Out-of-Pocket Cost. Sour
Slide 97: Focused investments in the customer experience required
Focused investments in the customer experience required Innovative Therapies Can Have More Complex Patient Journeys Complex Patient Journey Launch Coverage Delays Payer Utilization Mgmt Specialty Cost Sharing Access & Reimbursement Support Navigating Prior Auths and Medical Exceptions Benefits Verif
Slide 98: Planned Sales Strategy
Planned Sales Strategy Jeff Lotz VP, US Sales and Operations
Slide 99: Gated Build of Commercial Infrastructure
Majority of spending to occur closer to approval in 2025 Gated Build of Commercial Infrastructure 1/3 of hires pre-approval 2/3 of hires at approval Underway before SEQUOIA-HCM readout Market access strategy Pricing strategy Distribution approach Payer engagement Brand strategy Customer account iden
Slide 100: Initial HCM Customer Universe Includes 7-10K HCPs & ~500 Accounts
Initial HCM Customer Universe Includes 7-10K HCPs & ~500 Accounts Initial lists of HCPs and HCOs were defined based on: Diagnosers: HCM patient volume Treaters: BB/CCB, disopyramide claims, SRT, and mavacamten claims HCM trial investigators/sites HCM CoEs/Programs Source: Sales Ops team analysis as
Slide 101: 75% of HCM patient volume is treated by 10,000 cardiologists
75% of the HCM patient volume is treated by 10,000 cardiologists Cardiologists Located in Concentrated Geographic Clusters Across the US Note: includes only patients who are treated by a cardiologist - not all patients see a cardiologist; sample of 67K HCM patients Source: Symphony PTD (Patient Tran
Slide 102: Sales Team Designed Based on Efficiency & Customer Feedback
Several functions with very focused roles Overwhelmed customers, “It’s too much” Sales Team Designed Based on Efficiency & Customer Feedback Simple model creating quality experience Hire team with deep experience in specialty Traditional Models Our Design Principles CV Account Specialist Patient Ser
Slide 103: Highly Experienced Sales Leadership Team
Sales leaders have extensive industry, leadership and cardiovascular experience Highly Experienced Leadership Team Average of 22 years in industry Average of 13 years in leadership Average of 14 years in cardiovascular therapeutic area Nearly 50% / 50% Big vs. Small Pharma 100% have launch experienc
Slide 104: Customer Coverage Evolves With Specialty Cardiology Franchise
Customer Coverage Evolves With Specialty Cardiology Franchise 30,000 ~9,000 +4,000 +1,000 14,000 HCM HFrEF HFpEF Cardiology HCPs Building Today … … To Lead Tomorrow ~6,000 Overlap 1,000 Overlap To optimize value capture for potential launch of aficamten To support future launches and establish Cytok
Slide 105: HCM KOL Panel
HCM KOL Panel Cytokinetics” Not for Promotional Use, For Investors Only
Slide 106: HCM KOL Panel
HCM KOL Panel Theodore Abraham, M.D., FACC, FASE Meyer Friedman Distinguished Professor of Medicine, Division of Cardiology, University of California, San Francisco; Co-director, UCSF HCM Center of Excellence; Director, UCSF Adult Cardiac Echocardiography Laboratory Caroline Coats, Ph.D. Clinical Se
Slide 107: HFpEF Landscape & CK-586
HFpEF Landscape & CK-586 Stuart Kupfer, M.D. SVP, Chief Medical Officer CK-586 is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established.
Slide 108: Heart Failure with Preserved Ejection Fraction
Heart Failure with Preserved Ejection Fraction Thickened, stiff muscle surrounding left ventricle Irregular heartbeat Edema Dyspnea, exercise intolerance, cough Fatigue Heart failure with preserved ejection fraction (HFpEF) is a condition where pumping of the heart is impaired despite relatively nor
Slide 109: CMI eligible HFpEF population is ~770K
CMI eligible patient population of LVEF ≥ 65% without severe comorbidities is ~770K HFpEF Diagnosis Expected to Grow Faster than the General Population 2033 – CMI Eligible Prevalent Patient Population in U.S. Source: DataMonitor, Rosano 2022 ESC Heart Fail, Bellanca 2023 BMC,Feldman 2020 Arch. Cardi
Slide 110: 30-40% of HFpEF not well-managed by SoC
30-40% of HFpEF without severe comorbidities are not well-managed by SoC & remain symptomatic High Residual Risk in HFpEF Despite Benefit of SGLT2 Inhibitor Therapy Source: Journal of American College of Cardiology, April 19, 2023 Time to Worsening HF or CV Death Source: Solomon SD et al., 2022 NEJM
Slide 111: nHCM is a Human Model of HFpEF Subgroup
nHCM patients are similar to subgroups of HFpEF patients with hypercontractility nHCM is a Human Model of HFpEF Subgroup Symptoms and pathophysiology are similar in both conditions
Slide 112: CK-586: Distinct Mechanism of Action from Aficamten
CK-586 is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. Based on preclinical testing CK-586: Distinct Mechanism of Action from Aficamten Single-headed Myosin (S1) Two-headed Myosin (HMM) CK-586 inhibits actin-activated ATPase
Slide 113: CK-586: Shallow In Vivo Concentration-Response
CK-586 is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. CK-586: Shallow In Vivo Concentration-Response CK-586 is predicted to have a shorter half-life in humans than aficamten Pharmacodynamic window Fractional shortening IC50
Slide 114: CK-586 is Efficacious in ZSF1 Obese Rat Model of HFpEF
Model is representative of hypertensive, diabetic, metabolic aspects of HFpEF CK-586 is Efficacious in ZSF1 Obese Rat Model of HFpEF Reduced Fractional Shortening Improved Diastolic Function Reduced Fibrosis 10 weeks of treatment improved diastolic function and reduced cardiac fibrosis CK-586 is an
Slide 115: CK-271: Efficacious in Dahl Salt Sensitive Rat Model of HFpEF
Significant reduction in fibrosis in DSS rats on high salt diet in the absence of a change in blood pressure Model is characterized by hypertension, LV hypertrophy, and heart failure CK-271: Efficacious in Dahl Salt Sensitive (DSS) Rat Model of HFpEF Perivascular Interstitial Low Salt (LS) High Salt
Slide 116: CK-586: First-in-Human Study Design
Single and multiple ascending doses in healthy participants CK-586: First-in-Human Study Design Single Ascending Dose Cohorts Recently completed SAD cohorts, progressing to MAD cohorts 2 Participants CK-586 N=1 (Sentential Participant) Placebo N=1 CK-586 N=7 Placebo N=1 >24 Hours Safety Follow-up Ra
Slide 117: Cardiac Sarcomere Inhibition May Address Multiple Unmet Patient Needs
Cardiac Sarcomere Inhibition May Address Multiple Unmet Patient Needs nHCM Non-Obstructive HCM HFpEF Heart Failure with Preserved Ejection Fraction oHCM Obstructive HCM Cardiac myosin Inhibitors aficamten aficamten CK-586 Aficamten and CK-586 are investigational drugs and are not approved by any reg
Slide 118: Expected 2023 Milestones
Continue enrollment of ACACIA-HCM, pivotal Phase 3 trial of aficamten in nHCM Expected 2023 Milestones Aficamten Aficamten Continue enrollment of MAPLE-HCM, second Phase 3 trial of aficamten in oHCM Omecamtiv Mecarbil Pursue international approvals for omecamtiv mecarbil Emerging Pipeline Expect dat
Slide 119: Cytokinetics” Not for Promotional Use, For Investors Only
Cytokinetics” 119 Not for Promotional Use, For Investors Only
Slide 120: Closing Remarks
Closing Remarks Robert Blum President & CEO
Slide 121: Key Takeaways
Key Takeaways Cytokinetics is building a specialty cardiology franchise, led by aficamten, to address patient populations of high unmet medical need. Topline Results from SEQUOIA-HCM Expected by EOY Long-Term Data Support Safety and Efficacy of Aficamten Commercial Readiness Advancing CK-586 Aficamt
Slide 122: Cytokinetics: Uniquely Positioned for Success
Strong cash runway Access to capital through Royalty Pharma transaction Pioneer in CMI space Multiple drug candidates arising from our research Core research engine Cytokinetics: Uniquely Positioned for Success Late-stage HCM program HFrEF opportunity in Europe Early-stage HFpEF research Early-stage
Slide 123: Solid Financial Foundation & Prudent Spending
Solid Financial Foundation & Prudent Spending Strong cash position Access to additional capital Gated spending
Slide 124: Expected 2023 Milestones
Expected 2023 Milestones Aficamten Aficamten Continue enrollment of MAPLE-HCM, second Phase 3 trial of aficamten in oHCM Omecamtiv Mecarbil Pursue international approvals for omecamtiv mecarbil Emerging Pipeline Expect data from Phase 1 study of CK-136 in 2H Continue Phase 1 study of CK-586 Expect t
Slide 125: Thank You
Thank You ©2023 CYTOKINETICS, All Rights Reserved. CYTOKINETICS® and the C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries.