Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (May 2024)
63 slides from Cytokinetics's investor presentation, May 2024
Slide 1: Empowering muscle, empowering lives
muscle EMPOWERING EMPOWERING lives
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
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: Our vision: Leading with Science, pioneering medicines
Achieve regulatory approvals for drugs arising from our pipeline Build commercial capabilities to market and sell our medicines reflective of their innovation and value Our vision is to be the Generate sustainable and growing revenues from product sales leading muscle biology biopharma company that
Slide 5: A Great Place to Work; Uncommon Continuity of Team
A Great Place to Work; Uncommon Continuity of Team VALUES RETENTION patients are our North Star science is in our soul we > me make it happen <5% Turnover rate of leadership; low attrition AWARDS Winner >7 yrs in Wellness 3rd San Francisco Business Times Out of 25 Large Average tenure of leadership;
Slide 6: Sarcomere Directed Drug Development
Sarcomere Directed Drug Development The sarcomere is a molecular structure found in skeletal and cardiac muscle that enables myocytes to contract and generate force ACTIVATE INHIBIT INHIBIT ACTIVATE Troponin Omecamtiv CK-136 Aficamten CK-586 Mecarbil (Cardiac) (Cardiac) (Cardiac) Myosin (Cardiac) Tr
Slide 7: Contractile Dysfunction Underlies Cardiac Diseases
Contractile Dysfunction Underlies Cardiac Diseases Decreased Increased / Preserved Cardiac Contractility Cardiac Contractility • Heart Failure with Reduced • Non-obstructive Hypertrophic Ejection Fraction (HFrEF) Cardiomyopathy (nHCM) • Genetic Dilated • Obstructive Hypertrophic Cardiomyopathy Cardi
Slide 8: A Commitment to Muscle-Directed Cardiac Medicines
A Commitment to Muscle-Directed Cardiac Medicines Building a specialty cardiology franchise anchored by aficamten Protein Target Therapeutic Area Drug Candidate Research Pre-Clinical Phase 1 Phase 2 Phase 3 Approval Preparing for regulatory oHCM Aficamten submissions in 2H 2024 Myosin oHCM Aficamten
Slide 9: Building a Specialty Cardiology Franchise Anchored by Aficamten
Building a Specialty Cardiology Franchise Anchored by Aficamten Growing addressable patient market through specialty cardiology franchise strategy Myosin-Targeted Myosin Therapies Troponin Troponin-Targeted CK-136 Therapies 800K3 Heart failure Potential to HFpEF + EF ≥ 65% expand to in 2030 Omecamti
Slide 10: Specialty Cardiovascular Portfolio
Specialty Cardiovascular Portfolio Aficamten Omecamtiv Mecarbil CK-586 CK-136 10
Slide 11: Aficamten
Aficamten G Aficamten is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) Cytokinetics’ or any regulatory agency. The safety and effectiveness of this product has not been established. W
Slide 12: HCM Prevalence: Significant and Growing Globally
HCM Prevalence: Significant and Growing Globally HCM prevalence estimates vary across geography and over time Estimated HCM Prevalence Rates HCM True Patient Prevalence (Est. 2021) China 1,100 Europe GER: 0.07% (1) USA IT: 0.05-0.07% (5, 7) 0.02% (3), 0.08% (12), EU: 0.2% (13) EU 1,000 Asia 0.17% (6
Slide 13: Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients
Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients Potential for nearly 200K patients eligible for CMIs in 2025 Prevalence of HCM1 700K to 1.1M ~65% ~35% US oHCM1,3 nHCM1,3 USDiagnosed HCM oHCM Prevalence ~300K2 nHCM Prevalence 450-700K1,3 250-400K1,3 Diagnosed oHCM Diagnosed nHCM ~200K2,3
Slide 14: Aficamten: Proposed Mechanism of Action
Aficamten: Proposed Mechanism of Action Aficamten stabilizes myosin in the released post-powerstroke state unable to hydrolyze ATP “Fewer hands pulling on the rope” Before Aficamten After Aficamten Mechanochemical domain AF ATP Post-Powerstroke State Actin sliding Actin sliding Aficamten is an inves
Slide 15: Aficamten: Aspirational Target Profile
Aficamten: Aspirational Target Profile Potential next-in-class cardiac myosin inhibitor No clinically Rapid Rapid Speed to Predictable No meaningful onset reversibility optimal dose dose response teratogenicity P450 liabilities Aspirational information. Aficamten is an investigational drug and is no
Slide 16: REDWOOD-HCM: Cohorts 1 & 2 Design
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 17: REDWOOD-HCM: Robust Reduction of LVOT Gradients
REDWOOD-HCM: Robust Reduction of LVOT Gradients Cohorts 1 & 2 Consistent, clinically meaningful reductions in LVOT gradients within two weeks No treatment interruptions or discontinuations Reversibility of drug effect demonstrated Resting LVOT-G Valsalva LVOT-G 80 100 Combined Placebo 80 60 Aficamte
Slide 18: Change from Baseline in NT-proBNP & NYHA Class
Change from Baseline in NT-proBNP & NYHA Class Cohorts 1 & 2 Change from Baseline NT-proBNP to 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% NT-proBNP (pg/mL) (n=9) -400 60 % Total -600 40 6
Slide 19: Improved Cardiac Structure and Diastolic Function
Improved Cardiac Structure and Diastolic Function Cohorts 1 & 2: Early signs of improvement in cardiac structure and myocardial relaxation Cardiac Structure Treatment with aficamten for 10 weeks resulted in: • Significant reduction in left atrial volume index • Trend towards a reduction in LV mass i
Slide 20: Response Rates on Treatment with Aficamten
Response Rates on Treatment with Aficamten Cohorts 1 & 2 1/13 11/14 13/14 100 Responder # / Total # 8% 79% 93% Incomplete LVOT-G response • Consistent, clinically Complete LVOT-G response 80 meaningful reductions in LVOT Responder Definition: Resting LVOT-G <30 gradients within two weeks mmHg and po
Slide 21: REDWOOD-HCM: Cohort 4 Design
REDWOOD-HCM: Cohort 4 Patients with symptomatic nHCM on background therapy Results presented at Heart Failure 2023 End of Study Screening Patients with symptomatic nHCM on background Aficamten + SoC therapy Study Visits Screen W-1* D1 W2 W4 W6** W8* W9* W10 W12 W14* Ambulatory Cardiac Monitoring PK
Slide 22: Significant Improvements in KCCQ & NYHA Class
Significant Improvements in KCCQ & NYHA Class Cohort 4 85% of patients achieved 15 mg dose; no discontinuations due to adverse events Kansas City Cardiomyopathy Questionnaire Categorical Changes at Week 10 in KCCQ-CSS NYHA Functional Class Mean improvement in KCCQ of 10.6 points 56% of patients impr
Slide 23: Change in Baseline in Biomarkers & Angina Frequency
Change in Baseline in Biomarkers & Angina Frequency Cohort 4 Proportional Change from Baseline in Cardiac Seattle Angina Questionnaire Angina Biomarkers Frequency (SAQ-AF) Mean reduction in high-sensitivity cardiac troponin of 21% Reduction in frequency of angina from daily or weekly, to weekly or m
Slide 24: FOREST-HCM: Baseline Characteristics
FOREST-HCM: Baseline Characteristics FOREST-HCM data cut as of September 15, 2023 Baseline characteristics indicate substantial disease burden; ~2/3 patients achieving 15 or 20 mg FOREST-HCM oHCM Dose of Aficamten N=143 Age (Years), Mean (SD) 60.4 (13.2) Female, n (%) 65 (45.5) BMI (kg/m2), Mean (SD
Slide 25: Few Dose Reductions During Maintenance
Few Dose Reductions During Maintenance Dose Titration Phase Maintenance Phase Down-titration triggered 0.5% • No treatment-related LVEF <50% • 579 monitoring echocardiograms during the titration period completed* in oHCM patients • Of the 94 patients having completed • None with LVEF <40% requiring
Slide 26: Observed Durable Effects of Aficamten on LVOT-G & LVEF
Observed Durable Effects of Aficamten on LVOT-G & LVEF FOREST-HCM data cut as of September 15, 2023 • Resting & provoked gradients remain below diagnostic threshold for >2 years, LVEF remains flat after titration Aficamten is an investigational drug and is not approved by any regulatory agency. Its
Slide 27: Observed Durable Effects on Cardiac Structure, Function & NT-proBNP
Observed Durable Effects of Aficamten on Cardiac Structure, Function & NT-proBNP Maximal Wall Thickness LA Volume Index Lateral E/e’ NT-proBNP Data cut as of October 31, 2023 Data cut as of October 31, 2023 Data cut as of October 31, 2023 Data cut as of September 15, 2023 Mean and 95% CI in all figu
Slide 28: Observed Durable Effects on Clinical Endpoints
Observed Durable Effects of Aficamten on Clinical Endpoints KCCQ-CSS NYHA Class Guideline-Eligible for SRT Data cut as of September 15, 2023 Data cut as of September 15, 2023 Data cut as of October 31, 2023 71% of patients had ≥ 5-point KCCQ-CSS increase ~50% of patients were asymptomatic at 1 year
Slide 29: Safety Data: Phase 2 & OLE
Safety Data: Phase 2 & OLE oHCM Cohorts 1, 2, & 3: After 10-weeks of treatment • Almost all eligible patients choose to participate in the OLE • 2 SAEs reported in 41 aficamten-treated none were related to • Echocardiography-guided dose titration of aficamten is managed aficamten treatment entir
Slide 30: SEQUOIA-HCM: Phase 3 Trial
SEQUOIA-HCM: Phase 3 Trial Announced positive topline results in December 2023; presented primary results at Heart Failure 2024 Primary endpoint: Change in pVO2 by CPET from baseline to Week 24 Randomization Aficamten + SoC End of Study Patients with Screening oHCM treated Secondary objectives inclu
Slide 31: SEQUOIA-HCM: Efficacy & Safety Summary
SEQUOIA-HCM: Efficacy & Safety Summary Efficacy Safety • Primary endpoint and all 10 pre-specified secondary endpoints were clinically meaningful and • Aficamten was safe and well-tolerated with an statistically significant (all p-values < 0.0001) overall incidence of adverse events similar to that
Slide 32: SEQUOIA-HCM: Probability Values (p-value)
SEQUOIA-HCM: Probability Values (p-value) Endpoints p-value Primary Endpoint pVO2 change from baseline to Week 24 <0.0001 Secondary Endpoints KCCQ-CSS change from baseline to Week 24 <0.0001 NYHA Class Improvement by at least 1 class at Week 24 <0.0001 Valsalva LVOT-G change from baseline to Week 24
Slide 33: SEQUOIA-HCM: Baseline Characteristics
SEQUOIA-HCM: Baseline Characteristics Baseline characteristics reflect highly symptomatic patient population with reduced exercise capacity Baseline Characteristics (N=282) n (%) or Mean (SD)a Baseline Characteristics (N=282) n (%) or Mean (SD)a • Significant symptom Demographics HCM Medical Therapi
Slide 34: Preparing for Regulatory Submissions to FDA, EMA
Preparing for Regulatory Submissions to FDA, EMA • Participated in two meetings with FDA in Q1 2024 • Type B meeting with FDA to occur in Q2 2024 2024 • Meetings with EMA in Q2 2024 Positive Results from • Expect to submit NDA to FDA in Q3 2024 and SEQUOIA-HCM MAA to EMA in Q4 2024: development of a
Slide 35: MAPLE-HCM: Phase 3 Monotherapy Trial
MAPLE-HCM: Phase 3 Monotherapy Trial Currently enrolling Active-comparator trial of aficamten as monotherapy vs. metoprolol in patients with oHCM (if applicable) • Trial to enroll Recently diagnosed 2 Week SOC LVOT-G (mmHg) Washout or treatment naïve Resting ≥ 30 approximately Randomization with sym
Slide 36: ACACIA-HCM: Pivotal Phase 3 Trial in nHCM
ACACIA-HCM: Pivotal Phase 3 Trial in nHCM Currently enrolling Patients with: Randomization • Trial to enroll approximately Aficamten End of Study Symptomatic 420 symptomatic nHCM N = 420 Screening (1:1) (NYHA Class patients II/III) nHCM, KCCQ-CSS Placebo • Primary endpoint: change in ≥ 30 and ≤ 85 K
Slide 37: CEDAR-HCM: Clinical Trial in Pediatric Population
CEDAR-HCM: Clinical Trial in Pediatric Population Currently enrolling • Expected to enroll initial Adolescent cohort of ~40 adolescent cohort criteria Randomization Aficamten 2 Week SOC Washout End of Study patients aged 12 to 17 Screening LVEF ≥ 60% 2 • Data from adolescent patients Valsalva LVOT-G
Slide 38: Aficamten: Clinical Development Plan for HCM
Aficamten: Clinical Development Plan for HCM Phase 1 Phase 2 Phase 3 SAD & MAD REDWOOD-HCM Cohorts 1-3 SEQUOIA-HCM Healthy obstructive HCM obstructive HCM Target IND Filed Volunteers Placebo controlled; echocardiography endpoints Pivotal trial with exercise endpoint (peak VO2) NDA Potential for Well
Slide 39: Aficamten: Planned Commercial Approach
Aficamten: Planned Commercial Approach Driven by a relentless focus on our North Star: the HCM patient Learn Design Build Leverage deep Engage with all Tap into deep functional understanding of stakeholders to design experience to build patients, HCPs, payers, an optimal customer operational excelle
Slide 40: Market Research Shows Aficamten May Achieve High Share & Grow Category
Market Research Shows Aficamten May Achieve High Share & Grow Category oHCM CMI Preference Shares in • Potential target product profile for aficamten Eligible Patient Population* interest creates share opportunity in newly treated CMI patients • Aficamten is also expected to expand the total CMI mar
Slide 41: Majority of CMI-Eligible Patients Available at Launch
If Aficamten is Approved, Expect Majority of CMI-Eligible Patients Available at Launch Diagnosis of HCM anticipated to grow 5x the rate of the general population US HCM Patients (in ‘000) Illustrative Potential Potential nHCM Launch 500K1,2 oHCM Launch >80% CMI-Eligible >90% patients available 300K1
Slide 42: Cardiologists Located in Concentrated Geographic Clusters Across the US
Cardiologists Located in Concentrated Geographic Clusters Across the US 75% of the HCM patient volume is treated by 10,000 cardiologists HCM Patient Concentration by Cardiologist Geographic Distribution of HCM Patients 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 7,000 10,000 … 30,000 Note: includes
Slide 43: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Majority of spending to occur closer to approval in 2025 2/3 of hiring to occur at-approval Key activities after SEQUOIA-HCM readout Continued insight generation Commercial leadership Market access strategy validation Marketing Pricing strategy finalization D
Slide 44: US Commercial Readiness Milestones for Aficamten
US Commercial Readiness Milestones for Aficamten 2024-2025 2024 2025 Launch Final GTM Launch Launch Ready Planning Strategy Tactical Plan Market Digital / HCP Branded Messages Final Development Omnichannel & Campaign Finalized Marketing Positioning Full Campaign Patient Campaign Development Finalize
Slide 45: Omecamtiv Mecarbil
G Cytokinetics” 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. 45
Slide 46: Omecamtiv Mecarbil: Current Status
Omecamtiv Mecarbil: Current Status Received CRL from FDA Withdrew MAA from EMA GALACTIC-HF not sufficiently Withdrew the MAA from the EMA persuasive to establish substantial based on feedback from the CHMP evidence of effectiveness for indicating that the Committee will reducing the risk of heart fa
Slide 47: CK-586
CK-586 G CK-586 is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) or any Cytokinetics’ regulatory agency. The safety and effectiveness of this product has not been established. 47
Slide 48: Novel Approach May Address Multiple Unmet Patient Needs
Novel Approach May Address Multiple Unmet Patient Needs oHCM Obstructive HCM aficamten Cardiac myosin Inhibitors aficamten CK-586 nHCM HFpEF Non-Obstructive HCM Heart Failure with Preserved Ejection Fraction 48
Slide 49: Heart Failure with Preserved Ejection Fraction (HFpEF)
Heart Failure with Preserved Ejection Fraction (HFpEF) Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor1 8.5 million ~50% ~75% ~84% Americans will have HF patients have HFpEF patients will HFpEF patients will heart failure by HFpEF3
Slide 50: CK-586: Distinct Mechanism of Action from Aficamten
CK-586: Distinct Mechanism of Action from Aficamten CK-586 inhibits actin-activated ATPase of HMM only; aficamten inhibits both S1 and HMM Single-headed Two-headed Myosin (S1) Myosin (HMM) Based on preclinical testing CK-586 is an investigational drug and is not approved by any regulatory agency. It
Slide 51: CK-586: Shallow In Vivo Concentration-Response
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 /IC10 ratio mavacamten 2.8x aficamten 9.9x CK-586 9.3x IC10: plasma concentration at 10% relative reduction in fractional shorteni
Slide 52: CK-586 is Efficacious in ZSF1 Obese Rat Model of HFpEF
CK-586 is Efficacious in ZSF1 Obese Rat Model of HFpEF Model is representative of hypertensive, diabetic, metabolic aspects of HFpEF 10 weeks of treatment improved diastolic function and reduced cardiac fibrosis Reduced Fractional Shortening Improved Diastolic Function Reduced Fibrosis CK-586 is an
Slide 53: Phase 1 Data Support Advancement to Phase 2 Clinical Trial
Phase 1 Data Support Advancement to Phase 2 Clinical Trial Full data to be presented at a medical congress in 2H 2024 Phase 1 Design Key Findings • Pharmacodynamics were evaluated using echocardiography and consistent with expectations • 7 SAD cohorts (10 mg to 600 mg) comprised of 10 participants e
Slide 54: CK-136
CK-136 G CK-136 is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) or any Cytokinetics’ regulatory agency. The safety and effectiveness of this product has not been established. 54
Slide 55: CK-136: Mechanism of Action
CK-136: Mechanism of Action Key biochemical and cellular features The first selective cardiac troponin activator Contractability Strongly Calcium Transients Unchanged Greater ATPase Activity Greater ATPase Activity Activated After Treatment After Treatment 1PD Window = Maximum Tolerated Concentratio
Slide 56: CK-136: Exposure Response Relationship
CK-136: Exposure Response Relationship Exposure-response of troponin activator is shallower than myosin activator Completed Phase 1 study and have begun analyzing data Animal Models of Cardiac Function Healthy Rats PD Window1 MI Rats PD Window1 Healthy Dogs PD Window1 ≥15X ≥15X ≥15X 1PD Window = Max
Slide 57: Corporate Profile
Corporate Profile G Cytokinetics” 57
Slide 58: Robust Pipeline, Solid Financial Position
Robust Pipeline, Solid Financial Position Pipeline 1 Potential commercial launch in 2025 3 Clinical stage programs Ongoing muscle biology directed research HCM Heart Failure Ongoing Aficamten o SEQUOIA-HCM: Positive Phase 3 results Omecamtiv mecarbil o Considering potential next CK-136 R&D Programs
Slide 59: Expected Value Unlocked with Future Catalysts
Expected Value Unlocked with Future Catalysts Myosin platform drives value and growth with multiple data milestones and expected approvals Aficamten Aficamten SEQUOIA-HCM oHCM Potential Enhancing Results Approval shareholder value Emerging Aficamten Pipeline MAPLE-HCM Results Aficamten Aficamten oHC
Slide 60: Cytokinetics: Uniquely Positioned for Success
Cytokinetics: Uniquely Positioned for Success Leadership Depth Relationships Access in muscle biology in cardiology with stakeholders to capital Pioneer in CMI space Late-stage HCM program Seasoned commercial team Strong cash runway based on HFrEF opportunity in Europe 2024 financial guidance Multip
Slide 61: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance Approximately 2 years of cash runway based on 2024 guidance* 2024 Condensed Balance Sheet 2024 Financial Guidance As of 3/31/2024 in millions in millions Total Total Cash and investments $634.3 Cash Revenue $3-5 Accounts receivable $0.8 Operating Expenses $420-450
Slide 62: Expected 2024 Milestones
Expected 2024 Milestones Aficamten Aficamten CK-586 Present primary results from Share full data from Phase 1 study Continue enrollment of ACACIA-HCM of CK-586 in 2H 2024 SEQUOIA-HCM at HFA in Q2 2024 in 2024 Initiate Phase 2 study Submit NDA to FDA in Q3 2024 and Continue enrollment of CEDAR-HCM of
Slide 63: Thank you
CG Cytokinetics’ thank you