Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (June 2023)
47 slides from Cytokinetics's investor presentation, June 2023
Slide 1: Empowering muscle, empowering lives
empowering muscle empowering lives Sarcomere directed therapies
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: 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 ACTIVATE Troponin Omecamtiv Reldesemtiv CK-136 Aficamten CK-586 Mecarbil (Cardiac) (Cardiac) (Skeleta
Slide 6: 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 (HFrEF)* Aficamten (oHCM) Aficamten (nHCM) CK-136 (Heart Failure, other) CK-586 (HFpEF) SKELETAL MUSCLE Reldesemtiv (ALS)** Additional Skeletal Muscle Activators OTHER Mu
Slide 7: Specialty Cardiovascular Portfolio
Sarcomere Directed Drug Development Specialty Cardiovascular Portfolio Aficamten Omecamtiv Mecarbil Emerging Pipeline – CK-136 & CK-586 7
Slide 8: Aficamten
Aficamten G Aficamten 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.
Slide 9: 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 10: In US, Large HCM Population With Many Undiagnosed
In US, Large HCM Population With Many Undiagnosed 280K Diagnosed HCM Patients; Estimated 400-800K Undiagnosed Current US HCM Prevalence Growing HCM Prevalence Total US 700K –1.1M HCM Prevalence 700,000-1.1M1 Undiagnosed Patients Diagnosed 280,0002 Diagnosed nHCM Patients 280K Diagnosed oHCM 190K Dia
Slide 11: 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 Post-Powerstroke State Actin sliding Actin sliding Not for Promotional Use,
Slide 12: Aficamten: Aspirational Target Profile
Aficamten: Aspirational Target Profile Potential next-in-class cardiac myosin inhibitor Rapid Onset Precise Dosing Simplicity of Use Rapid Reversibility Symptom relief as early Echo guided dose No off-target effects and Washout of as within 2 weeks titration allows both dose use in combination with
Slide 13: 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 14: REDWOOD-HCM: Efficacy
REDWOOD-HCM: Efficacy Cohorts 1 & 2 Results published in JACC in January 2023 Resting LVOT-G Valsalva LVOT-G 80 100 Combined Placebo 80 60 Aficamten: Cohort 1 60 Aficamten: Cohort 2 mmHg mmHg 40 LVOT-G ≥50 mmHg 40 * ** ** ** * 20 ** ** *** *** ** 20 * P < 0.05 *** ** ** ** ** P < 0.001 mean ± SEM **
Slide 15: 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 16: 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 17: 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 18: REDWOOD-HCM: Cohort 4 Design
REDWOOD-HCM: Cohort 4 Patients with symptomatic nHCM on background therapy Initial results presented at ACC.23; additional data to be presented at ESC Heart Failure End of Study Screening Patients with symptomatic nHCM on background Aficamten + SoC therapy Study Visits Screen W-1* D1 W2 W4 W6** W8*
Slide 19: 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 im
Slide 20: 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 21: FOREST-HCM: Open Label Extension
FOREST-HCM: Open Label Extension Long-term treatment shows sustained improvement in LVOT-G 48 Weeks: Resting LVOT Gradient 48 Weeks: Valsalva LVOT Gradient †P<0.001; ‡P<0.0001 Aficamten is an investigational agent and is not approved by any regulatory agency. Its safety and efficacy has not been est
Slide 22: FOREST-HCM: Open Label Extension
FOREST-HCM: Open Label Extension Long-term treatment shows sustained improvement NYHA class and KCCQ 48 Weeks: Improvement in NYHA Class 24 Weeks: Change from Baseline KCCQ Scores Aficamten is an investigational agent and is not approved by any regulatory agency. Its safety and efficacy has not been
Slide 23: Safety Data: Phase 2 & OLE
Safety Data: Phase 2 & OLE • oHCM → Cohorts 1, 2, & 3: After 10-weeks of treatment • oHCM → FOREST-HCM: 45 patients and up-to 12- months of treatment (as of Q1 2023) • 2 SAEs reported in 41 aficamten-treated → none were related to aficamten treatment • No SAE’s related to aficamten treatment • No tr
Slide 24: SEQUOIA-HCM: Phase 3 Trial
SEQUOIA-HCM: Phase 3 Trial Currently completing enrollment; expect results Q4 2023 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 include measuring with SOC with post-Valsalva 1 ch
Slide 25: MAPLE-HCM: Phase 3 Monotherapy Trial
MAPLE-HCM: Phase 3 Monotherapy Trial Opening to enrollment in Q2 Active-comparator trial of aficamten as monotherapy vs. metoprolol in patients with oHCM • Trial to enroll approximately 170 patients • Primary endpoint: change in peak VO2, assessed by CPET from baseline to Week 24 • Secondary endpoin
Slide 26: Monotherapy Trial, Supported by FOREST-HCM
Monotherapy Trial, Supported by FOREST-HCM Initial FOREST-HCM data on reduction/withdrawal of background medications supports monotherapy trial Reduction or Withdrawal of Standard of Care Therapies Valsalva LVOT-G NYHA Class LVEF A: All patients **** = p < 0.0001 B: On background therapy (BT) *** =
Slide 27: Aficamten: Clinical Development Plan for HCM
Aficamten: Clinical Development Plan for HCM MAPLE-HCM to begin in Q2 2023; pivotal Phase 3 trial in nHCM beginning 2H 2023 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 obstructive HCM NDA
Slide 28: 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 Not for Promotional Use, For Investors Only OVERVIEW AFICAMTEN OMECAMTIV MECARBIL EMERGING P
Slide 29: Aficamten: Targeting Patients with Unmet Need
Aficamten: Targeting Patients with Unmet Need Positive HCP Anticipation Characteristics of the Ideal for Aficamten US HCM Patient for Aficamten • Symptomatic, uncontrolled (non- Significant number of KOLs potentially responsive, refractory) to standard- see aficamten as an improvement to of-care sta
Slide 30: Aficamten: Brand Strategy
Aficamten: Brand Strategy Aspirational Brand Goal: Establish aficamten as foundational therapy for HCM patients COMPETE: EXPAND: MAINTAIN: GROW: In HCM Market Customer Base Patient on Therapy Undiagnosed • Differentiate on product • Leverage differentiated • Ensure access through • Invest in disease
Slide 31: Aficamten: Market Access Strategy
Aficamten: Market Access Strategy Develop value Get rapid and Clear pricing based proposition parity access on benefit and value story • Learn from first to market • Relative pricing position to be • Driven by clinical benefit and access experience supported by market research utility relative to al
Slide 32: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Re-deployment of cardiovascular franchise commercial team to aficamten Activities initiated upon key de-risking events Underway Pre-NDA filing Headquarters team in place Market access Pricing strategy Distribution approach • Commercial leadership Payer engage
Slide 33: Omecamtiv Mecarbil
Omecamtiv Mecarbil G Omecamtiv mecarbil 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.
Slide 34: Omecamtiv Mecarbil: Current Status
Omecamtiv Mecarbil: Current Status No plans to conduct additional clinical trial of omecamtiv mecarbil • Engage with FDA to understand what may be required to support potential Received CRL from FDA approval of omecamtiv mecarbil Feb 28, 2023 • Continue to pursue international GALACTIC-HF not suffic
Slide 35: Emerging Cardiovascular Pipeline CK-136 & CK-586
Emerging Cardiovascular Pipeline CK-136 & CK-586 35
Slide 36: Early Development Supports Cardiovascular Portfolio
Early Development Supports Cardiovascular Portfolio CK-136 CK-586 Additional Research Cardiac troponin activator Cardiac myosin inhibitor Advancing pre-clinical for the potential treatment of designed to potentially research in the mechanics of patients with heart failure reduce the hypercontractili
Slide 37: 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 38: CK-136: Exposure Response Relationship
CK-136: Exposure Response Relationship Exposure-response of troponin activator is shallower than myosin activator Phase 1 study in progress Animal Models of Cardiac Function Healthy Rats PD Window1 MI Rats PD Window1 Healthy Dogs PD Window1 ≥15X ≥15X ≥15X 1PD Window = Maximum Tolerated Concentration
Slide 39: 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) Not for Promotional Use, For Investors Only OVERVIEW AFICAMTEN OMECAMTIV MECARBIL EMERGING PIPELINE RELDESEMTIV
Slide 40: Skeletal Muscle: Reldesemtiv
Sarcomere Directed Drug Development Skeletal Muscle Reldesemtiv 40
Slide 41: Reldesemtiv
Reldesemtiv G Reldesemtiv 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.
Slide 42: Reldesemtiv Development Program: Current Status
Reldesemtiv Development Program: Current Status COURAGE-ALS Phase 3 clinical trial of reldesemtiv in ALS Assessing next steps First interim analysis 2022 Second interim analysis 2023 and closing clinical Designed with two trial program DMC recommended DMC recommended planned interim analyses continu
Slide 43: Corporate Profile
Sarcomere Directed Therapies Corporate Profile 43
Slide 44: Robust Pipeline, Solid Financial Position
Robust Pipeline, Solid Financial Position Pipeline 1-2 Potential commercial launches in 2025 5 Clinical stage programs 10 Development programs by 2025 HCM Heart Failure Ongoing Aficamten o SEQUOIA-HCM ongoing (Phase 3 trial in oHCM) Omecamtiv mecarbil CK-136 R&D Programs o Engaging with FDA o Result
Slide 45: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance >2 years cash runway based on 2023 guidance 2023 Condensed Balance Sheet 2023 Financial Guidance As of 3/31/2023 in millions in millions Total Total Cash and investments $704.4 Cash Revenue $5 Accounts receivable $1.0 Cash Operating Expenses $420-450 PPE $78.9 Net
Slide 46: Expected 2023 Milestones
Expected 2023 Milestones Aficamten Aficamten Omecamtiv Mecarbil Emerging Pipeline Begin MAPLE-HCM, second Phase 3 trial of aficamten in oHCM in Q2 Engage with FDA regarding CRL for Expect data from Phase 1 study omecamtiv mecarbil of CK-136 in 2H Complete enrollment in SEQUOIA-HCM in Q2 2023; result
Slide 47: Thank You
Thank You Sarcomere directed therapies