Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (March 2023)
43 slides from Cytokinetics's investor presentation, March 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 ACTIVATE Troponin Omecamtiv Reldesemtiv CK-136 CK-601 Aficamten CK-271 Mecarbil (Cardiac) (C
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 MAA on file Omecamtiv Mecarbil (Heart Failure) with EMA Aficamten (oHCM) Aficamten (nHCM) CK-136 (Heart Failure, other) CK-586 SKELETAL MUSCLE Reldesemtiv (ALS)* Additional Skeletal Muscle
Slide 7: Key Priorities in 2023
Key Priorities in 2023 Continue execution of SEQUOIA-HCM and advance broad development program and go-to-market strategy for aficamten Request meeting with FDA Continue execution regarding CRL for omecamtiv mecarbil of COURAGE-ALS and OLE Expand research beyond contractility to Advance development o
Slide 8: Cardiac Muscle
Sarcomere Directed Drug Development Cardiac Muscle Aficamten Omecamtiv Mecarbil 8
Slide 9: 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 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 Symptomatic 190K Diagno
Slide 11: 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 12: REDWOOD-HCM: Cohorts & Randomization
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 13: 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 14: 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 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: REDWOOD-HCM: Cohort 4
REDWOOD-HCM: Cohort 4 Patients with symptomatic nHCM on background therapy Initial results presented at ACC.23; additional data expected in 1H 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*
Slide 18: Significant Improvements in Symptoms & Biomarkers
Significant Improvements in Symptoms & Biomarkers Cohort 4 85% of patients achieved 15 mg dose; no discontinuations due to adverse events Change from Baseline NT-proBNP Improvement in NYHA Class Change in Baseline hs-cTroponin I Average decrease of 66% with P<0.0001 54% of patients experienced a cha
Slide 19: FOREST-HCM: Open Label Extension
FOREST-HCM: Open Label Extension Long-term treatment shows sustained improvement in LVOT-G, NYHA class, KCCQ Treatment with aficamten eliminated SRT eligibility in all patients eligible at baseline 48 Weeks: Resting LVOT Gradient 24 Weeks: Change from Baseline KCCQ Scores 48 Weeks: Improvement in NY
Slide 20: Safety Data: Phase 2 & OLE
Safety Data: Phase 2 & OLE • oHCM → Cohorts 1, 2, & 3: 10-weeks of treatment • oHCM → FOREST-HCM: 45 patients and up-to 12-months of treatment • 2 SAEs reported in 41 aficamten-treated → none were related to aficamten treatment • No SAE’s related to aficamten treatment • No treatment interruptions o
Slide 21: SEQUOIA-HCM: Phase 3 Trial
SEQUOIA-HCM: Phase 3 Trial More than two-thirds of patients enrolled; on track to complete enrollment in Q2 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 SO
Slide 22: 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 23: 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 24: 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 25: 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 CARDIAC MUSCLE SKELETAL MUSCLE CORPORAT
Slide 26: 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- Majority of KOLs see aficamten as an responsive, refractory) to standard- improvement to standard-of-care of-care given th
Slide 27: 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 28: 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 29: 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 30: 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 31: Omecamtiv Mecarbil: Current Status
Omecamtiv Mecarbil: Current Status No plans to conduct additional clinical trial of omecamtiv mecarbil • Engage with FDA to understand what Received CRL from FDA may be required to support potential Feb 28, 2023 approval of omecamtiv mecarbil • Continue to pursue international GALACTIC-HF not suffic
Slide 32: Skeletal Muscle
Sarcomere Directed Drug Development Skeletal Muscle Reldesemtiv 32
Slide 33: 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 34: 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, 150 mg BID (n = 110) Australia and Europe evaluating
Slide 35: Primary Endpoint: Percent Predicted SVC Change From Baseline
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 36: Phase 2 Clinical Trial 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 37: Post-Hoc Analyses Inform Phase 3 Design
Post-Hoc Analyses Inform Phase 3 Design Change From Baseline in ALSFRS-R Majority of Patients Who Meet 24/44 Criteria Have Short by Progressor Tertiles or Intermediate Predicted Survival 24/44 criteria: symptoms for ≤24 months; baseline ALSFRS-R total score ≤44 Time (weeks) All patients in COURAGE-A
Slide 38: Phase 3 Clinical Trial Design
Phase 3 Clinical Trial Design >75% of patients enrolled; on track to complete enrollment in Q2 Second interim analysis expected in 1H 2023 (futility & potential fixed increase in enrollment) Enrolling patients with ALS in the US, Canada, Australia Reldesemtiv (N= 555) 300 mg BID End of Study and Eur
Slide 39: Corporate Profile
Sarcomere Directed Therapies Corporate Profile 39
Slide 40: Robust Pipeline, Solid Financial Position
Robust Pipeline, Solid Financial Position Pipeline 1 Potential commercial launch in 2024 2 Programs in Phase 3 trials 2 Potential FDA approvals by 2025 5 Clinical stage programs 10 Development programs by 2025 HCM Heart Failure ALS Ongoing Aficamten o 1 ongoing Phase 3 trial in oHCM Omecamtiv mecarb
Slide 41: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance >2 years cash runway based on 2023 guidance 2022 Condensed Balance Sheet 2023 Financial Guidance As of 12/31/2022 in millions in millions Total Total Cash and investments $829.3 Cash Revenue $5* Accounts receivable $0.1 Cash Operating Expenses $420-450 PPE $80.5 Ne
Slide 42: Expected 2023 Milestones
Expected 2023 Milestones Aficamten Aficamten Omecamtiv Mecarbil Reldesemtiv Early Pipeline Begin MAPLE-HCM, Present results from Engage with FDA Expect second Expect results from second Phase 3 trial Cohort 4 of REDWOOD- regarding CRL for interim analysis Phase 1 study of of aficamten in HCM at ACC.
Slide 43: Thank You
Thank You Sarcomere directed therapies