Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (January 2023)
52 slides from Cytokinetics's investor presentation, January 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 Omecamtiv Mecarbil (Heart Failure) NDA Filed PDUFA: 02/28/23 Aficamten (oHCM) Aficamten (nHCM) CK-271 CK-136 (Heart Failure, other) SKELETAL MUSCLE Reldesemtiv (ALS)* CK-601 Additional Skel
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 Engage with FDA ahead of February 28 Continue execution PDUFA date for omecamtiv mecarbil of COURAGE-ALS and OLE Expand research beyond contractility to Advance earl
Slide 8: Cardiac Muscle: Cardiovascular Franchise Strategy
Sarcomere Directed Drug Development Cardiac Muscle Cardiovascular Franchise Strategy Aficamten Omecamtiv Mecarbil 8
Slide 9: Cardiovascular Franchise Strategy
Cardiovascular Franchise Strategy 9
Slide 10: Go-to-Market Synergies for Aficamten & Omecamtiv Mecarbil
Go-to-Market Synergies for Aficamten & Omecamtiv Mecarbil Sales Given target overlap, leveraging same sales team Team Commercial Support Utilize resources across brands (e.g., access, analytics, …) Functions Significant Cost Medical Savings MSs qualified to cover both HFrEF and HCM Affairs Corporate
Slide 11: 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 12: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Engagement ongoing with FDA post Advisory Committee meeting Cardiovascular franchise commercial team comprised of 75, with 10 dedicated to omecamtiv mecarbil 2/3 of hiring to occur after potential approval Activities initiated upon key de-risking events Under
Slide 13: Aficamten
Aficamten G Aficamten is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) or Cytokinetics any regulatory agency. The safety and effectiveness of this product has not been established.
Slide 14: 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 15: 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 16: REDWOOD-HCM: Cohorts & Design
REDWOOD-HCM: Cohorts 1 & 2 Patients with symptomatic oHCM on background therapy excluding disopyramide Two sequential dose-finding cohorts Aficamten + SoC Randomization Patients with End of Study Screening symptomatic oHCM, 2 and resting or provoked LVOT 1 gradient ≥ 50 mmHg Placebo + SoC Study Visi
Slide 17: 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 18: 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 19: 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 20: 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 21: REDWOOD-HCM: Cohort 4
REDWOOD-HCM: Cohort 4 Patients with symptomatic nHCM on background therapy Patient enrollment completed in Q4 2022; results expected 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* Ambulat
Slide 22: FOREST-HCM: Open Label Extension
FOREST-HCM: Open Label Extension Initial data through 24 weeks shows improvement in LVOT-G, NYHA class, KCCQ Treatment was well-tolerated: one temporary discontinuation, one temporary down-titration (neither related to treatment) Resting LVOT Gradient Valsalva LVOT Gradient Improvement in Change fro
Slide 23: Safety Data
Safety Data • REDWOOD-HCM 2 SAEs reported in 41 aficamten - • FOREST-HCM 3 SAEs reported out of 42 patients with treated patients from Cohorts 1,2 and 3 (10-weeks of up-to 6-months of treatment treatment) • None were related to aficamten treatment per investigator • None were related to aficamte
Slide 24: SEQUOIA-HCM: Phase 3 Trial
SEQUOIA-HCM: Phase 3 Trial Plan to enroll at >100 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 oHCM treated Secondary objectives include measuring with SOC with post-Valsalva 1 chan
Slide 25: 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 26: Aficamten: Clinical Development Plan for HCM
Aficamten: Clinical Development Plan for HCM Second Phase 3 trial in oHCM beginning in 1H 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
Slide 27: Novel Approach May Address Multiple Unmet Patient Needs
Novel Approach May Address Multiple Unmet Patient Needs 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 OVERVIEW CARDIAC MUSCLE SKELETAL MUSCLE CORPORATE PROFILE 27
Slide 28: 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 29: 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 30: 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 31: 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 Cytokinetics (FDA) or any regulatory agency. The safety and effectiveness of this product has not been established.
Slide 32: Omecamtiv Mecarbil: Current Status
Omecamtiv Mecarbil: Current Status Advisory Committee Engaging Preparing for PDUFA Conducted with FDA Launch Feb. 28, 2023 Dec. 13, 2022 8 to 3 vote that the Ongoing engagements Continuing launch PDUFA target action date benefits of omecamtiv with FDA preparedness and is February 28, 2023 mecarbil d
Slide 33: 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 annually1 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 34: HFrEF Patients Have Challenges Getting & Staying on Optimal Therapy
HFrEF Patients Have Challenges Getting & Staying on Optimal Therapy Challenges Getting on Therapy1 Challenges Staying on Optimal Therapy2 HFrEF patients have at least one Cycling through GDMT pillars2 comorbidity that prevents use of at • 50% of HFrEF patients have cycled through least one guideline
Slide 35: 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 36: 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 37: Primary Composite Endpoint
Primary Composite Endpoint Time to First Heart Failure Event or Cardiovascular Death Primary Composite Endpoint (Overall Population) Primary Composite Endpoint (EF <30%) 50 HR=0.92 (95% CI, 0.86–0.99) Placebo 70 HR=0.85 (95% CI, 0.77–0.93) p=0.025 Omecamtiv p<0.001 Cumulative Incidence, % Cumulative
Slide 38: Greater Treatment Effect in Worsening HF
Greater Treatment Effect in Worsening HF Primary Outcome in Severe HF Primary Outcome in Patients with LVEF ≤28% (Severe HF: LVEF ≤30%, NYHA III/IV, HF hosp ≤ 6 mos)1,2 HR= 0.84 (95% CI = 0.77, 0.92) 70 HR = 0.80 (95% CI = 0.71, 0.90) Placebo p < 0.001 60 Cumulative Incidence, % 50 Omecamtiv mecarbi
Slide 39: Greater Treatment Effect in Worsening HF with GDMT Intolerance
Greater Treatment Effect in Worsening HF with GDMT Intolerance Primary Outcome In Patients with LVEF ≤28% CV Death In Patients with LVEF ≤28% Intolerant of ACE/ARB/ARNI Treated with ACE/ARB/ARNI 90 70 HR = 0.69 (95% CI = 0.44, 1.06) HR = 0.62 (95% CI = 0.43, 0.88) Placebo 80 60 Placebo Cumulative In
Slide 40: Laboratory and Safety Events
Laboratory and Safety Events Variable Relative Risk or Difference (95% CI) Laboratory value change from baseline to Week 24 Systolic blood pressure – mmHg, mean (SD) -0.1 (-0.9, 0.6) Heart rate, bpm, mean (SD) -1.6 (-2.2, -1.0) Cardiac Troponin I, ng/L, median (Q1, Q3) 0.004 (0.003, 0.005) NT-proBNP
Slide 41: Skeletal Muscle: Reldesemtiv
Sarcomere Directed Drug Development Skeletal Muscle Reldesemtiv 41
Slide 42: Reldesemtiv
Reldesemtiv G Reldesemtiv is an investigational agent and has not been approved for use by the U.S. Food & Drug Administration (FDA) or Cytokinetics any regulatory agency. The safety and effectiveness of this product has not been established.
Slide 43: 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 Parallel group, dose Placebo (n = 110) ranging study enrolled 458 patients with ALS in the US, Canada, Australia and Europe 150 mg BID (n = 110) evaluating
Slide 44: 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 45: 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 46: 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 47: Phase 3 Clinical Trial Design
Phase 3 Clinical Trial Design >300 patients enrolled 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 Europe Screening Randomization evaluating cha
Slide 48: Corporate Profile
Sarcomere Directed Therapies Corporate Profile 48
Slide 49: Robust Pipeline, Solid Financial Position
Robust Pipeline, Solid Financial Position Pipeline 1 Potential commercial launch in 2023 2 Programs in Phase 3 trials 3 Potential FDA approvals by 2025 5 Clinical stage programs 10 Development programs by 2025 HCM Heart Failure ALS Ongoing Aficamten o 2 Phase 3 trials in HCM Omecamtiv mecarbil CK-13
Slide 50: Balance Sheet (Q3 2022) & Estimated 2023 R&D Spending
Balance Sheet (Q3 2022) & Estimated 2023 R&D Spending 2023 guidance to be provided on Q4 2022 earnings call 2022 Condensed Balance Sheet in millions 2023 Estimated R&D Spend* As of 9/30/2022 Total Cash and investments $896.2 Accounts receivable $2.3 PPE $80.3 Leased assets $75.1 Other assets $22.1 ~
Slide 51: Expected 2023 Milestones
Expected 2023 Milestones Aficamten Aficamten Omecamtiv Mecarbil Reldesemtiv Early Pipeline Begin second Complete conduct Continue to engage with Expect second Expect results from Phase 3 trial of in Cohort 4 of FDA in advance of interim analysis Phase 1 study of aficamten in REDWOOD-HCM; results Feb
Slide 52: Thank You
Thank You Sarcomere directed therapies