Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (November 2022)
58 slides from Cytokinetics's investor presentation, November 2022
Slide 1: Empowering Muscle, Empowering Lives
Sarcomere Directed Therapies EMPOWERING MUSCLE EMPOWERING LIVES Nefertari, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALS CYTOKINETICS® and the C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries Copyright©2022 CYTOKINET
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: Executing On Our Vision
Executing On Our Vision • Positive Phase 3 results from • Scientific innovation driven by GALACTIC-HF modulating cardiac myosin • Phase 3 trial, SEQUOIA-HCM, • First-in-class myosin activator enrolling patients with oHCM • Next-in-class myosin inhibitor • Cohort 4 of Phase 2 trial, • Expansion beyon
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 ACTIVATE ACTIVATE Troponin Omecamtiv Reldesemtiv CK-136 CK-601 Aficamten CK-271 Mecarbil (Cardiac) (C
Slide 7: 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 NDA Filed Omecamtiv Mecarbil (Heart Failure) PDUFA: 02/28/23 Aficamten (oHCM, nHCM, HFpEF) CK-271 CK-136 (Heart Failure, other) SKELETAL MUSCLE Reldesemtiv (ALS)* CK-601 Additional Skeletal
Slide 8: Cardiac Muscle
Sarcomere Directed Drug Development CARDIAC MUSCLE Omecamtiv Mecarbil Aficamten 8
Slide 9: Contractile Dysfunction Underlies Cardiac Diseases
Contractile Dysfunction Underlies Cardiac Diseases Increased / Preserved Decreased Cardiac Cardiac Contractility Contractility • Non-obstructive • Heart Failure with Hypertrophic Reduced Ejection Cardiomyopathy (nHCM) Fraction (HFrEF) • Obstructive Hypertrophic • Genetic Dilated Cardiomyopathy (oHCM
Slide 10: Omecamtiv Mecarbil
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. 10
Slide 11: 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 12: Significant Unmet Need in HFrEF
Significant Unmet Need in HFrEF Proprietary market research suggests need for novel therapy Market research Drugs that Drugs that Disease Drugs that do Drugs that suggests need do not affect enhance cardiac modifying not affect BP increase QoL for novel therapy renal function performance therapies P
Slide 13: 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 14: Baseline Characteristics
Baseline Characteristics OM Placebo OM Placebo Characteristic Characteristic (N=4120) (N=4112) (N=4120) (N=4112) Demographics Vitals and Laboratory Parameters 1977 2025 NT-proBNP (pg/mL), median (Q1, Q3) Age (years), median (Q1, Q3) 66 (58, 73) 66 (58, 73) (980, 4061) (1000, 4105) SBP (mmHg), mean (
Slide 15: 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 OM p<0.001 Cumulative Incidence, % Cumulative Incide
Slide 16: Greater Treatment Effect in Worsening HF
Greater Treatment Effect in Worsening HF Primary Outcome in Severe HF: HR = 0.80 (0.71, 0.90) Primary Outcome in Patients with LVEF ≤28%: (Severe HF defined as NYHA III-IV, EF ≤30%, HF hosp <6 mos)1,2 HR 0.84; 95% CI 0.77, 0.92 Severe HF-Placebo Not severe HF-Placebo Severe HF-Omecamtiv Not severe H
Slide 17: Greater Treatment Effect in Patients with Low Blood Pressure
Greater Treatment Effect in Patients with Low Blood Pressure Patients with Low BP at high risk of CV death & HF events, often hard to treat Primary Outcome, SBP ≤100 • 1,473 patients (17.9%) had low BP (≤100 mmHg) • Greater treatment effect observed from omecamtiv mecarbil in patients with low BP on
Slide 18: Laboratory and Safety Events
Laboratory and Safety Events Omecamtiv Mecarbil Placebo Relative Risk or Difference Variable (N=4110) (N=4101) (95% CI) Laboratory value change from baseline to Week 24 Systolic blood pressure – mmHg, mean (SD) 1.4 (15.3) 1.5 (15.6) -0.1 (-0.9, 0.6) Heart rate, bpm, mean (SD) -2.1 (12.6) -0.5 (12.8)
Slide 19: 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 20: High Cost Burden Primarily Due to Hospitalizations
High Cost Burden Primarily Due to Hospitalizations Omecamtiv mecarbil reduced clinical events, resource utilization & costs related to HF events Omecamtiv mecarbil reduced costs Over next decade, HF cost burden Mostly due to cycle of hospitalizations related to HF events in is expected to increase o
Slide 21: Omecamtiv Mecarbil: Value Proposition
Omecamtiv Mecarbil: Value Proposition In HFrEF, patients with lower ejection Hospitalization reductions seen in fractions are hospitalized more often clinical trial of omecamtiv mecarbil In HFrEF, every 10 points lower EF, is proven to drive Clinically meaningful and statistically significant higher
Slide 22: Small Subset of Cardiologists Manage Majority of Patients
Small Subset of Cardiologists Manage Majority of Patients HFrEF Patient Concentration in Cardiologists Distribution of High-Volume Cardiologists 100% % of Patients 50% 0% 0% 50% 100% % of Cardiologists Allows for more targeted field team approach, focusing on <10,000 HCPs Symphony APLD (1/1/2019 – 1
Slide 23: Medicare Is Major Payer with Select Key Players
Medicare Is Major Payer with Select Key Players Medicare is largest payer; enrollment highly concentrated with nearly 3 of 4 patients in only 5 plans Medicare Part D Enrollment (2019) Estimated Payer Mix Entresto Based Payer Mix on Entresto® (2018) 2018 Data Managed Medicaid 8% Top 5 plans have 75%
Slide 24: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Majority of spending to occur post-approval 2/3 of hiring to occur post-approval Activities initiated upon key de-risking events Underway Pre-NDA filing Market access Commercial leadership Pricing strategy Marketing Distribution approach HEOR Payer engagement
Slide 25: Aficamten
Aficamten Aficamten 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. 25
Slide 26: In US, Large HCM Population With Many Undiagnosed
In US, Large HCM Population With Many Undiagnosed HCM Prevalence Potential Undiagnosed Patients Currently ~400-800K ~280K diagnosed, 700 – ~190K oHCM 1,100K symptomatic patients Estimated ~400-800K nHCM* 280K Diagnosed Patients un-diagnosed patients oHCM* ~280K Mava success 190K Now Future nHCM: non
Slide 27: Aficamten: Aspirational Target Profile
Aficamten: Aspirational Target Profile Potential next-in-class cardiac myosin inhibitor Functional Improvement: Improved exercise capacity Efficacy Symptom Improvement: One or two class improvement in NYHA class Quality of Life: KCCQ improvement Minimal drug-drug interactions Safety and Maintain LVE
Slide 28: REDWOOD-HCM: Cohorts 1 & 2
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 29: Baseline Characteristics
Baseline Characteristics Cohorts 1 & 2 Placebo Aficamten Characteristic (n = 13) (n = 28) Age (Years), Mean (SD) [Range] 57.2 (9.6) [36,69] 56.6 (13.6) [33,78] < 65 Years 10 (77%) 17 (61%) Sex, n (%) Female 8 (62%) 15 (54%) Race = White, n (%) 12 (92%) 28 (100%) NYHA Class, n (%) Class II 11 (85%) 1
Slide 30: REDWOOD-HCM: Efficacy
REDWOOD-HCM: Efficacy Cohorts 1 & 2 Reductions in LVOT gradients 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 *** mean ± SEM
Slide 31: 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 32: 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% (n=9) NTproBNP (pg/mL) -400 60 % Total -600 40 69
Slide 33: Safety Data
Safety Data • 2 SAEs reported in Cohort 1 and none in Cohort 2 • No patients met the “stopping criteria” of LVEF < 40% • Stress Cardiomyopathy: 55-year-old female assigned to • No treatment interruptions or discontinuations Placebo, with associated cardiogenic shock after IP discontinuation at end o
Slide 34: 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 35: REDWOOD-HCM: Cohort 4
REDWOOD-HCM: Cohort 4 Patients with symptomatic nHCM on background therapy Patient screening completed; 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* Ambulatory Cardiac
Slide 36: FOREST-HCM: Open Label Extension
FOREST-HCM: Open Label Extension Initial data through 24 weeks shows improvement in LVOT-G, NYHA class Treatment was well-tolerated: one temporary discontinuation, one temporary down-titration (neither related to treatment) FOREST-HCM was previously known as REDWOOD-HCM OLE FOREST-HCM is enrolling p
Slide 37: FOREST-HCM: Open Label Extension
FOREST-HCM: Open Label Extension Significant improvement in symptoms & quality of life; successful reduction/withdrawal of background medications Change from Baseline in KCCQ Scores Reduction or Withdrawal of Standard of Care Therapies Not for Promotional Use, For Investors Only OVERVIEW CARDIAC CAN
Slide 38: 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 Secondary objectives include measuring oHCM treated with SOC with 1 post-Valsalva chan
Slide 39: Aficamten: Clinical Development Plan for HCM
Aficamten: Clinical Development Plan for HCM SEQUOIA-HCM enrolling patients with oHCM; second Phase 3 trial beginning in Q4 2022 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 HC
Slide 40: 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 CANDIDATES FRANCHISE STRATEGY SKELETAL CANDIDAT
Slide 41: Franchise Strategy
Sarcomere Directed Drug Commercialization FRANCHISE STRATEGY 41
Slide 42: Go-to-Market Synergies for Omecamtiv Mecarbil & Aficamten
Go-to-Market Synergies for Omecamtiv Mecarbil & Aficamten Sales Given target overlap, leveraging same sales team Team Commercial Support Utilize resources across brands (e.g., access, analytics, …) Functions Synergy PV of ~ $500M Medical MSLs qualified to cover both HFrEF and HCM Affairs Corporate S
Slide 43: 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 44: Expanding Franchise Reach in Key Geographies
Expanding Franchise Reach in Key Geographies Europe: Seek co-development and co-commercialization partnership for omecamtiv mecarbil; pursue bridge to independent go-to-market strategy for aficamten in certain countries in Europe Omecamtiv Aficamten Mecarbil Japan: Seek partnership for omecamtiv mec
Slide 45: Skeletal Muscle: Reldesemtiv
Sarcomere Directed Drug Development SKELETAL MUSCLE Reldesemtiv 45
Slide 46: Reldesemtiv
Reldesemtiv Reldesemtiv 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. 46
Slide 47: 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, Australia and 150 mg BID (n = 110) Europe evaluating
Slide 48: 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 49: Phase 2 Clinical Trial Results: SVC and ALSFRS-R
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 50: Subgroup Analyses
Subgroup Analyses* Percent Predicted SVC ALSFRS-R Total Score No. of Patients LSM Difference No. of Patients LSM Difference (pbo/reldesemtiv) (95% Cl) Estimate P value (pbo/reldesemtiv) (95% Cl) Estimate P value Percent predicted SVC at baseline Percent predicted SVC at baseline <80 38/102 1.037 0.5
Slide 51: Post-Hoc Analyses Inform Potential Path Forward
Post-Hoc Analyses Inform Potential Path Forward Probability of No New DME Over Time Change From Baseline in ALSFRS-R With Treatment With Reldesemtiv by Progressor Tertiles DME (Durable Medical Equipment): Manual wheelchair, power wheelchair, NIV, Time (weeks) Augmentative Language Device, PEG 0 1.0
Slide 52: Phase 3 Clinical Trial Design
Phase 3 Clinical Trial Design >300 patients enrolled; trial continuing following first interim analysis for futility Enrolling patients with ALS in the US, Canada, Reldesemtiv Australia and (N= 555) 300 mg BID End of Study Screening Randomization Europe evaluating 2:1 change from baseline ALSFRS-R S
Slide 53: Corporate Profile
Sarcomere Directed Therapies CORPORATE PROFILE 53
Slide 54: 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 Heart Failure HCM ALS Ongoing Omecamtiv mecarbil o Positive trial results Aficamten o Phas
Slide 55: Monetizing Our Pipeline to Bolster Balance Sheet
Monetizing Our Pipeline to Bolster Balance Sheet Symmetry of deals for omecamtiv mecarbil and aficamten affords synergies for development and potential launches and supports franchise strategies Sold 4.5% royalty Sold 3.5-4.5% royalty Transactions on worldwide net sales of on worldwide net sales of
Slide 56: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance 2022 Condensed Balance Sheet 2022 Financial Guidance As of 9/30/2022 in millions in millions Total Total Cash and investments $896.2 Cash Revenue $20 – 25 Accounts receivable $2.3 Cash Operating Expenses $375– 385 PPE $80.3 Net ~ $360 - 365 Leased assets $75.1 Othe
Slide 57: Expected Upcoming Milestones
Expected Upcoming Milestones Participate in Advisory Launch omecamtiv Submit MAA for Committee meeting for Begin Phase 1 study of mecarbil in the U.S. subject omecamtiv mecarbil omecamtiv mecarbil on CK-136 in Q4 2022 to FDA approval in Q1 2023 to EMA by the end of 2022 December 13, 2022 Continue en
Slide 58: Thank You
Sarcomere Directed Therapies THANK YOU Nefertari, diagnosed with heart failure Jillian, diagnosed with HCM Chuck, diagnosed with ALS Copyright©2022 CYTOKINETICS, All Rights Reserved Actual patients who consented to use of their name, image, and condition.