Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (May 2024)
56 slides from Cytokinetics's investor presentation, May 22, 2024
Slide 1: Empowering muscle, empowering lives
Exhibit 99.1 EMPOWERING muscle 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, Incorporated (“Cytokinetics” or the “Company”) disclaims any intent or obligation to update these forward-looking statement
Slide 3: Structured Financing Transaction with Royalty Pharma
Structured Financing Transaction with Royalty Pharma Four Separate Components Providing $250M upon Closing; up to $575M Total Royalty Pharma R&D Partnership, Royalty Monetization, Long-term Debt and Equity Investment Diversifies access to capital to support potential commercial launch and monetize/a
Slide 4: Vision and strategic priorities
Achieve regulatory approvals for drugs arising from our pipeline Build commercial capabilities to market and sell our medicines reflective of their innovation and value Generate sustainable and growing Our vision is to be the revenues from product sales leading muscle biology biopharma company that
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 Troponin Omecamtiv CK-136 Aficamten CK-586 Mecarbil (Cardiac) (Cardiac) (Cardiac) Myosin (Cardiac) Tr
Slide 6: 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 7: Building a Specialty Cardiology Franchise Anchored by Aficamten
Building a Specialty Cardiology Franchise Anchored by Aficamten Potential patient market for specialty cardiology franchise strategy Myosin-Targeted Therapies Myosin Troponin CK-136 Troponin-Targeted Therapies Heart failure 3 800K Potential to HFpEF + EF ≥ 65% expand to in 2030 subsets of heart Omec
Slide 8: Aficamten
Aficamten 5 Cytokinetics’ a ne 8
Slide 9: Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients
Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients 1 Prevalence of HCM 700K to 1.1M ~65% ~35% 1,3 1,3 Diagnosed HCM oHCM nHCM US US 2 ~300K oHCM Prevalence nHCM Prevalence 1,3 1,3 450-700K 250-400K Diagnosed oHCM Diagnosed nHCM 2,3 2,3 ~200K ~100K Sympt. Sympt. 4,5 4,5 >130K >40K Projection
Slide 10: Aficamten: Mechanism of Action
Aficamten: Mechanism of Action Aficamten stabilized myosin in the released post-powerstroke state unable to hydrolyze ATP “Fewer hands pulling on the rope” Before Aficamten After Aficamten Mechanochemical domain ATP AF Post-Powerstroke State Actin sliding Actin sliding Aficamten is an investigationa
Slide 11: 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 12: Aficamten: Clinical Development Plan for HCM
Aficamten: Clinical Development Plan for HCM Phase 2 Phase 1 Phase 3 SAD & MAD REDWOOD-HCM Cohorts 1-3 SEQUOIA-HCM Healthy obstructive HCM obstructive HCM Target Volunteers Placebo controlled; echocardiography endpoints Pivotal trial with exercise endpoint (peak VO2) IND Filed NDA Potential for Well
Slide 13: SEQUOIA-HCM: Phase 3 Trial
SEQUOIA-HCM: Phase 3 Trial Primary endpoint: Change in pVO by 2 CPET from baseline to Week 24 Patients with Aficamten + SoC oHCM treated 1 with SOC with Secondary objectives include measuring post-Valsalva peak LVOT-G change in KCCQ & improvement in 1 ≥50 mmHg & NYHA class II/III Placebo + SoC NYHA
Slide 14: SEQUOIA-HCM: Baseline Characteristics
SEQUOIA-HCM: Baseline Characteristics Baseline characteristics reflect highly symptomatic patient population with reduced exercise capacity Aficamten Placebo Aficamten Placebo n=142 n=140 n=142 n=140 Background HCM therapy, n (%) Age, y 59.2 ± 12.6 59.0 ± 13.4 Beta-blocker 86 (60.6) 87 (62.1) Female
Slide 15: SEQUOIA-HCM: Dosing
SEQUOIA-HCM: Dosing Mean ± SD, n (%), or median Placebo 5 mg 10 mg 15 mg 20 mg (IQR) n=140 n=5 n=18 n=49 n=68 Aficamten dose at Week 8 % per treatment group 100% 3.5% 12.7% 34.5% 47.9% (end of titration) Background HCM therapy Beta-blocker 87 (62.1) 5 (100.0) 10 (55.6) 31 (63.3) 40 (58.8) 3% Calcium
Slide 16: SEQUOIA-HCM: Primary Endpoint
SEQUOIA-HCM: Primary Endpoint Significant improvement in exercise capacity compared to placebo Results presented at Heart Failure 2024 and published in NEJM Absolute Change from Baseline to Week 24 LS mean Change from Baseline to Week 24 P=0.000002 Aficamten 2.5 Placebo 21 2.0 1.5 Data are mean and
Slide 17: SEQUOIA-HCM: Subgroup Analysis
SEQUOIA-HCM: Subgroup Analysis Results consistent across all prespecified subgroups including patients receiving or not receiving background beta-blockers Mean difference Mean difference n Aficamten Placebo n Aficamten Placebo (95% CI) (95% CI) (Afi/Plb) LS mean LS mean LS mean LS mean (Afi/Plb) Age
Slide 18: SEQUOIA-HCM: Secondary Endpoints
SEQUOIA-HCM: Secondary Endpoints Statistically significant improvements in all 10 pre-specified secondary endpoints Endpoints P value Primary Endpoint pVO change from baseline to Week 24 <0.0001 2 Secondary Endpoints 1. KCCQ-CSS change from baseline to Week 24 <0.0001 2. NYHA Class Improvement by at
Slide 19: SEQUOIA-HCM: Secondary & Exploratory Endpoints
SEQUOIA-HCM: Secondary & Exploratory Endpoints Significant improvement in post-Valsalva left ventricular outflow tract gradient (LVOT-G) LS mean difference: Resting LVOT-G Valsalva LVOT-G - 50 mmHg 100 100 90 90 80 80 70 70 60 60 50 50 40 40 30 30 20 20 0 2 4 6 8 12 16 20 24 28 0 2 4 6 8 12 16 20 24
Slide 20: SEQUOIA-HCM: Secondary & Exploratory Endpoints
SEQUOIA-HCM: Secondary & Exploratory Endpoints LS mean difference: ≥1 NYHA FC Improvement KCCQ-CSS 7 points 100 100 90 80 58% 90 70 60 80 50 40 30 70 20 10 60 0 0 2 4 6 8 12 16 20 24 28 2 4 6 8 12 16 20 24 Weeks Weeks 78 fewer days 80% reduction Guideline Eligibility for SRT NT-proBNP spent SRT-elig
Slide 21: SEQUOIA-HCM: Responder Analysis
SEQUOIA-HCM: Responder Analysis Significant improvement in exercise capacity and symptoms in composite responder endpoint Aficamten Placebo n=142 n=140 ≥1.5 mL/kg/min increase in pVO and ≥1 NYHA FC improvement 2 or 60 (42) 19 (14) ≥3.0 mL/kg/min increase in pVO and no worsening of NYHA FC, n (%) 2 ≥
Slide 22: SEQUOIA-HCM: Safety Data
SEQUOIA-HCM: Safety Data Placebo Aficamten Event, n (%) (n=140) (n=142) Overall AEs 99 (70.7) 105 (73.9) Headache 10 (7.1) 11 (7.7) Hypertension 3 (2.1) 11 (7.7) Palpitations 4 (2.9) 10 (7.0) AEs with ≥5% incidence Upper respiratory infection 12 (8.6) 9 (6.3) COVID-19 9 (6.4) 8 (5.6) Dyspnea 8 (5.7)
Slide 23: SEQUOIA-HCM: Change in LVEF
SEQUOIA-HCM: Change in LVEF Modest reduction in LVEF in patients on aficamten resulted in large reductions in LVOT-G Distribution of Categorical Changes in Core Laboratory Mean Change in Core Laboratory LVEF Over 24 Weeks LVEF from Baseline to Week 24 Placebo corrected 100 Washout ΔLVEF = -4.8% Afic
Slide 24: SEQUOIA-HCM: Low Incidence of LVEF <50%
SEQUOIA-HCM: Low Incidence of LVEF <50% 5 (3.5%) of patients on aficamten had LVEF <50% determined by the core laboratory Site Interpreted Core Laboratory • No treatment interruptions occurred LVEF <50% LVEF <50% o 1 Analysis • No heart failure was experienced by any aficamten-treated patient with L
Slide 25: SEQUOIA-HCM: Low Overall Incidence of LVEF <50%
SEQUOIA-HCM: Low Overall Incidence of LVEF <50% Core lab LVEF was prespecified source for statistical analyses LVEF <50% assessed at 3.5% by core lab and 4.9% by site Prespecified Analysis Lowest Matching Matching Study Week NT-proBNP, Down- Age, y, Aficamten NYHA Next Visit BL Core LVEF, % With Low
Slide 26: Implementation of Dosing in Real-World Setting (FOREST-HCM)
Implementation of Dosing in Real-World Setting (FOREST-HCM) Low incidence of LVEF <50% in patients with oHCM treated with aficamten N = 282 N = 267 5% 5% 4% 4.2% 4% 3% 3% 3.0% 2.8% 2% 2% 1% 1% 1 patient in common 0% 0% Core Lab Site Site ü No treatment interruptionsü No treatment interruptions ü No
Slide 27: SEQUOIA-HCM: Conclusions
SEQUOIA-HCM: Conclusions Trial underscores potential clinical efficacy & safety of aficamten in patients with symptomatic oHCM • Patients treated with aficamten observed to have: • Clinically meaningful improvements in exercise capacity (pVO ), consistent 2 across all prespecified subgroups • Signif
Slide 28: 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 • Expect to submit NDA to FDA in Q3 2024 and Positive Results from MAA to EMA in Q4 2024: development of all SEQUOIA-H
Slide 29: Aspirational Profile and SEQUOIA-HCM Results Inform Potential REMS
Aspirational Profile of Aficamten & Results from SEQUOIA-HCM Inform Potential REMS REMS Existing Aficamten Aspirational Profile Potential Unique REMS Challenges • Rapid onset • Rapid reversibility • Speed to optimal dose Potential for: Echo frequency • SEQUOIA-HCM: No treatment interruptions due to
Slide 30: Few Dose Reductions Occurred During Maintenance
Few Dose Reductions Occurred During Maintenance FOREST-HCM data cut as of September 15, 2023 Dose Titration Phase Maintenance Phase Down-titration triggered 0.5% • 579 monitoring echocardiograms • No treatment-related LVEF <50% completed* in oHCM patients during the titration period • None with LVEF
Slide 31: Ongoing Clinical Trials of Aficamten
Ongoing Clinical Trials of Aficamten Pivotal Phase 3 of aficamten as Pivotal Phase 3 clinical Clinical trial in a pediatric Open-label extension monotherapy vs. metoprolol trial in nHCM population clinical study in HCM as monotherapy in oHCM Aficamten is an investigational drug and is not approved b
Slide 32: Poised to Compete in the Specialty Cardiology Business
Cytokinetics Poised to Compete in the Specialty Cardiology Business Potential for high return on investment Broad Cardiology Specialty Cardiology Example Therapies Heart failure, cholesterol, blood thinner HCM, TTR amyloidosis Prescribers Broad: Cardiologists, PCPs (50K+) Concentrated: Subset of car
Slide 33: Market Research Shows Aficamten May Achieve High Share
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 could also be expected to expand the total C
Slide 34: 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 U.S. population US HCM Patients (in ‘000) Illustrative Potential 1,2 Potential 500K nHCM Launch oHCM Launch >90% >80% CMI-Eligible patients available
Slide 35: Cardiologists Located in Concentrated Geographic Clusters
Cardiologists Located in Concentrated Geographic Clusters Across the US ~75% of the HCM patient volume is treated by ~10,000 cardiologists Geographic Distribution of HCM Patients HCM Patient Concentration by Cardiologist 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 7,000 10,000 30,000 … Note: include
Slide 36: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Majority of spending to occur closer to potential approval in 2025 2/3 of hiring to occur at-approval Key activities after SEQUOIA-HCM readout Continued insight generation Market access strategy validation Commercial leadership Pricing strategy finalization M
Slide 37: Omecamtiv Mecarbil
Omecamtiv Mecarbil "e Cytokinetics” cen esta 37
Slide 38: Omecamtiv Mecarbil: Mechanism of Action
Omecamtiv Mecarbil: Mechanism of Action Omecamtiv mecarbil shifted equilibrium in favor of the pre-powerstroke state “More hands pulling on the rope” Before Omecamtiv Mecarbil After Omecamtiv Mecarbil OM Mechanochemical P i ADP domain Pre-Powerstroke State Actin sliding Actin sliding Malik, et al. S
Slide 39: GALACTIC-HF: Clinical Trial Overview
GALACTIC-HF: Clinical Trial Overview Phase 3 clinical trial Event-driven clinical trial; 8256 patients randomized in 35 countries at 944 clinical trial sites Chronic HFrEF Patients Currently hospitalized for Inpatients Omecamtiv mecarbil + Standard HF Therapy primary reason of HF (25% of enrollment)
Slide 40: Primary Composite Endpoint
Primary Composite Endpoint 50 Placebo HR = 0.92 45 (95% CI, 0.86–0.99) Omecamtiv 40 P = 0.025 mecarbil 35 CV Death 30 HR = 1.01 (95% CI, 0.92–1.11) 25 P = 0.86 20 Omecamtiv 15 mecarbil 10 5 0 18 0 6 12 24 30 36 Months (30 days) since randomization Patients at risk, n Placebo 4112 3310 2889 2102 1349
Slide 41: Benefit Observed to Increase As Baseline LVEF Decreased
Benefit Observed to Increase As Baseline LVEF Decreased Incidence of Primary Composite Endpoint Relative Treatment Effect on Primary Endpoint 60 1.2 50 Placebo 40 Treatment 1.0 Effect 30 0.8 Omecamtiv mecarbil 20 0.6 2414 patients 5,842 patients 10 10 15 20 25 30 35 10 15 20 25 30 35 Ejection fracti
Slide 42: In Post-Hoc Analysis, Greater Benefit in Patients with Worsening HF
In Post-Hoc Analysis, Greater Benefit in Patients with Worsening HF Omecamtiv mecarbil is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. 42
Slide 43: Safety Results in Low LVEF Subgroup
Safety Results in Low LVEF Subgroup Were Observed to Continue Incidences of SAEs, ventricular arrhythmias, & cardiac ischemic events were similar LVEF ≤28% Overall Population Incidence of stroke was lower with omecamtiv mecarbil Omecamtiv Omecamtiv Mecarbil Placebo Mecarbil Placebo N=4110 N=4101 N=2
Slide 44: 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 45: Omecamtiv Mecarbil: HFrEF Epidemiology
Omecamtiv Mecarbil: HFrEF Epidemiology Heart Failure Prevalence All HF Patients 2023, US 8.0 18% 6.0 4.0 7.1 7.1 7.1 2.0 0.0 Tsao 2023 AHA Racine 2022 CVrg Bionest 2021 LVEF <30% LVEF >30% 7.1M (2023) Circ Heart Fail. 2012;5:720-726 REAL HFrEF Study 2021 Omecamtiv mecarbil is an investigational drug
Slide 46: SOC Not Addressing Needs of Patients with EF <30%
Omecamtiv Mecarbil: SOC Not Addressing Needs of Patients with EF <30% Proposed Patient Type for Omecamtiv Mecarbil Physician Experience with HFrEF Treatment • EF <30% • Not responding to current Physicians have treatment options, recently many tools in their They’re balancing They’re still looking h
Slide 47: CK-586
CK-586 Cytokinetics”
Slide 48: CK-586: Distinct Mechanism of Action from Aficamten
CK-586: Distinct Mechanism of Action from Aficamten “Fewer hands pulling on the rope” Before CK-586 After CK-586 Mechanochemical CK- domain 586 ATP Post-Powerstroke State Actin sliding Actin sliding CK-586 is an investigational drug and is not approved by any regulatory agency. Its safety and effica
Slide 49: Heart Failure with Preserved Ejection Fraction (HFpEF)
Heart Failure with Preserved Ejection Fraction (HFpEF) 1 Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor ~50% ~75% ~84% 8.5 million Americans will have HF patients have HFpEF patients will HFpEF patients will 3 2 heart failure by H
Slide 50: CK-586: Shallow In Vivo Concentration-Response
CK-586: Shallow In Vivo Concentration-Response CK-586 will have a shorter half-life in humans than aficamten Pharmacodynamic window Fractional shortening IC /IC ratio 50 10 mavacamten 2.8x aficamten 9.9x CK-586 9.3x IC : plasma concentration at 10% relative reduction in fractional shortening 10 IC :
Slide 51: 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 52: Corporate Profile
Corporate Profile "e Cytokinetics” 52
Slide 53: Myosin Platform Drives Multiple Data Milestones and Potential Approvals
Myosin Platform Drives Multiple Data Milestones and Potential Approvals Potential Results Aficamten Aficamten FDA Approval oHCM SEQUOIA-HCM Potential For illustrative purposes only Results Approval Enhancing shareholder Aficamten Emerging value Pipeline MAPLE-HCM Results Aficamten Aficamten oHCM SEQ
Slide 54: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance Approximately 2 years of cash runway based on 2024 guidance* 2024 Condensed Balance Sheet in millions As of 3/31/2024 Total $634.3 Cash and investments 2024 Financial Guidance Accounts receivable $0.8 $68.0 PPE • GAAP Operating (R&D and G&A) $535 to $555 million Le
Slide 55: Planned 2024 Milestones
Planned 2024 Milestones Af Aic fica am mtt ee nn CK-586 Share full data from Phase 1 study Complete enrollment of MAPLE-HCM Submit NDA to FDA in Q3 2024 and of CK-586 in 2H 2024 MAA to EMA in Q4 2024 in Q3 2024 Initiate Phase 2 study Continue enrollment in ACACIA-HCM of CK-586 in Q4 2024 Continue en
Slide 56: Thank you
G Cytokinetics’ thank you