Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (May 2024)
62 slides from Cytokinetics's investor presentation, May 2024
Slide 1: Empowering muscle, empowering lives
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 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
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: Leading with Science, pioneering medicines
Achieve regulatory approvals for drugs arising from our pipeline Build commercial capabilities to market and sell our medicines reflective of their innovation and value Our vision is to be the Generate sustainable and growing revenues from product sales leading muscle biology biopharma company that
Slide 5: A Great Place to Work; Uncommon Continuity of Team
A Great Place to Work; Uncommon Continuity of Team VALUES RETENTION patients are our North Star science is in our soul we > me make it happen <5% Turnover rate of leadership; low attrition AWARDS Winner >7 yrs in Wellness 3rd San Francisco Business Times Out of 25 Large Average tenure of leadership;
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 Troponin Omecamtiv CK-136 Aficamten CK-586 Mecarbil (Cardiac) (Cardiac) (Cardiac) Myosin (Cardiac) Tr
Slide 7: Contractile Dysfunction Underlies Cardiac Diseases
Contractile Dysfunction Underlies Cardiac Diseases Decreased Increased / Preserved Cardiac Contractility Cardiac Contractility • Heart Failure with Reduced • Non-obstructive Hypertrophic Ejection Fraction (HFrEF) Cardiomyopathy (nHCM) • Genetic Dilated • Obstructive Hypertrophic Cardiomyopathy Cardi
Slide 8: 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 9: 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 Myosin Therapies Troponin Troponin-Targeted CK-136 Therapies 800K3 Heart failure Potential to HFpEF + EF ≥ 65% expand to in 2030 Omecamtiv subsets of h
Slide 10: Aficamten
Aficamten G Aficamten 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. 10
Slide 11: 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 12: Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients
Opportunity for CMIs in Diagnosed, Symptomatic HCM Patients Prevalence of HCM1 700K to 1.1M ~65% ~35% US oHCM1,3 nHCM1,3 USDiagnosed HCM oHCM Prevalence ~300K2 nHCM Prevalence 450-700K1,3 250-400K1,3 Diagnosed oHCM Diagnosed nHCM ~200K2,3 ~100K2,3 Sympt. Sympt. >130K4,5 >40K4,5 Projections and forec
Slide 13: Aficamten: Proposed Mechanism of Action
Aficamten: Proposed 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 AF ATP Post-Powerstroke State Actin sliding Actin sliding Aficamten is an inves
Slide 14: 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 15: Aficamten: Clinical Development Plan for HCM
Aficamten: Clinical Development Plan for HCM Phase 1 Phase 2 Phase 3 SAD & MAD REDWOOD-HCM Cohorts 1-3 SEQUOIA-HCM Healthy obstructive HCM obstructive HCM Target IND Filed Volunteers Placebo controlled; echocardiography endpoints Pivotal trial with exercise endpoint (peak VO2) NDA Potential for Well
Slide 16: SEQUOIA-HCM: Phase 3 Trial Design
SEQUOIA-HCM: Phase 3 Trial 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 change in KCCQ & improvement in peak LVOT-G ≥50 mmHg & 1 N
Slide 17: 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 Age, y 59.2 ± 12.6 59.0 ± 13.4 Background HCM therapy, n (%) Beta-blocker 86 (60.6) 87 (62.1) • Sign
Slide 18: 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% 13% Cal
Slide 19: 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 Aficamten 2.5 P=0.000002 Placebo 21 2.0 ΔpVO2 (mL/kg/min) pVO2
Slide 20: SEQUOIA-HCM: Subgroup Analysis
SEQUOIA-HCM: Subgroup Analysis Results consistent across all prespecified subgroups including patients receiving or not receiving background beta-blockers n Aficamten Placebo Mean difference n Aficamten Placebo Mean difference (Afi/Plb) LS mean LS mean (95% CI) (Afi/Plb) LS mean LS mean (95% CI) Age
Slide 21: 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 ΔLVEF = -4.8% Washout Decl
Slide 22: 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% 1o Analysis • No heart failure was experienced by any aficamten-treated patient with LV
Slide 23: 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 pVO2 and ≥1 NYHA FC improvement or 60 (42) 19 (14) ≥3.0 mL/kg/min increase in pVO2 and no worsening of NYHA FC, n (%) ≥1.
Slide 24: SEQUOIA-HCM: Secondary Endpoints
SEQUOIA-HCM: Secondary Endpoints Statistically significant improvements in all 10 pre-specified secondary endpoints Endpoints P value Primary Endpoint pVO2 change from baseline to Week 24 <0.0001 Secondary Endpoints 1. KCCQ-CSS change from baseline to Week 24 <0.0001 2. NYHA Class Improvement by at
Slide 25: 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 Resting LVOT-G (mmHg) Valsalva LVOT-G (mmHg) 80 80 70 70 60 60 50 50 40 40 30 30 20 20 0
Slide 26: SEQUOIA-HCM: Secondary & Exploratory Endpoints
SEQUOIA-HCM: Secondary & Exploratory Endpoints LS mean difference: ≥1 NYHA FC Improvement KCCQ-CSS 7 points Proportion of patients with ≥1 100 100 NYHA FC improvement (%) 90 80 58% 90 KCCQ–CSS 70 60 50 80 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%
Slide 27: SEQUOIA-HCM: Integrated Exercise Performance
SEQUOIA-HCM: Integrated Exercise Performance Aficamten improved novel integrated exercise performance metric Integrated Exercise Performance (Z-score pVO2 & VE/VCO2) Aficamten Adjusted Difference (95% CI) P value Placebo Mean ± SD Mean ± SD 0.35 (0.25, 0.46) 0.0000000006 Baseline Week 24 Baseline We
Slide 28: 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) There were no D
Slide 29: 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 (pVO2), consistent across all prespecified subgroups • Signific
Slide 30: 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 Positive Results from • Expect to submit NDA to FDA in Q3 2024 and SEQUOIA-HCM MAA to EMA in Q4 2024: development of a
Slide 31: Observed Durable Effects of Aficamten on LVOT-G & LVEF
Observed Durable Effects of Aficamten on LVOT-G & LVEF FOREST-HCM data cut as of September 15, 2023 • Resting & provoked gradients remained below diagnostic threshold for >2 years, LVEF remains flat after titration Aficamten is an investigational drug and is not approved by any regulatory agency. It
Slide 32: Observed Durable Effects of Aficamten on Clinical Endpoints
Observed Durable Effects of Aficamten on Clinical Endpoints KCCQ-CSS NYHA Class Guideline-Eligible for SRT Data cut as of September 15, 2023 Data cut as of September 15, 2023 Data cut as of October 31, 2023 71% of patients had ≥ 5-point KCCQ-CSS increase ~50% of patients were asymptomatic at 1 year
Slide 33: 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% • No treatment-related LVEF <50% • 579 monitoring echocardiograms during the titration period completed* in oHCM patients • Of the 94 pati
Slide 34: Safety Data
Safety Data FOREST-HCM data cut as of September 15, 2023 • Almost all eligible patients choose to participate in the OLE • Echocardiography-guided dose titration of aficamten was managed entirely by the treating physicians • 2/3 of patients achieved higher doses; no low LVEF events requiring treatme
Slide 35: MAPLE-HCM: Phase 3 Monotherapy Trial
MAPLE-HCM: Phase 3 Monotherapy Trial Currently enrolling Active-comparator trial of aficamten as monotherapy vs. metoprolol in patients with oHCM • Trial to enroll (if applicable) Recently diagnosed 2 Week SOC LVOT-G (mmHg) Washout or treatment naïve Resting ≥ 30 approximately Randomization with sym
Slide 36: ACACIA-HCM: Pivotal Phase 3 Trial in nHCM
ACACIA-HCM: Pivotal Phase 3 Trial in nHCM Currently enrolling Patients with: Randomization • Trial to enroll approximately Aficamten End of Study Symptomatic 420 symptomatic nHCM N = 420 Screening (1:1) (NYHA Class patients II/III) nHCM, KCCQ-CSS Placebo • Primary endpoint: change in ≥ 30 and ≤ 85 K
Slide 37: CEDAR-HCM: Clinical Trial in Pediatric Population
CEDAR-HCM: Clinical Trial in Pediatric Population Currently enrolling • Expected to enroll initial Adolescent cohort of ~40 adolescent cohort criteria Randomization Aficamten 2 Week SOC Washout End of Study patients aged 12 to 17 Screening LVEF ≥ 60% 2 • Data from adolescent Valsalva LVOT-G ≥ Aficam
Slide 38: Aficamten: Planned Commercial Approach
Aficamten: Planned Commercial Approach Driven by a relentless focus on our North Star: the HCM patient Learn Design Build Leverage deep Engage with all Tap into deep functional understanding of stakeholders to design experience to build patients, HCPs, payers, an optimal customer operational excelle
Slide 39: Cytokinetics 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 40: Market Research Shows Aficamten May Achieve High Share & Grow Category
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 41: 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 Potential nHCM Launch 500K1,2 oHCM Launch >80% CMI-Eligible >90% patients available
Slide 42: Cardiologists Located in Concentrated Geographic Clusters Across the US
Cardiologists Located in Concentrated Geographic Clusters Across the US ~75% of the HCM patient volume is treated by ~10,000 cardiologists HCM Patient Concentration by Cardiologist Geographic Distribution of HCM Patients 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 7,000 10,000 … 30,000 Note: include
Slide 43: 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 Commercial leadership Market access strategy validation Marketing Pricing strategy fina
Slide 44: US Commercial Readiness Milestones for Aficamten
US Commercial Readiness Milestones for Aficamten 2024-2025 2024 2025 Launch Final GTM Launch Launch Ready Planning Strategy Tactical Plan Market Digital / HCP Branded Messages Final Development Omnichannel & Campaign Finalized Marketing Positioning Full Campaign Patient Campaign Development Finalize
Slide 45: 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. 45
Slide 46: 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 47: CK-586
CK-586 G CK-586 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. aq
Slide 48: 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 48
Slide 49: Heart Failure with Preserved Ejection Fraction (HFpEF)
Heart Failure with Preserved Ejection Fraction (HFpEF) Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor 1 8.5 million ~50% ~75% ~84% Americans will have HF patients have HFpEF patients will HFpEF patients will heart failure by HFpEF
Slide 50: CK-586: Distinct Mechanism of Action from Aficamten
CK-586: Distinct Mechanism of Action from Aficamten CK-586 inhibited actin-activated ATPase of HMM only; aficamten inhibits both S1 and HMM Single-headed Two-headed Myosin (S1) Myosin (HMM) Based on preclinical testing CK-586 is an investigational drug and is not approved by any regulatory agency. I
Slide 51: 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 IC50 /IC10 ratio mavacamten 2.8x aficamten 9.9x CK-586 9.3x IC10: plasma concentration at 10% relative reduction in fractional shortening IC50: pl
Slide 52: CK-586 is Efficacious in ZSF1 Obese Rat Model of HFpEF
CK-586 is Efficacious in ZSF1 Obese Rat Model of HFpEF Model is representative of hypertensive, diabetic, metabolic aspects of HFpEF 10 weeks of treatment improved diastolic function and reduced cardiac fibrosis Reduced Fractional Shortening Improved Diastolic Function Reduced Fibrosis CK-586 is an
Slide 53: 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 54: CK-136
CK-136 G CK-136 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. 5A
Slide 55: 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 56: CK-136: Exposure Response Relationship
CK-136: Exposure Response Relationship Exposure-response of troponin activator is shallower than myosin activator Completed Phase 1 study and have begun analyzing data Animal Models of Cardiac Function Healthy Rats PD Window1 MI Rats PD Window1 Healthy Dogs PD Window1 ≥15X ≥15X ≥15X 1PD Window = Max
Slide 57: Corporate Profile
Corporate Profile G Cytokinetics’
Slide 58: Robust Pipeline, Solid Financial Position
Robust Pipeline, Solid Financial Position Pipeline 1 Potential commercial launch as early as 2025 3 Clinical stage programs Ongoing muscle biology directed research HCM Heart Failure Ongoing Aficamten o SEQUOIA-HCM: Positive Phase 3 results Omecamtiv mecarbil o Considering potential next CK-136 R&D
Slide 59: Myosin Platform Drives Multiple Data Milestones and Potential Approvals
Myosin Platform Drives Multiple Data Milestones and Potential Approvals Potential Results Aficamten FDA Approval Aficamten oHCM SEQUOIA-HCM For illustrative purposes only Potential Results Approval Enhancing shareholder Emerging Aficamten Pipeline MAPLE-HCM value Results Aficamten Aficamten oHCM SEQ
Slide 60: Balance Sheet & Financial Guidance
Balance Sheet & Financial Guidance Approximately 2 years of cash runway based on 2024 guidance* 2024 Condensed Balance Sheet As of 3/31/2024 in millions Total Cash and investments $634.3 Accounts receivable $0.8 PPE $68.0 Leased assets $78.2 2024 Financial Guidance Other assets $26.8 Total Assets $8
Slide 61: Planned 2024 Milestones
Planned 2024 Milestones Aficamten Aficamten CK-586 Submit NDA to FDA in Q3 2024 and Complete enrollment of MAPLE-HCM Share full data from Phase 1 study MAA to EMA in Q4 2024 in Q3 2024 of CK-586 in 2H 2024 Initiate Phase 2 study Continue enrollment in ACACIA-HCM Continue enrollment of CEDAR-HCM of C
Slide 62: Thank you
CG Cytokinetics’ thank you