Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Presentation (January 2023)
52 slides from Cytokinetics's investor presentation, Jan 9, 2023
Slide 1: Cytokinetics: empowering muscle, empowering lives
CG Cytokinetics empowering muscle empowering lives Sarcomere directed therapies Chuck, diagnosed with ALS
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
To bring forward new medicines to improve the healthspan of people with devastating cardiovascular and neuromuscular diseases of impaired muscle function. Sarcomere Directed Therapies Our Mission
Slide 4: Our Vision: Leading with Science
Our vision is to be the leading muscle biology biopharma company that meaningfully improves the lives of patients with diseases of impaired muscle function through access to our pioneering medicines Achieve regulatory approvals for at least two drugs arising from our pipeline Build commercial capabi
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 Actin Tropomyosin Myosin head Myosin lever arm Calcium ATP Thin filament Thick filament CK-136 (Cardiac) Myosin Omecamtiv Mecarbil (Car
Slide 6: Pipeline of Novel Muscle-Directed Drug Candidates
Pipeline of Novel Muscle-Directed Drug Candidates * Astellas to provide co-funding in exchange for low single-digit royalty All drug candidates above are investigational products and are not approved as safe or effective for any indication. CARDIAC MUSCLE Omecamtiv Mecarbil (Heart Failure) Aficamten
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 Continue execution of COURAGE-ALS and OLE Engage with FDA ahead of February 28 PDUFA date for omecamtiv mecarbil Advance early-stage pipeline of contractility drug c
Slide 8: Cardiac Muscle Cardiovascular Franchise Strategy
Cardiac Muscle Cardiovascular Franchise Strategy Aficamten Omecamtiv Mecarbil Sarcomere Directed Drug Development Omecamtiv mecarbil and 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 effec
Slide 9: Cardiovascular Franchise Strategy
Cardiovascular Franchise Strategy
Slide 10: Go-to-Market Synergies for Aficamten & Omecamtiv Mecarbil
Go-to-Market Synergies for Aficamten & Omecamtiv Mecarbil Commercial Support Functions Medical Affairs Corporate Support Functions Utilize resources across brands (e.g., access, analytics, …) MSs qualified to cover both HFrEF and HCM Avoid costs of duplication (IT, Finance, HR, …) Sales Team Given t
Slide 11: Building deep, long-term relationships with cardiologists
To optimize value capture for potential launch of omecamtiv mecarbil Building deep, long-term relationships Limited Incremental Cost For Future U.S. CV Launches Cardiologists Building Today … … To Lead Tomorrow <10,000 Hospitals & HF Clinics <1,000 Additional Targets ~15-30% Coverage of vast majorit
Slide 12: Gated Build of Commercial Infrastructure
Gated Build of Commercial Infrastructure Engagement ongoing with FDA post Advisory Committee meeting 1/3 of hires pre-approval 2/3 of hires post-approval Underway Pre-NDA filing Market access Pricing strategy Distribution approach Payer engagement Brand strategy Sales force planning Initiated upon N
Slide 13: 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.
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 Now Undiagnosed Patients Future 700K –1.1M 280K 190K Diagnosed oHCM Patients Growing HCM Prevalence nHCM: non-obstructive HCM; oHCM: obstructive HCM CVrg: Heart Failure 2020-2029, p 44; Maro
Slide 15: Aficamten: Aspirational Target Profile
Aficamten: Aspirational Target Profile Potential next-in-class cardiac myosin inhibitor Precise Dosing Simplicity of Use Rapid Reversibility Symptom relief as early as within 2 weeks initiation and dose adjustment possible biweekly if indicated Echo guided dose titration allows both dose increases a
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 PK Echocardiogram Dose 1 Dose 2 Dose 3 Patients with symptomatic oHCM, and resting or provoked LVOT gradient ≥ 50 mmHg Study Visits Screen W-1 D1 W2 W4 W6 W9 W10
Slide 17: REDWOOD-HCM: Efficacy
REDWOOD-HCM: Efficacy Cohorts 1 & 2 Maron M, et. al. Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy. JACC. January 2023. Weeks Dose finding study Cohort 1 (n=21), Cohort 2 (n=20) Results published in JACC in January 2023 Weeks 0 2 4 6 8 10 0 20 40 60 80 mmHg Rest
Slide 18: Response Rates on Treatment with Aficamten
Response Rates on Treatment with Aficamten Cohorts 1 & 2 Responder Definition: Resting LVOT-G <30 mmHg and post-Valsalva LVOT-G <50 mmHg at Week 10 1/13 11/14 13/14 Responder # / Total # Placebo Aficamten: Cohort 1 0 20 40 60 80 100 % Total Not Responder Responder 21.4% 7.1% 7.7% 78.6% 92.9% 92.3% A
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 * p = 0.003 for Pooled Cohort 1 & 2 vs. Placebo 0 -200 -400 -600 -800 -1000 NT-proBNP (pg/mL) * Placebo Aficamten: Cohort 1 Aficamten: Cohort 2 Combined Placebo (N=13) Aficamten: Cohort 1 (N=14) Af
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 Treatment with aficamten for 10 weeks resulted in: Significant reduction in left atrial volume index Trend towards a reduction in LV mass index Improved diastoli
Slide 21: REDWOOD-HCM: Cohort 4
REDWOOD-HCM: Cohort 4 Patients with symptomatic nHCM on background therapy Dose 1 Dose 2 Dose 3 Cohort 4 5 mg 10 mg 15 mg hs-cTnl: high- sensitivity cardiac troponin *Telephone visits **Patient can only be down-titrated at Week 6 Patient enrollment completed in Q4 2022; results expected 1H 2023 PK P
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) FOREST-HCM was previously known as REDWOOD-HCM OLE FOREST-HCM is enrol
Slide 23: Safety Data
Safety Data FOREST-HCM 3 SAEs reported out of 42 patients with up-to 6-months of treatment None were related to aficamten treatment per investigator assessment. No treatment interruptions or discontinuations. No patients met the “stopping criteria” of LVEF < 40% Transient decrease in LVEF < 50% oc
Slide 24: SEQUOIA-HCM: Phase 3 Trial
SEQUOIA-HCM: Phase 3 Trial Plan to enroll at >100 sites in US, Europe and Asia** Dose Options (Dose optimization completed by Week 8) Dose 2 Dose 3 5 mg QD 10 mg QD 15 mg QD 20 mg QD SOC: standard of care * Focused echocardiogram ** Plan to enroll in US, Italy, France, Germany, Czech Republic, Denma
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 A: All patients B: On background therapy (BT) C: Patients with background therapy reduction/withdrawal
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 Well tolerated dose with desired PD effects REDWOOD-HCM Cohorts 1-3 obstructive HCM Placebo controlled; echocardiography endpoints SEQUOIA-HCM obstructive H
Slide 27: Novel Approach May Address Multiple Unmet Patient Needs
Novel Approach May Address Multiple Unmet Patient Needs nHCM Non-Obstructive HCM HFpEF Heart Failure with Preserved Ejection Fraction Obstructive HCM oHCM Aficamten (Cardiac myosin Inhibitor)
Slide 28: Aficamten: Targeting Patients with Unmet Need
Aficamten: Targeting Patients with Unmet Need Symptomatic, uncontrolled (non-responsive, refractory) to standard-of-care or Contra-indication for standard-of-care or other cardiac myosin inhibitors or Newly diagnosed patients Majority of KOLs see aficamten as an improvement to standard-of-care given
Slide 29: Aficamten: Brand Strategy
Differentiate on product attributes of value to patients and physicians Ensure access through patient support services Provide patient support tools to manage dosing regimens and persistence Leverage differentiated safety profile and limited drug-drug interactions Leverage CV franchise infrastructur
Slide 30: Aficamten: Market Access Strategy
Aficamten: Market Access Strategy Clear pricing based on benefit Develop value proposition and value story Learn from first to market access experience Leverage existing access relationships Secure profitable access to support efficient, desired prescribing position Devise distribution network to co
Slide 31: 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.
Slide 32: Omecamtiv Mecarbil: Current Status
Omecamtiv Mecarbil: Current Status Engaging with FDA Preparing for Launch 8 to 3 vote that the benefits of omecamtiv mecarbil do not outweigh its risks for the treatment of HFrEF Advisory Committee Conducted Dec. 13, 2022 PDUFA Feb. 28, 2023 Ongoing engagements with FDA Continuing launch preparednes
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 Increase in Americans living with HF through 20301 46% Cost increase of HF through 2030 (increasing from $43.63 billion to $69.7 billion)4 127% HF patients who will die within 5 years1
Slide 34: HFrEF Patients Have Challenges Getting & Staying on Optimal Therapy
HFrEF Patients Have Challenges Getting & Staying on Optimal Therapy Cycling through GDMT pillars2 50% of HFrEF patients have cycled through 3+ pillars since 2015 Only 23% are on 3+ pillars in Q2/22 Reaching optimal/therapeutic dose2 Patients do not reach optimal doses, with many on low doses of GDMT
Slide 35: Large and Growing Heart Failure Patient Population
Large and Growing Heart Failure Patient Population * HF Event: Urgent, unscheduled outpatient visit or hospitalization ** Due to renal impairment, low BP and/or hyperkalemia 1. National Center for Health Statistics. National Health and Nutrition Examination Survey (NHANES) as accessed 4/1/2019 at we
Slide 36: GALACTIC-HF Pivotal Phase 3 Trial Design
Pivotal Phase 3 Trial Design *An HF event defined as the presentation of the subject for an urgent, unscheduled clinic/office/ED visit, or hospital admission, with a primary diagnosis of HF, where the patient exhibits new or worsening symptoms of HF on presentation, has objective evidence of new or
Slide 37: Primary Composite Endpoint
Primary Composite Endpoint Time to First Heart Failure Event or Cardiovascular Death Cumulative Incidence, % 0 6 12 18 24 30 36 50 40 30 20 10 0 Placebo Omecamtiv Mecarbil HR=0.92 (95% CI, 0.86–0.99) p=0.025 Months (30 Days) Since Randomization Cumulative Incidence, % 0 6 12 18 24 30 36 70 60 40 20
Slide 38: Greater Treatment Effect in Worsening HF
Greater Treatment Effect in Worsening HF Primary Outcome in Severe HF (Severe HF: LVEF ≤30%, NYHA III/IV, HF hosp ≤ 6 mos)1,2 1. Felker GM, Omecamtiv Mecarbil in Patients with Severe Heart Failure: An Analysis from GALACTIC-HF, ESC Heart Failure 2021, June 2021 2. Felker GM, et al. Assessment of Ome
Slide 39: Greater Treatment Effect in Worsening HF with GDMT Intolerance
Greater Treatment Effect in Worsening HF with GDMT Intolerance Placebo 113 63 43 28 15 9 3 OM 113 76 64 46 30 9 3 Placebo 113 91 75 51 30 15 5 OM 113 96 83 62 40 15 5 Patients at risk, n Primary Outcome In Patients with LVEF ≤28% Intolerant of ACE/ARB/ARNI CV Death In Patients with LVEF ≤28% Treated
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
Skeletal Muscle Reldesemtiv Sarcomere Directed Drug Development
Slide 42: 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.
Slide 43: Phase 2 Clinical Trial in ALS
Parallel group, dose ranging study enrolled 458 patients with ALS in the US, Canada, Australia and Europe evaluating change from baseline in the percent predicted slow vital capacity (SVC) at 12 weeks of treatment with reldesemtiv or placebo Phase 2 Clinical Trial in ALS Double-Blind, Placebo-Contro
Slide 44: Primary Endpoint: SVC
Primary Endpoint: SVC Change from baseline in percent predicted SVC at week 12 *Based on Mixed Model for Repeated Measures (MMRM) with the contrasts of (-5, -1, 3, 3) for placebo, reldesemtiv 150 mg, 300 mg and 450 mg BID, respectively Primary Analysis* P = 0.11 for weighted dose-response relationsh
Slide 45: Phase 2 Clinical Trial: SVC and ALSFRS-R Change From Baseline
Phase 2 Clinical Trial SVC Change From Baseline (All Active vs Placebo) ALSFRS-R Change From Baseline (All Active vs Placebo) *post hoc analysis FORTITUDE-ALS did not achieve statistical significance, but patients on all dose groups of reldesemtiv declined less than patients on placebo Relative redu
Slide 46: Post-Hoc Analyses Inform Phase 3 Design
Post-Hoc Analyses Inform Phase 3 Design Change From Baseline in ALSFRS-R by Progressor Tertiles SP reldesemtiv combined (n=117) SP placebo (n=35) MP + FP reldesemtiv combined (n=227) MP + FP placebo (n=79) LS mean change from baseline in ALSFRS-R Treatment difference 1.15; P = 0.0112 Risk Group (Pre
Slide 47: COURAGE-ALS 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) (N= 555) Randomization 2:1 Stratification: Riluzole & Edaravone Placebo Reldesemtiv 300 mg BID End of Study 14 days Reldesemtiv 300 mg BID Screening En
Slide 48: Corporate Profile
Corporate Profile Sarcomere Directed Therapies
Slide 49: Robust Pipeline, Solid Financial Position
Programs HCM Heart Failure Omecamtiv mecarbil ALS Reldesemtiv Phase 3 trial, COURAGE-ALS ongoing Ongoing R&D Additional research in muscle biology, energetics & metabolism Robust Pipeline, Solid Financial Position Foundations ~400 Full time employees >$800M At EOY 2022 >2 years Cash runway based on
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 in millions Total Cash and investments $896.2 Accounts receivable $2.3 PPE $80.3 Leased assets $75.1 Other assets $22.1 Total Assets $1,076.0 Debt $545.0 Liability related to sale of future ro
Slide 51: Expected 2023 Milestones
Aficamten Expected 2023 Milestones Continue to engage with FDA in advance of Feb 28, 2023 PDUFA for omecamtiv mecarbil Begin second Phase 3 trial of aficamten in oHCM in 1H 2023 Complete conduct in Cohort 4 of REDWOOD-HCM; results expected 1H 2023 Continue enrollment in SEQUOIA-HCM through 1H 2023;
Slide 52: Thank You
CG Cytokinetics Thank You Sarcomere directed therapies (| diagnosed wit HCM Chuck, diagnosed with ALS