Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Investor Day (October 2021)
124 slides from Cytokinetics's investor day presentation, Oct 7, 2021
Slide 1: Program to begin at 8:30 AM ET
Program to begin at 8:30 AM ET N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 2: Forward-Looking Statements
Forward - Looking Statements Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 2 This Presentation contains forward - looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”)
Slide 3: Company Speakers
Stuart Kupfer, M.D. SVP , C h i e f M e d i c a l O ff i c e r A nd r e w C a ll o s EVP , C h i e f C o mm e r c i a l O f f i c e r F a d y M a li k , M .D . , P h .D . EVP , R e s ea r c h & D e v e l o p m e n t Company Speakers R ob e r t B l u m P r e s i d e n t & C E O J o a nn a S i e g a l
Slide 4: Expert Panel
Expert Panel T a r i q A h m a d , M D , M P H A ss o c i a t e P r o f e s s o r o f M e d i c i n e ; M e d i c al D i r ec t o r o f A d v a n ce d He a r t F a i l u r e , C a r d i o va s c u l a r M e d i c i n e , Y a l e S c h o o l o f M e d i c i ne A lan n a M o rr i s , M D M S c , F H F
Slide 5: Today's Agenda
Charting the Commercial Course: Today’s Agenda Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 5 Topic Presenter Intro J o a nn a S i e g a l l Welcome R o b e r t B l u m H e a r t Fa il u r e L a n d s c a p e F a
Slide 6: Engaging in Today's Meeting
Engaging in Today’s Meeting Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 6 In Person Attendees: • Masks : Masks are not required for those who are fully vaccinated. However, we encourage mask wearing whenever you
Slide 7: Introduction
Introduction Robert Blum, President & CEO N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 8: Our Mission
8 T o b r i n g f o r w a r d n e w m e d i c i n e s t o i m p r o ve t h e h e a l th s p a n o f p e op l e w i t h devastating cardiovascular and neuromuscular diseases of impaired muscle function. Sarcomere Directed Therapies OUR MISSION
Slide 9: Our Vision
Our vision is to be the leading muscle biology biopharma company that m e a n i n g f u ll y i m pr o v e s t h e li v e s of patients with diseases of impaired muscle function through access to our pioneering medicines A c h i e v e r e g u l a t o r y a pp r o va l s f o r a t l e a s t two drugs
Slide 10: Executing On Our Vision
Executing On Our Vision • Scientific innovation driven by m o d u l a t i n g c a r d i a c m y o s i n • First - in - class myosin activator • Next - in - class myosin inhibitor • Expansion beyond contractility to muscle energetics, metabolism • R e g u l a r i n p u t , c o ll a b o r a t i o n an
Slide 11: 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. Research Pre - Clinical Phase 1 Phase 2 Phase 3 C A R
Slide 12: One Molecular Target Supports Emerging CV Franchise
Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 1 2 One Molecular Target Supports Emerging CV Franchise A c t i n Tropomyosin T h i c k f i l a m en t M y o s i n h ea d M y o s i n l e v e r a r m C a l c i u m A T
Slide 13: HF Treatment Landscape
HF Treatment Landscape Fady Malik, M.D., Ph.D. E V P , R e s e a r c h & D e v e l op m e n t N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 14: Heart Failure Is a Public Health Emergency
Heart Failure Is a Public Health Emergency 46% Increase in Americans living with HF through 2030 owing to aging population and decline in mortality 1 HF: heart failure 127% Cost increase of H F t h r o u g h 203 0 ( i n c r e a s i n g fr o m $43.6 2 b i llio n t o $69. 7 b i llio n )3 Charting the
Slide 15: Hospitalization & Rehospitalization Rates Are Burdensome
Hospitalization & Rehospitalization Rates Are Burdensome HF, heart failure; HFbEF, heart failure with borderline ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction. 1. B e n j a m i n E J , et a l . C i r c u l a t i o n . 20
Slide 16: Foundational GDMT – Problem Solved?
Foundational GDMT – Problem Solved? Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 16 2021 E S C G u i d e li n e s f o r t h e D i a g n o s i s a n d Treatment of A c u te a n d C h r o n i c Heart Failure G D M
Slide 17: Not Yet – Event Rates in HFrEF Remain Startling High
50 40 30 20 10 0 60 All - cause Death/ H F H o s p i t a l i z a t i o n H F H o s p i t a l i z a t i o n A l l C au s e D e a t h D uk e C o h o r t 1 N o t H o s p w / i n 1 y r H o s p w / i n 1 y r Not Yet – Event Rates in HFrEF Remain Startling High Event Rates in Placebo Group of GALACTIC - H
Slide 18: Not Yet – Event Rates in HFrEF Remain Startling High
Not Yet – Event Rates in HFrEF Remain Startling High Event Rates in Placebo Group of GALACTIC - HF on Excellent GDMT I n c i d e n c e ( p e r 10 0 p a t i e n t - y e a r s ) E j e c t io n F r a c t io n 1 > m ed i a n ≤ m e d i a n N Y H A C l a s s * C l a s s I I C l a s s I I I / I V 40 40 30
Slide 19: Higher Risk Patients Tolerate Less GDMT
Higher Risk Patients Tolerate Less GDMT The sickest patients are the most difficult to treat with GDMT 90 80 70 60 50 40 30 20 10 0 Risk - Treatment Mismatch in HF: Canadian EFFECT Study Low Risk Average Risk High Risk 1 - Year M o r t a li t y R a t e 1 - Year Follow - Up At Hospital Discharge Lee
Slide 20: After Foundational GDMT – What Next?
A f t e r F o und a t i o n a l G D M T – W h a t N e x t ? Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 20 P a t i e n t s w i t h w o r s e n i n g H F n ee d a l t e r n a t i v e s GDMT: Guideline directed me
Slide 21: Significant Unmet Need in HFrEF
Significant Unmet Need in HFrEF Proprietary market research suggests need for novel therapy Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 21 Drugs that d o n o t a ff e c t r e n a l f un c t i o n Drugs that do n
Slide 22: GALACTIC-HF: Omecamtiv Mecarbil
GALACTIC - HF Stuart Kupfer, M.D., SVP, Chief Medical Officer O m e c a m t i v M e c a r b i l : N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 23: Pivotal Phase 3 Trial Design
23 Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 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
Slide 24: Baseline Demographics
24 Charting the Commercial Course : Analyst & Investor Day 2021 Baseline Demographics W o r s e n i n g H F p o pu lati o n w it h h ig h l e v e l o f G D M T Characteristic OM ( N =4120 ) Placebo ( N =4112 ) Demographics A g e ( y e a r s ) , m e d i a n ( Q 1 , Q 3 ) 6 6 ( 58 , 73 ) 6 6 ( 58 , 73
Slide 25: Positive Primary Composite Endpoint
Positive Primary Composite Endpoint Time to first HF event or CV death – 8% relative risk reduction Placebo 4112 3310 2889 2102 1349 647 141 OM 4120 3391 2953 2158 1430 700 164 Patients at risk, n C u m u l a t i v e i n c i d en c e , % 0 0 6 12 18 24 M o n t h s ( 3 0 d ay s ) s i n c e r a n do m
Slide 26: Treatment Effect Increased Progressively as Baseline LVEF Decreased
T r ea t m e n t E ff e c t I n c r ea s e d P r o g r e ss i v e l y A s B a s e li n e L V E F D e c r ea s e d 10 15 20 25 E j e c t io n f r a c t io n ( % ) 3 0 35 10 20 30 40 60 50 I n c i d e n c e R a t e ( p e r 10 0 p y ) Placebo O m e c a m t i v mecarbil T r ea t m e n t Effect T r e a t
Slide 27: Greater Treatment Effect with Higher NT-proBNP
Greater Treatment Effect with Higher NT - proBNP McMurray JM, Efficacy of omecamtiv mecarbil in HFrEF according to NT - proBNP level: Insights from the GALACTIC - HF trial, ESC Heart Failure 2021, June 2021 H R = 1 ( un i t y ) 95%CI Continuous HR H R = 1 ( un i t y ) P l a c e b o b e tt e r O M b
Slide 28: Greater Treatment Effect in Higher-Risk, Worsening HF
Greater Treatment Effect in Higher - Risk, Worsening HF Results of the primary outcome in pre - specified subgroups showed greater treatment effect in patients with markers of worsening heart failure, i n c l u d i n g p a t i e n t s w i t h L VEF ≤28%: (n=4,456) HR 0.84; 95% CI 0.77, 0.92 Subgroup
Slide 29: Greater Treatment Effect in More Severe HF
Greater Treatment Effect in More Severe HF Severe HF defined as NYHA III - IV, EF ≤ 30%, HF hospitalization in last 6 months T r ea t m e n t e ff e c t f o r p r i m a r y endpoint in severe HF HR = 0.80 (0.71, 0.90) Absolute risk reduction 8.3 events/100 pt - years NNT = 12 Felker GM, Omecamtiv Me
Slide 30: Clinically Meaningful Treatment Effect in North America
Clinically Meaningful Treatment Effect in North America Significant Risk Reduction of the Primary Composite Outcome Primary Composite Outcome: Time to first HF event or CV death P r i m a r y O u t c o m e , N o r t h A m e r i c a 0 . 5 0 0 . 4 0 0 . 3 0 0 . 2 0 0 . 1 0 0 . 0 0 0 6 12 24 30 18 Mont
Slide 31: Safety and Tolerability Profile Comparable to Placebo
Safety and Tolerability Profile Comparable to Placebo Variable Omecamtiv Mecarbil (N=4110) Placebo ( N =4101 ) R e l a t i v e R i s k o r D i ff e r en c e (95% CI) Laboratory value change from baseline to Week 24 S y s t o li c b l oo d p r e ss u r e – mm Hg , m e a n ( S D ) 1 . 4 ( 15 . 3 ) 1 .
Slide 32: Greater Effects in HF Patients with Highest Need
Greater Effects in HF Patients with Highest Need • Significant risk reduction of the primary composite endpoint in patients with worsening HF receiving excellent GDMT • Greater treatment benefit in higher risk patients • Lower baseline LVEF • Higher baseline NT - proBNP • Higher baseline NYHA Class
Slide 33: Selected Comments from Key Opinion Leaders
Selected Comments from Key Opinion Leaders “ T h i s i s t h e h ol y g r a i l f o r i n o t r o p e s ” “The first inotropic agent that doesn’t increase arrhythmias or mortality” “OM’s greatest potential is in severe, sicker patients ” “ Omecamtiv mecarbil can serve a large, unmet need ” “ U n i q
Slide 34: Expert Panel
Expert Panel Moderated by Fady Malik, M.D., Ph.D., EVP, Research & Development N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 35: Expert Panel
35 Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y Expert Panel T a r i q A h m a d , M D , M P H A ss o c i a t e P r o f e s s o r o f M e d i c i n e ; M e d i c al D i r ec t o r o f A d v a n ce d He a r t F a
Slide 36: Filling an Unmet Patient Need
Filling an Unmet Patient Need Andrew Callos, EVP, Chief Commercial Officer O m e c a m t i v M e c a r b i l : N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 37: Omecamtiv Mecarbil: Value Proposition
Omecamtiv Mecarbil: Value Proposition K E Y M A RK E T D Y N A M I C S OM VALUE PROPOSITION OM delivers clinical v a l u e t o w o r s en i n g H F patients OM is an add - on therapy for worsening HF patients OM reduces hospitalizations and their associated costs 1 Large unmet need Limitations of cu
Slide 38: Key US HFrEF Market Dynamics
K e y U S H F r E F M a r k e t D y n a m i cs Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 38 1. National Center for Health Statistics. National Health and Nutrition Examination Survey (NHANES) as accessed 4/1/2
Slide 39: Large and Growing Heart Failure Patient Population
Large and Growing Heart Failure Patient Population 1. National Center for Health Statistics. National Health and Nutrition Examination Survey (NHANES) as accessed 4/1/2019 at website. https://www.cdc.gov/nchs/nhanes/ . – data from 2013 - 2016 as quotes in Benjamin 2019 Circulation. 2019;139:e56 – e5
Slide 40: HFrEF Treatment Approaches and Guidelines Are Evolving
H F r E F T r ea t m e n t A p p r o a c h e s a n d G u i d e li n e s A r e E vo lv i n g T r e n d i n t r e at m e n t a pp r o a c h e s t o p r e s c r i b e i n i t i a l m u l t i - d r u g r e gi m e n s ea rl i e r … … A l s o r e f l e c t e d in upd at e d 202 1 E S C g u i de li n e s 2
Slide 41: Recent Entrants Have Expanded Treatment Options
Recent Entrants Have Expanded Treatment Options H F r E F e xp a n s i o n ( A CC / E S C guidelines) & LIFE study results I n c r ea s ed S G L T c o m p e t i t i o n Indicated following HF hospitalization or outpatient IV diuretics F i r s t S G L T t o H F m a r k e t Company press releases or i
Slide 42: Co-Morbidities & Tolerability Can Lead to Under-Treatment
Co - Morbidities & Tolerability Can Lead to Under - Treatment Low BP Renal I n s u ff i c i en c y E l e v a t e d S e r u m Potassium % P a t i en t s R e c e i v i n g Target Dose ACEi/ARB X X X 17% ARNI X X X 14% B e t a B l o c k e r X 28% MRAs X X X 77% P a ti e n t s n o t r e a c h i n g re c
Slide 43: HF Patients Often Cycle Through Frequent Hospitalizations
HF Patients Often Cycle Through Frequent Hospitalizations 24% ~25 - 50% 44% 66% Heart Failure Hospitalization <1 m o n t h 4 ,6 <2 m o n t h s 7 <6 months 5 <12 m o n t h s 3 ,8 . . . Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s
Slide 44: Lower EF Associated With Increased Risk of Hospitalization
Lower EF Associated With Increased Risk of Hospitalization Adapted f rom Angaran P, Association of Left Ventricular Ejection Fraction with Mortality and Hospitalizations, Journal of theAmerican Society of Echocardiography, July 2020. Based on 27,323 patients evaluated over 4+ years follow - up; * EF
Slide 45: Heart Failure Cost Burden 2020-2030
2020 2030 1. Urbich, M., Globe, G., Pantiri, K. et al. A Systematic Review of Medical Costs Associated with Heart Failure in the USA (2014 – 2020). PharmacoEconomics 38, 1219 – 1236 (2020). https://doi.org/10.1007/s40273 - 020 - 00952 - 0 2. Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J,
Slide 46: Tremendous Burden on Patients and Caregivers
50% 46% 42% 39% Tremendous Burden on Patients and Caregivers 1 McHorney CA, et al. (2021) The impact of heart failure on patients and caregivers: A qualitative study. PLOS ONE 16(3): e0248240. https://doi.org/10.1371/journal.pone.0248240 https://journals.plos.org/plosone/article?id=10.1371/journal.p
Slide 47: US Go-To-Market Strategy
U S G o - T o - M a r k et Strategy Andrew Callos, EVP, Chief Commercial Officer Jennifer Laux, VP, Cardiovascular Marketing Diann Potestio, VP, Global Value, Access & Distribution N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 48: Omecamtiv Mecarbil: GTM is Critical Step for Our Vision 2025
Omecamtiv Mecarbil: GTM is Critical Step for Our Vision 2025 C o mm e r c i a l G o a l s a n d Aspirations Market • Wh e r e t o f o c u s ? - Segmentation - Targeting - … • How to win? - Positioning - Value - Access - Medical - … Internal • How to organize? - B u il d v s B u y - Field Force - Dig
Slide 49: GTM Is Based on Target Product Profile for Omecamtiv Mecarbil
GTM Is Based on Target Product Profile for Omecamtiv Mecarbil Demonstrated in patients with symptomatic chronic heart failure with EF ≤ 30 % (N= 5 , 842 ), 12 % (p< . 002 ) RRR in composite of CV death or HF events vs . placebo (translates into 3 . 8 % ARR, NNT= 27 ) Efficacy Omecamtiv mecarbil is t
Slide 50: Our GTM Strategy: Gated Build of Core Capabilities
Our GTM Strategy: Gated Build of Core Capabilities S t r at e gic c h o ic e s a c r o s s e a c h G T M b l o c k S e q u e n ce , a n d g a t e b u il d - o u t ba s e d o n p r e - defined m il es t o n e s an d m e t ri c s to r e d u c e r i sk L e v e r a g e d ee p un d e r s t an d i n g of
Slide 51: Building a World Class Commercial Organization
Building a World Class Commercial Organization Driven by a relentless focus on our North Star: the patient Make strategic choices and investments enabled by data Enables scalability beyond first product launch Experienced leaders Deep f un c t i o n a l e x p e r ti s e Nimble d e c i s i o n making
Slide 52: Gated Build Based on Key Milestones to Enable De-Risking
Gated Build Based on Key Milestones to Enable De - Risking NDA NDA Submission Acceptance 2021 2022 P D U F A Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 52 N o r e gr e t * i n v e s t m e n ts S e q u e n c e d
Slide 53: Deep Understanding of the Patients, HCPs and Institutions
Deep Understanding of the Patients, HCPs and Institutions Insights Education Access Support Worsening heart failure patient requiring more intensive treatment due to decreasing LVEF (≤ 30 % ), recent heart failure event (≤ 12 months), often with co - morbidities / tolerability issues limiting GDMT t
Slide 54: High Unmet Need in Patients with Worsening Heart Failure
Patient High Unmet Need in Patients with Worsening Heart Failure Insights Education Access Support R e c e n t E v e n t HF Event* ≤ 12 months C a r d i a c F un c ti o n + LV E F ≤ 30 % W H F : W o r s e n i n g h e a r t f a i l ur e * HF Event: Urgent, unscheduled outpatient visit or hospitalizat
Slide 55: Tremendous Burden of WHF on Patients and Caregivers
Tremendous Burden of WHF on Patients and Caregivers “This condition takes my life from me ” “ I ca n ’ t w a lk anymore, or walk my dog” “I dread having to be taken to the hospital again” “ Despite all these meds , I still can’t tend to my garden” “Caring for my loved one with HF is an exhausting fu
Slide 56: Multiple Ways to Initiate Omecamtiv Mecarbil
Multiple Ways to Initiate Omecamtiv Mecarbil G D M T m axe d o u t S y m p t o m s d e t e r i o r a t i n g Further decrease in EF T o l e r a b ili t y i s s u e s * P o t en t i a ll y li m i t e d b y c o - m o r b i d i t i e s / t o l e r a b il i t y Worsening H e a r t F a il u r e GDMT* Cha
Slide 57: Deep Understanding of HCPs Managing WHF Patients
HCP D ee p U nd e r s t a nd i n g o f H C P s M a n a gi n g W H F P a t i e n t s Insights Education Access Support High Prescribers A bo u t o n e t h i r d o f c a r diolo g i s t s s e e m a jo r i t y o f W H F patients Cardiologists A f f ili a t e d w i t h c a r di o l o g y p r a c t i c e
Slide 58: Small Subset of Cardiologists Manage Majority of Patients
S m a l l S u b s e t of C a r d i o l o g i s t s M a n a g e M a j o r i t y of Pa t i e n t s Symphony APLD (1/1/2019 – 12/31/2020); Physician Interviews; Analysis includes n = 25,510 cardiologists and n = 110,114 PCPs who see at least 1 HFrEF patient during the two - year market map period H F r
Slide 59: Positive HCP Reactions to Product Profile
P o s i t i ve H C P R ea c t i o n s t o P r o du c t P r o f il e Proprietary market research Investigational products. Not approved as safe or effective for any indication High remaining unmet need in patients with worsening heart failure “I often run out of treatment options as my heart failure
Slide 60: Deep Understanding of the Institutional Settings
Institutions Deep Understanding of the Institutional Settings Insights Education Access Support H i g h W H F p a t i en t vo l u m e , e a r l y a dop t e r s , c o m p r eh e n s i v e c a r e t e a m s 1. Symphony APLD (1/1/2019 – 12/31/2020); H F C li n i cs M a n a g i n g W H F p a t i en t s
Slide 61: Hospitals Increasingly Change Treatment Regimens
Hospitals Increasingly Change Treatment Regimens I Q V I A 20 6 - 2018 , I Q V I A 202 0 % o f H F r E F P at i e nt s A drug in new c l a s s i s a dd e d A drug is replaced In same class T i t r a t i o n o f c u rr e n t treatment or no change 2016 - 201 8 2020 T r ea t m e n t C h a n g e s D u
Slide 62: Educating and Engaging HCPs
Educating and Engaging HCPs Insights Education Access Support • Despite COVID impact, in - person details continue to rise • Personalized engagement approach via targeted sales force interactions and digital channels Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot
Slide 63: Despite COVID, In-Person Details Continue to Rise
Despite COVID, In - Person Details Continue to Rise 33% 50% 53% 54% 57% 61% 62% 66% 66% 66% Cardiology E n d o c r i n o l o g y Respiratory Gastroenterology Neurology N e ph r o l og y Dermatology Primary Care Psychiatry R h e u m a t o l og y Oncology In Person Details as % Baseline I Q V I A – C
Slide 64: Engagement Approach Allows Customizing and Broadening
Engagement Approach Allows Customizing and Broadening Targeted H F S p e c i a l i s t Targeted Community C a r d i o l o g i s t Broadening R e a c h B ey on d I n i t i a l T a r g e t D i g i t a l a ll o w s b r o a d e r r ea c h ~ ~ ill u s t r a t i ve ~ ~ Customizing engagement by different
Slide 65: Getting Access
Getting Access Insights Education Access Support • Omecamtiv mecarbil may create significant value by reducing hospitalizations (and associated costs) 1 • Given importance of Medicare Part D, we aim to minimize time to coverage given annual bid process • To accelerate access, we are investing in hig
Slide 66: Omecamtiv Mecarbil: Value Proposition
Omecamtiv Mecarbil: Value Proposition I n H F r E F , p a ti e n t s w it h l o w e r e j e c ti o n f r a c ti o n s a r e h o s p it a liz e d m o r e o f t e n H o s p it a liz a ti o n r e d u c ti o n s s ee n in c li n i c a l t r i a l o f o m e c a m t i v m e c a r b i l Clinically meaningf
Slide 67: Medicare, By Far The Largest Payer, Will Be a Key Focus
M e d i c a r e , B y F a r T he L a r g e s t P a y e r , W il l B e a K e y F o c us (CVS) (ESI) National Trends in Heart Failure Hospitalizations and Readmissions From 2010 to 2017 Agarwal, Fonarow, and Ziaeian; JAMA Cardiol, Feb 10, 2021 (Table 2 Payer Status); https://www.kff.org/medicare/issue
Slide 68: To Accelerate Access, Hiring Highly Experienced Staff
To Accelerate Access, Hiring Highly Experienced Staff Individually, 15 - 25 years of experience Collectively ~ 200 years of Payer / PBM Relationship Experience ≥250 years of Bio - Pharma Industry Experience Cytokinetics Account Director Customer Relationship Experience Charting the Commercial Course
Slide 69: Supporting Patients and Caregivers
Supporting Patients and Caregivers Insights Education Access Support • Providing patient and caregiver education about disease and (post - approval) about product • Evaluating innovative models for patient services, including a patient hub and digital approaches Charting the Commercial Course : Anal
Slide 70: We Put The Patient At The Center of Our GTM Strategy
We Put The Patient At The Center of Our GTM Strategy Patient A n a l y t i cs A f f o r d a b ili t y Access A d heren c e Caregiver HCP P h a r m a c y Payer Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 70
Slide 71: Evaluating Innovative Hub Models for Patient Services
Evaluating Innovative Hub Models for Patient Services A n a l y t i cs A f f o r d a b ili t y Patient Access A d heren c e Caregiver HCP P h a r m a c y Payer M ix o f : H i g h - t o u c h s u pp o r t f o r p a t i e n t s a n d caregivers D i g i t a l a ss i s t a n t f o r p a t i e n t a n d
Slide 72: Evaluating Innovative Hub Models for Patient Services
Evaluating Innovative Hub Models for Patient Services M ix o f : H i g h - t o u c h s u pp o r t f o r p a t i e n t s a n d caregivers D i g i t a l a ss i s t a n t f o r p a t i e n t a n d H C P office staff • Free product ( t r i a l , s a m p l e s ) • C o mm e r c i a l c o - p a y support •
Slide 73: Realizing The Promise of Omecamtiv Mecarbil
Realizing The Promise of Omecamtiv Mecarbil Offering new hope for patients with worsening heart failure Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 73 Our Value Proposition Addresses large unmet need OM is an ad
Slide 74: Q&A
Q&A To ask a question in the room, please raise your hand. To ask a question online, type it into the tab on the left. N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 75: Break
B r e a k N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly 2 - 5 m i nu t e s
Slide 76: HCM Landscape
HCM Landscape Andrew Callos, EVP, Chief Commercial Officer N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 77: Large HCM Population With Many Undiagnosed
I n U S, L a r ge H C M P o pu l a t i o n W i t h M a n y U nd i a g n o s e d N o w F u t u r e Currently ~280K diagnosed, ~190K oHCM symptomatic patients Estimated ~400 - 800K un - diagnosed patients 70 0 – 1 , 100 K 280K n H C M * 190K o H C M * Potential Undiagnosed Patients ~400 - 800K Diagnos
Slide 78: Multiple Activities Under Way to Increase HCM Diagnosis
Multiple Activities Under Way to Increase HCM Diagnosis G e n e t i c T e st Companies G e n e t i c t e s t s Guidelines R a i s e d A wa r e n e ss F r o m N e w T r e a t m e n t s Academia and industry partnering to support early HCM detection (incl AI - based) and monitoring Genetic testing com
Slide 79: The Unmet Treatment Need in oHCM
U n m e t Need Be t a - B lo c k e r CCB D i s o p y r a m i de a nd / o r S e p t a l R e d u c t i o n The Unmet Treatment Need in oHCM B e t a - B l o c ke r CCB Disopyramide 30% NYHA C l a s s I 40% NYHA C l a s s II 30% NYHA C l a s s I I I / IV HCM with Outflow Obstruction ( ≥ 3 0 mm H g a t r
Slide 80: Current oHCM Treatments Have Significant Limitations
Pharmacological • C u r r e nt S t and a r d o f C a r e - B e t a B l o cke r s - C a l c i u m C h a n n e l B l o c ke r s • F o c us o n s y m p t o m r e li e f • R es u l t s a r e o ft e n i na d e q u a te • I n d i r ec t m ec ha n i s m s o f a c t io n • S y s t e m i c s i de e ff ec t s
Slide 81: Significant Cost Burden With Current Treatments
Medical A nnu a l m e di c a l c o s t s m o r e t ha n do u bl e d f o ll o w i n g d i a gn o s i s Cost Per Patient ($K) 20 Total HCM - related costs increased by ~4x one year after diagnosis Also, Significant Cost Burden With Current Treatments 6 P r e Dx P o s t Dx B u t z n e r e t a l . 202 1
Slide 82: Remaining Areas of Unmet Need in oHCM
Remaining Areas of Unmet Need in oHCM Drugs that can i m p a c t l on g t e r m complications Drugs that p r e v e n t H C M i n G e n e + v e p a t i e n t s Drugs that work i n m o r e s e v e r e patients Drugs that p r o v ide r eve r s e r e m o d e l b e n e f i t Drugs that i m p r ov e f un
Slide 83: Aficamten: A Next Generation Therapy
R e du c e ti m e t o o p ti m a l d o s e W i den t h e r a p e u ti c w i n d o w F e w e r d o s e a d j u s t m e n ts N o p l a s m a m o n it o r i n g A f i c a mt e n : A N e xt G e n e r a t i o n T h e r a p y A tt r i b u t e s m a y t r a n s lat e i nto A c c e l e r a t e d S y m p t o
Slide 84: Key Components of Aspirational Target Profile
Key Components of Aspirational Target Profile Functional Improvement: Improved exercise capacity Symptom Improvement: One or two class improvement in NYHA class Q u a li t y o f L i f e : K CC Q i m p r o v e m e n t Efficacy M i n i m a l d r u g - d r u g i n t e r a c t i o n s Maintain LVEF: >50
Slide 85: Three Key Sources of Patients for Aficamten
Three Key Sources of Patients for Aficamten 2022 A f i c a m t e n Launch Undiagnosed Patients F u t u r e Diagnosed Patients Mava success ~~ ill u s t r a t i v e ~~ O t h e r t r eat m e n ts Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r
Slide 86: Aficamten: Value Proposition
Aficamten: Value Proposition Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 86 Profile addresses all oHCM patients regardless of severity of disease or risk No anticipated contraindications and minimal drug interac
Slide 87: Aficamten: Potential Next-In-Class Therapy
Potential Next - In - Class Therapy Steve Heitner, M.D., Senior Medical Director, Clinical Research Cardiovascular A f i c a m t e n : N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 88: Aficamten: Leveraging Pharmacology for Clinical Practice
A f i c a m t e n : L e v e r a g i n g P h a r m a co l o g y for C l i n i c a l P r a c t i ce P r e c i s e D o si n g Simplicity of Use Rapid Reversibility Symptom relief as early as within 2 weeks initiation and dose adjustment possible bi w ee k l y i f indi c a t e d Echo guided dose titrati
Slide 89: Phase 2 Clinical Trial Design
Phase 2 Clinical Trial Design Two sequential dose - finding cohorts (with third cohort assessing patients on disopyramide ) I P D o s i n g Echocardiogram D o s e 1 D o s e 2 D o s e 3 P a t i e n t s w i t h s y m p t o m a t i c o H C M , and resting or provoked LVOT gradient ≥ 50 mmHg S t u d y V
Slide 90: Patient Enrollment and Dosing
Patient Enrollment and Dosing 41 Total Enrolled Patients Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 90 Final Dose Achieved (N) 5 mg 10 mg 15 mg 20 mg 30 mg N = 14 Cohort 1 4 5 5 N = 14 Cohort 2 9 4 1
Slide 91: Baseline Characteristics
Characteristic P la c e b o (n = 13) Aficamten (n = 28) A g e ( Y e ar s ) , M e a n ( S D ) [ R a n g e ] 57.2 (9.6) [36,69] 56.6 (13.6) [33,78] < 65 Years 10 (77%) 17 (61%) S e x , n ( % ) Female 8 (62%) 15 (54%) Race = White , n (%) 12 (92%) 28 (100%) NYHA Class , n (%) C l a s s I I 11 (85%) 17
Slide 92: High Response Rates on Treatment with Aficamten
High Response Rates on Treatment with Aficamten Responder Definition: R e s t i n g L V O T - G < 3 0 mm H g a n d po s t - V a l s a l v a L V O T - G < 5 0 mm H g a t W ee k 1 0 1 / 1 3 11 / 1 4 13 / 1 4 Responder # / Total # P l a c e b o Charting the Commercial Course : Analyst & Investor Day 20
Slide 93: REDWOOD-HCM: Efficacy Resting LVOT-G
REDWOOD - HCM: Efficacy Resting Left Ventricular Outflow Tract Gradient (LVOT - G) M e a n “ S E M R e s t i n g L V O T - G ( mm H g ) Baseline W ee k 2 W ee k 4 W ee k 6 W ee k 1 0 P l ac e bo ( n = 1 3 ) 52.1 45.0 47.1 49.0 44.0 C o h o r t 1 ( n = 14 ) 53.8 24.3 27.3 13.9 13.4 p - v a l ue v s p
Slide 94: REDWOOD-HCM: Efficacy Valsalva LVOT-G
REDWOOD - HCM: Efficacy Va l s a l v a LV O T - G M e a n “ S E M V a l s a l v a L V O T - G ( mm H g ) Baseline W ee k 2 W ee k 4 W ee k 6 W ee k 1 0 P l ac e bo ( n = 1 3 ) 84.6 71.3 71.3 73.4 76 C o h o r t 1 ( n = 14 ) 74.4 51.3 46.1 37.1 38.1 p - v a l ue v s p l a c e bo – 0.097 0.038 0.0003
Slide 95: REDWOOD-HCM: Efficacy Changes in LVEF
REDWOOD - HCM: Efficacy Changes in Left Ventricular Ejection Fraction over Study Period C o m b i n e d P l a c e b o ( N = 13 ) A f i c a m t e n : C oh o r t 1 ( N = 14 ) A f i c a m t e n : C oh o r t 2 ( N = 1 4 ) W eek s Washout Treatment 40 2 4 6 8 1 0 12 * * * * * * * D o s e r e d u c t io n
Slide 96: Change from Baseline in NT-proBNP & NYHA Class
Change from Baseline in NT - proBNP & NYHA Class C h a n g e f r o m B a s e li n e N T - p r o B N P t o W ee k 1 0 * P = 0 . 00 3 fo r P ool e d C o h o r t 1 & 2 v s . P l a c e b o 0 - 200 - 400 - 600 - 800 - 1000 NTproBNP (pg/mL) * P l a c e b o A f i ca m t en : Cohort 1 A f i ca m t en : Coho
Slide 97: REDWOOD-HCM: Safety Data
REDWOOD - HCM: Safety Data • No patients met the “stopping criteria” of LVEF < 40% • N o t r e a t m en t i n t e rr u p t ion s o r di s c o n t i nu a t io n s • T r e a t m en t E m e r g e n t A dv e r s e E v en t s • P l a c e bo 85 % o f pa r t i c i pa n t s • A f i c a m t e n 88 % o f pa r
Slide 98: REDWOOD-HCM: Cohort 3
REDWOOD - HCM: Cohort 3 Dose 1 Dose 2 Dose 3 C o h o r t 3 5 mg 1 0 mg 1 5 mg A m b u l a t o r y C a r d i a c M o n i t o r i n g E c h o c a r d io g r a m D o s e t i t r a t io n P a t i e n t s w i t h s y m p t o m a t i c o H C M , and resting or provoked LVOT gradient ≥ 50 mmHg S t u d y V
Slide 99: Open Label Extension Trial
Open Label Extension Trial Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 99 REDWOOD - HCM OLE open for eligible patients who completed REDWOOD - HCM • P r i m a r y e ndp o i n t: i n c i d e n c e of A E s & L V
Slide 100: Aficamten: Clinical Development Plan for HCM
W e l l t o l e r a t e d d o s e w i t h d e s i r e d P D e ff e c t s o H C M p a t i e n t s P l a c e b o C o n t r o ll e d E c h o c a r d i o g r ap h y E nd po i n t s o H C M p a t i e n t s E x e r c i s e E n d p o i n t ( p e a k V O 2) E x t e n s io n s t u d y L o n g - t e r m s a f
Slide 101: Novel Approach May Address Multiple Unmet Patient Needs
Novel Approach May Address Multiple Unmet Patient Needs N o F D A - a p p r o v e d t h e r a p i e s nHCM No n - O b s t r u c t i ve H C M HFpEF He a r t F a i l u r e w i th P r ese r v e d E j ec t i o n F r a c t i o n O b s tr u c t i ve H C M oHCM Aficamten ( C a r d i ac m y o s i n Inhibito
Slide 102: Introducing SEQUOIA-HCM
Introducing SEQUOIA - HCM Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 102
Slide 103: SEQUOIA-HCM: Strategic Objectives
SEQUOIA - HCM: Strategic Objectives In patients with symptomatic, uncontrolled oHCM treated with aficamten , demonstrate: • Robust improvement in exercise capacity using gold standard methodology • Parallel alleviation of heart failure symptoms and improvement in QoL • High level of achievement of t
Slide 104: SEQUOIA-HCM: Key Entry Criteria
SEQUOIA - HCM: Key Entry Criteria Males and females between 18 and 85 years of age, inclusive, at screening Body mass index <35 kg/m 2 Diagnosed with oHCM per the following criteria: • Has LV hypertrophy and non - dilated LV chamber in the absence of other cardiac disease AND • Has end - diast
Slide 105: SEQUOIA-HCM: Endpoints
SEQUOIA - HCM: Endpoints Primary Objectives and Endpoints Exercise capacity in patients with oHCM ∆ pVO 2 by CPET from baseline to Week 24 Secondary Objectives and Endpoints To evaluate the effect on health status ∆ i n K CC Q f r o m b a s e li n e t o W eek 1 2 a n d W eek 2 4 To evaluate the effe
Slide 106: SEQUOIA-HCM: Phase 3 Trial Design
SEQUOIA - HCM: Phase 3 Trial Design Individualized dose up - titration based on echocardiography: LVEF ≥55%, Post - Valsalva LVOT - G ≥30 mmHg Echocardiogram CPET K CC Q N Y H A Echocardiogram P a t i e n t s w i t h o H C M t r ea t e d w i t h standard of care w i t h po s t - V al s al v a p ea k
Slide 107: CMR Sub-Study: Exploratory Objectives, Endpoints
CMR Sub - Study: Exploratory Objectives, Endpoints Cardiac Magnetic Resonance Serial imaging gives us the highest definition images that can non - invasively quantify : • C a r d i a c s t r u c t u r e • C a r d i a c f un c t i o n • Tissue composition Charting the Commercial Course : Analyst & In
Slide 108: Trial On Track to Start by Year End
T r i a l On T r a c k t o S t a r t b y Y e a r E n d Aficamten : SEQUOIA - HCM Probable Sites US 35 Canada 2 Italy 10 France 7 Germany 9 C z ec h R e p u b l ic 2 Denmark 3 Hungary 1 Netherlands 3 Poland 3 Portugal 2 Spain 5 UK 3 Israel 5 China ~8 Japan TBD Charting the Commercial Course : Analyst
Slide 109: Franchise Strategy
Franchise Strategy Andrew Callos, EVP, Chief Commercial Officer N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 110: Launch Guiding Principles Strengthen Franchise Build
Launch Guiding Principles Strengthen Franchise Build Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 110 Design commercial organization to optimize U.S. launch of omecamtiv mecarbil , enable geographic expansion & p
Slide 111: Limited Incremental Cost For Future U.S. CV Launches
Limited Incremental Cost For Future U.S. CV Launches Building Today … To optimize value capture for launch of o m e c a m t i v m e c a r b i l • B u il d i n g d ee p , l o n g - t e r m r e l a t i o n s h i p s Cardiologists … T o L e a d T o m o r r o w T o s upp o r t f u t u r e lau n c h e s
Slide 112: Significant GTM Synergies Between OM, Aficamten
Significant GTM Synergies Between OM, Aficamten C o mm e r c i a l Support Functions M e d ic a l Affairs C o r p o r a te Support Functions Utilize resources across brands (e.g., access, analytics, …) MSLs qualified to cover both HFrEF and HCM Avoid costs of duplication (IT, Finance, HR, …) Sales T
Slide 113: Commercializing Aficamten Leverages Launch Build-Out
C o mm e r c i a li z i ng A f i c am t e n L e v e r a g e s L a un c h B u i l d - O ut C o mm e r c i a l l e a d e r s h i p S c a l a b l e o r g a n i za t io n d e s i g n M a r ke t i n g & a n a ly t i cs F i e l d t ea m s M e di c a l A ff a i r s i n c l . M S L s S y s t e m s a n d b u
Slide 114: Financial Foundation & Corporate Development
Financial Foundation & Corporate Development Ching Jaw, CFO F o r I n v e s t o r s O n ly
Slide 115: Current Financial Summary
Current Financial Summary Debt 2021 Guidance Cash Runway ~$183M Term loan plus convertible debt Est. net cash utilization for 2021 ~3 YRs ** E s t . c a s h r un w a y @ YE 2 1 C a s h o n H a n d t o E O Y ~$600M * E s t . c a s h b a l a n c e @ YE 2 1 *Excludes potential proceeds from business de
Slide 116: Building Cytokinetics' Business on Solid Financials, Deals
Building Cytokinetics’ Business on Solid Financials, Deals Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 116 B a l a n c e d a pp r o a c h to r a i s i n g c a p i t a l t h r o u g h e q u i t y r a i s e a n d
Slide 117: Financing History
Financing History Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 117 Capital raised: combination of strategic partners and investors As of 6/30/2021 Financing Equity U p f r o n t C a s h , O p t io n , & Milestone
Slide 118: We Are Aware of Investor Concern Regarding CV Launches
C o m p a n y C c o mm e r c i a li z e d a n e w m e di c i n e absent compelling pharmacoeconomic rationale. HEOR drives payer response B e tt e r t o f o c u s t o m a r ke t s w i t h h i g h m o r b i d i t y / m o r t a li t y an d h i g h e c o n o m i c b u r d e n F a il u r e t o l e a r n
Slide 119: Gating Commercial Spending to Achieve Profitability
Gating Commercial Spending to Achieve Profitability R e v enu e s E x p en s e s i f n o cost synergy E x p en s e s w i t h cost synergy Gate commercial investments to milestones: • N D A s u b m i s s i o n • N D A f ili n g by t h e F D A • N D A a p p r o v a l • S a l e s t h r es ho l ds Lever
Slide 120: Q&A
Q&A To ask a question in the room, please raise your hand. To ask a question online, type it into the tab on the left. N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 121: Closing Remarks
Closing Remarks Robert Blum, President & CEO N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly
Slide 122: One Molecular Target Supports Emerging CV Franchise
Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y 12 2 One Molecular Target Supports Emerging CV Franchise A c t i n Tropomyosin T h i c k f i l a m en t M y o s i n h ea d M y o s i n l e v e r a r m C a l c i u m A
Slide 123: Building a Cardiovascular Franchise
123 Charting the Commercial Course : Analyst & Investor Day 2021 N o t fo r P r o m ot i o n a l U s e , F o r I n v e s t o r s O n l y Building a Cardiovascular Franchise Continued Life Cycle Management, Expanded Development Overlapping Physician, Hospital, Payor Customer Segments Uncommon Franchi
Slide 124: B o x e d l u n c h e s a v
B o x e d l u n c h e s a v a ila b l e t o go Recording and slides to be made available online at cytokinetics.com N o t F o r P r o m ot io n a l U s e , F o r I n v e s t o r s O n ly