Cytokinetics, Inc. : Cytokinetics Announces Publication of Results from Phase II Trials of Tirasemtiv in Patients with ALS

Cytokinetics, Inc. : Cytokinetics Announces Publication of Results from Phase
                 II Trials of Tirasemtiv in Patients with ALS

Manuscripts Support the Design and Conduct of the Ongoing BENEFIT-ALS Trial

South San Francisco, CA, August 22, 2013 - Cytokinetics, Incorporated (Nasdaq:
CYTK) announced the  publication of  two manuscripts reporting  data from  two 
clinical trials of tirasemtiv, a novel mechanism fast skeletal muscle troponin
activator, in  patients  with  amyotrophic  lateral  sclerosis  (ALS).  These 
manuscripts are published  in the  journal Amyotrophic  Lateral Sclerosis  and 
Frontotemporal Degeneration  and  highlight  results from  Phase  II  clinical 
trials designed  to evaluate  the safety,  tolerability, pharmacokinetics  and 
pharmacodynamics of two different dosing regimens of tirasemtiv.

"These manuscripts  highlight  encouraging results  from  two prior  Phase  II 
clinical trials of tirasemtiv in patients with ALS," stated Jeremy M. Shefner,
M.D., Ph.D.,  Professor and  Chair,  Department of  Neurology at  the  Upstate 
Medical University, State  University of  New York,  and lead  author of  both 
publications. "Activation  of skeletal  muscle with  tirasemtiv, as  assessed 
under different  dosing regimens  in these  studies, appears  to be  generally 
well-tolerated and  to  impact positively  tests  of strength,  endurance  and 
respiratory function that may be relevant to preserving the functional  status 
of patients with ALS. I am looking forward to the availability of  additional 
data from the continuing development of this promising compound."

"We are  pleased  to  have  these data  published  in  a  prestigious  journal 
dedicated to reporting significant advances  in the treatment of ALS,"  stated 
Andrew A. Wolff,  MD, FACC,  Cytokinetics' Senior Vice  President of  Clinical 
Research and  Development  and Chief  Medical  Officer. "Results  from  these 
trials informed  our design  of BENEFIT-ALS,  our ongoing  Phase IIb  clinical 
trial of tirasemtiv, which we hope may demonstrate longer term safety and  the 
potential durability of clinically meaningful  effects of this drug  candidate 
in patients suffering from this grievous illness."

Manuscripts Published in Amyotrophic Lateral Sclerosis and Frontotemporal

One manuscript,  titled  "A  Study  to Evaluate  Safety  and  Tolerability  of 
Repeated Doses of Tirasemtiv in Patients with Amyotrophic Lateral  Sclerosis," 
reports data from two Phase II clinical  trials, designated as CY 4024 and  CY 
4025. In these trials, tirasemtiv  appeared to be well-tolerated by  patients 
with ALS, including  when receiving a  reduced dose of  riluzole. The  trials 
cited in this manuscript evaluated the tolerability of tirasemtiv at doses  up 
to 500 mg daily for up to three  weeks.  In CY 4024, tirasemtiv was given  in 
single daily doses of 125 mg, 250 mg, or 375 mg versus placebo for two  weeks, 
in one  cohort  without concomitant  riluzole  and  in a  second  cohort  with 
riluzole administered at a reduced dose of 50 mg once daily. In CY 4025,  the 
dose of tirasemtiv was titrated over three weeks of administration,  beginning 
with 125  mg twice  daily to  a  target of  250 mg  twice daily.  Safety  and 
tolerability were assessed, as well  as measures of function, muscle  strength 
and endurance. Results  showed that  tirasemtiv was  well-tolerated in  these 
patients, with dizziness  the most  common adverse event.  As predicted  from 
earlier non-clinical  and clinical  studies, co-administration  of  tirasemtiv 
with riluzole  approximately  doubled  the plasma  concentration  of  riluzole 
compared to the  administration of  riluzole without  tirasemtiv. Trends  were 
noted for improvement in the  ALS Functional Rating Scale-Revised  (ALSFRS-R), 
Maximum Minute Ventilation, and Sniff Nasal Inspiratory Pressure. The  authors 
concluded that  positive  trends  in  multiple  exploratory  outcome  measures 
support the further study of this  drug candidate for the potential  treatment 
of ALS. 

In the second  manuscript, titled "The  Relationship Between Tirasemtiv  Serum 
Concentration and  Functional  Outcomes in  Patients  with ALS,"  the  authors 
concluded that tirasemtiv appears  to have concentration-dependent effects  on 
both function and measures of strength and endurance when administered for  up 
to 21 days, even  when time is  eliminated as a  cofactor. In addition,  they 
reported that  both single  and repeated  dose studies  suggested  potentially 
beneficial effects on  measures of  function, muscle  strength and  endurance. 
Since the  outcomes measured  were  identical in  previous Phase  II  clinical 
trials of tirasemtiv in patients with ALS  and the duration of all the  trials 
was 21 days or less, the authors pooled data from all the trials and  assessed 
the relationship  between outcomes  and  plasma concentrations  of  tirasemtiv 
toassess consistency of observations and to increase sensitivity. The authors
pooled data  for ALSFRS-R,  three  pulmonary function  measures,  quantitative 
muscle strength, and submaximal handgrip endurance. Up to 855 values from  143 
patients   were   plotted    againstconcentrations   oftirasemtiv.    Linear 
associations between concentrations of tirasemtiv and changes from baseline of
clinical measures  were  estimated  using  a  repeated-measures  mixed  model. 
Statistically significant relationships between increases in these  functional 
measures and increasing plasma concentration  of tirasemtiv were observed  for 
all measures  except for  vital capacity.  The authors  concluded that  these 
findings support  the development  of this  drug candidate  for the  potential 
treatment of ALS.

Development Status of Tirasemtiv in ALS

Tirasemtiv (formerly CK-2017357) is  currently being evaluated in  BENEFIT-ALS 
(Blinded Evaluation of Neuromuscular  Effects and Functional Improvement  with 
Tirasemtiv  in   ALS).  BENEFIT-ALS   is  an   international,   double-blind, 
randomized, placebo-controlled, Phase IIb clinical trial designed to  evaluate 
the safety, tolerability and potential  efficacy of this novel drug  candidate 
in patients with  ALS. BENEFIT-ALS  is designed to  enroll approximately  680 
patients who  will  first  complete  one week  of  treatment  with  open-label 
tirasemtiv at  125 mg  twice  daily. Following  completion of  the  open-label 
period, patients  will  be randomized  to  receive 12  weeks  of  double-blind 
treatment with twice-daily oral ascending doses of tirasemtiv beginning at 125
mg twice daily and increasing weekly up to 250 mg twice daily or a dummy  dose 
titration with placebo.  Clinical assessments will  take place monthly  during 
the  course  of  treatment;  patients  will  also  participate  in   follow-up 
evaluations one and four  weeks after their final  dose. The primary  efficacy 
analysis of BENEFIT-ALS will compare the mean change from baseline in the  ALS 
Functional Rating Scale in  its revised form  (ALSFRS-R) on tirasemtiv  versus 
placebo. Secondary endpoints will include Maximum Voluntary Ventilation  (MVV) 
and other  measures  of respiratory  and  skeletal muscle  function.  Patients 
taking riluzole at the  time of enrollment and  who are randomized to  receive 
tirasemtiv will receive riluzole at a reduced dose of 50 mg daily.

About Cytokinetics

Cytokinetics is  a clinical-stage  biopharmaceutical  company focused  on  the 
discovery and development of novel  small molecule therapeutics that  modulate 
muscle function for the  potential treatment of  serious diseases and  medical 
conditions.  Cytokinetics'  lead  drug  candidate  from  its  cardiac   muscle 
contractility program, omecamtiv mecarbil, is in Phase II clinical development
for the potential treatment  of heart failure. Amgen  Inc. holds an  exclusive 
license worldwide to develop and commercialize omecamtiv mecarbil and  related 
compounds,   subject    to    Cytokinetics'    specified    development    and 
commercialization  participation   rights.   Cytokinetics   is   independently 
developing tirasemtiv,  a  fast  skeletal muscle  activator,  as  a  potential 
treatment for diseases  and medical conditions  associated with  neuromuscular 
dysfunction. Tirasemtiv is currently the subject of a Phase II clinical trials
program and has been granted orphan drug designation and fast track status  by 
the U.S. Food and Drug Administration and orphan medicinal product designation
by the European Medicines  Agency for the  potential treatment of  amyotrophic 
lateral  sclerosis,  a  debilitating  disease  of  neuromuscular   impairment. 
Cytokinetics is collaborating with Astellas Pharma Inc. to develop CK-2127107,
a  skeletal  muscle  activator  structurally  distinct  from  tirasemtiv,  for 
non-neuromuscular indications. All of these  drug candidates have arisen  from 
Cytokinetics' muscle  biology focused  research  activities and  are  directed 
towards  the   cytoskeleton.  The   cytoskeleton  is   a  complex   biological 
infrastructure  that  plays  a  fundamental  role  within  every  human  cell. 
Additional   information    about   Cytokinetics    can   be    obtained    at

This press release  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  Harbor  for  forward-looking 
statements. Examples  of such  statements  include, but  are not  limited  to, 
statements  relating  to   Cytokinetics'  and  its   partners'  research   and 
development activities, including the conduct, design, enrollment,  progress, 
completion and results of clinical trials, and the significance and utility of
clinical  trial  results;  and  the  properties  and  potential  benefits   of 
tirasemtiv and Cytokinetics' drug candidates, including the potential benefits
of tirasemtiv in  treating patients  with ALS.  Such statements  are based  on 
management's current expectations,  but actual results  may differ  materially 
due to  various  risks  and  uncertainties, including,  but  not  limited  to, 
Cytokinetics anticipates that  it will  be required  to conduct  at least  one 
confirmatory Phase III clinical trial of tirasemtiv in ALS patients which will
require significant additional funding,  and it may be  unable to obtain  such 
additional funding on acceptable terms,  if at all; potential difficulties  or 
delays  in   the  development,   testing,  regulatory   approvals  for   trial 
commencement, progression or product sale  or manufacturing, or production  of 
Cytokinetics' drug candidates that could slow or prevent clinical  development 
or product approval, including risks that current and past results of clinical
trials or preclinical studies may not be indicative of future clinical  trials 
results, patient enrollment for or conduct of clinical trials may be difficult
or delayed, Cytokinetics'  drug candidates  may have adverse  side effects  or 
inadequate therapeutic  efficacy, the  U.S. Food  and Drug  Administration  or 
foreign regulatory agencies may delay or limit Cytokinetics' or its  partners' 
ability to conduct clinical trials, and  Cytokinetics may be unable to  obtain 
or maintain patent or trade  secret protection for its intellectual  property; 
Amgen's and  Astellas'  decisions  with respect  to  the  design,  initiation, 
conduct, timing  and  continuation  of development  activities  for  omecamtiv 
mecarbil and CK-2127107,  respectively; Cytokinetics  may incur  unanticipated 
research and development  and other costs  or be unable  to obtain  additional 
financing necessary to conduct development  of its products; Cytokinetics  may 
be  unable  to  enter  into  future  collaboration  agreements  for  its  drug 
candidates and programs on acceptable terms, if at all; standards of care  may 
change, rendering Cytokinetics' drug candidates obsolete; competitive products
or alternative  therapies may  be developed  by others  for the  treatment  of 
indications Cytokinetics' drug  candidates and potential  drug candidates  may 
target; and risks  and uncertainties  relating to  the timing  and receipt  of 
payments from  its  partners, including  milestones  and royalties  on  future 
potential product sales under Cytokinetics' collaboration agreements with such
partners. For further information regarding  these and other risks related  to 
Cytokinetics' business, investors  should consult  Cytokinetics' filings  with 
the Securities and Exchange Commission.


Cytokinetics, Inc.
Joanna L. Goldstein (Investors & Media)
(650) 624-3000


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Source: Cytokinetics, Inc. via Thomson Reuters ONE
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