Diane Weiser - Vice President of Corporate Communications and Investor Relations Sharon Barbari - EVP, Finance and CFO Robert Blum - President and CEO Andrew Wolff - SVP and CMO Fady Malik - SVP, Research and Development.

Jason Butler - JMP Securities Chad Messer - Needham & Company Joe Pantginis - Roth Capital Partners Roy Buchanan - Piper Jaffray Vernon Bernardino - MLV Company George Zavoico - Jones Trading.

Good afternoon and welcome, ladies and gentlemen, to Cytokinetics' Second Quarter 2015 Conference Call. At this time, I would like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call for questions and answers after the presentation.

I will now turn the call over to Diane Weiser, Cytokinetics' Vice President of Corporate Communications and Investor Relations. Please go ahead..

Good afternoon and thank you for joining us on this conference call today. Leading today's call is Robert Blum, our President and Chief Executive Officer.

Following Robert's initial comments, Andy Wolff, our Senior Vice President and Chief Medical Officer, will provide an update regarding the start of VITALITY-ALS, our Phase III clinical trial for tirasemtiv, our first-in-class fast skeletal muscle troponin activator, which we are developing for the potential treatment of Amyotrophic Lateral Sclerosis or ALS.

Then Fady Malik, our Senior Vice President of Research and Development will provide an update on our clinical development program for CK-27107 or CK-107, our next generation fast skeletal muscle troponin activator, and our plans for our Phase II clinical trial in spinal muscular atrophy or SMA.

Fady will also provide an update on the clinical development program for omecamtiv mecarbil, our first-in-class cardiac myosin activator, which is being developed for the potential treatment of heart failure.

Sharon Barbari, our Executive Vice President of Finance and Chief Financial Officer will then provide a financial overview for the quarter and Robert will conclude with additional perspective and comments on our key milestones for 2015. We will then open the call for questions.

Please note that the following discussion, including our responses to questions, contains statements that constitute forward-looking statements for the purposes of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to statements related to our financial guidance and collaborations with Amgen and Astellas, to the initiation, enrollment, design, conduct and results of clinical trials and to other research and development activities.

Our actual results might differ materially from those projected in these forward-looking statements.

Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our most recent annual report on Form 10-K, our quarterly reports on Form 10-Q, and our current reports on Form 8-K.

Copies of these documents may be obtained from the SEC or by visiting the Investor Relations section of our website. These forward-looking statements speak only as of today. You should not rely on them as representing our views in the future. We undertake no obligation to update these statements after this call.

And now I will now turn the call over to Robert..

Thank you, Diane and thank you to everyone on the line for joining us for this call today. I first want to take a moment to formally introduce and welcome Diane who joined our company a few months ago to lead our corporate communications and investor relations function.

Diane brings nearly 30 years of communications experience to this newly created position at Cytokinetics. We are thrilled to have her join our team to take our external and internal communications to the next level at a time when we have so many exciting milestones ahead of us.

Recently, we achieved a watershed moment at Cytokinetics which also was very important to the ALS community at large. We started a Phase III clinical trial for tirasemtiv, our first-in-class a fast skeletal muscle troponin activator which we are developing for the potential treatment of ALS.

VITALITY-ALS is the Company’s first Phase III clinical trial and we believe is the only multinational Phase III Clinical trial enrolling patients with ALS at this time. The trial is designed to confirm and extend results observed in BENEFIT-ALS, our Phase IIb trial for which results were presented last year.

In that trial tirasemtiv reduced the decline of slow vital capacity a key measure of respiratory function in patients with ALS. Based on these findings we have designed VITALITY-ALS to assess the effects of tirasemtiv versus placebo on slow vital capacity and also other measures of respiratory function in patients with ALS.

Andy will elaborate on the trial design and on our progress getting the trial up in running shortly.

The launch of VITALITY-ALS comes at an exciting time coincident with the one year anniversary of the Ice Bucket Challenge, the world wide social media phenomenon that significantly raised awareness of this devastating disease as well as substantial funds for research and patient support services.

We are honored to have been awarded recently a $1.5 million grant from ALS Association to support the conduct of VITALITY-ALS as well as the collection of clinical data and plasma samples from patients in VITALITY-ALS in order to help advance the discovery of potential useful biomarkers in this disease.

This is a unique collaboration between a non-profit academia and industry and represents the first time plasma samples from an industry sponsored clinical trial are being shared with the ALS research community.

Through this collaboration we hope to fundamentally alter the treatment paradigm for this devastating disease and arm the ALS community with meaningful new information that may lead to additional avenues of clinical research.

We’ve also advanced planning for our Phase II clinical trial with CK-107 for the potential treatment of spinal muscular atrophy of SMA an orphan hereditary disease for which there are no current therapies most often diagnosed in infants and young children.

We continue to engage with leading researchers in the field along with our partner Astellas to design a clinical trial that will be focused on older children, adolescence and adults with SMA, a population that has not been the primary focus of other recent investigational approaches to the treatment of this disease.

This follows our recent poster and on oral presentation of three Phase I studies at the 19th International SMA Researcher Meeting during the CureSMA conference on which Fady will expand shortly. Turning now to our Heart Failure Program with Omecamtiv Mecarbil, our first-in-class Myosin Activator.

More than 400 patients have now concluded dosing and the expansion phase of COSMIC-HF. We are nearing completion of this trial and we look forward to announcing data from this our last planned Phase II trial in the United States in the fourth quarter.

In anticipation of this data, we held meetings with our partner Amgen to plan a potential Phase III program to evaluate Omecamtiv Mecarbil heart failure patients which we anticipate could begin in 2016.

Let me now turn the call over to Andy so that he can elaborate on the start of VITALITY-ALS our Phase III Clinical trial of tirasemtiv in patients with ALS..

Thank you Robert. VITALITY-ALS which stands for Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices after Treatment for a year in ALS is a Phase III clinical trial designed to assess the effects of tirasemtiv versus placebo on slow vital capacity or SVC and other measures of respiratory function in patients with ALS.

The objectives of the trial are to confirm and expand the results observed in our Phase IIb study benefit ALS from which we learned many lessons that have been applied to this study design. I will quickly recap what we learned from BENEFIT-ALS and then discuss the study design of VITALITY-ALS.

BENEFIT-ALS was the first clinical trial of its size to demonstrate a positive and potentially clinically meaningful effect on respiratory muscle function and skeletal muscle strength in patients with ALS.

The effect of tirasemtiv to reduce the decline in SVC and benefit ALS was robust, specifically the effect was similar in magnitude across all pre specified and other sub groups evaluated and were statistically significant within the majority of those sub groups.

Tirasemtiv may have cumulative effects on vital capacity that persist beyond the discontinuation of treatment, something we will attempt to confirm in VITALITY-ALS.

Vital capacity is a clinically meaningful measure used to inform important clinical decision and to predict disease progression, thus the effect of tirasemtiv to reduce the decline in vital capacity may be clinically meaningful updations [ph] with ALS and warrants further investigation for a longer duration in VITALITY-ALS.

VITALITY-ALS is a multinational randomized double blind placebo controlled trial that is designed to enrol 445 patients with possible, probable or definite ALS diagnosed within 24 months and with a base line vital capacity at least 70% have predicted based on age, sex and height.

Patients maybe enrolled whether or not they are [Indiscernible] all therapy. The primary endpoint of the trial is the change from base line in SVC to be assessed after 48-weeks of double blind placebo control treatment.

Secondary endpoints to be accessed after 48-weeks of double blind placebo control treatment include time to decline in any of the three respiratory demands of the ALSFRS-R, or death.

The other secondary endpoints were listed in our press release announcing the start of VITALITY-ALS and can be found in clinical trials.gov and includes the time to various milestones in the decline in respiratory function associated with disease progression in patients with ALS.

Patients enrolled in VITALITY-ALS will receive two weeks of open-label treatment with tirasemtiv administered at 250 milligrams per day and will then be randomized to double blind treatment with placebo or one of three target tirasemtiv dose levels, 250 milligrams per day, 375 milligrams per day or 500 milligrams per day in a 3:2:2:2 ratio for a total of 48 weeks of randomized double blind placebo controlled treatment.

Then, in a four-week double blind tirasemtiv withdrawal case, patients on tirasemtiv will be randomized either to continue the double blind tirasemtiv dose they were receiving or to be withdrawn to placebo in a one to one ratio.

Patients who had been receiving placebo during the 48-weeks of double blind placebo control treatment will continue to receive placebo during this phase. We expect VITALITY-ALS to be conducted in more than 75 centers in North America and Europe and to include most of the sites to participate and benefit ALS.

As Robert has previously mentioned, the design for a VITALITY-ALS was finalized following interaction with both FDA and EMA.

Based on these communications, we believe SVC is an appropriate primary endpoint in conjunction with secondary endpoints which would associate a reduction in the progressive decline in SVC by tirasemtiv to prolongation of the time to clinically meaningful events such as the initiation of mechanical ventilation, the onset of respiratory insufficiency and other respiratory events associated with these progressions in patients with ALS.

Turning to our start up activities, during the quarter we met with many of our North American and European investigators at an Investigator Meeting to the VITALITY-ALS in San Fransisco and in London.

We were pleased to be received with such enthusiasm at both meetings as we unveiled the details of the trial and provided training regarding the necessary assessment as a means to ensure consistent, conduct and the trial of the prop side locations. We anticipate enrolling patients into the trial over the next six to nine months.

In parallel, we have remained engaged with our partners in the U.S. and Europe. ALS Advocacy community will continue to represent the powerful voice of the patients and caregivers.

Finally, we are honored to have been awarded a $1.5 million grant from the ALS Association to support VITALITY-ALS as well as the unique collaboration between the ALS Association narrowing our logical constitute and Cytokinetics during the conduct of VITALITY-ALS.

As part of the trial and for the first time platinum samples and longitudinal clinical data will be obtained from patients enrolled in VITALITY-ALS which will be integrated into the integrated into the NEALS Repository to support ongoing activities within the scientific community for research on biomarkers from patients with ALS.

The NEALS Repository is a resource for the academic research community to identify biomarkers that may help to access disease progression and underlying disease mechanisms in ALS. We are extremely gratified to have the opportunity to contribute this way to the ALS community.

With that update on our plans for tirasemtiv, I will now turn the call over to Fady for an update on our SMA and heart failure programs..

Thank you Andy. Turning first to the development of CK-107, our next generation skeletal muscle troponin activator which is partnered with Astellas. We continued to make progress against our goal of initiating a Phase II clinical trial in patients with SMA in the second half of this year in accordance with an agreed plan with Astellas.

As you know SMA is a disease in great need of new therapies to address functional limitations and modified disease progression and we believe CK-107 has the potential to improve muscle function especially in adolescence and adult patients when used alone or in combination with other therapeutic approaches that are being pursued, including replacement therapy or correction of the faulty SMN1 gene, modulation of the low functioning SMN to backup gene and neuroprotection of motor neurons affected by the loss of the SMN protein.

In June, we presented a poster at the Annual CureSMA conference and were pleased to be selected onsite for oral presentation of data from three of our completed Phase I studies that evaluated the safety, tolerability, PK and PD effects of CK-107 in healthy volunteers.

In these studies, CK-107 was well tolerated at single doses up to 4000 milligrams and the PK profile was linear and those proportional across the range doses study.

Data from the Phase I studies also showed significant dose concentration and frequency dependant increases in the force and muscle contraction elicited by nerve stimulation in healthy volunteers. Increases in force were most evident in the midrange of nerve stimulation frequency.

Consistent with preclinical studies and correlated to the activities of daily living. Therefore we concluded that by directly increasing scalable muscle function CK-017 may enhance physical performance in patients with neuro muscular diseases including SMA.

These data prompted the expansion of our collaboration with Astellas to include in our muscular indication and a decision to proceed to a Phase II trial in patients with SMA which we will begin later this year in the fourth quarter. We outlined the plan for the study at our R&D day, but let me briefly recap it.

We plan to focus on SMA type 2, 3, and 4 patients those are both ambulatory and non-ambulatory and evaluate a range of endpoints including respiratory and other measures to scalable muscle function all in treatment to steady state with CK-107.

We anticipate enrolling approximately 75 patients treated for one or two months for up to 10 or 12 centers in the U.S. Turning to the development of omecamtiv mecarbil and COSMIC-HF the last of our planned Phase II trials. More than 90% or 400 patients have now concluded dosing in the expansion phase of the trial.

Data monitoring committee met during the quarter and again more recently and requested no changes in the conduct of the trial. As Robert mentioned we are on track to have data from this trial in the second half of this year but specifically in Q4.

And as we have previously stated the data from COSMIC-HF coupled with data from the ATOMIC-AHF trial will inform the potential progression of Omecamtiv Mecarbil into a Phase-III outcome study which we anticipate could begin in 2016.

As you’ll recall, from short term trials we’ve conducted with Omecamtiv Mecarbil over the years we know the signature pharmacodynamic effective Omecamtiv Mecarbil is to increase systolic ejection time, the amount of time that the left ventricle is contracting and injecting blood.

Corresponding increases in stroke volume, decreases in heart rate and other measures of cardiac performance occur. In addition, we have observed changes in the size of enlarge heart of these patient is reflected by decreases in end-systolic and end-systolic diameters.

COSMIC-HF trial is looking to confirm whether these effects are durable and maintained during 20 weeks of treatment. Again there is no pre-specified primary clinical efficacy endpoint rather the trials design to assess the safety, tolerability, pharmacokinetics and pharmacodynamic of longer term treatment with Omecamtiv Mecarbil.

Importantly will be eager to see pharmacodynamic affect for long treatment on cardiac performance on patients with heart failure due to systolic dysfunction which we hope maybe predictive over the long term clinical outcome.

As Scott Solomon of the Brigham and Women's Hospital committed at our R&D Day this quarter, what is unique about Omecamtiv Mecarbil is its potential ability to improve the true contract out function of the heart.

Finally this quarter we continue collaborating with Amgen on clinical and non-clinical development activities, as well regulatory and other planning activities related to the potential movement Omecamtiv Mecarbil into a Phase-III development program.

And with that on our cardiac and skeletal sarcomere program, I’ll turn the call over to Sharon for an update on our financials..

Thank you, Fady. As our press release contained detailed financial results for the second quarter of 2015 I’ll refer you to that public statement for the details of our P&L and balance sheet.

We ended the second quarter with approximately $108.2 million in cash, cash equivalents and investments which represents over 18 month of going forward net cash burns based on our revised 2015 financial guidance. Our guidance includes estimated cost of our planned Phase-III development activities for tirasemtiv in 2015 and 2016.

Revenues for the second quarter of 2015 were $6.5 million compared to $7.8 million during the same period in 2014.

Revenues for the second quarter of 2015 included $3 million of license revenues and $2.9 million of research and development revenues from our collaboration with Astellas, and $0.6 million in research and development revenues from our collaboration with Amgen.

Revenues for the same period in 2014 included $2.7 million of license revenues and $4.2 million of research and development revenues from our collaboration with Astellas, and $0.8 million of research and development revenues from our collaboration with Amgen.

Our second quarter 2015 R&D expenditures totaled $12.6 million from a program perspective for the second quarter approximately 79% of our R&D expenditures were attributable to our skeletal muscle contractility research and development activities which included both expenses associated with tirasemtiv and CK-107, 11% to our cardiac muscle contractility activities, and 10% to our other research activities.

Today we also announced revised financial guidance for 2015. We anticipate cash revenue to be in the range of $44 million to $47 million, cash R&D expenses to be in the range of $58 million to $61 million and cash G&A expenses to be in the range of $18 to $21 million.

This guidance includes the $30 million upfront payment from Astellas that will be deferred and recognized over a two year period ending in 2016 under generally accepted accounting principles and it also exclude the $15 million milestone payment earned in 2015 from Astellas and an estimated $3.6 million in non-cash related operating expenses primarily related to stock compensation.

That concludes the financial portion of today’s call. With that I’ll now turn the call back over to Robert..

Thank you, Sharon. In summary the second quarter of 2015 was a filled with momentum building events. We expect much of the same in the second half of the year. Starting the company’s first Phase-III clinical trial in patients with ALS is a key milestone for Cytokinetics.

We’re extremely encouraged by the enthusiasm from the ALS community as VITALITY-ALS gets underway.

The promise of advancing what could be the first new medicine to treat patients with ALS in over 20 years and the potential of the first drug that may slow the progressive decline in respiratory function that is a hallmark of the disease and the usual cause of death in patients with ALS should not be under estimated.

As you know, ALS patients faced a ruthlessly progressive disease that generally ends in respiratory failure, so the opportunity to slow that decline is extraordinary. We are equally excited by the feedback we are receiving from the SMA community as we advanced plans for our planned Phase-II trial of CK-107 in SMA.

At a time when there is growing interest in new therapeutic possibilities for this relentless disease. Cytokinetics leadership in neuromuscular diseases, muscle biology and drug development creates another perfect storm that is widely recognized by patients and caregivers and we are proud to stand alongside them.

Finally, we look forward to results for Omecamtiv Mecarbil from COMIC-HF which could be Cytokinetics most important value driver this year. The burden of heart failure is significant particularly given the aging of the population and Medicare’s increasing focus on reducing re-hospitalization for heart failure, a hallmark envious cycle of the disease.

Given the mortality and readmission rates in heart failure we believe that significant unmet clinical need still exist for potential drugs that can improve the underlying deficit of declining cardiac muscle function.

Therefore we believe the prospect of advancing Omecamtiv Mecarbil to a Phase-III trial in 2016 augurs well for adding a first-in-class cardiac Myosin activator to the suite of available therapies. Now, I’ll recap our expected milestones for the remainder of 2015.

For Tirasemtiv, we anticipate enrollment of VITALITY-ALS over the next six to nine months. For CK-107 we expect to initiate a Phase-II trial of CK-107 in patients with SMA in the fourth quarter of 2015. For Omecamtiv Mecarbil we expect results from COSMIC-HF to be available in the fourth quarter of 2015.

And we expect to continue joint development activities and collaboration with Amgen directed to the potential advancement of Omecamtiv Mecarbil to a Phase-III clinical development. Operator, that concludes the formal portion of our call today. I’d now like to open the call to questions, please..

[Operator Instructions] And our first question comes from the line of Jason Butler with JMP Securities..

Good afternoon, Jason..

Hi, Robert. Thanks for taking questions and congratulations on a progress.

First question just actually let me start on the financial side for Sharon, the increase in expense guidance, the small increases you had, are they driven by any changes in the clinical development programs, any trial design changes that you’ve made?.

Yes. So, when we gave our initial financial guidance on the fourth quarter call that financial guidance didn’t have the finalized protocol for this VITALITY-ALS. This guidance now has the final estimated for VITALITY. As well as we also signed revenue agreement for research with Amgen, so that’s the increase in the research or in the revenue amount..

Okay, great.

Then on VITALITY-ALS, Robert I understand it’s early, but any initial signals from the enrolling centers that gives you confidence in your enrollment time lines?.

No. I think you answered your own question. It is early. We’re focused right now generally to start up activities and what that means is site initiation visit et cetera, so I think it’s premature to comment on whether those enrollment projections of six to nine months are valid.

I hope that by the time of the next earnings call we’ll be able to do that..

Great. And then last question from me. Forgive me if I didn’t hear this correctly, but I think you said in your opening comments that you continue to have dialogue with Amgen about the Phase-III plans for Omecamtiv.

Is there any additional color you can give us there about how both you and Amgen view the program today obviously with the fact that you still need the data from COSMIC?.

So I’ll comment and maybe then ask Fady, if he wants to elaborate, but what I’d say is, by our preceding to his point with COSMIC and with the DMC having in each quarter reviewed the data and given us the thumps up. Well, I can speak for Amgen, I can say, certainly we find that to be highly encouraging.

The work streams are both non-clinical and clinical in regulatory and we and Amgen are jointly preparing for advancement to Phase-III something that isn’t definitive but increasingly looking like something we need to be best prepared to make happen in 2016.

So, the assumption is that we may proceed to those preparations with the idea towards getting a study underway in 2016 and there’s nothing that I would suggest otherwise..

Okay, great. Thank you. And thanks again for taking questions..

Thanks..

And your next question comes from Chad Messer with Needham & Company..

Hi, Chad..

Hi. Thanks Robert. Thanks for taking my question.

I just have one for you, so I’m going to ask you in a bit of blunt way because I’ve ask in other ways before and the reason I’m doing it because its remains the number one question that I get pretty much continually when I talk to investors about Cytokinetics right now and that’s about potential for an SPA for VITALITY.

I know in the past you’ve said something you’re still potentially discussing, but even if you were to take more time to get, I just A, anything you can comment on where you on the process and B, why you.

And I totally get why SVC is an endpoint that make sense for Phase-III but given that’s a new one why it’s not the best thing for shareholders to get an SPA before starting this study?.

Thank you for the question and you are being consistent by asking that question again. What I’ll say, if even you’ve asked it more bluntly I don’t know that I can give you any more of a satisfactory answer than I’ve given before.

To be clear, interactions we’ve had with each of FDA and EMA, we’ve been informed that they do not believe that SVC in and of itself would be approvable as an endpoint rather as we hope might be the case SVC together with secondary endpoints.

So I want to be clear about that, that’s why we use the expression confirm and extend the findings from BENEFIT-ALS, extending referring to both at a later time point, in this case 24 weeks versus 12 weeks as measured in BENEFIT-ALS, but also very importantly I should correlate with other secondary endpoints which we hope will favor tirasemtiv in VITALITY-ALS those including time to fall in respiratory questions in the ALSFRS and also time to other interventions.

Those secondary endpoints are just to be clear as well are listed in the description of VITALITY-ALS as could be found on the clinicaltrials.gov website. So your question relates to SPA and here again despite the fact that I gather it’s a question that you are getting.

I don’t think that we’ll be able to respond to your satisfaction simple to say that those conversations that we maybe having with regulatory authorities remain confidential.

There are advantages to having a SPA as we’ve discussed and there can be also disadvantages especially in a new indication area where we want to not limit the degrees of freedom we may have in a clinical trial that will be hopefully unprecedented in terms of demonstrating affects on respiratory functions. So maintaining flexibility is important.

I don’t think I’m going to be able to do any better than that. I’m certainly not willing on a call such as this to walk through the new ones and the play by play on our ongoing regulatory interactions. I don’t know Fady or Andy, if there is any further you would want to add..

No. I don’t think so..

I don’t think that probably what you were hoping for Chad, but that maybe the best I can do..

Okay. Well, thank you. And best of luck to you guys. And best of luck for the ALS patients..

Thank you, Chad..

Your next question comes from Joe Pantginis with Roth Capital Partners..

Hi, Joe..

Hi, all. Thanks for taking the questions and thank for the update. Robert, this maybe a question for Andy, but the question is with regard to inclusion criteria, obviously they are very similar with regard to VITALITY and BENEFIT and what I’m pointing to is the commentary about diagnosis whether it’s possible, probable or affinitive.

And I guess I wanted to see how those characteristics might have impacted patients in Phase-II.

Do they have the same sort of levels of generation or how does it really impact the study or an inclusion?.

So that is like just absolutely above standard inclusion criteria for any recent ALS study for the past decade or more. It’s always that same definition. So it’s no different from what we get in BENEFIT-ALS, or what other sponsors have done recently.

The big difference is that I would point you to is the vital capacity is higher than it was in BENEFIT-ALS, is they have to have 70% predicted vital capacity whereas in BENEFIT we began at 60% of predicted and reduce it to 50% of predicted before the study was over. And there are two reasons for that.

One, as you’ve heard after the open label treatment periods there’s fully over a year of double-blind treatment. So, we wanted just like patients that we felt could stay in the trial for long enough to provide meaningful data.

And two, as you may recall as discussing earlier there was evidence from BENEFIT-ALS when we did the sub-group analysis of vital capacity looking at those patients who are in the upper half at baseline versus those that were at the lower half at baseline.

The ones that had the high vital capacities that baseline also appeared to have a somewhat larger benefit from tirasemtive. So that was another reason to elevate that number. And then the only other real difference is this some limitations that they must have been diagnosed within two years. We didn’t have that in BENEFIT-ALS.

And the reason again why, it was a much shorter study. Now we have a longer study and we want to try to have a little more homogeneity about the patient population that we’re enrolling..

Got you. That’s very helpful. Thank you. And I guess to your points on the upper half in the vital capacity maybe to your earlier comment in your prepared script about how, you’d maybe seeing cumulative effects on vital capacity.

And I guess I would ask the question in the following way, based on that data and the fact that you are the only drug to show this effective at this point. The question is going to be highly speculative here sort of like the home run question.

You obviously need to complete the entire study, but with regard to the primary endpoint assessment at week 24 what is the regulatory potential to not stop the study early but being able to make drug available even on an accelerated basis?.

So we won’t – although the endpoint is assess at a time point that’s after 24 weeks of treatment, we won’t know any of the results of the study until after the full study has been completed.

And then at that point we certainly have every intention to allow those patients who have completed the study and who wish to continue on open label treatment to do so. But a broader program than that is beyond our ability to comment right now..

Right. And then I was alluding to even like you see many times with oncology where the SMB would look at it, and you’re are still blinded and they basically say, which just doesn’t make sense to have patients on placebo at this point, but I understand. Thank you very much..

Thank you, Joe..

Your next question comes from Roy Buchanan with Piper Jaffray..

Hi. It’s Roy in for Charles. Thanks for taking the questions..

Hi, Roy..

Hi.

I had a feel on BENEFIT, actually sorry, on VITALITY, so has the first patient been randomized or you still screening?.

Right now, again we’re focused to the startup activities, the site initiation visits, et cetera. So that’s the extent to which we are making comments about where we are..

Okay.

And then can you remind me if the study interims and with the screen failure rate you’re assuming?.

Andy just answered the question about interims. Right now we don’t have any interim looks into the data rather instead we’ll complete treatments on all patients before we’ll have an opportunity to see any of the data including the 24-week data.

What was your other question?.

Screen failure rate assumption?.

So we’ve been pretty conservative about that right now and we’re looking to the benefit ALS experience primarily to inform both screen failure as well as potential early terminations.

And in that way the study could be as we’ve taken certain steps and measures to hopefully improve tolerability and other aspects of the study, we may ultimately have improved upon that from what our experience was in BENEFIT-ALS..

Okay.

And then back to BENEFIT, do you guys to plan upload the patient level data to NEALS or PRO-ACT or somewhere else?.

You’re talking about after the conclusion of VITALITY-ALS?.

No.

Before I guess or anytime, I’m talking about the BENEFIT data?.

BENEFIT-ALS, we don’t have any current plans right now to upload that data to any public data basis. It’s something that’s been asked to us. And frankly right now we haven’t yet gotten that far where we might decide finally on how to approach it.

You could imagine as some companies have done that you would upload the placebo, arms of those studies and while the drug is still being evaluated no yet the treatment arms, but we have even gotten that far in our consideration of the issue..

Okay.

And then quick one on COSMIC, so it seems like the last patient should be on mid August, can you help us, maybe expect the data in early 4Q, last 4Q, to get some of your ideas there?.

I don’t think we’re going to refine the guidance anymore than that, I think we and Amgen both in our earnings call are pointing to Q4. You can do the math as it sounds like you may already be doing based on when we announced completion of enrollment.

But that said I wouldn’t focus simply to last treatment visit, rather last dosing because there is follow-up visits and also time to collect data, analyze or rather time to collect data, database lock and analysis and in that regard I think your best bet would be to focus to Q4..

Okay. Very good. Thank you..

Thank you..

Your next question comes from Vernon Bernardino with MLV Company..

Good afternoon, Vernon..

Hi, Robert. Good morning and thanks for taking my question. I just and you probably can’t answer this question, but I’m going to ask it in anyway.

Regarding your conversations with FDA can you share with us perhaps what the opinion may have been regarding SVC as important predictor of disease progression in ALS?.

Sure.

I’m going characterize obviously but our meetings with FDA and I’d say also with EMA there was a consensus view that SVC is indeed an important prognostic and predictive factor, it’s a good measure, its quantitative, but it is a measure that should be correlative presumably therefore also with other effects in endpoints that track with respiratory function as well.

As we’ve stated I think in meetings with you and others, SVC happens to be vital capacity.

It happens to be that measure that in the published literatures demonstrated to be both prognostic of disease progression, the rate of progression also survival, also the published guidelines underscore how vital capacity should be an important measure to inform other interventions for instance, non-invasive ventilation.

I don’t think there is any questioning of that in our conversations with regulatory authorities both FDA and DMA understand that and they point back to us and it’s a very valid one is if in fact this drug is having an effect to slow the decline in vital capacity.

So to should it correspond with these other endpoints in terms of increasing the time to a fall in respiratory domains of ALSFRS or time to interventions, time to respiratory failure and we agree.

So that’s why we have design this study both with the primary endpoint of vital capacity something that we know well from BENEFIT-ALS and we can understand best how use that information in the conduct of VITALITY-ALS but also to extend this study to later time points, we’re hopefully we’ll see these effects on secondary endpoints as well, and I think that was what FDA and EMA ask about it, when they said confirm and extend these findings..

So then, to also paraphrase they then going to look at the totality of data and its hard, too early have an idea what waiting they’re going to put on any measure that will help them decide that you now have a package that where they would recommend you submit an NDA [ph]?.

I think your point is a good one.

That’s the crops [ph] of the issue and to the earlier question and my response it is always, to always thus with FDA and DMA it’s the totality of the data and that’s where we’ve designed VITALITY-ALS with the objective of demonstrating in effect we hope that favors tirasemtiv both with respect to the primary efficacy endpoint but also one or more secondary endpoints..

And as you know I’m speaking to you and Andy the cumulative effect on SVC as always intrigued me, what are the measures that come together will give you the picture as to the cumulative effects and them being positive in aggregate giving an idea that the cumulative effects are responsible for a so and so measure of improvement or slowing of declines?.

So maybe to answer that question I’ll ask Andy first to comment on the ordering of the secondary endpoints and then maybe ask Fady to comment on why we might had prophesized that tirasemtiv could have effects downstream and even cumulative on some of those secondary endpoints..

Well first of all I think what I thought we meant when we were talking about cumulative effects was just the fact that in BENEFIT-ALS as you may recall the difference between the tirasemtiv group and the placebo group continued to increase overtime.

The curves were divergent throughout the 12-weeks of the study, so that and four weeks the difference between the two groups was on the order of around three percentage points and by 12 it was close to six percentage points.

And so, in VITALITY-ALS where we study patients for much longer and there is no reason to suspect that the curves [ph] may not continue to diverge that way and so we might have a much larger treatment effect later on in the trial.

If that is true therefore then one would imagine if vital capacity is declining more slowly in patients on tirasemtiv and because it is such a reliable predictor of disease one would imagine that had studied much longer than benefit ALS as we have now you would begin to see patients on placebo having declined in the three questions related to respiratory function in the ALSFRS-R and not so many happening in the patients being treated with tirasemtiv.

So that’s the first secondary endpoint is trying to decline one point in any of the three respiratory questions in ALSFRS-R [Indiscernible] debt. And then the next one is time to a decline of at least 20 percentage points in the SVC and you can and at this time I’ll just remind you, you can go onto clinical trials.gov and they are there.

And they are in the order in which they would be analyzed in the so-called close testing procedure that we used to account for multiple testing and keeping the error and the P value appropriate..

Thank you for that clarity. So obviously it’s the goal is to slow this decline and therefore hopefully the result is a longer life for these patients. Now at the conclusion of the study have you thought or are there any plans for an extension phase of treatment for these patients..

Yes we do believe that after the study have completed, well not even after the study has completed but more accurately as patients complete the study they would be offered the opportunity to go onto open label tourist center..

Terrific, and that leads me to the question that was first asked by Ted and that is perhaps not at FDA but if there is a profound benefit that you see at the end of this study and therefore you go to an extension phase, would that put you in a position where you could perhaps request accelerate the approval whereby the FDA could give you conditional approval and therefore an extension phase therefore confirmed the long term benefits of tirasemtiv..

It’s conceivable but as Robert has already mentioned it’s going to depend on totality and the strength of the data. If we see a just whopping effect on vital capacity and clear effects on some of the secondary endpoints it might not even be an accelerated approval. It might just be an outright approval, but that would be the homerun scenario.

And I think you can imagine things in between that and the negative trial. We don’t expect the negative trial, so it really will depend on how robust and how large the treatment effect is that we observe..

So couple of points just to add one is, to your point that is an option that is on the table at that point in time but it would not necessarily require data from the open label extension in order to be able to have a conversation about either accelerated or conventional approval either with FDA or EMA those are things that I think are all fair game.

Secondly, as just underscore in Andy’s comments you referred to percentage points and I want to make certain that you and others understand that’s absolute percentage points on a background of a decline of roughly three percentage points per month in the placebo patients in their slow vital capacity that magnitude of difference approximately five to six percentage points at the end of 12 weeks represents a relative reduction of over 60% I should say.

So, I just want to make sure that that was also clear..

Okay, so and just to confirm that, that’s relative to base line and not relative to improvement over placebo..

That’s relative to – while in both cases it’s changed from baseline both with respect to placebo and also in the treated group..

Right, to elaborate we are just testing the hypothesis that change from base line which will almost really be a decline as it wouldn’t benefit the decline from base line in patients on placebo will be significantly greater than the decline from base line in patients onto your center..

Terrific. Thanks for the clarity and I’m looking forward to the pieces coming together..

Thank you..

And our final question comes from the line of George Zavoico with Jones Trading.

Hi George, good afternoon..

Hi Robert, Andy, Fady, Sharon. Just maybe delayed with that point a little bit more.

What is the powering of the study, you’ve cut the number of patients almost in half, but you’ve increased the duration so you’re going to see a larger change in SVC and you’re most likely going to see a large change in SVC but what is the powering they have allowed to do that now in a number of patients and what is the exact what was the parameter that you are looking forward to see a change the 15% change in SVC they expect to see between the two groups..

So I’ll take a first stab at that and Andy you can add to it as you wish. The powering is certainly a function of a lot of different assumptions including the not only the number of patients and the magnitude of effect but also the early termination rate as we experienced and benefit ALS.

So we designed VITALITY-ALS to detect at 24 weeks the magnitude of effect that was observed and benefit ALS at 12 weeks.

And in using the same assumptions with respect to early termination at 24 weeks we have over 80% power to detect that difference using those much more conservative assumptions as we may see early termination rates decline with more longer, slower dose titration and other measures that we’ve implemented in VITALITY-ALS compared to benefit ALS that number approaches 90% and can exceed 90% depending on what numbers you use in those assumptions.

And so it’s difficult to say how is the study powered, in effect it depends on which assumptions you use on early termination and magnitude of effect.

As Andy pointed out, the magnitude of difference favoring tirasemtiv versus placebo was increasing from week four to week eight and week eight to week twelve and benefit ALS and may continue to increase as we now take patients out to 24 weeks.

But to be conservative we built VITALITY-ALS around the magnitude of effect observed at 12 weeks in BENEFIT-ALS..

Yes so you are queuing your results to favor – for a more favorable outcome by doing so..

I think we’ve leaned to the conservative in the design of this study..

Yes I mean that seems apparent and as Andy indicated even if the curves don’t diverge but they stay constant, yes the 24 weeks is still going to meet your end point it sound like..

I think in that case we have at least 80% and possibly over 90% power to detect that depending on what assumptions you use with regard to early terminations..

Okay..

So that seems to be the first hurdle, the second hurdle then is the mix of secondary endpoints that you are going to be measuring and it seems to me that both you and the FDA and the EMA, when you are talking about the totality of effect there are so many variables in there and there is so many they were outcomes that it’s almost like you are inventing your own endpoint together with the SVC could in fact turn out to be registerational..

Here’s where we are exploring the new pharmacology in as much as tirasemtiv we believe is the first investigational medicine to demonstrate effects on respiratory function.

As such the choice of secondary endpoints the rank order again hierarchy of them and how you proceed through them in a statistical way all have to be pre specified in a statistical analysis plan.

But to your point you are going to want to see the totality of that data in order to understand where the cumulative effect may lie and that’s where this has to be a dynamic process..

Okay. Sounds like a very interesting design conservatively planned with an outcome that I hope for everybody’s sake especially the patients will be a positive on. Thanks very much..

Thank you, George..

Thank you, George..

Thank you. And I would now like to turn the conference back over to Mr. Blum for any closing remarks..

Thank you, operator. And thank you to all the participants of our teleconference today. I hope you’ll agree that we had a productive quarter in the second quarter and we have some exciting prospects as we look forward to the second half of this year.

We appreciate your continued support and interest in Cytokinetics and operator with that we can now conclude the call..

Thank you for your participation. This does conclude today's conference call and you may now disconnect..