Cytokinetics' (CYTK) CEO Robert Blum on Q1 2014 Results - Earnings Call Transcript

Cytokinetics, Inc. (NASDAQ:CYTK)

Q1 2014 Earnings Conference Call

May 6, 2014 4:30 PM ET

Executives

Sharon Barbari – Executive Vice President-Finance and Chief Financial Officer

Robert I. Blum – President and Chief Executive Officer

Andrew A. Wolff – Senior Vice President-Clinical Research and Development, and Chief Medical Officer

Fady I. Malik – Senior Vice President-Research and Early Development

Analysts

Roy Buchanan – Piper Jaffray & Co.

Chad J. Messer – Needham & Co. LLC

Larry Smith – SmithOnStocks

Operator

Good afternoon and welcome ladies and gentlemen to the Cytokinetics’ First Quarter 2014 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 request of the company, we will open the call for questions and answers after the presentation.

I will now turn the call over to Sharon Barbari, Cytokinetics’ Executive Vice President of Finance and CFO. Please go ahead.

Sharon A. Barbari

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. Robert will be making opening remarks regarding recent corporate highlights. Following Robert’s initial comments, Andy Wolff, our Senior Vice President of Clinical Research and Development and Chief Medical Officer will provide comments relating to the clinical development of tirasemtiv, which will include a summary of recently reported results from BENEFIT-ALS, our completed Phase IIb trial, which evaluated tirasemtiv for the potential treatment of ALS, or afterwards, Robert will provide additional comments and perspectives on our company’s plans in light of the results of BENEFIT-ALS.

Following those remarks, Fady, our Senior Vice President of Research and Early Development will provide you with an update on the clinical development of omecamtiv mecarbil for the potential treatment of heart failure. In addition, he will also provide an update on progress with Phase I clinical trial of CK-2127107, or CK-107 in healthy volunteers. I’ll then provide a financial overview for the quarter. Robert will then conclude the call with comments regarding how company activities align with our corporate strategy and projected milestones for 2014. We’ll then open the call for questions.

Please note the following discussion including our responses to questions contains statements that constitute forward-looking statements for purposes of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to statements relating to our financial guidance, and collaborations with Amgen and Astellas, to the initiation, enrolment, 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 report 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.

I’ll now turn the call over to Robert.

Robert I. Blum

Thank you, Sharon and thank you to everyone on the line for joining us for this call today. The first quarter of 2014 was an important one for Cytokinetics, but that does not diminish our disappointment that as we recently reported BENEFIT-ALS did not meet its primary endpoint.

Andy will elaborate on the results from BENEFIT-ALS that we reported on April 29 at the annual meeting of the American Academy of Neurology or AAN and again, during our investor webcast on April 30. On behalf of all my colleagues at Cytokinetics, I would like to express our gratitude to the BENEFIT-ALS investigators, and their evaluators and coordinators, as well as to the patients who participated in their families and caregivers, all of them dedicated so meaningfully to the conduct of this important clinical trial.

While BENEFIT-ALS did not meet its primary efficacy endpoint, that result appears to be confounded by tolerability issues related to tirasemtiv in this trial. Extensive analysis of the data from BENEFIT-ALS are underway, in order for us to understand the relationships between tolerability and the results of tirasemtiv on the ALS functional rating scale in the trial.

Results from benefit-ALS on certain pre-specified secondary endpoints show effective tirasemtiv that we believe to be potentially clinically meaningful and that we believe our unprecedented in a clinical trial of patients with ALS. These effects are not on subgroups of patients in BENEFIT-ALS, nor they as determined post hoc, but rather as perspectively defined and deemed important in the design of the trial and in accordance with its pre-specified statistical analysis plan.

We believe that we owe into patients living with ALS who are in such dire need of a therapy that can impact a lots of muscle function to understand as fairly as possible the results we have from BENEFIT-ALS. We understand the challenges in front of us.

Cytokinetics made the wrestling with these issues for weeks to months, while at the same time, we intend to continue to execute on key objectives across our other research and development programs. In the first quarter, while our organization was engrossed in completing BENEFIT-ALS, we demonstrated progress with respect to each of omecamtiv mecarbil, our cardiac muscle activator, which is partnered with Amgen and CK-107 by follow-on fast skeletal muscle activator, which is partnered with Astellas.

In the quarter, we announced at the expansion phase of COSMIC-HF open to enrollment and Fady will elaborate more on progress in that trial later in this call, in parallel, we progressed our ongoing Phase I studies of CK-107. With the initiation of CY-5012, our multiple ascending dose Phase I trial of CK-107 and healthy volunteers, we earned a $2 million milestone payment from Astellas.

Cytokinetics is purposely developing a pipeline of novel mechanism drug candidates with strategic partners to enable the company to manage risk inherent in the pursuit of innovation. Our conviction remains strong and we believe our company remains on solid footing.

As you’ll here now in more detail from my colleagues, we have constructed a portfolio of development stage programs that enable multiple path to potential successes. Let’s begin with the summary of what we know and still must learn from BENEFIT-ALS and tirasemtiv.

I’ll now turn the call over to Andy.

Andrew A. Wolff

Thank you, Robert. In the first quarter, we concluded dosing and follow-up of patients in Benefit-ALS. More recently, we completed the data collection, database lock and the analyses to inform the presentation by Jeremy Shefner, trial’s lead investigator at AAN.

As you know, BENEFIT-ALS was a Phase IIb multinational, double-blind, randomized, placebo-controlled, clinical trial designed to evaluate the safety, tolerability and potential efficacy of tirasemtiv in patients with ALS. BENEFIT-ALS enrolled 711 patients from 73 centers in eight countries. 605 patients were randomized to double-blind treatment, of those 302 were randomized to placebo and 303 to tirasemtiv.

We had previously reported that a programming error committed by our data management vendor caused 58 patients initially randomized to and treated with tirasemtiv to be subsequently dispensed and treated with placebo. To preserve the scientific integrity of the trial, a protocol amendment excluded from the primary efficacy analysis all 156 patients who were randomized in blocks that included any of the 58 affected patients.

The primary efficacy analysis of BENEFIT-ALS compared to change in the ALS functional rating scale and its revised form, or the ALSFRS-R from baselines of the average score after eight and 12 weeks of double-blind treatment on tirasemtiv versus placebo.

BENEFIT-ALS did not achieve its primary endpoint. The ALSFRS-R declined to 2.98 on tirasemtiv, versus 2.40 points on placebo with the p-value of 0.11. Consequently, BENEFIT-ALS joined the long list of clinical trials that have built to demonstrate an effect on the ALSFRS-R.

While tirasemtiv did not affect the ALSFRS-R in BENEFIT-ALS, several clinically important measures of respiratory performance and other measures of skeletal muscle function and fatigability were the protocols specified secondary endpoints. While the effective tirasemtiv on the secondary endpoint was inconsistent, statistically significant and potentially, clinically important increases versus placebo and slowed by our capacities and muscle strength more to serve on tirasemtiv.

Slow Vital Capacity or SVC is the most routinely performed measure of pulmonary function in patients with ALS. This measures the maximum volume of air, which can be exhaled in a slow and steady manner. SVC is generally viewed as a clinically useful measure of these progressions and its rates are defined as an important predictor of survival.

In BENEFIT-ALS, SVC declined more than twice as quickly in patients on placebo as on tirasemtiv, specifically 2.7 percentage points per 30 days on placebo versus 1.2 on tirasemtiv, while we believe this reduction in the rate of decline in SVC on tirasemtiv versus placebo, maybe clinically meaningful, it is definitely statistically significant that the p-value of 0.0006.

In addition, the rate of decline in muscle strength, as reflected by the percent change from baseline in the Mega-Score of muscle strength was also statistically, significantly lower on tirasemtiv versus placebo. The Mega-Score is a composite measure of strength of five muscle groups on each side to our knowledge, no prior clinical trial in patients with ALS as demonstrated statistically significant and potentially clinically meaningful effects on measures of respiratory performance and skeletal muscle function.

These findings are encouraging, but did not explain by treatment with tirasemtiv and BENEFIT-ALS did not demonstrate an effect on other measures of pulmonary function and the ALSFRS-R. however, we have begun to understand what may be confounding the results of BENEFIT-ALS in connection with the effect of tirasemtiv on ALSFRS-R.

We observed issues with the tolerability of the tirasemtiv dosing regimen employ in BENEFIT-ALS. for example, 99 patients terminated treatment prematurely after randomization to tirasemtiv versus 33 on placebo. the majority of adverse events observe on tirasemtiv were mild, however, patients with gastrointestinal adverse events lost significantly more weight than those who did not report them and such adverse events were reported more often on tirasemtiv and on placebo specifically, 44% of patients are tirasemtiv versus 26% on placebo.

As a result, patients on tirasemtiv lost 0.9 kilograms more weight over 12 weeks of double-blind treatments and patients on placebo, while weight loss is a concern in patients with ALS that may also be the key to understanding a lack of an effective from tirasemtiv on the ALSFRS-R in BENEFIT-ALS.

Patients who are less than the medium weight loss on tirasemtiv during the trial did moderately better on tirasemtiv at placebo, reflecting a specifically significant interaction between the amount of weight loss and the effect of tirasemtiv on the ALSFRS-R. this could mean that tirasemtiv may benefit those ALS patients who can target.

as a result, we working to understand better the relationships between the tolerability and the potential efficacy of tirasemtiv and we’ll need to consider the findings from these additional analyses in the context of our broader skeletal muscle troponin program.

Additional presentation of BENEFIT-ALS data, our plans are occurred during the annual meeting of the European network for the Cure ALS or ENCALS in Leuven, Belgium May 22 to May 24 and the European Federation of Neurological Societies, European Neurological Society, Joint Congress of European Neurology 2014 in Istanbul, Turkey from May 31 to June 3. I ensure these results from BENEFIT-ALS and our perspective on those.

I will now turn the call back to Robert.

Robert I. Blum

Thank you, Andy. These findings are still coming together and do not change the primary efficacy analysis that BENEFIT-ALS, however in line with the fact that BENEFIT-ALS was a Phase IIb trial and did demonstrate statistically significant effects on certain important pre-specified secondary measures, it is internally legitimate and frankly imperative to explore these questions of the data and considered their implications on the further potential development of tirasemtiv.

Considering the tirasemtiv as the new chemical entity with a novel mechanism of action, and ALS is a disease for which no drug is available to improve function for desperate patients who suffer progressive loss of muscle function. it is incompetent loss to delve deeply into the data, underlying the results of BENEFIT-ALS. This landmark trial will be the subject of an extensive data analyses and reporting for sometime.

It was the largest Phase II trial ever conducted in patients with ALS and to our knowledge, the only clinical trial to show an impact on the measures of vital capacity and muscle strength.

BENEFIT-ALS evaluated three specified measures of muscle function that we believe reflect the well-characterized mechanism of action of tirasemtiv. a trial such as BENEFIT-ALS can be very informative to the ALS community. we believe that fast skeletal troponin activation by tirasemtiv may have inferred a clinical benefit to certain patients.

And we look forward to diligently working through these matters. The last patient, last visit in BENEFIT-ALS occurred only a little more than a month ago and we moved certainly to collect the data from this large international trial lock the database and analyze and report the top line findings as promptly as we could.

Our team with Cytokinetics in all of the studies sight personnel and our CROs did an extraordinary job making sure that happened less than two weeks after a database lock, reporting results as soon as they were available was the proper thing to do for patients with ALS who urgently required new treatment options.

The complete results from BENEFIT-ALS will not be more fully appreciated for what maybe months to follow. What we know now is that we have a biologically active compound and we need to understand whether it may be possible to dose tirasemtiv to better tolerability to optimize its treatment potential in patients with this devastating disease.

Please note that we will do the right thing and investigate the results of BENEFIT-ALS fairly before we determine our next steps in conduction with tirasemtiv.

I’d now like to ask Fady Malik to provide an update on activities in connection with our other clinical development programs and I’ll return later in the call to speak to all of our corporate priorities.

Fady I. Malik

Thank you, Robert. Firstly, curious to the development of omecamtiv mecarbil, in the first quarter, Cytokinetics announced that the expansion phase of COSMIC-HF opened through enrollment. So I’ll remind you, omecamtiv mecarbil was a first-in-class cardiac myosin activator that we’re developing for the potential treatment of heart failure in collaboration with Amgen.

COSMIC-HF is the Phase II, double-blind randomized, placebo-controlled, multicenter clinical trial designed to assess the pharmacokinetics and tolerability of omecamtiv mecarbil in patients with left – heart failure and left ventricular systolic dysfunction.

The secondary objectives are to assess the changes from baseline in systolic ejection time, stroke volume, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, heart rate and N-terminal pro-brain natriuretic peptide, to the biomarker associated with the severity of heart failure, all during 20 weeks of treatment with omecamtiv mecarbil.

The expansion phase of COSMIC-HF is expected to enroll heart failure patients from approximately 100 clinical sites internationally. And this trial is being conducted by Amgen in collaboration with Cytokinetics. Also during the first quarter, Cytokinetics began preparations for the initiation of CY 1211, following the review of the protocol for the trial with the FDA.

CY 1211 is the Phase I single center placebo-controlled double-blind study, comparing the pharmacokinetics of omecamtiv mecarbil between healthy Japanese and Caucasian volunteers. CY 1211 will be conducted by Cytokinetics in collaboration with Amgen.

I’ll now provide an update relating to CK-107, our next generation skeletal muscle troponin activator that is partnered with Astellas. During the quarter, we completed CY 5014, a Phase I study of CK-107 in healthy male volunteers. CY-5014 was a randomized open label two period crossover study designed to assess the relative bioavailability, pharmacokinetics, safety and tolerability of two forms of CK-107, administered orally in a liquid suspension.

Also in the quarter, Cytokinetics initiated enrollment in CY-5012, a double-blind, randomized, placebo-controlled, parallel group study in which the primary objective is to assess the safety, tolerability, and pharmacokinetics of CK-107 following multiple ascending doses in healthy volunteers.

With that update on our cardiac and skeletal sarcomere activators, I’ll turn the call over to Sharon to update our financials.

Sharon A. Barbari

Thank you, Fady. As our press release contains detailed financial results for the first quarter 2014, I’ll refer you to that public statement for the details on our P&L and balance sheet. In the past quarter, as you’ve heard on today’s call, we have broadly been focused on the completion of BENEFIT-ALS. We ended the first quarter with approximately $101 million in cash, cash equivalents and investments, which represents approximately 20 months to 22 months of going forward net cash burn based on our current 2014 financial guidance.

Revenues for the first quarter of 2014 were $8 million. This revenue included the recognition of $2.1 of license revenues and $5.2 million of research and development revenues from our collaboration with Astellas, along with $0.7 million of research and development revenues from our collaboration with Amgen. Our first quarter 2014 R&D expenditures totaled $12.5 million.

From a program perspective, for the first quarter, over 80% of our R&D expenses were attributable to our skeletal muscle contractility program activities. This includes both the development of tirasemtiv, which we are performing independently, and research and development activities that we are performing under our collaboration with Astellas, which includes the development of CK-107. Astellas reimbursed us our agreed cost under our agreed research and development plan.

In addition, approximately 10% of our R&D expenditures were attributable to our cardiac muscle contractility activities, Amgen reimburses that for certain agreed research costs performed in connection with our agreed research plan directed to next generation cardiac sarcomere activators.

The reminder of our research costs are attributable to our other research activities. At this time, we are reiterating our cash based financial guidance for 2014 of cash revenue in the range of approximately $19 million to $21 million, cash R&D expenses in the range of $50 million to $53 million and cash G&A expenses in the range of $15 million to $17 million. This financial guidance is on a cash basis and does not include approximately $10 million in revenue deferred from 2013 into 2014 under generally accepted accounting principles and an estimated $3 million in non-cash related operating expenses, primarily related to stock compensation expense.

In addition, this guidance does not reflect potential revenues from milestone payments that we were or may be achieved in partnered programs. Once we more fully understand the implications of the BENEFIT-ALS data on the potential future of tirasemtiv, we will provide updated financial guidance.

We believe that we have sufficient financial resources to enable our focus to be on the further analysis of data from BENEFIT-ALS, as well as to advance our other research and development program.

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

Robert I. Blum

Thank you, Sharon. Cytokinetics is committed to pursuing the portfolio approach to our research and development. With the continued advancement of the development program for omecamtiv mecarbil, we are optimistic about the potential of this novel mechanism compound to address unmet needs in the treatment of heart failure.

We believe that omecamtiv mecarbil in both intervenes and oral forms may demonstrate a clinical profile that can represent significant innovation for both acutely ill and chronic care patients. We look forward to updating you on the progress of this promising program.

As you also heard today, we continue to make progress in the development of CK-107. We have completed two Phase I trials and recently initiated a third. We are executing well on Phase II readiness activities in accordance with agreed plans and under the joint oversight of Cytokinetics and Astellas.

Together we are setting the stage for the investigation of CK-107 in non-neuromuscular disease indications. We believe CK-107 offers promise to address highly unmet needs in an array of syndromes and conditions associated with muscle fatigue and weakness. We look forward to sharing future updates throughout the year.

Not only do our partnered programs represent meaningful upside in therapeutic categories with high commercial potential, but they also provide risk diversification, balance and funding. We believe Cytokinetics is well-positioned operationally, financially and programmatically to return value.

We have a job to do with respect to tirasemtiv and BENEFIT-ALS. We must understand the results especially as they may inform a next potential trial. Candidly, the results we know now represent both the stepping stone and a potential hurdle to what lies ahead. We are encouraged by certain results and confounded by others, that is not at all an expected for a Phase II trial in a disease for which no precedent exists for what we’re trying to do.

We will need to consult with experts in the field and engage directly with regulatory authorities to understand what a registration program for tirasemtiv in ALS could look like. We already know we have the support of ALS investigators, patients with ALS and ALS advocacy groups to proceed, how about they occur is still to be determined.

We have received feedback from them that underscores their belief that the effects on pulmonary function and muscle strength observed in BENEFIT-ALS are potentially, clinically meaningful, and they form the basis for registration is confirmed, that is to be determined. We believe there may be relevant precedents that we must better understand. Could we dose tirasemtiv to greater tolerability in ALS patients? We have preliminary ideas on how that may be possible, but there is still much to be learned from our data.

However, we approach funding of potential mixed trials and could that be done with a partner. That depends on several factors that includes scope, and timing and cost and must be still determined. We will update you as we obtained clarity on these issues that can inform our potential plans. We intend to do right by patients who can benefit from medicines like tirasemtiv, as well as our other first-in-class compounds that we believe are uniquely positioned to push forward.

Now let me turn back to our expected milestones for 2014. Firstly, for tirasemtiv, Cytokinetics expressed to continue to analyze the data from BENEFIT-ALS to inform potential further development in ALS. Next, for CK-107, Cytokinetics expressed to conduct additional Phase I studies and certain Phase II readiness activities in 2014 pursuant to our collaboration agreement with Astellas. And next for omecamtiv mecarbil, Cytokinetics anticipates commencement of patient enrollment in CY 1211 to occur by mid-year 2014 and Cytokinetics expressed both the enrollment of patients and the expansion phase of COSMIC-HF, as well as the conduct of CY 1211 to be completed in 2014.

In conclusion, we remain optimistic about the future development of tirasemtiv, however, further analyses of data from BENEFIT-ALS would be critical to informing decisions with respect to the potential further development of tirasemtiv.

In addition, we are pleased with Cytokinetics’ progress and execution in the last quarter in the development programs for omecamtiv mecarbil in CK-107. And we’re looking forward to the planned progress for these programs in 2014. As a company, we are on solid footing with over $100 million in cash and we are resolute in our commitment to maintain multiple paths for potential successes.

Operator, that concludes the formal portion of our call today. I’d now like to open the call to questions please.

Question-and-Answer Session

Operator

(Operator Instructions) And your first question comes from Charles Duncan from Piper Jaffray.

Robert I. Blum

Hi, Charles.

Roy Buchanan – Piper Jaffray & Co.

Hi, it’s Roy in for Charles actually. Thanks for taking the question.

Andrew A. Wolff

Hi Roy.

Fady I. Malik

Hi.

Roy Buchanan – Piper Jaffray & Co.

Hi, just I guess first question is, if you can speculate, maybe if you think there might be an easy pick for the GI adverse events?

Robert I. Blum

Your question is, do we think there may be an easy fix for the GI adverse events. I’ll tell you what’s still premature for us to speculate on that, recognizing these data are still just days old, but I will ask Andy to comment.

Andrew A. Wolff

I think it is hard to know at this point, what we have enabled to find out and there’s more to deal with that they tend to be mild for the most part and what it appears we have an onset that maybe is a little later than the types of adverse events that tend to be most associated with early termination, particularly from open-label treatment.

So I don’t think these GI adverse events actually got a lot of attention from the investigators during study, because the great majority of them really were not intolerable. But in another trial was more perspective focused on them, I think it may be possible to manage them better, but I can’t really say that right now.

Robert I. Blum

What I might add to Andy’s comments is, for those of you who haven’t yet had an opportunity, I would encourage you to listen to the webcast from our presentations on April 30, where investigators and non-investigators with BENEFIT-ALS commented on just that and other data and in particular, the adverse effects.

We know that the tolerability profile of tirasemtiv in this trial was not as anticipated in some respects and that is in particular, with regard to GIAEs based on what we know today. But as you’ll hear on that webcast, there was a strong sentiment that these kinds of GIAEs are able to be managed well in clinic and that with the common administration of other meds, or just simply as Andy pointed out, knowing about them in advance may contribute to more favorable tolerability in the next study. That’s still something that we need to understand and we need to delve much more deeply into the data in order to inform what could be the design of a potential next study.

Roy Buchanan – Piper Jaffray & Co.

Okay, helpful thanks. And patients on tirasemtiv had their really well dose limit of 50 milligrams, correct, was that also the case in viral studies?

Robert I. Blum

In small earlier Phase III studies, yes, in patients who receive the lack of tirasemtiv, there really is all those, which reduce to 50 milligrams point fairly.

Roy Buchanan – Piper Jaffray & Co.

Okay. Can you remind me, as we know what the source of the business, might be if there is a mechanistic basis there?

Andrew A. Wolff

Your question relates to, do we know what might be contributing to the deadliness signal associate with tirasemtiv and I do think we have just some handle on that based on both preclinical and other earlier clinical work, I’ll turn it to my colleague, Fady Malik to address that.

Fady I. Malik

We know that tirasemtiv is probably for drain barrier, so if it enters the brain, or it might have effect on receptors in the P&S. Maybe, it’s difficult to obtain specific receptor down, but the – we have noted in effect of tirasemtiv on gather beta-adrenergic receptors that can be implicated in dealing some dizziness and things like that. So we’ve obviously looked at that as a potential target. but there is no, there probably are a lot of P&S receptors that can cause dizziness and then our – and our other program in our follow-on molecule taking an approach there, potentially just trying to keep it out in the P&S, so that we wouldn’t encounter that in the future molecule.

Andrew A. Wolff

So based on what we knew from the Phase IIa studies, we knew to look for lightheadedness and dizziness that was information convey to investigators and also patients and we did see as expected that when dizziness did occur, it tended to abate as we would have expected after roughly about a week. The reason you do clinical trials is to learn things about the tolerability of the drug before you might advance them forward, and certainly, in this Phase II study, we learned more about tolerability of tirasemtiv over longer duration treatment, and that is information that can inform the potential path forward, were that to be our choice to proceed to next steps and certainly in order to know that we have to dive much deeper into these data.

Roy Buchanan – Piper Jaffray & Co.

Thank you. I’ll turn back in queue.

Andrew A. Wolff

Thank you.

Operator

(Operator Instructions) And we do have a question for Chad Messer from Needham and Company.

Robert I. Blum

Hi, Chad.

Chad J. Messer – Needham & Co. LLC

Hi, thanks for taking my question. I know as you mentioned, you still have quite a bit of reviewed it to with your data. I wanted to know if it’s possible to share with us even in general terms that kind of additional analyses you think are important to query the database where that the sort of subset analyses looking at different patients by what those they received or what kind of questions do you still have to ask at the data and then just a second quick follow-up, any update or idea or thoughts on timing with getting in front of the FDA with this data? thanks.

Robert I. Blum

Chad, very good questions, and I’m not sure I can give you satisfactory answers yet, but I’ll try. With regard to your first question, there are many hundreds of analyses that are pre-specified and still need to be preformed as well as others that these data now suggest need to be done, and there are things relating to correlations between adverse effects and also with dose and exposure and what we can learn through the course of the study in connection with riluzole also patients not on riluzole there, subgroups that we want to better understand.

there is a tremendous amount that was prioritized to occur after the presentation at AAN, in order to ensure we had data as soon as we could for presentation, but where now I would make sense to spend the time the necessary weeks at least and potentially months to understand these data, in their full meaning. And as such, I think it’s pretty mature to even speculate on when that’s going to be completed and what will then have in terms of a timeline for discussion with FDA. I understand why you asked the question, but we’re going to be very careful to do a deliberately careful job of analyses, in order to run the next informed as to what would be timelines and plans from that point. And I guess I’ll just have to ask for your patients in understanding as we go deep into these data.

Chad J. Messer – Needham & Co. LLC

Right, well thank you and good luck with the analysis.

Robert I. Blum

Thank you. Chad.

Operator

Your next question comes from Charles Duncan and Roy Buchanan.

Robert I. Blum

Good morning.

Roy Buchanan – Piper Jaffray & Co.

Hi, guys. I’m Roy. just a couple of follow-ups. Was anything done in the protocols that total patients in the dizziness and was that, I guess maybe ineffective and was there any dropouts and what happened there?

Robert I. Blum

Andy I’ll turn it you the question relates to, was anything done to coach the patients regarding dizziness and we’re successful at that with regard to the early terminations and those were continued.

Andrew A. Wolff

Well, certainly patients knew that and we had known that dizziness did tamp to abate with continued treatment in most patients. But that did not prevent dizziness from being the most common reason for early termination from both the open-label phase, as well as the double-blind phase. So they have the information, but it’s still resulted in – it’s still with the single adverse event that resulted in the most early terminations.

Robert I. Blum

And we knew that would likely be the case and as such as Andy has spoken before the efficacy analysis were really driven by those patients who tolerated the open-label titration and had at least one efficacy visit, the first one occurring that we explore following randomization. So I do think that we are enough experienced with the lightheadedness, that we know how to mange that for clinical trials and now we need to understand some of these other issues. We also need to understand what might have contributed to the weight loss and how that confounded the results on ALSFRS. We don’t believe that weight loss had effect to any of the other effects and certainly we think it stands independent of Slow Vital Capacity. So these are things that we want to go much deeper into understand.

Roy Buchanan – Piper Jaffray & Co.

Okay great. Then I had one last question. I guess on the confusional state, if you guys could characterize that a little bit more how severe it was and what actually it looks like?

Robert I. Blum

Most of these adverse events were reported as mild, a minority were moderate, very few were severe, patients for and I’ll tell you what, I’m not sure that the confusional state is different from that dizziness, I think, it depends a lot on how what word the patients would choose to describe it and then it maps, differently so some patients don’t lightheaded in that space, use the term lightheaded that complaint maps to the standard adverse event term of dizziness. Others might have said they felt, but as we prevailed before that goes the euphoric mood and others might have said, they were having difficulty thinking and that would go to confusional stage. All of them appear to be related to the presence of driving the central nervous system.

Robert I. Blum

May be just to add to that, what we also know is that these same terms and adverse effects are not uncommon in ALS and we’re also observed in placebo treated patients albeit, it is an issue that we think is more common amongst those treated with tirasemtiv. So again we just need to be able to understand it’s correlation with plasma exposure, with dose, with time, things that might have contributed to other ways that certain patients responded and others did not. That’s not straight forward, but important to do.

Roy Buchanan – Piper Jaffray & Co.

Thanks guys.

Operator

Your next question comes from Larry Smith from SmithOnStocks.

Robert I. Blum

Hi Larry.

Larry Smith – SmithOnStocks

Hi Robert. I was moving onto COSMIC-HF, when I look at the secondary end point, those are very important measures of heart function. But we’re only looking at 20 weeks of treatment. I wonder what we should be expecting in terms of data, are we going to be looking at trends or could some of these measures revise the level of those statisticals significance.

Andrew A. Wolff

Very good question. So as you know well having followed the company for a long time, omecamtiv mecarbil has been dosed for hours and days as demonstrated effects that are measurable and statistically relevant on echocardiographic parameters and the goal COSMIC-HF is to understand in a less ill population, but as dosed chronically over weeks of treatment, if some of those effects are also durable. I’ll turn it to Fady Malik to elaborate.

Fady I. Malik

Hi Larry, I think it’s good question, I think, the answer lies in how large of a magnitude set to you it is one thing is clinically relevant. And in terms of remodeling and things like that, really quite small changes are thought to be meaningful, especially if you’re only dosing for 20 weeks. I can underline there is that smaller the change obviously the harder is to speak to statistical significant. And so I think again just speaking for ourselves I can’t really speak on behalf of our partners at Amgen. If we were to see trials in a number of echocardiographic variables that are heading in the right direction, not necessarily achieving statistical significance, but where there’s, the big, large picture all kind of make sense. And I think that is sufficient really for us to conclude that we’re having a side effect on cardiac function.

And to that point there is no pre-defined primary efficacy endpoint in COSMIC, no specific hurdle for efficacy that we have to hit, in order for that to be deemed the positive strengths. So to Fady’s point, our goal is to ensure safety and tolerability and PK and PD that are within the range of expected values during this longer term treatment with omecamtiv.

Larry Smith – SmithOnStocks

I have one other question on tirasemtiv. I don’t know if I’ve heard you correctly, I think it was on the call on Wednesday. You mentioned that in myasthenia gravis the patients were younger and the side effects were more benign. I don’t know if that’s correct or not. But if it is correct why have you put more emphasis on myasthenia gravis either paralleling with ALS or that possibly even going before ALS?

Robert I. Blum

So I’ll answer your second question after Andy addresses the point about age and the mg study.

Andrew A. Wolff

A word in generally younger, and there were overall less habilitated and we have see over the course of now looking at patents with three different diseases, corrugation with lowered myasthenia gravis will average under and ALS patients through were in middle. That the tolerability and in particular these CNS adverse event are correlated with age. I don’t if I can give you a good mechanistic explanation for that, but it’s unsurprising to me, especially the CNS is the – really a time to look into this gastrointestinal, or to that level we got.

Robert I. Blum

And to your question about strategy, we had to make choices and prioritizations and based on what we know about ALS, what we knew then and we still know now, it’s an areas of higher urgent unmet need with a more concentrated clinical trials network, highly motivated patients that would participate in clinical research and we thought from a return on investment standpoint and an urgency that will be an area where we could make a bigger impact sooner and also that would be an area where we found the regulatory constructors were well defined.

The mechanism of action of fast skeletal muscle activation is something that extends as you know broadly the ALS and other neuromuscular diseases, as well as to non-neuromuscular diseases associated with muscle weaknesses and fatigue we have to make certain choices given our limited access to capital and other resources. And now together with ALS experts together with a broader audience of neuromuscular experts, we can think about tirasemtiv, but also we can consult with our partners at Astellas about our non-neuromuscular indications given the focus of that deal and CK-107’s development program. And I think we’ll have a lot more to say after we’ve had a time to digest these data and have these consultations.

Larry Smith – SmithOnStocks

And one final question, when do you think we could see top-line data on COSMIC-HF.

Robert I. Blum

So, its too early to say enrollment is proceeding well in the expansion phase, but it’s too early to point to when that may occur, certainly we’re intending that that could be in 2015 and when in 2015 will depend on the enrollment rate. Maybe we’ll have more to say about that I hope with our next earnings call, based on the rate of the enrollment at that time.

Larry Smith – SmithOnStocks

Okay. Thank you.

Robert I. Blum

Thank you.

Operator

There are no further questions at this time. I would now like to turn the call back over to you Robert Blum, President and CEO.

Robert I. Blum

So, thank you everyone for your participation in today’s call. We’ve had a number of press releases in recent days and also the webcast on Wednesday last week, this earnings call and webcast today. So I do believe there’s extensive information out there regarding Cytokinetics, our priorities and our plans we do look forward to updating you, as those continue to evolve.

And with that I’ll conclude the call and look forward to the next opportunity once we have more product we can share.

Operator

Ladies and gentlemen, that does conclude today’s conference call. You may now disconnect.

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