Diane Weiser – Vice President-Corporate Communications and Investor Relations Robert Blum – President and Chief Executive Officer Fady Malik – Senior Vice President-Research and Development Andy Wolff – Senior Vice President and Chief Medical Officer Sharon Barbari – Executive Vice President of Finance and Chief Financial Officer.

Joe Pantginis – Roth Capital Partners Jason Butler – JMP Securities Esther Pang – Needham Ritu Baral – Cowen George Zavoico – JonesTrading Vernon Bernardino – FBR Company Sarah Weber – Piper Jaffray.

Good afternoon and welcome ladies and gentlemen, to the Cytokinetics’ Third 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 request of the company, 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, Fady Malik, our Senior Vice President of Research and Development will 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 and the recent announcement regarding results from COSMIC-HF.

Then Andy Wolff, our Senior Vice President and Chief Medical Officer, will provide an update on VITALITY-ALS, our Phase III clinical trial of tirasemtiv, our first-in-class fast skeletal muscle troponin activator which we are developing for the potential treatment of amyotrophic lateral sclerosis or ALS.

Andy will also provide an update on our clinical development program for CK-2127107 or CK-107 our next generation fast skeletal muscle troponin activator, including an update on the soon-to-be-initiated Phase II clinical trial in patients with spinal muscular atrophy or SMA.

Then Sharon Barbari our Executive Vice President of Finance and Chief Financial Officer will provide a financial overview for the quarter and Robert will conclude the call with additional perspectives and comments on key milestones for the remainder of 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 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 Investors and Media 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 turn the call over to Robert..

Thank you Diane and thank you to everyone on the line for joining us for this call today. During the third quarter we have been firing on all cylinders across our three clinical development programs as well as our ongoing research activities.

Earlier this week, we announced top line results from the expansion phase of COSMIC-HF or Phase II clinical trial of omecamtiv mecarbil in patients with heart failure. Sufficed to say we are very pleased and encouraged with the results and believe the data exceeded expectations.

We look forward to further discussing the data with our partner Amgen and preparing to submit the results for presentation at an upcoming medical conference. Fady will provide more details on COSMIC-HF in a moment.

In the third quarter we began our first ever Phase III clinical trial of tirasemtiv which we are developing for the potential treatment of ALS. We believe this is the only multinational Phase III trial currently enrolling patients with ALS and we are encouraged by the early enthusiasm and support from the investigator community.

We have designed VITALITY-ALS to assess the effects of tirasemtiv versus placebo on slow vital capacity and also another measures of skeletal muscle strength including respiratory function in patients with ALS.

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

We have finalized the clinical trial protocol with our partner Astellas and we look forward of initiating this trial later this quarter.

Based on our discussions with our lead investigator professor John Day of Stanford University and others in the SMA community, we know there is great anticipation for this trial, particularly because it will be focused on patients 12 years and older, a population that is typically not eligible for other ongoing trials which are more focused on an infant population.

Shortly Andy will provide further details on both tirasemtiv and CK-107 development programs. Finally during the recent quarter we made progress on our joint research program with Amgen directed to the discovery of next generation cardiac sarcomere activators.

In addition, we continue to make progress under our joint research program with Astellas directed to the discovery of next generation skeletal muscle activators. Let me now turn the call over to Fady, so that he can provide some perspectives on omecamtiv mecarbil and the recently announced positive top line results of COSMIC-HF..

Thank you, Robert. As Robert mentioned and as you all saw earlier this week together with Amgen we just announced top line results for COSMIC-HF. Our Phase II clinical trial of orally administered omecamtiv mecarbil for the potential treatment of systolic heart failure.

These results come almost 10 years to the day after omecamtiv mecarbil first entered human clinical trials in September 2005. With over a dozen clinical trials now completed, we now have a deep understanding of the pharmacokinetics pharmacodynamic tolerability and safety of omecamtiv mecarbil how much to bill.

We certainly have more work to do as we look forward to potentially advancing to a Phase III outcome trial in 2016. We are pleased to see that what we have observed in earlier trials over shorter duration has now reproduced in COSMIC-HF following 20 weeks of treatment in chronic heart failure patients with systolic dysfunction.

We believe this trial is the last stepping-stone towards potential initiation of a Phase III program.

To remind you, COSMIC-HF is a double-blind randomized placebo controlled multi centre dose escalation study designed to assess the pharmacokinetic and tolerability of 3 oral modified release formulations of omecamtiv mecarbil in patients with heart failure and left ventricular systolic dysfunction and to select 1 formulation for further evaluation.

During the dose escalation phase 96 patients randomized one to one to one to one, to placebo of 1 of 3 different oral formulations of omecamtiv mecarbil and each of 2 ascending dose escalation cohorts. Then one of these 3 of the oral formulations was selected for use and the expansion phase of the trial.

The expansion phase of the trial enrolled 448 patients randomized one to one to one to receive placebo or omecamtiv mecarbil at either 25 milligrams twice daily or target dose of 50 milligrams twice daily.

Escalation to the 50 milligram dose that we gave depending on plasma concentrations of omecamtiv mecarbil following 2 weeks of dosing with 25 milligrams twice daily, consequently because all patients randomize for this group actually were titrated up to 50 milligrams twice daily.

We refer to as a dose titration group rather than referring to any particular dose level. The primary objective of expansion phase was to characterize the pharmacokinetics of oral omecamtiv mecarbil during 20 weeks of treatment.

The secondary objective included evaluation of safety, tolerability and echocardiographic measures to cardiac function, heart rate and N-terminal pro-brain natriuretic peptide or NT-proBNP. Our biomarker associated with a severity of heart failure, during 20 weeks treatment.

Approximately 100 sites in 13 countries participated in 1 our both phases of COSMIC-HF. On Tuesday morning we reported top line data from the expansion phase of COSMIC-HF. First you take away is that pharmacokinetics or PK guided dose titration, appear to adequately control patient exposure to omecamtiv mecarbil.

In the dose titration group this was achieved simply by measuring plasma concentration of omecamtiv mecarbil and basing the decision to titrate the dose upward on a single trial plasma concentration. This precision medicine approach appears well suited for preventing excessive exposures to omecamtiv mecarbil.

Very importantly we also saw specifically significant improvements in several pre-specified eco cardio graphic measures that cardiac function measured at 20 weeks following randomization.

These pharmacodynamic effect of omecamtiv mecarbil were generally dose dependant systolic ejection time the pharmacodynamic signature of the mechanism of action that has been followed throughout the development program increased in a statistically significant manner that persisted over the 20 weeks of dosing.

Similarly in the dose titration group we observe statistically significant and potentially clinically meaningful decreases in cardiac, dimensions which were evident after 20 weeks of dosing. They were increases in stroke volume accompanied by decreases in heart rate, lower heart rate being a very good reflection of the increased cardiac efficiency.

These changes were gratifying as we had observe similar changes in prior studies of acute dosing and now have observed them following 20 weeks of chronic oral therapy. As you may recall the signature pharmacodynamic effect of omecamtiv mecarbil has been a prolong systolic ejection time.

In this study we were looking to see if this effect might produce a durable effect on other measures of cardiac function which we did observe. Finally, we saw a decrease in the neurohormone NT-proBNP, something non-observed in prior studies that employed short term dosing of omecamtiv mecarbil.

NT-proBNP increased the severity of heart failure and consequently decreases in this biomarker sound to predict clinically meaningful decreases in the occurrence of negative clinical outcome such as death in the hospitalization for heart failure.

Adverse event including serious adverse events in patients on omecamtiv mecarbil appears comparable to those on placebo. Small increase in component within among subjects receiving omecamtiv mecarbil, increases in troponin or independently adjudicated and none were determined to be due to clinical events of myocardial ischemia or infarction.

There was imbalance in death and cardiac adverse event, but generally balance between placebo and active treatment groups. In summary, we are very enthusiastic about the consistency and durability of the pharmacodynamic measures and the balance of major adverse event of interest, in this first clinical trial chronic oral dosing of omecamtiv mecarbil.

I would like to thank the patients and the investigators who participated in COSMIC-HF as well as my colleague in Cytokinetics and collaborators with Amgen for the dedication and substantial commitment for the development of this novel mechanism of action for the potential treatment of heart failure.

An anticipation of the data and potential progression of Phase III, during the quarter we continue to conduct collaborative planning activities in the areas of clinical development, manufacturing and market research with our partner Amgen.

On the clinical front, we held an advisory meeting with leading heart failure experts to gain insight and perspective into our proposed Phase III trial design and have continued to refine the design of a potential Phase III outcome study. Additionally in the quarter we attended the annual meeting of the Heart Failure Society of America.

Based on themes the HFSA and meetings we had with the leadership of the organization few opinion leaders including physician. We believe that addressing the burden of heart failure remains a significant challenge given the still high event rate, cardiovascular death and heart failure hospitalization.

As well as the cost to society associated with these events. Despite the recent introduction of new therapy, we believe there is a large on that need for therapy like on omecamtiv mecarbil it has a potential that impacted clinical outcomes by directly increasing systolic function.

We look forward to continuing the advanced development of omecamtiv mecarbil, I believe the results of COSMIC-HF supports the movement of Phase III. Our goal will be make this decision jointly with Amgen in the next few months.

And with that update on our cardiac program I will turn the call over Andy for an update on the skeletal muscle activator programs..

Thank you, Fady. As you know this past quarter we began VITALITY-ALS our Phase III clinical trial design to assess the effects of tirasemtiv versus placebo on slow vital capacity or FET and other measures at skeletal muscle strength including measures of respiratory function in patients with ALS.

I reviewed the study design on our last call, so I won’t go into that to tale again, it’s available on clinicaltrials.gov. I would however like to highlight some of the key design elements we included in VITALITY-ALS to address some of the challenges we encountered during benefit ALS.

First we have expanded the open-label lead in phase from 1 to 2 weeks in VITALITY-ALS to give patients a little more time to acclimate to any potential adverse events in the experience and also to give them along with their physicians more time to determine if they can tolerate starting dose over a longer duration after randomization.

As you may recall the 1 week open-label lead in phase in benefit ALS may have been too short to allow an adequate consideration of the tolerability of the starting goes of 125 milligrams twice daily and consequently this contributed to a higher than expected drop out rate from the tirasemtiv group after randomization.

Additionally, unlike and benefit ALS in which attempted to titrate all patients to 500 milligrams daily. In VITALITY-ALS we targeting 3 different dose levels well again enabling patients to up and down titrate based on tolerability. Together we believe these design changes in VITALITY-ALS may decrease the early termination rate.

We observed after randomization and benefit ALS and help to determine the optimal tirasemtiv dosing strategy going forward. Regarding our start-up activities, during the quarter we focused on initiating our North American and Canadian sites.

We will turn our attention to our European sites this quarter and expect that the majority of centre should be enrolling by year end. In fact, based on continued interest and increased enthusiasm for VITALITY-ALS.

We have decided add sites in additional European countries, bringing our plan totals for more than 75 centers in 11 countries in North America and Europe. Based on current enrollment rates, we anticipate enrollment to complete in the first half 2016 and except results from VITALITY-ALS by mid 2017.

In parallel, we also engaged in manufacturing commercial planning and advocacy related activities this quarter in support of VITALITY-ALS and tirasemtiv. We also conducted a webinar for key advocacy groups in North America and Canada to review the trial design and ensure they were well equipped to provide information to their patient constituencies.

You will recall that we received $1.5 million grant award from the ALS associations proceed from the Ice Bucket Challenge for the conduct of VITALITY-ALS, including the collection of clinical data and plasma samples from patients in VITALITY-ALS in order to help to advance the discovery of potential use for biomarkers in ALS.

During the quarter we achieved a milestone payment in accordance with our agreement with ALS Association.

Turning to the development of CK-107, our next generation skeletal muscle troponin activator partnered with Astellas we continue to make progress toward our goal of initiating of Phase II clinical trial in patients with SMA and the fourth quarter of this year in accordance with an agreed plan with Astellas.

As you know SMA ischemia is a disease in great need of new therapies to address functional limitations and we believe CK-107 has the potential to improve muscle function in the adolescent and adult patients we intend to enroll in our trial, whether the drug is used alone or in combination with other therapeutic approaches being pursued.

We have finalized the protocol following our investigator meeting which we held last weekend. As this has been our practice we will provide additional details regarding the trial design when it is open to enrollment that I will quickly recap the key elements.

We planned to focus on the SMA types 2, 3 and 4 including both ambulatory and non-ambulatory patients and evaluate end points including respiratory and other measures at skeletal muscle function following treatment to study state with CK-107.

We anticipate enrolling approximately 75 patients and to treat them for 8 weeks at approximately 10 to 12 centers in the United States. Our study in patients with SMA is only one at several studies at CK-107 that will get underway under our collaboration with Astellas.

While our study in CK-107 in patients with SMA will be the first Phase II trial of CK-107 and will occur in patients with a neuromuscular disease, in parallel Astellas is focusing on non-neuromuscular disorders in which there is also impaired muscle function.

Toward that objective we expect Astellas to initiate a Phase II trial of CK-107 in patients of chronic obstructive pulmonary disease or COPD in the first half of 2016. The goal of this trial is to evaluate the potential of CK-107 to increase the measures of exercise performance and time to muscle of the cheek.

With that update on our plans for our skeletal muscle program, I will now turn the call over to Sharon for an update on our financials..

Thank you, Andy. As our press release contains detailed financial statements for third quarter 2015, I'll refer you to that public statement for the details on our P&L and balance sheet.

We ended the third quarter with approximately $98 million in cash, cash equivalents and investments, which represents over 15 months of going forward net cash burn based on our 2015 guidance. Our guidance includes our current estimated cost for VITALITY-ALS for tirasemtiv in 2015 and 2016.

Revenues for the third quarter of 2015 was $7.9 million compared to $9.4 million during the same period in 2014.

Revenues for the third quarter of 2015 included $4.1 million of license revenue and $3.2 million of research and development revenue 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 2015 included $2.7 million of license revenues and $4.8 million of research and development revenues from our collaboration with Astellas and $1.9 million of research and development revenues from our collaboration with Amgen.

Our third quarter 2015 R&D expenditures total a $11.6 million from a program perspective to the third quarter approximately 77% of R&D expenses were attributable to our skeletal muscle contractility research and development activity, which includes those expenses associated with tirasemtiv and CK-107, 13% to our cardiac muscle contractility activities and 10% to our other research activities.

Revenues for the nine months ended September 30 2015 were $18.9 million compared to $25.2 million during the same period in 2014.

Revenues for the nine months ended September 30 2015 included $8.8 million of license revenue and $8.2 million of research and development revenues from our collaboration with Astellas and $1.9 million in research and development revenues from our collaboration with Amgen.

Revenues for the same period in 2014 includes $7.6 million of license revenue and $14.1 million of research and development revenue from our collaboration with Astellas and $3.4 million of research and development revenues from our collaboration with Amgen. For the 9 months ended September 30 2015 R&D expenditures totaled $33.1 million.

From a program perspective for the third quarter approximately 76% of R&D expenses were attributable to our skeletal muscle contractility research and development activities which includes those expenses associated tirasemtiv and CK-107. 13% to our cardiac muscle contractility activity and a 11% to our other research activities.

Today we also updated our financial guidance for 2015, the company anticipates cash revenue will remain in the range of $44 million to $47 million. Cash R&D expenses will be in a range of $51 million to $54 million and cash G&A expenses will be in the range of $18 million to $21 million.

This guidance includes approximately $30 million in revenue which will be deferred and recognized over a 2 year period ending in 2016 under generally accepted accounting principle. This guidance excludes an estimated $4.6 million in non-cash related operating expenses primarily related to start compensation expense.

During the quarter we also established a $40 million control equity offering or ATM line or Cantor Fitzgerald as part of our ongoing financial stewardship. As proactive we have put ATMs in place and the path and accept them opportunistically based on the capital markets in the timing of company event. Our intent is to use this ATM in a similar manner.

We also recently announced that we entering into a growth capital loan with Oxford Financial and Silicon Valley Bank. This growth capital loan allows the company to access up to $40 million in a series of term loan.

Upon signing of the loan agreement the company received $15 million, we may at our sole discretions borrowed from the lenders additional capital provided the pre-specified conditions under loan agreement on that.

So the ATM and the growth capital loan provide us with the flexibility to fund the company in 2016 as we prepare for data with VITALITY-ALS and begin the Phase III development program for omecamtiv mecarbil. That concludes the financial portion of today’s call. With that I will now turn the call back over to Robert..

Thank you, Sharon. So as you have heard we really dialed up our momentum in the third quarter of 2015 across all of our clinical programs and we believe we are the midst of the transformational time at Cytokinetics.

We are extremely encouraged by the results from COSMIC-HF and we believe we are in a stronger position to advance the planning activities that have already been underway for many months in collaboration with Amgen.

For the rest of 2015 and into early 2016 we’ll focus our activities on continued data analysis, planning for potential progression to Phase III and preparations for the full disclosure of the data from COSMIC-HF at an upcoming medical conference.

The results from COSMIC-HF reinforced and validate our commitment to and progress in muscle biology and illuminate the substantial promise that our first-in-class cardiac sarcomere activator may hold for patients suffering from heart failure.

We also believe our other development stage programs may similarly hold great promise for patients battling diseases characterized by impaired muscle function.

As I mentioned earlier, during the recent quarter we also continued research activities under our joint research program with Amgen directed to the discovery of next generation cardiac muscle activators as well as under our joint research program with Astellas directed to the discovery of next generation skeletal muscle activators of note together with Astellas we have recently selected a skeletal muscle activator candidate and anticipate initiating IND enabling studies in 2016.

We will continue working diligently with trial sites in VITALITY-ALS to progress activation and patient enrollment, particularly as you have heard on the European front with a goal of having the majority of sites up and running by year-to-end.

We deeply recognize the urgency within the ASL community to advance new medicines for people battling this progressive debilitating disease and we remain fully committed to doing our part.

We are also encouraged by the tremendous momentum within the ALS community to advance guidelines to accelerate drug development and regulatory approval of potential medicines for ALS. We are working to lend our support to the ALS association on these initiatives.

Starting this, our very first Phase III clinical trial was a key milestone for Cytokinetics and the ALS community at large.

We very much appreciate how important a potential therapy that may slow the decline of respiratory function and potentially reduce the time to assisted ventilation and other such independence limiting activities can be for patients and their caregivers.

We are equally excited to begin our Phase II trial of CK-107 in patients with SMA that will occur we expect in the coming months.

The feedbacks from the SMA community continues to be positive and encouraging and we recognize the opportunity to advance this potential new medicine especially at a time when adolescent – an adult patients have no therapeutic options.

We are very proud of the strive that Cytokinetics is taking as a leader in neuromuscular disease and muscle biology in general and no patients are counting on us.

As a company we spend considerable time with patients and their loved ones and this quarter participated a number of fundraising walks, bike rides and other civic activities as well we participated in the second annual ice bucket challenge with our employees. Finally, you may have noticed something new on today’s press release.

We have recently launched new branding for Cytokinetics including a new corporate logo and website. Our goal was to better reflect the company’s evolution and maturation over the years, from our initial loops in cell biology to are now becoming a recognized leader in muscle biology with multiple drug candidates advancing towards commercialization.

We encourage you to check out our new website. Now I’d like to recap our expected milestones for the remainder of 2015. For tirasemtiv, we anticipate concluding enrollment of VITALITY-ALS over the next 6 to 9 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.

In addition we expect Astellas will initiate a Phase II clinical trial of CK-107 in patients with COPD in the first half of 2016. And for omecamtiv mecarbil we expect to continue joint development activities and collaboration with Amgen directed to the potential advancement of omecamtiv mecarbil to Phase III clinical development.

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

[Operator Instructions] And our first question comes from Joe Pantginis with Roth Capital Partners..

Hey guys good afternoon, thanks for taking the question and congregations on the omecamtiv data.

Couple of quick questions first, with regard to the data I know you’re looking to maintain the data for a medical conference, but I was just curious if there is anything you can comment on with regard to the improvements that you saw with heart functions relative to the standard of care that’s currently out there and also potential synergies between those drugs as you anticipate the future landscape for omecamtiv?.

Okay, so thank you Joe. I’m going to stop sort of making any comparative statement certainly this is a Phase II study we are evaluating omecamtiv mecarbil.

What I can say is that we are very pleased with the consistency in the totality of the effects it’s now like we saw effects in 1 echo cardio graphic parameter and not others in such a way that would give us pause for concern rather instead the consistency across these measures as were detailed in our press release is what I think is especially gratifying..

I think we should also point out in response to another element of your question; the study was done over a background of standard of care. So these solitary findings that we described in our press release were in addition to beta-blockers, diuretics, ace inhibitors, ARBs etcetera..

The other thing I might underscore Joe is that this is the first time we’ve had an opportunity to evaluate oral dosing of omecamtiv for weeks duration of treatment and in that way we were able to unveil other advantages perhaps of this therapy as we may want to now further verify those in a potential Phase III study..

That’s helpful, thank you.

And then if I could just switch gears for my second question to VITALITY, may be can you remind us with regard to the potential for any interim analysis, looking forward with rosy colored glasses hopefully if you were to see something dramatic regarding the positive impact on breathing function, could the DSMB halt the study early ethical reasons?.

So let me answer the question and then I’ll turn it over my colleague Fady to also elaborate. So I remind you that this is a study that has as its primary efficacy end point that change from baseline in slow vital capacity as measured at 24 weeks on patients receiving tirasemtiv versus those receiving placebo or standard of care.

But then also we are continuing the conduct of the study in a double-blind randomized way so that all patients continue through to later time points and at 48 weeks we’ll be measuring certain secondary end points including time to follow in the ALSFRS respiratory domains time to mechanical ventilation respiratory failure, et cetera.

So certainly, in order to be able to satisfy the objectives of both the primary and secondary end points we need to have patients preceding through to the secondary end points as measured to 48 weeks. Now, I’ll turn it over to Fady to comment on the potential for early stopping..

Yes, I think, as Robert indicated, in order to maintain the integrated study, well, it’s preceding to 48 weeks, there are no pre-specified stopping rules per se, most of the time when you implement those, those are related to overwhelming efficacy on an endpoint that it’s similar to mortality or something like that.

So in the course of 48 weeks, not enough these patients really are going to die in that time course to trigger that sort of – triggers that sort of event.

But as Robert indicated, continuing to study in a double-blind fashion even as the primary endpoint maybe read out eventually as measured to 24 week time point, will enable us to see what the effects of the drug are over a longer term treatment..

So another way to put this, I’ll remind you is that in designing by VITALITY-ALS, our aim is to confirm an extent the findings we observed on SVC in benefit ALS, which were measured at 12 weeks.

So in this study, we’ve really do want to get patients longitudinally out to 48 weeks, there will be interim meetings of a DMC to review primarily safety, but not otherwise will they be charted to early stopping based on efficacy..

Okay, great. Thank you so much guys..

Thanks, Joe..

And your next question is from Jason Butler with JMP Securities..

Hi, Jason..

Hi, Robert. Thanks for taking the questions and congratulations on all the progress. I just wanted to ask another question on the omecamtiv results from COSMIC. And this is a topic that we’ve discussed a lot about those drugs over the years.

So I guess, can you just put into context once again, the impact that this drug has on troponin levels and what you see for omecamtiv and the impact on troponin and it’s relevance to clinical outcomes. Thanks..

Certainly, I’ll started get and turn it over to my colleagues afterwards. So we have assessed omecamtiv mecarbil in multiple clinical trials over the years, as you point out.

And in earlier studies we have evidenced that excess concentrations of omecamtiv can sometimes induce a ischemic complication that can be associated at times with elevated troponins.

We also know that in heart failure patients that can be often times experience elevations of troponins whether patients are on omecamtiv or not, that’s a consequence of the disease.

So in this trial of 20 weeks duration of treatment, we had a good opportunity to evaluate background troponins and we agreed to do very intensive monitoring of troponins over many weeks of treatments and as patients came in for their visits and they were also getting evaluations of PK for exposures and concentrations, we’re also in a position to evaluate troponins and without going into numbers, what I can say is there were troponin elevations in both placebo and treated populations.

But as we agreed to do in this trial, I say we – it was of the part of the investigators, investigators we’re then asked in each case to submit all of the EKG’s another data associated with those patients when a troponin elevation was observed to independent third party for adjudication.

As you saw in the press release each and every instance where there were troponin elevations that trigger that adjudication in each and every case they were adjudicated negatively for either ischemia or infarction, that’s quite an impressive number, that number is zero.

So in light of that, well, I don’t think this will put the issue to bed, it certainly is encouraging that we can now see in 20 weeks of treatment, that these background troponins at least in this trial may not be associated with those adverse consequences.

Maybe, now, I’ll turn it over to Fady and Andy to comment on their perspective and in particular why, what we also observed with respect to proBNP is reassuring..

I’ll just made a comment that troponin is a biomarker as much like the other things that we saw, as Robert mentioned. In this case that’s biomarker was not associated with any clinical adverse events, so consequence none of those troponin increases were adjudicated as potential as myocardial infractions.

There were balanced in the other cardiac adverse events.

The other biomarkers on the other hand of potential benefit are things like the reduction in cardiac dimensions, reduction in NT-proBNP and other measures of cardiac function as well as decreases in heart rate, all of those things are biomarkers of potential benefit and I think, what a Phase III trial has do now is to, it will adjudicate the balance of those things and ask what wins and where does the risk benefit profile and looking like at the end of the day..

Great, that’s really helpful. And then just a question on CK-107 and the new plans to move into COPD, can you talk a little bit about the rationale for investigating the drug in COPD and whether it’s tied in some way to the impact on long function you see with tirasemtiv..

Yes, actually it’s isn’t ugly enough, it’s a – you might go in that direction, but it really have to do with the fact that patients with severe COPD have significant muscle wasting and even metabolic abnormalities of your skeletal muscle.

That probably contribute to their exercise limitation even more in these advanced patients than do their diminished lung function. In fact, in terms of their skeletal muscles of respiration in patients with really severe obstructive disease they actually tend to be hypertrophy because of the extra effort of breathing that these patients experience.

So we’re really targeting the appendicular muscles or legs in order to help them increase their exercise tolerance because they are diminished exercise tolerance is a significant part of their morbidity..

That’s really helpful. Thanks for taking the questions and congratulations again..

Thanks, Jason. I’ll just maybe summarize that by saying, we’re very pleased that Astellas is stepping up by doing this trial and also for the first time, we’ll have an opportunity to evaluate a skeletal troponin activator in a non-neuromuscular setting. As you know, we expanded our deal with Astellas in 2014.

And we’re also talking about other potential Phase II indications that may follow. So we’re really going to dial up the breadth of the clinical development programs around CK-107, and we should have more to say about that through 2016. Operator, we have the next question please..

Your next question is from Chad Messer with Needham..

Hi, Chad..

Hi, this is actually Esther Pang [ph] sitting in for Chad, thanks for taking my question. And congratulations on the COSMIC data..

Thank you..

My first question is actually about VITALITY, do you guys have any updates on the SPA – discussions with the FDA?.

No, and that’s a consistent question that we’re getting from Needham on these earnings calls. I don’t have an update for that and don’t expect that we will have one. If there is something more to say about that then we certainly will..

Thanks. And turning over to the COSMIC data I know you guys are holding out for a conference.

Do you have any ideas, which conference you might go to?.

So don’t yet – we know what we may have eligibility for so, the good news is the abstract submission deadline for ACC was earlier this week, AHA is coming out in just a few weeks and certainly it’s too soon relative to that conference, but one conceivable venue would be ACC which is in April 2016 and then we’ll consider whether there may be others as well..

And I have another question on omecamtiv, could you remind us what the IP on that?.

Okay, so the public information can be found in our quarterly filings with Form 10-Q, but the composition of matter pattern for omecamtiv mecarbil is due to expire without any extensions in 2027 and certainly we would expect extensions beyond then..

And lastly for the CK-107 program, describing in a little more on the COP the [ph] program.

What kind of endpoints that you expect would you do like a six end point or would it be more on one function?.

No again, as we were discussing it’s this is really about overall exercise parts now we will make some ancillary measures of inspiratory and expiratory pressure, but that really has more to do with what happens with air traffic [ph] in the lung during various exercise, primary end points will be duration a particular exercise test, frankly it’s a little bit more complicated than just a 6 minute walk test, it’s done on a special bicycle and we’ll have more details about that when we open study to enrollment in the next several weeks..

Okay, thank you..

Thank you very much..

And your next question is from Ritu Baral with Cowen..

Hi Ritu..

Hi, can you help us frame the systolic ejection time data that will be coming upon presentation of the data, speaking to KOL they haven’t given some of us – just spoken to them on consolation.

Any sort of minimally clinically important difference on that, but just in your understanding of that measure literature, natural history, what should we be looking for as far as magnitude?.

Sure, I’ll start and then I will turn it over to Fady.

So one thing I’ll point you to is a poster that was presented at the Heart Failure Society of America meetings recently by Scott Solomon and his group, which look historically as systolic ejection time and how it correlated with severity of heart failure in a population of cardiac disease patients and certainly, shorter systolic ejection time was associated with lower frequency of heart failure.

I’m sorry – with lower frequency shorter systolic ejection time associated with higher frequency of heart failure.

What I can tell you is that in this study, we had patients that were chronic heart failure patients and we haven’t yet reported on the baseline characteristics, but these are patients who as you saw in the press release did evidence statistically significant increases in systolic ejection time, the quantifications are need to wait a full presentation of the data, but maybe Fady can speak to what are for a population heart failure patients what would be typical systolic ejection time and how that might change overtime..

Yes. I think the systolic ejection time is probably one of the oldest markers in cardiac function. It was something like could be measured long before we had echocardiograms and another capture ways of measuring cardiac functions.

And as what Robert mentioned if you looked at data sets, as look at that measure systolic ejection time and then follow patients for years, shorter ejection times associated with the greater incidents of developing heart failure as well as cardiovascular mortality. So – and also, if your cardiac function gets worse, your ejection time get short.

The heart spending less time, it can generate less force and so, it can really eject blood for a shorter period of time. Omecamtiv mecarbil by increasing ejection time is increasing the amount of blood is being ejected from the ventricle and is sort of normalizing that decrease if you will.

I think the magnitude of change, small changes if you look again, the poster was presented heart failure meeting, small changes on the order 10 milliseconds had significant increases in cardiovascular morbidity.

And so one could expect, maybe potentially and reverse the small changes, small increases could also have potential improvements, but that’s something, that this drug mechanism really will be the first to demonstrate..

Yes. Well, certainly systolic ejection time appears to be the characteristic signature of the mechanism of action of omecamtiv mecarbil, where we need to see only that and not also associated increases and stroke volume and other reductions and dimensions et cetera that would be perhaps interesting, but not as compelling.

I think we’re compelled by the fact that in these data sets that we have reviewed there was a consistency of fact across the echocardiographic parameters for which we have more evidence that those things tend to be associated with improved clinical outcomes..

And that’s really helpful. And actually that leads into my second question, Robert.

When you’ve talked about statistically significant differences and dimensions, in echo dimensions, what were the measures taken and which ones do you believe that especially which are the most important dimensional measures that relate to cardiac function and extra sized capacity?.

Well, the literature – the most important metric, if you will, cardiac function that has thought to be associated with improved outcomes is a reduction in the cardiac volumes. And so, dimension, volumes, there basically is fine that the heart is getting smaller.

And so those are the kinds of things that one – because a heart failure would happen if the heart gets bigger to accommodate for the fact that it’s function is poor. So we find that the heart is getting smaller is a positive sign. It’s probably what people think of as the most important sign..

So it’s something like left ventricular volumes?.

Some volumes are what, – yes, volumes that generally were published in the literature as being – that they most – the key cardiac marker. Heart rate those also an important marker as this empty pro-PNP. So you again you can find many papers and literature showing that lower heart rate is better, patients have better outcomes, lower heart rates.

And patient with lower NT-proBNPs have better outcomes. That constellation is all a pleasing picture if you will in terms of the effects on cardiac function and hemodynamics..

Got it. Thanks for taking the questions..

Thank you, Ritu..

Your next question is from George Zavoico with JonesTrading..

H, George..

Hi, Robert. Hi, Barbari. Hi, Andy. Hi, Sharon. Congratulations on a good quarter and looks like also moving forward coming up soon. I have a couple of questions. First sort of continuation where we’re just talking about where we to – and that’s the change in the dimensions of the heart size that you’ve seen in the 20-week.

And it seems to be one of the Holy Grail if you will. In heart failure is positive remodeling. And this seems to be going in that direction, and that sort of deferred within 20 weeks, that’s certainly encouraging.

Could you provide instant context in terms of how fast it happened, where you talk a little bit about its significance? So maybe you don’t have to do that, but a typical standard of care now for heart failure, you’ve really do that.

Is that correct?.

So do I think like – what one sees in other situations is that the changes evolve over time. Not every – no, there aren’t studies that have looked at the time course of this. Often they look at 12 months and they look at the effects there.

But in terms of how rapid they’re produced, I think the period of time that we’ve studied them in COSMIC is probably the minimum amount of time one would want to look for those kinds of changes to occur..

So if the cycle ever happened, it is then you take it as a good time, but in the context of your current standard of care which really is a beta-blocker, thyroiditis et cetera, you really don’t see that, do you?.

You do see. So beta-blockers do produce reductions in cardiac, dimensions over time, and data have been published to that effect. That data goes back to the mid-90s basically..

Okay..

But certainly, in fact two drugs that are primarily acting by a mechanism to increase cardiac performance, this is an interesting finding and we want to follow it up with further clinical trails. But in order to be able to say anything about remodeling I think we’d have to be looking at a longer duration treatments.

And also you have to be able to assess that in a way where patients have the drug withdrawn as well, and then you can be able to assess whether that change diminishes.

So that’s going to be one of those things that would be very interesting to pursue in further clinical trials in over time, but you can be sure that that’s a provacative interest in finding that we will want to pursue..

No not only that, but as you’re saying a longer duration dosing should provide a lot more interesting information as well. So I imagine we’ll see that in the next trial. My question regards to titration, because you titrate omecamtiv to certain plasma level.

This is just the patients are on this drug omecamtiv mecarbil clinically we will need to go and get monitoring for dose levels once they reached a particular target and take there is any changes due to other comorbidities dietary changes like I’m taking orphan for example.

I don’t although I don’t definitive dietary change, if you comment on, how this might be monitored going forward, in terms of what that probably looks like?.

To be clear, what was done in the dose-titration group, it was not targeting any particular plasma concentration. Plasma concentration was measured only once, at the end of a dosing interval, we are at troche as we say in the morning and if it was above a certain threshold and the patient was kept on 25 milligrams twice a day and titrated up.

And if it was below a certain threshold then they got the dose increased. And while plasma concentrations were measured at subsequent visits, there were no decisions regarding dosing made they were just for our information from the study.

So if we were to do that again in Phase 3 and when the product is hopefully commercialized, it would just be based on one single plasma concentration, we are under a week or two after initiating treatment.

Now as we understand the data more fully, we may decide to modify that, if that algorithm a little bit in Phase 3, but that they will have the time to really consider that carefully..

Okay, and then definitely making more convenient if you wanted to do….

My question about VITALITY in the Phase 3, you’re targeting three different doses.

If they intense to in the Phase 3, ultimately the pick one dose, because it doesn’t seem to me yes, at least if there is any criteria, our biomarkers that you’re going to do acquisition for any particular dose?.

Well. So based on the data from benefiting ALS we couldn’t really, because we tried to get everybody up to the top dose of 250 milligrams twice a day, but 500 total daily dose, and about half of dose that finish the trial got there and about another quarter we’ve finished with 375 a day and the other at 250.

So when you look at their changes in vital capacity they were remarkably different across those three dose levels. But you have to remember that the patients want randomize to them.

So I think they got there based on tolerability, so we don’t really know if the patients, who ended the trial at 250 if they couldn’t got in the 500 might not have done better. We also don’t know if the patients who ended on 500 and just as well at 250. So right now is intended to answer that question.

So some patients will never titrate up, they will stay on that starting dose of 250 a day. Others with titrate once and others will the attempted to go up to 500.

They won’t unnecessarily stay there, based on tolerability but the data at the end of the trial, will tell us, whether the best strategy is never to titrate or to titrate once and then that’s enough or to try to get patients up to 500, if they can tolerate it, we don’t have the data, but VITALITY will provide that data..

Okay that really helps, great. Thank you very much looking forward to the progress. Thank you very much..

Thanks, George..

Thanks George..

Your next question is from Vernon Bernardino with FBR Company..

Hi, Vernon..

Hi, everyone and congratulations also from me regarding the COSMIC results. I am very excited for you guys. You had mentioned that you had already conducted findings activities for a Phase III with Amgen.

That certainly is a positive, now I guess the question that passing to my head was perhaps Amgen just as this part of the just the process or you think that Amgen was so optimistic about, perhaps the results being positive at. They certainly wanted to get ahead of these kinds of activities.

Because, I think you mentioned that some of these were clinical, but there were also certainly manufacturing, I just wonder if you could comment a little bit about the activities..

Sure, able to comment to the extent that I’m reflecting on Cytokinetics and our interest in, a lots of folks have been asking us what the Amgen going to do. And I think it is best to ask Amgen that question.

As far as what we have been doing collaboratively what I can say is, it is good prudent planning, in anticipation of results of the clinical trial, such as COSMIC-HF to be ready to go to the next level.

So over many months we and Amgen together have been engaged in planning processes that are typical of readiness associated with manufacturing, associated with regulatory interactions.

Associated with designing clinical trials and protocols getting budgets in the order and being in a best position to move promptly upon a decision to proceed, potentially to Phase 3. So I know that this is an activity and a series of work streams that we have been engaging for quite a long time together with Amgen.

And I guess that’s all I probably can and I should say..

Okay, so it sounds like, it’s just like I said, prudent part of the process. Now you had mentioned that you just got the data recently, what are the current activities now, as far as the data is concerned and what needs to be done before you perhaps make a call or request a meeting with the FDA or maybe even just getting together with Amgen..

So, I’m not going to be able to go into this, probably to a detail that you’ll find satisfying, but what I’ll say is these data are relatively fresh, relatively new and there is still a lot of going through the data that needs to occur.

So we want to understand this data from COSMIC and also integrating these data with other data that we generated from the ATOMIC another studies. It’s important to understand what we can learn from dose-response relationships, PKPD, exposure relationships, et cetera.

So there’s a lot of integrated kinds of analysis that I’m sure are going to be occurring as well. There’s still work that needs to occur to finalize the potential protocol for potential progression to Phase III that include certain statistical analysis and other sorts of readiness.

There’s other work that needs to occur as it pertains to getting feedback from regulatory authorities and also – even internally as we think about budgets, potential forecast, return on investments, et cetera.

So there are work streams across all facets and functions here at the company at Cytokinetics, so that we can be best poised to be a good partner to Amgen and help inform these decisions. And ultimately I suspect those things are occurring also at Amgen and then we’ll come together and we’ll make a decision together..

Terrific, that’s helpful. And this is a questions perhaps for Sharon, but – so assuming Amgen exercises your option you get the milestone payment.

How will the payment be treated as far as the income statement is concerned?.

It most likely will be amortized there’s another piece of that from an accounting rule that goes the long with that. And that happens to be our ability to opt in, in a similar type of timeframe. So that will dictate those two events don’t – aren’t necessarily being linked from an accounting treatment standpoint.

So we’ll have to take a look at that at the time those two takes place..

Okay, just want to experiment what your lumpy will be left untreated?.

Yes..

Okay, great. Thank you for taking my questions and congratulations again..

Thank you Vernon, I appreciate it..

And your next question is from Sarah Weber with Piper Jaffray..

Hi, Sarah..

Hi. This is Sarah, on for Charles..

Thank you, Sarah..

So congratulations on the data, I had one question just how are you thinking about the IV versus oral market for omecamtiv going into Phase III?.

How are we thinking about the marketplace or how we thinking about the use of the IV versus the oral in Phase III?.

I guess both but you can talk about Phase III..

So, with regards to the Phase III there is still discussions that we and Amgen are having about how best to design our Phase III program, whether we’re to proceed to one? What would it look like? Would that be one outcome study? Would that be multiple studies? Would it include hospitalized patients or just outpatients? Would it be patients who might – first receive the IV and then transition to the oral? Those are still things that are in conversation.

So no decisions have been made with regard to that. As you maybe alluding by your question, there are markets for each of the IV and the oral that come into play here, and the oral certainly can extend in hospital, as well.

So what we do know is that the biggest issue right now amongst the heart failure community, is what can we do better to treat patients such that we can reduce the high morbidity and mortality associated with the diagnosis right now of heart failure and also acute heart failure.

So many of these patients even upon discharge from hospitalization die or readmitted within three months, six months and 12 months. So as we and Amgen have spoken in the past our goal with potential outcome study or studies would be to try to make a dent in that.

And that means potentially taking patients to a higher risk of death and readmission and on a treatment regimen with omecamtiv mecarbil seeking to see whether or not we can reduce death and readmission in that population.

Whether that means starting patients on the IV and transitioning from the oral or starting them in the hospital on oral and transitioning them, outpatients on oral or starting patients who were recently discharged on oral, and continuing on oral, those are all things that are subject to active dialogue..

Thanks, that makes sense. And then just one question on the VITALITY study.

So in addition to enrollment, will we get any updates on patient characteristics or the dropout rate?.

It’s a good question, it’s too early for that now, but that maybe something that we’re going to better position to speak to in 2016 especially as we’re nearing or completing enrollment. We maybe in a position to talk about some of those things, check back with us and that’s something that we’ll be determining.

I don’t want to do anything that would buy us the conduct of the study. So we have to make sure that wouldn’t put us at risk in that way..

Great. Thanks for taking the question..

Thank you..

And your next question is from Ritu Baral with Cowen..

Hi, Ritu..

Hi. Thanks for taking the follow-up. It’s on 107, you gave us some messy tone, Phase II that will start. Could you give us certainly more granularity on the efficacy endpoints the respiratory and skeletal muscle function.

Specifically are you looking at function or you looking at strength and when you look at respiratory, what’s more important in a disease like this, are you looking for like myth or math or are you looking for something like vital capacity?.

Just to clarify, are you referring to the Phase II study in patients with SMA?.

Yes, yes..

Yes. So we can give you a sense of with the kinds of things we’ll be assessing. We’ll go into more detail when we do initiate enrollment. But suffice is to say that in this populations we’ll be doing, like we’ve done before, a Hypothesis-generating study. So we’ll be looking at a multitude of different assessments both respiratory and otherwise.

But may be I’ll turn it to Andy, if you want to take that?.

I think that – about what we should say at this point, we will provide additional scale when the studies open to enrollment. And we are looking at a variety of different measures, they’re not of pulmonary function measures.

Some of them look at what kind of activities the patients can actually do there’s a fairly standard scale called the hammersmith scale that’s used for these patients, which is a specially important for the non-ambulatory patients. Those who can walk, we can do a six minute walk test in.

So that will give you I think, an idea and there’ll be more detail when we open the studies for enrollment..

Yes. To that point we are and as we communicated already publicly, we are looking at a patients in different cohorts, those that are both ambulatory and also non-ambulatory and the assessments will vary depending on that..

Got it. Thanks for answers..

Sure. Thank you..

And we have no further questions in queue. Thank you, at this time. And I would like to turn the conference back over to Mr. Blum..

Thank you, operator. So these are especially important in gratifying times at the Company.

Some of these events really have quite significant implications to our forward business and we are especially grateful for the patients and the care givers who participate in these studies and also to our partners Amgen and Astellas in the conduct of these trials.

We’d also like to thank all the participants on our teleconference today for your continued support and interest to Cytokinetics, with that operator we can conclude the call..

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