Cytokinetics, Incorporated (CYTK) Q2 2013 Earnings Report, Transcript and Summary

Good afternoon, and welcome ladies and gentlemen to Cytokinetics' Second Quarter 2013 Conference Call. At this time, I would like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the Company's request, we will open the call for questions-and-answers after the presentation. I will now turn the call over to Sharon Barbari, Cytokinetics' Executive Vice President of Finance and CFO. Please go ahead.

Good afternoon and thank you for joining the Cytokinetics senior management team on this conference call today. Also present during this call are, Robert Blum, our President and Chief Executive Officer; Dr. Andrew Wolff, Senior Vice President of Clinical Research and Development and Chief Medical Officer; and Dr. Fady Malik, Senior Vice President of Research and Early Development. Following the forward-looking statement disclaimer, Robert will provide an overview of the past quarter highlighting our recently announced corporate partnering transactions, Fady will update you regarding recent progress in the clinical development of omecamtiv mecarbil for the potential treatment of heart failure, and Andy will then provide an update on the clinical development of tirasemtiv in patients with amyotrophic lateral sclerosis or ALS and on the Phase I clinical trial of CK-2127107 or CK-107 in healthy volunteers. I'll then provide a financial overview and updated financial guidance. Robert will then conclude the call with additional comments regarding how these recent activities come together to align with our corporate strategy and expected next steps and projected milestones for 2013. We will then open the call for questions. The following discussion, including our responses to questions, contain 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, in 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. Now I'll turn the call over to Robert.

Thank you, Sharon. The second quarter has been a very busy and a highly productive one for Cytokinetics with the expansion of an existing collaboration agreement and the signing of a new collaboration agreement that have significant strategic implications for our respective cardiovascular and skeletal muscle programs. We executed well by closing these important transactions. We also continue to make important progress in the conduct of our later stage clinical trials for our investigational products arising from these programs. The deals infuse immediate cash but are also very purposely intended to afford us access to capital over the medium and longer term, in step with each program's respective progress and as sponsored by our partners in each case. Moreover, the deals go beyond monetizing returns on prior investments for Cytokinetics. Of course they do that too and those are prerequisite for any deal we do. However, each of these deals substantially augments our strategic reach; with Amgen, geographically towards Phase III and in an indication we are already pursuing, thereby reinforcing our existing relationship; and with Astellas, programmatically and towards Phase II in indications we could not have pursued alone but can now do so with a highly motivated leading multinational pharmaceutical company. Starting with the first deal we announced in June, we expanded our license relating to omecamtiv mecarbil with Amgen to include Japan. In connection with this expanded license, we received $25 million from Amgen comprised of a non-refundable license fee of $15 million and $10 million for Amgen's purchase of Cytokinetics' common stock. In addition we are eligible to receive pre-commercialization milestone payments for the development of omecamtiv mecarbil in Japan of about $50 million as well as royalties on sales of omecamtiv mecarbil in Japan. Executing on this transaction now positions us well to integration the development of omecamtiv mecarbil in Japan into a potential global registration program, as we are considering strategies for the Phase III clinical development program for omecamtiv mecarbil. Fady will provide an update on development activities and progress relating to omecamtiv mecarbil later in this call. Alongside announcing the expansion of our deal with Amgen, we also announced that results from ATOMIC-AHF will be presented at a Hot Line Session at the upcoming European Society of Cardiology Meeting, and today, we are announcing encouraging progress in the conduct of COSMIC-HF. We are optimistic about omecamtiv mecarbil and together with Amgen we are taking steps to ready for the potential advancement of this program, both in terms of the stage of trials and its expanded geographical scope. The second deal we announced in June was a new collaboration with Astellas, a deal which we announced within a week of announcing our Amgen deal. The collaboration with Astellas focuses on research, development and commercialization of skeletal muscle activators. The primary objective is to advance novel mechanism drug candidates for diseases and medical conditions associated with muscle weakness. Cytokinetics is eligible to receive over $40 million from Astellas over the next two years which comes in the form of a $16 million upfront non-refundable license fee and over $24 million in reimbursed sponsored research and development costs. In this deal, Cytokinetics has exclusively licensed to Astellas the right to co-develop and jointly commercialize CK-107, our next generation fast skeletal troponin activator currently in Phase I of clinical development for potential applications in non-neuromuscular indications. Through this collaboration, we will also jointly conduct research to identify additional skeletal muscle activators which may be nominated as drug candidates in the future. This deal affords us the ability to expand our R&D well beyond what we've been able to practically do ourselves. We're excited about working with Astellas in this emerging area of pharmacology. Astellas shares our strategic vision for next-generation skeletal muscle activators and augments and complements our capabilities in this area of novel mechanism biopharmaceutical R&D. Now I'd like to turn to our development of tirasemtiv, our first in class fast skeletal troponin activator, currently moving through the ongoing Phase IIb BENEFIT-ALS clinical trial. We have recently provided updates on this trial. We've announced that BENEFIT-ALS has enrolled over 500 patients to-date. I'm pleased with that progress and encouraged by the interest we've received from investigators as well as the patient community. As we have stated often, we have high hopes for tirasemtiv as the first potential treatment in nearly 20 years for this most grievous illness, ALS. We recently announced a study drug assignment error in BENEFIT-ALS that was detected as a direct result of Cytokinetics conducting regular oversight of study drug inventory. We promptly proceeded to investigate this serious matter and learned that the company responsible for the electronic study drug assignment in BENEFIT-ALS had committed an error in programming. As you will hear more from Andy in a moment, we identified the error and assure that it was fixed and we have put in place additional monitoring procedures with regard to the conduct of BENEFIT-ALS to better serve Cytokinetics and the proper development of tirasemtiv for the potential treatment of ALS. Following interruptions with the regulatory authorities and in particular with the FDA, we proceeded to file an amendment to the protocol for BENEFIT-ALS increasing the enrolment in a manner that we believe will enable us to preserve the intended statistical powering of BENEFIT-ALS. Andy will provide further details regarding the protocol amendment in a moment. We estimate that continuing BENEFIT-ALS under this protocol amendment will add to the cost of BENEFIT-ALS and delay the availability results from this trial. To be very clear, we are concerned that this error was committed by a third-party company engaged in the conduct of BENEFIT-ALS. Despite the setback, we remain optimistic and hopeful for tirasemtiv in this trial. The test of a company's mettle, and I would argue a predictor of its future successes, is often how it deals with adversity. Cytokinetics responded well to the challenge to benefit patient and shareholders. With that introduction, I'll turn the call over to Fady to elaborate on the recent progress that we've achieved with omecamtiv mecarbil, and later in the call, I'll return to provide additional perspectives relating to our future plans.

Thank you, Robert. To remind participants on this call, ATOMIC-AHF is an international randomized double-blind placebo-controlled Phase IIb clinical trial designed to evaluate the safety, tolerability and efficacy of an intravenous formulation of omecamtiv mecarbil compared to placebo in patients with left ventricular systolic dysfunction hospitalized with acute heart failure. As we previously announced in June, the results from ATOMIC-AHF have been accepted for presentation during a Hot Line Late Breaking Trials Session at the European Society of Cardiology or ESC on September 3 in Amsterdam. We are half there and are working diligently with our colleagues and Amgen as well as study investigators to prepare for that presentation. I'm also pleased to announce today that results from ATOMIC-AHF will be presented in the Late Breaking Clinical Trial Session at the Heart Failure Society of America or HFSA Conference on September 23 in Orlando, Florida. We are pleased the results from ATOMIC-AHF can be shared too in these important upcoming cardiology conferences. These are exciting times for this program and that arose for Cytokinetics research over 10 years ago and that offers promise for the treatment of this severe disease that has been asking meaningful innovation for a long time. With the completion of ATOMIC-AHF and the expected presentation of data in September, we and Amgen can now focus our attention on the progress of the COSMIC-HF trial. To remind you, COSMIC-HF is a Phase II double-blind randomized placebo-controlled multi-center dose escalation study designed to evaluate three modified release oral formulation to omecamtiv mecarbil for patients with heart failure and left ventricular systolic dysfunction. This international trial is anticipated to inform our understanding of the oral pharmacokinetic and longer term safety and tolerability of omecamtiv mecarbil in the chronic heart failure patients. In addition, we'll have an opportunity to evaluate the potential for sustained pharmacodynamic effect and the relation to the pharmacokinetics of this drug candidate. As we have mentioned, COSMIC-HF will be conducted in two phases. First, with a dose escalation phase which will compare the pharmacokinetic profile of three oral forms of omecamtiv mecarbil, first the 25 mg twice daily in cohort one and then at 50 mg twice daily in cohort two. Each cohort is dosed for seven days and will inform selection of a single-dose form. In the second phase, an expanded cohort of heart failure patients will be randomized to the selective oral form of omecamtiv mecarbil at either of two doses or placebo for three months of treatment. I'm pleased to announce today that in the last quarter, cohort one of COSMIC-HF was completed and cohort two of the dose escalation phase COSMIC-HF recently opened to enrolment. This trial is enrolling well in the United States and internationally. We expect to have data from cohort two to inform potential next steps in 2013 to include the potential progression of omecamtiv mecarbil to the expansion phase of COSMIC-HF and planning activities related to Phase III. The rate of enrolment of patients in the dose escalation phase of COSMIC-HF underscores the enthusiasm for omecamtiv mecarbil to meet the high unmet needs in the treatment of heart failure. Clinical investigator sides appear to be embracing the opportunity to participate in this first in class program and we remain encouraged by its progress and prospects. At Cytokinetics, we feel an obligation to see this program move swiftly to a broad based clinic program that may be supported by the results of ATOMIC-AHF and COSMIC-HF. The results that we now have from ATOMIC-AHF, a study performed in a high-risk patient population, are important to inform discussions between Cytokinetics and Amgen as well as between Company's key opinion leaders, regulatory authorities and others as we map for plans for omecamtiv mecarbil. In connection with that objective, as Robert mentioned a moment ago, with the timing of the expansion of our collaboration with Amgen to include Japan, Cytokinetics is proceeding with plans to conduct in collaboration with Amgen a Phase I pharmacokinetic study intended to support the inclusion of Japanese patients and a potential Phase III clinical development program. Taking that key next step forward is evidence of our confidence in our new novel mechanism of the cardiac myosin activator. Lastly, I'm also pleased to report that during the last quarter, Cytokinetics and Amgen reviewed results from the recently completed Phase I open label single-dose clinical trial designed to compare the pharmacokinetics of omecamtiv mecarbil in patients undergoing hemodialysis versus healthy volunteers. We are encouraged that no clinical meaningfully differences were observed in this study of the pharmacokinetics of omecamtiv mecarbil administered to patients undergoing hemodialysis versus healthy volunteers. The implications of the study are meaningful to the later stage registration program as many heart failure patients have renal dysfunction as a consequence of their heart failure or other common comorbidities. These data suggest that omecamtiv mecarbil may be dosed in patients with compromised renal function without dose adjustment. We're encouraged by these findings which are consistent with earlier work performed by Cytokinetics. We that update on clinical development activities for omecamtiv mecarbil, I'll turn the call over to Andy for an update on our skeletal muscle contractility program.

Thank you, Fady. I'm pleased to provide an update on recent developments in our skeletal muscle program. First, we've made solid progress in enrolling BENEFIT-ALS, our ongoing Phase IIb clinical trial of our fast skeletal muscle troponin activator, tirasemtiv. BENEFIT-ALS is a multinational double-blind randomized placebo-controlled clinical trial designed to evaluate the safety, tolerability and potential efficacy of tirasemtiv in patients with ALS. Let's start with the enrolment of BENEFIT-ALS. During our last earnings call on April 30, I announced that approximately six months after we dosed the first patient in BENEFIT-ALS, we had enrolled over 200 patients in the trial. Today, three months later, I am pleased to announce that we have enrolled over 500 patients in BENEFIT-ALS. The raised enrolment in this trial is a testament to the dedication of ALS patients, their caregivers, and BENEFIT-ALS clinical side personnel and investigators. We are grateful for their commitment to this trial. We at Cytokinetics and our colleagues in eight countries are working to ensure that BENEFIT-ALS progresses efficiently to inform us regarding the potential safety and efficacy of tirasemtiv during three months of treatment of patients with ALS. Along the way, we did suffer a setback. As we announced earlier this month, through our routine inventory management procedures, Cytokinetics detected an imbalance between supplies of tirasemtiv and placebo. Soon afterwards, we determined that a programming error in the electronic data capture system controlling study drug assignment implemented during the course of this study caused 58 patients initially randomized to and treated with tirasemtiv to receive placebo instead at a certain study visit subsequent to randomization and for the remainder of the study. No patients randomized to placebo received incorrect treatment. Once the error was detected, we took immediate steps to ensure that no further incorrect study drug assignments occurred and to correct the programming error. In addition, we convened the study’s Data Safety Monitoring Board or DSMB to assess whether this error had impacted the safety of the 58 affected patients. After review of the relevant data from BENEFIT-ALS, the DSMB reported no safety concerns regarding those 58 patients or any other patient safety. At that point, over 450 patients had been enrolled into BENEFIT-ALS and over 100 had completed 12 weeks of treatment. Despite the error, Cytokinetics and all clinical trial site personnel remained blinded to the specific patients affected by the error although we do know that they were enrolled across multiple countries. As Robert mentioned, following consultation with experts, clinicians and regulatory consultants, we've proposed to development regulatory authorities including of course FDA our plan to preserve the scientific value of BENEFIT-ALS. Following interactions with these regulatory authorities, we amended the protocol to exclude from the primary efficacy analysis not only the 58 affected patients but all patients randomized in any permutation block that included any of the affected 58 patients, regardless of treatment assignment. We believe that approach is appropriately conservative and ensures that all patients included in the primary analysis will have been randomized concurrently between the two treatment groups. In order to maintain the originally intended statistical power, we also amended the protocol to increase the overall target enrolment in BENEFIT-ALS to approximately 680 patients in order to replace the patients in permutation blocks now excluded from the primary efficacy analysis. As I mentioned, to date, we have enrolled over 500 patients into BENEFIT-ALS and expect enrolment to continue as the new amendment becomes effective at the participating study centers. We now expect a complete enrolment in BENEFIT-ALS during the second half of 2013. We expect to announce when enrolment has completed, and in anticipation of potential positive results from BENEFIT-ALS, we are preparing for next steps in this program. In the meantime, I will now turn to CK-107, our next generation fast skeletal troponin activator. In the last quarter, we continued to enrol patients in CY 5011, a Phase I first-time-in-humans clinical trial of CK-107 in healthy male volunteers, which is now conducted by Cytokinetics as part of our collaboration with Astellas. CY 5011 is a double-blind, randomized, placebo-controlled study designed to assess the safety, tolerability, and pharmacokinetics of single ascending oral doses of CK-107 administered to healthy adult males in a three-period dose escalation crossover design. CK 5011 is enrolling well and proceeding to higher dose cohorts. In addition, we are planning to initiate other Phase 1 and Phase II readiness activities specified under our development plans for CK 107 agreed with Astellas. Under that plan, Cytokinetics will be primarily responsible for the conduct of Phase I clinical trial including the completion of Company 5011 and we will conduct certain Phase II readiness activities for CK-107. Astellas will reimburse our agreed costs under the plan and will be primarily responsible for the conduct of subsequent development and commercialization of CK-107. Recent progress with CK-107 in Phase I together with our new collaboration with Astellas should enable Cytokinetics now to increase our commitment to the investigation of CK-107 in non-neuromuscular conditions associated with muscle fatigue and weakness. We are excited to expand and accelerate this program under our collaboration with Astellas in this emerging and promising area of pharmacology. With that update on the clinical development activities, I'll turn the call over to Sharon.

Thank you, Andy. This past quarter has certainly been busy on many fronts and that relates to the impact on our financials as well. As our press release contains detailed financial results for the second quarter 2013, I'll refer you to that public statement for the details on our P&L and balance sheet. As Robert mentioned, in June, we signed an amendment to our collaboration agreement with Amgen and we announced a new collaboration with Astellas, both together raising a total of $41 million coming in a combination of $31 million in upfront payments from Amgen and Astellas and the sale of $10 million in stock to Amgen. In June, we received $15 million in an upfront payment from Amgen through the licence development of omecamtiv mecarbil in Japan and $10 million from the sale of 1.4 million shares to Amgen. The Astellas upfront licence fees was received in July subsequent to the close of the second quarter. Including the proceeds from the Amgen transaction, we ended the second quarter with $75.7 million in cash and cash equivalent and investments which represents approximately 24 month of going forward net cash burn based on our updated guidance that we will discuss in a moment. In June, we also filed a Certificate of Amendment to our Certificate of Incorporation to effect a one-for-six reverse stock split. Following the reverse stock split, the company's capitalization table at the end of June reflects 28.7 million basic shares outstanding and 41.5 million shares on a fully diluted basis. The Company now has a total of 81.5 million shares of common stock authorized for issuance. On the capital front, the capital markets front, on July 1, when the Russell Investments reconstituted its comprehensive family of global indexes, Cytokinetics was added as a member of the Russell Global, Russell 3000, Russell 2000 and Russell Microcap Indexes. Russell indexes are widely used by investment managers and institutional investors for indexed funds and have benchmarks for both passive and active investment strategies. Turning now to how we invested our financial resources in R&D during the second quarter of 2013, our R&D expenditures totaled $12.3 million. From a program perspective for the second quarter, approximately 80% of our R&D expenses were attributable to our skeletal muscle contractility research development activities, 7% to our cardiac muscle contractility activities, and 13% to our other research activities. For the six months ended June 30, 2013, our R&D expenditures totaled $22.2 million. From a program perspective for those six months, approximately 77% of our R&D expenses were attributable to our skeletal muscle contractility activities, 7% to our cardiac muscle contractility program, and 16% to our other research activities. Today, we are announcing our updated financial guidance for 2013. The guidance is on a cash basis and includes both the additional revenue and expenses associated with the two collaboration agreements that we signed in June. In addition, it incorporates the additional expenses that we believe will be required to preserve the scientific value of BENEFIT-ALS clinical trial. We anticipate our 2013 cash revenue to be in the range of $40 million to $42 million. Our cash R&D expenses are estimated to be in the range of $52 million to $55 million and our G&A expenses to be in the range of $15 million to $16 million. This financial guidance is on a cash basis and does not include the deferral of approximately $10 million in revenue to future calendar years and an estimated $5.6 million in non-cash related operating expenses primarily related to stock compensation expense. In summary, the deals we announced in the second quarter have contributed to our now being in a substantially improved financial position. We have both added to our cash resources and expect to be the recipient of increased sponsorship of our expanding R&D activities thereby extending our cash runway. We are pleased to report these improved financials to our shareholders, and that concludes the financial portion of today's call. With that, I'll turn the call back over to Robert.

Thank you, Sharon. It has indeed been a productive period of time at Cytokinetics but more importantly perhaps is how does everything that we shared today fits together into our strategic framework. We recently celebrated 15 years since we commenced operations at the Company. Over that timeframe, we pioneered a new area of muscle biology and its translation to a portfolio of novel mechanism biopharmaceuticals. Along the way, we have had multiple successes and the occasional setback, but the [home words] (ph) of our activities have been clearly science, skilled execution, and yes, patience and perseverance. We've executed licensing deals and financings as we believe may best serve our near term and longer term R&D and other business interests. Today, we believe that we are well-positioned to realize the returns on determined investments which may come in the form of potential new medicines for patients. In the second quarter, we saw how persistent commitment to our research in the area of muscle biology has now contributed to another major collaboration that affords Cytokinetics and its shareholders another key vector for value creation while also affording us the opportunity to continue to prosecute tirasemtiv ourselves and as may enable us certain advantages given the high urgent unmet need in the area of ALS and other neuromuscular conditions. In addition, progress and the development of omecamtiv mecarbil has now resulted in an expanded collaboration with Amgen as we engage together towards the potential global Phase III program. These two deals combined have substantially altered our financials and our financial outlook. Cytokinetics is in strong cash position today and is eligible to receive in excess of $1 billion in milestone payments from our queued partner programs. In addition, we have retained significant participation rights in the co-development in both programs as well as co-promotion rights and economics upon commercialization. Moreover, doing these strategic deals has not come at the expense of our retaining full control over our lead development program for tirasemtiv which is soon to be concluding a larger international Phase IIb trial that may have implications for its registration for the potential treatment of ALS. As we all know, ALS is a ruthlessly grievous illness in which we believe our interest are well aligned with those of other stakeholders, including patients, caregivers, clinicians, reimbursement authorities and regulatory authorities. While to be sure, we are disappointed by the delay and additional costs associated with the conduct of BENEFIT-ALS trial, the test of a company is how it responds to inevitable adversity and I hope you may agree that Cytokinetics executed promptly and responsibly in connection with identifying and solving for the error committed in BENEFIT-ALS, much like we have done over 15 years in progressing R&D programs and building out our business with deals. We are pleased that we have a practical path forward and now understand the implications of the protocol amendment on enrolment in 2013 and the expected availability of results in early 2014. In the meantime, we are looking for the presentation of results from ATOMIC-AHF data in September in Europe and the U.S. as well as the continued progress in the COSMIC-HF trial, and in parallel, we are pleased to be dialling up activities with Amgen and also are pleased to increase R&D activities with our new partner, Astellas. We believe our collaborations with each of Amgen and Astellas enhance our ability to achieve our core business strategy which is to build a sustainable and durable biopharmaceutical company. Importantly, executing on our shared vision points to discovering, developing and commercializing novel mechanism therapies rooted in the pharmacology of muscle biology and that are directed to a broad array of clinical indications representing significant unmet needs. We believe these collaborations and also our progress in R&D during the second quarter represent important positive steps for Cytokinetics and the patients and their families that we aim to serve. Now, let me turn back to our expected milestones for the remainder of 2013. For omecamtiv mecarbil, results from ATOMIC-AHF are planned to be presented at the Hot Line Late Breaking Clinical Trials Session at the ESC Congress in Amsterdam on September 3, 2013 at 11.18 AM Central European Time, as well as at the Late Breaking Clinical Trials Session at the HFSA Conference in Orlando, Florida on September 23, 2013 at 4 PM Eastern Time. Also for omecamtiv mecarbil, by the end of 2013, Cytokinetics expects the opening to enrolment of the expansion phase of COSMIC-HF. Now, turning to tirasemtiv, in the second half of 2013, Cytokinetics anticipate completion of enrolment in BENEFIT-ALS. In concluding, we are pleased with Cytokinetics' progress and execution in this last quarter and remain hopeful for their implications for a very bright future for our Company and shareholders. Operator, that concludes the formal portion of our call today, I'd now like to open up the call to questions.

(Operator Instructions) Your first question comes from the line of Simos Simeonidis.

I guess the first one would be for the most, the one that's upcoming in four, five weeks from now, the ATOMIC data in Amsterdam, as you and Amgen are looking at these data and as investors are going to be looking at this data set, what do you think is the most important thing to pay attention to as these data are revealed? Is it going to be mainly the primary endpoint of dyspnea or is it still safety and tolerability or is it other secondary endpoints that are most important in your view in determining whether this is a successful trial and determining whether it's worth taking into Phase III, if you can help us understand how to, what to look for basically?

Sure, Simos. So I need to be very careful and I'll ask my colleagues as well. In as much as you know, now we do possess the data. So I think we should answer that question the very same way we would have answered it before we had the data, before we locked the database and unblinded the data. So to that point, as we've been saying since the study started enrolling, this is a Phase IIb study designed to assess safety, tolerability, pharmacokinetics and pharmacodynamics in this very high-risk acute heart failure population and this is a study that's coupled together with the study of the oral forms, COSMIC-HF, to inform Phase III. So we're looking at the primary efficacy analysis to be sure and also other secondary endpoints. It's going to be with an assessment of the totality of that data that we're in a best position to inform progression to Phase III. I think it might be helpful if I asked my colleagues maybe to speak to what is the primary efficacy analysis and then also what are the key secondaries.

This is Fady. The key primary efficacy analysis as you know is the effect of omecamtiv mecarbil on dyspnea resolution measured over the short term, 6, 24 and 48 hours, and the key secondary endpoint as Robert articulated already has to do with safety and tolerability as well as confirming the pharmacokinetics in what I'd call probably the most ill population that we will study with this drug. So what we're looking for are that the signals we see in those areas are consistent with what we've seen in the past as well as being supportive of continuing to develop the drug in the future and I think that's really what the key point of the study is all about.

So maybe just to elaborate a little bit Simos to that point, we've acknowledged publicly already that were this to be a Phase III study designed specifically to seek approval for the intravenous form of this drug and with the primary efficacy endpoint of dyspnea, we would have powered for dyspnea differently than we did in this Phase IIb study. What we're looking for most importantly in this trial is effects on these endpoints with a goal to see if they are dose and concentration dependent and also are they consistent with what else we know about this drug candidate, and is this drug candidate appropriately safe and well-tolerated in this very high vulnerability population. So I think that's maybe the best answer I can give you. I hope it's satisfactory.

Yes, that's very fair. Then in terms of COSMIC, the first cohort that you – I assume you have seen the data or you have the data, can you tell us anything about what you've seen in terms of safety and tolerability?

So we're not there really positioned to report the data I think being as much that we've escalated from cohort one now to cohort two, you can draw your own conclusions about the drug and its tolerability profile. What are we discussing with Amgen and also with the executive committee, when it might be appropriate to disclose data relating to this study, but to this point, there is no such plans.

Okay. And then, can you help us understand roughly when this trial including the expansion cohort will be concluded?

So we haven't given guidance for our 2014 yet, only here for the expected milestones in 2013. We did today announce that our expectation is we'll initiate the expansion cohort in 2013. Depending on how rapidly that may enrol, I think we'll be in a better position to speak to that. That may be something we can comment on at the next earnings call. We're not expecting data from the completed COSMIC-HF in this calendar year.

But will it be safe to assume that that Phase III trial or trials would be a combination of IV and oral, so you have to wait for COSMIC data before you start the Phase III, correct?

That's correct.

Okay. And final question, I will jump back on the queue, tirasemtiv, you said completion of around second half of the year, so data reporting end of first quarter or you're not going to really guide much other than saying early 2014?

I think early 2014 is the best we can say right now.

To that point, in as much as we had originally intended to see data presented at the ALS M&D Meeting by the end of this year, that does not look like that will be possible, certainly not final data. As to what would be the next logical place where we might want to present these data, we're looking into that and we'll be discussing that with the investigators in the trial but one potential place that we've spoken about publicly is the AAN Meeting which takes place in the early second quarter. That's not to say however that we wouldn't top line the results as we may have them in early 2014.

Your next question comes from the line of Jason Butler.

First one on omecamtiv, yesterday on their earnings call, Amgen talked about the need for morbidity and mortality outcomes to be assessed in the Phase III program. Can you talk about what you envisage the scope of an outcomes trial might envisage right now?

Sure, I'll turn it over to Fady.

I think the key there is morbidity and mortality. A program like this doesn't necessarily need to demonstrate [indiscernible] mortality endpoint alone but where mortality coupled with reduction in heart failure hospitalizations and other potential important cardiovascular endpoints in a combination endpoint would be key. That changes the powering of the study. I can't really comment on the exact size of the trial at this point until we've formally locked down if you will on what the primary endpoint would be, but it's certainly more than several hundred patients, it's probably into thousands.

Yes, suffice it to say that we and Amgen are having those conversations as well as together with key opinion leaders. Our thoughts on that matter really haven't changed since even before we entered into this collaboration agreement with Amgen. All along, we've been thinking about a composite endpoint that reflects outcomes in higher risk heart failure patients albeit ones who are longitudinally at risk in the post-discharge period of death and readmission and other events, and we continue to believe that that's the best way to demonstrate efficacy in this population and that's something that we'll consider together with our partner and also regulatory authorities.

I think Jason the key thing to understand in heart failure is, there isn't necessarily a surrogate biomarker for clinical outcomes that we're interested in, and so clinical trials need to be powered to examine those clinical outcomes rather than surrogate biomarkers.

Let's review any question about it, it is true that it's the combination of ATOMIC-AHF and COSMIC-HF, that will best inform our planning for Phase III, but even as we await data from COSMIC-HF, we're having those conversations.

Okay, then onto COSMIC then, are you able to say at this point whether the pharmacokinetics you're seeing with the oral formulations are predictable?

We haven't commented on that. I think what we'll be able to do is present actual data related to pharmacokinetics in Amsterdam, those in the acute heart failure population from ATOMIC-AHF and then we'll be in a better position to comment. What we did share at our R&D Day were the PK data from cohorts one and two in ATOMIC-AHF and as you may recall those data did demonstrate that the PK was as projected based on the work we had done previously.

Great, thanks. And then my last question is on tirasemtiv, can you provide any more details around what the new statistical plan is that you agreed with FDA and for example does this allow for an analysis that does not include the 58 patients that were impacted by the drug refinement error?

So I'm going to turn this question over to Andy to respond but I might pose the question so that he can respond also to a related question which I imagine some people have, which is, why are we studying an additional 180 patients and not simply an additional 58 patients?

So we did address it during the call but I would acknowledge it is a little bit more complex than is usually appreciated when you hear it for the first time or read it for the first time, but we want to make sure that in the primary analysis that at the end of the day, the placebo patients and the tirasemtiv patients were enrolled concurrently. There could be temporal factors due to earlier patients enrolled or different from later patients enrolled. So we want to make sure that those two groups in the primary efficacy analysis were randomized at same time. So we proposed to exclude more than just the 58 patients but actually all the patients in anywhere in the randomization blocks that included any one of the 58 patients. So that's more than just those 58 patients. And knowing what we know about the raised dropout from the open label phase, we would estimate that increasing the enrolment overall to a total of about 680 patients will allow us to replace in the primary analysis those patients that we're now going to exclude from the primary analysis. And then, I'll answer another question you didn't ask but I'm anticipating you might get, we can't just ignore those patients and we will do secondary analysis that will include them. What we do, we have amended the protocol following discussion with regulatory authorities to make a primary analysis, exclude the patients in those affected randomization blocks.

Okay, great, that's very helpful.

Our next question comes from the line of Charles Duncan.

Congratulations on a good quarter of progress. So Robert, regarding the ATOMIC results that we're going to see in September, I guess I'm a little bit confused on the need or the opportunity present at two different meetings, and I know you're not going to really be able to tell us what we're going to see at those two meetings, but how do you think of those two meetings in terms of the audience or the type of data to present, and then in addition, the actual presenter at ESC versus HFSA?

Good questions. So this is a study that enrolled over 600 patients, a majority of whom came from outside the United States. So it's only fitting that it be presented at a venue where there would be an international audience, and correct me if I'm wrong Fady but I think the European Society of Cardiology Meeting now is the largest if not one of the largest cardiology meetings internationally.

Yes, it's now the largest cardiovascular meeting internationally, and that includes the [indiscernible] cardiology. I think as Robert points out, it's a good venue for general cardiologist from around the world to gather, John [indiscernible] will be the presenter. And it's not uncommon for the Heart Failure Society of America given the proximity of that meeting to the ESC as well as the fact that it's focused on mostly American and also some specialists in heart failure to deal with what I'd call encore presentations where the data may be presented again just to a different audience that might not have been at the ESC for instance.

That said, this study, given its primary and secondary endpoints and related analyses, will fully comprise of presentation at each venue and there will likely be additional analyses and additional presentations from some time to follow. There's quite a lot of very rich data here that I think would be of interest to the cardiology community.

Sure that's the case. Robert, if you could also speak to, I understand this is, you are looking at activity over a couple of hours or even maybe a couple of days, but is there any potential for being able to see the symptomatic improvement, if you're seeing any, as potentially having predictive value for an impact on improved outcomes over time?

Charles, I'll say that I think acute treatments like this over 48 hours notwithstanding recent data presented with other agents are pretty unlikely to show a long-term benefit, unless there is say some sort of change that is permanent in the way the heart functions or is affected by the heart failure during the hospitalization. So that's why in the long term, we want to couple this to continue to roll up there, so that we have a much greater chance of impacting long-term mortality and morbidity.

Yes, I guess I'm kind of asking about that recent data that you said was now withstanding those observations?

I don't think it's for me to comment on that just other than thinking if one looks at the history of acute therapeutics, the short-term therapies in general, they have difficulty showing sustained impacts in reducing heart outcomes in the long-term like re-hospitalization, and in fact that's been a focus of the heat failure community is how you transition away from a dyspnea endpoint which is a relatively short-term outcome to something that might be more impactful for the acute heart failure patient.

Perhaps another way to approach this Charles is that it was never our expectation or objective that we would in a study of a 48-hour intravenous infusion of omecamtiv mecarbil require longer-term outcomes to inform the movement to Phase III. What we're seeking here is what we said before, which is really to see dose-dependent and plasma concentration related effects on these other endpoints. We are collecting data out to 30 days and out to six months and there one wants to make certain that there is no adverse outcomes associated with the treatment versus placebo, but it's not perhaps reasonable to assume that a drug that's administered over a very short period of time is going to have a treatment benefit that increases over time out to six months.

That makes sense. If we could perhaps move on to tirasemtiv, I had a question on that, I know that you're treating, that you've got a totally different approach to statistical analysis here, but in terms of those 58 patients and then the other patients that were enrolled concurrently at that time, how many doses were given in general? I mean do you have patients that had actually received substantial number of doses, upwards of I'll define it as call it half the number of doses that you would've anticipated, or were they only really exposed to say one dose a drug?

We haven't been that precise, so I don’t think I can, but what I can tell you it was not just a single dose of drug, it was an impressionable period of time before they were switched over to placebo.

So that could be actually a pretty interesting secondary analysis.

Oh yes.

It might help Charles if I just ask Andy to elaborate on the design of BENEFIT-ALS and the time over which there are study business post randomization, so there are multiple study business post randomization and during that 12 week treatment period.

So everybody knows they have a week of all the patients, have a week of open label tirasemtiv before they are randomized, and then they are randomized and although of course they may be getting placebo and they may be getting tirasemtiv, the active dose would be 125 mg twice a day for a week in that first top of line week, they come back to us after that week, they come back again in a week where they would be increased optimally with tolerability 125 mg in the morning 250 mg at night, they come back again in a week, they are increased to 250 mg in the morning and 250 mg at night, and then they come back again in a week, now they have been on treatment for four weeks where they get their first double-blind assessment of the ALS [indiscernible] and other secondary endpoints such as the MPV. At this point, the tolerability in an individual patient is then pretty well determined and so they don't come back again for another four weeks, after eight weeks total, and then they are soft again, and then four weeks after that, where there's the final efficacy and safety assessments on double-blind are made.

So what we know is that this randomization error occurred at one of those subsequent study visits, and then from that point forward, during a period of time that the study was being conducted, and that's what Andy was referring to before when he referred to that randomization block from that specific study visit and then subsequent to that in any patients who were randomized after that point to drug or placebo once this programming error occurred.

Okay, and then my final question, I appreciate your patience with all these but on the 107 deal with Astellas, and congratulations on that, I guess I'm kind of wondering how you define non-neuromuscular indications. Does that deal include or exclude the potential for developing 107 in ALS?

So the way we have defined it, it relates to those diseases that are primarily treated by a neurologist and in that regard ALS is excluded as well as other neurology or neuromuscular indications, many of which we've talked about on this call and in meetings for long period of times. So it's all of those indications that we've been considering for tirasemtiv are excluded from a development plan that would relate to CK-107.

That's helpful. Thanks for the added color, folks.

Your next question comes from the line of Chad Messer. Chad Messer - Needham & Company: In the COSMIC trial, can you just give us a broad idea of what the difference between the three oral dose formulations you're testing is, in other words what kind of attributes to an oral formulation are you playing around with or trying to optimize?

It's a very good question because these oral forms are ones that we studied as you may recall in a prior Phase I study and they are not all that different one to another, just in a way that the technologies are intended to address the pharmacokinetics of the drug. And with that I'll turn it over to Fady, the different forms, three oral forms.

So all forms of the drug are really designed (inaudible) the absorption of the drug and all of them do that, they (inaudible) the viability of the drug to a great extent, and so we're really looking for our drug formulation (inaudible) as well as (inaudible) variability in terms of dosed patient population kinetics.

Was that helpful? Chad Messer - Needham & Company: Yes, I think that was. And then I understood that the studies, primary endpoint is safety, tolerability, pharmacokinetics, that set obviously I'm sure you're going to collect from efficacy data, could you just run us through what kind of efficacy data we'll see and are there any, in the back of your mind whether it's formal or informal, sort of efficacy hurdles for this study?

Again, this is a study that is not powered to look at kinds of endpoints, so we will be looking at it in Phase III but we are going to be looking at echocardiographic signs of drug effect really sort of first time over sustained dosing and looking to see what sorts of changes in cardiac dimensions may occur, like [indiscernible] size, heart rate, things in terms of cardiac physiology that may be indicative of a positive effect on cardiac function. Chad Messer - Needham & Company: Alright, very good. And then just one on tirasemtiv, and a little speculative I know and you forgive me, but the studies given there was already an appreciable sized study and now it's up to 680 patients, I'm sure some of those won't be in the primary analysis but you'll get lots of great safety data, any chances this could be registration or an accelerated approval, and if not and you had to do another study, how much bigger would it would have to be or how would it have to be designed differently?

So we continue to believe that more likely than not the likelihood is that we'll have to do another confirmatory Phase III study and that the treatment duration would probably be longer, at least six months, and because we want to study to have 90% power would be bigger as well, not as much bigger as BENEFIT is turning out to be but bigger than it was initially designed to be. That all said, I think the regulatory climate for a drug intended for a disease like ALS where the unmet medical need is so high has continued to evolve, the last Prescription Drug User Fee Act mandated two things, a patient center drug development initiative which to make a long story short resulted in a public hearing at FDA regarding ALS at the end of February where one of the major messages the agency heard as summarized by the division director at the end of the day after mostly testimony by ALS patients and family members was, we hear you telling us that you have a greater appetite for risk than you feel we're letting you take and we hear that, so there's that. And then there's this new designation of breakthrough therapy which we do not yet have but we may have and that provides for what's called a condensed development program, there's not a lot of guidance around what that means yet. So if we need the primary efficacy endpoint on the ALSFRS-R, in the amended protocol with the new efficacy analysis data set of patients as we would find them and the data are not just borderline but quite convincingly good and the secondary endpoints line up in a nice way and so forth, it could conceivably support some sort of accelerated approval, but I would again end where I started, that is not our base case assumption at this point.

I think it frames for us what admittedly is a bit of a challenge. We're going to need to be prepared for the possibility that BENEFIT-ALS is supportive of an accelerated registration while at the same time what is our most probabilistic case is that we are moving swiftly to a potential Phase III trial. So one of the exercises that we're engaged in here at Cytokinetics and with our Board is what do we do in each scenario so as to be most responsive to the opportunity, and that's something that we will have more to say about as we map out those plans, understand the cost implications and ready for that possibility. Chad Messer - Needham & Company: Alright, I understood you got a plan for both scenarios and I appreciate you're keeping a conservative base case, I just presumably here what we've seen in the FDA recently that provided the safety is good and the efficacy is clear, I would think it has a good shot but I appreciate all of the insights and congratulations on a productive quarter.

Thanks very much. I do appreciate that sentiment and as we manage the Company and think about what we need to be doing to properly execute, you can be sure that we're going to be ready for both. Next question please.

Your next question comes from the line of Ritu Baral.

A quick question to start on 107, can you reveal for us again some of the PK characteristics of that drug including if it crosses the blood-brain barrier or not, specifically my question gets towards whether you think it might have some of the same seeing side effects as would see with tirasemtiv?

This is Fady. I think CK-107 was designed from the ground up really do try to avoid crossing the blood-brain barrier to avoid the potential for what might be the CNS effect. So tirasemtiv, it also was engineered from a completely different chemical series, and we do a lot of preclinical work to assess its potential for those kinds of effect, so we're optimistic and hopeful that we will not see the same sorts of effects with tirasemtiv and personally I'd be surprised if we did. In terms of other characteristics, we talked about with tirasemtiv that there is a drug interaction potential with tirasemtiv in particular in the ALS study we're conducting, we do a dose adjustment to really solve that's related to an addition of cytochrome P450 182 by tirasemtiv and CK-107 was also engineered to eliminate potential for drug interaction and there we really have no preclinical evidence that there is a potential for that. So in different ways, CK-107 was meant to be a next-generation compound and we took an extra couple of years to come up with that compound but we do hope and obviously Astellas thought that was well worth the effort.

Got it. And on the tirasemtiv trials, sorry to beat this to death, [indiscernible] that ALS was originally designed, were there any stratifications across different criteria, and if so, were any of them compromised as you expand the trial or can you preserve them?

The only stratification variable was patients who were taking riluzole versus those that were not taking riluzole and they were randomized separately. So on riluzole, more than one placebo or tirasemtiv; not on riluzole, one-to-one placebo or tirasemtiv, and because the primary analysis now will exclude the entire randomization to us, the stratification will be intact.

Got it. And last question just [indiscernible], what are you sort of quick thoughts on how the heart failure space is changing, especially with some new classes of therapy that are approaching Phase III or are in Phase III?

I'll make a comment and then I'll let Fady, but I think much of what we see – I mean there are some novel things but there are other flavors or different ways to evaluate and maybe new mechanisms but I don’t know that the pharmacology is so much different, I'm not aware of anything that actually directly is proposing to improve to contract our function of the heart which is as you know what we are dealing with omecamtiv mecarbil and I don’t think there's any question but the drug does that and we're now at more regulatory and clinically relevant question is, can we associate that clinical [indiscernible] benefit, I think the pharmacodynamic effect is clear.

Yes.

Your next question comes from the line of Joseph Schwartz.

I was wondering if you could comment on how the product that Amgen paying the right to drill from Servier might fit in with omecamtiv and the heart failure treatment paradigm.

Great question. So I'll ask Fady to comment on its mechanism but I'll talk about it firstly with regard to the strategy and the deal. Just in case there's any question about this, because I have received this question several times, this is a deal that requires Cytokinetics consent. Amgen have the rights to sublicense its commercial rights in certain countries in Europe but only as would be consented by the Cytokinetics, and we saw that this was in the interest of Cytokinetics and Amgen and the program in order to have access to the insights of Servier, in particular with regards to the commercialization environment in Europe and where that could be beneficial to ultimately informing the development activities and then obviously in time also the commercial activities. So we were pleased to be a party to those conversations and also to provide our consent once we understood more about what it was that Amgen and Servier had in mind. With regard to Amgen taking a license to Servier's product, this I think also serves Cytokinetics very well because it means that Amgen will begin conversation and dialog not only with FDA but also with reimbursement authorities and ultimately the customers in terms of what might be of interest in heart failure. We don't see that this compound is at all competitive but rather quite complementary to what we have in mind with omecamtiv mecarbil and we think this will afford a leg up on the potential commercial activities relating to omecamtiv. I'll turn it to Fady now to speak about how that drug works.

So [indiscernible] is a blocker of [IF channel] (ph) which to an ion channel in the pacemaker cells of the heart, it controls the repolarization of those cells and by blocking its function, it takes longer for the cell to repolarize and thereby fire again initiating the next heartbeat. So it really is a – as we think of omecamtiv as a drug that purely increases cardiac contractility, this is a drug really that purely controls heart rate, decreases heart rate and it's unique in that perspective. There aren't really any other drugs to do that that don't have other effects that are potentially undesirable including beta blockers and calcium channel blockers. So the two drugs I think could be complementary, they certainly do different things, they obviously have been studied extensively in heart failure and its potential benefits in that area are better to find, but they don't if you will overlap with the potential pharmacodynamics efficacy that omecamtiv produces and as well as the potential clinical efficacy that omecamtiv may produce.

Okay, great. Can I just ask one on tirasemtiv, there I was wondering how this expansion of enrolment impacts physicians who were already enrolling patients in the study, in particular I'm sure the demand was pretty great for the trial but there might have been some patients that a physician would choose to enrol sooner rather than later and earlier would give them, basically select them for enrolment versus others, can you talk about that dynamic and whether you think there might be any difference between the disease, among the disease characteristics of a patient a physician would choose to enrol earlier versus later and how that fits in to the expansion of enrolment? I don't know if you opened up to additional sites as well.

I don't think we will need to add size to the study. I think the raised enrolment prior to we to amend the protocol was pretty brisk and I think this period of time, while the amendment is being considered by the various authorities including regulatory authorities and apex committees I reviewed, is allowing investigators to continue to identify patients knowing that in each of the eight countries enrolment will begin again over time. So we may expect to see a robust enrolment as the study opens up again and positions tirasemtiv's integral kind of pre-screening if you will and lining patients up for enrolment into the study, once that possible. Again, this will happen at different times in different centers in different countries, probably as early as next month [indiscernible].

So your question also pointed to whether we might expect that patients enrolled now might be different or have different characteristics than those enrolled earlier in the study, I don't think we have any reason to assume that may be the case. Unfortunately this is a study that continues to afflict many people and I think our assumption is that patients coming in will have the same sorts of characteristics in August, September, et cetera, as they did earlier this year.

Right, you are not selecting for a certain type of patient, it's still all commerce?

Yes, but I think you raise an interesting point, I mean while I don't know of any reason absent when you amend the protocol to change the inclusion and exclusion criteria which is something that's reasonably common, while you would expect earlier patients enrolled to be different from later one, you could speculate on those sorts of things. I think the important thing is to recognize that it could happen. Even without any obvious reason at the time, the study is ongoing and that's why I think it was important to be sure that we preserved concurrent randomization of placebo patients in tirasemtiv treated patients because if you determine something like that to happen given in retrospect and given [indiscernible] concurrent randomization will be too late to fix it.

Right. That was a great recovery and best of luck.

Your next question comes from the line of George Zavoico. George Zavoico - McNicoll, Lewis & Vlak: I'll try to make it really short since time is getting on, quick question to Andy regarding the 58 patients or the 180 extra patients, I guess to maintain the statistical power, basically you'll still only have 500 valuable patients for primary efficacy because that's what the original goal was, and of the 180 patients that may no longer be analysed for primary efficacy, I imagine to maintain a blinding there still on the trial, and the 58 that had the tirasemtiv and then ones on the placebo, I imagine they're still getting placebo, is that a correct interpretation of what's happening out of the trough?

We said that those that were switched to placebo will maintain placebo treatment through the remainder of their participation in the study. George Zavoico - McNicoll, Lewis & Vlak: And still basically 500 available patients and 180 that won't be able to be evaluated?

I don’t think we can give that level of detail. What I will say is, we have capped everything you said from the beginning in terms of enrolment, and enrolment starting on to the open label treatment. So not everybody gets enrolled, it gets randomized, and not everybody that gets randomized finishes, but what I can tell you is the 680 patients total should maintain the originally intended statistical power. George Zavoico - McNicoll, Lewis & Vlak: Okay, yes, that makes perfect sense. Okay, and a quick question regarding ATOMIC and COSMIC, the overall strategy planned, it still involves, it hasn't changed regarding going from IV to oral and then perhaps also just going oral alone, and so depending on how you progress the oral formulation, it may not necessarily, although possibly, very helpful to see what happens in ATOMIC.

So your first statement is a correct one that nothing has changed with respect to what we believe to be the strategy in the registration program which would be one that would pivot around both the IV and the oral. We're looking at the atomic data, Amgen is looking at the atomic data together with us and we'll consider that data alongside of the COSMIC data to design the Phase III program ultimately that will propose to regulatory authorities, and in that regard it's hard to answer your question because the ATOMIC data is relevant, but I guess to your point, it's not essential, it's not pivotal, it's part of the totality of what we'll be considering for the fact that we'll be looking at these higher risk heart failure patients, both those that may be admitted and enrolled in this study while they are at their most acutely ill but also when they are in the post-discharge setting. George Zavoico - McNicoll, Lewis & Vlak: Okay, that makes sense. Thank you very much.

So operator, I think this call has gone on perhaps longer than others but I think it was very constructive and I appreciate all of the questions. I think with that maybe we'll say thank you to all the participants who participated in this call today and thank you all for your continued support and interest in Cytokinetics, and operator, with that I guess we should now conclude the call.

Ladies and gentlemen, this does conclude today's conference call. You may now disconnect.