Cytokinetics Inc (CYTK) 2013 Q2 法說會逐字稿

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 transaction. 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 atrophic lateral sclerosis, or ALS, and on the Phase I clinical trial of CK217 -- sorry, 212707 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 and 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 and collaborations with Amgen and Astellas through the initiation, enrollment, design, conduct and results of clinical trials and to other research and development activities. Our actual results might differ materially from those projected in these forward-looking statements.

Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our most recent annual report on Form 10-K, our quarterly reports on Form 10-Q and our current reports on Form 8-K. Copies of these documents may be obtained from the SEC or by visiting the Investor Relations section of our website.

These forward-looking statements speak only as of today. You should not rely on them as representing our views in the future. We undertake no obligation to update these statements after this call.

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 a signing of a new collaboration agreement that has significant strategic implications for our respective cardiovascular and skeletal muscle programs. We executed well by closing these important transactions.

We also continued 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 that is a 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 up to $50 million, as well as royalties on sales of omecamtiv mecarbil in Japan.

Executing on this transaction now positions us well to integrate 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 an expansion of our deal with Amgen, we also announced the results from ATOMIC-AHF will be presented at a hotline 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 up-front, 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 rights to co-develop and jointly commercialize CK-107, our next-generation fast skeletal troponin activator currently in Phase I 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 have 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 assured 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 interactions with the regulatory authorities, and in particular with the FDA, we proceeded to file an amendment to the protocol for BENEFIT-ALS increasing the enrollment 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 metal, 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 patients 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 will 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 hotline, late-breaking trial session at the European Society of Cardiology, or ESC, on September 3rd in Amsterdam. We have the data and are working diligently with our colleagues at 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 a late-breaking clinical trial session at the Heart Failure Society of America, or HFSA, conference on September 23rd in Orlando, Florida.

We are pleased that the results from ATOMIC-AHF can be shared soon in these important upcoming cardiology conferences. These are exciting times for this program and that arose from Cytokinetics' research over 10 years ago and that offers promise for the treatment of a severe disease that has been absent meaningful innovation for a long time.

With the completion of ATOMIC-AHF and expected presentations 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 formulations of omecamtiv mecarbil in patients with heart failure and left ventricular systolic dysfunction. This international trial is anticipated to inform our understanding of the oral pharmacokinetics 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 pharmacokinetics effects and their relation to the pharmacokinetics of this drug candidate. As we have mentioned, COSMIC-HF will be conducted in two phases. The first is a dose escalation phase which will compare the pharmacokinetic profiles of three oral forms of omecamtiv mecarbil; first at 25 milligrams twice daily in cohort one, and then at 50 milligrams 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 selected 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 of COSMIC-HF recently opened to enrollment. 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. This will include the potential progression of omecamtiv mecarbil to the expansion phase of COSMIC-HF and planning activities related to Phase III.

The rate of enrollment of patients in the dose-escalation phase of COSMIC-HF underscores the enthusiasm for omecamtiv mecarbil amidst the high unmet needs in the treatment of heart failure. Clinical investigative sites 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 Phase III program as 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 both companies and key opinion leaders, regulatory authorities and others as we map forward plans for omecamtiv mecarbil.

In connection with that objective, as Robert mentioned a moment ago, with the signing 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 in a potential Phase III clinical development program. Taking that key next step forward is evidence of our confidence in our new -- our novel mechanism of this cardiac myosin activator.

Lastly, I am also pleased to report that during the last quarter Cytokinetics and Amgen reviewed results from a 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 meaningful -- meaningfully differences were observed in the 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 doses in patients with compromised renal function without dose adjustment. We are encouraged by these findings, which are consistent with earlier work performed by Cytokinetics.

With 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 enrollment of BENEFIT-ALS. During our last earnings call on April 30th I announced that approximately six months after we dosed the first patients 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 rate of enrollment in this trial is a testament to the dedication of ALS patients, their caregivers and BENEFIT-ALS clinical site 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 the 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 a study status 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, nor any other patient safety. At that time 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 remain 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 expert statisticians and regulatory consultants, we proposed to the relevant regulatory authorities, including of course FDA, a 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 enrollment 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 enrollment to continue as the new amendment becomes effective at the participating study centers. We now expect a complete enrollment in BENEFIT-ALS during the second half of 2013. We expect to announce when enrollment 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 muscle troponin activator. In the last quarter we continued to enroll 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 collaborative 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-escalating crossover design.

[CK-5011] is enrolling well and proceeding to higher-dose cohorts. In addition, we are planning to initiate other Phase I and Phase II readiness activities specified under our development plan for CK-107 agreed with Astellas. Under that plan Cytokinetics will be primarily responsible for the conduct of Phase I clinical trials, including the completion of CY 5011, and we will conduct certain Phase II readiness activities for CK-107. Astellas will imburse 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 collaborative 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 our 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 up-front payments from Amgen and Astellas, and the sale of $10 million in stock to Amgen.

In June we received $15 million in an up-front payment from Amgen for the license of omecamtiv mecarbil in Japan and $10 million from the sale of 1.4 million shares to Amgen. The Astellas up-front license fee 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 equivalents and investments, which represents approximately 24 months 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 1st, 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 index fund and as 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 programs perspective, for the second quarter approximately 80% of our R&D expenses were attributable to our skeletal muscle contractility research and 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 collaborative 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 deal 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 fit 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 hallmarks of our activities have been quality science, skilled execution and, yes, patience and perseverance. We've executed licensing deals and financings as we believe may best serve our nearer-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 persistence 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 this may enable us certain advantages given the high, urgent unmet need in the area of ALS and other neuromuscular conditions.

In addition, progress in the development of omecamtiv mecarbil has now resulted in an expanded collaborative with Amgen as we engage together towards a potential global Phase III program.

These two deals combined have substantially altered our financials and our financial outlooks. Cytokinetics has a strong cash position today and is eligible to receive in excess of $1 billion in milestone payments from our two partnered 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 large 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 interests 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 addition costs associated with the conduct of the 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 enrollment in 2013 and the expected availability of results in early 2014. In the meantime, we are looking forward to the presentation of results from ATOMIC-AHF data in September in Europe and the US, as well as the continued progress in the COSMIC-HF trial.

And in parallel, we are pleased to be dialing up activities with Amgen; and also, we're pleased to increase our 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 hotline, late-breaking clinical trial session at the ESE Congress in Amsterdam on September 3rd, 2013 at 11.18 a.m. Central European Time, as well as at the late-breaking clinical trial session at the HFSA Conference in Orlando, Florida on September 23rd, 2013 at 4 p.m. Eastern Time.

Also for omecamtiv mecarbil, by the end of 2013 Cytokinetics expects the opening to enrollment of the expansion phase of COSMIC-HF.

Now, turning to tirasemtiv. In the second half of 2013 Cytokinetics anticipates completion of enrollment 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.) And your first question comes from the line of Simos Simeonidis.

Good afternoon, Simos. How are you?

Hi. Good. How are you? Thank you for taking the questions.

I guess the first one would be for the most -- the one that's upcoming in four or five weeks from now, the ATOMIC data in Amsterdam. As you and Amgen are looking at these data and as us 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 in 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.

So, the -- 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 endpoints, as Robert articulated already, have 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 this 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 intravenous form of this drug and with a 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 the 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. 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 in really a position 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. We're going to be discussing with Amgen, and also with the Executive Committee, when it might be appropriate to disclose data relating to the study but, to this point, there's no such plans.

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

So, we haven't given guidance for 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 enroll, 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, it would be safe to assume that if the -- that the Phase III trial or trials would be the combination -- a combination of IV and oral, so you have to wait for the -- for COSMIC data before you start the Phase III, correct?

That's correct.

Okay. And a final question then I will jump back on the queue. Tirasemtiv. You said completion of enrollment second half of the year. So, data reporting end of first quarter or you haven't -- you're not going to really guide much other than saying early '14?

I think early '14 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 ALSMND 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.

Okay. Thank you so much for taking the questions.

Thank you, Simos.

Your next question comes from the line of Jason Butler.

Hey, Jason.

Hey, thanks for taking the questions. 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 that over to Fady.

Yes. Hi, Jason. I think the key there is morbidity and mortality. A program like this doesn't necessarily need to demonstrate efficacy on a mortality endpoint alone, but where mortality coupled with reduction and heart failure and hospitalizations and other potential important cardiovascular endpoints and 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 in the 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 safe -- or 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 is that in heart failure there isn't necessarily a surrogate biomarker for the clinical outcomes that we're interested in. And so, clinical trials need to be powered to examine those clinical outcomes rather than surrogate biomarkers.

Sure. And then --.

Lest there be 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 on to COSMIC, then. Can -- 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 relating 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 predicted 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've agreed with FDA? And for example, does this allow you -- allow for an analysis that does not include the patients, the 58 patients that were impacted by the drug assignment 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 this during the call, but I would acknowledge that it is a little bit more complex than -- it's easily 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, that there could be temporal factors that earlier patients enrolled are different from later patients enrolled. So, we want to make sure that those two groups, in the primary efficacy analysis, were randomized at the same time.

So, we proposed to exclude more than just the 58 patients but actually, all the patients in any one of 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 rates of dropout from the open-label phase, we would estimate that increasing the enrollment 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 anticipate we might get. We can't just ignore those patients and we will do secondary analyses that will include them, but we do -- we have amended the protocol following discussion with regulatory authorities to make the primary analysis exclude the patients in those affected randomization blocks.

Okay, great. That's very helpful. Thanks for taking the questions.

Thanks, Jason.

Our next question comes from the line of Charles Duncan.

Hi, Charles.

Hi, guys. Thanks for taking my question and congratulations on a good quarter of progress.

Thank you.

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 to 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 American College of Cardiology.

I think as Robert points out, it's a venue for general cardiologists from around the world to gather. John Teerlink 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 subspecialists in heart failure to do what are called 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 a presentation at each venue and there will likely be additional analyses and additional presentations for some time to follow. There's quite a lot of very rich data here that I think will be of interest to the cardiology community.

I'm sure that's the case. Robert, if you could also speak to -- I understand this is -- you're 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 improvements, if you're seeing any, as potentially having predictive value for an impact on improved outcomes over time?

So, Charles, I'll say that I think acute treatments like this over 48 hours, not withstanding recent data presented in other -- with other agents, are pretty unlikely to show long-term benefit unless there is say some sort of a change that is permanent in the way that the heart functions, or is affected by the heart failure during hospitalization. So, that's why in the long term we want to couple this to continued oral therapy, 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 not 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, that short-term therapies in general have difficulty showing sustained effects in reducing heart outcomes in the long term, like rehospitalization. And in fact, that's been a focus of the heart failure community, is how do you transition away from a dyspnea point, which is a relatively short-term outcome, to something that might be more impactful for the acute heart failure patients.

Okay.

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's 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.

It 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 have anticipated, or were they only really exposed to, say, one dose of drug?

Well, we haven't been that precise, so I don't think I can be. But, what I can tell you, it was not just a single dose of drug. It was an appreciable period of time before they were switched over to placebo.

So that could be, actually, a pretty interesting secondary analysis.

Oh, yeah.

And then, my --.

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

So, everybody knows they have a week -- all the patients have a week of open label tirasemtiv before they're randomized. And then they're randomized and -- although, of course, they may be getting placebo and they may be getting tirasemtiv, the active dose would be 125 milligrams twice a day for a week in that first double-blind week. And they come back after that week, they come back again in a week where they would be increased optimally with tolerability, 125 in the morning, 250 at night. They come back again in a week, they're increased to 250 in the morning and 250 at night. And then they come back again in a week. Now they've been on treatment for four weeks where they get their first double-blind assessments of the ALS, FRSR and other secondary endpoints such as the MPV.

At this point the tolerability in an individual patient has been pretty well determined, and so they don't come back again for another four weeks, after eight weeks total, and then they're assessed again and then four weeks after that, where they're -- 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 and any patients who were randomized after that point to drug or placebo once this programming error occurred.

Okay. And then my final question -- and I appreciate your patience with all of these, but on the 107 deal with Astellas - and congratulations on that, the -- 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've 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 a long period of time. 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 color, folks.

Thank you.

Your next question comes from the line of Chad Messer.

Hi, Chad.

Hi. Hi and thanks for taking my question.

In the COSMIC trial, can you just give us a broad idea of what the difference between the three oral dose formulations your testing is? In other words, what kind of attributes to an oral formulation are you playing around with or trying to optimize?

That'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, except in the way that the technologies are intended to address the pharmacokinetics of the drug. And with that, I'll turn it over to Fady in terms of the different forms, the three oral forms.

Yes. So, the oral forms of the drug are really designed to (inaudible) the absorption of the drug. And all of them do that. They maintain the bioavailability of the drug to a great extent. And so, what we're really looking for are drugs in a formulation that (inaudible), as well as (inaudible) variability in terms of dose, patient population and kinetics.

Was that helpful?

Yes. Yes, I think that was. And then I understood that the study's primary endpoint is safety, tolerability, pharmacokinetics. That said, obviously I'm sure we're going -- you're going to collect 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 if it's formal or informal, sort of efficacy hurdles for this study.

Well, so the -- again, this is a study that is not powered to look at the kinds of endpoints that we will be looking at in Phase III, but we are going to be looking at echocardiographic signs of drug effect, really for the first time over sustained dosing and looking to see what sorts of changes in cardiac dimensions may occur, like the atrial size, heart rate, things in terms of cardiac physiology that may be indicative of a positive effect on cardiac function.

Alright, very good. And then just one on tirasemtiv. And a little speculative, I know, and you forgive me, but that's a -- the study's -- given that it was already an appreciable sized study and now it's up to 680 patients, and sure some of those won't be in the primary analysis but you'll get lots of great safety data. Any chance this could be registrational or accelerated approval and, if not and you had to do another study, how much bigger would it have to be or how would it have to be designed differently?

So, we've continued 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'd want the study to have 90% power, it 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-centered 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 meet the primary efficacy endpoint on the ALS/FRSR in the amended protocol, with the new efficacy analysis data set of patients as we have defined 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 an accelerated approval. But I would again, and/or I started, that is not our base case assumption at this point.

Yes. 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.

Alright. Understood. You've got a plan for both scenarios and I appreciate you keeping a conservative base case. I just -- personal belief here, what we've seen in the FDA recently that -- provided the safety is good and the efficacy is clear, I would think you'd have 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.

Hi, Ritu.

Hi, guys. Thanks for -- hi. Thanks for fitting me in.

A question -- a quick question to start on 107. Can you review 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 CNS side effects as was seen with tirasemtiv.

Yes. Hi, Ritu. This is Fady. I think CK-107 was designed from the ground up, really, to try to avoid crossing the blood-brain barrier to avoid the potential for what might be the CNS effects of tirasemtiv. It also was engineered from a completely different chemical series. And we did a lot of preclinical work to assess its potential for those kinds of effects. 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 of riluzole and that's related to inhibition of cytochrome P450-182 by tirasemtiv. And CK-107 was also engineered to eliminate potential for drug/drug interaction and there we really have on preclinical evidence that there is a potential for that.

So, 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 it was well worth the effort.

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

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

Got it. And the last question, just because it's getting late, what are your sort of quick thoughts on how the heart failure space is changing, especially with some of the new classes of therapies that are approaching Phase III or in Phase III?

Well, I mean, I'll make the comment and then let Fady. But I think much of what we see -- I mean, there are some novel things, but there are other flavors of -- or different ways to vasodilate. They may be 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 the contractile function of the heart, which is, as you know, what we are doing with omecamtiv mecarbil. And I don't think there's any question but that the drug does that. And we're now at the more regulatorily and clinically relevant question is, can we associate that with clinical benefit. I think the pharmacodynamic effect is clear.

Yes, I would agree with that.

Great. Thanks for taking the questions.

Thank you, Ritu.

Your next question comes from the line of Joseph Schwartz.

Hi, Joe.

Great, thanks. Hi, there. Thanks very much. I was wondering if you could comment on how the product that Amgen obtained the right to develop from Servier might fit in with omecamtiv in 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 was a deal that required Cytokinetics' consent. Amgen had the right to sublicense its commercial rights in certain countries in Europe, but only as would be consented by 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 regard 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 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 served 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.

Yes. So, ivabradine is a blocker of the IF channel, which is 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 those cells 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 that 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 complimentary. They certainly do different things. They -- ivabradine obviously has been studied extensively in heart failure and its potential benefits in that area are better defined. But they don't, if you will, overlap with the potential pharmacodynamic 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 enrollment 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 enroll sooner rather than later or earlier and give them -- basically select them for enrollment versus others.

Can you talk about that dynamic and whether you think there might be any difference between the disease in -- among the disease characteristics of a patient a physician would choose to enroll earlier versus later and how that fits into the expansion of enrollment? I don't know if you've opened up to additional sites as well.

I don't think we will need to add sites to the study. I think the rate of enrollment prior to needing 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 ethics committees, IRBs, is allowing investigators to continue to identify patients, knowing that in each of the eight countries enrollment will begin again over time.

So, we may expect to see a real burst of enrollment as the study opens up again. And physicians have spent this interval kind of prescreening, if you will, and lining patients up for enrollment into the study once that's possible again, which will happen at different times in different centers in different countries, probably as early as next month, the very earliest ones.

Yes. See, 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, etc., as they did earlier this year.

Right. Yes, they're not -- you're not selecting for a certain type of patient. It's still all comers.

Well, yes. I mean -- 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 frequently done, why you would expect earlier patients enrolled to be different from later ones.

You can 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 and tirasemtiv-treated patients. Because if you determine that something like that happened even in retrospect and you didn't ensure concurrent randomization, it would be too late to fix it.

Right. No, that was a great recovery and best of luck.

Thank you.

Your next question comes from the line of George Zavoico.

Hi, George.

Hi, Robert. Hi, everyone. Thanks for taking my call. I'll try to make it real short since it's -- time's getting on.

A 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 evaluable patients for primary efficacy because that's what the original goal was. And of the 180 patients that are no longer -- that may no longer be analyzed for primary efficacy, I imagine to maintain the blinding they're still on the trial. In other words, the 58 that had the tirasemtiv and then went on to placebo, I imagine they're still getting placebo. Is that a correct interpretation of what's happening now to the trial?

Right. We said that those that were switched to placebo maintained placebo treatment through the remainder of their participation in the study.

Oh, okay. And so you'll have 5 -- basically have 500 evaluable patients and 180 that'll -- won't be able to be evaluated.

Well, I don't think we can get into that level (inaudible) --.

(Inaudible.)

Of detail. What I will say is we have cast everything we've said from the beginning in terms of enrollment. And enrollment --.

Okay.

Starting onto the open label treatment. So, not everybody that gets enrolled gets randomized and not everybody that gets randomized finishes. But what I can say is the 680 patients total should maintain the originally intended statistical power.

Yes. Okay, yes. That's -- that makes perfect sense.

Okay. And a quick question regarding ATOMIC and COSMIC. The overall strategic plan, 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 of course it'll be 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's 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 the study while they're at their most acutely ill, but also when they are in the post-discharge setting.

Okay. That makes sense. Thank you very much.

Thank you.

And have a good evening.

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.