Cytokinetics Inc (CYTK) 2013 Q1 法說會逐字稿

Good afternoon, and welcome, ladies and gentlemen, to the Cytokinetics first-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 request of the Company, we will open the call for questions and answers after the presentation.

I will now turn the call over to Sharon Barbari, Cytokinetics' Executive Vice President of Finance and Chief Financial Officer. 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 advancements in our clinical development programs. Fady will then update you regarding recent progress in our clinical development of omecamtiv mecarbil for the potential treatment of heart failure. And Andy will then detail recent progress in our clinical development of tirasemtiv for the potential treatment of ALS and other neuromuscular diseases, and he will also provide an update relating to CK212-7107, or CK-107, our follow-on fast skeletal muscle activator.

I'll then provide a financial overview and comments with respect to our cash position and details on our investments in research and development activity. Robert will then conclude the call with additional comments regarding recent activities and expected next steps and projected milestones for 2013 for our development-stage programs. 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, from corporate partnering to the initiation, enrollment, design, conduct and results of clinical trials, and to other research and development activities. Our actual results might differ materially from those projected in these forward-looking statements.

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

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

I'll now turn the call over to Robert.

Thank you, Sharon. 2013 is proceeding, as planned, to be a very important year for Cytokinetics. We anticipate that data from our two Phase IIb clinical trials will inform the progression of our most advanced programs into potential Phase III trials. The first quarter demonstrated our progression towards these key milestones and our movement forward towards potentially meaningful value inflection points for the Company. Let me take a brief moment to highlight each of these milestones in a bit more detail.

During the last quarter, we reported that completion of enrollment in the third and final cohort in our Phase IIb clinical trial, ATOMIC-AHF, which stands for acute treatment of omecamtiv mecarbil to increase contractility in acute heart failure. It is particularly exciting for us to know that we will soon have clinical data that may allow us to assess the safety, tolerability, pharmacokinetics and pharmacodynamic effects of omecamtiv mecarbil in a high-risk population of patients hospitalized with acutely decompensated heart failure. Together with our partner Amgen, we are readying to lock the database to enable prospectively defined statistical analyses, which we hope may demonstrate that omecamtiv mecarbil is both well-tolerated and also shows clinically relevant effects in this rather sick population.

Most importantly, we hope that ATOMIC-AHF will provide supportive evidence for advancing omecamtiv mecarbil into Phase III. Once the full results from ATOMIC-AHF are reviewed together with Amgen, we look forward to reporting the findings from this Phase IIb clinical trial. We continue to anticipate those results to be made public in midyear 2013.

Underscoring further progress and an expansion of activities in our heart failure program, last month, we announced the initiation of another Phase II clinical trial of omecamtiv mecarbil called COSMIC-HF, which stands for chronic oral study of myosin activation to increase contractility in heart failure. This trial is evaluating the pharmacokinetics of three oral formulations of omecamtiv mecarbil in patients with heart failure and left ventricular systolic dysfunction.

We expect the results of this clinical trial to inform the selection of one of these oral formulations for possible advancement into the Phase III clinical program.

Fady will give you more color on the development of omecamtiv mecarbil in a few minutes, but I believe it is fair to summarize that 2013 offers much promise for the development of this novel drug candidate, and we are working closely with Amgen to ensure that results can be available from ATOMIC-AHF and COSMIC-HF to inform next steps towards potentially going into Phase III.

Now turning to our skeletal muscle contractility program. In the last quarter, we made very good progress in our Phase IIb clinical trial, BENEFIT-ALS, which stands for blinded evaluation of neuromuscular effects and functional improvement with tirasemtiv in ALS. The initiation of clinical trial sites and enrollment of patients are both proceeding well.

To remind you, we initiated patient dosing in this trial in November 2012, and since then have been busily opening additional sites to enrollment in the United States, in Canada and in five European countries. Patient enrollment has rapidly followed, and I'm proud to report today that we've enrolled over 200 patients in this trial, which may represent the most advanced clinical trial now underway for the potential treatment of ALS patients. Andy will report on impressive progress in BENEFIT-ALS, as well as a protocol amendment that we will be implementing to ensure we maintain the statistical rigor that we originally intended for this important clinical trial. We continue to believe that we are on target to complete BENEFIT-ALS and present clinical data by the end of 2013.

Lastly, in April, we announced the initiation of a Phase I clinical trial, CY-5011, which is the first time in humans clinical trial of CK212-7107, or CK-107, in healthy male volunteers. Like tirasemtiv, CK-107 is a novel small-molecule activator of the fast skeletal muscle troponin complex, discovered as a result of Cytokinetics' optimization of a different chemical series than that which produced tirasemtiv. Advancing CK-107 into Phase I evaluation in healthy subjects is consistent with Cytokinetics' corporate strategy to characterize a potential follow-on compound to tirasemtiv in humans and to enable the future evaluation of fast skeletal muscle troponin activation in a potentially broader set of clinical indications and beyond ALS.

With that introduction, I will now 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. As Robert mentioned, I'm happy to share good news regarding the development of omecamtiv mecarbil. Together with Amgen, we've made encouraging progress during the past quarter with the development of each of the intravenous and oral forms of omecamtiv mecarbil.

We are pleased that the ATOMIC-AHF trial has completed patient enrollment of this third and final cohort this quarter. To remind you, ATOMIC-AHF is an international, randomized, double-blind, placebo-controlled, Phase IIb clinical trial of an intravenous formulation of omecamtiv mecarbil in patients hospitalized with acutely decompensated heart failure. Study enrollment increased in momentum over time and with each successive cohort enrolling faster than the previous cohort.

During the enrollment phase of ATOMIC-AHF, the data monitoring committee or DMC convened at predefined interim points, including following completions of cohort one and two, and during the conduct of a third cohort. At each DMC meeting, the committee reviewed unblinded safety data in considerable detail, but we and Amgen remain blinded at this time.

The demographics and baseline characteristics of those patients enrolled in ATOMIC-AHF point to a fairly sick acute heart failure patient population. We find it encouraging that the DMC allowed the study to complete according to plan without recommending changes to the doses of omecamtiv mecarbil. This speaks to our most important clinical development objective to be informed by this study, which is to assess the safety and tolerability of omecamtiv mecarbil in these most vulnerable patients.

While we will also be looking for potential signals of clinical efficacy in this acute heart failure population, such as improvements in the primary efficacy endpoint of dyspnea relief, or another secondary endpoint. In our view, most critical to the potential progression of omecamtiv mecarbil to Phase III will be the safety and tolerability assessments in this highly monitored, acutely ill heart failure patient population.

In addition to the progress made in closing enrollment of ATOMIC-AHF, as Robert mentioned, we also recently announced the initiation of COSMIC-HF, a Phase II double-blind, randomized, placebo-controlled, multicenter dose escalation study designed to evaluate three modified release oral formulations of omecamtiv mecarbil in patients with heart failure and left ventricular systolic dysfunction.

Enrollment is continuing in the first cohort of the dose escalation phase of this trial and clinical trial sites are being initiated in several countries. As enrollment progresses, we will be in a better position to comment on when we might expect to proceed to the next cohort. And to remind you, the trial will be conducted in two phases. The first is a dose escalation phase, which will compare the pharmacokinetic profiles of three oral formulations of omecamtiv mecarbil -- first, at 25 milligrams BID in cohort one; and then at 50 milligrams BID in cohort two, dosed for seven days.

In the second phase, an expanded cohort of 300 heart failure patients will be randomized to one of these three oral forms of omecamtiv mecarbil at either of two selected doses or placebo for three months. This international trial is anticipated to inform our understanding of the oral pharmacokinetics and longer-term safety and tolerability of omecamtiv mecarbil in chronic heart failure patients.

In addition, we will have the opportunity to evaluate the potential for sustained pharmacodynamic effects and their relationships to pharmacokinetics of this drug candidate. Additional information on clinical trials of omecamtiv mecarbil can be found at www.clinicaltrials.gov.

And with that update on clinical development activities for omecamtiv mecarbil in the first quarter, I will turn the call over to Andy for an update on our skeletal muscle contractility program.

Thank you, Fady. The past quarter was indeed exciting for the development of omecamtiv mecarbil, and the same can be said about both drug candidates in our skeletal muscle program. To begin, on February 25, my Cytokinetics colleagues and I attended an important FDA public hearing on ALS. We were impressed by the FDA's engagement with the very motivated patient and advocacy community. We were all very moved by hearing patients with ALS describe the impact of the disease and their appreciation for their caregivers in the clinical community. These patients made impassioned pleas to FDA relating to their interests in participating in clinical trials and the evaluation of new drugs to treat this devastating disease.

At Cytokinetics, we feel our development of tirasemtiv may be responsive to the shared interests of FDA and patients with ALS and are optimistic that the results from BENEFIT-ALS may offer meaningful hope. To remind you, BENEFIT-ALS is a Phase IIb multinational, double-blind, randomized, placebo-controlled, clinical trial designed to evaluate the safety, tolerability and potential efficacy of our fast skeletal muscle troponin activator, tirasemtiv, in patients with ALS.

Over the last quarter, as Robert mentioned, we made significant progress in BENEFIT-ALS. To date, over 200 patients have been enrolled and dozens have now successfully completed three months of treatment. The trial enrolls patients who will be randomized one-to-one to receive 12 weeks of double-blind treatment with either tirasemtiv or placebo. All enrolled patients receive treatment with open-label tirasemtiv at 125 milligrams twice daily prior to randomization in order to ensure that randomized patients can tolerate that dose of tirasemtiv, and also to minimize the potential for unblinding treatment due to generally mild adverse events that, if observed, tend to occur early during treatment with tirasemtiv, and then usually resolve by the second week of continued treatment.

BENEFIT-ALS was originally designed to enroll approximately 400 patients, randomized one-to-one to receive 12 weeks of double-blind treatment with tirasemtiv or placebo. Recently, however, our review of the double-blind aggregate data from the trial indicated that the standard deviation about the primary endpoint, which is the change from baseline in the ALS functional rating scale in its revised form, or ALSFRSr, is actually slightly higher than the estimate we used to calculate the sample size for the study. That original estimate was based on data from the northeastern ALS, or NEALS database, which includes several recent completed clinical trials in ALS patients.

Consequently, in order to preserve our intended statistical power, we are amending the protocol to allow us to enroll approximately 500 patients, or about 100 more than we originally planned. Taking into account that some patients will terminate during the open enrollment phase and others during the post-randomization phase, we expect that approximately 400 patients will complete all 12 weeks of treatment with double-blind study drug.

Clinical assessments take place monthly during the course of treatment. Patients also participate in follow-up evaluations at both seven and 28 days after their final dose.

In addition to the primary endpoint, the ALSFRSr, secondary endpoints include maximum voluntary ventilation, or MVV, and other measures of skeletal muscle function. It is not unusual to submit a protocol amendment to reflect observations in an ongoing clinical trial, and we believe that our doing so can improve the opportunity for us to increase the statistical power of BENEFIT-ALS while also adhering to our original timeline for trial results.

I will now turn to another key first-quarter event from our clinical development program for tirasemtiv, which is our recent report of data evaluating tirasemtiv in patients with myasthenia gravis, the third patient population in which we have demonstrated a pharmacodynamic effect of this drug candidate.

Last month, we announced that data from our Phase IIa evidence of effect clinical trial of tirasemtiv in patients with generalized myasthenia gravis, or MG, known as CY-4023, were presented at the American Academy of Neurology meeting in San Diego. CY-4023 was a double-blind, randomized, three-period crossover, placebo-controlled pharmacokinetic and pharmacodynamic study evaluating single doses of tirasemtiv. Treatment with tirasemtiv was associated with statistically significant dose-related increases in skeletal muscle endurance in patients with MG, as assessed by the quantitative MG score.

We are encouraged by these data, as they further accentuate the potentially broad clinical application of fast skeletal muscle activation. As a reminder, this clinical trial and preclinical research on tirasemtiv in MG were funded by a grant from the National Institute of Neurological Disorders and Stroke.

Lastly, as Robert also mentioned, we recently announced the initiation of CY-5011, a Phase I first time in humans clinical trial of CK-2127107, or for short, CK-107, in healthy male volunteers. The 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. The primary objective of this study is to determine the safety and tolerability of single doses of CK-107 administered orally to healthy male volunteers. The secondary objective is to evaluate the pharmacokinetic profile of single doses of CK 107.

Putting a second fast skeletal muscle activator into clinical trials further underscores the opportunity for Cytokinetics to diversify chemical and pharmaceutical risk, as well as to potentially broaden the clinical landscape associated with our pioneering development of an entirely new pharmacology for fast skeletal muscle activation.

As always, additional information about our completed or ongoing clinical trials can be found at www.clinicaltrials.gov. With that update on our clinical development activities, I'll turn the call over to Sharon.

Thank you, Andy. As our press release contains detailed financial results for the first quarter 2013, I'll refer you to that public statement for the details on our P&L and balance sheet. As you can garner from our discussions thus far, during the past quarter, we have been focused on deploying our capital resources on the progression of our skeletal muscle contractility program, in particular, our BENEFIT-ALS trial.

We ended the first quarter with approximately $61.6 million in cash, cash equivalents and investments, which represents over 14 months of going forward net cash burn based on our 2013 financial guidance.

Our first-quarter 2013 R&D expenses totaled $9.8 million. From a program perspective, for the first quarter, approximately 74% of our R&D expenses were attributable to our skeletal muscle contractility research and development activities, 6% to our cardiac muscle contractility activities and 20% to our other research activities.

In 2013, we anticipate focusing our financial resources largely on the progression and completion of our BENEFIT-ALS clinical trial. We believe that this program, together with our cardiac muscle contractility program, partnered with Amgen, represent opportunities for nearer term value generation for the Company, as both are expected to generate key Phase IIb trial results in 2013.

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

Thank you, Sharon. We are very pleased with the progress that we made in the first quarter. As we look at what 2013 holds for Cytokinetics and the potential advancement of both of our first-in-class muscle contractility programs, we are proud of our execution of key development activities, which accompanies the high-quality science that led to the discovery of our drug candidates.

Our mission, to define an entirely novel pharmacology rooted in the mechanics of muscle contractility and function, has already yielded pharmacodynamic evidence supporting our therapeutic hypothesis that activating cardiac myosin can improve systolic function, reflected by increases in stroke volume and ejection fraction in heart failure patients.

Similarly, we have observed that activating skeletal muscle troponin resulted in increased muscle power, force and endurance that may preserve or prolong independence and the quality of life in patients with ALS.

We look forward to ATOMIC-AHF and BENEFIT-ALS results in 2013 hopefully providing support for continued advancement of our two programs into Phase III clinical development.

We proudly assume the leadership for what we hope will be the next key advances in the care of heart failure and ALS patients. The fact that FDA recently held a public hearing to obtain input from stakeholders on the needs and preferences of ALS patients and their caregivers is evidence of the high-visibility attention FDA is affording the development of new medicines for ALS. We are encouraged that FDA is actively soliciting input on the scientific evaluation, marketing, authorization and post-marketing surveillance of potential products to diagnose or treat ALS. We look forward to participating in the constructive dialogue regarding the development of potential new therapies for ALS.

Similarly, the EMA has been soliciting public commentary on alternative ways to [lead] regulatory oversight to developing next-generation medicines for each of ALS, as well as heart failure. We believe that both of Cytokinetics' later-stage clinical development programs are well positioned for high visibility and hopefully high impact in therapeutic areas that could surely benefit from innovation to afford patient and their families better treatment outcomes.

Now let me turn to our expected milestones for 2013. For omecamtiv mecarbil, in mid-2013, we expect to report results from ATOMIC-AHF. For tirasemtiv, by mid-2013, we anticipate completion of enrollment in BENEFIT-ALS, and by the end of 2013, we expect to report results from BENEFIT-ALS.

With clinical trials data expected from each of ATOMIC-AHF and BENEFIT-ALS in 2013, we are pleased with Cytokinetics' progress and execution in the last quarter, and we remain hopeful for their implications for a bright future for our Company and shareholders. That concludes the formal portion of our call today, and operator, I'd now like to open up the call to questions, please.

(Operator Instructions) Simos Simeonidis, Cowen and Company.

Thank you for taking the questions. First, I'd like to ask about the amendment to the protocol. First of all, the only change is going to be the increase in size of the trial. Is that correct?

So right now, what we are able to share with you is the change as it relates to the enrollment. That will be going from a targeted initial enrollment of 400 to what now will be 500 patients.

In order to get there, we may consider some other changes in the eligibility criteria, but that is not yet something that we have locked in on. But I do believe that the key information today relates to the change in the enrollment.

Okay. And then you said that the powering is going to be maintained as prior to this change, correct?

That's right.

And you are shooting, if I remember correctly, for roughly a 20% to 25% improvement in the revised ALSFRS?

Precisely what we are powering this study to do is to have 80% power to detect a difference in the change from baseline in the ALSFRSr between tirasemtiv and placebo of 1.18 points. That's actually a little more on a percentage basis.

Okay, great. And then trying to understand this -- how you got to this difference in the -- rather to this change in the protocol. Is it something special about this patient population you are enrolling? Because you are using recent NEALS trials to get to your estimate. Are you surprised that there is a slightly higher deviation from the primary endpoint?

I'm not, really, and let me give you some perspective on what a small difference it actually is. The database that we used provided us with an estimate around the change from baseline -- from baseline to three months, I should say, in the ALSFRSr of around four points, so four-point standard deviation. And what we are seeing in our own database, which I want to emphasize is looking at the aggregate data in a blinded fashion -- so all we're looking at is the variability in this change from baseline; it is not segregated by tirasemtiv versus placebo, because the data are not unblinded -- we are seeing a standard deviation around of around 4.2 or 4.3 points.

So it is not a huge difference. Our entry criteria are not exactly the same as those in earlier studies. And one of them that I know patients with ALS appreciate very much is we do not have a maximum criterion for how long the patients may have had the disease before they can enroll. So to some extent, we've been willing to enroll somewhat sicker patients than earlier trials, and that may contribute to the variability.

Or it may just literally be variability in the variability, and in the second half of the trial, we might find those patients have an overall standard deviation about their change from baseline of 3.8, and at the end of the day, we'll have an SD of four. But we can't know that right now, and so I think the prudent thing to do is to provide for enrolling a few more patients so that we can wind up with about 400 complete.

Okay.

(multiple speakers) gets to the crux of the matter. And I think to underscore something else we said in our prepared remarks, we think this is an appropriate step to take to maintain the same statistical rigor and at the same time complete enrollment in the same timeframe. And as you can also conclude, within the same budgetary envelope.

That was going to be my next question. Robert, you mentioned that the timing is going to be the same, and I know that at least being one of the most advanced or if not the most advanced trial, enrollment has been really picking up. So even though you are adding 100 patients, you are still going to finish at the same time? And there is no additional cost to enrolling these additional patients?

There would be an additional cost to enrolling the patients, but we think we can absorb that cost within the same budget that we initially assigned to this study. And yes, we do believe that we'll be in a position to complete enrollment in the same timeframe as originally projected.

We are maintaining our guidance that we have -- that we provided on our fourth-quarter earnings call. So we are probably going to be more at the upper end of that guidance from an operating expense standpoint, but we are still within in the envelope.

Okay, great. And then a quick one on omecamtiv mecarbil, and I'll jump back in the queue. Once we have the ATOMIC data in the middle of the year, can you walk us through what are the next steps before you can go to a -- you and Amgen can go to the combined Phase III trial with an IV and oral formulations, before you can design and initiate that?

Is the only step that is left to wait for the COSMIC data? And if that's the case, how long is that time between ATOMIC readout and COSMIC read-out? I know that is not a simple answer because you have the dose escalation that is ongoing with COSMIC, but can you help us understand -- from the time at the middle of the year you have ATOMIC until you can start a Phase III, assuming both ATOMIC and COSMIC are successful, how long is the time and what are the intermediate steps? Thank you.

It is a very good question. I'll do my best to try to answer it and also ask Fady to help me. I hope this will be deemed satisfactory. Obviously, there are things that we can't know today. And also, these are discussions that must be had with Amgen, of course.

What I will say is that with ATOMIC concluding this summer, we do hope that we'll be in a position to have data that we can suggest will inform the potential progression to Phase III. But certainly, as we've been quite public, our Phase III plans contemplate both the intravenous and the oral forms of omecamtiv mecarbil, and we therefore will need the COSMIC data to inform the ultimate design of Phase III; and, as you could anticipate, what would then be a need for an end of Phase II meeting prior to entry into Phase III.

We have not committed to specific timelines, and I can't speak for that, especially in light of the fact that those are decisions made jointly with Amgen. But what I can say is that with COSMIC enrolling, we think that will have information that will inform that progression. When COSMIC concludes, I can't know. With more patients enrolled, we hope to be able to give more concrete guidance. And then from there, together with Amgen, we can perhaps construct scenarios under which we might begin Phase III. I'm thinking that's the best I can do for you today.

No, that's great. Thank you, Robert.

Thank you.

Charles Duncan, Piper Jaffray.

Thanks for taking my question, and congratulations on the progress in the quarter.

Thank you.

So my first question is on tirasemtiv, getting back to this variability. It seems like you are increasing the size of this study by roughly 25% on the initial projection of approximately 400 patients. So is there an equivalent or similar difference in the variability of ALSFRS than you had originally projected, or are you in effect actually increasing the power of the study as well?

We are actually undertaking this to maintain the power that we originally intended to have and to actually amplify a bit further on what is driving this. And we did reference this briefly in our prepared comments.

But it is partly because the standard deviation about the change from baseline in the ALSFRSr is a little bit bigger than we used when we calculated our sample size. It's also because the dropout rate from the open-label and then post-randomization is a little bit higher than we had projected as well. We expected about 10% dropouts from randomized patients and we are actually running a little bit under that. But we're running a little bit over the number of patients that aren't completing the open-label phase and being randomized.

So we believe that by randomizing 500 patients, we should complete 400 that will go through the 12 weeks of double-blind treatment. And that 400, with the slightly higher standard deviation that we are seeing in the patients enrolled to date, we believe will keep the same statistical power that we originally intended to have, and that is [80%] power to detect a difference between tirasemtiv and placebo in that primary endpoint of 1.18 points.

And let me ask you about that dropout between randomization and enrollment. Is that -- do you think that is a function of tolerability of tirasemtiv, or do you think that is a function of -- given maybe the severity of disease or the state of the type of patients that you are enrolling?

I think it's a combination of many things. There are some patients who really do have adverse events that may be well related to tirasemtiv. And another patient may find them not problematic and this patient does.

There are other reasons why patients have dropped out from the open-label, though, that aren't related to tirasemtiv tolerability. And whatever the reason, if they come out from open-label, they don't get randomized. But it isn't all tolerability of tirasemtiv. To some extent, it is. In some cases, the disease is maybe a little more severe. The patients get into the trial and just decide that it is more effort than they want to expend. Had a couple of issues with patients not being able to swallow the blinded product. So it is a mish-mosh of things.

And then this may sound a little Pollyanna, but is there any readthrough? I mean, I understand that this is a blinded look, but could you have larger variability due to bigger differences between the two arms?

Probably not. Generally speaking, it is a common standard deviation, and it's unusual, actually, for the two treatment groups to wind up having different standard deviations. I know that sounds a little bit counterintuitive, but I've been through it enough times with enough different Ph. D-level statisticians that I can assure you that is not likely to be the situation.

Okay. Thanks for that added color. Let me ask one quick question on omecamtiv, and it's kind of related to the financial projections. We are not projecting any milestones yet this year, but it seems like consensus might be projecting a milestone this year. Is it the case that you would generate a milestone payment from Amgen if the omecamtiv moves forward into Phase III? And just to be clear, I think what you said, Robert, was that you probably need both ATOMIC and COSMIC to inform progression into Phase III for the drug.

Yes, Charles, I'm sorry, I'm not able to comment on what triggers milestone payments. Nor in that way, would I be able to comment on whether the consensus that you are referring to is correct or not. I'm sorry.

What I can say is that as we've been quite public and in conversation with Amgen, it has also been confirmed is that we, together, believe that the best opportunity is to develop both an IV and an oral form of omecamtiv in concert as part of an integrated regimen in Phase III in clinical study. And in that regard, both ATOMIC and COSMIC are rate-limiting to entry into Phase III.

Okay, thanks for that added color. Looking forward to the ATOMIC results midyear.

Thanks, Charles.

Jason Butler, JMP Securities.

Thanks for taking the question. Just wanted to ask another follow-up on the tirasemtiv data that you are looking at, when you are talking about a standard deviation. Does that data specifically include that dexpramipexole data from Biogen Idec? And have you used that data to assess the standard deviation of the control group?

No, the NEALS database at that point in time did not include those data.

Okay, so is there any data we have from that trial that supports or contradicts the historical experience in these patients that you can use in your -- when you look at the design empowering assumptions of this trial?

I think the best data that we have are our data from our trial. And as I said, we can look at the aggregate data in a blind fashion and see what the standard deviation about that change from baseline and the primary endpoint is. And quite frankly, I don't think the difference from what we assumed going in is sufficiently great to be worrisome. It is not very different, and I think what we are doing is actually with an abundance of caution.

As I said -- and I'm going to repeat it -- we may well get to the end of the study, when we've enrolled all the patients, and find that the overall standard deviation is 4.0, just as we originally estimated that it would be. But in the event that is a little bit higher, I think what we are doing is the right thing.

What I will suggest, Jason, is you might be referring to the fact that in Biogen Idec reporting of the dexpramipexole data, there are some indications that the rate of progression in ALSFRSr might have been slightly faster than what had been historical norms, or at least thought to be the historical standard for a population of ALS patients. That is not information that factored into this decision. This decision really relates more to standard deviation within a population.

Okay, great. Thanks a lot for taking the question.

There are no further questions at this time. I turn the call back over to the presenters.

Thank you to all the participants on the Cytokinetics teleconference today. We thank you for your continued support and interest in Cytokinetics. With that, operator, we can conclude the call.

This concludes today's conference call. You may now disconnect.