Cytokinetics Inc (CYTK) 2011 Q2 法說會逐字稿

Good afternoon and welcome, ladies and gentlemen, to the Cytokinetics second quarter 2011 conference call. (Operator Instructions).

I would 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; and Dr. Andrew Wolff, Senior Vice President of Clinical Research and Development and Chief Medical Officer.

Following the forward-looking statement disclaimer, Robert will provide an over of the past quarter along with highlights on the advancement of our clinical development pipeline. Andy will then provide details of the progress of the company's clinical development programs, and I will provide some brief comments with respect to our cash position and our investments in research and development activities. Robert will then conclude the call with additional comments regarding our recent activities, next steps for our development-stage programs, including omecamtiv mecarbil and CK-2017357, which we'll refer to as CK-357, and a discussion of the projected company milestones for the remainder of 2011. We'll then open the call for a brief question-and-answer session.

The following discussion, including our responses to questions, contain statements that constitute forward-looking statements for purposes of the Safe Harbor Provision of the Private Securities Litigation Reform Act of 1995, including but not limited to, statements relating to our financial guidance, 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 report on Form 10-Q, and our current report on Form 8K. 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, and we undertake no obligation to update these statements after this call.

I'll now turn the call over to Robert.

Thank you, Sharon.

During the second quarter, Cytokinetics made important progress in the advancement of both our cardiac and skeletal muscle activator development programs. Certainly one key highlight of the past quarter was the initiation of dosing in our Phase IIb trial of omecamtiv mecarbil in patients hospitalized with acutely decompensated heart failure. We are pleased that this international Phase IIb trial of omecamtiv mecarbil is underway with the trial open to enrollment in the United States, Canada, the European Union and Australia.

This matter has been a priority and a substantial undertaking on the part of Amgen and Cytokinetics. We look forward to updating you on the progress of this clinical trial as enrollment proceeds. And in addition, Amgen and Cytokinetics are now planning additional trials with the objective of evaluating multiple oral formulations of omecamtiv mecarbil, initially in healthy volunteers, and then in stable heart failure patients. We'll have more to say about those plans as they're finalized.

Another highlight during the quarter was the opening to enrollment and the more recent dosing of patients in a Phase II multiple-dose safety tolerability pharmacokinetic and pharmacodynamic clinical trial of CK-357 in patients with ALS. This is our second trial of CK-357 in ALS patients and, as Andy will describe shortly, this trial was design to examine the safety and tolerability of two weeks of daily oral dosing of CK-357 in this patient population.

During the quarter, we also presented data from a second Phase IIa Evidence of Effect clinical trial of CK-357, this one in peripheral artery disease patients with claudication. This data, which Andy will summarize shortly, provide additional support for our mechanistic rationale and resulting therapeutic hypothesis that a fast skeletal muscle troponin activator can improve skeletal muscle performance in patients with impaired skeletal muscle function due to a variety of causes.

In this second Phase IIa trial of CK-357, we have now shown that CK-357 can increase the physical work performed by skeletal muscles impaired by ischemia due to peripheral artery disease, thus extending our observations from our earlier trial in ALS patients in which we generated evidence that CK-357 can increase function in skeletal muscles weakened by a very different pathophysiology, namely denervation.

In addition, we believe the increases in endurance and work that these patients' muscles achieved while receiving CK-357 are clinically relevant and warrant further clinical testing. Overall, we are encouraged by the results obtained and are committed to advancing CK-357 into Phase IIb development to follow in 2012.

Now I'll turn the call over to Andy to elaborate on the specific progress achieved during the last quarter in our clinical development programs, and later in the call, I'll provide some additional insights into our plans for the future.

Thank you, Robert.

During the first half of 2011, our clinical teams focused on positioning our two lead programs for Phase IIb clinical trials. As Robert mentioned, omecamtiv mecarbil is now the subject of an international randomized, double-blind, placebo-controlled Phase IIb clinical trial. This trial is planned to enroll approximately 600 patients with left ventricular systolic dysfunction, hospitalized for acutely decompensated heart failure, into three sequential ascending dose cohorts.

In each cohort, patients will be randomized to receive omecamtiv mecarbil or placebo in order to evaluate the effects of 48 hours of treatment with the intravenous form of omecamtiv mecarbil by measures of dyspnea, patients' global assessments, change in the end-terminal pro-brain-type natriuretic peptide, which is a biomarker associated with the severity of heart failure, and short-term clinical outcomes in these patients.

Also, as Robert mentioned, this trial is currently open for enrollment in the United States, Canada, the European Union and Australia. This alone required substantial coordination of operations from around the world.

While it is too early to speak to enrollment rates, I was personally involved in the design and planning of the trial and, more recently, attended investigator meetings in the United States, Europe and Australia. And as a result, I am very encouraged by the breadth of the investigators' enthusiasm for this trial.

With the initiation of this sizable Phase IIb trial behind us, Amgen and Cytokinetics are now turning our attention to planning clinical trials designed to assess the safety, tolerability and pharmacokinetics of different oral formulations to occur sequentially, first, in healthy volunteers, and then in stable heart failure patients. The objective of these trials is to select the best oral formulation for evaluation in Phase III clinical trials and in conjunction with the further development of our intravenous formulation of omecamtiv mecarbil.

Turning to our skeletal muscle program, in recent months we initiated a Phase II safety, tolerability, pharmacokinetic and pharmacodynamic clinical trial of 14 days dosing of CK-357 in patients with ALS who are not taking Riluzole, which is the only drug currently approved for the treatment of ALS. This trial was originally planned to enroll approximately 24 ALS patients from clinical centers across the United States. However, as I will explain shortly, we plan to expand this trial to include an additional cohort of approximately 24 patients who'll receive CK-357 and Riluzole together. We believe the results from this trial may add important insights to our evolving understanding of how the mostly mild side effects observed in the single-dose trial of CK-357 in ALS patients, particularly dizziness, respond to continued exposure to the drug candidate.

Over the past quarter, my colleagues and I have been increasingly committed to the further development of CK-357 in ALS. We are planning a Phase IIb clinical trial that we expect will treat hundreds of ALS patients with CK-357 for several months, and preparing for associated discussions of our proposed clinical development program in ALS with regulatory authorities.

To inform those discussions, we recently completed dosing of healthy volunteers in a Phase I drug-drug interaction study designed to evaluate the effects of CK-357 on the pharmacokinetics of Riluzole and other drugs when administered orally, as well as the pharmacokinetics of CK-357 when administered orally after a meal and also when fasting.

We have not yet analyzed all the data for this trial however, we are encouraged by the results concerning the pharmacokinetic interaction between CK-357 and Riluzole which is why, as I mentioned earlier, we are now expanding the ongoing Phase II 14-day trial of CK-357 in ALS patients to include an additional cohort of approximately 24 patients who will receive CK-357 and Riluzole together.

In addition, we recently convened consultant meetings to inform our potential registration path for CK-357 in ALS. We look forward to continuing these planning sessions and to our expected discussions with regulatory authorities over the next several months.

As we plan these next steps in ALS, in June, at the 22nd annual scientific sessions of the Society for Vascular Medicine, we presented data from our Phase IIa Evidence of Effect clinical trial of Ck-357 in patients with claudication associated with peripheral artery disease. The trial demonstrated that CK-357 increased calf muscle performance in these patients, as evidenced by an increase in work achieved during bilateral heel raise testing. In addition, these increases in calf muscle performance appeared related both to the increasing dose and to the CK-357 plasma concentration.

These results were enthusiastically received by the vascular physicians and investigators at the conference who were encouraged by this signal of potential efficacy in treating the often debilitating symptom of claudication and who frequently articulated their view that there is currently a significant unmet need for effective medical therapy for this condition.

In addition, as Robert mentioned earlier, these data provide additional support for our therapeutic hypothesis as we have now observed potentially clinically useful pharmacodynamic effects of CK-357 in skeletal muscles affected by ischemia with peripheral artery disease and by denervation in patients with ALS.

Lastly, we continue to enroll patients in our third Phase IIa Evidence of Effect trial CK-357 in patients with generalized myasthenia gravis. To remind you, this trial, like our other Evidence of Effect trials, is a double-blind, randomized, placebo-controlled three-period crossover pharmacokinetic and pharmacodynamic study. At least 36 and up to 78 patients may be enrolled at approximately 15 study centers in the United States. Patients enrolled in the trial will receive single oral doses of placebo, 250 mg and 500 mg of CK-357 in random order. This trial is enrolling according to our plans.

As always, additional information about all of our Phase II trials can be found at www.clinicaltrials.gov.

With that update on our clinical development activities in the second quarter, I will turn the call back over to Sharon.

Thank you, Andy. As our press release contains detailed financial results for the second quarter 2011, I'll refer you to that public statement for the details of our P&L and balance sheet.

We ended the second quarter with approximately $66.9 million in cash and cash equivalents and investments, excluding restricted cash, which represents approximately 14 to 16 months of going-forward net cash burn based on our 2011 financial guidance. Our second quarter 2011 R&D expenses total $10.5 million.

From a program perspective for the second quarter, approximately 66% of our R&D expenses were attributable to our skeletal muscle contractility research and development activities, 6% to our cardiac muscle contractility activities, 15% to our smooth muscle contractility program, and 13% to our other research activities.

For the six months ended June 30, 2011, our R&D expenditures totaled $19.7 million, and from a program perspective for the six months, approximately 65% of our R&D expenses were attributable to our skeletal muscle contractility activities, 5% to our cardiac muscle contractility activities, and 14% to our smooth muscle contractility program, and 15% to our other research activities.

We continue to focus our financial resources largely on the progression of our skeletal muscle contractility research and development program. We believe that this program, together with our cardiac muscle contractility research and development program that has partnered with Amgen, represents the nearest-term value generation for the company, as Robert will outline in a moment with the remaining milestones for 2011.

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

Thank you, Sharon.

With each passing quarter, we continue to see the breadth of our innovative research and development activities which have produced our novel mechanism drug candidates, gain increasing attention and enthusiasm from the scientific and medical communities, and even increasingly from certain patient constituencies. We believe the recent initiation of key Phase II clinical trials in each of our cardiac and skeletal contractility programs demonstrate the increasing value of our pharmaceutical pipeline as our science translates into the clinic.

As evidence, in May, at the European Society of Cardiology's heart failure meetings in Sweden, our partner, Amgen, presented the design for the now ongoing Phase IIb clinical trial of omecamtiv mecarbil in patients hospitalized with acutely decompensated heart failure, elaborating on the background of and rationale for this global trial. We are pleased that this important trial and the potential of this novel drug candidate continue to be well-received by the worldwide heart failure community.

In addition, the rapid advancement of CK-357 into a second Phase II clinical trial in ALS patients underscores a similar enthusiasm for the promise our novel skeletal muscle activator may offer for potential improvements and functional status and quality of life in that patient population. Recent data from our Phase IIa EoE trial in patients with claudication presented at the Annual Meeting of the Society for Vascular Medicine add to that enthusiasm and provide further evidence of translation of the mechanism of action of CK-357 into another patient population, in this case, with skeletal muscle dysfunction due to ischemia, is the result of a completely different pathophysiology than the denervating disease affecting the skeletal muscles of patients with ALS.

Over years at Cytokinetics, we have deliberately and carefully characterized the safety, tolerability, pharmacokinetics and pharmacodynamics of each of omecamtiv mecarbil and CK-357 in a broad array of Phase I and early Phase II studies. This has taken time and a substantial commitment on the part of patients as well as a persistent infusion of investment capital. I'm pleased to say that we are moving aggressively forward into late-stage clinical trials with both of these programs even as we are continuing to add to our emerging pipeline with other programs that build on our expertise in muscle mechanics arising from continuing research and non-clinical development activities.

To be clear, going forward, our top priorities at Cytokinetics are the partnering of our skeletal muscle activator program, which we expect may occur in 2011, and the advancement of CK-357 into a Phase IIb trial which we are planning to initiate in 2012. I continue to be optimistic about our delivering on both of these key company priorities and look forward to sharing additional details when appropriate.

As we have outlined for you what the first half of 2011 has delivered, let me now turn to the milestones for the remainder of the year.

For omecamtiv mecarbil, we anticipate finalizing ongoing discussions between Cytokinetics and Amgen related to the initiation of additional studies designed to assess the safety, tolerability and pharmacokinetics of multiple oral formulations of omecamtiv mecarbil. These studies are expected to occur first in healthy volunteers and then in stable heart failure patients. Cytokinetics expects to provide updated guidance on the timing of these studies following further discussions with Amgen.

Turning to our skeletal muscle contractility program, we anticipate that data will be available from our Phase I drug-drug interaction study of CK-357 in healthy volunteers in the second half of 2011. We anticipate that data will be available from the Phase II multiple-dose safety, tolerability, pharmacokinetic and pharmacodynamic clinical trial of CK-357 in patients with ALS, that to occur by the end of 2011.

Lastly, we anticipate that data will be available from the ongoing Phase IIa Evidence of Effect clinical trial of CK-357 in patients with generalized myasthenia gravis, that also to occur by the end of 2011.

And with that, operator, that concludes the formal portion of our call today. I'd now like to open up the call to questions please.

(Operator Instructions).

Your first question comes from Charles Duncan with JMP Securities.

Hi, guys. This is Jason in for Charles. Thanks for taking the questions and congratulations on a good quarter.

My first question was, was there anything mechanistically that made you want to expand the 357 ALS trial to include a combination with Riluzole? Is there a reason to believe that there could be some kind of additive or even synergistic efficacy?

So I'll start and then I'll turn it over to Andy. As we've reported previously in the prior single-dose Evidence of Effect study, we did see with CK-357 co-administered in some patients who were taking Riluzole that there were some plasma concentration increases of Riluzole as could have been predicted based on preclinical evidence with the mean increase being about a two-fold increase in those plasma concentrations. But that was not conducted in a systematic fashion as we wanted to understand in further studies. So that's one of the reasons why we've proceeded with the plan to do both the drug-drug interaction study as well as the multiple-dose study. And with that, I'll turn it over to Andy to elaborate.

So, I think maybe to your question, this is not intended to evaluate anything but the pharmacokinetics of Riluzole when co-administered at different doses of CK-357. The study is partially small to appreciate whether or not there will be any additive effect on any pharmacodynamic measurements that we might make in these patients. But we were encouraged by the data from healthy volunteers in the study we mentioned earlier because, as Robert just explained, while we expected the Riluzole levels to be increased by co-administration with 357, what we found is that the variability within the population is actually decreased. So in other words, Riluzole concentrations in the presence of 357, while higher, are actually less variable than they are in the absence of 357.

So that was encouraging, suggested that this interaction, this pharmacokinetic interaction, would be feasible to manage in larger, longer studies. And so we wanted to be able to obtain some actual data now at differing doses of 357 and a constant dose of Riluzole to inform the design of our upcoming larger Phase IIb trial that we mentioned earlier.

Does that answer your question?

Great. Absolutely. That's helpful. And then maybe just on the myasthenia gravis trial, could you maybe review for us some of the metrics of success that we can take from the results? Obviously, as with the other evidence of efficacy trials, we're not looking for clear statistical differences, but maybe you could just give us an overview of the metrics we should be looking for?

They will not be dissimilar to the ones that you saw coming out of the ALS trial, measures of strength and fatigability. There are also symptom scores that have been designed specifically for myasthenia gravis that accumulate a variety of different functional tasks that the patients can do. So, without going into an extreme amount of detail, I think if you look at what we have disclosed about what we measure in ALS, it will not be real dissimilar to that.

Okay, great. Thanks for taking the questions.

You're welcome. Good to speak with you.

Your next question comes from Ritu Baral with Cannacord.

Hi, Ritu.

Hi, guys. Thanks for taking the question. So I'll start with the ALS program. Can you guys comment on how you're seeing enrollments going for this trial and how you might anticipate enrollment going in future trials given Biogen Idec's EMPOWER trial for their dexpramipexole?

Sure. Good question. This study moved very, very rapidly through the processes of contracts and protocol review, IRB approval, etcetera. Now, some of these centers are ones that participated with us before in the prior Phase IIa Evidence of Effect study, but others are not. And to this point, all I can say is that the enrollment seems to be proceeding well independent of any other studies that are also enrolling patients. And I don't think these studies will necessarily compete with each other given ours is a relatively short-term study and would not preclude participation of those same patients in other studies, to our knowledge.

I don't really have more to add.

Sorry. You said it wouldn't preclude involvement in the other studies. So they could do yours and then move in to the other ones?

That's our understanding.

Okay. Got it. And actually, so moving to the second cohort that you discussed today, the combination cohort, do you anticipate that doses of 357 in that cohort being the same as the doses in the initial cohort given the pharmacokinetics and the drug-drug interaction you're seeing?

Yes, because it's the 357 that affects the concentrations of Riluzole and not the other way around.

Got it. So you're going to keep the Riluzole doses steady in here as well?

There was no Riluzole in the first cohort. It was only 357 and then we'll use those same 357 doses in the second cohort and add a fixed dose of Riluzole to each of them.

Got it. And then moving to the heart failure program for a second. Since I guess there's been another ripple of discussion about design of heart failure trials now that ASCEND HF has actually hit paper publication. Have you guys had any thought, you and Amgen, had any thought to what a registration program endpoint would be and how the data that you're generating from this IIb and future plan IIb's would help you design that?

Yes. So I'll mention, it's a very good question, I'll mention that we, being aware of these ASCEND data with nesiritide long before they were published simply because they'd been presented, we appreciated already what were some of the idiosyncratic things that can oftentimes happen with the short-term administration of a drug in the acute heart failure setting.

So, to this point, our strategy has been consistent, that our objective is ultimately to couple the intravenous and the oral form, as you know, in a regimen for the treatment of heart failure patients as they transition IV in hospital to oral outpatient. That hasn't changed any of these recent data. In fact, it only I think serves to confirm that our strategy is a sound one. With that said, the study that we're doing right now, the Phase IIb study, does employ dyspnea as an endpoint, and we recognize that dyspnea has previously been acceptable as a registration endpoint for those drugs that are being evaluated strictly for the acute heart failure indication. And in that way, we still think it speaks to clinical benefit and therefore is the appropriate thing to measure for the ongoing IV study in Phase IIB patients where that may afford us the ability to translate the pharmacodynamic effects we've seen previous to a clinical benefit that leads on that portion of the patient's stay in hospital. So we see it as a proof-of-concept-like study, albeit we recognize that's not necessarily going to be the registration endpoint that we aim for in Phase III.

In Phase III, we have always said from the beginning that the endpoint that we would propose to use would be death, and we've not ever been so specific as whether it would be cardiovascular death, all-cause death. That's something to be considered. And re-hospitalization for heart failure, with that composite. And that would be the endpoint in studies in which patients are enrolled directly under the oral and maintained on the oral and in studies in which they begin on the IV and then transition to the oral. But we're fortunate that we have that oral formulation so that we can treat patients chronically with the compound no matter how they initially come to treatment with it, as outpatients put on the oral, as inpatients who are discharged on the oral before going home, or as in patients who come in and need the IV, and then transition to the oral.

So the dyspnea endpoint in the ongoing trial, while registerable, is not really the primary focus of the development program and hasn't really ever been.

Great. And can you guys talk about how various business development and/or partnership conversations are going?

So I assume you're referring to CK-357 and the skeletal muscle.

Right. The skeletal program.

Yes. I think they continue to go well. I don't know that there's much more I can say other than we continue to believe that a deal is possible in this 2011 timeframe, and that continues to be our and my highest priority.

And last question before I hop back in the queue. The follow-on candidate to 357, how is that one's development going?

So we have now two compounds that we've advanced into non-clinical development, and we are comparing those two compounds, they come from different chemical series and they both may afford certain advantages relative to CK-357 that we're looking to characterize further. So that's proceeding well, and our goal is to select, from within that grouping of two compounds, one that would therefore advance. That may be something we do ourselves, that may be something we ultimately do with a partner, and that's to be determined.

Great. Thanks, guys.

Thank you, Ritu.

Your next question comes from Mark Monane with Needham & Company.

Hello, everybody. Hello, Robert. Hello, everybody. Thanks for taking my questions. Greetings from New York City. It's both a partly cloudy and a partly sunny day.

And I guess that brings me to our next question, and that is, when you're looking at outcomes from the 357 study, clearly you're looking at some primary physiological parameters, but you're also importantly looking at some quality-of-life parameters. This may or may not be related, and which ones do you think might be primarily important to the patient and then to the FDA?

Actually it's clearing outside. FDA has agreed to register compounds for ALS on the basis of diminished decrements in the ALS functional rating scale. It hasn't -- no program has succeeded in doing that yet, but the FDA has agreed that that would be an appropriate endpoint. And that's one that measures the patient's view of their own function with their ALS. So, clearly, that's important to patients and that's important to FDA.

I think there are parameters, respiratory function, that are pretty important as well both to the patient and probably to regulators, as secondary endpoints, because, as you know, it's the inability to breath appropriately that is what kills most patients with ALS.

Thank you. That was helpful. And then when we think about the different diseases -- you tackling different diseases, is there a reason to believe that a different dose might be responsible or might be helpful given that some will be, maybe in the real world, a single agent, others in combination? And the diseases are somewhat -- have some diversity associated with them? Versus the cancer model basically, which was a former area of interest where basically the taxanes are given pretty much at the same dose in different indications.

Well, so we, you know, what we have right now at this point is single-dose data from patients with ALS and single-dose data from patients with claudication, and also some interesting pharmacodynamic data that you may recall in healthy volunteers. And at least to date, I don't see a whole lot of difference in terms of what plasma concentration generates a pharmacodynamic effect.

Now, as we get into longer-term trials, with patients that have muscle dysfunction on the basis of very different pathophysiologies, that may change. But at least as of now, the animals, the healthy volunteers and the patients we studied are all responding to more or less the same plasma concentration range.

That's helpful. And then, Robert, when you talk about partnership, when you close your eyes and you're dreaming of that partner, what does -- what qualities does that partner have?

So that's a good question. I think, more than anything else, we want to make certain that we have excellent alignment on how best to proceed given that this is a novel mechanism of action, and we're interested in a partner that's going to be interested to broadly exploit that potential and do so with the kind of urgency that we have. We have already conducted a number of clinical trials with our skeletal muscle troponin activator, and I think we've laid the groundwork and foundation for what needs to happen in late-stage development.

I would be, and we would be, averse to engaging in a partnership where we're at risk of that slowing down for the patients so desperately need this kind of drug and mechanism of action. So that's very important. And we have to get deep inside the psychology of some of these companies to understand how they're thinking about this. While everybody will preach that they're interested in compounds with novel mechanism of action, some may approach this quite conservatively and maybe in a more singular or linear fashion where we believe that there's a benefit to doing this aggressively and broadly. So that's very important.

Obviously, we also need for this partnership to deliver to our financials. We need to add to our balance sheet and also have effect to reduce our net burn and extend our cash runway. So that matters also.

And speaking of net burn and cash runway, can you help us understand what your current thoughts are going forward? And given that you run the -- it's such a -- you have an appropriately conservative style, maybe you can tell us a little bit about what it might look like without a partnership going forward.

So, as we reported with our press release and, as Sharon reported today, we've got between 12 and 18, and more specifically, 14 to 16 months of cash at our current burn rate, which includes the forecasted spend associated with our conducting the Phase IIb study by ourselves without benefit of a partner. That's certainly not what we would necessarily expect may occur, and therefore, we're hopeful that we'll be in a position to extend our cash runway with a deal.

We also don't include any potential upfronts or milestones related to this deal or, for that matter, our deal with Amgen. So as you point out, we are being somewhat conservative, as we should be, with those projections. And with a deal, we could potentially be in a much better situation. If we can't get a deal, and certainly that's a possibility -- no deal is done until it is done -- if we can't get a deal, then the current burn rate that we have is something that we would have to address. And that could be done by extending timelines; that could be done by putting certain programs on more of a backburner. There are different ways that could be done, and we have always contingency plans associated with those potential outcomes. But certainly, that's not our favorite scenario.

That was very helpful. Thanks for that information. We'll look forward to all those events happening next quarter.

Thank you, Mark.

Your next question comes from Brian Klein with Lazard Capital Markets.

Hi, guys. Thanks for taking the questions. So now that the omecamtiv Phase IIb trial is up and running, can you give us some idea on your expectations for enrollment rates and when we might see data?

So, as we discussed in the past, data from this study -- and you can look at clintrials.gov to see conservatively what is being projected for this study, to conclude with final data in the first half of 2013 -- data from this study obviously is a function of the pace of enrollment. And I think until we see enrollment rates that are farther along and the study is more mature, that's the best way to project here. And that's what we and Amgen believe is the right to be speaking to.

We're not expecting to have data on cohort-by-cohort, but rather speak to enrollment and how it's progressing as we may proceed from cohort 1 to cohort 2, from cohort 2 to cohort 3, and that's going to be based on an assessment of a safety review group, an external group, evaluating these data, and we will not be privy to the unblinded or blinded data. Only will we be able to communicate that the study is progressing, albeit the progression from cohort 1 to cohort 2 in this study design where we are escalating doses should be construed as a positive. I think that's the best thing we can share with you now. And as the study matures, we'll hopefully be able to give you those kinds of updates.

Okay, great. Can you confirm if there are any milestone payments associated with the Phase IIb trial or with either of Phase I trials for the oral formulations?

So, all I can say is that there have been no milestone payments earned, and we have initiated Phase IIb, and as we've said in the past, we can't comment otherwise on what may be future triggers for milestone payments. That's a matter of confidential disclosure, and that's not something that we're privy to discuss. So I'm not sure I can do any better than that today.

Great. Thanks so much.

Thank you.

Your final question comes from the line of Christopher James with McNicoll Lewis & Vlak.

Hi, Chris.

Hi, Robert and Andy. Thanks for taking my questions. I'll be real brief here. Maybe I'm missing something, but what's the scientific rationale for developing 357 in ALS and myasthenia gravis, one that involves antibodies acetylcholine receptor versus upper and lower motor neurone disease?

Well, in each case, but for different reasons, we have a situation where the muscles are weak, not because there's anything intrinsically wrong with the muscles, but because the signal that they're receiving from the nerve is diminished. In one case, as you just mentioned, because it's not being properly transmitted across the neuromuscular junction, in myasthenia gravis, and then ALS because the nerves themselves are dying. And what we saw very clearly from our preclinical studies is that, especially at nerve stimulation frequencies that are associated with kind of normal daily activities, not at the very fast frequencies associated with maximum effort, but at those low- to mid-range frequencies, that is where the effect of the drug to increase skeletal muscle performance was actually most prominent.

So you can get, if you will, more muscle strength bang for your nervous input buck in the treatment of these diseases with 357. So that's exactly what we're trying to do here. In both of these two diseases, there's not quite so much neuromuscular input as would be desired, but in the presence of the drug, we hypothesize that that diminished input could result in a normalized forced production.

Okay, I get it. And then on to omecamtiv, I know you're looking at dyspnea as one of your primary endpoints, but you also mentioned in proBNP. Why would you look at that versus BNP, and then how do you control for the inter-patient variability and the brain-natriuretic peptide?

Well, hopefully, randomization in the placebo group take care of that. It is a variable measure, but it's also a pretty big trial. So with 200 patients in each of three treatment groups, one of placebo and -- I'm sorry, with 200 patients in each -- strike that. Two hundred patients in each cohort, which in the end will give us 300 patients on placebo and 100 on each dose level of OM, there should be sufficient power to discriminate a change, if there is one.

Okay. And then finally, what can you tell us about the therapeutic window for 357? And how does that compare to omecamtiv?

So, obviously these are entirely different programs, different mechanisms of action, so I'm not sure that comparing them would be all that useful. These are apples and oranges, if you will.

Right.

CK-357, as we evaluated in Phase I studies in healthy volunteers, we saw a maximally-tolerated dose of 2,000 mg with the 2,500 mg dose producing some intolerable effects in healthy volunteers, principally light-headedness. In the multiple-dose study of CK-357 in healthy subjects, we have data to suggest that the drug is well-tolerated, achieving steady-state kinetics around four to six days, and where there may be reason to think that with multiple dosing, some of the light-headedness may abate. So that's healthy volunteers.

As we've moved into patient populations, firstly, in ALS patients and then in peripheral artery disease patients, we've been looking at doses quite a bit lower than that maximally-tolerated dose. These single-dose studies have looked at doses in the range of 250 mg and 500 mg, and as you have seen with those data, we're seeing mostly mild AEs and only occasionally some moderate AEs at those dose levels.

So we think we've got a good therapeutic window, at least as defined by these pharmacodynamic studies, albeit really to answer your question, we're going to have to do longer-term dosing such as we're doing right now in the ALS population, dosing out to two weeks. And I think we'll be able to better answer your question with these additional data, and we're optimistic that we'll be able to point to two weeks of dosing in ALS patients that these doses are well-tolerated. We'll know that soon enough. We should know that, as I mentioned, by the end of the year.

All right. Thanks, Robert, that's really helpful. Thanks, Sharon, thanks, Andy.

Appreciate your interest. Thanks so much.

Great.

There are no further questions, so I will turn the call back over to Robert Blum, CEO and President, for closing remarks.

Okay. So, thank you to all the participants on our teleconference today. We appreciate your continued interest in Cytokinetics. And operator, with that, we can conclude the call.

Thank you to all the participants on our teleconference today for the time and your continued interest in Cytokinetics. Ladies and gentlemen, you may now disconnect.