Cytokinetics Inc (CYTK) 2010 Q4 法說會逐字稿

Good afternoon and welcome, ladies and gentlemen, to the Cytokinetics fourth-quarter and year-end 2010 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 to Sharon Barbari, Cytokinetics' Executive Vice President of Finance and CFO.

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 overview of the past quarter, along with an update on the investment of our development pipeline, focused on the biology of muscle function. Andy will then provide highlights and details on the progress of the Company's clinical development programs. I will then provide some brief comments with respect our financials and our investment in research and development activities. Robert will then conclude the call with additional comments regarding our recent activities, next steps for our clinical program for CK-2017357, which we'll referred to as CK-357 for the remainder of the call, in patients with ALS and discuss the projected Company milestones for 2011. We will then open the call for a brief question and answer session.

The following discussion, including our responses to questions, contains statements that constitute forward-looking statements for purposes of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to statements relating to our financial guidance, 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 quarterly report 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, and we undertake no obligation to update these statements after this call.

Now I will turn the call over to Robert.

Thank you, Sharon. In 2010 Cytokinetics took significant steps forward in connection with our strategic commitment to advance our first-in-class muscle biology programs. We are particularly pleased with the progress we've made this past year with the advancement of our skeletal muscle program. We initiated two Evidence of Effects hypothesis-generating trials in 2010 with our lead skeletal muscle activator, CK-357, one in patients with ALS and one in patients with claudication associated with peripheral artery disease.

More recently, in January we initiated a third Evidence of Affect trial, this trial enrolling patients with myasthenia gravis. In December we successfully concluded and reported the results from the first of these Phase IIa trials and shared these data with both ALS patients and clinicians attending the ALS/MND Symposium.

In a moment, you will hear a summary of the results from this trial from Andy, and also he will elaborate on how we believe that the data from this trial provide a framework for the next steps in our clinical development program for CK-357.

Similarly, we recently made significant progress with our lead clinical development program relating to omecamtiv mecarbil under joint development with Amgen for the potential treatment of heart failure.

As we announced last week, our collaborative activities over the past several months have resulted in a protocol and related regulatory submissions for a next planned Phase IIb clinical trial of an intravenous form of our novel cardiac myosin activator. Andy will speak to the specific design for this trial designed to evaluate its safety and efficacy in patients with left ventricular systolic dysfunction hospitalized for acute heart failure.

I'm also pleased to report that last quarter Cytokinetics and Amgen agreed on a joint research planned for 2011, which is focused on collaborative research activities that will be directed toward potential next-generation compounds in our cardiac muscle contractility program.

In addition to our business overview for the quarter, towards the end of the call, I will share with you our planned milestones for 2011, which include the anticipated timing of our planned clinical trials of omecamtiv mecarbil, CK-357 in ALS, and have CK-2066260 or CK-260, a second fast skeletal troponin activator.

Now I would like to turn the call over to Andy to elaborate on the specific clinical progress achieved during the last quarter in our drug candidate development programs and also to provide some insights into our plans for the future.

Thank you, Robert.

As Robert mentioned, 2010 was a year during which we made steady progress on several fronts. Beginning with our cardiac muscle contractility program, we announced last week an update to our development plans for omecamtiv mecarbil. These plans were the result of collaborative activities between Cytokinetics and Amgen to define the development path for omecamtiv mecarbil and develop a detailed protocol and related regulatory submissions pertaining to a randomized, double-blind, placebo-controlled multicenter Phase IIb clinical trial of an intravenous formulation of this drug in patients with left ventricular systolic dysfunction who have been hospitalized for acute heart failure. This Phase IIb clinical trial is planned to be an international, multicenter, randomized, double-blind, placebo-controlled study in approximately 600 patients enrolled sequentially in three ascending dose cohorts.

In each cohort, patients will be randomized to receive either omecamtiv mecarbil or placebo. The primary objective of the Phase IIb clinical trial will be to evaluate the effect of 48 hours of intravenous or IV omecamtiv mecarbil compared to placebo on dyspnea or shortness of breath in patients with left ventricular systolic dysfunction hospitalized for acute heart failure.

The secondary objectives will be to assess the safety and tolerability of three dose levels of IV omecamtiv mecarbil compared with placebo and to evaluate the effects 48 hours of treatment with IV omecamtiv mecarbil on additional measures of dyspnea, patients' global assessments, change in N-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.

In addition, the trial will evaluate the relationship between omecamtiv mecarbil plasma concentrations and echocardiographic parameters in patients with acute heart full-year.

Moving now to our skeletal muscle activator program, another major highlight of the quarter for Cytokinetics was the presentation in December of data from over Phase IIa Evidence of Effect trial in patients with ALS. This presentation was made by the trial's principal investigator, Dr. Jeremy Shefner at the 21st International Symposium on ALS/Motor Neurone Diseases, and to ALS healthcare providers and their patients received the data with significant interest and enthusiasm.

To remind you, this is a hypothesis-generating trial designed with no specific primary endpoint. Instead, in order to determine whether the mechanism of action of CK-357 could produce clinically relevant pharmacodynamic effects in ALS patients that could justify further testing, we evaluated a broad range of parameters, including patient and physician global assessments, as well as measures of muscle strength and fatigability and also indices of pulmonary function.

The trial employed a randomized, placebo-controlled, three-period crossover design and was intended to evaluate the pharmacokinetics and pharmacodynamics of single doses of CK-357 in ALS patients. In all, the trial enrolled 67 patients with ALS. Patients were administered single doses of placebo and a CK-357 at each of 250 mg and 500 mg in a double-blind fashion and in random order administered at least six days apart. Patients underwent the evaluations described above before each dose of study medication and again at three, six and 24 hours afterwards.

Results from the trial demonstrated that both patients and investigators perceived a positive change in the patient's overall status at six hours after dosing with CK-357 based on a global assessment in which the patient and the investigator each independently were asked whether the patient was better, the same, or worse compared to just before dosing on that day.

Furthermore, there was a clear relationship between improvements in these global assessments in both the CK-357 dose and plasma concentration. The investigators proposed that the improvements observed in patients and investigators' global assessments may have resulted from a decrease in the fatigability of their muscles as evidenced by data from a test of sub-maximal hand-grip fatigability. Certain parameters of pulmonary function also trended towards improvement after treatment with CK-357, which the investigators also believe might have contributed to the improved patients' and investigators' global assessments.

Finally, investigators also concluded that these single doses of CK-357 appear to be safe and generally well tolerated by the patients in this trial. There were no serious adverse events judged to have been drug-related, and most adverse events were classified by the investigators as mild. Most reports of dizziness, the most frequent and most clearly dose-related adverse event in the trial were classified as mild, and none were determined to be severe.

In speaking with investigators about these reports of dizziness, the effects were typically not associated with symptoms of vertigo or a loss of balance, but rather as a lightheaded feeling similar to the effects of an alcoholic average.

In addition, some of the investigators even noted that if they had not been continually inquiring as to how the patients were feeling, many of the patients may not even have reported this symptom. We believe that this trial did exactly what it was intended to do. It generated hypotheses for this novel mechanism of action that can now be tested in subsequent clinical trials.

As I already mentioned, these data have been very well received by the ALS scientific, physician and patient communities, not only by those who directly participated in our trial, but also by those who have subsequently learned the trial's results. We are very pleased to announce today that in April data from this trial has been expected to be presented during plenary session at the 63rd Annual Meeting of the American Academy of Neurology.

I would now like to share with you our plans for the further clinical development of CK-357, which include the anticipated initiation of two additional clinical trials in 2011, in addition to the two ongoing trials of this novel drug candidate. One is a Phase I drug/drug interaction study of CK-357 in healthy volunteers.

The first part of this study is designed to evaluate the effect of CK-357 on the pharmacokinetics of Riluzole, the only drug currently approved for the treatment of ALS. The second part of this study will evaluate the effect of CK-357 on the pharmacokinetics of other drugs and is also intended to evaluate the effects of food on the pharmacokinetics of orally administered CK-357.

The other clinical trial planned for 2011 is a Phase II clinical trial of CK-357 in ALS patients who will receive daily oral doses of CK-357 for 10 to 14 days. The primary objectives of this trial are to evaluate the safety, tolerability and pharmacokinetics of multiple doses of CK-357 in ALS patients.

In addition, patients will be asked to report their ALS symptoms using the revised version of the ALS Functional Rating Scale, also known as the ALSFRS-R as our. The ALSFRS-R is a patient-reported outcomes measure that has been used as a primary endpoint in several recent longer-term studies in patients with ALS. Patients will also undergo various pharmacodynamic tests of muscle fatigability, certain indices of pulmonary function, as well as patients' and investigators' global status assessments. This trial will not be powered to demonstrate specifically significant effects of CK-357 on any of these pharmacodynamic endpoints, but rather is intended to allow us in a cost-effective manner to determine the safety and tolerability of multiple doses of CK-357 in these patients.

The trial is designed potentially to answer questions relating to the mostly mild episodes of dizziness that were reported in our recently completed single dose Phase IIa trial that I have just discussed. It may be that we will see some abatement of this dizziness with continued dosing in CK-357. This Phase II trial may be initiated after we have completed the initial part of the Phase I drug/drug interactions study, which, as previously mentioned, will focus on a drug/drug interaction with Riluzole.

Also, as we mentioned, we continue to enroll and dose patients in our second Phase IIa Evidence of Effect trial of CK-357 in patients with intermittent claudication associated with peripheral artery disease.

We have spoken previously about the specific design of this trial, but to repeat, in this trial multiple assessments of skeletal muscle function and fatigability are performed, including the number of contractions, time and work to onset of claudication and to intolerable claudication pain or to maximum calf muscle fatigue during bilateral heel-raised testing. A six-minute walk test is also performed during each dosing period.

During the fourth quarter, our research and development teams readied for the recently announced initiation of our third Phase IIa Evidence of Effect clinical trial, this one in patients with generalized myasthenia gravis or MG. This trial and associated research activities are primarily funded by a $2.8 million grant from the National Institute for Neurologic Disorders and Stroke or NINDS part of the American Recovery & Reinvestment Act of 2009.

This trial, like our other Evidence of Effects trials, is a double-blind, randomized, placebo-controlled, three-period crossover pharmacokinetic and pharmacodynamic study. At least 36 and up to 38 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.

The primary objective of this hypothesis-generating clinical trial is to access the effects of CK-357 on measures of muscle strength, muscle fatigue, and pulmonary function using the standardized, quantitative MG score, manual muscle testing, and the MG composite score. The secondary objectives of this clinical trial are to evaluate and characterize the relationship if any between the doses and plasma concentrations of CK-357 and its pharmacodynamic effects to evaluate the safety and tolerability of CK-357 administered as single doses to patients with MG and to evaluate the effect of CK-357 on investigator- and patient-determined global functional assessment and the modified MG symptom score.

Additional information about both of these ongoing trials can be found at www.clinicaltrials.gov.

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

Thank you, Andy. As our press release contains detailed financial results for the fourth quarter and year ended December 31, 2010, I will refer you to that public statement for the details on our P&L and balance sheet. We ended the fourth quarter with $72.8 million in cash, cash equivalents and investments, excluding restricted cash, which represents approximately 16 months of going forward gross cash burn based on our 2011 financial guidance.

Our fourth-quarter 2010 R&D expenditures totaled $9.2 million from a program perspective for the fourth quarter. Approximately 74% of our R&D expenses were attributable to our skeletal muscle contractility research and development activities, 2% to our cardiac muscle contractility activities, and 24% to our other research and non-clinical development activities, including our smooth muscle contractility program.

For the 12 months ended December 31, 2010, our R&D expenditures totaled $38 million, and from a program perspective for the 12 months, approximately 77% of our R&D expenditures were attributable to our skeletal muscle contractility activities, 4% to our cardiac muscle contractility activities, and 19% to our other resource and non-clinical development activities, including our smooth muscle contractility program.

As you can see, we continue to focus our financial resources largely on our skeletal muscle research and development program, which two together with our cardiac muscle contractility development program partnered with Amgen, we believe provides the nearest term value generation for the Company as Robert will outline in a moment with our 2011 milestone.

We also announced financial guidance for 2011. The Company anticipates cash revenue to be in the range of $2 million to $4 million, cash R&D expenses to be in the range of $40 million to $45 million, and cash G&A expenses to be in the range of $13 million to $15 million. This financial guidance is on a cash basis, does not include an estimated $4.8 million in non-cash operating expenses primarily related to stock compensation expense. This guidance does not reflect potential revenue from any new potential collaborations or partnerships.

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

The fourth quarter with the presentation and announcement of data from our Phase IIa trial of CK-357 in patients with ALS capped off a successful year for the Company during which we made great strides in advancing our skeletal muscle contractility program. In one year, we have expanded our pipeline to where today we are testing CK-357 in three indications that could potentially set the stage for additional clinical trials in multiple neuromuscular indications. I'm pleased with what we accomplished while recognizing that we have a good deal more work to do in the coming year.

As Andy mentioned, Amgen and Cytokinetics have together been busy in connection with our omecamtiv mecarbil program. We look forward to a productive 2011 with the planned initiation of a Phase IIb trial. The Company has also taken steps to evolve its board with the recent additions of Sandy Costa and Dr. Wendell Wierenga. Both Sandy and Wendell bring with them long and successful careers in the areas of pharmaceutical research, development and commercialization, as well as quite significant prior board experience with successful biopharmaceutical companies that have realized the aspirations that Cytokinetics has in building out our business through leveraging our proprietary R&D platform. We believe their skills complement those of other members of our board and will enhance the governance and oversight of Company performance as we execute on our plans for 2011 and afterwards.

As many of you have inquired about our strategy surrounding a possible development partner for CK-357, I wanted to provide some details.

While it is always difficult to provide specific guidance on partnerships, what I can tell you is that we are continuing to engage with multiple companies and that we're looking at a number of different deal structures that vary as to scope of engagement and licensing. However, we are not providing guidance as to the timing of a possible deal.

Now, I would like to review our milestones for 2011 related to each of the programs in clinical development.

For omecamtiv mecarbil, we anticipate that in the first half of 2011 Amgen will initiate an international, randomized, double-blind, placebo-controlled Phase IIb clinical trial of an intravenous formulation of omecamtiv mecarbil in hospitalized acute heart failure patients with left ventricular systolic dysfunction.

Cytokinetics and Amgen are in active discussions regarding the development strategy for oral formulations of omecamtiv mecarbil. We anticipate that these plans may include studies designed to investigate the safety, tolerability and pharmacokinetics of multiple oral formulations of omecamtiv mecarbil. Additional information will be provided following the finalization of these plans.

Turning now to our skeletal muscle contractility program, we look forward to the planned presentation of data from the Phase IIa Evidence of Effect clinical trial of CK-357 in ALS patients during a plenary session at the 63rd Annual Meeting of the American Academy of Neurology in April in Honolulu, Hawaii. We anticipate that in the first half of 2011 data will be available from the ongoing Phase IIa Evidence of Effect clinical trial of CK-357 in patients with symptoms of claudication associated with peripheral artery disease. We anticipate initiating in the first half of 2011 a Phase I drug/drug interaction study of CK-357 administered orally to healthy volunteers. This study is intended to evaluate the effects of CK-357 on the pharmacokinetics of Riluzole and other drugs and the pharmacokinetics of CK-357 when administered after a meal and when fasting.

We anticipate initiating a Phase II multidose safety, tolerability pharmacokinetic and pharmacokinetic clinical trial of CK-357 in patients with ALS. This trial, which may begin at midyear 2011, following the availability of data from the Riluzole arm of the Phase I drug/drug interaction study, is expected to evaluate patients receiving daily oral doses of CK-357 for 10 to 14 days.

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

With respect to CK-260, we anticipate filing an investigational new drug application for this potential drug candidate by midyear 2011. We also anticipate initiating a first in humans Phase I clinical trial with CK-260 in healthy volunteers in the second half of 2011.

With respect to each omecamtiv mecarbil, CK-357 and CK-260, we will provide further guidance on the expected availability of data from these yet to be initiated clinical trials following each trial's initiation and an assessment of patient enrollment.

I should mention that we're especially pleased to be advancing our potential drug candidate, CK-260, towards an IND. We believe the parallel development of CK-357 and CK-260 is prudent in light of risks inherent in the development of novel drug candidates and believe the strategy also affords the possibility of an expanded development program directed towards diseases or conditions associated with skeletal muscle weakness or wasting.

In closing, we rang in 2011 with the initiation of our third Evidence of Effect trial and with it still yet further demonstration of our commitment to developing novel therapeutics based upon our focus to muscle contractility.

With the progress we've made in 2010, I believe that 2011 holds great promise as we planned to initiate multiple clinical trials and further our continuing research activities, all with the goal of creating greater value for our shareholders.

Operator, that concludes the formal portion of our call today, and I would now like to open up the call to questions.

(Operator Instructions). Mark Monane, Needham & Company.

Thank you, Robert, and thanks to the team for the comprehensive reviews of 2010 and what we should look for in 2011. Greetings from New York City -- 56 degrees, a nice quantifiable number, a nice day here.

Speaking of quantification, can you help us understand how many patients might be needed in the Phase II 357 study that you're about to initiate to answer the questions from that trial?

So how many patients in the ongoing claudication study?

No, no, I'm sorry. In the 357 ALS trial that you are planning for 2011, how many patients might be needed to answer the questions that you are answering?

You are referring to the multi-dose study that would begin we expect in the second half of 2011?

Yes. Thank you.

I will refer that to Andy then.

It will be a small trial, Mark. We haven't finalized the protocol yet, but it is not going to be more than some dozens of patients and probably a low number of dozens of patients.

And then in thinking about the outcomes of the study, multi-dose study, it would be nice if you outlined what safety concerns you're looking for? I thought I heard you say that you would be using a (inaudible). Is that correct, and is that the type of scale you might bring into a (inaudible) trial going forward?

The ALS Functional Ratings Scale in its revised form is the now standard form of the ALSFRS, and it has been used in a number of larger registration trials recently as a primary endpoint. So it would be what we would use in a larger longer study of patients with ALS.

So we want have anything close to statistical power, but we may get some idea just what sort of responses we may see with dosing patients now for a period of some days instead of just a single dose.

I think to add to that, Mark, in the interest of maybe a common theme being prudent drug development, one of the things we would look to do in that study is pilot -- even as we recognized the study would not be powered for statistical significance -- pilot certain endpoints that we think could be then studied further in a Phase IIb study that would be a registration study, potentially leading to a Phase III study or otherwise standing on its own.

All right. That was helpful. And then last question on the omecamtiv mecarbil trial, I noticed that these patients that you and Amgen are going to focus on are already hospitalized patients with heart failure. I guess the question is, some trials have looked at re-admission or prevention of re-admission as an outcome from biomarkers, too. As you develop this drug going forward, what registration type outcomes do you think at this time might be the most appropriate for an IV drug (inaudible)?

For the IV, you are really not in a good position to look at prevention of re-admission. There is an example of a therapy that did manage to have discernible effects out for some days after its administration. But, in general, it is a risk because you are administering something acutely. It is present for a short period of time. You expect to see the pharmacodynamic effects when the drug is present, and we don't have much expectation to imagine in this particular kind of situation that those benefits could persist for much time after the drug is no longer on board.

So, for an IV-only study, we really have to look at outcomes that can be assessed during the period or shortly thereafter of drug administration, and that is dyspnea, and dyspnea is a well-recognized endpoint in acute heart failure trials. It is accepted as registrable both in the United States and in Europe, and it certainly is something that is easier to power a trial to see changes in and would be mortality where, as I'm sure you're familiar, that the in-hospital mortality of these patients is actually pretty small. It is low single digits in this day and age. The problem is they come back so frequently where they die out of hospital.

That is the kind of endpoint that I think and we have discussed this many times before that we can probably -- at least we believe we can according to our therapeutic hypothesis -- we can affect survival and re-admission with an oral compound that can be administered daily over a chronic basis. But for acute use, I do believe we are well advised to stick to endpoints that can be measured with reasonable statistical power in hundreds of patients during their hospitalization.

With that said, I will just caveat and add one further comment, even in this Phase IIb study of the intravenous form of the drug, it would be our expectation to follow these patients in the post-hospital period just to ensure that nothing were to suggest that the drug after discharge would introduce any added safety concern.

Thanks very much for the added information.

Ritu Baral, Canaccord.

Thanks for taking the question. My first question is focused on the design of the next ALS 357 trial, why choose the 10- to 14-day treatment period? A lot of ALS investigators, at that that I had spoken to, expressed interest in seeing, say, a three-month treatment period, basically indicating that that is sort of the timeframe you would be looking at for a real impact in the ALSFRS? And further, will you be looking at additional doses and any sort of special dizziness measure to keep track of that side effect?

So I will start and then turn it over to Andy. So this study is not intended as a substitute for what would be a study to evaluate potential effects on ALSFRS as maybe measured up to three months or more. Rather instead, this is a study intended to understand safety, tolerability and PK of multi-dosing so as to best select the doses around which we might then proceed to that next study.

So based on what we know from the single dose study, including, as you suggest, the adverse effect of lightheadedness, we think it's prudent to do this additional study so that we can best understand the safety tolerability in PK on a multidose basis before proceeding.

I don't know, Andy, if you want to add?

I don't have that much to add. It is a bit of a bridge to the longer, more definitive study. I just want to make sure we understand the issues, if there are any, with multiple dosing of the drug.

And will you be looking at the same doses that you did in the single dose?

Well, no. Not exactly because now we will be giving them every day, but we will be looking at multiple dose regimens that will not exceed by much if at all the plasma concentrations generated by single doses of 500 mg, which was the higher of the two doses in the first study.

So in that regard, this is quite similar to what we did in healthy volunteers. We did a single dose study, followed by a multidose study, to understand what level of accumulation may occur with multidosing and at what time point to achieve steady-state. Based on that knowledge and knowing that the single dose study predicted very well in healthy volunteers what we ultimately saw in ALS patients, we similarly now want to look at a multidose regimen in ALS patients, but again targeting the same steady-state plasma concentrations, albeit starting with lower doses because we do know there is some accumulation with multi-dosing.

Got it. And any special measures for the lightheadedness or dizziness?

No, not really. We've looked into it, but I don't think in a study of this size, we can do much more than just to do patient self-reports of dizziness.

Okay. And then last question, CK-260, your second skeletal muscle drug, how is the profile of that drug different than 357?

Very good question. So just to repeat what we said on prior calls, we advanced a backup this compound we referred to CK-260 into IND-enabling studies last year, and we continue to do research on potential follow-ons much like we did in our cardiac program and other programs at Cytokinetics as just good prudent drug development.

This particular compound does seem to have some different physiochemical properties, one of which is that while it does cross the blood brain barrier, it appears it does so to a lesser extent than the CK-357. So to the extent that lightheadedness may be an issue, albeit at this point we don't think it is based on single dose issue, an issue that would preclude the advancement of the drug into further clinical trials, but as may now be understood with multi-dosing, we do think it is prudent to have CK-260 available as we are moving forward both as it relates to CK-357, but also, as we've said time and time again, we think there's an advantage to advancing multidrug candidates here because, as you know, we have a wide array of indications that we could be interested in pursuing.

Great. Thanks for taking the questions.

Charles Duncan, JMP Securities.

Congratulations on a nice year of progress. My question is first on 357, I'm just not clear. If you could provide us the milestones, would you anticipate finishing the multidose study yet this year? And then do you think that will inform well the design? Will that be sufficient to design a Phase IIb or true clinical proof of concept study for next year?

So it is a very good question, and I'm going to stop short of giving specific guidance until we know when that study might start and how quickly it may enroll. But given the size of the study, it is possible that if that study were to start reasonably soon after the availability of data from the drug/drug interaction study, that that study could be producing data this year, and just as you are projecting, we could be in a position to initiate a Phase IIb study next year. So that is certainly something we might hope could occur, but, again, until we see a) the drug/drug interaction data, b) until we have finalized a protocol for the multidose study and have signed up centers and seen an enrollment rate, it may be premature to point to a specific timeframe under which that data could be available.

And I know we're taking our really kind of high-powered binoculars out and looking through them with my next question or to answer my next question, but do you think that a Phase IIb trial given the unmet medical need could prove to be a registrational support on an NDA for this drug, and if so, do you think it would be a three-month duration of treatment that would be sufficient?

I think some of that will wind up in the end being data-driven. Certainly if we appropriately specify our primary objective and hypothesis which we would intend to do and right now as we're thinking it would probably be the ALSFRS-R and we were to show statistically significant increases in that versus placebo or at least reductions in the rate of decline but better than placebo, it could be even at three months most likely, and I don't want to be speaking for FDA. That is a slippery slope. But I want to be very clear I'm not doing that. But in my own personal view, it is not unlikely that it could definitely be viewed as supporting registration.

But whether a single study in that number of patients would due by itself at three months, it would be a real discussion today, and this is where I say it is data-driven. If we were absolutely just knocking the ball out of the park and the patient scores were actually improving from baseline and staying up beyond baselines for those three months while the patients on placebo were deteriorating, that might be sufficiently compelling to have something done rather quickly given, as you say, the dire nature of the disease. If it is something that is clearly discernible but maybe not quite so amazing, then I think it is more likely that we would have to either do a longer or a bigger trial or another trial.

And, Andy, understanding that you are several steps away from being able to definitively answer this, but would it be your goal to start such a trial in call it the first half of next year?

I think it would be a goal. As Robert has already said, that goal, its achievability, will depend upon how quickly the studies that we haven't done yet actually enrolls.

Sure, understood. You also alluded to something in your commentary -- and this is consistent with some of the diligence we have done with thought leaders -- but it seems like the one comment observation in the earlier studies is this lightheadedness or dizziness could go away if, call it, investigators are appropriately prepared for that observation. Do you agree with that, and secondarily, do you think there is any mechanistic rationale besides the, call it, partitioning of the drug into the brain to believe that there is any real signal there?

I think that we have seen the dizziness so consistently and in a dose-related fashion in healthy volunteers and in patients with ALS and in patients with claudication that I have to believe that the signal is there, and we do believe, as you suggested, that it is as a result of the drug getting into the brain. You don't know that it does in patients, but we know it does in the animals, and we have, therefore, every reason to believe it does in patients as well.

But there are a number of CNS effects like dizziness, somnolence, other side effects, too, that are sometimes used, nuisance effects that actually do abate with continued dosing, and our investigators have just speculated that this may be the case. But we have no mechanistic rationale for why it may abate. It is just mainly a phenomonolgy that has been observed with other similar side effects of other drugs.

Okay. That's helpful. If I could just hop over to omecamtiv quickly, Robert mentioned having plans with the oral formulation and working on that with Amgen. Is there a certain work to date would you anticipate that roughly midyear this year, or is that something toward the end of the year?

I will speak to that. So much of last year, as you know, was focused toward a strategy to enable the progression of omecamtiv mecarbil into Phase IIb with an intravenous form, and I'm pleased that we now can point to when we expect that will be underway in the first half of this year.

We can now be turning our attentions collaboratively to what makes sense with respect to the oral development program. And the only reason why we are not pointing to specific milestones and giving guidance to timing right now is we just haven't finalized those plans, and we're discussing with Amgen how we might choose to proceed. So I do expect we will be in a position to provide some clarity as to those plans at a subsequent time perhaps with one of these earnings calls. But until such time as we have something where we could really reliably and credibly point to a plan and timing, we thought it would be premature to do that on this call.

Okay. One additional 357 question -- sorry for taking so much time. With regard to the myasthenia gravis data that you mentioned by the end of 2011, can you give us some sense as to that will be presented, or will that be topline data, and is that by the end meaning like fourth quarter, or is that in the second half?

We will really have to see how the enrollment goes in what we see, when we do, if we do an initial interim. I think what we've said is what we can say, that there will be data by the end of the year.

Andy, what would the basis of the interim be just as a reminder in terms of design?

Well, the design of all three of these Evidence of Effect studies is very open. So we can do one any time we want really because there is no primary endpoint, and there are no alpha penalties taken for early looks or meaningful comparisons. So we will just monitor the study as one always does without unblinding the patients, and if we don't see any signals of concern given the experience that we have already had now with these doses in patients with ALS, I would probably be less prone to do an early interim just in view of conserving resources. It's not a trivial exercise to get all the data in and clean it up and analyze it. If we're not seeing any issues -- or, on the other hand, the other thing we could be seeing is certain patients having whopping improvements that might make us want to look earlier rather than later. But in the absence of that, I'm probably less prone to do one because we have gotten a fair experience with the drug at this point in single doses.

Yes, as Andy points out, while we did do interims with each of the ALS study and the claudication study, we take those learnings to this myasthenia gravis study, and it may not require us to do an interim as we then decided it makes sense. So we will play that one by ear right now. Currently we do not have plans to do an interim in the myasthenia gravis study.

Thank you for the added color.

Brian Klein, Lazard.

Thanks a lot for taking the questions. Just two quick questions. If the drug/drug interaction trial proceeds as you expect, will patients on Riluzole be eligible for the Phase II multiple dosing trial?

We have not finalized the design of the Phase II study. And I think what you are hearing is that we think it is prudent to have the data available from that study before proceeding into the ALS study. So I would need to know what those data look like before really being able to answer your question.

That's fair. And then second housekeeping question, are you guys forecasting or are you expecting a milestone payment with the initiation of the Phase IIb trial for omecamtiv?

That is something that comes up pretty much on every one of these calls and oftentimes from the Lazard analysts. I will only mention that in each prior time that it has come up, we have indicated that unfortunately we can't comment. That is something that is a matter of some confidentiality with Amgen. I would like to be able to provide that clarity were I able to, but I'm not able to.

Okay. Thanks so much.

David Nierengarten, Wedbush Securities.

I just had a couple of quick questions. Most of mine have already been asked. I was just wondering with the drug/drug interaction trial with Riluzole results, are there any other drugs in particular that you're looking at, or is that really the only one?

Well, there are other generic probes that we will look at in the second portion of the study.

Perhaps you could refresh my memory. So there is just nothing in particular, or are there other drugs that really stand out that might have an interaction with 357 in ALS patients?

Based on our in vitro data, there are other cytochrome isoforms that are worth evaluating in this setting, and I don't want to enumerate them right now because I don't want to get any of them wrong. I don't want to misspeak. But there are a couple of others. They are common.

I will to you what one is not. One is not 3A4, which is a very common culprit. So that is not one of them. One of them is not 2D6, which is another common culprit. A few others that are less commonly the major metabolizers of frequently administered drugs. I don't want to sound as though I'm completely ignorant of them, but I don't want to give an answer that is incomplete or in any case incorrect.

I will underscore that previously we have mentioned that in the study of CK-357 as a single dose in ALS patients, we did see some increase in Riluzole concentrations, and we think given that this is a drug that is used in a majority of ALS patients, it is prudent to understand that potential drug/drug interaction, and therefore, that's why we're doing that particular study.

Okay. Thanks. And one other question regarding 260 and its cumulation versus 357, you mentioned that there was somewhat less accumulation due to less blood brain barrier penetration or I should say less -- you are hoping or there is less blood brain penetration I should say. Do you think there is also less accumulation, or are the PK/PD dynamics here a little bit different than 357 in that regard, too?

I think it is very risky to predict what the human PK will look like relative to 357's human PK based on animal data. That's a good way to get tripped up over and over.

What we do know is that, yes, it would appear to penetrate the blood brain barrier less effectively, so that could be an advantage. And, otherwise, we will just have to see what the PK data show, and we would do the first time in a human study.

I don't want to make too much of this human blood brain barrier activity either. It's one of the distinguishing characteristics that appears between CK-260 and CK-357. That may prove to be an advantage or otherwise not be required.

Thanks.

Mark Monane, Needham & Company.

Sharon, would you be willing to go over explicitly what you expect the use of cash to be in 2007? Is it simply being an addition of the numbers that you have in the press release?

You mean 2011, right?

2011, excuse me.

So when you -- I want to make sure understand your question with respect to how the cash will be used?

No, I got the -- I think you went over it -- but the total use of cash, what will be the cash burn that you expect in 2011?

In 2011 between the two pieces you're looking at somewhere between I think it is $51 million to $56 million, if I'm not mistaken. Let me look at my notes here. So that is total cash, yes, $51 million to $56 million the revenue minus the expense guidance.

Is your question related to how it might break out by program area?

No, I think she went over that in good detail, mostly on 357.

That was for 2010, but we don't typically give going forward guidance with respect to the uses. I will tell you the revenue of the $2 million to $4 million contains a component of revenue related to Amgen reimbursing us for the research FTEs that Robert spoke of in his script and is also outlined in the press release, as well as reimbursement from the NIH related to the myasthenia gravis study. So that is the revenue component.

So those expenses are included in your expense guidance for research. So you can subtract $2 million to $4 million off of that research guidance number to get the net spend for research and development.

That was helpful. And then why is the ideal number -- how many people are now at Cytokinetics, and what is the main number for this year and going forward?

So right now we have approximately 105 full-time equivalents at the Company. It is difficult to say what is the ideal number because ideally we would be doing things that we can't afford to do right now, and right now I think what we are doing, we are rightsized for the ability to prosecute these programs while maintaining some research in programs that may deliver drug candidates in the future.

So we're a smaller company than we were last year, and over the last several years, much of that has been through some standard attrition, and we have been I think very disciplined about which positions we might choose to fill. We have not had any restructurings or anything of that sort since, as you may recall, 2007. But we have been managing to ensure that we are keeping the Company at appropriately sized organizations to be able to deliver on these types of value-enhancing milestones.

Perfect. Thanks, again, for the added information.

There are no final questions.

Thank you to all the participants on our teleconference today for your continued interest in Cytokinetics, and Operator, with that, we can conclude the call, wishing everybody a good day.