Cytokinetics Inc (CYTK) 2009 Q3 法說會逐字稿

Good afternoon, and welcome ladies and gentlemen to the Cytokinetics third quarter 2009 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 up the call for questions-and-answers after the presentation.

I will now turn the call over to Sharon Barbari, Cytokinetic's Executive Vice President of Finance and CFO. Please go ahead.

Good afternoon, and thank you for joining the Cytokinetic senior management team on this conference call to discuss our third quarter 2009 results. Also present during this call are Robert Blum, our President and Chief Executive Officer; and Dr. Andrew Wolff, Senior Vice President of Clinical Research of 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 advancement of our development pipeline focused on the biology of muscle contractility. And Andy will provide highlights and details on the progress of the Company's clinical development program. I'll then provide some brief comments with respect to our financials and our investment capital allocations in research and development. Robert will then conclude the call with additional comments regarding our recent activities and summarize our current progress in the context of our remaining projected Company milestones for 2009. We'll 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 the purposes of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Our actual results may differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to materially differ 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 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 Web site. These forward-looking statements speak only as of today. You should not rely on them as representing our views in the future. We undertake no obligation to update these statements after this call.

I'll now turn the call over to Robert.

Thank you, Sharon. The third quarter was, indeed, a very busy and productive one for Cytokinetics coming on the heels of Amgen's exercise of its option, relating to omecamtiv mecarbil. We have been especially busy closing out and transitioning certainly activities related to this, our most advanced clinical stage program. Moreover, we have been working together with Amgen in planning for our upcoming development activities. Andy will provide an update on our collaborative activities in a moment. Against this backdrop of advancing our cardiac muscle contractility program, we felt it was then appropriate to begin to share with the investment community more details concerning the depth of Cytokinetics development pipeline beyond omecamtiv mecarbil.

In September, at our first research and development day, Cytokinetics was able to lift the veil to, so to speak, on the Company's breadth of research and development portfolio focused to the biology of muscle function. I was pleased to have alongside me at that event members of our executive team, who together highlighted the technical synergies, capital efficiencies, and overall productivity and promise associated with our novel drug discovery and development activities. At that time, we reviewed non-clinical and clinical results and progress across our three muscle biology programs focused on cardiac, skeletal, and smooth muscle. We were also joined by clinical key opinion leaders who offered their own perspectives relating to these programs, and in particular highlighted the unmet needs that still persist and the potential indications we are targeting, which may be addressed by our programs. I believe there was a great deal of enthusiasm in the room for the future of our programs, and we were pleased to host this event and share results achieved to date.

We have received positive feedback from those who participated in the event, as well as those who listened in the replay, indicating that the presentation set a helpful context for our future business plans as well. We were pleased to share these additional details, as they may point to other vectors for parallel value-generating events as we continue to build out our Company with an eye toward sustainable investments in a pipeline of novel mechanism compounds directed toward modulating muscle function. In particular, our principle objectives for the R&D day pivoted around disclosing more recent progress achieved with our skeletal sarcomere activator program and our drug candidate CK-2017357, or CK-357, which is currently in Phase I studies, and moving nicely toward Phase II trials, anticipated to be initiated in 2010. I will summarize some of the key take aways related to our progress in this area and prospects for the program later in the call.

I would now like to turn the call over to Andy to elaborate on specific development stage progress achieved in the last quarter in our respective drug development programs.

Thank you, Robert. During the quarter, at the annual meeting of the European Society of Cardiology, or ESC, and the 2009 Heart Failure Society of America, or HSSA annual meeting, Cytokinetics presented final data from the Phase IIa trial omecamtiv mecarbil and stable heart failure patients. The authors concluded that patients with reduced stroke volumes -- that is, less than 50 millimeters at baseline -- had generally greater pharmacodynamic responses to omecamtiv mecarbil than those patients with greater volumes of stroke at baseline, demonstrating robust pharmacodynamic activity in this more severely effected sub-population of patients from the study. Statistically significant increases in systolic ejection time, and in stroke volume, cardiac output, fractional shortening, and ejection fraction (all measures of cardiac function), occurred across the patient population in a concentration-dependent manner. In addition, the data demonstrated statistically significant correlations between increasing plasma concentrations of omecamtiv mecarbil and decreases in left ventricular end-systolic volume, left ventricular end-diastolic volume and heart rate.

In addition, during the quarter, and also at the ESC and SHFFA annual meetings, Cytokinetics presented final data from the Phase IIa clinical trial of omecamtiv mecarbil in patients with ischemic cardiomyopathy and angina. The authors concluded that in heart failure patients with ischemic cardiomyopathy and angina who theoretically could be most vulnerable to the possible deleterious consequences of systolic ejection time prolongation, treatment with omecamtiv mecarbil, at plasma concentrations previously demonstrated in other Phase IIa trials to increase cardiac function, did not adversely affect a broad range of safety assessments in the setting of exercise. Cytokinetics and Amgen have agreed on next steps for the further development of omecamtiv mecarbil. The companies are planning a clinical trial designed to further assess the pharmacokinetics of both modified and immediate release oral formulations of omecamtiv mecarbil and patients with stable heart failure using active pharmaceutical ingredient and drug product manufactured by Amgen. In addition, the companies are planning to conduct another pharmacokinetic trial to evaluate omecamtiv mecarbil in patients with renal dysfunction, along with additional preclinincal activities.

Cytokinetic Amgen anticipate the initiation of the Phase IIb clinical trial program to occur in 2011, but the companies are discussing how the time line could be accelerated into 2010. With our increased focus toward creating a clinical development pipeline that builds on our expertise in the biology of muscle contractility, we continue to advance fast skeletal muscle troponin activator, CK-357, in the first time in humans, sending a single dose, placebo-controled, double-blind Phase I clinical trial designed to assess its safety, tolerability, and pharmacokinetic profile and to determine its maximum tolerable dose in plasma concentration in healthy male volunteers. In the third quarter, the continued dose escalation in this trial and readied for the initiation of a multidose pharmacokinetic trial. Although the trial is still ongoing and thus remains blinded, to date no adverse events have been observed in participants to indicate that an intolerable dose has been administered. Consequently, the maximum tolerated dose has not yet been determined. However, doses that produced CK-357 blood levels associated with increased skeletal muscle function in pre-clinical models have now been tolerated by the healthy volunteers in this study. This is a two-part study we expect to initiate before the end of the year, the second part or part B of the ongoing trial, which is designed to assess the pharmacodynamic effects of CK-357 in healthy volunteers.

With that update on our clinical development programs for the third quarter, I'll turn the call back over to Sharon.

Thank you, Andy. As our press release contains detailed financial results for the third quarter and nine months ended September 30th, 2009, let me refer you to that public statement. But also provide you with a little more detail on the capital allocation of our research and development or R&D spending. Our third quarter 2009 R&D expenditures totaled $9.9 million. From a program perspective for the third quarter, approximately 18% of our R&D expenses were attributable to our cardiac muscle contractility development and research activities, 50% to our skeletal muscle contractility research and development activities, 8% to our [mitotic kinesis inhibitor] development research activities, and 20% to our other research and non-clinical development activities, which include our smooth muscle contractility program.

For the nine months ended September 30th, 2009, our R&D expenditures totaled $30 million. From a program perspective for the third quarter, approximately 30% of our R&D expenses were attributable to our cardiac muscle contractility development and research activities, 35% to our skeletal muscle contractility research and development activities, 11% to our mitotic kinesis inhibitor development and research activities, and 21% to our other research and non-clinical development activities, which include our smooth muscle contractility program. As of September 30th, 2009, cash, cash equivalents and investments, excluding restricted cash in the put option on our option rate securities, totaled $119.2 million.

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

Thank you, Sharon. As Andy and Sharon have outlined for you both here today and at the R&D day in September, Cytokinetics is highly focused toward our programs in muscle contractility. I would like to provide some additional commentary starting with our cardiac muscle contractility program.

Strategically, while Amgen has assumed the future cost associated with the development of omecamtiv mecarbil, we remain actively engaged in collaboratively designing and operationalizing this program. Together with Amgen we are interested in further assessing the pharmacokinetics from the two oral formulations from which we will select one for advancement into Phase IIb. Understanding the factors that may contribute to variability in the pharmacokinetics and diverse heart failure patients, will enable us to ensure we are better prepared for the start of Phase IIb. We recognize this will have an effect to the start of Phase IIb but also appreciate the importance of characterizing dosing and formulation ahead of advancing to that next level. We will have more to say about the expected timing of phase IIB once we have clarity on those plans with Amgen.

Moving next to our skeletal muscle contractility program, we are planning to move CK-357 forward in Phase II in 2010. We are interested in fully exploring the pharmacology of this novel mechanism's approach to increasing muscle force and power in populations who are suffering from muscle weakness, fatigue, and impairment. We are busily preparing for an additional multidose Phase I safety and pharmacokinetics trial anticipated to be conducted in the current quarter, as well as Phase IIa studies that we expect to be initiated and read out in 2010. One possible indication that we may choose to investigate is amyotrophic lateral sclerosis, otherwise known as ALS or Lou Gehrig's disease. In addition, we are considering the study of CK-357 in conditions of muscle impairment associated with claudication, or as is observed in immobilized patients. We are also considering the feasibility of assessing the effects of CK-357 in frail or aged patients. As such, our strategy involves the execution of several small and quickly executed evidence of effect or EOE studies that would be in diseased or compromised patients. These studies would be expected to provide us key information before conducting larger clinical trials.

Our goal is to initiate and report data from EOE studies in 2010. At the same time, as we are preparing for these clinical studies, we are engaging potential partners in discussions relating to alternative structures for collaboration that may afford the possibility of parallel development of CK-357 and related compounds across an array of possible indications. This could provide Cytokinetics flexibility and participation in the joint clinical development of CK-357 for certain indications through proof of concept trials, and even possibly to commercialization. We believe this approach my offer the most effective and expeditious development path for this novel mechanism drug candidate, while also offering opportunities to increase shareholder value. We believe that in light of these business objectives, Cytokinetics may now be better positioned to progress on a more balanced and risk-managed vector across all of our novel R&D programs.

As we continue to build our Company on the biology of muscle function, I would like to share with you our key milestones for our skeletal and smooth muscle programs for the remainder of 2009. In December, we are scheduled to present non-clinical data from CK-357 at the Society on Cachexia and Wasting Disorders' 5th Annual Cachexia Conference in Barcelona. In this quarter, we anticipate initiating the second portion of our two-part Phase I study of CK-357 designed to assess the safety, pharmacokinetics and pharmacodynamic effects of the drug candidate in healthy volunteers. In this quarter, we anticipate initiating a Phase I multidose study of CK-357 in healthy volunteers. In November, we are scheduled to present non-clinical data from our smooth muscle myosin inhibitor at the 2009 scientific sessions of the American Heart Association meeting in Orlando. In 2009, we plan to continue to progress our smooth muscle myosin inhibitors in non-clinical development activities. In September we are scheduled to present data from the Phase I portion of the Phase I/II clinical trial evaluating SB-743921, or SB-921, in patients with Hodgkin or non-Hodgkin lymphoma at the Annual Meeting of the American Society of Hematology in New Orleans. In November, GSK is scheduled to present pharmacogenomic and drug combination data evaluating GSK-295, our [SENPE inhibitor] with a MEK inhibitor in preclinical models at the AACR-NCI-EORTC Conference in Boston.

As we began this call, I would also like to say now in closing, that I am pleased that during this most recent quarter, we at Cytokinetics had an opportunity to publicly present how we are leveraging our knowledge and expertise in muscle contractility towards our goal of building a more durable bioceutical company. The take away messages from our recent R&D day reflect that we believe our research engine is indeed robust and right-sized for our current plans going forward. Moreover, the novel compounds that have arisen from our novel research and are now progressing in development are strategically aimed at diseases of high unmet medical need and population and market sizes that are intended to balance our abilities to prosecute programs ourselves as well as in collaboration with world-class partners. We have harnessed what we have learned in development of omecamtiv mecarbil with the goal of executing efficient and comprehensive development paths for our muscle contractility platform. Lastly, we remain committed to evolving the science and business with a persistent eye toward increasing shareholder value. We appreciate your support, look forward to providing additional updates, and hope you share our excitement in these recent developments.

That concludes the formal portion of our call today, and I'd now like to open the call up to questions. Operator, if you will?

(Operator Instructions). Your first question comes from the line of Mark Monane with Needham & Company.

Hi, Mark.

Hi. Thank you. Good afternoon, and thanks for reviewing current events. Thinking about going forward, we're intrigued by the Phase IIb program that Amgen is going to put forward. Do we know a little bit more about the intravenous portion as well as IIb and how it might fit in, and then what two-way studies need to be done in order to prepare for the IId.

I'm going to turn this over to Andy, but as we have already mentioned, the focus of the additional PK work to be done speaks specifically to an interest in characterizing the pharmacokinetics and variables that may contribute to varying pharmacokinetics and clearance with the oral formulations. We don't have specific intention right now to advance the intravenous form of the compound independent of the oral forms as we've discussed in the past. Andy, I don't know if you want to elaborate anything further on that.

I would say it's clear the intention of both companies to develop the IV in concert with the oral, as Robert just said, neither standing alone. However, in our more recent discussions, it may be that there might not be a focus on the IV in Phase IIb, but it will come back into the equation in Phase III part of the program.

And for the Phase IIa studies, do you feel you have a dose with the current formulation, or will it be an opportunity to go over a number of different formulations and a number of different doses?

I'm -- we have a formulation that will be adequate for Phase IIb, and I think it's just a matter of looking at new material that Amgen has now manufactured and doing some confirmatory work.

And after the IIb, we assume that there would be a IId program and we would look forward to probably a very large Phase III program with the oral product as a lead candidate there.

We are currently viewing the oral and the IV. So at that point, you then will see patients being treated directly with the oral and the others going on the IV and then to the oral.

Mark, the last several months together with Amgen has not really pointed so much to new ways of thinking about Phase IIb or Phase III, frankly, but rather what might be required to best position us to do the best Phase IIb clinical trials program, and that's where we are specifically as we think into 2010 looking at additional PK work.

Got it. And with the research and development day in September, I was -- I would like -- if you would spend a moment talking about prioritization of programs. We noticed that the skeletal activator program is targeting relatively rare or well defined conditions. I'm not going to say niche. I'm going to say focused conditions, which may be suitable for Cytokinetics to do on its own versus the smooth muscle inhibitor program, which is looking at possibly very broad indication, which look like they're done by a partner. Is that a fair assessment going forward?

Partly yes, partly no. If you look at how we're spending capital, you see that we are significantly spending more in the areas relating to skeletal muscle than smooth muscle. Both skeletal muscle and smooth muscle have opportunities that you could argue are attractive to a Company with more limited resources as well as offer up opportunities that may be better suited for large national pharmacompanies to be our collaborator; but given where we are in terms of wanting to manage our burn more prudently as well as advance our skeletal program more aggressively than we are currently investing in our smooth program, I think the next near-term value drivers relate more to the skeletal program than the smooth program.

Fair enough. I'll step back into the queue. Thanks for the added information.

Thank you, Mark.

Your next question comes from the line of Michael Aberman with Credit Suisse.

Hey, Michael.

Hey, guys. In terms of the idea that the Phase IIb is going to start in 2011, should we anticipate early 2011, based on your comments, that you could accelerate in 2010?

I think it's pretty mature to even conclude that until we see the data as it's going to come from these Phase IIa, these additional PK studies. I think it's unclear how many different dosing cohorts we might ultimately have to do and what variables may contribute to the final interpretation of the data as it reads to Phase IIb. I don't want to say yet -- and frankly, with Amgen we haven't determined that.

And have you done renal suggestion tests already? Is there some suggestion -- Can you remind us about the renal excretion?

There was very little renal excretion in preclinical studies. We have not done renally impaired patients yet. That's something that both companies have an interest in having done prior to the entry into Phase IIb, because as we have discussed in the past, we would imagine this mechanism to be especially beneficial for patients who is have the cardio renal syndrome where, because their forward cardiac out put is so poor, any attempt to try to [direse] relieve their pulmonary congestion winds up ]underperfusing] their kidneys, and you see worsening renal dysfunction even as their pulmonary congestion improves. We would imagine that 452 would be very good for reversing that situation. So consequently it's in our interest to be able to enroll in Phase IIb studies patients with the most significant renal dysfunction that we think we can safely enroll.

You may recall, as we gave some guidance prior to knowing if Amgen was going to exercise its option, we had then an interest in initiate Phase IIb, and possibly as we may be able to afford it, do an additional renal study in parallel. Now, with Amgen together as our partner on this program, we're in a position where that can be done ahead of the Phase IIb study, thereby allowing the possibility that we can enroll more patients in Phase IIb.

And in terms of the PK, will you have clinical end points and cardiac end points? Why should it take a year? If you're doing -- what duration of trials and whatnot? Is this going to be a repeat of what you've already done with their material in terms of taking cardiac measurements to judge -- I mean, are these pharmacodynamic measures you want to do? Or is it pure pharmacokinetics?

It's really purely pharmacokinetics as things are envisioned now, but it's a desire to ensure that we understand not just the effects on the average heart failure patient, but not going into larger studies and thicker populations, we have characterized the outlyers as well as we can.

So you may recall we had already initiate a PK study comparing these formulation in heart failure patients. This affords us an opportunity to enroll more patients in regulatory jurisdictions, more -- different centers and different locales that we had been doing previously ourselves.

Okay. And moving to 357 for a second, could you clarify for us timing, and when we might see -- are we going to see muscle data from these Phase I in normal volunteers, and when might we see you start potential trials in patients with abnormal muscle function?

So as we mentioned on the call, part B of the ongoing first-time human studies is designed to look at the effect of the compound in healthy volunteers, so while I anticipate that we will see evidence of a pharmacodynamic effect, and you will see a measurable and significant increase in skeletal muscle performance, it will be normal muscle, and while that's good that's not all the way there. Beginning in the early part of 2010, we will be doing what we have come to call these evidence of effects studies, where we're looking at patients whose diseases include some level of skeletal muscle wasting or dysfunction, and we have -- we want to have those data available in 2010.

Last question before I hop off, is, I really couldn't follow what you were saying about the potential structuring and partnering of CK-357. Can you clarify your intention here? Is this something that is going to be a novel structure, or are we looking for a straight partnership by indication?

It would be our goal to strike a deal that affords us the opportunity. We have not only this compound, CK-357, but also a backup compound. You can imagine a scenario by which there are certain indications that we can go forward with independent of our partner and others where our partner may take those indications, and we share in the development and commercialization. What I'm pointing to is our interest to have more responsibility for the downstream development activities. Given the breadth of indications that are possible here.

Okay. I appreciate it. Thanks.

Thanks, Michael.

Your next question comes from the line of Charles Duncan with JMP Securities.

Hi, Charles.

Hi, guys. Thanks again for taking the question, and congratulations, and it's nice progress recently.

Thank you.

Many of my questions have been answered, but I did have a question related to your statements on the alternative structures that you're looking at. Are you primarily talking with pharmaceutical or biotech companies or, say, patient advocacy type organizations, or are you talking with financial partners?

I didn't mean to imply the latter. We are in conversations with biopharma and pharma companies, but in as much as this program offers a breadth of potential, and we have multiple compounds here, one can imagine going in parallel with a partner, but in a more broadly defined program. Not to say we aren't interested in working with the advocacy groups as you mentioned, but I didn't mean to imply that we're going to strike a particularly unusual structure that way. We want to make sure that our partners are best positioned to address what could be the multiple opportunities here, and in that way, I still am hopeful that we will have a collaboration with one of those types of companies.

Okay. That makes sense. Thank you for that, Robert. Perhaps a question for Andy. On 357, I'm intrigued with some of the parallels with the work that you did in the congested heart failure program early on. You mentioned that you are pursuing (inaudible) and that in animal studies, you've gotten to these doses and safely been able to change muscle performance. Could you perhaps elaborate on that? And in addition, what types of -- I'll call it dose limiting effects could you see with 357?

So we are beyond concentrate -- the plasma concentrations that we have produced in the healthy volunteers and the ongoing studies are now beyond those at which we began to see increases in skeletal muscle function in various models of skeletal muscle function. It doesn't mean therefore, that those concentrations will be associated with skeletal muscle function in humans, but it's encouraging to be sure. So as we go forward into part B, we will be using doses that we've already demonstrated to be well tolerated in part A of this study, and that are associated with concentrations which have produced increases in skeletal muscle performance in a variety of different animal species and models. In terms of what we see as excessive doses in the preclinical studies -- and I'll remind you as we discussed on the call, we have not gotten there yet in a clinical study. We have not administered a dose of this drug that has yet to be poorly tolerated, but animals basically sort of stiffen up. They don't move so much and so quickly.

And, Andy, how is 357? What is the primary mode of excretion for 357, and is the backup different or the same?

We are not in a position to comment in detail on that just yet.

And then perhaps one question regarding the smooth muscle programs. Could you help us understand perhaps the basis of selectivity that you're kind of targeting with those programs?

I can start with that. At the bio chemical level, an opportunity here as we have developed our screening paradigm and our optimization program to ensure selectivity by a target, by molecular target as well as by tissue type. In addition, by use of various formulations, we are in a position to ensure the drug is delivered to have maximal effect at a particular tissue type of interest. So I think it's through a combination of the bio chemistry, but also the formulation sciences that we're achieving selectivity that way.

To amplify on what Robert just said, there is muscle activity which we ensure invitro early on, that we are hitting the smooth muscle myosin, and then there's tissue bed selectivity, where we are going after maybe pulmonary smooth muscle, or a vascular or a bronchial smooth muscle than any place other than that done better via delivery.

And then some of the different types of formulation, things you're looking at might include inhalation or localized injection?

Right now with the compound, we have in non-clinical development and related compounds, we are primarily focused to what can best deliver, knowing that we have a faster-acting, shorter-acting compound we're looking at inhaled and intravenous routes of administration.

And then, Robert, you mentioned 921 data at ash. I believe that abstracts have been accepted, so can you give us a sense of not what the data are, but what the data would tell you or what you would look for in that data to decide whether or not to continue to pursue that?

Yes. In particular, you may recall that with this compound 921, we're looking at lymphoma patients in a dose escalating Phase I study or an acute 14-day treatment schedule, and here in particular, these data will point to where we are relative to MTD and what we have seen relative to objective response data in those patient populations.

Okay. Thanks for the added color.

Thank you, Charles.

Your next question comes from the line of Joel Sendek with Lazard Capital Markets.

Hi, Joel.

Hi. Thanks. Just a short question. I'm wondering if you're eligible for any milestone payments from Amgen from on the basis of what you expect to do in 2010?

It's a very good question. Unfortunately the answer would be violating terms of our confidentiality with Amgen. I cannot say.

Okay. Fair enough. And then you said, in the past, that, one of the benefits of having them do further tests prior to the start of Phase IIb would be the potential of accelerated pathway of that trial. Can you give us a sense of how long it might take to finish once you might start it?

The Phase IIb study? I think it's going to be of a magnitude that it's going to be not something that will complete inside of a year.

Okay. So one year or more, from start to finish? .

Yes. We're talking about a study that obviously would enroll, as we have already previously given guidance, hundreds of patients, if not more, as well as we have expectation that we may take more than one dosing group in. So I think you can do the math given those parameters.

Okay. Great. Thank you very much.

Thank you, Joel.

Your next question comes from the line of George Zavoico with [West Coast Capital].

Hi, George.

Hello.

Hello.

Another great quarter. Thank you for all the information. Just a couple of quick questions, because you've covered things pretty well already. The Amgen manufacturing switchover. How -- was that pretty efficient, pretty quick, and do you have any leftover stock piles of 457 that need to be used, or are you switching over completely to the Amgen drug?

So we are in the process still of transitioning some of that, and with that material will be made available to Amgen for use in clinical trials in 2010 together with a drug product that will be manufactured by Amgen. So our role here has been that those methods and processes and inventory have been provided to Amgen enabling them to be in the best position to oversee those activities going forward.

Sot it's no change in manufacturing processes or procedures or anything like that?

Not per se. I mean, Amgen and Cytokinetics together in 2010 are expected to continue to work towards what may be improving manufacturing methods and formulation sciences. There's an ongoing optimization of those types of activities at this stage of the program. So we'll do that together with them.

Great. Nice to have someone like Amgen to do that with you, I suppose, with all their expertise.

That's true.

A question about the skeletal muscle program. Can you say how many dose levels you've already gone up in the Phase I trial?

We haven't disclosed that yet. I don't think we probably should quite yet now, but we will be doing that reasonably soon when we're in a position to comment on the data in more full detail.

I mean, I would just suggest that to say the number of dose levels that we study doesn't really tell you anything any way, because we might have been tweaking them up by 10% at a time or tripling them. I think what's relevant is that we have exceeded, by some amount, the concentrations that were necessary to achieve clear evidence of increase in skeletal muscle performance with the doses we've administered, and they've been well tolerated.

Yes, that's a really nice out come. And finally on 357, I know during your conversation, it was nice to hear how you're sort of doing the design of the program in parallel. I was looking at the investor day program, and you had some rat treadmill exercises, but those, I presume were healthy rats. The cardiac muscle, the 452, you have the heart failure dog model. Are that any animal models of skeletal muscle that you can use similarly that you used the dog model to show that you're getting better enhanced performance with abnormal muscle rather than normal muscle?

There are models that are available and that we have used. I don't think we have discussed them publicly, but I can answer your question to say, yes, there are such models, and yes, we have studies of compounds in them.

I think it's reasonable to assume, George, that as we go forward with this program, more of that preclinical data will be shared at the appropriate scientific and medical Congresses where we want to set the stage, so to speak for the work we're going to be doing in these EOE studies. But rather than have presented those at the R&D day it's best to present those at the right scientific forum.

Sure. That makes great sense. I can't wait to see the data when it is presented.

Thank you.

Your next question comes from the line of [Retu Boral] with [Canaccord].

Good afternoon, Retu.

Hi. Thanks for taking my question. On 357, would you guys -- the trials for the different indications pretty much simultaneously or maybe in a staggered fashion in order to accumulate even more data as you go along; and then just following up on that, do you think the evidence in those trials would be designed to yield interim data, and do you think that by the end, you have data sufficient to start partnership or strike partner for certain indications?

All good questions. Let me just say that we're in the process of putting finishing touches on our budget for 2010 to be discussed with our board and as such we are looking forward to the possibility of conducting some of these EOE studies in parallel so we will be generating data in a some rapid-fire format. The goal there to be to have an assessment of functional status improvements in multiple settings in 2010 and not have this conducted in a serial way. That would allow us to further the partnering conversations are already underway. Instead we're not waiting for that data to really get serious and dial up those activities. That's something that's already in process.

Great. Thanks. Looking forward to 2010.

Thank you so much.

There are no further questions at this time.

Thank you, operator, and thank you to all of the participants today for your continued interest in Cytokinetics. We look forward to updating you more in 2010, and, Operator, with that, we conclude the call. Have a good day.

Thank you. This does conclude today's conference call. You may now disconnect.