Oct 30, 2013
Executives
Sharon Barbari – EVP, Finance and CFO Robert Blum – President and CEO Fady Malik – SVP, Research and Early Development Andrew Wolff – SVP, Clinical Research and Development, and Chief Medical Officer
Analysts
Simos Simeonidis – Cowen and Company Charles Duncan – Piper Jaffray Paul Matteis – Leerink Swann, LLC Chad Messer – Needham & Company Jason Butler – JMP Securities
Operator
Good afternoon and welcome ladies and gentlemen to Cytokinetics third quarter 2013 conference call. At this time I would like to inform you that this call is being recorded and that all participants are in a listen-only mode.
At the company’s request we will open the call for questions-and-answers after the presentation. I will now turn the call over to Sharon Barbari, Cytokinetics’ Executive Vice President of Finance and CFO.
Please go ahead.
Sharon Barbari
Good afternoon and thank you for joining us on this conference call today. Leading today’s call is Robert Blum, our President and Chief Executive Officer.
After Roberts opening comments Dr. Fady Malik, our Senior Vice President of Research and Early Development will update you regarding recent progress in the clinical development of omecamtiv mecarbil for the potential treatment of heart failure.
Next Dr. Andrew Wolff, our Senior Vice President of Clinical Research and Development and Chief Medical Officer will provide an update on the clinical development of tirasemtiv in patients with atrophic lateral sclerosis or ALS and also will provide an update on the Phase I clinical trial for CK-2127107 or CK-107 in healthy volunteers.
I’ll then provide a financial overview for the quarter. Robert will then conclude the call with additional comments regarding how these recent activities come together to align with our corporate strategy and projected milestones for the remainder of 2013.
We will then open the call for questions. Please note that the following discussion, including our responses to questions, contain statements that constitute forward-looking statements for purposes of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to statements relating to our financial guidance, and collaborations with Amgen and Astellas, to the initiation, enrolment, design, conduct, and results of clinical trials, and to other research and development activities.
Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our most recent annual report on Form 10-K, our quarterly reports on Form 10-Q and our current report on Form 8-K.
Copies of these documents may be obtained from the SEC or by visiting the Investor Relations section of our website. These forward-looking statements speak only as of today.
You should not rely on them as representing our views in the future. We undertake no obligation to update these statements after this call.
Now I’ll turn the call over to Robert.
Robert Blum
Thank you, Sharon. And thank you to everyone on the line for joining us for this call today.
We had a productive quarter and made important progress. I’ll start by giving a brief overview of the third quarter developments before than asking each of Fady and Andy to elaborate on the specifics of clinical development progress for each of our programs and then asking Sharon to put this all into the context of a financial overview.
Our focus continues to be on advancing our development stage drug candidates that have arisen from each of our cardiac and skeletal muscle programs, to complete comprehensive Phase II development programs before then potentially proceeding in later stage clinical development. Consistent with our stated plans we continue to execute on those major priorities and we had another very positive quarter.
In 2014 we expect to have the key data that will materially inform our plans. Starting with our cardiac muscle contractility program with presentations of results from ATOMIC-AHF at the ESC conference and additional analyses from this clinical trial presented a few weeks later at this HSFA conference we were pleased with the encouraging feedback we received from a wide cross section of the cardiology community who expressed enthusiasm for omecamtiv mecarbil in this Phase II B clinical trial.
In particular expert clinicians who reviewed the results support the continued development of omecamtiv mecarbil for the treatment of heart failure. Fady will provide commentary regarding conclusions from ATOMIC-AHF and he will also provide an update on COSMIC-HF in patients with chronic heart failure.
We anticipate that the outcome of the COSMIC-HF trial along with the data from ATOMIC-AHF will inform final decisions regarding the progression of omecamtiv mecarbil into Phase III development for the potential treatment of heart failure. In the mean time we continue to prepare for that possibility and to dial up our activities in expectations of those decisions.
Moving towards skeletal muscle contractility program and in particular our activities in support of tirasemtiv with focus to the BENEFIT ALS trial we are now nearing in completion of enrollment in that trial. I am pleased to report that over 600 have been enrolled in BENEFIT-ALS and over 300 patients have completed 12 weeks of treatment.
This large international Phase IIb trial is designed to inform our global registration plans and we are now preparing for multiple scenarios that we see as real possibilities for 2014 in order to capitalize on potential positive clinical results. In addition we believe we are off to a great start in our collaboration with the Astellas in the development of CK-107 and in the conduct of joint research.
During the last quarter we completed our first time in humans Phase I clinical trial CY-5011 and more recently we have initiated another Phase I trial CY-5014. Both of these trial are intended to assess the safety, tolerability and pharmacokinetics of CK-107 in healthy volunteers prior to our possibly assessing its potential for the treatment of non-neuromuscular diseases in Phase II trials.
Andy will elaborate on both these programs following Fady’s update. With that introduction I will turn the call over to Fady for an update on the progress of our cardiac contractility program.
Fady Malik
Thank you, Robert. As Robert mentioned we reported the results from ATOMIC-AHF for the first time at the ESC Congress in Amsterdam.
Additional analyses of the data from this trial at HFSA Annual Scientific Meeting at Orlando, Florida. To remind you ATOMIC-AHF was designed as a dose finding study to investigate pharmacokinetic, pharmacodynamic and heat safety parameters in this high risk and symptomatic heart failure population.
The trial was international, randomized, double-blind placebo-controlled Phase II clinical trial that enrolled 613 patients, hospitalized with acute heart failure and three sequential ascending dose cohorts. Each cohort of approximately 200 patients was randomized one-to-one omecamtiv mecarbil or placebo.
The primary objective of this trial was to evaluate the effect of 48-hours of intravenous omecamtiv mecarbil compared to placebo on dyspnea in patients with left ventricular systolic dysfunction that were hospitalized for heart failure. The secondary objectives was to assess the safety and tolerability of these three dose levels of omecamtiv mecarbil compared with placebo and to evaluate the effects of 48-hours of treatment with the intravenous omecamtiv mecarbil on additional clinical and pharmacodynamic measures.
One needs to examine the totality of the data to fully appreciate the performance of omecamtiv mecarbil in this clinical trial. Although the primary endpoint of dyspnea symptom response is not met they were favorable and statistically significant relationships between the dose and plasma concentration of omecamtiv mecarbil into this new response.
The incidents of worsening heat failure within seven days of initiating treatment was lower in each of the cohorts on omecamtiv mecarbil compared to the pooled placebo group patients and the rates of adverse events or AEs, serious AEs, adjudicated death and hospitalizations were similar between omecamtiv mecarbil and placebo groups. Accordingly the data obtained in the sick heart failure population continued to support the initial therapeutic hypothesis for this program.
Omecamtiv mecarbil was not associated with an increased incident of tachyarrhythmias nor were heart rate or blood pressure adversely affected. In fact heart rate decreased to a greater extent on omecamtiv mecarbil than placebo.
Systolic ejection time, the echocardiographic signature of omecamtiv mecarbil increased in a concentration-dependent manner similar to that previously reported in healthy volunteers and in stable heart failure patients. So with pharmacokinetic data from over 300 patients and estimates of the placebo response rate in the symptomatic acute heart failure population we now have a unique and a valuable dataset to informed dose selection and design for potential Phase III trials of omecamtiv mecarbil.
ATOMIC-AHF is one of the two final Phase II studies meant to inform the potential progression of the program into Phase III, COSMIC-HF is the other. The primary clinical development objectives of COSMIC-HF are to select an oral modified-release formulation of omecamtiv mecarbil and to characterize its pharmacokinetics in patients with heart failure and left ventricular systolic dysfunction.
Secondary objectives are to assess safety, tolerability, changes from base line and cardiac function and dimension as measured by cardiography heart rate and end terminal pro-brain natriuretic peptide which is a biomarker associated with the severity of heart failure. The trial’s a double-blind randomized placebo controlled multicenter trial with a dose escalation phase followed by an expansion phase.
During the escalation phase over 40 patients were randomized one-to-one-to-one-to-one to placebo or one of three different oral formulations of omecamtiv mecarbil in each of the two ascending dose cohorts. Omecamtiv mecarbil was dosed at 25 milligrams twice daily for 1 week in the first cohort and 50 mgs twice daily for one week in the second cohort.
I am pleased to report that these two cohorts are now complete and oral formulation of omecamtiv mecarbil has been selected for evaluation in the planned expansion Phase of the trial. Cytokinetics’ management are discussing the amendment of the protocol of COSMIC-HF prior to initiating enrollment in the planned expansion phase.
This is an important step forward for omecamtiv mecarbil and this program and I am pleased to share this news relating to COSMIC-HF. I am also happy to report that recently Cytokinetics and Amgen agreed on the protocol and budget for a planned Phase I pharmacokinetic study of omecamtiv mecarbil in healthy volunteers of both Japanese and non-Japanese ethnicity.
The trial, CY 1211 will be conducted by Cytokinetics in collaboration with Amgen. The costs of the trial will be reimbursed by Amgen.
Following the expansion of our collaboration with Amgen to include Japan, that we announced in June we will now move plans forward so that this next study can inform the potential inclusion of Japan in the global registration program in Phase III. So with that update on clinical development activities for omecamtiv mecarbil I will turn the call over to Andy for an update on the skeletal Muscle Contractility program.
Andrew Wolff
Thank you, Fady. I am pleased to provide an update on recent development in our skeletal muscle program, especially because we can announce that we are nearing completion of enrollment in BENEFIT-ALS.
This Phase 2b trial is a multinational double-blind randomized placebo-controlled clinical trial designed to evaluate the safety, tolerability and potential efficacy of tirasemtiv in patients with ALS. During our last earnings call on July 31, I announced that over 500 patients had been enrolled in BENEFIT-ALS.
Today I am pleased to report that over 600 patients have been enrolled and over 300 patients have completed 12-weeks of treatment all of which illustrate the dedication of ALS patients, their caregivers and BENEFIT-ALS clinical site personnel and investigators to research for potential treatments for this grievous disease. We continue to be grateful for their commitment to this trial.
We at Cytokinetics and our colleagues in eight countries are working to ensure that BENEFIT-ALS progresses as efficiently as possible. To that end I am also pleased to report that the Data Safety Monitoring Board recently completed another scheduled meeting to review data from BENEFIT-ALS and recommended that we continue the trial without making any changes to the protocol or to the conduct of the study.
We still expect to complete enrolling in BENEFIT-ALS during the fourth quarter of 2013 and we’ll announce when enrollment has completed. Turning now to the development of CK-107, in the last quarter we completed enrollment of CY-5011, a Phase I first-time-in-humans clinical trial of CK-107 in healthy male volunteers conducted by Cytokinetics under our collaboration with Astellas.
CY5011 is a double-blind randomized placebo controlled study designed to assess the safety, tolerability and pharmacokinetics of single ascending oral doses of CK-107 administrated to healthy adult males in a three period dose escalating crossover design. We are compiling the data and look forward to presenting results at an appropriate medical conference in the near future.
Also recently, we initiated CY5014, a Phase I clinical trial of CK-107 in healthy male volunteers. This trial is a randomized open-label, two period crossover study to assess the relative oral bioavailability, pharmacokinetics, safety and tolerability of two oral forms of CK-107.
We expect that these two Phase I studies of CK-107 alongside others planned for 2014 will inform decisions regarding potential progress into Phase II. Our recently announced collaboration with Astellas has already enabled Cytokinetics to increase our commitment to the investigation of CK-107 in non-neuromuscular conditions associated with muscle fatigue and weakness.
We look forward to providing further updates regarding CK-107 when appropriate. With that update on our clinical development activities I will turn the call over to Sharon.
Sharon Barbari
Thank you, Andy. As our press release contains detailed financial results for the third quarter 2013 I will refer you to that public statement for the details of our P&L and balance sheet.
In the past quarter we were focused on the enrollment of BENEFIT-ALS and executing on the development and research plans associated with the Astellas collaboration that we signed at the end of June. We ended the third quarter with approximately $85.4 million in cash, cash equivalents and investments, which represents approximately 20 months of going forward net cash burn based on our 2013 financial guidance.
Revenues for the third quarter 2013 was $4.5 million. This revenue included the recognition of $1.4 million of the $16 million Astellas license fee and $2.3 million in program expense reimbursement and other revenues related to that agreement.
Revenues for the third quarter also included revenues from our collaboration with Amgen of $0.6 million and $0.2 million from our collaboration with MyoKardia. Revenues for the nine months ended September 30 were $6.3 million.
This revenue included the recognition of $1.4 million of the $16 million Astellas license fee and $2.3 million in program expense and other revenues associated with that agreement as well as $1.5 million in revenue from our Amgen collaboration and $1 million in revenue from our MyoKardia collaboration. The company will recognize the Amgen license fee of $15 million associated with that collaboration in the fourth quarter of 2013.
Our third quarter 2013 R&D expenditures totaled $13.4 million. From a program perspective for the third quarter approximately 86% of our R&D expenses were attributable to our skeletal muscle contractility research and development activities which include both the development of tirasemtiv and the research and development of CK-107.
With respect to 107 Astellas will reimburse our agreed cost under the research and development plan and will be primarily responsible for the conduct of Phase II development and commercialization. In addition 7% of our R&D expenses were attributable to our cardiac muscle contractility activities and 7% to our other research activities.
For the nine months ended September 30, 2013 our R&D expenditures totaled $35.6 million. From a program perspective for those nine months approximately 80% of R&D expenses were attributable to our skeletal muscle contractility activities, 7% to our cardiac muscle contractility program and 12% to our other research activities.
Today Cytokinetics affirmed its previous financial guidance for 2013. Cash revenues are expected to be approximately $40 million to $42 million, cash R&D expenses are expected to be in the range of $52 million to $55 million and cash G&A expenses are expected to be in the range of $15 million to $16 million.
This financial guidance is on a cash basis and does not include the deferral of approximately $10 million in revenue to future calendar years and an estimated $5.6 million in non-cash related operating expenses, primarily related to stock compensation expense. The company again, the company will recognize the license fee of $15 million associated with the June 2013 amendment to our collaboration agreement with Amgen in the fourth quarter of 2013.
With the added cash resources from the Amgen and Astellas deals transacted in June of this year we believe we are in a solid financial position headed into potentially key value driving events from our clinical development program in heart failure and ALF. That concludes the financial portion of today’s call.
With that I’ll now turn the call over to Robert.
Robert Blum
Thank you, Sharon. The third quarter was a busy period.
The results underscore significant progress for Cytokinetics. Recently in the fourth quarter we have [dialed] up activities even more in anticipation of potentially positive clinical trial results from our lead development programs in 2014.
I would like to take this opportunity to thank the very dedicated employees of Cytokinetics for their diligence, especially in light of multiple planning scenarios. As we’ve discussed on several of these earnings teleconferences at Cytokinetics we take pride not only in the quality of our execution but also in the quality of our planning.
Going into 2014 we must prepare for different contingencies and alternatives not knowing what our clinical trials may demonstrate. In the third quarter we positioned the company for potential successes in clinical trials programs for each of omecamtiv mecarbil, tirasemtiv and CK-107.
All three programs are poised for major milestones in 2014. We must continue to ensure we are well positioned to capitalize on those corporate events.
The ATOMIC-AHF results support the continuing development of Omecamtiv Mecarbil and we are pleased that we now selected an oral formulation of this novel cardiac myosin activator following review of data from the dose escalation phase of COSMIC-HF with our partners at Amgen. We look forward to initiating the expansion cohort of COSMIC-HF and enrollment in that phase of a trial will inform guidance or results to be potentially available in 2014.
Preparing for success in the third quarter we’ve began a series of meetings with heart failure experts to discuss ways we may approach the design of a Phase III program for Omecamtiv Mecarbil. We are optimistic about the development of this novel mechanism compound.
Similarly with regard to tirasemtiv the benefit ALF trial is now nearing completion of enrollment. We are pleased with the recent DSMB decision to allow us to continue the trial without changes to the protocol and we now expect enrollment to conclude by the end of the year.
On that schedule this large international Phase IIb clinical trial should read out results in the first half of 2014. This is an especially important time for Cytokinetics and the patients who suffer from ALS.
We are optimistic about the potential for this trial to generate positive results that may support the value of Skeletal Muscle activation as a clinically beneficial treatment strategy for patients suffering from this grievous illness. In these last few months we’ve been scaling up and optimizing the manufacturing of both the active pharmaceutical ingredients as well as tablets of tirasemtiv.
We are preparing for each of two scenarios with tirasemtiv in 2014. One, that has Cytokinetics initiating a Phase III trial of tirasemtiv next year and the other which has us potentially ready to file applications for marketing authorization with regulatory authorities.
We are also taking other steps from the corporate development standpoint to inform practical strategies for commercialization of tirasemtiv. We have placed an emphasis in recent internal strategic planning and budgeting exercises on plans intended to ensure Cytokinetics is well positioned to capitalize on potentially positive results for the benefit of patients with ALS, their caregivers and also our shareholders.
Lastly we have made important progress in the third quarter under our recently initiated collaboration with Astellas. We are pleased to have both completed enrollment in the first time in human Phase I trial of CK-107 and to have recently initiated enrollment in the second Phase I trial of CK-107.
Under our collaboration agreement we are responsible for Phase I studies and other Phase II readiness activities. We are executing well on these trials in 2013 in accordance with agreed development plan and also under the joint oversight of Cytokinetics and Astellas.
Together we are setting the stage for the investigation of Skeletal Muscle activators in non-Neuromuscular disease indications. The promise for CK-107 to address syndromes and conditions associated with muscle fatigue and weakness remains our priority and we look forward to sharing future updates.
In concluding we are pleased with Cytokinetics’ progress and execution in the last quarter and remain hopeful for the implications for a bright future for our company and shareholders. Operator, that concludes the formal portion of our call today.
I would now like to open up the call to questions please.
Operator
(Operator Instructions). Our first question comes from the line of Simos Simeonidis with Cowen and Company.
Robert Blum
Hi, Simos good afternoon.
Simos Simeonidis – Cowen and Company
Hi, Robert, hi everyone. Thank you for taking the questions.
If you can tell us what the amendment in the protocol in COSMIC is and what is the rationale behind it? That will be my first question.
Robert Blum
Certainly so I won’t be able to go into those details today. Rather what I’ll be able to share with you is that for what will be data that came out of the escalation phase relating to the PK and relating to plans that we now have that may potential read on implications for Phase III design we think a protocol amendment may be appropriate.
We’re discussing that with Amgen and for what will be I hope primarily administrative matters we’ll be in a position to initiate the expansion phase here soon enough.
Simos Simeonidis – Cowen and Company
So does this amendment translates into a delay in starting the expansion and if yes, how significant a delay?
Robert Blum
So it will an effect delay, a delay that I don’t think will be particularly long based on our current planning I am hoping that we’ll have that amendment file here soon and we may be in a position to initiate dosing in the expansion phase also soon.
Simos Simeonidis – Cowen and Company
And maybe you won’t be able to answer this but I’ll try does the amendment have anything to do with dosing or frequency of dosing or is it something different?
Robert Blum
Again I don’t think I could go into it until we know that together with Amgen we are on the same page about how to approach an amendment. Soon enough we’ll be in a position I think we can elaborate on that to your full satisfaction.
Simos Simeonidis – Cowen and Company
Okay and then you said that you have 600 patients enrolled in BENEFIT ALS. Just to get an idea when the trial’s going to be at fully enrolled you said fourth quarter.
Can you tell us whether you think it might be November or December or how quickly you are enrolling patients in terms of rate of enrollment, let’s say on a per day or per week basis?
Robert Blum
So I’ll point you to the statement that Andy made regarding where we were on the last earnings call and where we are on to this one, but also point out that in that intervening period a substantial number of the centers were going through the administrative processes of then approving a protocol amendment. So patients were not being enrolled for a large portion of that time.
However I think that as you were seeing between our Q1 earnings call and our Q2 earnings call we were enrolling patients at quite a rapid rate. I believe that we are enrolling at a rate similar there and in that regard I think you might be able to do the math and answer your question.
What I’ll say is that I think we are very confident that we can complete enrollment in this fourth quarter and once we do so we’ll make the announcement. Andy do you think if there is anything else you want to add.
Andrew Wolff
I don’t think there is anything to add to that.
Simos Simeonidis – Cowen and Company
Okay. And then in terms of your thoughts on partnership, are discussion still ongoing?
I know you spoke towards the end of the call about corporate development and being ready to act if you had a positive result. How are you thinking about corporate or a partnership right now?
Robert Blum
Good question I should elaborate. With regard to corporate development I was not referring to business development and licensing as much as I was referring to what might be required of Cytokinetics if we were to build out a commercial business, a commercial business that would be in major markets, not only in North American but internationally.
And in that regard we are preparing for that potential scenario and understanding what would be from a market access standpoint, from a tax, legal, IP, human resources and clinical sales and marketing standpoint, understanding all the implications of what it would take to build affordably a business that could return significantly on investment. If we did choose to partner the program having that information would certainly be informative to any partnering discussions.
But partnering tirasemtiv is not currently a priority for Cytokinetics.
Simos Simeonidis – Cowen and Company
So the current thinking is to build out a commercial infrastructure in the U.S. at least?
Robert Blum
I think that’s fair.
Simos Simeonidis – Cowen and Company
And ex-U.S.?
Robert Blum
That’s what we are evaluating now by going through this exercise.
Simos Simeonidis – Cowen and Company
Okay, great. Thank you very much I’ll jump back in the queue.
Robert Blum
Thank you Simos.
Simos Simeonidis – Cowen and Company
No problem.
Operator
Our next question comes from the line of Charles Duncan with Piper Jaffray.
Robert Blum
Hi Charles.
Charles Duncan – Piper Jaffray
Hi, guys thanks for taking the questions and congratulations on the recent progress.
Robert Blum
Thank you.
Charles Duncan – Piper Jaffray
My questions are primarily on tirasemtiv. I am not sure if I heard you correctly or I am interpreting something you said in your prepared remarks regarding manufacturing and possibly getting ready for a Phase III or to file for regulatory approval applications.
Is, did I hear that correctly for 2015 activities and then perhaps does that reflects any insight on how things are going with BENEFIT-ALS?
Robert Blum
So I’ll answer that and then also turn to my collogues in R&D. We are preparing for those scenarios with anticipation that we will have potentially positive results and therefore not knowing until we have further discussions with data in hand with regulatory authorities, whether we have a basis with trial results to support a standalone registration.
We certainly need to know what that entails as we prepare to do that, if the data are sufficiently positive to warrant that. But more probabilistic for programs such as this in Phase IIb we should assume that the next incremental step would be a Phase III trial.
We also have to be well prepared for that. So each scenario carries with it different investments, different timelines, different priorities and urgencies and in that regard we are spending so that we ensure that we are able to react with data to which scenario we may then find ourselves on.
And Andy can speak to that from the, maybe clinical R&D standpoint and maybe I’ll ask Fady to elaborate on then on-clinical R&D.
Andrew Wolff
Well I think as we’ve discussed may times before our base case assumption is that a positive BENEFIT-ALS would still need conformation by a larger and longer Phase III study. But there are scenarios where a remarkably positive results from BENEFIT may encourage regulatory authorities to approve the drug sooner than that on the basis of some post approval commitments that would need to be negotiated.
So given that possibility I think it’s prudent to make these preparations as Fady can speak to this next but in particular one of the questions is with respect to manufacturing the drug substance and tablets and we would need that whether we were on a Phase III scenario or whether we were on an early commercialization scenario.
Fady Malik
Yeah Charles I think as Andy laid it out one just needs to invest prudently to be prepared with enough drug supply to embark on either scenario. If it’s a Phase III trial we need drug supply to minimize the startup time in that trial.
If we were going forward to registration we need to able to demonstrate that we can reproduce and manufacture the drug and do all those things as well. So there are different aspects, each scenario that sort of both involve the same thing.
Charles Duncan – Piper Jaffray
So it sounds like you are making prudent steps for the future without a lot of information and not necessarily reading into anything in terms of the trial with regard to making these observations?
Robert Blum
If you are asking if we have any insights into the data, the answer is no. We do know the study enrolled well and we do know the DSMB has given us a green light to proceed to complete enrollment and in that regard we know that investigators are enthusiastically embracing the study and that to us encourages us to want to make certain that we are well prepared to return that confidence with our being poised to act promptly on data with the goal that we could be either filing a registration application or proceeding to Phase III.
We can’t know which one it will be or it may be neither of course we certainly have to prepared for the positives and in that regard we want to make certain that we don’t have delays in the supply chain, we want to make certain that we are in a best position on the non-clinical and clinical side to discuss with regulatory authorities what might be required for potential registration.
Charles Duncan – Piper Jaffray
Okay, Robert that makes sense. And then with regard to the DSMB meeting, can you review the criteria that they might have considered for continuing the study?
Was there any efficacy component of that analysis?
Robert Blum
They review all the data in an unblinded fashion.
Charles Duncan – Piper Jaffray
Okay. And then final question is you said that 300 or so patients have been on the drug for twelve weeks.
Could you please remind me what happens after twelve weeks. Do they stop taking the drug or are they given the option to continue taking the drug?
And if so what percentage of them have continued to take the drug?
Andrew Wolff
So they finished as twelve weeks of double blind treatment and they stopped and maybe I’ll remind everyone that they really do receive 13 weeks of treatment because the first week is open label, everybody gets a 125 milligrams twice a day and then patients are randomized for an additional twelve weeks dose transpiration on active tirasemtiv or placebo. After those 12 weeks of double blind therapy they come off treatment there is no option for them to continue and they have follow-up assessments seven and 28 days after terminating double-blind treatment.
Robert Blum
But however also just to be explicit to your questions we do not have for this study continued enrollment program, so patients do come off of study drug.
Charles Duncan – Piper Jaffray
Okay, thanks for that.
Robert Blum
Thank you.
Operator
Our next question comes from the line of Paul Matteis with Leerink.
Robert Blum
Hi Paul.
Paul Matteis – Leerink Swann, LLC
Hey thanks a lot for taking my question. So you know I know you can’t disclose any of the details regarding your amendment to COSMIC but can you help us understand kind of what exactly constitutes success with this trial, relative to ATOMIC and kind of what do you believe you need to see and what Amgen needs to see in order to advance the program to Phase III?
Robert Blum
So I won’t comment as to what I think Amgen needs to see because I shouldn’t speak for Amgen. I’ll tell you what the study is designed for and I think that will hopefully address what Cytokinetics and Amgen will be considering in light of decisions regarding potential progression to Phase III.
The study is designed primarily for safety, tolerability pharmacokinetics and understanding potential effects on pharmacodynamics. This is not a study that has a principal efficacy objective or clinical outcome.
So it really is about understanding if the oral form that has now been selected is well tolerated and produces predictable PK and a pharmacodynamic effect that is durable. So as you know this is a study that will enroll patients now for weeks of treatment and we’ve seen already in prior studies that the drug is safe and well tolerated at plasma exposure levels that are similar to the ones that are being investigated here.
What we also know is that very sensitive measures of drug effect are found in echocardiographic parameters. So we’ll be looking at echocardiographic parameters here again with more patients in order to be able to understand if those are maintained and durable out to longer term evaluations.
Maybe I’ll turn to Fady and see if there is anything further you want to add.
Fady Malik
Yeah I think just in a nutshell this will the first time where we have dosed patients for sustained period of time and we want to demonstrate safety and tolerability of that. In conjunction we are seeing some changes in the echocardiogram of these patients that might look favorable in terms of cardiac function and structure.
Robert Blum
I’ll point you back to the ATOMIC data and are remind you that systolic ejection time with relatively few patients that participate in the echocardiographic sub-study of ATOMIC produced dose depended and plasma concentrated related effects that were consistent with the therapeutic hypothesis and the mechanism of this novel cardiac myosin activator and we’ve seen in study after study that systolic ejection time and some of these other echocardiographic parameters can be quite responsive to this new mechanism. So that’s the kind of thing that we’ll be looking again at here and in that regard I think that COSMIC is designed in such a way that we’ll be able to answer some questions about what pharmaco dynamically we may be hopefully able to one day correlate with clinical outcomes.
I want to underscore how significant it is that we did select an oral form for progression to the expansion cohort. I’ll remind you that last year we were looking at six oral forms and we were doing that in healthy volunteers in Phase I and then we initiated the COSMIC study to compare three of those oral forms versus placebo and dose escalation and now we’ve selected an oral form and we look at that as a big positive.
Paul Matteis – Leerink Swann, LLC
Great thanks that’s really helpful. And then just now that you are initiating the trial in Japan and also there is the protocol amendment.
I am just kind of wondering exactly do you still expect COSMIC data in 2014. When do you expect to potentially see data from the Japanese study?
And then after those two data read outs occur what’s kind of the time frame for which Amgen could decide whether or not Phase III is a go or no go?
Robert Blum
So firstly the decision to proceed to Phase III is a joint development committee decision that Amgen and Cytokinetics makes together. I want to underscore that that’s the way our collaboration agreement is setup.
Regarding timing it really does have to do with how quickly we can process this protocol amendment and be then in a position to initiate enrolment and have enrollment informed, the answer to your question. I do believe that as enrollment may go quickly in the study than we will be in a position to answer those key questions in 2014.
But we are not on this call giving guidance to 2014. More importantly we’ll see enrollment and be hopefully in a position to do that with our next earnings calls.
As far as the Japanese ethnicity pharmacokinetic study, I’ll point out that that’s the study that will be done in the United States. I didn’t want to implied by your comments and your question that it will be performed in Japan.
It will be performed in the United States but in healthy volunteers including those who have Japanese ethnicity and that’s a study that Cytokinetics will do here and under the IND but which will produce data which will allow us to potentially include Japan in a registration program that we are looking forward to that data in 2014.
Paul Matteis – Leerink Swann, LLC
All right, great yeah, thanks a lot I appreciate it.
Operator
Our next question comes from the line of Chad Messer with Needham & Company.
Robert Blum
Hi Chad.
Chad Messer – Needham & Company
Yes, thanks for taking my question. Just quickly on 107 as a lot of my questions on the other programs have been answered, the fact that you’ve completed dosing and the dose escalation Phase I does that imply you’ve reached the dose limiting toxicity and is there anything you can share with us on what that might be?
Robert Blum
So that’s an excellent question and one that I can’t comment on and nor can my colleagues comment in large part because these data are very fresh and we want to share them with our colleagues at Astellas and be then in a position to communicate them together. What I’ll tell you is that the study was a single ascending dose study, not so much intended to look for a dose limiting effect but rather to assess and evaluate doses up to a maximum level.
Chad Messer – Needham & Company
Okay, great. And then may be a quick one for Sharon, just on the Astellas collaboration I know you recognized some of the revenue from the two portions of the revenue that you are getting from that collaboration.
Can you just remind me how that’s going to be recognized going forward? I think I was expecting it over eight quarters but it doesn’t look like a straight line, is it like percent of completion or reimbursement or are just how is that going to hit your P&L?
Sharon Barbari
It’s going to be on a proportional performance basis. So percent completion it’s basically looking, it’s one single unit of accounting.
And so we’ll look at the total cost incurred and then it will be done proportionately over time.
Chad Messer – Needham & Company
All right thanks guys congratulations on the progress.
Robert Blum
Thank you.
Operator
Our last question comes from the line of Jason Butler with JMP.
Robert Blum
Hi Jason.
Jason Butler – JMP Securities
Hey, Robert thanks for taking the questions. And just on the BENEFIT-ALS trial could you just walk us thorough your expectations of timing from the completion of enrollment until when you expect to be able to give top line results?
Robert Blum
So I think we are still quite comfortable with the kind of feedback we gave to that same question earlier which is to say that following last patient last visit in what will amount to weeks we hope to be in a position to have data collected in order to then proceed to data base lock, analysis of data and reporting of the data. So we are talking about weeks to may be a couple of months but not longer than that.
The reason I say that we are making a big push right now for patients who have already completed enrollment to collect those data and be in a position so that when the last patients come off study drug we have many fewer patients that we have to collect data for in order to able to proceed to locking the database. In prior calls we pointed to where we think we could be in a position to present these data and while this is not formal guidance we would like to be in a position to present these data in the first half of 2014 and in that regard one potential place where those data could be presented would be the AAN meeting which is at the end of April in Philadelphia.
Jason Butler – JMP Securities
Okay, great thanks. And then just a question for Sharon.
You say in the press release that you expect to recognize the $15 million from Amgen as revenue in 4Q. Have you already, did you receive that cash in 3Q?
Sharon Barbari
We actually received that cash in 2Q. So we received that cash...
Jason Butler – JMP Securities
Okay, so you have already received that cash.
Sharon Barbari
Yeah, we received that cash, we just didn’t meet the criteria for revenue recognition until the fourth quarter.
Jason Butler – JMP Securities
Okay, great. Thank you very for taking the questions.
Robert Blum
Thank you. Operator, are there any other questions?
Operator
There seem to be no further questions at this time.
Robert Blum
Thank you then. And also thank you to all the participants of the teleconference today for your continued support and interest in Cytokinetics, in our progress and operator with that we can conclude the call.
Thanks very much.
Operator
Ladies and gentlemen, this concludes today’s conference call. We thank you for your participation.
You may all disconnect.