Feb 6, 2014
Executives
Sharon Barbari - EVP, Finance and CFO Robert Blum - President and CEO Dr. Andrew Wolff - SVP, Clinical R&D and Chief Medical Officer Dr.
Fady Malik - SVP, Research and Early Development
Analysts
Ritu Baral - Canaccord Simos Simeonidis - Cowen & Company Jason Butler - JMP Securities Paul Matteis - Leerink Swann
Operator
Good afternoon and welcome ladies and gentlemen to Cytokinetics Fourth 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 question-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 remarks 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 for the potential treatment of ALS and also will provide an update on the Phase I clinical trials of CK-2127107 or CK-107 in healthy volunteers.
Next Dr. Fady Malik, our Senior Vice President of Research and Early Development will update you regarding recent progress in clinical development of omecamtiv mecarbil for the potential treatment of heart failure.
I’ll then provide a financial overview for the quarter. Robert will then conclude the call with additional comments regarding how the company activities align with our corporate strategy and projected milestones for 2014.
We will then open the call for questions. Please note 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, 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.
I’ll now turn the call over to Robert.
Robert Blum
Thank you and good afternoon. Thanks to everyone on the line for joining us on this call today.
2013 was a successful for Cytokinetics. In 2013, Cytokinetics delivered on key objectives in research and development and in other areas relating to business development and overall across the company.
Taking all together our company’s solid execution in 2013 now positions us well in 2014. In R&D we progressed each of our clinical development programs to important milestones, that progress was accompanied by our new alliance with Astellas and our expanded strategic alliance with Amgen.
I am proud of the progress Cytokinetics made last year. Looking forward we’re focused to the continued development of our three clinical stage programs as well as further corporate development initiatives that we expect can position the company to deliver on our mission in the results and potential returns for all our stakeholders.
Starting with a look at the progress made during 2013 and our skeletal muscle contractility program. In the fourth quarter we completed the enrollment of BENEFIT-ALS with 711 patients.
We’re now focused to the completion of the trial and look forward to the potential presentation of results from BENEFIT-ALS in April at the Annual Meeting of the American Academy of Neurology. This large international Phase IIb clinical trial tirasemtiv is designed to inform our global registration plans for this promising drug candidate and we’re evaluating strategic scenarios for the further development and the potential commercialization of tirasemtiv.
In addition, in 2013 we made progress under our new collaboration with Astellas for the development of CK-2127107 or CK-107 and in a conduct of joint research to identify next generation skeletal sarcomere activators. During the last quarter, we reported results from our first time in humans Phase I clinical trial CY 5011 as Andy will elaborate in a moment.
More recently, we completed dosing in another Phase I trial CY 5014 evaluating the relative bioavailability of two different liquid oral forms as CK-107. Both of these trials are part of an agreed development plan with Astellas that is focused to the characterization of CK-107 for potential evaluation as a treatment for non-neuromuscular diseases in Phase II trials.
In our cardiac muscle contractility program, together with Amgen in the last quarter we prepared for the continuation of COSMIC-HF and progression of this ongoing Phase II clinical trial of oral omecamtiv mecarbil to the expansion phase. We recently reported on changes to the trial design of COSMIC-HF that are included in the protocol amendment agreed with Amgen.
We believe that implementing these changes in COSMIC-HF enables us to evaluate a plasma concentration guided dose titration strategy in Phase II that we anticipate implementing in the potential Phase III development of omecamtiv mecarbil and that may better reflect real world clinical practice. Fady, will describe the recent changes to the protocol of COSMIC-HF in more detail later in this call.
Looking forward in 2014, we are focused to preparations for the commencements of enrollment in the expansion Phase of COSMIC-HF and the Phase I study to compare the safety, tolerability and pharmacokinetics of omecamtiv mecarbil in healthy volunteers of Japanese ancestry with Caucasian counterparts. We are also collaborating with Amgen on a number of other work streams intended to inform potential progression to Phase III.
So, with that introduction I'll turn the call over to Andy for an update on the progress of our skeletal muscle contractility program.
Dr. Andrew Wolff
Thank you Robert. I'm pleased to provide an update on recent developments in our skeletal muscle program especially because can look forward that we have concluded enrollment in BENEFIT-ALS with 711 patients and rolled it over 75 centers in eight countries.
Over 400 of those patients now have completed the 12 weeks of double-blind treatment. As we know, BENEFIT-ALS is a Phase 2b multinational double-blind randomized placebo controlled clinical trial designed to evaluate the safety, tolerability and potential efficacy of tirasemtiv in patients with ALS.
In December, the study’s lead investigator Dr. Jeremy Shefner provided an update on BENEFIT-ALS during a platform presentation at the international symposium on ALSMMD.
Dr. Shefner's presentation included double-blind aggregate data that was well received by conference attendees and that underscore the ALS community’s enthusiasm for results from this trial.
More recently, in January the Data Safety Monitoring Board or DSMD for BENEFIT-ALS convened and reviewed data relating to potential safety, tolerability and efficacy of tirasemtiv from the trial. We are pleased to report that DSMD recommended that BENEFIT-ALS proceed to completion without any changes to the protocol.
I'm also happy to confirm that an abstract intended to include the first public announcement of the results from BENEFIT-ALS has been accepted by the American Academy of Neurology or AAN for presentation by Dr. Shefner during the platform session at their annual meeting in Philadelphia at the end of the April.
At that meeting, we expect Dr. Shefner will present the major efficacy, safety and tolerability measures from BENEFIT-ALS.
Given that the last patient visit in the trial is not expected to occur until the end of March, we realize that it is an aggressive goal for us to resolve all outstanding data queries, block the trial database and complete the required statistical analyses in time for a presentation of results from BENEFIT-ALS at AAN. But we will be working diligently to try to achieve that objective.
If we are not able to complete analyses in time to make the first presentation of the BENEFIT-ALS data at AAN, we hope to do so approximately a month later in Istanbul as the joint Congress of European Neurology organized by the European Federation of Neurological Societies in collaboration with the European Neurological Society. Between now and those upcoming meetings, Cytokinetics’ priorities are also focused on preparations for the further development of tirasemtiv as may follow the reporting of results including the conduct of manufacturing and related activities and other initiatives consistent with Phase III planning.
Turning now to the development of CK-107, in the last quarter, we reported data from CY-5011 of Phase I first time in humans clinical trial of CK-107 in healthy male volunteers, conducted by Cytokinetics under our collaboration with Astellas. CY-5011 was a double blind randomized placebo controlled study designed to assess the safety, tolerability and pharmacokinetics of single ascending oral doses of CK-107 administered to healthy adult males in the three period dose escalating crossover design.
The primary objective of this trial was to evaluate the safety and tolerability of single doses of CK-107 administered orally to healthy male volunteers. The secondary objective was to evaluate the pharmacokinetic profile of single doses of CK-107.
Planned single doses of CK-107 up to 4,000 milligrams, the highest dose administered in this trial were well tolerated; therefore a maximum tolerated dose could not be defined. Pharmacokinetic profile of CK-107 was one year, and dose proportional across the dose range study with the mean terminal half life compatible with once or twice daily dosing.
Also during the quarter, we completed dosing in CY-5014, 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 bioavailability, pharmacokinetic, safety and tolerability of two forms of CK-107 when administered orally in a liquid suspension.
We are compiling the data from CK-5014 and look forward to reporting the results later in 2014. I’m pleased with the results from the ongoing development of CK-107, which suggest an encouraging tolerability and pharmacokinetic profile for this novel activator of skeletal muscle.
Results from CY-5011 along with the results from other ongoing and planned Phase I clinical trials and related non-clinical development activities will inform plans for the further potential clinical development of this drug candidate. As we continue to collaborate with Astellas for the readying of Phase II development, we look forward to providing further updates regarding CK-107.
With that update on our skeletal sarcomere activators, I will turn the call over to Fady for an update on our cardiac contractility program.
Dr. Fady Malik
Thank you, Andy. As reported with our Q3 earnings, Cytokinetics and Amgen selected an oral formulation omecamtiv mecarbil based on the results of ascending dose cohorts in COSMIC-HF and agreed to proceed to the expansion phase in the ongoing clinical trial.
Last year we also announced that Cytokinetics and Amgen agreed to amend the protocol for COSMIC-HF before proceeding. More recently, we announced details of the protocol amendment.
Under the protocol amendment, three key changes to the expansion phase of the trial are being implemented. First, we revised one of the three treatment arms of the trial to include dose titration step.
Originally one arm was to receive 25 milligrams twice daily, another was to receive 50 milligrams twice daily and a third was to receive placebo. The amendment now implemented dose titration step in the 50 milligram arm.
The other two arms are unchanged. Patients in the 50 milligram arm will receive 25 milligrams twice daily for eight weeks and then titrate upto 50 milligrams twice daily for the remaining 12 weeks if eligible to do so based on a trough plasma concentration of omecamtiv mecarbil measured in week two.
Patients not eligible to titrate upwards will continue on 25 milligrams twice daily for the rest of the study. The second revision to the protocol is to increase the duration of the expansion phase from 12 weeks to 20 weeks.
Purpose of this change is to allow time to conduct the bio-analyses of the trough plasma sample taken at two weeks and have the data available for just a decision regarding dose titration at eight weeks. Extending the duration to 20 weeks in total allows for patients in the titration arms to have the 50 milligram dose for the full 12 weeks as well as increases the overall duration of exposure to omecamtiv mecarbil in all active dose groups.
We believe that the implementation of this dose titration strategy may maximize the number of patients who achieve targeted plasma concentrations of omecamtiv mecarbil while reducing the number of patients who might experience excessive exposures. We also believe that the strategy may yield important information and may guide and simplify our planning for Phase III.
The third revisions to the protocol is that we increase the number of patients enrolled in the expansion phase from 300 to 450 patients. We believe that this change will increase this typical power to protect differences in echocardiographic endpoints that we are evaluating and provide for a larger pharmacokinetic and safety data set.
Recently Cytokinetics and Amgen have been collaborating to response information request to receive from regulatory authorities relating to their ongoing review of the protocol amendments submitted for COSMIC-HF. And while COSMIC-HF continues to progress towards initiation of the expansion cohort, our companies are working together to plan for potential Phase III activities.
In parallel, we have begun making preparations for the Phase I clinical trial of omecamtiv mecarbil known as CY 1211. This trial is a single center placebo controlled, double-blind study comparing the pharmacokinetics of omecamtiv mecarbil between healthy Japanese and Caucasian volunteers.
This trial is being conducted by Cytokinetics in collaboration with Amgen and is provided for under our recently expanded aligns with Amgen. CY 1211 is the first step towards potential inclusion of Japanese patients in the global registration trial dossier.
We expect to share more details relating to this trial on the coming months. In the meantime we are collaborating with Amgen to respond information request from regulatory authorities relating to their ongoing review of the protocol for CY 1211 as well.
So with that update, I will turn the call over to Sharon.
Sharon Barbari
Thank you, Fady. As our press release contains detailed financial results of fourth quarter 2013, I'll refer you to that public statement for the details on our P&L and balance sheet.
In the past quarter, we were focused on completing the enrollment of BENEFIT-ALS and executing on the development and research plans associated with the Astellas collaboration. While we reported a profitable quarter with net income of $6.5 million, we do not expect this to continue in the future as it is largely reflected of the recognition of license revenue of $17.2 million from our Amgen collaboration which in not recurring.
We ended the fourth quarter with approximately $80.2 million in cash, cash equivalents and investments, which represents approximately 16 months to 18 months of going forward net cash burn based on our 2014 financial guidance, which I will cover in a moment. Revenues for the fourth quarter of 2013 were $24.3 million.
This revenue included the recognition of $2.4 of the $16 million Astellas license fee and $4.1 million in program expense reimbursement and other revenue. Revenues for the fourth quarter also included license revenues from our collaboration with Amgen of $17.2 million and $0.6 million from program expense reimbursement.
Revenues for the 12 months ended December 31, were $30.6 million. This revenue included the recognition of $3.9 million of the $16 million Astellas license fee and $6.4 million in program expense reimbursements and other revenues as well as the $17.2 million in license revenue from our Amgen collaboration along with the $2 million from program expense reimbursement.
In addition, $1 million in revenue from our MyoKardia collaboration which ended in August of 2013. Our fourth quarter 2013 R&D expenditures totaled $13.8 million.
From a program perspective, for the fourth quarter, approximately 88% of our R&D expenses were attributable to our skeletal muscle contractility program activities. These include both the development of tirasemtiv, which we are performing independently and research and development activities that we are performing under the collaboration with Astellas, which includes the development of CK-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 activity. In addition, 7% of our R&D expenses were attributable to our cardiac muscle contractility activities and 5% to our other research activities.
For the 12 months ended December 31, 2013, our R&D expenditures totaled $49.5 million. From a program perspective for those 12 months, approximately 82% of our total R&D expenses were attributable to our skeletal muscle contractility activities, 7% to our cardiac muscle contractility program and 11% to our other research activities.
Moving on to our financial guidance for 2014, the company anticipates cash revenue will be in the range of approximately $19 million to $21 million, cash R&D expenses will be in the range of $50 million to $53 million and cash G&A expenses will be in the range of $15 million to $17 million. This financial guidance is on a cash basis and does not include approximately $10 million in revenues deferred from 2013 into 2014 under generally accepted accounting principles and an estimated $3 million in non-cash related operating activities primarily related to stock compensation expense.
In addition, this guidance does not reflect potential revenues from milestone payments that maybe achieved in partnered program. We believe that our financial resources in the next 12 months will largely be focused on the completion of BENEFIT-ALS and the analysis of data from that trial, as well as certain readiness activities necessary to support substantial further development and commercialization of tirasemtiv.
That concludes the financial portion of today’s call. With that I’ll turn the call over to Robert.
Robert Blum
Thank you, Sharon. So you’ve heard on our call today, we've been busy advancing our clinical stage programs.
Our progress in 2013 positions Cytokinetics well for continued progress in 2014. As a result of what we accomplished in 2013, this year has the potential to be a watershed year for Cytokinetics.
In preparation for potentially positive results from BENEFIT-ALS, we've been engaged in planning for next steps relating to tirasemtiv and at the making preparations on multiple fronts across the company. Our base case scenario for tirasemtiv contemplates our proceeding to conduct a Phase III clinical trial and we are conducting a series of readiness activities including certain manufacturing and other non-clinical activities.
In addition we’re engaging in regulatory and clinical development work streams to position the company to advance tirasemtiv into the expected final stages of an international registration program. At the same time, we are poised to execute on next steps in connection with the more probable base case scenario.
We also recognized the urgency associated with advancing new investigational medicines to patients with ALS and the important role we may play to address these high unmet needs. Therefore, we’ve also engaged in planning activities to inform practical and affordable strategies for the potential commercialization of tirasemtiv, both in North America and outside of North America.
We believe that Cytokinetics is taking prudent, but appropriately aggressive actions to position the company to respond to several potential outcomes related to BENEFIT-ALS in 2014. For our omecamtiv mecarbil development program, we’re looking forward to initiation of patient enrollment and expansion cohort of COSMIC-HF.
While administering to the protocol amendment has necessitated delays in the timeline to data from this ongoing Phase II trial, more importantly taking these actions now provides for a larger and potentially more meaningful dataset from COSMIC-HF. In preparing for the potential progression of omecamtiv mecarbil, we continue to engage heart failure experts to discuss ways we may design a Phase III program for omecamtiv mecarbil.
We’re optimistic about the continued development of our novel mechanism compound and are collaborating with Amgen on activities that anticipate potential progression to Phase III. The unmet need in heart failure remains high and we believe that omecamtiv mecarbil in both intervenes and oral forms may demonstrate a clinical profile that can represent a significant innovation for both acutely ill and chronic care patients.
We look forward to continued progress with regards to this promising program throughout 2014. And lastly as you’ve heard, we continue to make important progress under our collaboration with Astellas.
We’re pleased to have completed two Phase I trials of CK-107 in the six months since our collaboration was initiated. Under our collaboration agreement, we are responsible for Phase I studies and other Phase II readiness activities for CK-107.
We are executing well in accordance with an agreed development plan and under the joint oversight of Cytokinetics and Astellas. Together with our partner, we are setting the stage for the investigation of CK-107 and other skeletal muscle activators in non-neuromuscular disease indications.
We believe CK-107 offers great promise to address high unmet needs in a wide array of syndromes and conditions associated with muscle fatigue and weakness. We look forward to sharing future updates throughout 2014.
Now, let me turn back to expected milestones for 2014. For tirasemtiv, Cytokinetics expects to report data from BENEFIT-ALS at the American Academy of Neurology annual meeting in Philadelphia in April.
For CK-107, Cytokinetics expects to conduct additional Phase I studies and certain Phase II readiness activities in 2014 in pursuant to our collaboration agreement with Astellas. For omecamtiv mecarbil, Cytokinetics expects commencement of patient enrollment in both the expansion of COSMIC-HF and in CY-1211 to occur in the first half of 2014 following Regulatory Authorities’ review of responses relating to information request providing in connection with the protocols submitted for the two trials.
And Cytokinetics expects both the enrollments of patients and expansion phase of COSMIC-HF, as well as the conduct of CY-1211 to be completed in 2014. In concluding, we are pleased with Cytokinetics’ progress and execution in the last quarter and in 2013.
And we're hopeful for their implications for a bright future for our company and all shareholders. Operator that concludes the formal portion of our call today, I'd now like to open up the call to questions please.
Operator
(Operator Instructions). Our first question comes from the line of Ritu Baral with Canaccord.
Robert Blum
Hi Ritu.
Ritu Baral - Canaccord
Hi guys. Thanks for taking the question.
Yeah, as we all look forward to BENEFIT-ALS data, can you give us a little more detail on these next step readiness activities that you mentioned? And also walk us through what you're thinking as far as the scenario analysis.
Positive data, what would the next trial potentially look like and what threshold of data you think that you’d need to see in order to may be contemplate early filing?
Robert Blum
Okay. So those two to three questions, we'll try to pick up one at a time.
So in terms of readiness activity, Ritu, there are so many. I'll start with what's going on in the CMC and non-clinical side.
That’s where we want to make sure that to the best of our abilities, we’re not in a position where supply would be rate limiting to the start of a Phase III program. Our goal would be data permitting at the end of Phase II meeting with regulatory authorities permitting that we’d be in a position to progress tirasemtiv into Phase III by the end of the year.
That’s not part of our formal guidance right now, because it’s awaiting the data and those conversations. But in order to be able to make that timeline, there are things we have to be doing in terms of optimizing, manufacturing of drug substance and drug product, doing it at scale, making sure those batches are validated and serving our longer term potential interest as it relates to commercial quantities and quality.
So there is a lot of things going on in the CMC and non-clinical side. There are other non-clinical studies that we have to be geared up for.
And there are regulatory conversations; there are conversations we have with disease and patient efficacy organizations there is market research and forecasting, there is all sorts of planning that goes alongside of the organization that would be required to conduct a Phase III study for other market access and other kinds of commercial development and planning work streams. So I just touched on it in a very high level but hopefully that gives you a flavor.
I am going to turn to Andy and talk about expectations for what we might see out of the data could support Phase III, but I will remind you that our base case is that the data supports Phase III and would not be yet the subject of an accelerated registration. But at the same time we need to be poised for that if the data, which speak to that and also the regulatory conversations we have would render that more practical.
So we are preparing for both the base case and the best case even as we recognize more prudently and practically we should be poised for Phase III.
Dr. Andrew Wolff
So I think if we see from BENEFIT ALS, a very clear separations of patients treated with tirasemtiv versus placebo and there ALSFRS are scores. And specially if we have confirmatory data from the key secondary endpoint, the mass regulatory volume and the sniff nasal inspiratory pressure et cetera that we would probably proceed into a Phase III study even if we possibly miss the p value less than 0.05.
I think in that situation the magnitude is a difference between tirasemtiv and placebo and the consistent direction of the other secondary end points would drive our decision more than a bright line around 0.05 especially if they were very close. We would need another confirmatory trial, but it would appear to be rational to do one.
And furthermore we would have 711 patients worth of data informing us better regarding ample size calculations inclusion and exclusion criteria et cetera. For [SQ] contemplate filing after a single study, clearly we would need to have a p-value less than 0.05 on the primary end point and probably more than just barely less than 0.05 but significantly less than 0.05.
And without any internal inconsistencies that might raise any questions meaning, we are not seeing all of the effects coming from one center or a small group of centers, the secondary end points are all lining up in the same direction and are confirmatory. And no new emerging safety or tolerability concerns.
So that would be the kind of result we need to think we could go into regulators and propose an early approval.
Robert Blum
So I’ll remind you that the Phase IIb study is powered with 80% power to detect a lesser difference in treatment versus placebo at 12 weeks with a p less than 0.05. And that's not uncommon that a Phase IIb study would have 80% power where with Phase III you would expect to have higher power.
And as we think about Phase III, I’ll ask Andy to comment here in a minute, we would be looking for learnings from Phase IIb in a BENEFIT ALS study which is of course we know it’s the largest Phase II study that's been done in a population of ALS patients to the lot that we can learn from that as we think about Phase III. If we start to see in these data that patients are better than their own baseline that 12 weeks they’re improved relative to when they came into the study, and as Andy points out that’s consistent across endpoints, I think we would certainly want to engage regulatory authorities, understand whether that would be (inaudible) global to submit for an accelerated review and potential approval, but I don’t want to get too far out of our ski zone, we’ll wait and see what the data hasn’t stored for us and then we’ll set proper expectations afterwards.
Dr. Andrew Wolff
So then finally, Ritu you offer us what a Phase III would look like if that’s what we were moving toward. And clearly anything have about to say we need to be refined and reexamined up against things that will come out of BENEFIT-ALS like you observed variability in the change from baseline in the ALSFR -- I am trying to say ALSFRS-R as well as things that with now this much larger data set we may believe tend to predict better responders versus those who may not respond as well.
But based on what we know now and going in we would imagine that we need to be of six months duration. And now because it would be a Phase III we even want 90% power to see our treatment effect.
Both of those things caused the study to need to be larger, so it would probably be something over a 1,000 patients between a 1,000 and 1,500 to be refined again based on what we see from BENEFIT-ALS. I think it wouldn’t be a bad guess to say it’d be somewhere right in the middle there around 1,200, 1,300.
Ritu Baral - Canaccord
Great. Thanks for taking all the questions.
Robert Blum
Sure. Does that get to all your questions?
Ritu Baral - Canaccord
Yes. So that was all three.
Robert Blum
I think they were two.
Ritu Baral - Canaccord
Thanks.
Robert Blum
You are welcome.
Operator
Our next question comes from the line of Simos Simeonidis with Cowen and Company.
Robert Blum
Hi Simos.
Simos Simeonidis - Cowen & Company
Hi, Robert. How are you?
I am going to shift to omecamtiv mecarbil if I may. And for the expansions phase of COSMIC-HF, you mentioned that you expect to complete the trial by the end of the year.
So my questions are the following. Do you have a rough estimate of when enrollment can start again after the new protocol?
Second one would be, so the trial given guidance was going to end in ‘14, we assume we are not going to have data until probably sometime in Q1 or Q2, ‘15. And finally how should we think about the scenarios where Amgen decide, Amgen and you decide to go into a Phase III trial, is there something that will happen after you have the data from COSMIC, could it come at an earlier point?
And so let’s take that.
Robert Blum
Yeah. So a couple of questions, I will take few of those and turn it over to Fady as well.
With respect to Phase III, I would not assume that we are going to get started with Phase III before we have completed COSMIC, certainly we are encouraged by the data from ATOMIC. We think it supports progression of Phase III but we also want to see the results from COSMIC before we would engage in that final activity in support of movement of Phase III.
And I think that is consistent with comments we have been making and also Amgen’s been making. The start of commencement of enrollment in the expansion phase of COSMIC with this release, we are saying would happen in the first half of the year and that could be Q1.
But in order to be conservative, we're suggesting that it's first half of the year and when it happens, we'll announce that. And the enrollment could proceed very quickly.
We saw in the dose escalation phase of COSMIC that with a number of centers enrolling that those cohorts enrolled very, very rapidly. So, we expect that we can enroll the COSMIC study in the expansion phase, probably not in a matter of weeks, but certainly in the matter of months.
And certainly we feel comfortable with our guidance that that’s going to occur in 2014, that's not necessarily at the end of 2014, that could very well be much sooner. But I’ll ask Fady maybe to comment on given that patients are going to be getting treatment for longer periods of time, what that means in terms of possible data.
Dr. Fady Malik
So, I think the adjective in terms of data and the trial still remain similar that we're going to be examining the pharmacokinetics of a molecule in a large group of patients looking at echocardiogram. So, I think the main things that time gets us here is obviously a longer time if you look at the impact of omecamtiv mecarbil on cardiac function and dimension over time.
And so the -- and I wouldn't underestimate as well that now we're moving towards sort of five months of continued treatment. If you think of what these patients eventually will be studied is in a trial in Phase III that would put them on continuous treatment and definitely having five months is substantially better I think than having three months of exposure data.
So safety data will also be expanded in that respect and more confidence like given in that respect too.
Robert Blum
So given that it is an expansion phase that’s getting started here in 2014 and not at the end of ‘13 as was at one-time our goal, it does mean that data from COSMIC is more likely to be coming in 2015, and when in 2015 will depend on how rapidly it enrolls and we’ll hopefully be able to point with some more guidance around that when we see enrollment completing. Did that help?
Simos, I feel we lost you.
Simos Simeonidis - Cowen & Company
Yeah, can you hear me?
Robert Blum
Yeah.
Simos Simeonidis - Cowen & Company
Okay, sorry about that. I just had two very quick ones also on omecamtiv mecarbil.
With the expansion of your partnership with Amgen to include Japan, could you also remind us or speak about the rationale, the significance of doing the Phase I trial in Japanese and non-Japanese patients, what’s the role of that trial? And the final question is, is there any update on the either a small trial in patients with renal insufficiency, is there anything to report there, are we going to see this data, just provide us an update if you could?
Thank you.
Robert Blum
So, let me -- you are welcome. Let me start with the strategic implications.
So when we announced in June of last year that we expanded our alliance with Amgen to include Japan, it was very much with the view that we wanted to be working together to enable the possibility that Japan could be included in the global registration program for omecamtiv mecarbil, which means the possibility of enrolling patients in Japan in a Phase III program. So, there is obviously things that have to be done in between to enable that to happen.
And we've been talking to Amgen about how best to do that. And it’s nice for us at Cytokinetics to be able to ourselves be conducting this study which will be conducted in patients of Japanese ancestry here in the United States comparing to Caucasian subjects.
This is a very common approach to getting safety and tolerability but primarily PK data to support when there will be recessions with regulatory authorities around what might else be required in order to be able to make that goal happen. So this is the first step and this is a study that we’ll be doing under an agreed protocol with Amgen, under their sponsorship and it’s a study that we also be to start and finish this year.
With respect to its design, if you have any questions about that, maybe I’ll turn to Fady and also with respect to the renal study. But I will tell you that these are studies that we don’t always communicate at scientific forums being that they’re Phase I and otherwise more in keeping with what would be typical for those medical meetings.
Dr. Fady Malik
Yeah Simos, I think Robert summed up Japanese bridging study well. I mean the major -- I will just add that the major objective there in terms of initiating a development program in Japan is to ensure that the dose of the drug that you are using that you’ve settled on by doing studies in non-Japanese patients is the same that you would apply in the Japanese population, which is they certainly have precedent for lower doses being used in Japanese population.
So, this study really is meant to service the bridge and then to enable the selection and design of proper dose to be used in subsequent studies in Japanese population. And its design is fairly simple.
It basically uses two arms compared to oral dosing and IV dosing in Japanese population and coincidently treated Caucasian population. The renal study, we’ve previously summarized the results and as far as the implications to development, the statement that we made which is that there were no meaningful differences in the pharmacokinetics of omecamtiv mecarbil in patients for dialysis dependent meaning no renal function at all and match comparators that were -- had normal renal function that there are no differences between those two groups is the bottom line.
And what that means for the development program is that we don’t need to worry about dose adjusting omecamtiv mecarbil based on renal function. And in heart failure that’s relatively important because renal function can be impacted by the disease and also variable over the course of the disease.
And it was one of the reasons we selected omecamtiv mecarbil in the first place was because we didn’t think its PK will be impacted by renal function. This study in the small very select patient population confirms that.
Robert Blum
And just to follow up on I think epidemiologic studies indicate that over half of patients with heart failure also have compromised renal function, so it’s important thing to know and it’s an advantage we think for omecamtiv that we wouldn’t have to approach those patients differently.
Simos Simeonidis - Cowen & Company
That’s great. That is very helpful.
Thank you for taking all the questions.
Robert Blum
Thank you, Simos. Good talking to you.
Simos Simeonidis - Cowen & Company
Thanks.
Operator
Our next question comes from the line of Charles Duncan with Piper Jaffray.
Robert Blum
Hi Charles.
Unidentified Analyst
Hi guys. (Inaudible) Roy in for Charles.
Thanks for taking the question. Just a very quick one, most have been answered.
Have you guys disclosed is there any discontinuations from the escalation phase in COSMIC? Thank you.
Robert Blum
Discontinuations from the escalation phase in COSMIC.
Dr. Andrew Wolff
We haven’t really disclosed the details of that particular part of the trial.
Unidentified Analyst
Okay, good enough. Thank you.
Robert Blum
Sure, thanks.
Operator
Our next question comes from the line of Jason Butler with JMP Securities.
Robert Blum
Hi Jason.
Jason Butler - JMP Securities
Hey, Robert. Thanks for taking the question.
Just wanted to stay on the titration in COSMIC-HF and maybe look forward more to clinical practice and commercialization. How feasible is this kind of plasma directed titration going to be to incorporate into everyday clinical practice?
How do you see this playing out with the physicians?
Robert Blum
I am going to ask Andy to comment, both Andy and Fady as you know as practicing clinical cardiology I think will share with you why this is quite common for cardiovascular drugs.
Dr. Andrew Wolff
This is done all the time and sometimes you have a more biological readout by blood pressure or heart rate and you push the dose that way. But it’s not uncommon at all especially in cardiovascular medicines to measure plasma concentration and increase that way.
And I think once we're in clinical practice with this compound, there will be a point-of-care assay that will make this quite easy to do. So that it's not something where you have to send it off to a lab and in other state and wait days for your result, you'll have it essentially, immediately and can decide what you do next.
Dr. Fady Malik
Yeah. I'll just, I'll add I mean there are large classes of drugs that are -- I think the important thing to focus on is that a blood test is potentially required, blood tests are commonly used to titrate drugs; as Andy pointed out, not just on drug concentrations, but whether you check renal function and after you change the dose with an Ace inhibitor or cholesterol after you change the dose for (inaudible) or leave clotting simple.
So, cardiologists were used to taking blood test to monitor the effects of drug. I don't think it's really a difference to them whether that test is a biological board parameter or a drug concentration, they do both.
Jason Butler - JMP Securities
That's great. Thanks a lot for taking the question.
Operator
Our next question comes from the line of Paul Matteis with Leerink Swann.
Robert Blum
Hey Paul.
Paul Matteis - Leerink Swann
Hey, how are you Robert? Thanks for taking my question.
I was just wondering how many patients now you have of a valuable data for BENEFIT? Not the number that actually finished the trial thus far, but how many of you anticipate to be part of the primary efficacy analysis, because I know you said you have 711 enrolled and there are some excluded from the CRO debacle.
And then getting on to that, just kind of wondering, what that implies in terms of the powering of the study, because I know you're 80% power assumption was also predicated on both in enrollment assumption and a standard deviation assumption in the primary endpoint? Thanks.
Robert Blum
Yeah, so I will be able to answer, but maybe now with the precision that you might prefer, what I will say is, we over enrolled the study as you know not by a lot but by roughly 5% in connection with what had been a approximate 680 and we enrolled 711. With today’s press release, we announced that over 400 patients have completed treatment; the number is higher than that 400, but we haven’t been specific.
There are still patients on treatment and as we are expecting most of those patients to complete all of their treatment we are thinking that the last treatment period would potentially be this month that less patient last visit given that there is a seven day and 28 day follow-up after last treatment will be at the end of March. So in recognition of those parameters we do see data albeit as blinded and aggregate and we have a sense of standard deviation, we have a sense of early terminations I guess what I can say is we’re very comfortable that we have the statistical power we were intending in the design of this study, but I am not sure there is much more than that I can say unless Andy you tell me…
Dr. Andrew Wolff
If you don’t think you can say more than that I don’t think I can say more than that, but I would agree and what I would like to just remind everyone the study was originally powered to have 80% power to be able to detect a 1.18 point difference from placebo and the change from baseline to the end in the ALSFRS score and I will just reiterate what Robert said from everything we know and our best guess is because it’s still blind I think we are right on that.
Paul Matteis - Leerink Swann
Okay, great. That's very helpful.
And then just one more question about the 1.18 point difference, where exactly does that come from? I mean it’s the scale I think is the 36 point scale, so it seems like a relatively small difference.
Can you help us understand exactly what the clinical or practical implications to the 1.18 difference would be? And how you think that could be viewed by physicians that they did generate p-value below 0.05?
Dr. Andrew Wolff
So first of all, it’s actually 48 point scale. So that being said, the 1.18 is even a smaller percentage than you were suggesting.
But I think what it is more instructive is the way in which we understand the scoring system to behave. So as you probably know, patients go down about 20 per month on average and in fact in the recent EMPOWER trial (inaudible) they went down a little bit faster than that about 1.1 points per month.
So we would expect that on placebo patients who -- and patients who have a decrease overall of around three points from their baseline. So 1.18, I tend to do (inaudible).
But it’s probably around 35 or 40% improvement in that decline. When ALS specialists have been surveyed it what they thought would be meaningful in terms of a treatment effect on this endpoint, they always come out around 20% or 25%.
So it would actually be a much more substantial treatment effect than what they have said in the past they would find to be clinically meaningful. And then finally just to try to personalize what it would mean to save a point better than placebo, if you’ve ever taken the time to actually look at the individual [cravations] in each one of the domains, four is perfect function zero is no function at all.
But the key things are what that mean to be a three rather than a four or a two rather than a three. And I think if you look at the scale, you’ll find that there is not any place where you would tell yourself well I don’t care if I am three instead of a four, it doesn’t matter to me if I’m a two rather than a three.
Each one of those points slot is a very significant decrement in an area of critical importance to functional independence. So I am confident that with both ALS patients and their caregivers and their clinicians if we hit that there will be variable question about clinical relevance.
Dr. Fady Malik
I’ll add if we hit that it will be the first time that’s ever occurred that our dug has demonstrated a statistically relevant effect like that against the ALSFRS.
Robert
So there is a poster on our website, we can also send it to you, Paul that was presented back in 2011 by Cytokinetics at the International ALS/MND Meeting which traces the ALSFRS in its revision over 20 years and there are citations in that poster that refer back to the publications Andy is referring to regarding surveys of clinicians and what they think to be clinically meaningful.
Blum
So there is a poster on our website, we can also send it to you, Paul that was presented back in 2011 by Cytokinetics at the International ALS/MND Meeting which traces the ALSFRS in its revision over 20 years and there are citations in that poster that refer back to the publications Andy is referring to regarding surveys of clinicians and what they think to be clinically meaningful.
Paul Matteis - Leerink Swann
Yeah that sounds good, I’d love to see that. Thanks for the clarity.
I look forward to particularly AM, I’m sure we’ll see there. Thanks a lot.
Robert Blum
Looking forward to it.
Operator
And that seems to be our last question for today. I’ll now hand the call back over for closing comments.
Robert Blum
Okay. So, thank you to all the participants on our teleconference today.
Thank you for your continued support and your interest in Cytokinetics. We’re looking forward to what we hope maybe a very promising 2014.
We look forward to keeping you informed of our progress. And with that operator, we can now conclude the call.
Operator
Ladies and gentlemen, thank you for joining us today for our conference call. You may now disconnect.