Cytokinetics, Incorporated (CYTK) Q1 2016 Earnings Report, Transcript and Summary

Good afternoon and welcome, ladies and gentlemen, to the Cytokinetics First Quarter 2016 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. [Operator Instructions]. I will now turn the call over to Diane Weiser, Cytokinetics' Vice President of Corporate Communications and Investor Relations. Please go ahead.

Good afternoon, everyone, and thanks for joining us on the call today. Robert Blum, our President and Chief Executive Officer, will kick us off with highlights from the quarter. Then, Fady Malik, our EVP and Head of Research and Development, will provide an update on the clinical development program for omecamtiv mecarbil. Andy Wolff, our SVP and Chief Medical Officer, will then provide updates on tirasemtiv and the ongoing VITALITY-ALS Phase III clinical trial in patients with ALS; as well as see CY 5021, the Phase II clinical trial of CK-2127107, or CK-107, in patients with spinal muscular atrophy or SMA. Sharon Barbari, our EVP of Finance and Chief Financial Officer, will provide a financial overview for the quarter. And Robert will wrap things up with additional corporate updates before we open the call for questions. Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and future performance rather than historical facts, and constitute forward-looking statements for purposes of the Safe Harbor provision of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements may include statements relating to our financial results and guidance; our strategic initiatives, including Vision 2020; our plans for raising additional capital; our collaborations with Amgen and Astellas; our ability to achieve certain milestones and collect related milestone payments; our ability to collect royalty and other payments; our and our partners' research and development activities, including the initiation, conduct, design, enrollment, progress, continuation, completion, and results of clinical trials; the significance and utility of preclinical study in clinical trial results; and the properties and potential benefits of our drug candidates. 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 reports on Form 8-K. Copies of these documents may be obtained from the SEC or by visiting the investor relations section of our website. These forward-looking statements speak only as of today. You should not rely on them as representing our views in the future. We undertake no obligation to update these statements after this call. Now I will turn the call over to Robert.

Thank you, Diane, and thanks, everyone, for joining us on the call today. I'm pleased to tell you that we started 2016 strong. We made significant progress across the breadth of our muscle biology pipeline during the first quarter. In particular, we made important strides advancing the clinical program for omecamtiv mecarbil, and in collaboration with Amgen. We participated in a series of regulatory interactions regarding our potential plans for a Phase III program. The feedback we received was consistent; it was positive; and it lends support for our shared objectives for a potential Phase III outcomes trial. Based on the feedback we received from FDA and EMA and Health Canada, we are finalizing a protocol for a potential pivotal Phase III trial, as well as a proposed statistical plan and budget for the trial. We are awaiting a final decision from Amgen regarding a corporate commitment to proceed to Phase III with omecamtiv mecarbil. However, in the meantime, teams at Cytokinetics and Amgen are collaborating with the assumption that we'll initiate a Phase III trial and maintain timeline under our collaboration later this year. To be clear, while there are no guarantees, a decision to potentially move to Phase III with Amgen is nearing, and we're hopeful we can provide clarity during Q2. Fady will elaborate on other developments relating to omecamtiv mecarbil in a moment. Switching gears, as you'll hear more from Andy, enrollment in VITALITY-ALS is also on track. A number of ALS patients have been on therapy for more than six months. That's the longest duration of therapy of tirasemtiv since we began the clinical trials program. We are proceeding towards completion of enrollment in VITALITY-ALS, and we expect that patients will be moving to an open label extension trial in the second half of the year. During the quarter, we also continued our collaboration with key stakeholders in the ALS community on initiatives to improve the conduct, efficiency, and design of clinical trials evaluating new treatments for ALS, and to accelerate the regulatory review and approval of new medicines intended to improve the lives of patients with ALS, as well as their caregivers. In parallel with these clinical and regulatory initiatives, we also recently announced a collaboration with Origent Data Sciences. Origent is a company focused on patient-level predictive modeling for neurologic conditions, including ALS. The goal of the collaboration is to refine and prospectively validate an Origent computer model to predict disease progression in ALS, leveraging data from our clinical trials of tirasemtiv. This is an exciting collaboration for Cytokinetics and the ALS community. Because if the models are indeed validated, they may enable more nimble, cost-effective execution of ALS clinical trials, as well as potentially facilitate the development of therapies for patients. Regarding CK-107, enrollment continues in our Phase II clinical trial in patients with SMA. During the quarter, we also made progress with Astellas on plans to initiate a Phase II trial in patients with COPD. Andy will provide further details on CK-107 shortly. And, with that, let me now turn the call over to Fady so he can elaborate on our progress with omecamtiv mecarbil.

Thanks, Robert. We’ve had an extremely productive quarter regarding the development of omecamtiv mecarbil. Firstly, in collaboration with Amgen, we’ve participated in multiple regulatory meetings with FDA, EMA, and Health Canada, to further inform a potential Phase III development program. During the meetings, we had the opportunity to review data from COSMIC-HF as well as to get feedback on our proposed Phase III outcomes trial. We asked questions pertaining to patient inclusion and exclusion criteria, endpoint definitions, dosing strategies, and safety monitoring. Overall, we are pleased with both the written and verbal feedback from regulatory authority. We and Amgen are aligned on how to incorporate that feedback into a final protocol that informs a statistical analysis plan. Over many months, we have engaged in several work streams with Amgen involving clinical, biometric, safety, regulatory, and commercial counterparts, and we believe Cytokinetics end Amgen are aligned on what to do next. And as you heard from Robert, we expect a decision on omecamtiv mecarbil potentially proceeding to Phase III in the coming months. In the meantime, during the quarter we started a Phase II clinical trial in Japanese patients with heart failure due to reduced ejection fraction. Details are available on clinicaltrials.gov, but I will summarize the design. The ongoing clinical trial will evaluate approximately 80 patients with chronic stable heart failure due to reduced ejection fraction over 16 weeks, randomized 1 to 1 to 1 to 1 to receive either placebo or omecamtiv mecarbil twice-daily at 25 milligrams, 37.5 milligrams, or 50 milligrams. Patients randomized to 37.5 milligrams or 50 milligrams it will be up-titrated from an initial dose level of 25 milligrams twice daily, using a PK-guided dose titration strategy similar to what was employed in the COSMIC-HF trial. The trial is designed to assess the pharmacokinetic safety and tolerability of omecamtiv mecarbil in Japanese patients with heart failure due to reduced ejection fraction. And in addition, the trial will measure changes from baseline and systolic ejection time measured at week 16. Finally, during the quarter we worked closely with Amgen through our joint development committee and subcommittees on clinical operations and manufacturing activities to ensure we are on timeline to potentially start a Phase III trial later this year. Now I’ll turn it over to Andy to provide an update on our skeletal muscle programs.

Thanks Fady. I’ll start with an update on VITALITY-ALS, our Phase III clinical trial which, as you know, is designed to assess the effects of tirasemtiv versus placebo on slow vital capacity, or SVC, and other measures of skeletal muscle strength in patients with ALS. During the quarter, we focused on activating our European clinical trial sites and continued patient enrollment. We now have over 350 patients enrolled toward our objective of enrolling approximately 600 patients. In addition, we continue to see that the longer open-label phase and slower dose titration among patients randomized to the three different target dose levels of tirasemtiv in VITALITY-ALS are reducing post-randomization dropouts compared to what we saw in BENEFIT-ALS. As Robert mentioned, we remain on track to complete enrollment in the first half of 2016, with data anticipated in the second half of 2017. Also I’m pleased to report that the data monitoring committee for VITALITY-ALS recently held its first meeting. The committee reviewed unblinded safety and efficacy data, and recommended continuing the trial without any proposed changes to the protocol. In addition, we are working with investigators and regulatory authorities to finalize the trial design and protocol for an open-label extension trial that will enroll patients who have completed VITALITY-ALS, with the first among them to enter this open-label extension trial in the fourth quarter of this year. Finally, I am proud also to report that several of us at Cytokinetics have been engaging with research, clinical, and advocacy groups focused on musculoskeletal diseases. We recently participated in the Muscular Dystrophy Association’s National Clinical Conferences and presented our analyses of SVC in patients from three separate sources one, the placebo data from our Phase IIb study, BENEFIT-ALS, two, the placebo data from the Phase III study of study of dexpramipexole in ALS, known as EMPOWER, and three, the open-access PRO-ACT database. You may recall that the analyses of these three data sources in combination demonstrated that the reduction in the rate of decline in SVC in patients from the other two data sources was essentially identical to what we observed in BENEFIT-ALS, and was linear for over a year of observation. Additionally, analyses of the EMPOWER data set showed that patients with a slower rate of decline in SVC have a meaningful reduction in the risk of important clinical events, including the risk of a decline in any one of the three respiratory questions of the ALSFRSr or death, the risk of the first occurrence of respiratory insufficiency, or death; and the risk of the first occurrence of tracheostomy or death, providing further rationale for the design of VITALITY-ALS. As Robert mentioned, we also continued our collaboration with the ALS Association and other leaders in the ALS community participating in several meetings to advance both the clinical trial guidelines and FDA guidance initiatives. These are two priority projects that stakeholders in the ALS community are leading with participation from clinicians, researchers, industry representatives and a former FDA Advisory Committee members. These projects are focused on aligning the community on meaningful clinical trial endpoints in ALS, accelerating the conduct of clinical trials in ALS, and facilitating faster approvals of new medicines for people living with ALS. As you know, we are committed to do everything we can at Cytokinetics to support these activities. And we are proud to be working alongside such dedicated professionals for these initiatives. Turning to the development of CK-107 with our partner Astellas, our Phase II clinical trial in patients with FMA, CY 5021 is progressing as we continue to activate sites throughout the United States and enroll patients. The second Phase II trial, which will study CK-107 in patients with COPD, is expected to be underway in the second quarter. As a reminder, the goal of this trial, to be conducted by Astellas, is to evaluate the potential of CK-107 to increase measures of exercise performance and time to muscle fatigue in patients with COPD. The rationale for studying CK-107 in patients with COPD is that these patients experience significant metabolic abnormalities and weakness in their limb muscles. In fact, exercise intolerance in COPD patients has been reported to be more related to their limb muscle dysfunctions than to their respiratory insufficiencies. In addition, a switch from slow to fast fiber predominance in the limb muscles in patients with COPD works to the advantage of CK-107 which, of course, is selected for fast skeletal muscle fibers. Because CK-107 has acute effect to increase force production and to reduce fatigueability in fast skeletal muscles, it may improve exercise tolerance in patients with COPD. We'll have more to say about the trial design soon. With that, I'll now turn the call over to Sharon for an update on our financials.

Thanks Andy. As our press release contains detailed financial results for the first quarter of 2016, I'll refer you to that public statement for the details of our P&L and balance sheet. We've ended the first quarter with approximately 108.6 million in cash, cash equivalents, and investments, which represents 16 to 18 months of going-forward net cash burn based on our 2016 revenue and expense guidance. Revenues for the first quarter of 2016 were $8.4 million compared to $4.4 million during the same period in 2015. Revenues for the first quarter of 2016 included $4 million of license revenues, $3.7 million of research and development revenues from our collaboration with Astellas, $0.6 million in research and development revenues from our collaboration with Amgen, and $0.2 million in research and development revenues from our collaboration with ALSA. Revenues for the same period in 2015 included $1.6 million of license revenues and $2.1 million of research and development revenues from our collaboration with Astellas, and 0.7 million of research and development revenues from our collaboration with Amgen. Our first quarter 2016 R&D expenditures totaled $13.5 million. From a program perspective, for the first quarter approximately 82% of our R&D expenses were attributable to our skeletal muscle contractility research and development activities. These include both expenses associated with tirasemtiv and CK-107; and 13% to our cardiac muscle contractility activities; and 5% to our other research activities. Lastly, I'd like to provide some words about our priorities on raising capital. Our first priority is to pursue non-dilutive forms of capital such as business development initiatives, which may include pursuing a partnership for tirasemtiv outside of North America and Europe, as well as the monetization of our option to buy up the royalty on omecamtiv mecarbil. We also anticipate the possibility of earning between $25 million to $50 million in milestones during 2016 and 2017. As such, we are not expecting to raise equity capital at the current stock price. Instead, we'll consider that possibility only after we have clarity on the meaningful R&D and business development progress this year. With that, I'll now turn the call back over to Robert.

Thank you, Sharon. So as you've heard, we had a productive first quarter and we are moving full-steam ahead as we execute against our Vision 2020 roadmap. I'm really pleased with the regulatory interactions we've had on the omecamtiv mecarbil front. And I want to add that the collaboration between Amgen and Cytokinetics teams has been equally impressive. Alongside these activities, at the recent American College of Cardiology meetings, we were reminded of the urgent need to reduce heart failure hospitalizations and mortality in an increasing number of heart failure patients. We strongly believe that novel mechanism drug candidates like omecamtiv mecarbil have the potential to enhance the standard of care in heart failure. It's also an exciting time for our two skeletal muscle activators: tirasemtiv that we are developing for the potential treatment of ALS, and CK-107 that we are developing in collaboration with Astellas. Both drug candidates represent potentially meaningful advances in the treatment of severe diseases of impaired neuromuscular function, ALS and SMA, respectively. Both offer meaningful hope to patients in desperate need. I'm also very proud of the work our team is doing in concert with advocacy initiatives to publish updated guidelines for clinical trials in patients with ALS, and regulatory guidance for the development of new medicines for people with ALS. Given our long-standing relationships with the ALS community, we are in a solid position as an industry leader to lend our support, expertise, and voice on behalf of the patients we are so committed to serving. And finally, we are looking forward to participating in education and awareness-building activities during ALS Awareness Month in May. We are excited to kick off the month in collaboration with the ALS Association, people living with ALS and their families, with a celebration as we ring the closing bell at NASDAQ headquarters in New York, next week, on May 2. We look forward to this especially symbolic way to recognize the valiant actions being taken by the ALS community, as well as the promise of potential new medicines. We also look forward to Astellas initiating a second Phase II trial of CK-107 in patients with COPD. Alongside that progress, I'm also pleased to share that we and Astellas have recently made a decision to move another next-generation skeletal muscle activator into IND-enabling studies. We anticipate achieving that milestone in the second quarter. With that milestone, we will have three skeletal muscle activators as well as a cardiac muscle activator advancing in development, further underscoring our commitment and leadership in muscle biology. With that, let me now recap our expected milestones, this quarter and for the remainder of the year. For omecamtiv mecarbil, we expect to make a decision regarding potential advancement to Phase III in the coming months. For tirasemtiv, we expect to complete enrollment of VITALITY-ALS in the first half of 2016. For CK-107, we expect to complete enrollment of CY 5021, the Phase II clinical trial in patients with SMA, during the second half of 2016. And we also expect Astellas will initiate a Phase II clinical trial of CK-107, in patients with COPD, in the first half of 2016. For preclinical research, we expect to continue research activities under our joint research program with Amgen, directed to the discovery of next-generation cardiac muscle activators; and also under our joint research program with Astellas, directed to the discovery of next generation skeletal muscle activators. Under our collaborations, we expect to advance potentially two next-generation compounds into preclinical development in 2016. And operator, with that, we can now move the call to questions.

[Operator Instructions] And our first question comes from the line of James Butler with JMP Securities.

Just starting off [indiscernible] I know you gave some useful color there on the focus for the regulatory meetings, but maybe just thinking about the historical context. Is there anything that you are thinking about this program now that would differ meaningfully from historical heart failure programs?

It's a good question. Maybe I'll kick off and ask Andy and Fady, also, to chip in. I think the answer is no. So, with the first quarter, we had quite a number of regulatory interactions, both in person and through written correspondence, and I mentioned in my prepared remarks, across the globe, each of those geographies. And I think the bottom-line is that what we received was all supportive of what we hope to be doing in Phase III, both in terms of what would be required to demonstrate efficacy and safety and what would be required, but also not required, in order to make this an affordable, practical, and meaningful clinical trial. So we’ve talked in the past about what types of clinical studies have been done in this area. And we’ve kind of bookended what we think is reasonable somewhere between what Novartis did with its ENTRESTO in PARADIGM-HF and what other studies, and what I think what we are looking at is quite similar. But, however, underscoring we’ve also talked about we’re looking at patients that may be deemed at higher risk of death and readmission and, therefore, that may underscore a more urgent opportunity to intervene. I don’t know, Fady for Andy, if you have anything further you want to add to that.

I think the main thing is that at a high level, it is very similar to what you may have seen in the past. But there are unique features of the trial that we’ll be executing that are more, maybe some people will consider details, but they are important details in terms of the way the patient population is defined and the way the endpoints are defined.

That's a very good point. We are doing this now in a more modern age where we’ve learned from other studies in terms of how best to define inclusion and exclusion criteria how to be very, very clear about what we mean by some of these endpoints that can be, therefore, deemed more responsive to some of the reimbursement and payor concerns. Those are all coming into play as we think about a Phase III protocol design.

Okay. Great, helpful. And then just thinking about the safety side, based on or where you sit now, are you anticipating any specific monitoring or sub-study focus on troponin?

No.

So the answer to that is no, we are not. So the interactions we’ve had with regulatory authorities have been throughout the quarter, but also very, very recently. And in that way, we are still synthesizing some of the feedback we got and discussing that with Amgen. But I think the bottom line is we are pretty optimistic that going forward, the kinds of things we might have to do from a safety monitoring standpoint are affordable and practical, and would not be, therefore, required and burdensome monitoring and adjudication and those kinds of things.

Great. And then just one quick question on the financials. Last quarter, or the fourth-quarter earnings call, you guided that the cash, including the $15 million from the growth loan, would get you through to roughly the end of 2017. Is that still the right way to think about the cash runway?

So, the update for us now is it’s between 16 and 18 months of going-forward cash, so that takes you into 2017. It doesn't get you to the end of 2017.

Okay, great. Thanks for taking my questions.

You’re welcome.

Your next question is from the line of Charles Duncan with Piper Jaffray.

This is Sarah on for Charles.

Hi, Sarah. How are you?

Hi, great. Thanks, can you talk a little bit about how patient enrollment and investigator interest is going for the SMA trial?

Absolutely. Maybe I’ll start, and then turn it over to Andy to comment. So, keeping in mind that you do these studies in stages, we focus to U.S. and Canada initially and more recently to Europe, I’m sorry, you said SMA. I apologize. Let me mention that this is a study that’s going to be in U.S. only and, as such, we have been rolling out the study and activating centers throughout the U.S. And, with that, maybe I’ll turn it over to Andy to comment on how that’s going.

I think we’ve had a lot of evidence of high investigator enthusiasm and a lot of patient interest. I will say that there have been more operational barriers to getting some of our sites up and running. But once they get up and running, I expect that enrollment will proceed apace.

To elaborate, what we’re finding is working with the SMA community, some of the things that we found to be already institutionalized in the conduct of ALS clinical trials is not always evident and available in all centers that perform clinical trials in SMA. So some of that we’ve had to help them build; for instance, equipment and other things. That’s all happening. And therefore, I think as we get through some of those initial startup issues, it should enroll pretty well. What’s interesting about the trial is that when we do activate these centers they tell us that there are no other competitive clinical trials enrolling patients, adolescents, and adults, type two, three, and four. And, therefore, they've got many more patients than we would find are required for us to complete this clinical trial.

Okay, thanks. And then just one other one. I know you had a poster at AAM with some of the EMPOWER data. Anything new to say there, or any other data at the meeting you’d call out as relevant to the VITALITY program?

What I'll mention is that we continued to analyze both the EMPOWER data sets that we received from Knupp [ph], but also other data sets. And with that, maybe I'll ask Andy to speak to some of the things we are doing, and where that may lead us.

I don't think that there is a whole lot new that we are going to be able to talk about from the data that we've analyzed so far. But as some of these data sets continue to accumulate, there may be additional analyses, just over longer periods of time.

Yes I think that's true. We are looking longitudinally at these data sets. And we, as you know, have presented some of the data already that underscore how predictive slow vital capacity is for those end points downstream, for instance, those that are secondary endpoints in the VITALITY-ALS trial, we think that slowing the decline of SVC could be quite relevant to extending the time to some of those other clinical interventions. As a result, we are talking to academics and others about what are the other data sets, longitudinal data sets, that could be useful as we contemplate what will be the comparators as we proceed towards an open-label extension? So that's something that's still very much a work in process. And over time, we'll be able to talk more and more about the things we might be doing there. The collaboration we announced with Origent Data Sciences is one such example of the kinds of very innovative things we are doing in connection with the broader ALS community along that dimension.

Your next question comes from the line of Vernon Bernardino with FBR and Company.

I'm glad to have you all here on the call. One thing I was wondering about the COSMIC-HF results, and from our -- from discussions with investors, they are seemingly hungry for more data, especially since we have quite a bit of data, and the data published from PARADIGM-HF. You know the Phase III results from -- for ENTRESTO. Just wondering, what would be the timing or venue for publication of the full COSMIC results? And perhaps if you could let us know what kind of other types of details may be gleaned from those results that could help us look at what kind of Phase III study you may be designing.

Good question. So we are continuing to analyze results from COSMIC, and I think we are going to be able to address your interest, as well as those of many others who asked that same question. I'll turn it over to Fady to talk in general about some of the things we are doing and how that may roll out.

I think the answer to the first part of your question in terms of a manuscript that that certainly has been prepared, and is going through the process of review and so forth. So I can't really comment further on that. But the -- there are upcoming meetings where we've either have presentations accepted. So at the European Heart Failure Association meeting, we do have a presentation accepted that will provide more details on when we announce that abstract, but also looking forward to the HFSA and AHA meetings. And you can imagine, PARADIGM was an 8,000-patient trial with a lot of data obviously. Even though COSMIC was quite a successful trial, it doesn't have the same data set that PARADIGM has. But we have a number of analyses with regards to the ECHO data we've acquired; some symptom data, time course data, PK data, things like that, that you will start to see emerge over time.

Does that answer your question, Vernon?

Yes perfectly, actually. From the PARADIGM studies, what may have you gleaned from the results there that are helping you with the Phase III design for omecamtiv?

We are learning a lot, not only from the PARADIGM study but also from what we are hearing from people using ENTRESTO now as it's available commercially. And there was a lot of talk about ENTRESTO at the recent ACC meetings. It's really apples and oranges when you talk about omecamtiv and ENTRESTO, in large part because they both address important opportunities to make a dent in heart failure death and readmissions, Omecamtiv as a potential investigational medicine for improving cardiac performance and doing so safely. But you can learn a lot about the patient population and what determines risk, who is more likely to be subject to mortality risk and readmission risk? But also, what are the kinds of things that render a study practical to conduct? And upon the results, how might that be viewed by payors as well as clinicians in terms of adopting a new therapy? To be clear, our goal is to establish omecamtiv mecarbil as part of the foundational standard of care. It would not, therefore, need to be replacing something else; but, rather, included amongst the other medicines that would be foundational. And in that regard, we are also not talking about something that would be step care, but rather part of the standard of care. So, I don't know if Andy, or you or Fady, have anything further to add. I think we are being really good students about what the heart failure community is doing in connection with the Novartis PARADIGM-HF data. That was a very impressive study and the results are meaningful. And the drug is an important add. But it is addressing a different part of the equation for heart failure, and competing with generic enalapril. And in that regard, we see it is a very different situation than the one we may be confronting with results from a potential Phase III trial of omecamtiv.

I quite agree. Definitely, the ejection fraction appears to be, at least from Phase II comparison to PARADIGM, is apples to oranges in omecamtiv's failure. Thanks for taking my question.

And our next question comes from the line of Chad Messer with Needham.

This is Esther on for Chad. Thanks for taking my questions. First, on Omecamtiv, if you presented COSMIC-HF data, can we assume that you won't be doing a Phase III study in acute heart failure?

I wouldn't make that assumption, although you can assume that that's not the priority in terms of what would be the next trial. Our goal is to move into Phase III with omecamtiv mecarbil hopefully by the end of this year, in a study that would be evaluating the oral form of omecamtiv mecarbil in a PK-guided dose titration strategy like we studied in COSMIC-HF and for patients that would be both hospitalized and outpatient, and where those would be included in one pivotal registration study. So, in that trial, we are not contemplating the intravenous form of omecamtiv mecarbil. But we and Amgen are still talking about how that intravenous form of the compound may still also figure into a longer-term program, and that's something that is still fluid.

Okay, thanks. That was helpful. And one more thing, on tirasemtiv, you mentioned a DMC meeting. How many more do you have throughout the trial, and will you be announcing those? And will we be getting more details then?

There is at least one more planned, and probably another one after that. And they tend to be about four months apart.

What we're doing, these are not formal interim analyses, if that was part of your question.

Yes.

These are with the data monitoring committee is chartered to look at safety and other things too. And we of course remain blinded to the data that they are seeing unblinded. But were there anything that was a pause for concern, that would certainly bring it to our attention. And we would have to take that under advisement.

And our next question comes from line of Ritu Baral, Cowen.

Thanks for taking the question. Can you confirm that there are no additional regulatory interactions needed with either US or Europe for omecamtiv as a gating factor to starting Phase III?

It's a very good question. I'm not sure I can answer it to your total satisfaction. What I can say is that we think we have all the regulatory feedback we need in order to be able to lock down on a protocol and statistical plan and move forward, staying on timeline for a potential Phase III trial to begin later this year. I will say that there is always regulatory interactions that are occurring, whether it's minuting certain meetings or otherwise, going back and getting a review of a statistical plan, or other kinds of ongoing communications. So I think your question is probably motivated by, tell me if I'm wrong, do we have what we think we need in order to make a final decision? And I think the answer to that is yes, albeit some of these meetings were so recent that we still have to fully digest all of what we heard in order to incorporate that in a final protocol and plan. But so far, we don't think we need to have any other interactions in order to make that decision.

Got it. But you are leaving the door open for potentially having additional interactions before you actually get IRB approvals for any set protocols.

The door never closes. The door is always open while we are having these planning meetings, and as even a study is being conducted. But we think we have all we need in order to make the decision.

Got it. And then can you just talk a little but about the 37.5 37.5 milligram arm in the Japanese study that you mentioned? That’s going to be another PK/PD potentially titrated arm. Other any particular reasons for that arm in this study, and any that could translate to anything meaningful in the Phase III?

That was a very good pickup on your part, and thank you for asking. Firstly I should say that the fact that that study has been started under our collaboration with Amgen should hopefully underscore that we are all leaning forward towards the plans to potentially begin a Phase III program later this year. I’ll ask Fady to comment on the inclusion of the 37.5 milligram strength.

I mean, I think the 37.5 milligram strength affords us the opportunity to fine-tune, if you will, the up-titration strategy from 25 milligrams to 50 milligrams. Some patients you would not like to make that large a jump. You would like an intermediate dose. Some of the COSMIC data suggested that we could up-titrate more patients from 25 milligrams if we had an intermediate dose. And then, in the Japanese population, some of the features of that population being generally smaller and lighter and so forth, having a little more fine-tuning of dose, dosing strategy we thought would be advantageous.

Got it, understood. And do you think that data from that arm would be useful in designing the final Phase III protocol?

Not necessarily. Because I think we have a wealth of data and very strong modeling that suggests how that dose can be used. But obviously the data from Japan would be supportive of the modeling that we've already conducted.

And I think it probably goes without saying that we believe that having data from the Phase II study in Japan enables the inclusion of Japan to be included in a potential global Phase III program.

Got it. Last question is on tirasemtiv in ALS. You mentioned the development of an open-label extension protocol. What might that protocol look like? And what sort of data might that generate, not just for a filing, but also pharmacoeconomic data for potential payor negotiations?

Good question. So firstly I’ll underscore that this is still very much a subject of some ongoing discussion here at Cytokinetics, and also with regulatory authorities. Maybe I’ll turn it over to Fady to comment about how we are approaching that right now; and, Andy, if there’s anything further you want to add. But keeping in mind that the first patient was enrolled in VITALITY-ALS last year in the fourth quarter, this is all getting locked down so that the first patient could be considering moving into the open-label extension later this year. So we still have a little bit of time, but not a whole lot of time, in order to be able to lock this down sufficiently for IRB and efficacy committees. But Fady, maybe you want to kick off.

I think the design is relatively simple. We want to be able to provide patients a way of transitioning to tirasemtiv once VITALITY is completed, and for the placebo patients to transition to tirasemtiv as well. So the study design would be basically focused on those patients who participated in VITALITY, and then continuing to monitor them with regards to some of the endpoints that we have articulated in VITALITY, to give a longer-range safety data as well as potentially some efficacy data going out. So that protocol is still in the process of being developed. And there are always the caveats of looking at open-label data, so I don’t want to make too much out of it at this point. But it’s primarily to look at long-term safety will be the primary objective. I think that captures it.

What I will say about it is there’s been a lot of talk about open-label studies recently. And in this particular case, we should hopefully have lots of patients that are rolling in, some of whom will have been on tirasemtiv for a year, others of whom will be on placebo for a year. And there’s an opportunity to look at those two groups differently. Is there some change in slope that comes with placebo patients rolling into the tirasemtiv arm? What do we see here in terms of comparatives of those two arms? And then also, as Fady underscored, certainly we want to know about longer-term safety. It won’t be as intensively monitored as the randomized, double-blind trial. But certainly it can provide supplemental data to what will be our primary registration strategy, which may hopefully arise out of the ongoing trial.

Understood. Thanks for taking all the questions.

And we have no further questions in queue at this time, and I'd like to turn the call back over to our presenters.

Thank you operator, and thank you to everyone listening in on the call today. Certainly there's a lot going on at Cytokinetics as we have closed Q1 and are peering into Q2. And through the remainder of the year, we are very optimistic, we are hopeful, we're pleased with progress. And we look forward to keeping you abreast of that progress through the remainder of the year. We invite any of your questions, if you want to reach out to us, and we welcome those sorts of involvements. Operator, with that, we can now conclude the call.

Thank you for your participation. This does conclude today's conference call, and you may now disconnect.