Cytokinetics Inc

NASDAQ:CYTK

Earnings Call Transcript 2021-Q3

[Operator]

Good afternoon and welcome ladies and gentlemen to Cytokinetics Third Quarter 2021 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, we will allow for up to two questions per participant.

I will now turn the call over to Joanna Siegall, Cytokinetics' Senior Manager of Corporate Communications and Investor Relations. Please go ahead.

[Joanna Siegall]

Good afternoon and thanks for joining us on the call today. Robert Blum, our President and Chief Executive Officer, will begin with an overview of the quarter and recent developments, then Fady Malik, our EVP of Research and Development, will provide an update on omecamtiv mecarbil including recently presented an additional analyses from GALACTIC-HF as well as an update on our ongoing next steps with the FDA.

Next, Stuart Kupfer our SVP and Chief Medical Officer, will provide an update on our development program for aficamten by recapping the results from cohorts one and two of REDWOOD-HCM elaborating on continuing activities and REDWOOD-HCM and reviewing the design of SEQUOIA-HCM our planned Phase 3 clinical trial of aficamten and patients with obstructive HCM.

He will also speak to initial progress in COURAGE-ALS our ongoing Phase 3 clinical trial of reldesemtiv in patients with ALS. Then, Andrew Callos, our EVP and Chief Commercial Officer will discuss our go-to-market strategy. For omecamtiv mecarbil, and our cardiovascular franchise development plans for the commercialization of aficamten.

Robert Wong, our VP and Chief Accounting Officer, will provide a financial overview for the past quarter and Ching Jaw our SVP and Chief Financial Officer, will discuss strategic planning our financial outlook and corporate development strategies before Robert Blum will provide concluding thoughts and expected key milestones for the remainder of 2021.

Please note that portions of the following discussion including our responses to questions contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. 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 material from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our third quarter 2021 financial results filed on Form 8-K today. We undertake no obligation to update any forward-looking statements after this call.

Now I will turn the call over to Robert.

[Robert Blum, President and CEO]

Thank you, Joanna. And thanks again to everyone for joining us on the call today.

We had a very productive third quarter marked by meaningful progress across all of our later stage programs. Most notably, our sharing positive results from our Phase II clinical trial REDWOOD-HCM which demonstrated the efficacy and the safety of Aficamten our next-in-class drug candidate in patients with obstructive hypertrophic cardiomyopathy.

As we've said, these results met our high expectations for this trial and we received positive feedback from the physician community. Stuart will elaborate more on these results in a moment. During the third quarter, we are also pleased to complete enrollment in Cohort 3 of REDWOOD-HCM, which as you'll recall enrolled patients also on disopyramide a medication, often prescribed to patients with more severe HCM.

We expect to share the results from Cohort 3 in the first quarter of 2022. Following previous interactions with FDA from which we receive feedback on our planned trial design. We continue to advance activities in preparation for SEQUOIA-HCM the Phase 3 clinical trial of our Aficamten in patients with obstructive HCM as we recently presented in a Stuart will elaborate. This trial was designed to potentially demonstrate a significant improvement in exercise capacity and evaluate safety in a broad population of patients with symptomatic obstructive HCM.

We're working with sites around the world, including many who participated in REDWOOD-HCM who are enthusiastic about also participating in SEQUOIA-HCM and we look forward to starting this trial soon. Moving now to our heart failure program, we continued activity supportive of our plans to submit an NDA for omecamtiv mecarbil, and we remain on track towards our goal of submission in this fourth quarter of this year Fady will have more to say about that in a moment.

Additionally, as outlined in our recent Analyst and Investor Day, we're making significant progress in refining and executing our go-to-market strategies for omecamtiv mecarbil across several work streams that Andrew will elaborate on in a moment. These commercial readiness activities represent a tremendous scope of work from our growing commercial organization and supporting our go-to-market strategies as well as our intention to build a cardiovascular business franchise by leveraging common denominators and synergies across our business inclusive of our plans both for the potential launch of omecamtiv mecarbil and a potential future launch of Aficamten.

As Fady will discuss in the third quarter, we presented additional results from GALACTIC-HF highlighted by an analysis of black patients enrolled in GALACTIC-HF showing that the treatment effect of omecamtiv mecarbil in black patients was consistent with the treatment effect in the overall population and also similar to the effect observed in white patients in the trial. This finding is important. Due to the fact that black patients tend to have a higher risk of heart failure and often have worse outcomes.

Additionally, an analysis of the severe heart failure subgroup in GALACTIC-HF was published in the Journal of the American Medical Association Cardiology illuminating a larger treatment effect when compared to the overall population of patients studied. This important manuscript was accompanied by an editorial suggesting recognition of a new classification for a group of severe heart failure patients who still prevailing high unmet need represents an increasing patient population with heart failure that contributes more and more to the clinical and the economic burden of this disease.

Finally, we were pleased in the most recent quarter to begin enrolling patients encouraged ALS our Phase 3 clinical trial of reldesemtiv in patients with ALS. The results from the Phase 2 clinical trial FORTITUDE-ALS were deemed compelling by investigators and physicians who treat patients with ALS and our advancement to Phase 3 is an exciting and important step forward for this program as is aligned with our dedication to the ALS communities.

The ALS communities are more assertively seeking new medicines and the FDA and public policymakers seem to be increasingly responding to these louder calls for action. It is an incredibly important time for our company. We're building our teams and capabilities as we are now on the precipice of a powerful transformation from an R&D company into one that is also a commercial organization. It has always been our strategic vision to ourselves deliver on the promise of our science and we're closer now to that than ever before.

These are exciting times to be sure, but how we execute on those plans will matter. Robert will speak to our current financials and Ching will comment on our progress and prospects in continuation of our long-standing practice to diversify our access to capital through both partnering and structured financings as is informed by annual strategic planning.

With that, I'll turn the call over now to Fady to elaborate on developments related to omecamtiv mecarbil.

[Fady Malik, EVP of R&D]

Thanks, Robert.

As you mentioned, results from additional analyses of GALACTIC-HF presented during the quarter at the Heart Failure Society of America Annual Scientific Meeting reinforce that outcomes with omecamtiv mecarbil in black patients enrolled in GALACTIC-HF were consistent with the overall population and like the overall study results were driven primarily by a reduction heart failure hospitalizations and heart failure events.

The treatment effect in black patients was also similar compared to white patients GALACTIC-HF enrolled the most black patients among recent heart failure trials and of patients enrolled in the U.S., 29% were black, which is important, not only because Black patients have historically been underrepresented in clinical research, but also because they have a higher risk of heart failure and suffered worse outcomes.

This disparity and outcomes is complex, but it's encouraging to see that the potential benefit of treatment with omecamtiv mecarbil remains consistent in this group. Expanding on the theme of higher risk patients with heart failure three weeks ago a manuscript entitled assessment of omecamtiv mecarbil for the treatment of patients with severe heart failure was published in JAMA Cardiology.

Following on the heels of the initial data presentation in late June at Heart Failure 2021 and International Congress of the European Society of Cardiology the analysis by Dr Michael Felker and co-authors looked at the treatment effect of omecamtiv mecarbil. On the primary composite endpoint in patients from GALACTIC-HF classified as having severe heart failure based on modified criteria from the heart failure association of the European Society of Cardiology advanced heart failure physician statement.

Patients in this subgroup had NYHA Class III, IV symptoms EFs of less than or equal to 30% and hospitalization for heart failure within the prior six months. Approximately 30% of patients enrolled in GALACTIC-HF met these criteria and had a win rate through approximately twice those patients without severe heart failure. In this post-hoc analysis those with severe heart failure who received omecamtiv mecarbil experienced a significant treatment benefit for the primary endpoint with a hazard ratio of 0.8-0, whereas patients without severe heart failure had no significant treatment benefit with the hazard ratio of 0.99.

The results for cardiovascular death or qualitatively similar patients with heart failure that was severe experienced a trend towards treatment benefit from omecamtiv mecarbil while patients without severe heart failure did not. Omecamtiv mecarbil was equally well tolerated in patients with and without severe heart failure with no significant changes in blood pressure, renal function or potassium compared to placebo.

Accompanying this manuscript was an editorial authored by Dr Yancey Adrian Hernandez and Greg [indiscernible] titled identifying treatments for Stage C2 heart failure in which stage C2 is proposed as a new addition to the currently defined four 4 stages of heart failure. A through D and as would encapsulate these severe heart failure patients who may be a priority for additional impactful therapy. This high unmet need was a focus of our panel discussion at our recent Analyst and Investor Day.

Despite the availability and adherence to guidelines directed medical therapy or GDMT patients with worsening heart failure is still have high event rate. As we heard from doctors Alanna Morris and Tarek Ahmad who are both specialists in heart failure at major academic medical centers, it can be a challenge to get patients on GDMT because many are unable to tolerate through medications due to side effects.

With omecamtiv mecarbil with a potential add-on therapy with a novel mechanism of action that could be used as a complement to and alongside existing therapies without increasing cardiac mortality. Physician feedback has indicated that their view is positive towards the clinical utility of omecamtiv mecarbil as an additional therapeutic option with a good safety and tolerability profile and that there is a clear need for therapy like omecamtiv mecarbil to fit into regular practice.

Moving on, we completed enrollment in METEORIC-HF at the end of the second quarter and we continued conduct of the trial in the third quarter. This trial will provide insight as to how omecamtiv mecarbil could benefit, another key aspect of improving the lives of people with heart failure, which is to improve their exercise capacity. The common concern of patients with heart failure is their inability or difficulty with everyday task, but current treatments have little to no impact on exercise capacity and stamina.

We expect to complete METEORIC-HF this year and look forward to reporting results in early 2022. Also in the third quarter, we conducted meetings with FDA to support the preparation and submission of our new drug application or NDA for omecamtiv mecarbil. We completed a pre-NDA meeting which confirmed the suitability for submission of content related to chemistry manufacturing and control clinical pharmacology and the non-clinical program as well as the format of data sets the integrated summary of safety and other components of the NDA.

We also had a meeting with FDA to discuss the assay for plasma concentrations of omecamtiv mecarbil in terms of its potential need to guide dosing as well as the regulatory pathway for its implementation. In sum, these meetings provided guidance to some of the content of our NDA, which is on track for submission this quarter. As we approach our goal of submitting our NDA to the FDA. We also continued simultaneously growing the scope and reach of our medical affairs activities by hiring therapeutic area lead medical directors and deploying additional field-based medical sciences.

We have developed a compliant framework for an investigator-sponsored studies program, which is a timely as we've started to receive requests for potential collaborative activities. The team is working on finalizing their scientific platform. For omecamtiv mecarbil, which forms the basis for communications with medical professionals, we also initiated vendor selection for the development of a medical contact center to be prepared to respond to request for medical information or direct questions to the proper personnel for response,

With that, I'll turn the call over to Stuart to provide an update on aficamten and reldesemtiv.

[Stuart Kupfer, SVP and Chief Medical Officer]

Thanks, Fady.

During the third quarter, in September we presented the full results from Cohorts 1 and 2 of REDWOOD-HCM the Phase 2 clinical trial of aficamten at the Heart Failure Society of America Annual Scientific Meeting in Denver. As we've mentioned, the results were positive and support our advancing aficamten to Phase 3, which I'll touch on in a moment.

As we previously shared in REDWOOD-HCM treatment with aficamten for 10 weeks resulted in statistically significant reductions from baseline, compared to placebo in the average resting left ventricular outflow tract for LVOT pressure gradient and the average post-valsalva at LVOT gradient. The majority of patients treated with aficamten 79% in Cohort 1 and 93% in Cohort 2 achieved the target goal of treatment defined as resting gradient less than 30 millimeters of mercury and post valsalva gradient less than 50 millimeters of mercury at week 10 compared to 8% for placebo.

These reductions in LVOT gradient were dose-dependent with patients achieving greater reductions of LVOT gradient with increasing doses of aficamten. Reductions in LVOT gradient occurred within two weeks of initiating treatment were maximized within two to six weeks of the start of dose titration and were sustained until the end of treatment at 10 weeks. Reversibility of LVOT gradient and they'll be ejection fraction reductions were observed after discontinuation of aficamten with levels returning to baseline at the end of the two-week washout period.

Patients also experienced statistically significant reductions in NT pro BNP and treatment with aficamten was associated with an improvement in New York Heart Association functional class with a substantial number of patients, improving by at least 1 class. As previously stated treatment with aficamten was well tolerated. The incidence of adverse events was similar between treatment arms. And there were no treatment-related serious adverse events.

Importantly, there were no treatment interruptions or discontinuations Director of hypertrophic Cardiomyopathy Center at Tufts University School of Medicine who presented the results of REDWOOD-HCM at HFSA underscored the potential clinical utility of aficamten based on the elimination of resting LVOT gradients in nearly all patients. Dr. Maron further commented on the substantial improvement in heart failure symptoms, rapid onset and reversibility of effect the ability to use precise echo-guided titration and the lack of dosing interruptions for low ejection fraction.

At the conference, we also received a positive reaction from physicians who manage patients with HCM and expressing their enthusiasm about the results and for a medication that potentially could be used for patients who have symptomatic obstructive HCM and are not responding to current standard of care therapies. Overall, we're very encouraged by the results so far and their potential translation of the clinical practice.

During the quarter, we also completed enrollment in Cohort 3 of REDWOOD-HCM in which patients with obstructive HCM who are receiving disopyramide as background therapy are treated with aficamten in an open label manner. This cohort will further inform the potential inclusion of this small, but important patient population in our planned Phase 3 trial. In addition, during the third quarter, we continued enrolling patients in REDWOOD-HCM OLE the open label extension trial of REDWOOD-HCM.

With the positive results in hand from REDWOOD HCM, we have been actively engaging and startup activities for SEQUOIA-HCM our planned Phase 3 clinical trial of aficamten in patients with obstructive HCM. At our Analyst and Investor Day meeting in October, we presented the design of the trial, which I'll recap at a high level now. SEQUOIA-HCM is a randomized double-blind placebo controlled international clinical trial designed to evaluate aficamten in patients with symptomatic obstructive HCM on background medical therapy for 24 weeks.

The primary objective is to evaluate the change from baseline to week 24 in peak oxygen uptake or peak VO2 measured by cardiopulmonary exercise testing or CPET which is a measure of exercise capacity among the secondary objectives. We are investigating the change in Kansas City Cardiomyopathy Questionnaire clinical symptom score in New York Heart Association functional class at Week 12 to evaluate a potentially early improvement in heart failure symptoms and again at week 24.

We plan to randomize 270 patients in a one-to-one ratio to aficamten or placebo in addition to standard of care. Each patient will receive up to four escalating doses of aficamten or placebo. With dose optimization based on achievement of echocardiographic targets the starting dose will be 5 milligrams once daily. Escalating to 10, 15 or 20 milligrams once daily as needed to achieve target gradients.

These four doses were selected based on the results from REDWOOD-HCM to facilitate selection of the optimal dose for each patient and maximize the individual benefit risk profile. Study startup activities, regulatory filings and IRB submissions are underway. With the first site initiations already completed drug product availability and early 2022 will enable the commencement of screening and enrollment of the first patients in this trial.

In anticipation of enrolling patients with obstructive HCM from China in SEQUOIA-HCM we continue to collaborate closely with our partner Ji Xing Pharmaceuticals. Ji Xing recently completed a Phase 1 study evaluating single and multiple doses of aficamten in healthy Chinese subjects. The pharmacokinetic results were similar to those observed in the Caucasian populations enrolled in our Phase 1 study of aficamten conducted in the U.S. and similarly showed dose proportional pharmacokinetics with a safety and tolerability profile comparable to placebo.

The results of this study support submission of the clinical trial application and enrollment of patients with obstructive HCM in China. On the neuromuscular front as Robert mentioned, during the third quarter, we began enrolling patients encourage ALS the Phase 3 clinical trial of reldesemtiv in ALS. COURAGE-ALS will enroll approximately 555 patients with ALS randomized 2 to 1 to receive reldesemtiv or placebo for 24 weeks, followed by a 24-week period in which all patients will receive reldesemtiv.

The primary endpoint is the change from baseline to 24 weeks in ALSFRS-R, a functional rating scale that indicates the progression of ALS. As we designed COURAGE-ALS, we incorporated feedback from patients and caregivers to remove key barriers to clinical trial participation and to help make the patient experience less burdensome. We are also working to provide continued access to reldesemtiv for all patients who complete COURAGE-ALS as well as patients who have previously participated in our ALS trial reflective of our goal to ensure ethical and equitable access for patients who are in need.

With that, I will turn the call over to Andrew to discuss our progress against the go-to-market strategy for omecamtiv mecarbil.

[Andrew Callos, CCO]

Thanks Stuart.

During the third quarter we advanced our go-to-market strategy for omecamtiv mecarbil, and we were pleased to present at our recent Analyst Investor Day. There are a few highlights to the strategy. I'd like to review on today's call. First, our go-to-market strategy is based on a gated build with a planned total investment to be titrated over time as de-risking events occur such as NDA submission NDA filing and approval by the FDA.

To illustrate we have around 10% to 15% of our planned commercial FTEs in place today, but we will have less than 1/3 of the total number of in place post NDA submission this level of commercial hires are sufficient for launch preparation. As Robert mentioned, we hired a seasoned team to implement this go-to-market strategy and we now have our full leadership team in place as well as our account manager team who call and payers and nearly all of our marketing organization.

The go-to-market strategy is based on four key pillars insights, education, access and support. Insights speaks to having a very deep understanding of who the worsening heart failure patient is where they are treated and who would the cardiologist are who treat them. Education means that omecamtiv mecarbil is approved, then we need to ensure that cardiologist clearly understand the data supporting our label including the evidence supporting omecamtiv mecarbil potential benefit for the subset of patients who have worsening heart failure.

Accessed speaks to our plans to have affordable co-pay for most patients as soon as possible after launch. And finally support and tells the programs that we will have and provide for patients like co-pay support for commercial patients patient assistance program and educational services. To support our goal of commercial - of affordable access our payer account management team has met with every major payer in the third quarter.

We have introduced our team and our company while engaging payers in a mutual understanding of the unmet need dark failure. Further support access our health economics and now research colleagues continue events outcomes research with the goal of multiple publications. In 2022 these publications are targeted documenting the value of omecamtiv mecarbil as illustrated by meaningful reductions in resource utilization, intensity and cost.

And we are preparing for the potential launch of omecamtiv mecarbil, we are simultaneously building our cardiovascular franchise strategy towards our plan for the potential launch of aficamten keeping in mind our corporate goal of bringing multiple medicines to market in the next several years. This strategy relies on several synergies. First in the cardiologist to treat these patients there is an 80% overlap between the cardiologist who treat patients with heart failure and HCM.

Cost efficiency is another synergy where we will share fuel cells, fueled medical, shared services and systems across the entire organization. Once we have established relationships and built system to support the launch of omecamtiv mecarbil. We are well positioned to accelerate and streamline the potential launch of aficamten. It is an incredibly exciting time to be working at Cytokinetics as we continue to grow our team and advance our plans. It remains an important for us to remember the driving force behind this motivation, patients and the clear unmet need in both heart failure and HCM.

And with that, I'll turn it over to Robert Wong, who will provide an update to our financials.

[Robert Wong, VP and CAO]

Thanks, Andrew.

I'll provide an update on cash revenue and spending and then Ching will review our financial outlook and corporate development strategies. More details on our actual results for the third quarter 2021 are included in the press release, which we released earlier this afternoon. We ended the third quarter with approximately $668.9 million in cash and investments.

Our revenue in third quarter of 2021 came primarily from our recognizing a $5 million milestone from Ji Xing Pharmaceuticals in anticipation of the start of SEQUOIA-HCM. Our third quarter 2021, R&D expenses increased to $48.4 million from $24.2 million in the third quarter of 2020 primarily due to increases in spending for our clinical development activities for our cardiac muscle inhibitor programs.

In addition, we incurred transition costs related to the termination of our collaboration with Amgen and our purchase from Amgen of approximately 7.3 million of materials including manufactured quantities of the active pharmaceutical ingredients for omecamtiv mecarbil, thereby completing our purchase commitment.

More than 70% of our R&D expenses were attributable to our cardiovascular programs as expected given activity related to transitions from our collaborations with Amgen the purchase manufactured quantities of active pharmaceutical ingredients ongoing activities associated with METEORIC-HF and also our cardiac myosin inhibitor programs, including the ongoing activities associated with REDWOOD-HCM and start-up activities related to SEQUOIA-HCM.

Remainder of our expenses were attributable to our early research and skeletal muscle program activity, our third quarter 2021 G&A expenses were $26.2 million, up from $12.3 million in the third quarter of 2020 due primarily to an increase in outside spending in anticipation of our potential commercial launch of omecamtiv mecarbil in 2022. Personnel-related costs, including stock-based compensation and facilities costs related to our new building.

And now Ching will review our financial outlook and corporate development strategies.

[Ching Jaw, SVP and CFO]

Thanks, Robert.

As is our annual practice, we recently conducted a comprehensive, strategic planning process with subsequent presentation and discussion with our Board this year the strategic plan was focus to prioritizing our expanding clinical pipeline to ensure that we focus on R&D programs that leverage our core competencies and competitive advantages in muscle biology and also address high unmet need opportunities that may for high return on investment potential.

In addition, we pressure tested plans to enrich our research pipeline with external collaborations that could complement and strengthen our internal innovation. Lastly, we focused in this year strategic planning process to critically evaluating and reformulating our cardiovascular and neuromuscular business franchise strategy that's to continually capitalized on lifecycle management of our most advanced drug candidates omecamtiv mecarbil, Aficamten and reldesemtiv.

To recap, our cash position we ended the third quarter with approximately $669 million in cash which includes $297 million raised in Q3 through an equity offering net of expenses. Therefore, our pro forma cash at year-end 2021 is expected to be in the range of $600 million to $610 million which represents more than three years of cash runway using our revised net cash utilization guidance of $195 million to $215 million in 2021.

With the potential commercial launch of omecamtiv mecarbil and the funding of 2 Phase 3 clinical trials SEQUOIA-HCM and COURAGE-ALS. We do expect our 2022 and 2023 cash burn rate to increase relative to 2021 spending and we will provide guidance on this in our fourth quarter earnings call and to occurred in early 2022. As we have stated, we continue to seek ways to strengthen our balance sheet and in the third quarter, we have been advanced partnering and structure financing discussions aligned with our corporate development strategy.

During the quarter, we continue our discussions with potential co-development and co-commercialization partners for omecamtiv mecarbil as well as aficamten with priority attention to business development in Asia and other complimentary geographies where we don't intend to go-to-market ourselves. Our plan is to preserve North American and potentially European rights for development and commercialization for both omecamtiv mecarbil and aficamten.

In parallel, we have also being advancing discussions with multiple entities and funds with share interest related to structure financings including royalty monetization and a structure that deals. To further support the commercial launch of omecamtiv mecarbil in our continued and expanded development objectives for aficamten. Our goal is to complete these deals in the fourth quarter which could enable us to end the year was two to three years of forward cash runway, even as we expect the spending in 2022 and 2023 to be higher than our expected spending this year.

As you know we have always built our business on a strong financial foundation and we have an established history of making non-equity dilutive deals to support our continued growth and progress. This transaction is expected to close this quarter. We believe we are positioned financially and strategically to ask that you and the potential launch of omecamtiv mecarbil and continue to advance our pipeline and business franchise strategies.

And with that, I will turn the call back over to Robert Blum.

[Robert Blum, President and CEO]

Thank you, Ching.

Within our vision, 2025 that we set forth in 2020 we laid out several goals, including achieving regulatory approvals for at least two drugs arising from our pipeline and expanding our discovery platforms. Over the past quarter, in addition to the clinical, regulatory and commercial progress we made, we also engaged in activities to broaden our research footprint in the years to come. Thinking even beyond 2025, we continue to forge ahead as leaders in muscle biology with focus to populations of high unmet need.

In the next year, you'll be hearing more about our activities as we've extended our muscle biology focus from the bio-mechanics of muscle contractility to the energetics growth and metabolism of muscle with novel mechanism drug candidates advancing in development. While much of our focus has been on our programs in cardiovascular disease as you heard with our starting COURAGE-ALS, our commitment to the ALS communities remains strong.

Along these lines, we also recently donated data from our completed clinical trials in ALS to the PRO-ACT database, which stands for pooled resource open access ALS clinical trials. PRO-ACT is available to members of the research community and it contains over 10,000 de-identified clinical patient records from multiple completed clinical trials, providing a powerful tool to advance research in the ALS field and also together observations related to disease progression and epidemiologic data.

We will be donating data from three completed trials in ALS BENEFIT-ALS, VITALITY-ALS and FORTITUDE-ALS which represents data from almost 600 patients. We're pleased to be working with the ALS Association with Price for Life and with the Neurological Clinical Research Institute at Mass General to share these data with the ALS communities to which we are altogether so importantly dedicated.

Further demonstrating our commitment to patient communities during the quarter, we renewed our partnership with Cure SMA to increase education awareness, public policy and fundraising for spinal muscular atrophy and we also announced the 4th Annual Cytokinetics Communications Fellowship Grant program which will award a total of $100,000 in grants to patient advocacy organizations in heart failure in HCM, in ALS and in SMA to support increased capacity in communications and outreach.

As we near the end of 2021, we look back on our very gratifying progress and achievements and we look ahead to what may be a watershed year for our company. We expect to end 2021 with two distinct programs advancing in Phase 3 clinical trials with our first potential medication moving towards a potential approval and commercial launch and all of that happening on the foundation of continued innovations in muscle biology directed to patients who rely upon us and in areas for which our leadership offers hope for diseases associated with muscle dysfunction and weakness.

We look forward to providing more updates on our continued progress and we welcome your questions and feedback. Now let me recap our expected milestones for the remainder of 2021. For omecamtiv mecarbil, we expect to submit an NDA to the FDA in this fourth quarter of this year. We also expect to complete the conduct of METEORIC-HF by year-end with results expected in early 2022.

For aficamten, we expect to continue with study start up with regulatory filings with IRB submissions and site readiness activities altogether for SEQUOIA-HCM and with availability of drug product in early 2022. We anticipate commencement of screening and enrollment of the first patients in that trial. And for reldesemtiv, we expect to complete enrollment of COURAGE-ALS throughout the remainder of this year.

And for our ongoing research, we expect to advance new muscle directed compounds and to conduct IND enabling studies and to potentially advance one to two potential drug candidates into clinical development over the next year.

Operator, with that update, we can now open the call up to questions please.

[Operator]

[Operator Instructions] Your first question comes from the line of Dane Leone with Raymond James.

[Robert Blum, President and CEO]

Hello, Dane.

[Dane Leone, Raymond James]

Great. Hi, Robert and team. Thank you for taking the questions and congratulations on all the updates. Just two for me if you will. Firstly, can you give us any more color in terms of the scale and scope of the SEQUOIA-HCM study, as we think about one modeling expenses and two time to run the study. Is it fair to use the EXPLORER-HCM study as a similar proxy and scale and scope for the patients required an enrollment?

And then my second question would be just to drill down a little bit more on the submission for omecamtiv, I know it's been asked before, but in terms of updating your communications back and forth with the FDA, any additional color in terms of the scope or scale of the label as it relates to baseline left ventricular ejection fraction. Thank you.

[Robert Blum, President and CEO]

Sure. Good questions. So I'll start and turn it over to Fady. He may also ask Stuart to elaborate. I don't think we're going to provide any specific financial guidance with regard to SEQUOIA, it may be premature to do that until we start dosing patients, but certainly we can give you some things to hold on to with regard to your projections. For instance, what might be our expectations in terms of time for enrollment and duration of the study.

I hope that could be helpful and certainly you know already the number of patients we aim to enroll. So why don't I turn it over to Fady first to talk to you about how we think it's going to enroll the number of sites, the number of countries, things like that. And then most likely once we start dosing presumably that will be in early 2022 will be at a better position to point to how we think it's going to be affecting our spending, and then we'll come back to your second question.

[Dane Leone, Raymond James]

All right. Thanks, Robert. I think we plan to enroll approximately 270 patients into SEQUOIA, which is a little bit more than was in roles and explore. I think the size and scope are comparable and certainly the number of sites and things like that. We will probably go to a few more sites than they did in explorer nearly a dozen countries and well over north of 80 sites. I think ultimately, when we get study fully up and going.

So our plan is to push hard and to enroll this as quickly as possible. But there are certain I think limitations in terms of study startup and things like that, that are hard to press once we have sites up and going, I think it would actually enrolled very rapidly.

[Robert Blum, President and CEO]

So then, your second question related to the NDA and how we're approaching what could be that which is contained within the NDA indication statement and otherwise. In particular, around ejection fraction. And as we've stated, we do believe that patients with the EF is less than 30% are seemingly benefiting a great deal of more than other patients in GALACTIC and we do think that it's in the interest of omecamtiv mecarbil in patients with heart failure that's where the label should point.

So we are hopeful that data including graphics could be included in the label ultimately upon potential approval, but that's obviously going to be subject to FDA review, but based on conversations we've been having in Fady can elaborate. We do feel encouraged that would be supportive and consistent with other things the FDA has done. Fady anything you want to add?

[Fady Malik, EVP of R&D]

No, I mean, I think we've had those discussions with FDA obviously what ends up in the label will be the outcome of the negotiations at the time that we negotiate the label. But in general, I think there are supportive of the concept, that the label should indicate where the benefit of the drug is concentrated and that provides physicians with the information needed to best use the drug. And in that context, EF is obviously an important indicator.

[Robert Blum, President and CEO]

And not only the label. I might suspect that could ultimately inform how omecamtiv mecarbil could be incorporated into guidelines also and you got a sense of that from some of the publications that Fady referred to in his statements.

[Dane Leone, Raymond James]

Excellent. Thank you very much and congratulations.

[Robert Blum, President and CEO]

Thanks, Dane.

[Operator]

Your next question comes from the line of Joe Pantginis with H.C. Wainwright.

[Robert Blum, President and CEO]

Hi, Joe.

[Joe Pantginis, H.C. Wainwright]

Hi, everybody, good afternoon. Thanks for taking the questions. I wanted to focus my first question and the concept that you guys are really in an important execution and logistics time for the company. So with that said, I'll even go off of, I want to Stuart's comments, and Robert you said it to about drug availability for -- early next year and executing COURAGE as well. Do you feel you've had to plan anything above and beyond for these studies, no matter what it is, including drug availability based on any anticipated issues around the global supply chain problems that we're seeing right now?

[Robert Blum, President and CEO]

Very good question, and I think that might be the first time on one of these earnings call that we really did get a question about the supply chain. It's an area of intense focus for us right now, as we're not only embarking on these large Phase III studies, but we're readying for the supply of omecamtiv into the marketplace and obviously had, we still been partnered with Amgen, that would be something we'd have relied on them for, but now it's our responsibility.

And we are executing well on contracts as well as conversion of drug substance to drug product and the like, and the study startup activities for SEQUOIA are proceeding nicely, we moved very swiftly from having completed Cohorts 1 and 2, reading out there results, having meetings with FDA and readying to start SEQUOIA, all of that occurring in a relatively short timeframe. So it seems like things are going well. That way, both in support of clinical trials and also commercialization. But we are building the supply chains.

At the same time we're executing on how the delivery of drug product into clinical trials is occurring. So it's something that I think is going to be continuing to be a focus for senior management as that is enabling of our success, and to this point, the good news is, we're working with some of the same contract manufacturing organizations with whom we have long-standing relationships with. And there may also be opportunities to consolidate programs, amongst them so that we're working with them for more than one program. And we're focused to small molecule drug candidates, and that in way, it's not like we're dealing with an incredibly novel way of approaching supply, but at the same time, we have to ensure capacity and deliverable timelines and that's what we're focus towards. Fady, anything you want to add to that?

[Fady Malik, EVP of R&D]

No, I think you summed it up, but I think we've been able to continue to advance drug supplies for our studies and things like that. I think the real major constraints this has to do with the spare capacity in the supply chain. There is just a lot of it's been squeezed out. So you have to be careful about how you plan things.

[Stuart Kupfer, SVP and Chief Medical Officer]

And what I might also say as Andrew and his team are very focused to the hand off between the manufacturers and then the logistics associated with distribution and all of the activities in connection with ensuring patients get reliable sources of drug as well and that speaks to potential patient hub services and other things like that. Over time, I expect you'll hear more about that from Andrew too.

[Joe Pantginis, H.C. Wainwright]

That's very, very helpful. Thank you. And then I guess two smaller questions. One maybe for Ching on the financial side. Are you -- we have this $7.3 million cost to pay Amgen for drug product for omecamtiv. Just curious, what might still be outstanding, they're going into the future or if that expense is essentially done? And then second, if I heard Fady, correct when he was discussing the future for omecamtiv as well. I could of sworn I heard him say potential ISTs, so that sounded like an interesting there. So I'm curious what kind of studies you might be looking at. Thank you.

[Fady Malik, EVP of R&D]

Yes, I mean…

[Ching Jaw, SVP and CFO]

Thanks.

[Fady Malik, EVP of R&D]

Oh. Got ahead, Ching. You go first.

[Ching Jaw, SVP and CFO]

Yes, I'll go first Fady. So, in regards to e-payment that we pay Amgen, the $7.3 million this quarter is the last of those payments. As we stated in our press release for the nine months ended September 30, 2021, we have pay them $46 million. So that was the total amount, and this was $7.3 million was the last of the payments.

[Joe Pantginis, H.C. Wainwright]

Thanks.

[Fady Malik, EVP of R&D]

And I think just in regards to investigator sponsor initiated study, we've begun to receive proposals, obviously we'll let them and decide which ones we can support things like that, they fall under a fairly broad range of interest. The people have really outside, some of them outside of the heart failure, population that we studied in GALACTIC, some of them within, but I think we'll elaborate more on those as we begin to see them through.

[Joe Pantginis, H.C. Wainwright]

Sure. Understood. Thank you very much.

[Fady Malik, EVP of R&D]

Thank you.

[Operator]

Your next question comes from the line of Yasmeen Rahimi with Piper Sandler.

[Robert Blum, President and CEO]

Hello, Yasmeen.

[Yasmeen Rahimi, Piper Sandler]

Hi, Robert. Thank you so much for taking my questions. But I have two questions for you. Maybe the first place to start is, a lot of our investors have been sort of surprised by the FDA recently by some of the actions that were taken a created sort of a nervous Nellie situation. So I get the question for you is, especially over the last few months as you've been interacting with the FDA. What sort of their tone, their body language, there into towards you. So if you could just elaborate, and how does discussions went, and I think that could be really important. And then I have a follow-up question?

[Robert Blum, President and CEO]

Sure. So what I'll say is oftentimes in these situations, biotech companies’ talk about having a pre-NDA meeting, they submit an NDA, it gets filed or doesn't get filed, and then they await approval. In our case, over the last year, we've had many interactions with FDA both in-person before COVID shut that down and then also subsequently by Zoom interactions and otherwise through written exchange of documents.

I found FDA to be very accessible and very interactive with us and providing guidance that informs both the formatting and the content of our planned NDA submission. So I'm very encouraged by the level of engagement and I should hopefully support our submission that would hopefully align with interest for approval. We've had all of our questions satisfactorily answered in order to provide for us now to go through the final mechanics of an NDA submission in order to get that done this quarter.

[Yasmeen Rahimi, Piper Sandler]

And thank you, Robert for answer. And maybe a follow-up question is, maybe giving me some insight when you speak with cardiologist whether these are in private practice, whether it is at the hospital setting, and sort of the level of appreciation, they have for omecamtiv in terms of a novel mechanism of action. Does it click right away when they know that it's the first myotropes being able to really, being able to improve cardiac contract. I think that might be really important like how important is the novelty of its mode of action for driving adoption in their enthusiasm beyond obviously the outstanding data form black in nature.

[Robert Blum, President and CEO]

So it's a little too early to talk about adoption of course in that as much as not approved, but certainly based on ad boards and interactions with key opinion leaders that have been driven out of medical affairs and also market research as is driven out of our commercial group. We're getting very positive vibes about how the novelty of the mechanism may translate into potential future adoption, maybe I'll turn it over to Fady first to speak about some of those activities that he is overseeing, and then I'll turn to Andrew as well.

[Fady Malik, EVP of R&D]

Yes, Yasmeen. I think the physician community certainly understands where this could play a role and it's been a finding a drug that can improve cardiac function safely and have benefit for patients has been a longstanding goal in this field. And if you listen to our Investor Day presentation, I think you might hear some of the enthusiasm in the two discussions we had, but it was similar amongst many ad boards that we conducted both in the U.S. and in Europe. And I think even as we go out to other stakeholders in the process, we're sensing their enthusiasm for something that is new, but on the other hand, we understand how it works and it's rational, it's rationale as to why you might use it.

[Andrew Callos, CCO]

This is Andrew. The only thing I would add is that when we talk with physicians, they excited by the mechanism enough for the mechanism alone, but it's a reason to believe relative to the data any evidence that we produced. So when they look at the mechanism and the evidence and the unmet need very well aligned, they are running out of options when patients can't tolerate guideline directed medical therapy. They are running out of options when they need products that what could be an add-on that neutral on kidney, neutral on blood pressure in working patients. And when you talk about the add-on and those type of effects think get very excited and a good reason to believe then kind of closing is a mechanism. So we're getting a lot of enthusiasm for a very specific subset of patients relative to the product.

[Yasmeen Rahimi, Piper Sandler]

Thank you for the answer.

[Robert Blum, President and CEO]

Thank you.

[Operator]

Your next question comes from the line of Jeff Hung with Morgan Stanley.

[Robert Blum, President and CEO]

Hi, Jeff.

[Jeff Hung, Morgan Stanley]

Hi, Robert. Thanks for taking the questions. Previously indicated that meetings with payers on omecamtiv mecarbil has been largely introductory, just curious if you have any updates that you can provide on payer feedback.

[Robert Blum, President and CEO]

Sure, I'll turn it over to Andrew to address that.

[Andrew Callos, CCO]

Sure. So I appreciate the question. So we've interacted with. As I've mentioned, we've hired all of our account managers, as well as the leader of that team. Many of them have existing relationships with all the major payers. We've interacted with the major payers and it's really more about introduction who is Cytokinetics and then making sure we aligned well on how they think about heart failure, how do they manage heart failure, what are their challenges and what are their needs.

So we've had those kind of baseline discussions and then where will go next is per FDA regs is kind of a pre-approval information exchange, we will start doing that incoming weeks. So the feedback has been 12, they do like that we can clearly identify those patients relative to benefit in EF. So then therefore that could indicate where they would target us from a prior authorization point of view, which is acceptable to us, because that gives us access to a very specific population that greatly benefit from omecamtiv. So hopefully the color of our interactions in the third quarter.

[Fady Malik, EVP of R&D]

The other thing to add is, there is a lot more forthcoming that you'll see in the published literature in 2022 that underscores the economic burden of heart failure, especially for those with worsening heart failure and where there could be opportunity for a new mechanism therapy like omecamtiv mecarbil based on results from GALACTIC to make a dent in that for payers. And payers are clearly aware of the economic burden associated with their management of heart failure patients. They're aware, especially of the high Medicare percentage of these patients for which there oftentimes penalized when these patients are readmitted. So a novel mechanism therapy that could reduce heart failure related events primarily hospitalizations would be something that would catch the retention, and that's something that we'll continue to investigate, this could be supportive of our plans for omecamtiv.

[Jeff Hung, Morgan Stanley]

Great, thanks. And I think I may have misheard, but did you say that you expect enrollment of COURAGE to be completed this year. Otherwise, any updates on this made timing or when you might be better able to gauge the pace of enrollment to estimate that time. Thanks.

[Fady Malik, EVP of R&D]

Yes, what I would I said are meant to say was that enrollment continues through this year, but also intended next year also. We expect that will enroll patients sufficient to enable a first interim analysis next year, the timing of which is still to be defined. But we expect that were it to pass through that interim analysis, hopefully it will. The study would continue through next year. So, no, it's not intended to complete enrollment this year.

[Jeff Hung, Morgan Stanley]

Okay, thank you.

[Fady Malik, EVP of R&D]

Thank you, Jeff.

[Operator]

Your next question comes from the line of Akash Tewari with Jefferies.

[Robert Blum, President and CEO]

Hello, Akash.

[Akash Tewari, Jefferies]

Hi, Robert. So, thanks so much for taking my questions. Can you talk about what drove your decision to look at exercise capacity as a primary endpoint for - and not the comps that I'd point that ahead why may exercise capacity be a more useful endpoint, both for the agency and clinicians. And additionally, have you heard any feedback from either the FDA or KOLs on the need for long-term outcomes data post-approval for our Aficamten. Thank you.

[Robert Blum, President and CEO]

Why don't we turn first to Stuart to address the first question and then maybe Fady and Stuart the second question.

[Stuart Kupfer, SVP and Chief Medical Officer]

Thank you, Robert. So, we focused on evaluating functional improvement in patients with obstructive HCM comparing Aficamten versus placebo. And with respect to the fact that these patients have very poor exercise tolerance.

We focus on one of the most rigorous objective measurements of exercise capacity and that is clearly peak VO2 as well as other parameters using cardiopulmonary exercise testing. And so we rather than combining this with, say, a more subjective component of the composite endpoint.

We really wanted to zero in on what we thought was the most sort of critical and quantitative measurement and objective measurement of exercise capacity. And you said that, we will be evaluating other endpoints as secondary endpoints that evaluate symptomatic improvements such as the Kansas City Cardiomyopathy Questionnaire New York Heart Association functional class et cetera. So those other kind of I'll say more traditional endpoints we will be evaluating in SEQUOIA.

[Fady Malik, EVP of R&D]

And your second question was -- why do you repeat that for me Akash?

[Akash Tewari, Jefferies]

Yes, absolutely. Have you heard any feedback either from the FDA or KOLs on the need for outcomes data post-approval?

[Fady Malik, EVP of R&D]

Yes. Outcomes, I think that the regulators and KOLs appreciate that outcomes data are very hard to come by in a symptomatic, although very heavily burdened patient population. These patients, unlike traditional heart failure patients don't get hospitalized, there mortality rates are usually quite low and lessen well under 5% per year. So you can't really do outcomes-based trial per se and I think that's well understood based on the event rate. That said, I think that there's also recognition that the therapy that has been developed for these patients is a lifelong therapy. And so, having a good understanding of it safety, long term is important and that's why we're conducting the open label extension in plan at least five years of follow-up in patients that we enroll in that, that rollout of either REDWOOD or SEQUOIA to enable us to better characterize the course of these patients who are being treated with aficamten.

[Robert Blum, President and CEO]

I think the advent of new pharmaceutical is going to drive a better awareness of the outcomes associated with a diagnosis of HCM as could be modified with add-on-therapy of Aficamten or Mavacamten, and you're going to see I think increasingly publication arising out of registries that speak to the real world evidence associated with these longitudinal studies. So we will be in a position to better understand what might be possible. And I do suspect that will play into ultimately the adoption of category, but to your original question is to whether regulators are pushing for it? I don't think that's likely going to factor into the registration of these new medicines at least not from what we've heard from FDA.

[Akash Tewari, Jefferies]

That super helpful. And if I may just follow-up here. Can you talk about the importance of showing to the FDA that patients are able to get stabilize on to a safe dose from this class of drugs. Is that something that the agency is focused on from a regulatory perspective? Thanks so much.

[Robert Blum, President and CEO]

It’s certainly something that we think is possible and achievable with Aficamten, and hope to be able to demonstrate that with SEQUOIA. If your question is pointed to, is that something FDA is pushing for, because of their review of another product that would not be appropriate for FDA to be signaling anything like that to us.

[Akash Tewari, Jefferies]

Understood. Thanks so much. Appreciate it.

[Operator]

Your next question comes from the line of Salim Syed with Mizuho.

[Robert Blum, President and CEO]

Hello Salim.

[Salim Syed, Mizuho]

Good afternoon, Robert and team. And congrats on all the progress. Just a couple from me, one on 274 and one on actually reldesemtiv. So, on 274, looks that Robert obviously the thesis here has gotten a lot more comfortable for a lot of long-only investors, right? And I'm curious in your mind what are the gating factors -- when you think about the story what are the gaining factors here for 274 that are really stopping you from turning on the after burners and starting to develop -- have path, which is it's a large indication more aggressively? And I guess we could also ask the same question for non-obstructive hypertrophic cardiomyopathy.

And the second question on reldesemtiv. So as we start to dig in here on the COURAGE design, you guys are enrolling looks like ALSFRS total score 44 or less. But when you look at the Phase 2 data, the slow progressors turtle [ph], which had a score of 41, didn't really show much of a difference between drug and placebo. So I'm curious how you guys are thinking about COURAGE. Are you going to limit somehow the slow progressors that are entering the trial? Or how are you ensuring that when we get to futility that you're having an over-enrolled slow progressors I guess is one way to ask it? Or how are you controlling that you're going to actually have enough medium or fast progressors that would show a larger benefit here potentially according to the Phase 2 data? Thank you.

[Robert Blum, President and CEO]

Sure. Both very good questions. Let's start with your first one around the development program for Aficamten. We've spent quite a bit of time over these last several months once we saw the REDWOOD results, considering what might be our next steps beyond SEQUOIA-HCM for Aficamten. And Fady and Stuart and Steve and others here at Cytokinetics are considering a number of different trial designs as we would be expected to expand the development program in non-obstructive HCM and in hefpath [ph]. It's premature for us to elaborate on them, but you should expect in 2022 to hear more about our plans that way. We intend to be pursuing the development of Aficamten along both those lines and not in a linear way per se, but in parallel ways that would be enabling of us to build on what we know for Aficamten. I'm just not in a position to do that on today's call. But certainly as we plan for budgets for 2022 and goals and considerable resources that we need to align in order to make that happen that's very much in the forefront of our planning. Your second question related to COURAGE-ALS and I'll ask Fady and Stuart to address. I think you might be misunderstanding a bit how we are designing the study. We are going to be prioritizing for those patients who are progressing, but they can elaborate.

[Fady Malik, EVP of R&D]

Yes. I think it's really an enrichment strategy Salim and so the entry criteria designed in such a way to enrich for the medium and faster progressors. And I can turn over Stuart a little bit to describe how that works. But ultimately it's also something that we can monitor, because you can look at progress -- you can look at the -- calculate the early progression rates in the study and ensure that you're enrolling the right patients in a blinded way. Stuart?

[Stuart Kupfer, SVP and Chief Medical Officer]

Yes. So Salim, I think you're referring to the post-hoc analyses that were conducted with the FORTITUDE-ALS and database. And why we observed trends of benefit in slow progressors, we observed greater magnitudes of benefit with respect to ALSFRS-R in the medium and fast progressing patients. And what we did was map that progression rate to critical entry criteria particularly a maximum ALSFRS-R of 44, as well as time from symptom onset of two years. And so, if we apply those apply those two main criteria that enriches as Fady mentioned for population, a faster progressing patients, while not excluding slow progressors, but we'll have a larger proportion of medium and faster progressing patients. And with that strategy, we anticipate that this will increase the sensitivity of detecting a beneficial treatment effect with reldesemtiv.

[Salim Syed, Mizuho]

Okay. Got it. So this is more you will be able to in your view do this based on entry criteria not having to calculate during the trial based on blinded data?

[Stuart Kupfer, SVP and Chief Medical Officer]

That's correct. Exactly.

[Salim Syed, Mizuho]

Okay. Thank you.

[Robert Blum, President and CEO]

Thank you, Salim.

[Operator]

Your next question comes from the line of Jason Butler with JMP Securities.

[Robert Blum, President and CEO]

Good afternoon, Jason.

[Jason Butler, JMP Securities]

Hi Robert. Thanks for taking the questions. Just wondering if you could talk a little bit more about the path for Aficamten in China. Is there data that you need beyond the completed PK study to open up the SEQUOIA trial to China? And then, just give us a sense of what proportion of patients in SEQUOIA you think could come from China? And then, could SEQUOIA as a standalone support registration in China? Or would you need additional data or an additional trial beyond that trial? Thanks.

[Robert Blum, President and CEO]

Yes. So, very good questions. We're still learning about what might be required. But it's our assumption that we're going to be in a position to start SEQUOIA in China and based on the Phase 1 data be enrolling China patients into the same study and as could be supportive of registration in China as well as outside of China, U.S., Europe elsewhere. So that's the intention and the plan obviously that's subject to regulatory interactions that are still to be had, but our partner Ji Xing is very much on top of these things and we're working very very well. Stuart is leading much of that activity for Cytokinetics. Stuart, anything more you want to add?

[Stuart Kupfer, SVP and Chief Medical Officer]

No. I think you've summarized it very well. We certainly rely on Ji Xing for guidance. They have more expertise in China regarding the regulatory requirements. But as you've -- as it has been laid out we expect the Phase 1 data to support enrollment of patients in China in SEQUOIA-HCM and that trial to support registration in China.

[Jason Butler, JMP Securities]

Great. Thanks for taking the questions.

[Robert Blum, President and CEO]

Thank you.

[Operator]

Your next question comes from the line of Charles Duncan with Cantor Fitzgerald.

[Robert Blum, President and CEO]

Hello, Charles.

[Charles Duncan, Cantor Fitzgerald]

Hello, Robert and team. Congratulations on good year of progress. Thanks for taking my question. I had a couple of questions. One on omecamtiv and then another on reldesemtiv. With regard to omecamtiv NDA filing, I guess I'm wondering are you planning on press releasing the submission or the acceptance for review or filing? And then, I guess, I just need to clarify something. I think it was to Dane's question. Would you be filing for a broad label claim with data pointing to the patient the cohort that had the greatest benefit? Or would you limit the filing claim to that cohort?

[Robert Blum, President and CEO]

Yes. So I'll take those and Fady may want to elaborate. With regard to the communications and the press release, we expect to be submitting an NDA in this quarter and we probably would not be communicating anything until such time as we have a read on its file ability whether it's filed or not filed by FDA. And then as to your second question I'll ask Fady to speak regarding how we might approach the indication statement and where it might be the information containing the patients that benefited the most.

[Fady Malik, EVP of R&D]

Yes. I can - I think if you look at different indication statements even recent ones there are different approaches, but and generally they reflect the patient population that was studied in the clinical trial at large. You can see in the ENTRESTO label after the PARAGON data were added that there was an additional statement with regards to where the benefit was concentrated i.e. in patients with below normal ejection fraction. So it may be that you could end up with the modifying statement in the indication. You certainly will have data in the clinical trial section that show the pre-specified subgroups, which one of which was ejection fraction as you know, and showed the benefit in the lower ejection fraction group, the NYHA 3-4 group and others -- and across the subgroups that we had pre-specified. So there are different places in the label where the information may be contained and ultimately it's hard to predict where we'll end up until we go through those discussions.

[Charles Duncan, Cantor Fitzgerald]

Okay. That's helpful. I consistent with what I kind of thought. Regarding METEORIC, I think you mentioned that you'd complete the conduct of it yet this year. Can you give us some sense on timing to data? Could that be in the first half of the first quarter? And then, can you confirm whether or not you think that that data would then be submitted to the agency and have any potential for impacting the review? It seems like it could be pretty early in the review cycle, so likely not.

[Robert Blum, President and CEO]

Yes. I think what -- we probably aren't going to give guidance with regards to first half or second half of the quarter with regards to METEORIC. Its conduct will wrap up this year, but it's really going to wrap up pretty late in the quarter. And then of course, it's a complicated study because there's a lot of central lab work in terms of the CPET evaluations and so forth. And the data sets are relatively complex to integrate. So time database lock may be not as swift as you might have in an event-based trial.

[Charles Duncan, Cantor Fitzgerald]

Okay.

[Robert Blum, President and CEO]

But I think the other aspect of your question that you're going to have to remind me of again now I got a lot of track of it.

[Charles Duncan, Cantor Fitzgerald]

Just impact on review cycle timing?

[Robert Blum, President and CEO]

Yes. No. I think having the results in hand and early in the quarter is not going to -- obviously, the FDA will see them as we release them and hope to see them presented, but they won't we think impact review. It will be -- the safety data will be probably part of an update during the review cycle, but that's it.

[Charles Duncan, Cantor Fitzgerald]

Okay. And then going on to reldesemtiv, just one quick question regarding the conduct of that trial. And I think you mentioned in the previous set of questions or a couple of before that you're kind of enriching for faster progressing patients. And so I guess I'm wondering are you explicitly asking for more bulbar onset versus limb onset patients seemed like to be consistent with that given that under two years since symptom presentation?

[Robert Blum, President and CEO]

Stuart, do you want to take that?

[Stuart Kupfer, SVP and Chief Medical Officer]

Yes. We're not seeing that restricted in terms of our enrollment. We're certainly enrolling patients in both categories. But as I mentioned before, major criteria to enrich for faster progressing patients based on that LSAFRS score at baseline and the time since symptom onset.

[Charles Duncan, Cantor Fitzgerald]

Okay. Thanks for taking the questions.

[Stuart Kupfer, SVP and Chief Medical Officer]

Thank you.

[Robert Blum, President and CEO]

Thank you, Charles.

[Operator]

Your next question comes from the line of Rohit Bhasin with Needham and Company.

[Robert Blum, President and CEO]

Good afternoon, Rohit.

[Rohit Bhasin, Needham and Company]

Hi. Good afternoon. This is Rohit on for Serge. Thanks for taking my question. Can you talk a bit about how the METEORIC-HF trial fits with the gold market strategy for omecamtiv. Do you expect a label expansion or better payer reimbursement?

[Robert Blum, President and CEO]

Sure. I'll ask Fady to speak to that and maybe Andrew might want to add.

[Fady Malik, EVP of R&D]

Yes. I think if METEORIC is positive we would at some point submit for a supplemental NDA filing an expansion of the label that would include the results of METEORIC. The clinical benefit there is important patients and certainly would be worth having in the label that wouldn't come until after the primary approval of omecamtiv mecarbil. And I think being -- that improving exercise capacity is something that is rarely shown with drugs that improve heart that would be a unique feature of omecamtiv mecarbil so the trial be positive. Maybe I'll turn it over to Andrew to see if he has anything else he wants to add there.

[Andrew Callos, CCO]

Sure. And we're going to be negotiating access pre-approval, post-approval and largely we'll be using the data from galactic. If we have a positive METEORIC trial that certainly will enhance the benefit. We could bring to patients especially in capacity. It could enhance our value argument. If patients feel better or could be more productive. So it's really going to depend on how the data read out and what the adjustments are to the label. But I wouldn't expect it to have a major impact on our overall access strategy or access levels.

[Robert Blum, President and CEO]

What it does do is it reinforces the mechanism as provides what could be differentiating benefits to patients beyond outcomes, this being a functional outcome. And in that way it could reinforce the use of omecamtiv mecarbil. But I agree with Andrew. It's not likely to drive a view things. It might very much have the effect of things like adherence and compliance of patients and also how physicians might ultimately view the category.

[Rohit Bhasin, Needham and Company]

Great. Thank you.

[Operator]

And there are no further questions in queue at this time. Robert, your closing remarks please.

[Robert Blum, President and CEO]

Thank you. Thanks very much to all the participants on our teleconference today. Thanks for your continued support and your interest in Cytokinetics. We're pleased to be able to provide you updates with respect to our progress as well as our prospects. Obviously, a lot is going on at our company and we're looking forward to continuing to execute well on our key milestones through the remainder of this year. And then peering into next year as mentioned, it could be quite a transformational year 2022. We look forward to sharing with you all of those updates. And with that operator we can conclude the call.

[Operator]

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