Cytokinetics Inc (CYTK) 2021 Q2 法說會逐字稿

Good afternoon, and welcome, ladies and gentlemen, to Cytokinetics' Second Quarter 2021 Conference Call. (Operator Instructions). I will now turn the call over to Diane Weiser, Cytokinetics' Senior Vice President of Corporate Communications and Investor Relations. Please go ahead.

Good afternoon, and thanks, everyone, 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 the secondary analyses from GALACTIC-HF, our positive Phase III clinical trial of omecamtiv mecarbil as well as recent interactions and next steps with the FDA.

Next, Andrew Callos, our EVP and Chief Commercial Officer, will provide an update on progress towards our go-to-market strategy for omecamtiv mecarbil and how those plans intersect with our franchise development strategies and our future plan for the commercialization of Aficamten or CK-274. Then Stuart Kupfer, our SVP and Chief Medical Officer, will provide an update on our development program for Aficamten with focus to recently announced results from REDWOOD-HCM, our positive Phase II clinical trial.

Next, 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 our financial outlook and corporate development strategies before Robert Blum will return to provide concluding thoughts and expected 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 may 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 current report regarding our second quarter 2021 financial results filed on Form 8-K.

We undertake no obligation to update any forward-looking statements after this call.

And now I will turn the call over to Robert.

Thank you, Diane, and thanks to everyone for joining us on the call today. We had a productive second quarter, which has continued with intensity more recently as we've delivered against multiple milestones across our cardiovascular and also our neuromuscular development programs. In the past few quarters, we've made tremendous progress on the clinical development front, punctuated by positive Phase III results from GALACTIC. Positive Phase II results from Redwood HCM, completion of enrollment in METEORIC-HF and initiation of COURAGE-ALS, the Phase III clinical trial of reldesemtiv in patients with ALS.

Looking forward, we're preparing for our first NDA submission and executing well against commercial readiness objectives while also advancing 3 distinct late-stage development programs, all expected to be in Phase III clinical trials by the fourth quarter. This is an extraordinary achievement for any company, much less one of our size, but it's a testament to our focus, our innovation, our resilience, our resourcefulness and our disciplined strategic corporate development.

Importantly, progress across our pipeline also catalyzed our recent equity offering, which fortified our balance sheet and which is expected at year-end to have us with over $600 million. This will ensure a strong financial position as we pass-through key milestones in building a sustainable and durable business anchored in our industry-leading muscle biology focus.

As Fady will elaborate, new analyses from GALACTIC-HF reinforce previous results, which reinforce that patients with higher risk factors, underscoring more severe heart failure, derived greater treatment benefit from omecamtiv mecarbil when added to standard of care, and they augur well for a defined clearly identifiable target patient population.

These patients remain amongst the toughest to treat despite the availability of guideline-directed medical therapy and based on continued feedback from the health care professional community, we believe omecamtiv mecarbil may fill an unmet need in the treatment armamentarium.

As you'll hear more in recent months, we've conducted several additional interactions with FDA towards our goal of submitting an NDA for omecamtiv mecarbil in this second half of the year. And concurrently, under Andrew's leadership, our commercialization strategy is also taking further shape. We have active work streams progressing across every element of our go-to-market strategy, including product positioning, market research, value proposition development, market access and manufacturing and other logistics scale up.

Turning to another underserved cardiovascular patient population, we were pleased to share top line results of REDWOOD-HCM, which met our high expectations for this dose-ranging trial and our next-in-class objectives. As pioneers in the science of modulating cardiac myosin, it's rewarding to see that the physiochemical properties that we prioritized in optimizing Aficamten are translating into clinically meaningful results for patients.

With positive results from Redwood HCM now in hand, we have received constructive FDA feedback from our recent Type C and end of Phase II interactions supportive of progression into our Phase III trial intended to get underway in the fourth quarter of 2021 with enthusiastic clinical trial sites across North America and Europe, we anticipate high interest for enrollment, and we'll provide updates as the trial gets underway.

And finally, with clarity on a submission strategy for omecamtiv mecarbil as well as positive results from REDWOOD-HCM, supporting a Phase III trial and a reinforced balance sheet, earlier this week, we announced the start of COURAGE-ALS, our Phase III clinical trial of reldesemtiv in patients with ALS. And as a reminder, under the terms of our amended collaboration agreement with Astellas, Cytokinetics now controls development and commercialization of reldesemtiv and Astellas will contribute $12 million towards the conduct of this trial.

We feel fortunate to be at a major turning point in our corporate development. The promise of modulating contractile proteins that drive muscle contractility is being realized with our positive clinical trial programs, and we're grateful to our shareholders for continuing to believe in the potential of this platform so that we may deliver to patients first-in-class and next-in-class drug candidates that may improve their health span and also overall quality of life.

And with that, I'll turn the call over to Fady to elaborate on recent developments related to omecamtiv mecarbil.

Thanks, Robert. As you mentioned, results from additional analysis of GALACTIC-HF presented during the quarter at Heart Failure 2021, an International Congress of the European Society of Cardiology, continue to build upon previous results, underscoring that patients with markers of more severe heart failure who are at greater risk, drive greater clinical benefit from treatment with omecamtiv mecarbil when added to standard of care.

Specifically, results of analyses in patients with higher baseline NT-proBNP and patients with severe heart failure based on modified criteria from the Heart Failure Association of the European Society of Cardiology, Advanced Heart failure position statement are presented. Despite the availability of and adherence to guideline directed medical therapy, many patients with severe heart failure remain at high-risk for significant clinical events. And based on these data, omecamtiv mecarbil may offer a new treatment option for more severe heart failure patients who are maxed out on standard of care and still in an out of hospital.

As I've said before, these results align well with the mechanism of action of omecamtiv mecarbil insofar as its ability to improve cardiac function and performance appears to impact the outcomes in patients who present with signs that their cardiac function is particularly limiting.

It's been affirming and encouraging to hear key opinion leaders share this perspective, especially given that the greatest need exists among those patients for which the benefits of omecamtiv mecarbil are most concentrated.

Specifically, we've heard that the results lend themselves to an opportunity to highlight a clear population of patients who may benefit from potential treatment with omecamtiv mecarbil. The many physicians with whom we've engaged, point out that options are limited in these patients. And if approved, omecamtiv mecarbil may provide a key addition to existing standard of care, given its mode of action and lack of adverse impact on hemodynamics or kidney function.

METEORIC-HF, the second Phase III clinical trial of omecamtiv mecarbil aims to expand on the nature of benefit by potentially demonstrating that a drug candidate that improves systolic function may enable patients to improve exercise capacity and stamina, allowing them to do more of the things they enjoy every day.

During the second quarter, we completed enrollment in METEORIC-HF, despite the headwinds of the pandemic and expect to complete its conduct by year-end, which would enable reporting results in early 2022.

Now on to the regulatory front. Since the beginning of the year, we participated in 3 productive meetings with FDA, including a top line meeting to review and gain feedback on initial results from GALACTIC-HF, a Type C meeting to elaborate on key aspects of results from GALACTIC-HF and the use of omecamtiv mecarbil, informing our approach to an NDA submission and a pre-NDA meeting to review results -- rather review details of the submission, including such things as specifics of its content and the format of data sets.

Together, these meetings have been engaging and constructive and has met our objectives to inform the content and format of our NDA submission. We remain on track as we continue to work towards the submission of our NDA in the second half of this year based on the results of GALACTIC-HF in combination with the rest of the development program, comprising over 30 clinical trials and informed by our long-standing regulatory discussions.

In parallel, we're also discussing with FDA our strategy to enable personalized dose optimization in patients being treated with omecamtiv mecarbil to be available at the time of potential approval and utilizing the most robust technology and a centralized approach to collect and process samples as well as to make patient data available to physicians.

We look forward to elaborating on this strategy for optimal personalized dosing in the future. As we move closer to our goal of submitting our NDA to the FDA for the potential approval of omecamtiv mecarbil, our growing team of medical science liaisons are working to educate hospital-based and community cardiologists on the challenge of impaired contractility in patients with heart failure with reduced ejection fractions, and we remain committed to helping physicians increase their understanding of the sarcomere in cardiac muscle function.

Additionally, we've made progress on development of a framework for an investigator-sponsored study program. And we expect to further elucidate the potential of omecamtiv mecarbil within the treatment armamentarium.

And with that, I'll turn the call over to Andrew to elaborate on progress against the go-to-market strategy for omecamtiv mecarbil.

Thanks, Fady. During the second quarter, our Board of Directors endorsed our proposed go-to-market strategy for omecamtiv mecarbil. And since then, we have proceeded in its implementation as we prepare for a potential commercial launch in 2022. We plan to present a deep dive into the strategy and how it intersects with our cardiac muscle franchise strategy and planning for the commercial launch of Aficamten at an Investor Day later this year. But today, I will share a few highlights of our progress.

From an organizational development perspective, in addition to the stellar team I joined, we are expanding the commercial organization at all levels with key hires in marketing, health economics and outcomes research, analytics, supply chain and logistics and market access. In addition, I anticipate having the full leadership team in place by the end of the summer.

As you heard from Fady, the results of the GALACTIC-HF and the secondary analyses provide clarity around the subset of heart failure patients in which the benefit of omecamtiv mecarbil are most concentrated. That is those with an ejection fraction less than 30 or who can no longer tolerate guideline directed medical therapy due to renal or blood pressure impairment or those recently hospitalized. Those patients likely to drive the most benefit from omecamtiv mecarbil represent 50% -- approximately 50% of all heart failure with reduced ejection fraction patients.

In addition, our market research has confirmed that they are managed by fewer than 30% of total cardiologists and in fewer than 15% of total hospitals in the U.S. that treat the majority of these severe patients. Targeting this well-defined intractable subset of cardiologists and hospitals also enables us to effectively launch with a lot of size specialty cardiology field force. Notably, there is also a significant overlap between heart failure and ATM directed accounts. Specifically, there are approximately 1,100 high-value hospitals and centers of excellence, treating both patient populations, so the cardiac muscle directed field force we are building today is purpose-driven to leverage the infrastructure and relationships we established in support of omecamtiv mecarbil or Aficamten in 2 to 3 years.

Put simply, we expect that our reps will have another product in their bag without need to build an independent field force. Furthermore, we recognize and appreciate the high cost burden of heart failure as it represents the most common hospital admission diagnosis for Medicare, hospitalizations and readmissions are considerably higher among patients with lower ejection fraction.

And as you may know, these are the patients who become their frequent flyers in hospitals given their increased risk of rehospitalization with every subsequent hospitalization event. Given the evidence from GALACTIC-HF demonstrating the risk reduction resulting from omecamtiv mecarbil was greatest among patients with lower ejection fraction levels, we are evaluating the cost effectiveness potential for patients being potentially treated with omecamtiv mecarbil.

Finally, it will be critical to our work with payers to ensure patients have access to omecamtiv mecarbil. The current heart failure reimbursement mix is approximately 55% Medicare Part D and approximately 30% commercial payers. We have initiated payer discussions with several of these key stakeholders and they're getting a better understanding of what drives their decision in the heart failure arena, particularly as they contemplate a host of new branded therapies to treat this patient population.

Toward this end, we're also developing a distinct value propagation based on the results from GALACTIC-HF, and we believe the well-defined patient population with severe heart failure will be a welcome strategy among the payer community.

And with that, I will turn it over to Stuart to provide an update on Aficamten and next steps in the cardiac myosin inhibitor development program.

Thanks, Andrew. As we announced in today's press release, during the quarter, we received final approval from the World Health organization and The United States Adopted Names for Aficamten to be used as the international nonproprietary name for CK-274.

About 3 weeks ago, we announced positive top line results from cohorts 1 and 2 of REDWOOD-HCM, the Phase II clinical trial of Aficamten. Since we held a dedicated conference call to report the results, I'm not going to go into detail, but rather recap the key data and focus on next steps toward opening a Phase III clinical trial by the end of this year.

Top line results from REDWOOD-HCM demonstrated that treatment with Aficamten for 10 weeks resulted in highly statistically significant reductions from baseline compared to placebo in the average resting and post Valsalva left ventricular outflow track pressure gradients in both cohorts 1 and 2.

In cohort 1, which evaluated a lower dose range of 5 to 10 milligrams, 79% of patients treated with Aficamten achieved the target goals 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.

In cohort 2, which studied a higher dose range of 10 to 30 milligrams, 93% of patients treated with Aficamten achieved the target goal. Patients treated with Aficamten experienced decreases in both resting and post Valsalva gradients by week 2 and a maximum treatment effect was achieved by week 6 after completion of dose titration, which was sustained through the final visit at week 10.

Treatment with Aficamten was generally well tolerated. The incidence of adverse events were similar between treatment arms. No serious adverse events were attributed to Aficamten and no treatment interruptions occurred on drug treatment. Importantly, we were pleased to see that only 1 patient experienced a transient decrease in left ventricular ejection fraction less than 50%, which required a dose adjustment but did not result in dose interruption.

Overall, feedback from the investigators of the trial has been quite positive and enthusiastic. Given the magnitude of the treatment effect, the proportion of patients who achieved response criteria and the overall safety and tolerability profile observed. In the quarter, we initiated the open-label extension trial of REDWOOD-HCM, which continues to enroll patients from cohort 1 and is now enrolling patients from cohort 2.

The primary objective of this trial is the evaluation of long-term safety of Aficamten and the secondary objectives focus on the evaluation of gradient reduction and pharmacokinetics with long-term administration of Aficamten.

We are also conducting a cardiac MRI sub-study to assess changes in cardiac morphology, function and fibrosis. Patients in the open-label extension will begin at the lowest dose of 5 milligrams and will be individually titrated to achieve target gradients as informed by cohorts 1 and 2.

As a reminder, we still have cohort 3 in REDWOOD-HCM ongoing, which includes patients treated with Aficamten who are also on disopyramide as background therapy. This cohort will further inform the inclusion of the small but important patient population in Phase III. We are moving rapidly to begin our Phase III clinical trial of Aficamten in patients with obstructive HCM in the fourth quarter, continuing preparations that began last December when we obtained results of the cohort 1 interim analysis from REDWOOD-HCM.

During the second quarter, we had a Type C meeting with the FDA to review our plan for the Phase III trial. In that meeting, we reviewed the design, endpoints and patient populations and found the feedback we received enabling of our plans to advance the Phase III.

Building on this informative Type C meeting, we recently received FDA feedback from our end of Phase II meeting. After review of the final doses selected for Phase III, namely 5, 10, 15 and 20 milligrams, and our proposal to continue individualized echocardiogram guided dosing, the agency agreed with our dose titration strategy.

We also received helpful feedback on other aspects of the overall development program, including nonclinical safety, clinical pharmacology and the preferred format for data sets, among other components. In addition, we initiated interactions with EMA during the quarter and received feedback and informed our proposed Phase III clinical trial design.

We anticipate additional engagements this quarter from HTAs to further inform our strategy for this program in Europe. Moreover, under our collaboration with Ji Xing Pharmaceuticals, during the second quarter, Ji Xing continued enrolling patients in a Phase I study of Aficamten in China and prepared for participation in the Phase III clinical trial of Aficamten in obstructive HCM.

As we finalize preparations for a Phase III trial and as part of our clinical development program for Aficamten, we are now considering the best path forward for a trial in patients with non-obstructive HCM and expect to clarify our approach later this year. And as we have previously stated, in addition to exploring the opportunity to address hypercontractility in obstructive and nonobstructive HCM, we believe there is also a subset of heart failure patients with preserved ejection fraction, whose underlying cause of their disease is driven by left ventricular hypercontractility and hypertrophy. These patients may also benefit from treatment with an optimized next-in-class cardiac myosin inhibitor, and we remain interested in pursuing this population as the development program matures.

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

Thanks, Stuart. I'll first provide an update on cash, revenue and spending, and then Ching will review our financial outlook, revised financial guidance for 2021 and corporate development strategies looking forward. More details on our actual results for the second quarter 2021 are included in the press release, which we released earlier this afternoon.

We ended the second quarter with approximately $424 million in cash and investment. Our revenues in Q2 2021 came primarily from our strategic alliances with Amgen and Astellas. Our second quarter 2021 R&D expenses increased to $36.4 million from $21.8 million in the first quarter of 2020, primarily due to the transition costs related to the termination of our collaboration with Amgen, the purchase from Amgen of approximately $7.3 million of materials, including manufactured quantities of active pharmaceutical ingredients for omecamtiv mecarbil and increases in spending on our clinical development activities for our cardiac myosin inhibitor programs.

More than 70% of our R&D expenses are attributable to our cardiovascular program, as expected, given activity for transition from Amgen, METEORIC-HF and the cardiac myosin inhibitor programs, and the remainder of our expenses were attributable to our early research and skeletal activity.

Our second quarter 2021 G&A expenses were $21.2 million, up from $14.2 million in Q2 2020 due to higher personnel-related costs, including stock-based compensation and higher commercial readiness spending.

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

Thanks, Robert. As Robert indicated, we ended the second quarter with approximately $424 million in cash. In addition, we recently raised approximately $297 million through an equity offering net of expenses. Therefore, our pro forma cash today is approximately $721 million, which represents more than 3 years of cash runway based on our revised net cash utilization guidance of $195 million to $215 million in 2021.

This new guidance includes nonrecurring new building construction costs of approximately $35 million and assumes receipt of $45 million under our funding agreement with RTW Investments. Net proceeds from the equity offering will support the conduct of a Phase III clinical trial of Aficamten in patients with obstructive HCM.

Expansion of the clinical development program for Aficamten to include other indications, planned commercial launch activities for omecamtiv mecarbil, the conduct of COURAGE-ALS are now ongoing Phase III clinical trial of reldesemtiv in patients with ALS and for research and general corporate purposes, including working capital.

During the second quarter, we also made progress against our twofold corporate development strategy to first seek potential royalty monetization and/or structured financing deals in order to further support commercial launch of omecamtiv mecarbil and continued development of Aficamten. And second, to seek a development and commercialization partner for omecamtiv mecarbil and Aficamten in complementary geographies to that where we intend to go-to-market ourselves.

Our partnership priorities are focused to Japan with the goal of securing a deal which bundles omecamtiv mecarbil and Aficamten to support co-funding of a life cycle management studies as well as regulatory and commercial activities, respectively.

Our focus will also be to China in order to secure a potential licensing agreement for omecamtiv mecarbil and selectively to Europe and other markets to enter into potential agreements with co-development and co-commercialization partners for omecamtiv mecarbil. As such, we expect to preserve North America and potentially European rights for development and commercialization.

I'm pleased to report that we've had encouraging and productive interactions to advance these strategies, and we look forward to continuing those discussions as may result in a deal or deals in the second half of the year.

Cytokinetics has always gained access to capital through a diverse array of deal structures, and we continue to believe that our path to commercialization and sustainable cash flows and profitability will be served by our continued monetization of our leadership in muscle pharmacology through deal-making.

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

Thank you, Ching. As we look towards the remainder of 2021 and our upcoming milestones, I'm reminded of the vision we established more than 2 decades ago. It was a time when most pharmaceutical and biotechnology companies were stepping away from research in cardiology, and Cytokinetics was boldly pursuing a novel scientific rationale discovery platform and biology.

Now that vision is coming into more refined focus as we continue to double down on our cardiovascular pipeline, with 2 muscle biology directed drug candidates advancing and with several others close behind. And as we make progress in our neuromuscular vertical based on regulatory, clinical, commercial and financial clarity.

In addition to the clinical, regulatory and commercial progress we made related to omecamtiv mecarbil during the quarter, we successfully reached several agreements to facilitate the transition of the programs for omecamtiv mecarbil and CK-136 from Amgen to Cytokinetics, including an agreement for the sale and our purchase of approximately 2 tons of active pharmaceutical ingredient of omecamtiv mecarbil.

As you can imagine, transition activities following the 15-year collaboration takes significant time and attention. And I want to thank my many colleagues who have been engaged diligently in this activity as we've assumed more responsibilities and built out our teams over the past 6 to 9 months.

On the neuromuscular front, we're also pleased to have COURAGE-ALS underway, and we believe its design leverages key learnings from FORTITUDE-ALS, our Phase II clinical trial of reldesemtiv in patients with ALS and as well the dynamics of ALS therapy development and the urgent needs of the patient community.

With greater efficacy seen in patients whose disease seems to be progressing more rapidly we believe the design of COURAGE-ALS is itself enriched towards that patient population accordingly.

Additionally, based on feedback from patients and caregivers and advocates and payers as well as health care professionals, the design of COURAGE-ALS incorporates important elements that are intended to remove key barriers to clinical trial participation, including our incorporating remote clinic and home nursing visits as well as mobile app-based endpoint measurements.

Importantly, we're working towards a goal to provide continued access to reldesemtiv for patients who complete COURAGE-ALS as well as for patients who have previously participated in our ALS trials. The program is being developed with the objective to ensure ethical and equitable access.

We fully recognize the urgency to bring new medicines to people living with ALS, and we're diligently working with purpose, passion and compassion.

In summary, we expect that the next 12 to 18 months may be even more transformational for Cytokinetics. With 2 positive late-stage trials for our lead cardiovascular programs, we look forward to advancing our goal towards NDA submission of omecamtiv mecarbil for the potential treatment of heart failure with reduced ejection fraction and also starting a Phase III clinical trial of Aficamten in patients with obstructive HCM. Together, these potential medicines may change the treatment landscape for these severe cardiovascular diseases by harnessing the power of myosin modulation and in that way, offering patients new hope.

Now let me recap our expected milestones for 2021. For omecamtiv mecarbil, we expect to submit an NDA to the FDA in the second half of 2021, and we expect to complete the conduct of METEORIC-HF by year-end with results expected in early 2022.

For Aficamten, we expect to begin a Phase III clinical trial of Aficamten in patients with obstructive HCM in the fourth quarter of 2021.

For reldesemtiv, we expect to continue enrollment of COURAGE-ALS throughout 2021. And for our ongoing research, we expect to advance programs and conduct IND-enabling studies with 1 to 2 potential drug candidates through the remainder of 2021.

And operator, with that, we can now open up the call to questions, please.

(Operator Instructions) Our first question comes from the line of Jason Butler with JMP Securities.

First one, just based on the regulatory feedback that you have on omecamtiv, can you talk about what you plan to propose to include in the label in terms of the analyses around patients with lower baseline ejection fraction? And then the second question for 274, can you talk about conducted or planned ex U.S. regulatory interactions? And specifically, how you think including patients from China can help impact enrollment and the regulatory dialogue there?

Okay. So to unpack that, let's start with omecamtiv, and you asked a question about our plans. Some of this, I'm not going to be able to speak to on this call, of course. But I'll tell you that for the fact that GALACTIC-HF was a positive clinical trial, we expect that it's indication as we will propose to FDA would be inclusive of those patients that participated in the study.

But to your specific question as would be potentially inclusive in the label of those data as highlights those patients that benefit the most. And we think there's ample precedent in already approved drugs in heart failure for the inclusion of data, especially as was, in our case, prespecified for those subpopulations that seem to be doing better than others. I hope that may answer that first question.

Your second question, I believe, related to CK-274 and our plans for regulatory outside the U.S., is that right?

Exactly, yes.

So that's something that is beginning, and I'd say ongoing, I don't think we can yet be as clear minded and definitive about that in light of those being still ongoing conversations.

Fady, anything you want to add to that?

I think only in that our plan is to conduct the Phase III outside of North America, so including Europe and China, of course, and regulatory interactions to enable that are underway.

Yes. And as it relates to your question about China, our expectation is through our collaboration with Ji Xing, that they will be ready to go so as to be enabling their enrollment of patients in China as part of the same global registration program and pivotal study.

Your next question comes from the line of Dane Leone with Raymond James.

I'll keep it brief. I just wanted to ask in terms of the FDA discussions on omecamtiv, it sounds like you're probably moving forward with the submission with ahead of the METEORIC data. Is that going to be integrated into the submission package at some point? Or do you feel like it is not necessarily relevant for the label that you're trying to get approved with the FDA at this point?

Good question. So we believe that our submission will stand on GALACTIC alone and that as METEORIC may provide further information, and we won't have that data until 2022, we could then consider whether -- and this may be occurring post-approval, hopefully, of omecamtiv, whether then the label might be then expanded to incorporate that, which incorporates results pertaining to omecamtiv in METEORIC-HF, but our strategy pivots on GALACTIC-HF.

Your next question comes from the line of Carter Gould with Barclays.

Robert, great to see all the progress. I guess 2 questions from us. First off, you've talked in the past around there being a distinction between your Phase III and EXPLORER. Now that you've had these meetings with FDA, does that still hold true? And will that expand beyond the potential inclusion of that population in cohort 3 of REDWOOD?

And then maybe just as we think about finally getting a look at the REDWOOD data presentation at an upcoming medical meeting, can you maybe just give a little bit more color on what other incremental analyses we might see in those upcoming medical presentations?

Sure. I'll turn it over to Fady, who may also then turn it over to Stuart, but I'll say that for having now a couple of interactions with FDA pertaining to CK-274, I think it's affirming of our plans for the Phase III trial and Fady and Stuart can pick it up from there.

Yes. I mean, our trial design for Phase III will certainly borrow from what was conducted with omecamtiv and EXPLORER, but we'll be different in other ways, and we'll elaborate on that later in the year.

We certainly have, I think, agreement on how we plan to go forward in Phase III with FDA, and maybe Stuart can comment on what we might plan to present at a subsequent medical meeting regarding REDWOOD.

Well, we'll certainly plan to expand on the results we publicized in the recent press release. We'll have details on our baseline characteristics, biomarkers, pharmacokinetic data and NYHA class, just as an example. So there's more interesting data to come. Thanks for the question.

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

Robert, I had a couple of questions on CK-274. So Bristol has had on their call a question on CK-274 versus Mavacamten. I'm just curious, they're saying that they don't see differentiation between the 2 molecules. And I'm curious how you guys are seeing it. Just everything that we've seen with the published EXPLORER data and everything that you've seen with CK-274, how confident are you that CK-274 is actually a differentiated molecule? And is there anything in the Phase III data set that you produced that you think could alter that thinking?

And then the second question just is in the myosin inhibition in general. Just curious how you would perceive an adcom if Mavacamten were to get one, would it be a net-net negative, positive? Are you expecting one? Or how are you thinking about this generally?

Sure. So very good questions. I'll start and ask my colleagues if they want to add. We do believe -- we very much believe that these are differentiated molecules. And in fact, if we didn't believe that, we wouldn't be taking Aficamten into Phase III. And we've verified that. So it's not just our own thinking, it's verified also by our conversations with Key Opinion Leaders and investigators in this space.

But I understand a perspective that would suggest that the data from REDWOOD are comparable. What I would underscore is that we believe that some of these things we specifically designed into CK-274 or Aficamten, like a more rapid time to onset of activity and enabling better, easier dose titration as well as more rapid reversibility.

These are things that enable in the conduct of future clinical trials, the inclusion and exclusion of patients. These are things that are enabling of a clinical trial design that should, in fact, further advance the category and the field if we didn't think that these properties of a next-in-class molecule didn't do that, we wouldn't be in a position to invest here as we expect could be advancing the field.

So we can't elaborate today on what will be those features and how they play out in a Phase III trial. But you'll know that soon enough. When we announced the start of this study, we'll talk about the clinical trial design, and hopefully, those will come into more clarity. So I think that's my answer to your first question.

Your second question, can you remind me?

Yes. Just on the Mavacamten adcom, you perceive that as a negative or a positive if we may ever were to get one?

Yes, why don't I turn to Fady, maybe to speak to that.

Yes. I frankly don't want to really speculate on whether or not they may or may not get an adcom. That's really up to FDA to determine and based on the submission that was made. So it -- we'll just have to wait and see if they decide to have one.

There hasn't been any suggestion yet that there will be an adcom. So we're certainly not assuming that there should be. But if there is, we'll certainly be prepared to be astute observers and how that might inform our planning as well.

Your next question comes from the line of Chad Messer with Needham & Company.

First of all, it's -- congratulations on your perseverance with all of these programs, it's great to see you guys have at least 3 exciting programs that are kind of in play, if you will, and could bring a great benefit to patients, they all have not had the easiest time.

Just a couple of questions on reldesemtiv. You guys are moving forward with the Phase III there, very excited for it. What's been the response from the ALS community because they've been waiting around for a while to hear about this, we all have, but I think maybe the patients the most anxiously.

And then maybe can you comment on what lessons you learned from FORTITUDE that you think will make the -- we're calling it the COURAGE. Is that right? Phase III trial, a higher probability success there?

Sure. I'll take the first part of that question, I'll ask Fady to take the second part. So in terms of the response from the ALS community, admittedly, the community was confused by what had been the delay between the announcement of results of FORTITUDE-ALS and our start of COURAGE-ALS because if you recall, when those results were first announced, they were characterized as amongst the most promising Phase II results ever seen in ALS, and that being an international placebo-controlled large study, it showed quite encouraging data lending support for Phase III.

But as we committed to shareholders, we wanted to make certain that before we advanced reldesemtiv to Phase III, we had a number of things that we had to accomplish first. We wanted to discuss those results with FDA but also with payers, both in the U.S. and in Europe. We wanted to discuss a design of a clinical trial that would be enabling of some looks into the data as would be enabling of an interim stop for futility, if it looked like that was appropriate.

And the second interim down the road as could also be expanding of the study if it looked like that may be warranted. We wanted to understand the cost of the study, and we wanted to renegotiate our collaboration agreement with Astellas in order to have them enable our lead in this area and also their co-funding of that trial. Both of those things we negotiated successfully.

We wanted to best understand what patients would be looking for in their participation in a clinical trial. Because as you may know, the landscape for trials in ALS has become more crowded, which is a good thing, but at the same time, we wanted to make certain we could be enrolling our study expeditiously and know that we would have the support of the patient community. It so happens that in these last couple of years, during this time when we were assessing these matters, the ALS community, as led by certain advocacy groups has become much more assertive and engaged. It's a good thing. And at the same time, they've been assessing and evaluating which clinical trials would be best to direct patients to participate in.

I'm really pleased to be able to share today that I AM ALS, one of those advocacy groups that does rate clinical trials gave our trial COURAGE-ALS its highest rating. And there are only a couple of trials that have that 5-star rating. They look at this design in terms of what's in the best interest of patients, and they scored it amongst their highest ever clinical trials.

So all of these things we wanted to line up before we started this trial in order to make certain that we could finish what we started and do so to give the drug and patients the best chance for success here. And I think we did that well. And hence, we've started courage ALS now.

With that said, I'll turn it over to Fady to answer the second part of your question.

Thanks, Chad. With respect to the design of COURAGE and how it may have a higher probability of success. I think you have to look back to our conduct of FORTITUDE, which you mentioned to begin with, FORTITUDE was a pretty sizable study in ALS. It enrolled over 450 patients. We had, I think, compelling signals of slowing of decline in both the primary endpoint of this Phase III study, the ALSFRS, as well as in slow vital capacity. And those signals were strengthened when you looked at patients that came into the study that were progressing more quickly than others.

And so in designing COURAGE, as others are doing now at ALS is focusing on enrolling patients that -- whose disease may be progressing more rapidly and other things that we've done and the design to optimize, we think, its chances for success. So we're fairly encouraged based on both the precedent FORTITUDE-ALS as well as the way we've implemented it in COURAGE.

From a portfolio standpoint, it was incumbent upon also to know that when we're advancing reldesemtiv in ALS, it's occurring alongside of the advancement of our pipeline for new cardiovascular medicines. So omecamtiv mecarbil moving forward as well as Aficamten moving forward, we believe, is enabling of our advancement of reldesemtiv in key ways and as is the interest of diversified product development risk as well as hopefully, maximizing potential shareholder value.

All right. Great. Thank you. I appreciate those answers on Aficamten. And once again, congrats on getting to this place with all 3 of the major programs as well as the other things you're working on.

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

Robert, just to clarify Jason's question earlier on omecamtiv mecarbil. Are you going for a broad label? Or would you expect that the label will focus on the more severe patients, specifically calling out patients with a lower ejection fraction?

Yes. Again, I'm not going to be so elaborative to our strategy, but I think it's fair to say that our intention, our objective is to go for a broader label, but as would also be inclusive of those data and results that are highlighting where the effects are more maximal. And as such, provide physicians more information as to guide therapy.

Okay. And then can you talk about the feedback that FDA has provided at the Type C and pre-NDA meeting on your plans to submit the NDA on the GALACTIC data? Has there been any pushback about the focus on the more severe patients? And have they suggested that any additional clinical work might need to be done? Or do they seem completely on board that the available data is sufficient?

So good questions. We believe in the multiple interactions we've had with FDA this year that we have heard what we need to hear in order to lend support for what I just said, which is to say, we believe that this filing should be built around GALACTIC-HF and the results and data that I am highlighting, in particular and including of those patients that may stand to benefit the most.

Your next question comes from the line of Emanuela Branchetti with H.C. Wainwright.

So you touched upon this maybe earlier, but can you share some of the feedback you received from the KOLs regarding the results obtained with REDWOOD, perhaps in relation to the differentiation from Mavacamten and their expectations around the design and the target population for the upcoming Phase III?

Sure. So specifically, your question relates to feedback we've received on Aficamten and how it may set the stage for Phase III.

Correct.

Yes. I think in presenting these results to our steering committee, we haven't -- obviously, since we haven't presented them more broadly, we've focused on those that were involved in the trial. They were really quite pleased with the profile of what we saw, the number of responders, the magnitude of effect, evidence of reversibility and the overall safety profile that we observed in the Phase II trial.

I think all of those things lend themselves to the design that we will implement in Phase III, which, as I said, we'll elaborate at a later time. But overall, feedback was quite enthusiastic.

Got it. Got it. And switching gears to reldesemtiv. It's nice to see the drug beginning the pivotal study as planned. And I know it's early, but I was hoping you could give more color around the expected time line for the enrollment. I saw you incorporated in the design remote visit. And so I just was just wondering based on your experience with the enrollment of ALS patients, do you expect the COVID-19 to have an impact on the trial. And so when should we expect the interim analysis to occur?

Well, I'll start. I'll turn it over to Stuart a little bit. But I think it's still very early to speculate on the timing for the trial. We're just literally starting to screen patients. We're still in the process of getting sites up and going. I think once we start to see the pace of enrollment, we can maybe provide some better estimated timing. Stuart, do you want to add anything to that?

Well, what I'll add is that I think we've all learned a lot about conducting clinical trials in a pandemic. I think on other programs, we managed reasonably well with respect to METEORIC and REDWOOD-HCM. But there have been lessons learned, and we've designed COURAGE-ALS to as much as possible preempt issues related to disruptions from the pandemic.

In large part, that includes a large portion of home visits, for patients who enroll in COURAGE-ALS. So we have very proactively specifically designed the trial to unburden patients. So they won't have to in most of the -- for most of the study visits actually to have to present themselves in person in the clinic. So all of this has been anticipated. We've incorporated these features into the study design, and we hope that will bode well for managing any further bumps in the rev related to pandemic.

And your last question will come from the line of Graig Suvannavejh with Goldman Sachs.

Thank you very much for the update and congrats on the progress. I was curious about earlier comments you made on the call about your early experience with commercial payers. I believe that was in relationship to omecamtiv mecarbil. I was wondering if you can share any of the insights from that early experience, certainly, there's still some time to go, but wondering what the initial feedback has been?

And then secondly, I wanted to get a sense of -- and I might have missed this before, so my apologies. As you think about the clinical trial design for Aficamten how similar or how different might that be from the Mavacamten Phase III as you could expect, many of us will be trying to see how apples-to-apples it may be, and it doesn't have to be, but I'm just curious if you could give us some high-level thoughts around how you're thinking about that Phase III trial.

Sure. So I'll ask Andrew to tackle the first question, which is relating to early feedback and perspectives relating to payers. And then maybe I'll ask Stuart to comment on the second part of your question relating to the trial for Aficamten. Andrew?

Sure, Robert. So the payer meetings, we've had about half a dozen payer meetings across large PBMs, Med-D and commercial. Most of the meetings have been introductory in nature and introducing our company, our science, our people, and we certainly have more substantial interaction scheduled as the year progresses. And we certainly anticipate filing for in December for Med-D inclusion in the 2023 reimbursement and access scheme. So overall, the interactions have been positive, but early.

Yes. I'd say that, in large part, these meetings are focused to socializing the science, introducing the company. We want to make sure we're on their radar screen. As you can well imagine, they do budgeting and other activities in anticipation of new product launches, and those things are already underway.

Now the second part of your question related to the Phase III design of Aficamten and how it might compare to Mavacamten and whether this is going to be an apples and oranges or an apples and apples. And I'll tell you, we believe that for the fact that REDWOOD-HCM delivered on its next-in-class profile that we need to design the study that is advancing the field. And therefore, it should be apples and apples, but there are different kinds of apples.

And with that, I'll just see if Stuart wants to add anything more.

Only that we certainly have learned a lot from the REDWOOD-HCM trial as well as the EXPLORER trial, and we'll take those learnings into our study design for Phase III. We're not really prepared to offer any details or discuss those today. The study design details will be forthcoming later this year.

Yes. You won't have to wait very long. We're going to be providing those details soon enough. Now that we've had these recent interactions with FDA, and we can lock in on the protocol, we expect to begin this study soon, and we'll elaborate on those design elements soon.

And there are no further questions at this time. I'd like to turn the call back over to management for any closing remarks.

Thank you, operator, and thank you to all the participants on our teleconference today. We've had a very productive second quarter, and it sets the table for what we hope will be our ability to continue to execute very well against other key milestones and metrics.

We thank you for your continued support and your interest in Cytokinetics, and we look forward to keeping you updated on our progress.

Operator, we can conclude the call.

Ladies and gentlemen, we thank you for your participation. This does conclude today's conference call. You may now disconnect.