Good afternoon, and welcome, ladies and gentlemen, to Cytokinetics' Third Quarter 2020 Conference Call. At this time, I would like to inform you that this call is being recorded [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 for joining us on the call today. Robert Blum, our President and Chief Executive Officer, will kick off the call with a recap of our top line results from GALACTIC-HF and an overview of our progress during the quarter.

Then Fady Malik, our EVP of Research and Development, will provide perspective on the top line results, what we can expect from presentations at AHA and an update on METEORIC-HF, the second Phase III clinical trial of omecamtiv mecarbil.

Next, Stuart Kupfer, our SVP and Chief Medical Officer, will update on recent progress with CK-274, our cardiac myosin inhibitor, which is a subject of REDWOOD-HCM as well as CK-271, our additional cardiac myosin inhibitor.

Then Robert Wong, our VP and Chief Accounting Officer; will provide a financial overview for the quarter; and Ching Jaw, our SVP and Chief Financial Officer, will discuss strategic planning and our financial outlook before Robert Blum provides concluding thoughts on the company's path forward and expected key milestones for the remainder of the year.

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 materially from those in these forward-looking statements is contained in our SEC filings. 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 again to everyone for joining us on the call today. I'll begin with our most recent news.

A few weeks ago, we were pleased to announce top line results of GALACTIC-HF, which demonstrated treatment with omecamtiv mecarbil, achieved the primary composite efficacy endpoint of the trial and demonstrated statistically significant effect to reduce the risk of cardiovascular death or heart failure related events compared to placebo in patients treated with standard of care and with a p-value less than 0.05.

GALACTIC-HF is a large-scale over 8,000 patient international trial, the first Phase III trial to test this novel mechanism. And admittedly, we and Amgen swung for the fences with this Phase III outcomes trial and the overall development program for omecamtiv mecarbil.

We had hopes of hitting a home run for patients with heart failure by decreasing heart failure events, reducing cardiovascular mortality, improving quality of life and extending patient stamina and endurance.

And while results from GALACTIC-HF may have fallen short of our most ambitious expectations by missing on the first secondary endpoint of cardiovascular death alone, we believe the results, as already communicated, put us in potential scoring position by hitting on the primary efficacy endpoint and by demonstrating balanced safety across treatment arms.

Considering the novel mechanism of action of omecamtiv mecarbil and the scope and scale of GALACTIC-HF having enrolled patients in 35 countries, both inpatients and outpatients and patients well maintained on standard of care, we believe there's a lot more to the results of this trial as will be illuminated by the presentation of the primary results at the upcoming AHA scientific sessions next week.

Already, GALACTIC-HF has revealed to be a very important clinical trial for heart failure patients and the heart failure community. Because we now have evidence that increasing contractility can safely improve meaningfully relevant outcomes important to physicians, patients and payers.

And of course, this is an important outcome for Cytokinetics and our employees and shareholders, a major event for us, in fact, having committed over 15 years to the clinical development of omecamtiv mecarbil, and more recently, the commercial readiness for the potential launch of our first-in-class cardiac myosin activator.

We are now immersed in ongoing analyses of data from GALACTIC-HF and discussions about potential next steps with Amgen as well as with members of the academic executive committee of the trial.

Together, we're continuing to conduct prespecified and supplemental analyses suggested by the top line results in preparation for the late-breaking presentation to be given by Dr. John Teerlink at AHA, as well as other activities to follow. We look forward to our ability to discuss these results in more detail very soon. Following Dr.

Teerlink's presentation at AHA, Cytokinetics will convene a publicly available investor and media call with Dr. Teerlink and others from the executive committee of the trial to review the results in the context of the high clinical unmet need for patients with heart failure as well as the growing economic burden of the disease.

Recognizing, we can't say too much more prior to the presentation at AHA, Fady will review the top line results in a moment and put them into the context of the trial design. He'll also provide an update on progress in METEORIC-HF, the second Phase III clinical trial of omecamtiv mecarbil. Turning to our cardiac myosin inhibitor program.

We continue to make progress and look forward to advancing REDWOOD-HCM to its cohort 2 by year-end.

Much like in heart failure, HCM patients are in great need of novel therapies to address the underlying contractile dysfunction of their disease, and we're working with urgency to progress our program on the heels of our licensing deal with Ji Xing Pharmaceuticals and our royalty deals with RTW.

Stuart will provide more details on progress for this program in a moment. And finally, during the third quarter, we continued readiness activities in preparation for the potential start of a Phase III clinical trial of reldesemtiv in patients with ALS.

And to remind you, we've communicated that we would make a decision regarding potential advancement of reldesemtiv to Phase III, following the review of results of GALACTIC-HF and that decision has not been made, it's still forthcoming.

We will have more clarity on our plans following the presentation of results of GALACTIC-HF at AHA as well as upon the conclusion of ongoing internal planning and budgeting and also discussions to be convenient with our Board later this quarter.

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

Thanks, Robert. I'd like to express my thanks to the research and development teams as well as all of our colleagues at Cytokinetics for their commitment to the program over these years and commend our colleagues at Amgen for their conduct of GALACTIC-HF and collaboration.

And as we announced a few weeks ago, the results of GALACTIC-HF show that treatment with omecamtiv mecarbil achieved the primary efficacy endpoint and demonstrated a statistically significant effect to reduce risk or the composite outcome of the time to a heart failure event or cardiovascular death, whichever occurred first compared to placebo in patients treated with standard of care.

Heart failure event was defined as an urgent clinic visit, an emergency department visit or hospitalization for worsening heart failure leading to treatment intensifications beyond changed oral diuretic therapy. The hazard ratio for this benefit was 0.92, with a p-value of 0.025. No reduction in the secondary endpoint of CV death was observed.

Adverse events, including major ischemic cardiac adverse events were balanced between treatment arms. Additional prespecified and supplemental subgroup analyses are ongoing and may suggest one or more populations in which the effect of the drug may be larger than in the overall population.

Given the science of GALACTIC-HF, some of these subgroups are quite sizable and in and of themselves are larger than many contemporary heart failure trial.

I'll remind you that we enrolled a broad and heterogeneous patient population, including patients within and outside of the hospital in patients with lower blood pressures and reduced kidney functions than is customary in many trials that preceded GALACTIC-HF.

We look forward to the upcoming presentation that John Teerlink will give virtually on November 13 and expect to expand ourselves on our -- in this initial presentation in the weeks and months to come.

While the opportunity for omecamtiv mecarbil in light of these top line results may be different and perhaps not as broad as we had anticipated, we believe it's novel mechanism drug candidate that improves cardiac contractility may play an important and complementary role along other therapies to increase cardiac function and performance as well as to reduce heart failure hospitalizations and events.

These remain a high unmet clinical and economic needs despite the availability of standard of care therapies.

We also look forward to learning about the effects of increasing cardiac contractility in patients with heart failure through the addition of omecamtiv mecarbil to standard of care as is being studied in METEORIC-HF, the second Phase III trial of omecamtiv mecarbil that continued during the third quarter.

METEORIC will provide insight into another key aspect aimed at improving the lives of patients with heart failure with reduced ejection fraction that is exercise capacity.

Exercise capacity is recognized by the FDA as appropriate to demonstrate benefits and in conjunction with the efficacy and safety data we've seen thus far from GALACTIC-HF, METEORIC-HF may elaborate further on the potential benefit of omecamtiv mecarbil.

During the quarter, METEORIC-HF continued enrollment in North America, and we saw enrollment accelerate in the EU during the summer and fall months. All countries involved in the trial of screen patients in nearly all of randomized patients.

We recently surpassed the 50% mark for the target number of randomized patients and are grateful to our participating sites for the momentum we regained after reopening the trial to enrollment following the pause earlier this year due to the COVID-19 pandemic.

As you all know, conditions remain unpredictable, but we're optimistic that METEORIC-HF will continue to enroll well over the coming months, given measurements we in our sites have implemented.

I'm pleased to share that during the quarter, the data safety and monitoring committee, or DMC for METEORIC-HF met to review data generated thus far and recommended the trial continue as planned with no changes to the protocol. We expect the complete enrollment of METEORIC-HF in the first half of 2021.

We remain enthusiastic about the potential for omecamtiv mecarbil to provide new mechanism therapy to the physician's armamentarium to address the progression of heart failure. And importantly, reduce the cycle of hospitalizations and rehospitalizations that plague patients' lives at significant cost to hospitals and payers.

We will be considering next steps together with Amgen in the coming weeks and months and continue to believe that increasing cardiac contractility with omecamtiv mecarbil, they represent a novel strategy to complement standard of care therapy in managing patients still at risk despite standard of care therapies.

And now I'll turn it over to Stuart to provide an update on our cardiac myosin inhibitor program..

Thanks, Fady. Let me start with an update on the REDWOOD-HCM Phase II clinical trial of CK-274 in patients with obstructive hypertrophic cardiomyopathy. I'm pleased to report that in October, we completed the enrollment of Cohort 1 and REDWOOD-HCM. To remind you of the trial design....

I'm sorry to interrupt, Stuart. I think that we'll have Fady pick up. There seems to be some major static on your line.

Fady?.

All right. I'll start. So let me start with an update on REDWOOD-HCM. The Phase II clinical trial of CK-274 in patients with obstructive hypertrophic cardiomyopathy. I'm pleased to report that in October, we completed enrollment of Cohort 1 in REDWOOD-HCM.

To remind you of the trial design, in a blinded manner, patients are randomized in a 2:1 fashion to placebo or escalating doses of CK-274. Daily doses of 5, 10 or 15 milligrams are employed in cohort 1 with dose titration individually determined on the basis of achieving specific echocardiographic targets.

Overall, the treatment duration is 10 weeks and will support assessments of safety and tolerability, pharmacokinetics and pharmacodynamic responses. We expect the last patient to complete dosing in this fourth quarter and to inform progression to Cohort 2 by the end of the year with full results available by mid-2021.

We are well positioned to initiate Cohort 2 with the majority of sites activated in North America and key countries in Europe, including Spain, the Netherlands and Italy.

Investigators and study teams remain enthusiastic to participate in this trial to characterize the benefit/risk profile of our next-in-class cardiac myosin inhibitor, and we look forward to further engaging with them.

In terms of what you can expect from our communications when we progress the Cohort 2, since the trial will still be ongoing and treatment assignments not fully unblinded, we anticipate providing the doses selected for Cohort 2 based on experience in Cohort 1 and perhaps directionality on aggregate data.

Ultimately, the goal of REDWOOD-HCM is to determine the optimal dosing regimen of CK-274 for a Phase III clinical trial on the basis of pharmacodynamic effects, such as reducing left ventricular outflow obstruction as well as the safety and tolerability profile of CK-274.

Our goal remains to initiate a Phase III registration program for CK-274 in patients with obstructive hypertrophic cardiomyopathy in late 2021. I'm pleased to report that during the quarter, the data monitoring committee for REDWOOD-HCM convened a meeting.

And after a review of the data thus far, the data monitoring committee recommended the trial continue as planned with no changes to the protocol. Also during the quarter, we made progress with our new partners, Ji Xing Pharmaceuticals.

We are proceeding to ready for the start of clinical development of CK-274 in China that would enable China to be part of the pivotal Phase III clinical trial. We believe that enrolling patients from China in a potential international registration trial may confer key advantages for a potential global registration program with CK-274.

In parallel, during the quarter, Cytokinetics continued planning for the conduct of clinical trials of CK-274 in potentially other indications, such as nonobstructive hypertrophic cardiomyopathy and in the subgroup of heart failure patients with preserved ejection fraction or HFpEF.

We look forward to sharing more regarding our potential plans for CK-274 in these areas in 2021. During the quarter, we also initiated the Phase I study of CK-271, our additional cardiac myosin inhibitor.

As a reminder, the primary objective of this first-in-human Phase I study is to assess the safety and tolerability and pharmacokinetics of single ascending oral doses of CK-271 in healthy adult subjects. We're on track to complete the study during this fourth quarter.

Finally, during the quarter, we're proud to provide a $1 million grant and enter a 4-year partnership with the HCM registry, a global registry of patients with hypertrophic cardiomyopathy focused on improving predictive measures of risk for complications and identifying biomarkers associated with adverse clinical outcome.

The registry has been funded to date by the National Heart, Lung and Blood Institute, part of the National Institutes of Health. And is being conducted by the University of Virginia and the University of Oxford. As an industry sponsor, Cytokinetics will join the HCM, our Steering Committee in an observational capacity.

Our long-term commitment to this important initiative is aligned with our dedication to outcomes research along with our own drug development in the interest of patient-centric engagement and improved health span. And with that, I'll turn it over to Robert Wong, who will provide an update on our financials.

Robert?.

Thanks, Fady. I'll first provide an update on cash, revenue and spending, and then Ching will review our strategic planning and financials looking forward. More details on our actual results for the third quarter are included in the press release, which we released earlier this afternoon.

We ended the third quarter with approximately $451 million in cash and investments. This balance does not include $85 million, which is expected upon the closing of our sale of a royalty on MyoKardia's mavacamten to RTW Investments.

Our revenue in Q3 2020 came primarily from license revenue for the RTW transaction and from our strategic alliances with Amgen and Astellas.

Our third quarter 2020 R&D expenses increased to $24.2 million from $20.2 million in the third quarter of 2019, primarily due to higher spending related activities associated with REDWOOD-HCM as well as readiness activities for a potential Phase III trial of reldesemtiv.

More than 50% of our R&D expenses were attributable to our cardiovascular program, as expected, given activity for METEORIC-HF and the cardiac myosin inhibitor program. And the remainder of our expenses were attributable primarily to our early research activity.

Our third quarter 2020 G&A expenses were $12.3 million, up from $9.8 million in Q3 2019 due primarily to higher personnel-related costs, including stock-based compensation. And now Ching will review our strategic planning and cash runway through year-end..

Thanks, Robert. As we have shared previously, we conduct a strategic planning process every summer in preparation for a presentation to and discussion with our Board in early September. For 2020, the focus of our strategic plan was on scenario planning for potential outcomes of GALACTIC-HF.

The results of GALACTIC-HF aligned with one of the scenarios we discussed with our Board, and I'm pleased to share that we have an operational plan in place to move the program and the company forward.

As we, together with our partner, Amgen, continue to analyze data, we will evolve that operational plan to ensure that we allocate the appropriate resources to support the potential plans for omecamtiv mecarbil at the right time.

As we approach year-end, we remain in a strong financial position as a result of several transactions we executed this summer.

The series of licensing, royalty monetization and equity financing deals now ensure we have ample cash runway to prepare for potential commercialization of omecamtiv mecarbil to advance the development plan for CK-274 and to potentially conduct a Phase III clinical trial of reldesemtiv in patients with ALS, which is a decision that has yet to be made and will follow ongoing discussions later this quarter.

As a reminder, we executed a series of transactions with affiliates of RTW Investments LP, and Ji Xing Pharmaceuticals Limited related to CK-274, whereby Cytokinetics will receive a combination of committed capital funding and sales proceeds of up to $250 million and is eligible to receive up to $200 million in milestone payments plus royalties on future sales of CK-274 in certain Asian countries.

We also raised $189 million in net proceeds from an underwritten public offering in July. To recap our cash position, we ended the third quarter with $451 million in cash, and now anticipate ending 2020 with more than $500 million in cash plus committed cash subject to closing conditions of royalty monetization portion of the RTW transaction.

We believe that our cash balance then will represent at least 3 years of forward cash based on our 2020 spending. In addition, we have an additional $90 million available to draw upon at our option for the further development of CK-274 per the RTW transaction.

As is our practice, we will provide 2021 guidance in concert with our Q4 earnings in early 2021 with the goal of deploying capital prudently against executing our Vision 2025 and ending the year with more than 3 years of forward cash. And with that, I'll turn the call back over to Robert Blum..

Thank you, Ching.

I'll end this call where I began it, that is, we're gratified to have recently shared results from GALACTIC-HF, the first large-scale Phase III clinical trial demonstrating that omecamtiv mecarbil reduced risk for the composite outcome of cardiovascular death or heart failure related events compared to placebo in patients treated with standard of care and with a p-value less than 0.05.

This is indeed an important event for the heart failure community and for Cytokinetics. We believe that our cardiac myosin activator has shown to increase cardiac performance and function and to reduce related clinical events in a landmark clinical trial with adverse events balanced between treatment arms.

We believe it, thereby, has the potential to offer physicians and their patients a welcome addition to manage the clinical and economic burden of heart failure, and we look forward to the sharing of additional results at AHA. Now we're discussing potential next steps with Amgen.

In addition, we may hold meetings with clinical experts as could inform our further conduct of market research and health economics and outcomes research and other commercial analyses that may better inform a potential path forward. We look forward to sharing more as we know more.

You heard from Fady about progress with our cardiac myosin inhibitor, so I won't repeat that. But I will say on the neuromuscular front, as you heard today, we continued in the third quarter, certain readiness activities in preparation for our potentially starting a Phase III clinical trial of reldesemtiv in patients with ALS.

We've maintained that this decision is dependent on what scenario we find ourselves in regarding GALACTIC-HF and what our cost of capital is at that point in time.

Now that we have more visibility we're discussing the path forward as a leadership team internally and with our Board and with the goal of making that decision whether to proceed by year-end.

Finally, during the quarter, we once again demonstrated Cytokinetics' commitment to the communities we serve by renewing our partnership with Cure SMA to increase education, awareness, public policy and fundraising for spinal muscular atrophy as well as announcing the third annual Cytokinetics Communications Fellowship Grant Program intended to support increased capacity in communications, awareness building and community engagement in heart failure, HCM, ALS and also SMA.

To summarize, we're approaching the final months of 2020 with continued focus and optimism toward our diversified pipeline, our research portfolio and our commercial prospects. Now let me recap our expected milestones for the remainder of 2020.

For omecamtiv mecarbil, we expect results from GALACTIC-HF to be presented in a late-breaking clinical trial session at AHA scientific sessions in this fourth quarter next week. And we expect enrollment of patients with heart failure in METEORIC-HF to be completed in the first half of 2021.

For AMG 594, we expect to continue discussing next steps in the development program with Amgen. For CK-274, we expect to have data from Cohort 1 of REDWOOD-HCM to inform progression of this Phase II clinical trial to a second cohort by the end of 2020. For CK-271, we expect to complete the Phase I study in the fourth quarter of this year.

For reldesemtiv, we expect to continue to prepare for a potential Phase III clinical trial and registration program in patients with ALS.

And for our ongoing research, we expect to continue research activities directed to the cardiac and skeletal sarcomere and our other muscle biology research programs, and we expect to continue research and collaboration with Astellas directed to the discovery of next-generation skeletal sarcomere muscle activators through the end of this year 2020.

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

[Operator Instructions]. Your first question comes from Salim Syed from Mizuho..

Just three for me, if I can, two on omecamtiv, 1 on CK-274. Robert, you mentioned that you're in potential scoring position for omecamtiv. So I'm just curious if you've actually met with the FDA or shared the data with them. And if there are any gating factors to submitting a regulatory application for approval there? And then just a couple for Fady.

Fady, I know you can't speak to the data that we'll be getting at AHA.

But perhaps, in theory, is there anything here that we can read into the mechanism as it relates to the inpatient population, why this drug may actually work better in inpatient population versus the outpatient, which would be the opposite of what we've seen in PARADIGM and DAPA trials? And then one on CK-274.

Can you just clarify if we'll be getting LVOT gradient data on the Cohort 1?.

So good questions. I'll start with the first one. And no, we haven't had interactions with regulatory authorities. We and Amgen have a lot of work to do around analyzing the data in order to understand the path forward. It would be premature to have any such discussions.

Fady, do you want to pick off the next two?.

Yes. I'll take the next one. With regards to your question about inpatient and outpatients, we haven't really pointed to any directionality in those two subgroups. Those data will be presented at AHA. I can't really expand on them.

In regards to CK-274, we won't necessarily present quantitative data with regards to the LVOT gradient, but we may discuss just some directionality there. Remember, the first cohort is just starting at the lower doses, meant to tell us what the lowest starting dose would be.

And so obviously, we're not expecting to reach maximal pharmacodynamic effects in the first group. So I think quantitative data more appropriate will wait until we've completed the study..

Your next question comes from Dane Leone from Raymond James..

Congrats on the updates. I wanted to, I guess, first, just kind of clarify, as the line was cutting out a little bit around REDWOOD to start. So just to make sure we're all on the same page here, the first cohort is fully enrolled.

And when will the last patient we have 10 weeks of follow-up? And is that what you would wait for before discussing or starting enrollment into Cohort 2? And then what's your projection in terms of enrollment on Cohort 2? I know you're rehashing some of this, but it was difficult to hear some of that..

Yes. As I said, we completed enrollment in Cohort 1, just at the very beginning of the quarter. So we'd expect all the patients to be through 10 weeks before the end of the year. The second cohort, we expect should enroll much faster. We have all this -- we have many more sites activated.

They'll have the opportunity to prescreen patients and get them, hopefully, a range for their visits and things. COVID-19 remains a wildcard. But so far, I think sites are well prepared, and hopefully, we'll see them continue to stay open through the winter months.

The data that inform the transition from Cohort 1 to Cohort 2 won't necessarily include every single patient in Cohort 1, but will include a substantial fraction of them enough so that we can set doses for the next group..

And Dane about the second cohort.

And we'll just say that during the time that the enrollment was interrupted, Fady and his team were able to add a whole bunch of centers onto the trial such that we now can expect more centers to be enrolling patients than we need patients in each cohort so that second cohort should enroll substantially faster than the first one we would expect..

Okay. Thanks for that clarification. Just one more on that topic. The data -- so you will not be blinded to the data that's informing the start of the second cohort.

You're just not going to kind of discuss it in granularity or -- sorry, I was trying to understand that comment in terms of what -- of how the unblinding works between Cohort 1 and then moving into Cohort 2?.

Yes. The teams will not be unblinded to patient level data. We'll have summaries that are aggregate data so that we can look at the effect of the drug on ejection fraction, the effect of the drug on left ventricular outflow gradient as well as adverse events as they may have occurred over the course of the trial.

That will help us set what doses we want to plan on for Cohort 2. The data monitoring committee will have unblinded data. But obviously, they will review those in confidence, and they will validate choice of doses that the blinded analysis suggest. Hopefully, that helps..

Yes. Sorry, just a really dumb question.

Why does Cohort 1 need to stay blinded once it completes 10 weeks of dosing?.

So the reason this stays on blinded is because the trial, obviously, is not complete. The placebo group in Cohort 1 is going to be combined with the placebo group in Cohort 2 to form an integrated placebo group. So remember, we're randomizing this trial in a 2:1 fashion.

So 12 patients on CK-274, 6 on placebo in Cohort 1 and then another 12 on active and another 6 on placebo in Cohort 2. Combining those 2 groups then gives us 12 placebo patients, 12 active patients on the lower doses, 12 active patients on the higher doses.

And we just think it's better trial conduct to leave it blinded to individual patient drug assignments until we've completed and unblinded the entire study..

Okay. So essentially, the data for Cohort 1 that you would discuss before year-end or around year-end would be an integrated data set of all patients, placebo and/or active drug? Or were you referring to kind of high-level data for actually the cohort that would be on active drug? I guess that's why I'm a little confused with that..

Yes. I think, Dane, I don't -- we haven't even seen the data, so I don't want to get in the details of exactly what we intend to construct in a press release. My -- the statements that we made just point to directionality.

Did we see the LVOT gradient start to decline? Did we have patients that had a discontinued drug with regards to EF below 50, things like that. I don't think we're going to get into specific numbers because we won't have unblinded the data. We will not have the appropriate comparator, which is the combined placebo group.

You can't calculate it placebo-corrected change from baseline if you don't have the placebo group, for instance..

Right. But you would -- the data you're talking about would actually be for the active drug, not the placebo group? I'm just trying to understand whether it did mix together in what you're saying..

We will be reporting the data presumably that we think are the active group. That's correct..

Your next question comes from Charles Duncan from Cantor Fitzgerald..

This is Pete Stavropoulos on for Charles. Congratulations on the GALACTIC study and all the progress made in the quarter. Have a couple of questions.

Can you discuss the patient population of METEORIC? And how would it compare to GALACTIC? And how could the study help to differentiate ome relative to other drugs in the space?.

Good questions. So METEORIC is enrolling patients who are outpatients and who are not as believed to be at risk, given they had not been admitted into the hospital with a diagnosis of acute heart failure within 1 year as the inclusion criteria for GALACTIC required. So these are more stable outpatients.

They have to be able to perform an exercise protocol, obviously, as well. So they're perhaps not as high-risk or lower risk than some of those in the GALACTIC trial, but still, these are patients with heart failure and low ejection fraction, systolic dysfunction.

And what was the second question?.

How can it help to differentiate ome relative to other drugs in the space?.

Yes. So that's a very good question. As we approached this Phase III clinical trials program, we being Cytokinetics together with Amgen, we thought about ways that we could differentiate from standard of care as well as potential new medicines that were on the horizon.

And it would be a real distinguishing feature if we had a drug that was increasing cardiac performance and function and also extending time to exercise fatigue or increasing endurance and stamina. Currently, there aren't part failure drugs that can do that, and that would be a meaningful distinguishing feature for a new medicine in heart failure.

So that's why we set about to do both a large outcomes trial and this trial of METEORIC. And we look forward to the results from METEORIC next year..

Okay. And one more for the GALACTIC results.

How should we think about the risk reduction observed relative to other recent studies in heart failure? And do you believe that only could be competitive in the space?.

It's a tough question to answer in the absence of your seeing the full results, as you will see next week at AHA. But I would caution you to think about these medicines as all directly substitutable one to another because they're not different mechanisms, different trial designs. It's really not an apples-and-apples comparison.

I guess the fact that Wall Street would like to line them up, but I don't think that's so feasible given the unmet need that still exists with standard of care. And that's where I think once we have presented the data next week, we can speak to your question a bit more constructively..

All right.

And just by some chance, do you believe COVID may have impacted those numbers on the secondary endpoint on the Q1?.

I don't think we have any reason to believe that right now. But of course, we're still doing additional analyses. But I don't see that, that's contributed to anything that we know of today..

Your next question comes from Jeff Hung from Morgan Stanley..

This is Hannah. Just two quick ones. What are your thoughts on being able to file for a doing additional studies....

Hannah, we're having a hard time hearing you. There is lot static on your line..

I think I the question is what do we think about the ability to file based on GALACTIC versus to wait for another trial? Is that what you said?.

Correct. Yes..

I think it's way too premature to talk about filing strategies or anything of that sort. Let us complete the analyses, let us discuss these matters with Amgen. You'll see these results in some more detail next week. And frankly, there'll be more analyses that will still follow and other activities.

And I think any conversation about regulatory strategy should weigh on a lot more work that needs to be done..

Okay.

And then have you been able to share any GALACTIC data with KOLs? And have you heard any early feedback from them?.

You know the investigators....

Are you asking about -- I'm sorry..

I think I understand the question, Diane. The question was have we shared data with investigators and gotten any feedback from them. The answer is no. We have not done that broadly yet. There will be a series of interactions after the AHA investigators..

Your next question comes from Jason Butler from JMP Securities..

Robert two quick ones.

First of all, can you just remind us of your cost obligations for omecamtiv from now through to approval? And then secondly, for AMG 594, just give us -- remind us of the -- what you had hoped to learn from the Phase I study, PK/PD parameters? And how that's reading on what the potential pharmacological attributes to the program product would be and the indications, therefore, that you -- that could potentially read on?.

I'll ask Ching to speak to the first question on costs we may be incurring with regard to omecamtiv. And then maybe I'll ask Fady to speak to the second one..

Yes. So Jason, I think you're referring to the conduct of the METEORIC trial. According to the agreement, Amgen is paying all of the out-of-pocket cost. And Amgen and Cytokinetics, each will fund 50% of the FTE related cost. That's per the agreement..

And Jason, I'm sorry, could you repeat your second question?.

Yes.

Just, Fady, on 594, just what you'd hope to learn from the Phase I program? How you're thinking about the pharmacology of the compound? And how that could read on potential indications?.

Yes. I think with the Phase I program, we want to look at the pharmacodynamic response as when increases dose and compare that to what we've seen with omecamtiv mecarbil.

So are there any pharmacodynamic differences? We believe there are, given the preclinical characterization that we've made, but it takes a fairly detailed and meticulous Phase I trial to put that all together. So what we hope to do is understand how they may be differentiated.

And then whether that leads as a basis for continuing to advance 594 into indications that are different than where we might apply on omecamtiv mecarbil..

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

This question has already been asked, but I try to ask it in a different way. I know you cannot disclose obviously the data. A lot of information about the data we are going to see at AHA.

But maybe you can provide a little bit of color or try to with regards to how do you envision the path forward for omecamtiv, meaning we are going to see data possibly showing differences in different population of patients.

I was wondering if any of these scenarios would require additional studies to be conducted with omecamtiv if there is any possibility of that.

And also, how we should look at the relevance of METEORIC in relation to the data that we are going see at the AHA?.

So I appreciate your trying to ask a question a different way, but I'm not sure I'm going to be able to give you much of a different answer. It's better that we have this conversation after the results are presented, and we can be more forthcoming about what the data say. But keep in mind that GALACTIC has an 8,000 patient clinical trial.

We've already published on the baseline characteristics, teaches us a lot about heart failure and where there still remains high unmet need and where omecamtiv mecarbil may have differential effects in different large prespecified subgroups.

So there's a lot still to be learned still a lot of work to do in order to understand what could be next steps. And we want to do right by our commitments to Amgen to have those conversations together and understand together what should be the next step. So I apologize. I don't think I can do better than that.

But I hope you understand and let's have these discussions again down the road..

Yes. Sure. I understand. And just to clarify, you mentioned that you're going to have a call after the AHA presentation. I'm not sure I understood correctly.

Is this call going to be the same day of the AHA presentation or it's going to be in the future?.

Diane, do you want to take that?.

Sure. It's going to be the same day. We'll actually announce the details tomorrow. But it will follow Dr. Teerlink's presentation. We have to cooperate with any embargos. So it will be soon after he presents the data at AHA. So on the 13..

Your next question comes from Ted Tenthoff with Piper Sandler..

Most of the questions are focused on the cardiovascular side, so I'll ask 1 from the muscle side.

But can you give us a little bit more of a sense in terms of what goes into the decision whether to progress on reldesemtiv? And the reason I ask it is, it seems to me like the primary gating factors should be whether or not the data support, and this is a drug. And if it is, then it seems to be worth pursuing.

So I want to make sure I understand sort of how you got size are framing or prioritizing that decision?.

Good question, Ted. And you're right. To be clear, as we've communicated several times, our first priority is to ready for the potential commercialization of omecamtiv mecarbil. Our second priority is to conduct development programs, plural with CK-274 in order to make sure we expand upon the opportunity there in HCM as well as other indications.

And then we need to make sure that we can finish what we start if we were to go forward with reldesemtiv. So we spent the better part of the year analyzing the data from the Phase II study, having conversations with FDA and EMA, interacting with HTAs in Europe and payers doing a whole bunch of market research and other things.

We had to renegotiate our deal with Astellas in order to be able to understand what would be their commitment and funding. And we had to discuss with academics, what would be a potential Phase III trial that could serve as registration and talk to FDA and EMA about that. So that takes time.

And all of that is important alongside of what does the Phase II data teach us about a path forward in Phase III. All of that comes together in terms of our ability to conduct an affordable trial and also make certain that it's not subtracting from the other things that we're doing.

And that's conversations we still need to finish internally and with our Board. But we'll get there, and we'll do that this quarter. And we want to understand much more our cost of capital, and that's in part going to be informed by how we might proceed with regard to omecamtiv mecarbil, given what we know from GALACTIC.

So all those things factored together, I hope you understand. The trial itself, if we were to do it, is a trial that would be perhaps in the range of $35 million to $40 million as would be conducted over a couple of years, so amortized over a couple of years. And we already have commented that Astellas would be funding about 1/3 of that.

So the trial would not be all that expensive relative to our current operating burn, but we still need to make sure it doesn't subtract from the other things we need to be prioritizing as well. So that's hopefully an answer to your question.

Does that help?.

Very much, Robert..

[Operator Instructions]. Our next question comes from Graig Suvannavejh from Goldman Sachs..

Graig, are you there?.

Yes, sorry about that. Congrats on the progress that you've been making. Just several questions, if I could. Fully realizing that we still need to see the AHA data, which is coming relatively shortly. I'm curious if -- a couple of things.

One, have you had the opportunity to discuss with Amgen the data? Or is that something that is going to happen post the presentation of the data at AHA? With the follow-up being in terms of being able to communicate to the market what's next, either from a regulatory perspective or from a commercial perspective, when should we expect to hear such an update? Is that something that perhaps is a first half of '21 event? Is it by the end of the year event? So let me stop there with that question..

Yes. So we have had many, many, many meetings with Amgen, but they've been focused to the data. And there are being many prespecified analyses and going through those analyses, inform other supplemental analyses that are also being generated and prioritized.

So the conversations we're having with Amgen are very focused to understanding the results from GALACTIC. And everything else that you're asking about would have to come later and only can be really initiated once we have our arms around the data and a sense of how they may be viewed by the heart failure community, starting with AHA next week.

But then obviously, there would have to be a bunch of market research and other HEOR another analyses that I mentioned in my prepared remarks. So it's hard to say right now, whether that's weeks or months or whether that's this year or next year.

And I would just ask that you permit us to continue those activities with our partners at Amgen, and we'll give you clarity once we have clarity..

My next question is just given at least what we've seen thus far in terms of GALACTIC and the results on the primary endpoint and the secondary endpoints. How should -- a, how do you think we should be thinking about a drug with such a profile? I'm giving both you and Amgen full credit for swinging for the fences with the trial.

But given the profile that we're seeing thus far and again, not knowing what the fuller profile will look like with AHA, but without a mortality benefit, I guess my question is, how are you thinking about that commercial opportunity versus if you did have a mortality benefit? And then second of all, have you done market research around with payers, in particular, how they view the value from a payer perspective, what a drug like omecamtiv, irrespective of whether there's a novel mechanism of action or maybe that has to be contemplated? How do you think payers think about that? I think we've heard some feedback from KOLs that they sometimes are getting difficulties getting reimbursement for drugs that are beyond kind of the triple kind of regimen gold standard?.

Yes. So it's a good question. Obviously, the heart failure landscape is evolving quite rapidly. And we have new medicines that are being made available, but these work by different mechanisms, and they were studied in trials that are different one to another. And even with these drugs, one sees that the unmet need here is quite high.

You're talking about morbidity and mortality that is higher than most cancers and for which there is a not only major clinical unmet need, but a very, very significant economic one incredibly costly to Medicare and other payers. So based on what we've already top lined, you can see that we have a drug that is safe.

We have a potential drug here that is increasing cardiac function and performance and that addressed and reduced clinically meaningful outcomes. Now granted, it did not achieve an effect on CV death alone, but I think it's going to be important to understand which patients did benefit more, which ones perhaps less.

And in an 8,000 patient trial, you've got ample opportunity to do that with prespecified subgroups. And that's ultimately where I think physicians and payers might consider new mechanism drugs.

You look at VICTORIA-HF and Merck and Bayer are quite bullish on the prospects for vericiguat, which demonstrated in VICTORIA-HF clinically meaningful reductions in outcomes, not unlike what we've already top lined, but for outpatients with worsening outcomes.

And that drug is going to be reviewed with priority review by FDA and has a PDUFA date coming up in Q1. So things like that will inform ultimately how the armamentarium for heart failure may continue to evolve.

And I suspect that given the high unmet need and the high economic burden that there'll be places for these various medicines as adjacent to one another, complementary to one another.

And you're right, not all of these will be used as foundational care in all patients, but there are meaningfully important subgroups and cohorts that are not well served. And that's where I would suggest once we can share our results and do the work we need to do that having that conversation down the road could perhaps be fruitful..

And if I could just squeeze in one last question just about REDWOOD. And you might have touched upon this before. So apologies if I missed this.

But in terms of what would be the bar for success? What do you think would look good in terms of the REDWOOD data?.

Fady, do you want to take that? What would look good with regard to the REDWOOD data?.

I cannot. Stuart is on the line, I think he'll maybe -- you want to try and take that, Stuart, have you solved your audio problem? Maybe I'll try that.

So the -- I think what we would expect out of, hopefully, the first group of patients is to begin to see reductions in their left ventricular outflow gradient and to see that the drug is well tolerated. Really all you can expect from what's the first dosing group of a study that's designed to have a lower dose group and a higher dose group.

And obviously, what will inform progress to Phase III and doses that we select for final doses for Phase III will be the second cohort as well..

Your next question comes from Chad Messer from Needham & Company..

This is Gil on for Chad. Sorry, if I might repeat some questions here. It's a little bit late. First off, I don't know if you guys talked about potential subgroup analyses.

Are there any chances we'll see any regional assessments of GALACTIC-HF patients? Because we recently some weird looking data from other studies where that you show the very different outcomes in U.S. versus ex U.S..

Yes. Those are among the prespecified subgroups. So those data will be presented..

Excellent. And kind of a follow- on that.

Do you feel that considering where the GALACTIC top line, does this put more emphasis on data that's going to come out of METEORIC? And how will the data coming out of METEORIC influence potential further development and kind of give us an idea of how omecamtiv functions?.

METEORIC won't finish enrolling until sometime in the first half of next year, and the trial won't actually complete until the end of next year. So I don't think meteoric is relevant to our deciding to move forward with the data in GALACTIC.

And I expect long before we have data from METEORIC that we'll have devised and decide what to do with regards to the GALACTIC data..

There are no further questions at this time. I will turn the call back over to the presenters..

Okay. Thank you to all the participants on our teleconference today. Thank you for your continued support and interest in Cytokinetics.

Obviously, the third quarter was an incredibly busy one for us, both in terms of advancement of our pipeline, in terms of doing deals and also -- and especially gratifying one in light of the recent announcement of the results of GALACTIC. We do look forward to sharing more with regard to those results at AHA and afterwards.

And we thank you for your continued interest in all that we're doing. Operator, with that, we can now conclude the call. Thank you..

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect..