Cytokinetics, Incorporated

Good afternoon and welcome, ladies and gentlemen, to Cytokinetic's second quarter 2021 conference call. At this time, I'd like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call for questions and answers after the presentation, and we will allow for up to two questions per participant. I will now turn the call over to Diane Wiser, Cytokinetic's 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. Ben Fatty-Malik, our EVP of Research and Development, will provide an update on Omicamptomacarbal, including the secondary analyses from Galactic HF, our positive phase III clinical trial of Omicamptomacarbal, as well as recent interactions and next steps with the FDA. Next, Andrew Kalos, our EVP and Chief Commercial Officer, will provide an update on progress towards our go-to-market strategy for Omicampton McCarble and how those plans intersect with our franchise development strategies and our future plans for the commercialization of Affy Campton, or CK274. Then, Stuart Kupfer, our SVP and Chief Medical Officer, will provide an update on our development program for Affy Campton 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 Jha, 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 might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our second quarter 2021 financial results filed on Form 8K. 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 rel-deceptive in patients with ALS. Looking forward, we're preparing for our first NDA submission. and executing well against commercial readiness objectives while also advancing three 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 Fatty 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 omicamptamicarbol 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 healthcare professional community, we believe omicamptomacarbal 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 omicamptomacarbal 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 afikampton 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 two interactions, supportive of progression into our phase three 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 Omicamptive McCarble, 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 rel-deceptive 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 rel-deceptive, and Astellas will contribute $12 million toward 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 Fadi to elaborate on recent developments related to Omicampt of McCarble.

Thanks, Robert. As you mentioned, results from additional analyses 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 derive greater clinical benefit from treatment with omicamptomacarbal 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 were 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, omicamptive macabre may offer a new treatment option for more severe heart failure patients who are maxed out on standard of care and still in and out of hospital. As I said before, these results align well with the mechanism of action of omicamptive macabre 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 omicamptomacarbal 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 omicamptomacarbal. The many physicians with whom we've engaged point out that options are limited in these patients, And if approved, omicamptomacarbal 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 three clinical trial of omicamptomacarbal, 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 by 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 onto the regulatory front. Since the beginning of the year, we've participated in three 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 Omicamptive McCarble 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 have 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 longstanding regulatory discussions. In parallel, we're also discussing with FDA our strategy to enable personalized dose optimization in patients being treated with omicamptomacarbone 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 the 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 Omicamps and McCarble, 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 that we expect to further elucidate the potential of Omicamp and McCarble 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 Omicamp and McCarble.

Thanks, Patty. During the second quarter, our board of directors endorsed our proposed go-to-market strategy for Omicamp's McCarvel. 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 Apicanthin 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 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 Fatty, the results of the Galactic HF and the secondary analyses provide clarity around the subset of heart failure patients in which the benefit of omicamptomacarbonyl 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 are those recently hospitalized. Those patients likely to derive the most benefit from omicamptomacarbonyl 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 and tractable subset of cardiologists and hospitals also enables us to effectively launch with a modest size specialty cardiology field force. Notably, there is also a significant overlap between heart failure and HCM-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 Omicamp and Bacarbal for Apicanthin in two to three 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 fractions. And as you may know, these are the patients who become the frequent flyers in hospitals, given their increased risk of re-hospitalization with every subsequent hospitalization event. Given the evidence from Galactus HF demonstrating the risk reduction resulting from omicamptomacarbol was greatest among patients with lower ejection fraction levels, we are evaluating the cost-effectiveness potential for patients being potentially treated with omicamptomacarbol. Finally, it will be critical to our work with payers to ensure patients have access to all McCamp and McCarville. 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 proposition based on the results from Calactic 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 afacantin 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 Name Council for Afikampton to be used as the international non-proprietary name for CK274. About three weeks ago, we announced positive top line results from cohorts one and two of Redwood HCM, the phase two clinical trial of Afikampton. 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 apicamptin for 10 weeks resulted in highly statistically significant reductions from baseline compared to placebo in the average resting and post valsalva left ventricular outflow tract 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 apicampin 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 two, which studied a higher dose range of 10 to 30 milligrams, 93% of patients treated with afecamptin achieved the target goal. Patients treated with afecamptin experienced decreases in both resting and post valsalva gradients by week two, and a maximum treatment effect was achieved by week six after completion of dose titration, which was sustained through the final visit at week 10. Treatment with afecampton was generally well-tolerated. The incidence of adverse events was similar between treatment arms. No serious adverse events were attributed to afecampton, and no treatment interruptions occurred on drug treatment. Importantly, we were pleased to see that only one 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 one and is now enrolling patients from cohort two. The primary objective of this trial is the evaluation of long-term safety of apicampin, and the secondary objectives focus on the evaluation of gradient reduction and pharmacokinetics with long-term administration of apicampin. We are also conducting a cardiac MRI substudy 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 one and two. As a reminder, we still have cohort three in Redwood HCM ongoing, which includes patients treated with apicamptin who are also on disipiramide as background therapy. This cohort will further inform the inclusion of the small but important patient population in phase three. We are moving rapidly to begin our phase three clinical trial of apicamptin in patients with obstructive HCM in the fourth quarter, continuing preparations that began last December when we obtained results of the cohort one 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 three trial. In that meeting, we reviewed the design, endpoints, and patient populations and found the feedback we received enabling of our plans to advance to phase three. 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 non-clinical safety, clinical pharmacology, and the preferred format for datasets, among other components. In addition, we initiated interactions with EMA during the quarter and received feedback that 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. under our collaboration with Jixing Pharmaceuticals. During the second quarter, Jixing continued enrolling patients in a phase one study of afecamptin in China and prepared for participation in the phase three clinical trial of afecamptin in obstructive HCM. As we finalized preparations for a phase three trial and as part of our clinical development program for afecamptin, we are now considering the best path forward for a trial in patients with nonobstructive 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, revise 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 Omicamp and McCarville, 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 activities. Our second quarter 2021 GNA 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 three years of cash runway based on our revised net cash utilization guidance of 195 to 215 million in 2021. This new guidance includes non-recurring 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 efekamtum in patients with obstructive HCM, expansion of the clinical development program for efekamtum to include other indications, planned commercial launch activities for omikantum carbol, the conduct of Courage ALS, our now ongoing phase three clinical trial of real incentive in patients with ALS, and for research and general corporate purposes, including working capital. During the second quarter, we also made progress against our two-fold corporate development strategy to first seek potential royalty monetization and or structured financing deals in order to further support commercial launch of Omicampton Macarbo and continued development of Aficampton. And second, to seek a development and commercialization partner for Omicampton Macarbo and Aficampton 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 Omicampton Macarbo and Epicampton to support co-funding of a lifecycle 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 Omicampton-Macarbo and selectively to Europe and other markets to enter into potential agreements with co-development and co-commercialization partners for only Canton Macaw. 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 Palm.

Thank you, Ching. As we look toward the remainder of 2021 and our upcoming milestones, I'm reminded of the vision we established more than two 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 two 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 omicamptomicarbol during the quarter, we successfully reached several agreements to facilitate the transition of the programs for omicamptomicarbol and CK136 from Amgen to cytokinetics, including an agreement for the sale and our purchase of approximately two tons of active pharmaceutical ingredient of omicamptomicarbol. As you can imagine, Transition activities following a 15-year collaboration take 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 six to nine 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 rel-deceptive 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 healthcare professionals, the design of Cura JLS 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 REL deceptive 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 two positive late-stage trials for our lead cardiovascular programs, we look forward to advancing our goal towards NDA submission of omicamptamicarbol for the potential treatment of heart failure with reduced ejection fraction and and also starting a Phase III clinical trial of afecamptin 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 omicamptomacarbal, 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 aficamptin, we expect to begin a phase three clinical trial of aficamptin in patients with obstructive HCM in the fourth quarter of 2021. For real deceptive, 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 one to two potential drug candidates through the remainder of 2021. And operator, with that, we can now open up the call to questions, please.

Ladies and gentlemen, if you'd like to ask a question, please press star and then the number one on your telephone keypad. And once again, please be aware that we will be taking two questions per participant. And your first question comes from the line of Jason Butler with JMP Securities.

Hello, Jason. Hey, thanks. Hi, Robert. Thanks for taking the questions. First one, just based on the regulatory feedback that you have on Omicamtiv, 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 XUS regulatory interactions and specifically how you think including patients from China can help impact enrollment and the regulatory dialogue there.

Thanks. Okay. So to unpack that, let's start with Omicamptive. 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 pre-specified 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 CK274 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. Fatih, anything you want to add to that?

I think only in that, you know, our plan is to conduct the phase three outside of North America. So, you know, including Europe and China, of course. and regulatory interactions to enable that are underway.

Yeah, and as it relates to your question about China, our expectation is through our collaboration with Zhejiang 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.

Great, that's helpful. Thanks for taking the questions.

Thank you, Jason.

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

Hello, Dane.

Your line is open. Hi. Good afternoon. How's it going? I'll keep it brief. I just wanted to ask in terms of The FDA discussions on Omicamptiv, it sounds like you're probably moving forward with the submission 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 omicamptive, whether then the label might be then expanded to incorporate that which incorporates results pertaining to omicamptive in meteoric HF. But our strategy pivots on galactic HF.

Okay, thank you.

Thank you.

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

Hello, Carter.

Hey, good afternoon, Robert. Great to see all the progress. I guess two questions from us. First off, you know, you've talked in the past around there being a distinction between your Phase III HF and Explorer. Now that you've had these meetings with FDAs, 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, you know, 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? Thank you.

Sure. I'll turn it over to Fatty, 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 CK274, I think it's affirming of our plans for the Phase 3 trial, and Fatty and Stuart can pick it up from there.

Yeah, I mean, our... Our trial design for phase three will certainly borrow from what was conducted with Mavik Kempton and Explorer, but will 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 three with FDA. Okay. 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 YHA class, just as an example. So there's more interesting data to come. Thanks for the question.

Our next question comes from the line of Saleem Saeed with Mizuho.

Hello, Saleem. Good afternoon, Robert and team. I had a couple of questions on CK274. So, you know, Bristol had on their call a question on, you know, CK274 versus Mavicam. I'm just curious, you know, they're saying that they don't see differentiation between the two 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 CK274. How confident are you that CK274 is actually a differentiated molecule? molecule, and is there anything in the phase three 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. I'm just curious how you would perceive an adcom if Mavikampton were to get one. Would it be a negative, positive? Are you expecting one? Or how are you thinking about this generally? Thank you.

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 Affy-Campden into phase three. 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 CK274 or Affy-Campden 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 three trial. But you'll know that soon enough when we announce 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?

Yeah, just on the Mavikampton adcom, if you perceive that as a negative or a positive, if Mavikampton were to get one.

Yeah, why don't I turn to Thadde maybe to speak to that?

Yeah, you know, 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, you know, based on the submission that was made. So, it, we'll just have to wait and see if they decide to have one.

You know, 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 in how that might inform our planning as well. Great. Thanks so much for the color and congrats on the progress. Thank you, Salim.

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

Hello, Chad. Hello. Great. Good afternoon, and thanks for taking my questions. First of all, congratulations on your perseverance with all these programs. It's great to see you guys have at least three 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 questions on REL Dissentive. You guys are moving forward with the Phase 3 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 three trial, you know, a higher probability success there.

Sure. I'll take the first part of that question. I'll ask Fatty 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 rel-deceptive to phase three, 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 a interim stop for futility if it looked like that was appropriate and a 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 five-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 Fatih to answer the second part of your question.

FATIH AHMED ALI- 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 three study, the ALS-FRS, 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 whose disease may be progressing more rapidly and other things that we've done in the design to optimize, we think, its chances for success. So we're fairly encouraged based on both the precedent for Fortitude ALS as well as the way we've implemented it in CURCH.

You know, from a portfolio standpoint, it was incumbent upon also to know that when we're advancing rel-deceptive in ALS, it's occurring alongside of the advancement of our pipeline for new cardiovascular medicines. So, omicamptamicarbol moving forward, as well as aficamptam moving forward, we believe is enabling of our advancement of rel-deceptive in key ways, and as is in 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 Semptive. And, you know, once again, congrats on getting to this place with all three of your major programs as well as the other things you're working on.

Thank you, Chad.

Thank you, Chad.

Operator?

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

Hello, Jeff. Hey, Robert. Thanks for taking the questions. Just to clarify Jason's question earlier on Omocanthobacarbul, are you going for a broad label, or would you expect that the label will focus on the more severe patients, specifically calling out, you know, patients with a lower ejection fraction?

Yeah. You know, 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, thanks. 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? You know, 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? Thanks.

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. Thank you. Thank you.

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

Hello, Emmanuel.

Hello. Good afternoon, guys, and thank you for taking my question. 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 Redwoods? perhaps in relation to the differentiation from Aficampton and their expectations around the design and the target population for the upcoming phase three.

Sure. So specifically, your question relates to feedback we've received on Aficampton and how it may set the stage for phase three.

Correct.

Yeah, I think, you know, in 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 in the phase two trial. You know, I think all of those things lend themselves to the design that we will implement in phase three, which, as I said, we'll elaborate at a later time. But, you know, overall, the feedback was quite enthusiastic.

Got it, got it. And switching gears to the 70s, it's nice to see the drug beginning the PIVOTEL study as planned. And I know it's early, but I was hoping you could give more color around the expected timelines for the enrollment. I saw you incorporated in the design remote visits. 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, you know, 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. You know, 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 we've all learned a lot about conducting clinical trials in a pandemic. I think in other programs we've 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. And 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, for most of the study visits, actually to have to present themselves in person in a 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 road related to the pandemic.

Got it. Thank you very much.

You're welcome.

And your last question will come from the line of Craig Savonavea with Goldman Sachs.

Hello, Craig.

Hey, Robert and team. How are you? Thank you very much for the update and congrats on the progress. I was curious about earlier comments you made in the call about your early experience with commercial payers. I believe that was in relationship to Omicamp to McCarble. I was wondering if you could share any of the insights from that early experience, certainly. There's still some time to go, but I wonder 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 Affey-Campden, How similar or how different might that be from the Mavacampt in Phase 3? 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 3 trial. Thanks.

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 Afikampton. Andrew?

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

Yeah, 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 three design of AFI Campton and how it might compare to Mavic Campton, and whether this is going to be in apples and oranges or in 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 a 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 FLORA trial, and we'll take those learnings into our study design for phase three. We're not really prepared to offer any details or discuss those in today's talk. You know, the study design details will be forthcoming later this year.

Yeah, 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 conclude the call.

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