Cytokinetics Q3 2023 Earnings Call Transcript

Quartr
Provided by Quartr
November 2, 2023

There are 19 speakers on the call.

Operator

And welcome, ladies and gentlemen, to Cytokinetics Third Quarter 2023 Conference Call. At this time, I would like to inform you that this call is being recorded and that all participants are in a listen only mode. At the company's request, we will open the call for questions and answers after the presentation. Will allow for one question per participant. I would now turn the call over to Diane Weiser, Cytokinetics, Senior Vice President of Corporate Communications and Investor Relations.

Operator

Please go ahead.

Speaker 1

Good afternoon, and thanks for joining us on the call today. Robert Blum, President and Chief Executive Officer, will begin with an overview of the quarter and recent developments. Fady Malik, EVP of R and D, will provide updates related to afacamten focused to Sequoia HCM and Forest HCM Stuart Kupfer, SVP and Chief Medical Officer, will provide additional updates for afacamten relating to Acacia HCM and Maple HCM will also discuss our early stage pipeline, inclusive of CK-five eighty six and CK-one hundred and thirty six. Andrew Kalos, EVP and Chief Commercial Officer will discuss commercial readiness activities for Assicamten Robert Wong, VP and Chief Accounting Officer, will provide a financial overview of the past quarter and Qing Zha, SVP and Chief Financial Officer, will discuss Financial Outlook and Corporate Development Strategies. And finally, Robert Blum will provide closing comments and review upcoming expected key milestones.

Speaker 1

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, 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 Q3 2023 financial results filed on Form 8 ks that was furnished to the SEC today. We undertake no obligation to update any forward looking statements after this call. And now I will turn the call over to Robert.

Speaker 2

Thank you, Diane, and thanks for joining us on the call today. I'm pleased with the progress we made in the Q3, particularly focused to affecamten, our top priority, and with emphasis on the execution of Sequoia HCM and advancement of its broad development program. Thanks to the diligence and dedication of our teams, we remain on track to share top line results from Sequoia HCM in late December. While this timeline is admittedly tight, we're confident due to the superb organization and oversight of Sequoia HCM by our clinical operations Like all of you on the call, we're eager to see these top line results. As Fady will elaborate, we have strong conviction that the top line results from SEQUOIA HCM will meet our high expectations for both safety and efficacy based on the patient population enrolled in SEQUOIA HCM as well as the unique attributes of afikamten.

Speaker 2

If Sequoia HCM meets our expectations on both efficacy and safety, we expect it may contribute to expansion of the cardiac myosin inhibitor or CMI category on both accounts. Simultaneously during the quarter, we continued to build our specialty cardiology franchise by advancing the ongoing clinical trials in the development program for afikamten as well as earlier stage clinical research. With enrollment underway in both Maple HCM and Acacia HCM, we foresee a near term future with multiple catalysts for afikamten. And rounding out our specialty cardiology franchise, are CK-five eighty six, a second cardiac myosin inhibitor and CK-one hundred and thirty six, a cardiac troponin activator, on which Stuart will provide an update. Our cash position at the end of the quarter represents over 18 months of cash runway is based on our 2023 net cash burden guidance.

Speaker 2

Importantly, as is our practice for both financial health and prudent planning, We're gating spending through the readout of top line results of Sequoia HCM and we're judiciously focusing our current spending on activities related to our top priorities, again, with focus to affecamten and a critical eye towards cost efficiencies. Today, you'll hear about the continued progress we made during the quarter and what to expect through the end of the year. As we approach 2024 and as you heard a few weeks ago at our Investor and Analyst Day, Cytokinetics remains laser focused to delivering on the promise of afikamten as well as to advancing our earlier stage pipeline as we build our specialty cardiology franchise for the potential benefit of both patients and shareholders. And with that, I'll turn the call over to Fady.

Speaker 3

Thanks, Robert. In the Q3, we made significant headway across the development program for Recently, we were pleased to present the baseline characteristics of patients enrolled in SEQUOI HCM, the pivotal Phase 3 clinical trial of apicamten at the HCM Society Scientific Sessions. The baseline characteristics met our objective for the intended trial population, having enrolled a global, diverse and real world population with a substantial deficit in exercise capacity and significant symptom burden despite existing standard of care. Patients enrolled in SEQUOIA HCM had an average peak oxygen uptake or peak VO2 of 18.5 milliliters per kilogram per minute is at baseline or 56.9 percent of that predicted for their age and sex, which is an objective indicator of the with an average KCCQ score of 74.7, further reflective of a highly symptomatic patient population despite will be subject to background treatment with guideline directed medical therapies. Background medical therapy included beta blockers, calcium channel blockers and disapiramide with patients permitted to receive combination background medical therapy.

Speaker 3

Beta blockers, which are known to blunt maximum exercise capacity due to their effect to slow heart rate, were used in 61% of the patients. We are very pleased to see that our objectives are achieved and that we enrolled the population that we intended. As we approach the readout of SEQUOI HCM later this year, we're confident in the completeness of the data and that we're outperforming the design assumptions for the trial. The extent of missing data and the standard deviation of the primary endpoint are all within our assumptions, which should augment the power of the trial to assess the change in the primary endpoint. I'm also pleased to report that nearly all patients have completed dosing and sites have not reported any patients with an LV ejection fraction less than 40%.

Speaker 3

We're eagerly anticipating sharing the top line results in late December. Our convictions are high

Speaker 4

that the results of Sequoia HCM will

Speaker 3

meet our expectations. These convictions are further reinforced by the long term At our recent Investor and Analyst Day, we shared new longer term data with data available in some patients for greater than 2 years. More than 200 patients have been enrolled in FOREST HCM to date and data from 143 patients with obstructive HCM were available for this analysis. The new data from FOREST HCM show that no patient had a treatment related LV ejection fraction less than 50% during the treatment period during the titration period and approximately 2 thirds are receiving 15 milligrams or 20 milligrams of apikamten. During the maintenance phase of forest HCM, there have been no instances of LVEF less will be recorded for 40%, which would require treatment interruption and only 3 instances of LVEF less than 50% that simply required a dose down titration.

Speaker 2

Of the

Speaker 3

579 monitoring echocardiograms completed during the maintenance phase of treatment, 99.5% of them did not result in a dose down titration. We also observed in these reported data from forest HCM that the mean resting and Valsalva LVOT gradients remain reduced and below the diagnostic threshold for has improved symptoms. Approximately half of patients were NYHA Functional Class 1 or asymptomatic and 80% of patients improved by 1 or more functional class. Furthermore, 90% of the SRT eligible patients at baseline were no longer SRT eligible at the time of this analysis. Apicamten has been generally well tolerated with no treatment related serious adverse events as assessed by investigators.

Speaker 3

Additionally, approximately 30% of patients have reduced doses of background therapy or discontinued it entirely at the discretion of the treating physician and or by request from the patient. This supports the rationale for Maple HCM, which Stuart will discuss next. These new results from FOREST HCM are quite compelling and we look forward to continuing to gather more longer term data for apicamten is subject to this open label extension. Shifting briefly back to Sequoia HCM, following the top is a complete online readout of the results in late December. We expect to hold a meeting with FDA in the Q1 of next year to discuss the top line results with the goal of potentially submitting a new drug application for apikempton in the second half of twenty twenty four.

Speaker 3

During that initial meeting to review the top line results, we'd expect to begin a dialogue about how did the safety and efficacy of apicamten observed in Redwood HCM, Sequoia HCM and Forest HCM would influence the design of a REMS program. We look forward to these interactions and will provide further updates next year. Now I'll hand it over to Stuart to elaborate on additional progress we've made for apukampson and provide an update is on our earlier stage clinical pipeline.

Speaker 5

Thanks, Fady. During the Q3, we started ACACIA HCM, the pivotal Phase 3 clinical trial of apukamten in patients with symptomatic non obstructive HCM. Enthusiasm among investigators is high as many of the investigators participating in Acacia HCM have prior experience with apikamten from Redwood HCM, Forest HCM and Sequoia HCM. Additionally, as you may know, patients with non obstructive HCM have limited treatment options. Standard of care medications, including beta blockers and calcium channel blockers are not very effective, and therefore, patients with non obstructive HCM often struggle with a high symptom burden.

Speaker 5

Our hope for this clinical trial is to gather evidence about the potential of apicamten for this important segment of the HCM population, which lacks treatment options. In the Q3, we also continued patient enrollment in Maple HCM, the Phase III clinical trial evaluating for the potential superiority of apikantin as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM. We're pleased to report that enrollment is progressing according to plan. If positive, Maple HCM should support the possibility for apicamten to be considered for first line therapy in obstructive HCM. Shifting to our earlier stage pipeline, as Robert mentioned, we also made progress advancing both CK-five eighty six and CK-one hundred and thirty six during the quarter.

Speaker 5

We've now completed the single dose cohorts of healthy participants in the Phase 1 study of CK-five eighty six, our cardiac myosin inhibitor in development for the potential treatment of a subgroup of patients with heart failure with preserved ejection fraction or HFpEF with hypercontractility. We've now concluded our analyses of the single dose cohorts, which are is recorded for proceeding to the multiple dose portion of the study, which we expect to start in this Q4. As the Phase 1 study progresses, we also recently unveiled new preclinical data for CK-five eighty six at our Investor and Analyst Day, is showing improved diastolic function and reduced cardiac fibrosis in an animal model of HFpEF. These data, along with the results observed with apikamten in non obstructive HCM, which has features similar to that of HFpEF with hypercontractility, support the potential benefit of CK-five eighty six in this patient population. Shifting to CK-one hundred and thirty six, is being recorded in our cardiac troponin activator.

Speaker 5

We completed the single ascending dose cohorts in the Phase 1 study in healthy participants, and we're now analyzing these data to inform potentially proceeding to the multiple dose cohorts of the Phase 1 study. With that, I'll turn the call over to Andrew.

Speaker 6

Thanks, Sophie. As we outlined at our Investor and Analyst Day, our approach to commercial readiness in 2023 is centered around with the intention of designing an optimal physician and patient experience. During the quarter, we continued to conduct market research to assess potential patient profiles and available market segments in obstructive HCM, which have confirmed a symptomatic patient population in need of disease modifying treatment with a potential next in class CMI. By anchoring our commercial strategies to this patient centric approach, we are preparing to address a high unmet customer need with the objective of positively impacting patients and shareholders is approved. At the same time, we're learning through our market research that physicians indicate a strong interest in the potential target product profile for apikamten,

Speaker 2

showing that

Speaker 6

there is room to capture share among newly treated ATM patients and potential to expand the total CMI market. Furthermore, we expect CMI penetration of eligible full of obstructive HCM patients to be less than 20% at the time of expected launch of afacamten, meaning that over 80% of the obstructive CM eligible patient population will remain untreated with a CMI. We are therefore focusing our commercial readiness strategies to those enabling expanded use of CMIs, building on the expected next in class profile of afikantin arriving from our clinical trials program. We also will strive to design a seamless and patient friendly TMI experience through a comprehensive patient support program will help address the emotional, financial and educational needs of a patient throughout their journey. With the patient experience in mind, we recently held in Ministry Theater Program at the HSSA Annual Scientific Meeting, where we facilitated a discussion surrounding the impact of obstructive HCM, which may have an impatient on patient quality of life, mental health and well-being, as well as how cardiologists can better understand and address these concerns.

Speaker 6

This approach of elevating the holistic and human centric view of HCM is resonating with HCTs And hope we hope it may help foster better physician patient conversations and raise more awareness of the myriad impact of ATM.

Speaker 2

Through the end of

Speaker 6

the year, we plan to continue our market research and go to market planning for apicamcin. In 2024, our experienced team will shift focus to the design and build of our commercialization strategies as informed by market research,

Speaker 7

Thanks, Andrew. We ended the Q3 with $554,700,000 in cash and investments. During the quarter, we received a 50,000,000 dollar milestone payment from Royalty Pharma upon the start of Acacia HCM, which is treated as a liability on our balance sheet in accordance with GAAP. In addition, recently, we received a $2,500,000 milestone payment from Jiaxing received upon the start of Acacia HCM. Our Q3 2023 R and D expenses increased to $82,500,000 from 62 point Our Q3 2023 G and A expenses were $40,100,000 down from $48,200,000 in Q3 2022 is due primarily to lower outside service spending.

Speaker 7

Now I'll hand it over to Qing to review our financial outlook and corporate development strategy.

Speaker 4

Thanks, Robert. As Robert mentioned, we ended the quarter with approximately $555,000,000 is on the balance sheet, which represents over 18 months of cash runway based on our 2023 net cash burn guidance. In the second half of the year, we have reduced our spending and are critically assessing our go forward spending priorities to help facilitate will provide the best return on our financial commitments. Our main priority remains epikempton. And as we approach 2024, We are being prudent in our spending around preparations for the potential commercial launch of epikamten.

Speaker 4

Towards that aim, we are gaining expenses ahead of our sharing the top line results of Sequoia HCM. Once we have the results and provided they are positive, we will be able to refine our assumptions further is on gate spending. As usual, we plan to provide guidance to our 2024 spending during the Q4 earnings call. As for access to capital, I'll remind you That through our transaction with Royalty Pharma, we remain eligible for 2 additional loan tranches under our development funding agreement, including $75,000,000 upon our potentially sharing positive results from SEQUOIA HCM and $100,000,000 upon acceptance of an NDA submission for epicantham in the U. S.

Speaker 4

As it relates to corporate development, over the year, we have engaged in a rigorous process in which we met with multiple potential partners. We have noted a high degree of interest in AffyCampton, both independently and in some cases in concert with potential to include omecamtiv mecarbil in regions outside of North America. This process has affirmed the value proposition to our Go to Europe strategies. With that said, we do not expect to enter into a partnering deal prior to announcing the top line results from Sequoia HCM and will continue to evaluate how we access and deploy capital as we will learn more about Epikhampton from Sequoia HCM. Now, I will turn the call back to Robert Blum.

Speaker 2

Thank you, Ching. As we proceed to close out 2023, we're approaching an important inflection point for our company. With apicamten representing the leading edge of our specialty cardiology franchise, will be a pharmaceutical company in 2024. In 2023, much was put into motion that is now carrying us closer to our goal of bringing forward new medicines for patients with diseases of impaired muscle function. While our priority remains apicamten and our earlier stage pipeline, during the quarter, we submitted a formal dispute resolution request to the FDA's Office of New Drugs regarding the CRL or complete response letter for omecamtiv mecarbil.

Speaker 2

Our objective is to appeal FDA's conclusion That substantial evidence of effectiveness has not been established to support approval of omecamtiv mecarbil. As I've said before, we do not currently have plans to conduct another clinical trial of omecamtiv mecarbil and we may not be able to address the deficiencies noted in the CRL. However, we still believe in the science underlying omecamtiv mecarbil and the demonstrated evidence to potentially benefit patients with advanced or worsening heart failure. If our appeal to FDA proves successful, we'll then consider potential next steps for omecamtiv mecarbil, albeit and importantly, as to the lens of a company for which our top priority is afikamten. We also continue to pursue potential approval for omecamtiv mecarbil outside of the U.

Speaker 2

S. Regarding Europe, we submitted our responses to the day 120 questions to the EMA and now await their feedback. As it relates to China, Our partner, Xijing, submitted a request for voluntary withdrawal of the NDA for omecamtiv mecarbil to the Center For Drug Evaluation of the National Medical Products Administration of the People's Republic of China, subject to potential resubmission upon receipt of favorable feedback from EMA or FDA with regard to potential drug approval for omecamtiv mecarbil in the EU or U. S. Respectively.

Speaker 2

Shifting now to business development. As Ching said and to be clear, We do not expect to partner AffyCampton leading into the readout of Sequoia HCM. Our focus remains on that which is under our control and that which is the most meaningful for our company and for patients and shareholders, which is advancing affikamten. However, it is reinforcing to our corporate strategies to have engaged with potential partners who have expressed a high level of interest in AffyCampton and ultimately validate our own planning. We believe that we are doing right by all of our stakeholders to objectively and critically evaluate our own plans.

Speaker 2

As a result, with the readout of results from Sequoia HCM, we'll be better prepared is on a year marked with both ups and downs admittedly. We have faced certain setbacks which tested our company's grit and resilience, But we've also made great progress. Today, we're uniquely positioned for success with a strong specialty cardiology franchise led by our own broad late stage development program for apicamten, complemented by earlier stage drug candidates that have arisen from our industry leading research and leadership in muscle biology and the mechanics of contractility. That plus our relationships with key stakeholders and our access to capital sets us apart, as does our passion, our dedication to our mission and our focus on doing right by patients. I look forward to 2024 with optimism and eager anticipation for what's yet to come.

Speaker 2

Lastly, and before I recap our upcoming milestones, I'd like to also mention that leading into the results and the readout of Sequoia top line in late December, we plan to enter a quiet period starting on Monday, December 4. Now our upcoming milestones. For apicamten, we expect to share top line results from Sequoia HCM in late December and continuing enrollment of patients in Maple HCM and AKASA HCM and continue to advance our go to market strategies is for afikamten. For omecamtiv mecarbil, we expect to continue to pursue potential approval for omecamtiv mecarbil in Europe. And for CK-one hundred and thirty six, we expect to analyze data from the single ascending dose cohorts of the Phase 1 study to inform potentially proceeding to the multiple ascending dose cohorts in that Phase 1 study.

Speaker 2

And finally, for CK-five eighty six, we expect to proceed to the multiple ascending dose cohorts in that Phase 1 study in this quarter Q4 2023. Operator, with that, we can now open up the call to questions, please.

Operator

Thank you. And our first question will come from Joe Pantginis from H. C. Wainwright. Your line is open.

Speaker 2

Good afternoon, Joe. Hi, everybody. Good afternoon. Thanks for taking the question. So curious on Fady's comments with regard to background therapy reductions and more importantly, how these, therapy reductions might improve the quality of life and the safety of these patients.

Speaker 2

And then secondly, just quickly, anything meaningful to discuss with regard to the cost impacts Sure. I'll let Fady answer your first question and I'll take the second.

Speaker 3

Thanks, Joe. I think with regard to withdraw a background therapy. The protocol, as we reported back at ACC, allows investigators to will slowly withdraw beta blockers or other background therapies such as disapiramide or even calcium channel blockers based on patient tolerance, and then at the same time, they're also allowed to up titrate apicamten as necessary to compensate. And so we see, can't give you exact percentages, but We see a substantial about 2 thirds I think withdraw from all background therapy. I think in most cases, they've been able to discontinue diazepiramide And also with beta blockers as well quite successful in terms of withdrawing from those.

Speaker 3

So I think from a patient point of view, it simplifies medical therapy. It gets them off of some of the troublesome Adverse events that they experience with those drugs and it simplifies their medical regimen.

Speaker 2

And to your second question regarding potential costs associated with our submitting The formal dispute resolution, they're really quite minimal. These are costs that relate to internal activities and together with Counsyl, no new studies, no new analyses, Nothing that would represent a meaningful investment of spending.

Speaker 8

Thank you, guys.

Speaker 2

Thank you.

Operator

Thank you. And our next question will come from Dane Leone from RJS. Your line is open.

Speaker 8

Hey, how's it going, Robert and team? Yes, we've been talking a lot lately. So really only one question For me that keeps coming up with investors is, given the late December nature of the top line of Sequoia, Can you just provide any detail of how you think the team will handle disclosure of the top line data? I think a lot of people point back to some of the early Redwood disclosures that your team made around description of some of the key primary endpoints and maybe some detail around left ventricular ejection fraction adverse events. But anything you can tell us Of how your team plans to handle, I think could be really helpful for setting expectations.

Speaker 8

Thank you.

Speaker 2

Sure. I'll do my best. Recognizing that we don't have the data, so it's hard to be as clear as you might want us to be. But our goal is to disclose all of that, which should hopefully convey our ability to have achieved is a next in class potentially best in class profile for afikamten. How much of that will be quantitative with P values, primary and secondary endpoints, safety and adverse effects is ultimately going to depend on that which we can consider alongside of hopefully the American College of Cardiology where we would hope to be presenting these data, albeit not for several more months afterwards.

Speaker 2

So our goal will be to be communicative as much as we can, But knowing we don't want to jeopardize any presentation at a proper scientific forum. So we recognize what is expected if we're going to have a next in class potentially best in class profile and those are the things that are top of mind for us as we will think about that which we can disclose. Obviously, we've got to disclose that which is deemed material to shareholders.

Speaker 9

Excellent. Thank you.

Speaker 2

Thank you.

Operator

Thank you. Our next question will come from Salim Syed from Mizuho. Your line is open.

Speaker 2

Good afternoon, Salim.

Speaker 9

Good afternoon, Robert. How are you doing? Just a question for me. I'll just follow-up on that on Sequoia. Just wanted to maybe hear from you or Fady, just so that we are all clear on How we should compare mavacamten to afacamten.

Speaker 9

They had a 1.4 change unit change on peak VO2 and I think there was about a 6% injection fraction sub 50%. Just curious If you can just framework for us the bookends, low end and high end on peak VO2, like is it a one point change and a 1.8 where it would be comparable? Or where do you actually start to feel like you can differentiate on efficacy? And the same question just on safety, how much different do you need to be versus mavacamten in order to feel like you can actually differentiate and how that speaks to our REMS, etcetera. Thank you.

Speaker 2

Sure, Shailene. So you won't be surprised for me to again emphasize that we're not going to be making comparative statements with mavacamten. The SEQUOIA HCM study is a different study than was the study EXPLORER HCM that led to the approval of mavacamten. All I can speak to and all Fady will speak to is that which relates to apicamten and what our expectations are ultimately labeling and positioning and how physicians see those 2 potential medicines will define will be our hope of expanding the category and best in class. So with that long caveat, Maybe I'll ask Fady to try his best to speak to what our expectations are around apicamten in Sequoia HCM.

Speaker 3

Yes, Salim, I think what we will see and hope to see is that the changes are going to be meaningful of magnitude such that the question isn't really one of whether there's a slight difference between 1 or the other. Both drugs are going to be, well, I should say mavacamten we know is quite effective in patients. We Hope to see afikamten be equally or even better effective. I don't think you can judge those types of things just based on Comparisons of a single number, you have to really look at the totality of the data across all the endpoints. You have to couple it with the safety profile as, again, as we might see in the study.

Speaker 3

And so there's not a simple answer to your question as I know you're hoping me to provide.

Speaker 9

Okay. No worries. I just wanted to ask the question, but I appreciate the answer. Thank you.

Speaker 2

Thank you, Selim.

Operator

Our next question will come from Jason Zimansky from BofA. Your line is open.

Speaker 2

Hello, Jason.

Speaker 10

Good afternoon. This is Cameron Boesdock from Bank of America Securities on for Jason Szymanski. Congratulations on the progress and thanks for taking our question. I'd like to ask a follow-up on ES, if I may. You recently reported data from FOREST HCM OLE where 3 patients had an LVEF reduction below 50%.

Speaker 10

What do you think you need to show regarding LVEF reductions in Sequoia to make regulators comfortable permitting fewer echos as part of a potential REMS? Does have to fall below EXPLORER 6% or following the death in MAVA's valor, are regulators to be more cautious on the class as a whole, at least initially?

Speaker 2

Sure. And thank you for the question. I've read some of the research that you guys have published relating to this matter and maybe I could clarify how we think about it. We're looking at data from SEQUOIA HCM with already having discussed with FDA in the design of SEQUOI HCM, a protocol that's permitting of down titrations when EF falls below 50 as opposed to dose interruption or dose termination, the consequences of down titration being well within the norm of cardiology group practices in this area. So we approach the data when it will be available from SEQUOIA HCM with those same optics, meaning I don't think it's really a question of its 3% or 6% or any number within that range, but how does that really affect patients and physicians and how likely would FDA feel a half life that's enabling of a relatively rapid return to normalcy with an EF such that if EF does drop, it may be inconsequential.

Speaker 2

And in that way, a simple down titration would be acceptable by physicians without any concerns and worry, we believe that could be very important for ultimately the profile of afikamten. So I wouldn't dwell on the number, even though as Fady reported, we've had in any adjustment to dose, but for the fact that these down titrations might occur occasionally, I would think that that will go a long way to be providing hopefully if the data in SEQUOIA bear out like we've seen in FOREST, is a profile that will be deemed next in class. Fady, anything you want to add to that?

Speaker 3

I just might add that cardiologists are really quite adept at managing drugs that have to be monitored. And if you think about, for instance, Heart failure therapies like mineralocorticoid receptor antagonist. These drugs have long been known to cause rises in Potassium, even life threatening increases in potassium. And if you read the label of a planone, for instance, in 1% to 4% Patients that receive these drugs and it's not Cardialis is no stranger to drugs that need to be monitored. So I don't think it's ultimately as one becomes familiar with the class that It's not surprising that one begins to see monitoring become is changing over time and that it becomes just part of standard practice.

Speaker 3

So I think as Robert said, what we've seen to date with apicamten coupled with familiarity with the class would hopefully lead to is something that's both reasonable for patients and physicians to execute and maintain patient safety.

Speaker 10

Appreciate the color. Thank you.

Speaker 2

Thank you.

Operator

Thank you. Our next question comes from Serge Belanger from Needham. Your line is open.

Speaker 2

Good afternoon, Serge.

Speaker 11

Good afternoon, Robert. A follow-up on a prior question regarding the data disclosure that we're expecting in late December. ACC has historically been pretty restrictive in what can be disclosed ahead of the late breaking Clinical trial presentations at their meeting. So in some cases, we've heard nothing more than whether it met primary endpoint. So just curious if you're confident that you will be allowed to provide more data than that on both the efficacy and safety side of the trial.

Speaker 11

Thanks.

Speaker 2

Thank you. Again, Not having the data, it's difficult to be as clear as you might ultimately want. But yes, I'm confident. I think we can communicate what we need to communicate to be satisfying both our objectives to be disclosing that which is deemed material for the benefit of shareholders and ultimately also enabling of a will be a proper presentation at the ACC when it comes. We've been down this path before, others have too, And I think this is something that can be accomplished.

Speaker 2

Is excellent.

Operator

Thank you. And our next question will come from Ashwani Verma from UBS. Your line is open.

Speaker 12

Hi. Good afternoon. Thanks Fatima here on behalf of Ashwin from UBS. Just two quick ones here. We understand that you have low beta blocker using your study from the baseline characteristics and that can help tease out the effect size But since beta blocker usage is really high in the real world, would afikamtine effect size in real world potentially be lower than what you're showing the SEQUORIA study?

Speaker 12

And just a second quick one. We want to get your views on what is the relationship between LVOT gradient reduction and peak VO2, we have some studies like one from Kemzyo that shows correlation, but there are other studies from beta blockers that show that there is no correlation. So What do you see as the causality or the correlation between these two endpoints when it comes to afacamten?

Speaker 2

Sure. So I'll just start and then ask Fady to speak to your questions. We designed and conducted a study Koya HCM that we believe is very representative of the population that we hope ultimately afikamten will be available to treat. So it's not an artificial construct, it's not a manufactured population, it's in fact real world. And in that way, we went to great pained to ensure that this was a study that was enabling of physicians ultimately upon the availability of data to apply these results to their own practices.

Speaker 2

And with that, I'll turn it to Fady.

Speaker 3

Yes. Let me remind you that I said 61% of the majority of patients are taking beta blockers. It's not out of line with what is seen in the real world. Additionally, you look at the use of calcium channel blockers, the allowance for combination therapy of calcium channel blockers and beta blockers or beta blockers and disoparamide. I would argue that Sequoia HCM provides a very relevant real world experience In terms of apicamten's effectiveness when we have those data.

Speaker 3

So I think that question is really answered by the baseline characteristics that show that there's a high degree of background medical therapy that's employed. I think the second point is, as we pointed out is that, background therapy may not be optimal for these patients. Ultimately, some of these background therapies may be holding them back and beta blockers being an example. One of the reasons you see less good correlations between LVOT gradient reduction and peak VO2 is because beta blockers disrupt that correlation. In the absence of being able to increase your heart rate during exercise, even as you've gotten rid of the gradient, you can't increase your exercise performance because you can't increase your heart rate.

Speaker 3

And so, it's more complicated Unfortunately, the NAKLING scientific experiment where you change one variable and measure another variable. But roughly, there is a good correlation. Reducing the gradients always been the target of both medical and surgical therapy. And obviously, there's precedent in the class that reducing the gradient improves peak VO2.

Speaker 12

Great. Thanks for taking my question.

Speaker 6

Thank you.

Operator

Thank you. And our next question will come from Jason Butler from JMP Securities, your line is open.

Speaker 13

Hi, thanks for taking the question. Hi, Robert. Just wondering if you could comment on, from a commercial planning perspective, how feedback from FDA, assuming positive data from SEQUOIA and you meet with FDA in 1Q24, how that feedback on a REMS program will impact your commercial planning and scenarios where the REMS could be similar to mavacamten or less burdensome than mavacamten? Thanks.

Speaker 2

So I just want to make sure I captured your question properly. Could you repeat the first part?

Speaker 13

Yes. Just when you get feedback from FDA on potential of what a REMS program may look like, How that would impact your commercial planning in scenarios where the REMS was similar to mavacamten or less burdensome than mavacamten.

Speaker 2

Okay. Now I understand. Thank you. I'm going to ask Andrew to speak to some of this, but please understand that, absent the data, Right now, these are abstract scenarios that we've contemplated in market research. And once we have their data, we'll be able to do more refined market research and ultimately as we may propose REMS, this is something that is is going to be achieved through interactions, the sponsor with FDA.

Speaker 2

So all of this is subject to still a great deal of uncertainty until we have the data around which it's based. But we do have certain expectations as we have seen Redwood data, as we've seen forest data, and as we've understood what's behind the REMS for the other cardiac myosin inhibitor, is speculative as you can imagine at this point in time. Andrew, can you speak to how you've approached this from the market research standpoint?

Speaker 6

Sure. So I guess there's 2 important things to understand. One is we probably won't have that much clarity in terms of exactly what a REMS program is going to look like early in the review process. That's something that we propose to the FDA. But relative to our patient support services, Independent of what the REMS will look like, there are certain elements of patient support we're going to offer.

Speaker 6

So we know we're going to offer things like patient assistance and co paper. We'll look at echo reimbursement. We'll help with benefits verification, education on disease So there are certain things that we know are at minimum and that we're going to do. There's other things that based on the complexity of the REMS that we'll do as well. Our assumption going into planning is that we're going to assume a complex REMS with all elements and it's a lot easier for us to Simplify or back down from that once the REMS program comes into view, because when it does come into view, it's a negotiation As you're negotiating label near the end and we would not have enough time to react.

Speaker 11

So hopefully that gives you a sense

Speaker 6

of how we're thinking about it.

Speaker 2

And just to add one more comment, if you read the summary basis of approval, there's a lot that one can learn about what the FDA was seeking to accomplish in putting in place the REMS program that does exist today and will obviously be is conditioned based on that prior knowledge to know what we need to glean from the evidence from will be recorded in order to hopefully enable something that is different. But ultimately that's something that comes is down the road following the acceptance and the review of a new drug application.

Speaker 14

Okay. Thank you.

Speaker 2

Thank you.

Operator

Thank you. And our next question will come from Shri Kripa Devarakhanda from Truist Securities. Your line is open.

Speaker 2

Good afternoon.

Speaker 15

Good afternoon, Robert and the team. Thank you so much for taking my questions, and really looking forward to the data, in about a couple of months, hopefully less than that. I have a question about MAPLE trial. You talked about enrolling patients that are naive to therapy as well as those who were is on background therapy, but withdrew from it. Can you remind me if there's any restriction in terms of How long these patients could have been on therapy, symptomatic and on a standard of care and how that featured into how the trial was powered?

Speaker 2

Very good questions. I'll turn to Fady, please. Well,

Speaker 3

I'll ask Stuart to answer since he discussed Maple in his section. But in general, patients could have been on beta blockers for any length of time, as long as they could be withdrawn. They were considered in certain classes And depending on the length of time, I'll ask Stuart to elaborate, please.

Speaker 5

Yes. Thank you for the question. The concept here was to evaluate apicamten as first line use or as an optional monotherapy for patients who have been treated with standard of care for, let's say, a number of years. And so, we sort of subgroup these patients into 1 group is either naive to beta blocker therapy or no longer receiving beta blocker therapy or on beta blockers for a short period of time versus those who have been treated with beta blockers or standard of care for is more than a year. And that's sort of the breakdown of and the strategy for evaluating Apicamten monotherapy, either as first line, versus again a possibly superior option versus standard of care as the apicamten monotherapy for patients who have been on standard of care for an extended period of time.

Speaker 5

So, the study is designed, of course, to evaluate the potential for superiority of afacamten monotherapy versus beta blocker monotherapy in either of those subgroups of patients.

Speaker 15

Got it. Thank you.

Speaker 2

Thank you. Thank

Operator

you. Our next question will come from Jeff Hung from Morgan Stanley. Your line is open.

Speaker 2

Hello, Jeff.

Speaker 10

Hi, good afternoon. This is Catherine on for Jeff. Thank you so much for taking our question. You mentioned previously that physicians have indicated their interest and excitement in africancin. We want

Speaker 16

to ask in either your research to date or in any feedback that you received, what aspects of aficantham's profile is the physicians may be finding most compelling?

Speaker 2

So Andrew, may I ask you to respond to that, please?

Speaker 6

Sure. So in our market research, when we put an aspirational profile in front of physicians, The things that they mentioned most excited about are preservation of LVEF function, Obviously, which is a safety element, change in New York Heart class or improvement going from a 3 to a 2, a 3 to a 1, a 2 to a 1, As an example, change in KCCQ and limited DDIs that really don't need to be monitored relative to dosing. So those are the things they mentioned that are most would drive their preference for apathympan.

Speaker 10

Okay. Thank you so much.

Speaker 2

Thank you.

Operator

Thank you. Our next question will come from Yasmeen Rahimi from Piper Sandler. Your line is open.

Speaker 2

Good afternoon, Yasmeen.

Speaker 16

Hi, Robert. Thank you so much for all your comments. I guess with data expected late December and you guys entering quiet period, I guess, December 4 is like, could you maybe highlight to us what is your definition of late December? And then secondly, just maybe comment on how has been this data cleaned up as you guys have been collecting it? Or is it just like, Do you start like cleaning up the data as soon as things get locked out in early December?

Speaker 16

Thank you. Appreciate if you could tackle both for me.

Speaker 2

Sure. So I hope this can be helpful. But Please understand as Fady shared with you, while nearly all of the patients have completed their maintenance phase not all of them have and there's still some additional visits that must occur from which data collection still must follow in order to be enabling of database lock. So while we're in the very late innings of this project, It's not yet done, so we can't be as precise as you might like in asking the question about what do we mean by late December. What we mean is it's going to be in December, whether that's towards if we thought it was early December, we would have said so.

Speaker 2

Late December probably means it's, as you can imagine, weeks into the month and that's ultimately going to be defined by how quickly can we get to database lock and the enabling of analyses. It's not uncommon where in a study like this it would typically take 4 to 6 or more weeks to go from database lock to tables, listings and figures from which one could distill top line results, We're going to try to do that faster and as fast as we can subject to what are still data to be collected. To this point in time, we feel very good about where we are with data collection, enabling of database lock and analyses and I hope that's helpful to your question.

Speaker 16

Thanks, Robert.

Operator

Thank you. Our next question will come from Charles Duncan from Cantor. Your line is open.

Speaker 14

Hey, Charles. Hi, Robert. Congrats on the progress by you and the team. Thanks for taking our questions. I had a couple of quick ones.

Speaker 14

A lot of great questions asked on SEQUOIA, but I did want to ask about the baseline data with regard to certain geographies and an interaction, I guess I'm wondering when you think about all the patients that are from China versus Europe or Israel, are there any, call it, phenotypic or, call it behavioral differences that you think may impact call it the read through from China versus Israel or Europe in terms of exercise capacity? Thanks.

Speaker 2

Good question. And I'll say I've been myself engaging with our colleagues to understand what could be is accomplished for our making this a truly international registrational study and what can we learn from prior studies and what do we know. So, I'll ask Fady to speak specifically to your question.

Speaker 3

Hi, Charles. I think with regards to exercise performance, you're an athlete. If you look at our Olympic level athletes, you see they come from all over the world and performances can be seen in all those populations at an extremely high level. So similarly, I think in studies like this, We have the opportunity to see improvements in exercise performance across the board. I've been pleased to really buy The quality of the data that we've received from all of those regions, we have experienced in GALACTIC, for instance, in in terms of response to omecamtiv mecarbil in all of those regions and the response to omecamtiv was quite strong, particularly in China In fact, so I don't have any concerns at the moment with regards to regional variability.

Speaker 3

Obviously, we'll see when the data

Speaker 2

emerged. Charles, just to add, if your question is in any way tied to is there additional risk For the fact that we're enrolling in some of those regions, I hope you can draw comfort from the fact that as Fady has pointed out, we're quite comfortable with the integrity of the data, the absence of missing data, The standard deviation and those things that ultimately read on statistics. So those are things that we continually monitor and we're quite pleased with where we sit.

Speaker 14

Yes. That actually answers both parts of the question, both in terms of at the patient level, but at the clinical site level. Let me ask you one last question, if you could wax poetic, if you will, Robert. But when you think about The vision of becoming a high growth specialist focused cardiovascular company, what are the analogs that you look to really be able to define success in the next couple of years? Thanks.

Speaker 2

I don't foresee that there's really an analog in biopharma today, is a company that is a specialty cardiovascular company. Obviously, there are specialty companies in other therapeutic categories like in the areas of CNS for instance, but what we're focused towards in the build out of our pipeline and corporate development strategies are those kinds of opportunities that are directed to concentrated customer segments where there would be both pricing and payer leverage, where there's limited sales and marketing infrastructure required to get to a high yield, high return on investment strategy. And we don't think the other predecessor cardiology companies in the biopharma space had those advantages, in order to be able to compete effectively. We think they do exist in those markets and for those programs where our science directed to cardiac muscle lends itself to a new business model in the biopharma space and one for which we do believe there are elements that translate to maximizing shareholder value. So, I hope that answers your question.

Speaker 14

Yes, it does. You've been a good student of the history of the industry. So I appreciate you providing your perspectives. Thanks.

Speaker 2

Thank you.

Operator

Thank you. And our next question will come from Ruana Ruiz from Leerink Partners. Your line is open.

Speaker 2

Good afternoon.

Speaker 17

Good afternoon. Thanks. So a quick one from me. I was curious if you could talk a bit more about the clinical meaningfulness of the 99.5 percent of monitoring echoes that did not need dose reductions in the FOREST data. And how does it actually compare to what physicians are seeing in clinical practice today with mavacamten?

Speaker 2

We'll address that, but I hope you'll understand if we don't make a comparative statement to mavacamten. But Fady, could I ask you to take that?

Speaker 3

Sure. I think the reason we made that point, in fact, I know the reason we made that point In terms of the number of echoes, the number that don't require a change in management, is to give some flavor to what the burden of monitoring is. If you do a test to is monitored for something and it only has a meaningful outcome In less than 0.5 percent of the measurements that you do, You have to ask yourself, are you appropriately deploying resources in a way that is efficient? And are there better ways deploy those resources that can maintain the same degree of safety, but not necessarily burden the system quite as heavily. So I think incumbent on us to understand what the determinants Are of those very infrequent events, how do we anticipate them and to eliminate

Speaker 14

What are

Speaker 3

99% of tests that have no clinical impact, but cost the System a lot in terms of resources, time and money. So I think that's ultimately why we made those points in our presentation.

Speaker 17

Got it. Thanks.

Speaker 11

Thank you.

Operator

Thank you. And our next question will come from Justin Kim from Oppenheimer and Co. Your line is open.

Speaker 2

Hello, Justin.

Speaker 18

Hi, Robert. Good evening, everyone. Sorry, I may have joined a little bit late, but I just had a quick question on the, I guess the SEQUOIA study and Inclusion of patients who are refractory to SRT, just because of, I guess, the young woman's experience that was presented a few weeks back. Curious like if that experience would be similar to what we saw in Explorer And any color

Speaker 2

there. So I think I just want to make sure that we're using the right language, I don't know that refractory to SRT is the right way to put it. What we were pointing out was those patients who were eligible for SRT pretreatment versus post treatment, but maybe Fady could speak to that. Yes. No, that's right.

Speaker 3

These patients meet the criteria for SRT, which is that they have New York Heart Association class of 3 or more And that they have a gradient of 50 or more. So in Forest, we, a couple of weeks ago, Look again at the percentage of those patients who remained eligible for SRT Once they started apacamten treatment and only about 10% of them met those criteria after therapy were of the ones that had met at the time of therapy. So we're not necessarily inclusive of Patients that are refractory to SRT, they just meet the criteria for SRT.

Speaker 14

Okay. I guess maybe just a clarification.

Speaker 18

I think there were patients who had residual gradients following surgery. I'm just wondering if the study includes those patients here, just given that these patients do benefit

Speaker 5

or have been shown to benefit.

Speaker 3

Yes. No, in patients that had septal reduction therapy is an exclusion for this particular trial for Sequoia.

Speaker 14

Okay, great. And maybe as

Speaker 18

a segue, I mean, just on the forest presentation, is there a sort of natural timing for the NHTM cohort and when we might be able to see any added long term treatment there.

Speaker 3

And with regards to Forest, yes, I mean, I think what we want to see is the NHCM cohort to age a little bit, So that we have about at least 6 months to a year's worth of follow-up before we report those data. So You'll probably see them in 2024.

Speaker 18

Okay. We'll look forward to that at ICC or AJAX.

Speaker 2

Thank

Operator

you. Thank you. And I am showing no further questions from our phone lines. I'd now like to turn the conference back over to Robert Blum, President and CEO for any closing remarks.

Speaker 2

Thank you, operator, and thanks very much To everybody for joining us on this call today, we covered a lot of ground. So I won't try to synthesize or summarize that other than to say, We do look forward to the results from Sequoia HCM and top lining them later in this quarter in late December. We thank you for your continued support, your interest in Cytokinetics. And operator, with that, we can now conclude the call.

Operator

Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a great day.

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Earnings Conference Call
Cytokinetics Q3 2023
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