Cytokinetics Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 3, 2023

There are 18 speakers on the call.

Operator

Good afternoon, and welcome, ladies and gentlemen, to Cytokinetics Second 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. We will allow for up to 1 question per participant.

Speaker 1

I will now

Operator

turn the call over to Diane Weiser, Cytokinetics' Senior Vice President of Corporate Communications and Investor Relations. Please go ahead.

Speaker 2

Good afternoon, and thanks for joining us on the call today. Robert Blum, President and Chief Executive Officer, we'll begin with an overview of the quarter and recent developments. Patti Malek, EVP of R and D, will provide updates related to apicamten's focus the Sequoia HCM, Redwood HCM and Forest HCM. Steve Heitner, VP Clinical Research and Therapeutic Area Lead, Cardiovascular is filling in for Stuart Cuthbert today and will provide additional updates for afacamten relating to Maple HCM I speak to the expected start of Acacia HCM. Andrew Kalos, EVP and Chief Commercial Officer, will speak about commercial readiness activities for apicamten and its market opportunity.

Speaker 2

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 our financial outlook and revised spending guidance for 2023. Finally, Robert Blum will provide an update on our early clinical programs in his closing comments and review expected upcoming milestones. 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 Q2 2023 financial results filed on Form 8 ks that was furnished to the SEC today.

Speaker 2

We undertake no obligation to update any forward looking statements after this call. And now, I will turn the call over to Robert.

Speaker 3

Thank you, Diane, and thanks for joining us on the call today. We made substantial progress in the 2nd quarter, not only by advancing and broadening the development program for afikamten, but also by making further strides in our earlier stage specialty cardiovascular pipeline. As Sadi and Steve will elaborate, our comprehensive clinical trials development program for afacamten is firing on all cylinders. During the quarter, we completed enrollment in Sequoia HCM, we began maple HCM and we prepared to start ACATIA HCM, the Phase 3 clinical we have accelerated the timeline for this trial and we now expect to open the trial to patient enrollment next month. It's notable that very soon we will have 3 ongoing Phase 3 clinical trials for afikamten plus the open label extension, which is operations teams as well as the high level enthusiasm and diligence of our clinical site investigators and their staffs.

Speaker 3

Now that enrollment in SEQUOIA HCM is complete, study conduct is progressing and we remain on track to share top line results by the end of this year. This trial has progressed through the dose escalation phase for all patients and we're monitoring key metrics in blinded data such as patients randomized baseline characteristics, standard deviation around endpoints, early terminations and missing data. And I'm pleased to report that across all of these measures, SEQUOIA HCM is proceeding well and meeting or exceeding our trial design assumptions. Moreover, alongside our preparations for the reporting on top line results, our regulatory supply chain and commercial readiness teams we have been actively engaging in numerous activities, including go to market plans that build towards potential approvals and commercialization of afikamten. Andrew will elaborate on some of those plans shortly.

Speaker 3

While apicamten may be top of mind, in parallel, our clinical research activities continue to push forward on other fronts as well. In the Q2, we advanced CK-five eighty six, a second cardiac myosin inhibitor into a Phase 1 study. We continued the Phase 1 study of CK-one hundred and thirty six, our cardiac troponin activator, and we continued non clinical research and IND enabling activities towards our goal of submitting 1 to 2 new INDs over the next 1 to 2 years. Moreover, in response to corporate setbacks earlier in 2023 and as we telegraphed on our last earnings call, we have reduced operating spending by approximately 15% relative to our initial 2023 financial guidance with a heightened focus on our priorities and pipeline, including preparations for the potential approval and commercialization of afecamten. That's all going to enable us to further extend our cash runway.

Speaker 3

Qing will provide more details and updated financial guidance for 2023 later in this call. As you will hear today, we're moving forward with momentum into the second half of the year with a broad early and late stage pipeline, ongoing research and a stronger financial foundation, giving us conviction and confidence in achieving our goals for the rest of the year as well as setting us up well afterwards. With that, I'll now turn the call over to Fady.

Speaker 4

Thanks, Robert. In the Q2, we made great progress across broad development program for apicamten. Most importantly, we completed enrollment and randomization in SEQUOI HCM, the pivotal Phase 3 clinical trial of afikamten with 282 patients randomized, surpassing our enrollment target of 270 patients and making it now the largest randomized clinical trial of an investigational therapy ever conducted in patients with obstructive HCM. The conduct of Sequoia HCM benefits greatly from our growing experience and learnings related to the use of cardiac myosin inhibitors as well as measures employed in the evaluation of their effectiveness, patients and physician preferences. I'm pleased to share that we also met or exceeded our enrollment objectives in terms of geography and patient characteristics.

Speaker 4

Sequoia HCM enrolled a diverse patient population from the U. S, China, Europe and Israel. Patients enrolled exhibit a substantial deficit in exercise capacity, a key element of the enrollment criteria considering that the primary endpoint assesses for a potential increase in exercise capacity. Further at this point, SequoiaCM employs an individualized dose titration strategy we are designed to optimize dose selection and maximize the potential benefit risk profile of apicamten. In fact, at this point, all patients progressed through at least the 8 week visit, which marks the end of the dose escalation phase.

Speaker 4

We are accumulating more and more blinded efficacy and safety data that we monitor closely, including things like the standard deviation around the primary endpoint, the completeness of endpoint capture, the number of early terminations and blinded safety data. Across all these measures, we feel SEQUOIA HCM is proceeding per plan, certainly matching or exceeding our trial design assumptions. Our development operations and medical teams are working hard to collect and clean the data as it accumulates as well as this program, the analyses and tables necessary to report the results expeditiously once we lock the database at the end of the trial. All this work has put us on track to report top line results by the end of the year. Now that all the patients from SEQUOI HCM are randomized, we expect to also present baseline characteristics these patients at the HCM Society Scientific Sessions in early October.

Speaker 4

Also during the quarter, we presented new data in patients with non obstructive HCM from Cohort 4 of Redwood HCM At the Heart Failure 2023 Congress, building on initial data presented earlier this year at ACC. The data showed that following only 10 weeks of treatment, apikamten was associated with an average improvement in the With 58% of the patients experiencing a clinically meaningful reduction in symptom burden of 5 points or more. Treatment with apicamten was also associated with improvements in NYHA functional class, angina frequency, high sensitivity cardiac troponin I and NT proBNP. We're pleased to see that most patients were able to achieve the highest available dose down titration events related to LVEF less than 50% and no events with LVEF less than 40%. We remain confident in the promise of apikamten in non obstructive HCM and look forward to starting a Phase 3 clinical trial we are in non obstructive HCM soon.

Speaker 4

Steve will elaborate on this trial in a moment. Before I hand it over to Steve, I want to also share an update on FOREST HCM, which is the open label extension study for patients in complete participation in Redwood HCM, Sequoia HCM and now Maple HCM as well. We're pleased to see that nearly all patients elect to continue into the open label extension and we now have patients who have surpassed 2 years on apikamten and FOREST HCM. In addition to providing data on the efficacy of long term use of apikamten in the treatment of obstructive HCM, Forest HCM is providing data on both safety and efficacy in a very clinically relevant real world manner with investigators empowered to adjust doses in accordance with their clinical judgment and even discontinue other background medical therapy for HCM to simplify we'll continue to periodically share data from FORWARD's HCM, which we expect to factor importantly enter the next in class profile for apicamten and shed light on its potential ease of use and safety, durability of effects and tolerability. With that, I'll turn the call over to Steve, who is filling in for Stuart, who is unable to join our earnings call today.

Speaker 4

Steve will speak to the expanding development program for apikamten. Thanks, Fady. During the

Speaker 5

quarter, we announced the start of patient enrollment in Maple HCM, Phase 3 clinical trial of afacamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM. We are pleased to report that the first patients have recently been randomized. While we do not foresee that MAPLE HCM is critical path to the potential for first FDA approval, if successful in demonstrating that afacamten is superior to metoprolol with respect to improvement of exercise capacity, heart failure symptoms and New York Heart Association functional class, we would expect to submit the results from this trial as a supplemental NDA for potential label expansion. Maple HCM has the potential to meaningfully expand how physicians foresee using afikamten as would likely be reflected in the treatment guidelines, potentially elevating it to first line therapy And potentially expanding the commercial opportunity. At the same time, in recent months, we have been continuing preparation for the pivotal Phase 3 clinical trial of afacamten in non obstructive HCM based on the favorable data arising from Cohort 4 of Redwood HCM.

Speaker 5

As noted in today's press release, we're calling this trial Acacia HCM in keeping with our theme of Northern California trees with non obstructive HCM. This pivotal clinical trial of afikamten in patients with non obstructive HCM is expected to open for patient enrollment next month, which is ahead of schedule, underscoring the high level of enthusiasm for this next trial. In advance, I'd like to share a few key points about its design. ACACI HCM is a Phase 3 multicenterrandomized double blind placebo controlled clinical trial expected to enroll approximately 420 patients with symptomatic non obstructive HCM, the primary endpoint is the change in KCCQ clinical summary score from baseline to week 36. While the primary analysis will take place at 36 weeks, patients will continue on treatment with afacamtenol placebo for up to 72 weeks in order to evaluate additional secondary and exploratory analyses, including the time to the first cardiovascular event.

Speaker 5

As previously mentioned, we expect to initiate patient dosing in Acacia HCM in September. With that, I'll turn the call over to Andrew.

Speaker 6

Thanks, Steve. Our commercial Readiness team is laser focused on key work streams in support of the potential approval and commercialization of afitamten in both the United States and Europe. During the quarter, we updated and continue to refine our go to market plans, executed against activities outlined within them, including development of the disease state education plan, branding, positioning, patient support programs, Salesforce deployment plans and pricing assessments. We have also conducted additional market research to gain greater clarity on HCM patient HCP experiences as well as how HCP's payers and patients would respond to our potential product profile. Many of these plans will be augmented once we have results in hand from Sequoia HCM, but our research to date is encouraging in terms of payer, patient and physician interest as well as enthusiasm for next in class cardiac myosin inhibitor.

Speaker 6

Our research continues to explore we believe there is and will remain a large unaddressed population of patients with obstructive HCM that may benefit from afikamtiv if approved. We are fortunate to have been able to redeploy members of our commercial team who had previously been focused on omecamtiv mecarbil to now focus on afacamten, a corporate pivot that has enabled the acceleration of our planning and efficient operationalization of our preparations for the potential approval and commercialization of afacamten. Meanwhile, conversations with payers progressed in accordance with compliant but about afikamten specifically in which they remain highly interested. We look forward to continuing to develop, expand and hone our go to market plans for the potential approval and commercialization of afikamten and simultaneously deliver on stepwise and systematic elements of the pre commercial runway. Toward that end, turning to market opportunity in Europe, we are pleased to have made our first new hire in Europe, bringing on our Head of Europe, who has a proven track record in launching new products, delivering growth and exceeding expectations in European and international markets we are looking forward to having both our European Head of Access and Medical Affairs join us by the end of Q3.

Speaker 6

We are pleased to be attracting top talent, thanks to our strong culture and pipeline. And with that, I will turn the call over to Robert Wong.

Speaker 7

Thanks, Andrew. We ended the 2nd quarter with $592,600,000 in cash and investments. Our revenue in Q2 2023 came from Astellas and is the remaining amount due to us from their $12,000,000 commitment associated with our conduct of Courage ALS, our Q2 2023 R and D expenses increased to $83,200,000 from $57,100,000 in the Q2 of 2022, primarily due to increased spending for our cardiac myosin Inhibition programs, which represents approximately 2 thirds of our R and D spend for the quarter. Our Q2 2023 G and A expenses we're $39,700,000 down from $42,700,000 in Q2 2022 due primarily to reduced outsourced we are now working on our financial outlook and corporate development strategies.

Speaker 8

Thanks, Robert. We ended the quarter with approximately $593,000,000 on the balance sheet, which represents nearly 2 years of cash runway based on our revised 2023 spending guidance announced today, On which I will now elaborate. Previously, we had expected our operating expenses for 2023 to be in the range of $420,000,000 to $450,000,000 and net cash utilization to be approximately 350,000,000 to $375,000,000 We have reduced our operating expenses to be in the range of 390 to $410,000,000 in response to our receipt of a CRL from the FDA regarding the NDA for omecamtiv Mecarbil and the discontinuation of COURAGE ALS, our net cash utilization is now expected to be approximately 310,000,000 to $320,000,000 This reduction represents savings of approximately 15%, which demonstrates initiatives to reduce spending and limit headcount growth in light of these setbacks. I will also remind you that as we have outlined in previous and revised guidance, we also expect to receive a $50,000,000 non refundable milestone payments from Royalty Pharma upon the initiation of patients' dosing in Acacia HCM, which is expected to start next month. Through this transaction with Royalty Pharma, we also remain eligible for 2 additional tranches of capital if we choose to take them.

Speaker 8

$75,000,000 upon our potentially sharing positive results from the SEQUOIA HCM and 100,000,000 upon the acceptance of NDA submission for epifemten in the U. S. We view this transaction as equivalent to a line of credit, which we can leverage to add to our balance sheet in 2024 if necessary. Towards that objective, we're in the midst of our annual strategic planning process, which critically evaluates corporate and pipeline scenarios, contingencies and risk mitigations and informed investment decisions as we calibrate with Board and shareholder alignment. And with that, I'll turn the call back over to Robert Bump.

Speaker 8

Thank you, Ching.

Speaker 3

As you've heard, in the Q2, we made substantial progress across the pipeline. To add to what my colleagues mentioned, during the quarter, we also participated in a Type A meeting with the FDA to understand FDA views related to the CRL for omecamtiv mecarbil. And outside the United States, omecamtiv mecarbil is under review in Europe and in China. And during the quarter, we continue to support these reviews and address questions from regulators. We also made progress with our earlier stage pipeline.

Speaker 3

During the Q2, we advanced CK-five eighty six into a Phase 1 single ascending dose and multiple ascending dose study we're pleased with initial progress to date. CK-five eighty six is a cardiac myosin inhibitor that is mechanistically distinct from afacamten and has the potential application for patients with heart failure with preserved ejection fraction or HFpEF for which there are few treatment options. For some people with HFpEF, their disease in many ways mimics non obstructive HCM due to their thickened hearts and increased cardiac contractility and symptom burden, encouraging data from cohort 4 of Redwood HCM in patients with non obstructive HCM are potentially a proxy for the therapeutic application of cardiac myosin inhibition in this patient population as we hope to further investigate with CK-five eighty six in 2024. At the same time, our consistent commitment to muscle biology research persists. In addition to the ongoing early stage programs for CK-one hundred and thirty six and CK-five eighty six, we expect to file 1 to 2 additional INDs for new drug candidates over the next 1 to 2 years, once these INDs are filed, we will have advanced 3 to 4 new drug candidates in a relatively short time span, an impressive figure for any biopharmaceutical company, which will enable us to expand our pipeline according to our Vision 2025 goals.

Speaker 3

There is a great deal of work progressing behind the scenes, And I must thank our diligent and dedicated employees for their commitment to our future. Meanwhile, on the finance and corporate development side, you heard from Ching how we're doing right by shareholders to prioritize company activities and associated spending, while also extending our cash runway. Moreover, we are continuing to advance business development initiatives with focus to Japan and Europe as we continue to seek potential partners for omecamtiv mecarbil and afecamten. Since opening the aperture to partnering for afecamten in Europe in Q2, we have been actively engaged with potential partners and we're pleased with the progress and level of interest that we've received as well, as well as the diligence and deal discussions as relate to both afikamten and omecamten of mecarbil. Our future is only made possible by what came before.

Speaker 3

And this year, we've been celebrating our 25th anniversary with a recent open house held at our headquarters in South San Francisco, we invited our local community of partners, former employees, investors, patients, advocates and community leaders, and we are honored to have been joined by esteemed local city and county elected officials as well as staff representing California State Senators. We were grateful to celebrate this joyous occasion with our longtime supporters and friends recognizing now that while much is the same as it was when we started Cytokinetics in 1998, much has also changed as we've made progress towards our ambitious goals. And still the best is yet to come when we hopefully bring forward our first approved medicines to the benefit of patients. Now, I'll recap our upcoming milestones. For afikamten, we expect to share top line results from SEQUOIA HCM by the end of the year.

Speaker 3

And we expect to continue enrolling patients in Maple HCM and start Acacia HCM in September 2023. And we continue to advance our ongoing go to market strategy during 2023. For omecamtiv mecarbil, we expect to continue to pursue potential international approvals for omecamtiv mecarbil in Europe and in China. And for CK-one hundred and thirty six, we expect single ascending dose data from the Phase 1 study in the second half of this year. And finally for CK-five eighty six, we expect to continue to enroll the Phase 1 study throughout this year.

Speaker 3

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

Operator

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

Speaker 3

Good afternoon.

Speaker 1

Hi, good afternoon. It's Fatima on behalf of Ash Warma from UBS. Thanks for taking our questions. I just have a quick one on CK-five eighty six. Just looking at the mechanism, it's very similar.

Speaker 1

It's distinct from afacamten like you noted. What gives you confidence that this mechanism of action will work for patients in HFpEF? And why not pursue this also in obstructive HCM? And just a quick second one, like what would be the benchmark for efficacy and what clinical properties are you looking for in this Phase 1 trial?

Speaker 3

Sure. So I'll turn this over to Fady and to Steve. But firstly, before I do, I'll just say that PK-five eighty six is intentionally being advanced as would be distinguishable from afikamten, which is being developed, as you know, in obstructive disease and non obstructive HCM now. And were we to have identified any issues or liabilities with afecamten, then perhaps, CK-five eighty six could be developed in those same indications, but we are not aware of any such issues and hence why we think 586 should stand on its own in a different disease state. So maybe now I'll turn it over to Fady to speak to why we believe this mechanism is translatable to HFpEF and what we may be looking for both as it relates to Phase 1 data and ultimately beyond that in HFpEF.

Speaker 4

Thanks, Robert. As you mentioned, CK-five eighty six, it has a distinct mechanism of action than apikamten, but It's still a cardiac myosin inhibitor. The distinction is really subtle at the point of where it binds and what form of the motor protein it inhibits. Fundamentally, it does the same thing. It reduces the number of active Cross bridges and reduces cardiac contractility.

Speaker 4

It has a shallow exposure response relationship, as does affecamten. And so fundamentally behaves very similarly. As Robert said, apicamten is doing wonderfully. We don't really think we need another drug in HCM, but HFpEF is a much different population And a very large population at that. What we're intending with 586 is to focus in this different indication and to a subset of patients with HFpEF whose phenotypes mimic some of our NHCM patients.

Speaker 4

They have Larger hearts, thickened hearts, high filling pressures, higher biomarkers, symptoms and And for exercise tolerance. And so in many ways, there are phenocopy, for those that have genetic, non obstructive HCM. And So we'll be advancing 586 in that direction. It's really premature for me to discuss

Speaker 3

Thanks. I hope that's helpful. Operator, maybe now we'll move to the next question, please.

Speaker 1

Great. Thank you so much.

Operator

And our next question will come from Rohit Bassin from Needham and Company. Your line is now open.

Speaker 6

Hi, this is

Speaker 9

Robin on for Serge. Thanks for taking our questions. Can you just talk about your expectations For the rate of enrollment for both the MAPLE and ACATIA trials, and then when do you plan on presenting new data disclosures in medical meetings? Thanks.

Speaker 3

Sure. So as it relates to both Maple and soon to start Acacia, I think it's too early for us to be guiding as to rate of enrollment. I do understand the question and we should get you that answer. Let's see how we get out of this startup phase and these initial enrollments before we might start guiding to enrollment rates in conclusion, I don't expect that there'll be any data from either of these studies In 2023, of course, and as we look to next year, I think it's also premature, we'll be in a better position to point to what to expect next year when we do our Q4 earnings in February.

Speaker 4

Thank you. Thank you.

Operator

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

Speaker 10

Hi, thanks for taking the question. Hi, Robert. Thanks for taking the question and congrats on the progress. You said in the prepared comments that all patients are in SEQUOIR are now through the titration phase. Just wondering if you could comment on whether you're seeing what you expected to see in terms of the proportion get to target doses?

Speaker 3

So, thank you for asking and that's a notable achievement as you highlight that we now are through that dose escalation phase. Keeping in mind, we're blinded to dose, but maybe I'll ask Steve if he wants to elaborate.

Speaker 5

Well, Jason, I think Robert just answered your question. This is obviously a blinded study and we are I'm in fact blinded to the actual dose that's administered. So we don't know the proportion of doses that patients are being exposed to in Sequoia, but you have already seen some of the data that has been presented with regard to the FOREST HCM study, which is unblinded, where there's a nice bell shaped distribution in the doses, patients being exposed 15 10 milligrams for the most part with a smaller proportion getting exposed to 5 20 milligrams.

Speaker 11

Okay, great. Thank you.

Speaker 3

Thank you, Jason. Thank

Operator

you. And our next question comes from Jason Zimansky from BofA. Your line is open.

Speaker 4

Good afternoon.

Speaker 1

Good

Speaker 12

afternoon. Congratulations on the progress and thanks for taking our question. I wanted to circle back to some of your comments Regarding Maple and the possibility of broadening the label of afacamten to include use in the first line setting, I'm curious, what do you see as the opportunity here? I mean, Tuniti here. I mean, obviously, the addressable market is sizable, but it seems like there could be potentially logistical or administrative hurdles, Thinking about pushback from payers or potential capacity issues from community prescribers, I mean, do you see afacamten as a valid option for all comers with obstructive HCM?

Speaker 3

Yes, I think we're following the lead of investigators themselves in forest who are choosing to take patients off of beta blockers and for reasons that matter importantly to physicians and patients. And ultimately, I think we'll be welcomed if Maple is successful by payers. Maybe I'll ask our clinical colleagues if they want to Add anything to that and maybe also Andrew if he wants to.

Speaker 4

Hi Jason, this is Fady. I might just add that in the context of a drug that addresses the underlying cause of the disease, there's obviously opportunity For disease modification. And so, Maple is not addressed not designed to

Speaker 3

address that

Speaker 4

point. But in terms of thinking about drugs selected for patients, at least we provide the evidence of which of the current number one choice initiated versus the newcomer, the CMIs, where might the best efficacy be found? And then over time, we would hope to broaden the case for using CMIs early based on the fact that they may Slow the progression of the disease or stabilize the progression of the disease. So I think this is the beginning of a strategy to establish CMI is first line therapy. Great.

Speaker 4

Appreciate

Speaker 6

it. Andrew, anything you want to add? Yes. Well, only maybe 1 or 2 things, Jason. First is that having evidence certainly helps inform guidelines.

Speaker 6

Guidelines will then Certainly help. Kind of the second point from a payer point of view, maybe get rid of the step edit that we have we'll likely have, I should say, as a category through beta blockers and or calcium channel blockers, which from our research seems to be important to physicians As well as patients, if there's evidence that a, afacamten alone can treat the disease effectively, Then we think that will certainly be a good strategy commercially as well.

Speaker 12

Great. Appreciate the color.

Speaker 3

Thank you.

Operator

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

Speaker 3

Hello, Joe.

Speaker 13

Hey, everybody. Thanks for all the details and looking forward to the start of Acacia. So Robert, I'm going to give you a bit of a run on sentence here of my question if you give me a little patience here. So with regard to the initiatives in Cost savings and what have you, would you consider the company rightsized at this point or can we expect any potential additional cost savings? And then with regard to afacamten, since this is a broad geographical study, are there any particular geographies that might have enhanced focused by you with regard To clinical trial conduct or treatment regimens that might be different from other regions.

Speaker 13

And lastly, with regard to Acacia, are there any external impacts that also assisted with regard to accelerating the start of the study? Thanks a lot.

Speaker 3

You're right. That was a long sentence and I'm trying to remember the component part. So let me start with what I remember to be the first part. I do believe and Qing can comment on this too if he likes, that we went through a very significant cost cutting exercise critically assessing what we need to be doing in 2023 to align better with a new reality, a reality that has us focused on afecamten and where omecamten mecarbil because of the CRL is not part of our near term future and recognizing that Reldesemtiv was not progressing in Phase 3. We needed to see where we could redeploy people to have them focused on that which was now our new priority and that's Afikamten 1st, 2nd and third.

Speaker 3

And in order to do that, we looked at outsource spending, we look at contractors and consultants and we looked at our internal headcount. We also looked at plans to grow headcount and we set some aggressive targets and we met those targets. And I think the team here at Cytokinetics did a great job pulling all in the same direction to ensure we could very meaningfully reduce operating spending, not just over the long term, but in the nearer term, So as to extend cash runway this year and that's what we achieved when we gathered for the Q1 earnings call. We knew we had ambitious targets and we had not yet concluded that exercise. We did conclude that exercise in Q2 And I think people tighten their belt quite substantially.

Speaker 3

Hence, I think we are right sized for what are our current priorities and knowing where we are today, recognizing that, affecamten is going to be paving the path for this company And we have to be in a best position to capitalize on that as soon as we know more from SEQUOIA and that'll be end of this year. So let me see firstly if Ching has anything to add to that.

Speaker 8

I think Robert covers it well. The only thing I would add is as part of our strategic planning process, we are also contemplating different scenarios if SEQUOIA readout does not meet our expectations and we have scenario planning to address those, but obviously we'll have to wait for data Before executing anything.

Speaker 3

I think the next part of your sentence related to geographic Variability potentially and where we noting anything or preparing for anything, maybe I'll turn to Fady or Steve to speak to that. Sure.

Speaker 5

So I'll take that one. This is Steve speaking. So your question alluded to whether there is specific geographies that we're Targeting, I think that the strategy that Cytokinetics has employed has been to cast a wide net and capture all geographies, you're right that there are treatment or strategic differences in how patients are treated in different parts of the world. However, the way that SEQUOIA was Captures all patients who have symptomatic obstructive HCM independent Of what medical treatment they have available to them, whether it includes disoperamide or not. I guess would be Japan where they have sibenzylene therapy and we're not running the study in Japan as you know.

Speaker 5

But independent of the availability of septal reduction therapy, whether it be septal myectomy or alcohol septal ablation, you've seen that we do have an endpoint that does measure the impact of avacamten on the eligibility of these patients for that. I think if you take a step back and look at the strategy that we've employed for HCM at large is that we have a development program that not only is targeting all patients with obstructive HCM independent of geography, But all patients with HCM independent of phenotype, including non obstructive patients, patients with mid ventricular obstruction that you've seen with our Redwood ACM Cohort 4, as well as hopefully in the future other subgroups.

Speaker 3

And then you had a third part to your sentence and I can't remember it.

Speaker 2

Any external impacts to

Speaker 4

Kaysha or May. Yes. I'll take that. I think for Maybel, there's a lot of enthusiasm giving the question that we are asking in that study and that patient population is a little different Then the other OHCM populations that have been studied to date, and obviously there are no large OHCM study is ongoing. With regards to NHCM, we think it's the first time A novel therapy has been studied in NHCM.

Speaker 4

I think investigator enthusiasm will be high, across the board.

Speaker 13

Thank you for the answers, everyone.

Speaker 3

Thank you, Joe.

Operator

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

Speaker 14

Hello, Dane. Hi, guys. This is Sean on for Dane. Thanks for taking the question. Can you talk about the strategic logic behind the sole primary endpoint of KCCQ for Acacia, given the parallel MAVA study has a KCCQ and peak VO2 as co primaries, what physician and FDA feedback drove that decision?

Speaker 14

And is the 36 week endpoint versus a 48 week time point in ODiSI Entirely driven by the expected duration of the titration period and if not, can you go into that decision making?

Speaker 3

Sure. I'll ask Steve to speak to those questions, please.

Speaker 5

Sure. So this is Steve. The primary endpoint for SEQUOIA, as we mentioned earlier on, is the sole endpoint of a change in KCCQ and we picked that based Our experience from our Phase 2 study, the Redwood Cohort 4 that was presented and you've seen the data. We also are aware that the majority of patients who have non obstructive HCM are receiving therapy with either beta blocker or calcium channel blocker, actually mostly a beta blocker. And as you know, that If we were to incorporate these 2 endpoints as a composite as your primary endpoint or dual primary endpoints for that matter, we would hamper the likelihood of success.

Speaker 5

Obviously, exercise capacity is important And we have incorporated this as Fady mentioned as a key secondary endpoint exercise capacity as measured by Cardiopulmonary exercise testing, but in essence, we felt that separating those 2 would increase the likelihood of technical success For Acacia HCM, there was a second part of the question.

Speaker 4

I'll take it. Just you asked with regards to 36 versus 48 weeks of therapy. And I think we've chosen 36 weeks and that gives us I think plenty of time to get to the maximum effects. We have a relatively short titration period in our study is mirrored by what we've executed in SEQUOIA and we've chosen that. And you'll see as we mentioned later, patients will be followed up after that primary endpoint for longer And we'll have the opportunity to see if there's any other accumulating efficacy over time.

Speaker 4

Thanks for your question.

Speaker 11

Thank you.

Operator

Thank you. And our next question will come from Tess Romero from JPMorgan. Your line is open.

Speaker 15

Great. Hi, Robert and team. Thanks so much for taking our questions. I wanted to ask a question on HCM epidemiology today, if I could. You've historically talked about a patient population 190,000 in the U.

Speaker 15

S. With diagnosed obstructive HCM with, of course, an undiagnosed patient population on top of that, as I recall, Bristol had talked about 75,000 identified diagnosed obstructive patients that we saw them quote around the time of their launch, can you help us close what the gap might be there? We just really like to get a better understanding of where your latest thinking is on the epidemiology in obstructive HCM as you think about diagnosed patients here at the time of a potential Affy launch and where you might see that evolving with time? Thanks so much.

Speaker 3

Sure thing. I'm going to turn to Andrew, who is very focused to these matters and also How the literature is evolving here?

Speaker 6

Sure. So thanks for the question, Tess. It's Andrew. So there are multiple publications, some older, that speak to lower numbers of epidemiology, we did a 5 year Longitudinal study on claims data on actual patients that are actually diagnosed. And then we you know, corroborated that with publications that are more recent around the 190, I can't speak to where BMS gets their number.

Speaker 6

I can only speak to that we're very confident in that 190,000 number and that number is growing a little higher than the rate of population on the OHCM. And again, that's based on actual data in claims. So we're going from that number The 190 of that 190 from our research furthermore is I think it's important to understand that probably around 60% of those patients are not currently optimized with treatment and still having symptoms and that's really the target of therapy.

Speaker 15

Great. Thanks so much for taking our question.

Speaker 3

Thank you.

Operator

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

Speaker 16

Good afternoon, Yasmeen. Good afternoon. Hi, Robert. First of all, congratulations on the big anniversary What a wonderful achievement for the entire company. Two questions that are directed to Steve and Fady and maybe also Andrew could comment on it.

Speaker 16

A question that we're getting from quite a lot of clients right now is, what do we want to see from a safety perspective in the upcoming Sequoia that could warrant a differentiated echo monitoring and what would be a favorable ramp. I think a lot of clients understand the absence of DDIs, we may want to understand sort of how the SEQUOIA data could maybe just get us really comfortable of a differentiated label. And I really appreciate your thoughtful comments around these questions. And I'll jump back in

Speaker 14

the queue.

Speaker 3

Sure. I'll turn first to Fady, but I'll underscore, of course, that what we're going to share are comments based on what we've seen already in Redwood and Forest and what we hope to and expect to see in Sequoia, But that's still to be known and afacamten remains an investigational compound. So with that, I'll turn to Fady to answer your question.

Speaker 4

Yes. Yasmeen, I think in terms of echo monitoring, we hope to see that the data from FOREST will we support a frequency of echo monitoring that is manageable by patients and their physicians. I'm not going to really make any comparative statements as you ask for differentiation. But you can imagine that as we are in force now monitoring patients for every 3 months, we would hopefully those data would support the lack of treatment decisions or safety events that are driven by all of those echoes. I think everyone recognizes the Cardiograms are a burden to the sites and to the medical system.

Speaker 4

And I think there's a which should be a general incentive to minimize the burden on patients in the medical system. And so we're very happy with how Forrest has been proceeding. As I said earlier, we now patients out to 2 years and we hope that that safety database will lend itself to Making a compelling argument for echo monitoring that say might be twice a year or even yearly at some point. And in terms of REMS, I think the question really is what physician education is going to be necessary in order to use apicamten and I can't really comment so specifically to your question other than it will be informed by the safety information and the other profiles of apicamten, which to date we don't think we have any meaningful drug drug interactions and other aspects of the drug that would not require extensive physician education. So stay tuned.

Speaker 4

The data evolves. I think we will hopefully have more to say.

Speaker 3

What's been especially reassuring in the clinical trials data that we've seen to date Is that we haven't observed any early terminations as a result of ejection fractions unexpectedly falling in patients with obstructive HCM and we'll be looking to see if that may continue with the unblinding of the Sequoia results, but that's the kind of thing that may ultimately factor into what would be considered a risk that would be mitigated by a potential REMS program and that's something that we're continuing to be quite hopeful for.

Speaker 16

Thank you so much for the thoughtful remarks. I'll jump back in the queue.

Speaker 3

Thank you.

Operator

Thank you. And our next question comes from Salim Syed from Mizuho. Your line is open.

Speaker 12

Great. Good afternoon, guys. Thanks for the question. So Robert, the number one question we get, I want to see I'm sure you get it too is, why is the stock back down at $30 I think a lot of people are trying to sort out why exactly it's there and nobody really thought it'd be there at any point in 2023 really. And then the reasons that we hear from folks Or it seems to be pointed to is the Kamsios NRx line and then potential deal risk around Affy.

Speaker 12

I know there's a one question real, so I'm going to really focus on the deal risk piece here. So given we are 4 months or so away from the Sequoia readout, just curious in your discussions with potential partners, how that particular aspect of the story is being perceived. Do people do you think folks will want to see that data? Or Can you make a decision to go to loan or partner prior to that data? Just give us if you can Set aside some context for us how timing of a potential deal if any or a go it alone or partner decision?

Speaker 12

Thank you.

Speaker 3

So any deal that we might do would have to be a deal that met our expectations to be able to go to Europe on our own, but would be supplemented by a potential partner's involvement and the hurdle is very, very high. We're not looking to do a deal for the deal's sake. And were we to do any deal, it would be as would be enabling of our continued corporate development with emphasis on our own to go to Europe, you heard Andrew say that we've already hired our Head of Europe, we're hiring some other folks there. It's our intention to build out our commercial business in Europe. So with our last earnings call, I did indicate we were opening the aperture to partnering Aviacamten potentially in Europe, but with focus to Japan and as would only be done if we could make a case that that's better than going it alone.

Speaker 3

And while I won't comment on what we've concluded, I will say that we continue to execute on our go to Europe strategy and we're looking very critically at what might be any alternatives to that plan. We think it's in the interest of shareholders That we objectively approach that decision. We've done that. We're doing that. And we continue to execute well on our own plans.

Speaker 3

I hope that answers the question.

Speaker 12

Yes, I think that was helpful. Thanks, Robert.

Speaker 3

Sure thing.

Operator

Thank you. And our next question comes from Carter Gould from Barclays. Your line is open.

Speaker 3

Hello, Carter.

Speaker 11

Hey, guys. You've got Evan on the line for Carter. Thanks for squeezing us in here. We just have a question on expectations For what you will disclose in the Sequoia top line press release, to what extent does the MyoKardia level of disclosure serve as a good bench Mark for what to expect. And then as a follow-up to that, considering Sequoia Rea on the horizon, what should we anticipate from you and or what will your presence be at the

Speaker 3

So we're going to be out in full force at HFSA and this year, as well as the HCM Society meeting in October, which falls in between. What I'll also say is, in as much as we've guided to results for sequoia by the end of the year, it's reasonable to expect that the full on presentation of those results would occur not at one of those meetings, but perhaps at ACC, which is in April 2024. An ACC has its own guidelines and restrictions as to what would be permitting of a presentation In their scientific sessions, which are different from other meetings, and if I recall correctly, when MyoKardia presented its Data, it was leading into the ESC meeting that year, ESC with different restrictions than does ACC. So I don't know that you can compare what will be our disclosure in a top line release to theirs. But what I will say is we will disclose that which we determined to be material and informative to shareholders without jeopardizing a presentation at ACC.

Speaker 3

And until we see the data, it's hard to know exactly where that falls. Thank you. Thank you.

Operator

Thank you. Our next question comes from Justin Kim from Oppenheimer and Co. Your line is open.

Speaker 3

Hello, Justin.

Speaker 14

Hi, Robert, and good evening, everyone. Now maybe just as a follow-up there, I just want to ask a question with respect to the presence at and maybe just what we might expect from ForRIS. Presumably you'd have some experience from sort of Sequoia completers. I'm just wondering like Is that something we can expect to see how some of those participants of the pivotal did once they were off the drug and we titrated or titrated up from placebo and sort of see that at later this year.

Speaker 3

Yes. So we're not guiding to any new data from forest@a but rather you heard us refer to baseline demographics from Sequoia at the HCM Society. As it relates to forest, it's not it's been our practice that we would provide updates at every medical meeting, but certainly we want to provide meaningful updates when there's significant new data to share and that's more likely as we'll be coming at ACC next year.

Speaker 14

Okay. Thank you.

Speaker 3

Thank you.

Operator

Thank you. And our last question will come from Sreekripa Devarakhanda from Truist Securities. Your line is open.

Speaker 3

Good afternoon.

Speaker 17

Good afternoon, Robert, and good afternoon to the team. Thank you so much for taking my question. Just to follow-up on what Robert you mentioned earlier in terms of the LVES drop, I think previously you had mentioned that there could be an unblinding event if the LVF drop was fairly low. I was wondering if you can What is the bar for fairly low? And if you if we haven't heard about it so far, can you assume that it didn't happen?

Speaker 17

Thank you.

Speaker 3

Good question. I'll turn it to Fady and maybe Steve if he wants to add.

Speaker 4

All right, Cripa. I think the protocol is pretty clear that if we see a patient has an Objection fraction fall below 40%, that the investigator and cytokinetics should be informed. To date, we haven't seen we haven't been informed of any such events and which is quite reassuring. We're not privy to any other drops in EF. The rest are blinded and will remain so until the study is complete.

Speaker 17

Thank you so

Operator

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

Speaker 3

Thank you, operator, and thanks to everybody who joined us on this call today. Obviously, quite a lot is going on at our company as we're reprioritizing, focusing to afikamten, reducing spending And advancing our pipeline, and we think we're doing that very well aligned with what shareholders should expect of us as we come forward to these important milestones, we look forward to keeping you abreast of our progress. We welcome there are further questions and look forward to updating you throughout the remainder of this year. With that operator, we can bring this call to a close.

Operator

Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect.

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Earnings Conference Call
Cytokinetics Q2 2023
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