Cytokinetics, Incorporated (CYTK) Earnings Call Transcript & Summary

Good afternoon, and welcome to Day 2 of the Barclays Global Healthcare Conference. My name is Carter Gould, senior biopharma analyst here at Barclays. I am pleased to welcome Cytokinetics to the stage. Already had a very exciting start to the year, is just coming off ACC 10 days ago. Joining from the company CEO and President, Robert Blum. Robert, welcome.

Thanks very much.

Do you want to make some opening comments and then we can get started or just jump into Q&A?

Very briefly. This year is a very important year for the company. We are in the midst of a pivot and redeployment and refocusing as is oriented towards aficamten, which is our next-in-class cardiac myosin inhibitor, the subject of a pivotal clinical trial due to readout in the fourth quarter and as well as a broadening of the development program around that same drug candidate. And I'm sure more to say about that through the Q&A. It's very important for us because this represents an opportunity for us to bring forward our pioneering and leadership in this area of science to a new area that still has a very high unmet need. We have 4 other programs in clinical study. Time permitting, I guess, we'll speak to those as well.

Okay. Perfect. So I think last year, we kind of did this in a reverse order in sort of the [indiscernible]. This year, we're going to start with afi. But before we kind of go into the nuance and all the back and forth on the base, I wanted to just start with kind of a high level concept -- or high level conversations coming out of ACC and that is when we think about the potential for this class to transform how we treat this disease. And if you see parallels between that and other kind of indications within cardiology and maybe kind of help frame that for folks.

Talking about obstructive first?

Yes.

So this time last year that were compelling clinical evidence, but we really weren't yet in a place where we could say a new medicine was available for patients with high symptom burden and obstructive HCM. And BMS launched Camzyos, a very good drug. We should know we played a role in its discovery. And that drug is changing the landscape for those patients. They are roughly 20,000 patients who have diagnosed obstructive HCM and substantially more than that were undiagnosed. And roughly 1% of patients right now may be getting that drug mavacamten or Camzyos, and they're benefiting from it. I think that aficamten has an opportunity as a next-in-class to dramatically expand the category in terms of who might be prescribing a myosin inhibitor and which patients may stand to benefit. And the data that we've been sharing up to now Phase II data later this year, Phase III data should hopefully make a compelling case for how aficamten can alter the landscape of those patients even more.

Okay. There's been a clear focus on the points of differentiation between the 2 programs between you and Bristol. Can you talk about sort of what's built into your Phase III SEQUOIA to kind of tease out some of those benefits, but also just to broadly get the program approved?

Yes. So apicamten was designed to be next in class. What does that mean? That means that it has physiochemical properties that should render it hopefully easy to use. We're confident to up-titrate to get to symptom relief sooner, more rapid offset and to be enabling of what would be a broad therapeutic window. Our goal is to enroll, in SEQUOIA, patients who may stand to benefit more, so more Class III patients, patients who may be in a position to go from New York Heart Association Class III to Class I, like we're seeing already in Redwood. We have an opportunity in SEQUOIA to optimize, if you will, how the enrollment might enable us to see amplified efficacy. So for instance, how many patients are on treadmill, how many patients are not on beta blockers. These are the kinds of things that as we're completing the enrollment of SEQUOIA, which is due to complete in Q2, we're focused on in order to hopefully enrich for what could be even more magnified activity in response.

Okay. And so it's kind of a lead into the next question in terms of enrollment and just ensuring -- well, first off, how is that going? And secondly, kind of you're maintaining that balance between regions, treadmill versus bike and some of the other kind of aspects. Can you just kind of talk.

Yes. So enrollment is going well. We're at that point in enrollment where you expect to see centers competing ultimately to enroll their patients so they get into a study before the study concludes. And we are seeing the kind of balanced enrollment that we intended that's balanced between North America and Europe, but also in China, where SEQUOIA will have patients that could be enabling of a potential approval in China also. So all that's going to our satisfaction. We're tracking it every day. And I do believe we're on track to complete enrollment in Q2, so as to have results in Q4.

Okay. And. Maybe just one other question. How should we expect sort of balance by sex relative to your Phase II and relative to EXPLORER?

So about by gender, this is probably more akin to what we're seeing in Phase II than what you should expect in Phase III. We don't yet have all the baseline demographics, obviously, because the study is still enrolling. But this is a disease population where there's not that variety. I think you can look at EXPLORER as to gender and our Phase II as to gender. And I don't think that you would expect much difference as it relates to SEQUOIA as to gender.

Okay. And when you are completing enrollment, are you guys press release that or we're just going to find out about that on an earnings call?

More likely on an earnings call.

Okay. Great. And then you've also disclosed the next study, MAPLE has named you disclosed that. You didn't give us any details behind it though.

We gave you a few.

A little bit.

A little bit. Yes.

When are we going to get the rest of the details? What do you think [indiscernible]

So as is customary, I mean we're still having those final discussions with regulatory authorities to be enabling of a lockdown [indiscernible] protocol. And that's not just FDA, that's regulatory agencies also. So that's going to be continuing in the first half of the year. More likely, you'll find out when we post it on clintrials.gov, and we announced open to enrollment. I wouldn't expect there to be much more closure of the study and its [indiscernible] until that's posted.

One of the data sets that did emerge at ACC was a competitor data set with some of the imaging data, longer-term imaging data, which speaks to the ability of the class to remodel. Can you talk about how SEQUOIA and potentially MAPLE are constructed to build upon that? And how important do you think that aspect of the class of profile will be important as you think about driving adoption and [indiscernible]

So you'll see imaging sub studies. It's not going to be in all patients, but there'll be sub studies that would be enabling of us to be able to track that also. I do think this is important ultimately for category expansion if you want to penetrate those undiagnosed patients, patients who may be genetic carriers, maybe not yet symptomatic. I think it's going to be interesting to see how some of these remodeling data might ultimately open up the use. I wouldn't be looking to that as tell tail, meaning definitive, until which time is there are clinical studies that are randomized that look at something like that, but I think it will be encouraging of what could be the design of those studies.

Okay. But those subsidies will be larger than what we saw in the substudies in EXPLORER?

Yes.

Okay. Maybe let's turn to what was actually one of the newer data sets from you at ACC, which was the nonobstructive data. Can you help put that in context of what we've seen before from mava and the read through from that to not just starting a Phase III, but also the classes potential in heparin?

So I'm reluctant to make specific comparisons between our Cohort 4 and the MAVERICK study for mavacamten. Firstly, MAVERICK was placebo-controlled. Cohort 4 was not. Cohort 4 looked at patients who were in open-label fashion with nHCM receiving aficamten, where the goal of Cohort 4 was to get patients to the top dose. It's a dose finding aging study. We've got 85% of the patients up to 50 mg. That was a win. And along the way, we saw very compelling effects on BNP reductions and NYHA-class improvements. Keep in mind that these patients, while they don't have a gradient like their OHCM counterparts, they still have symptom burden. And if you can take, as we did so many patients from Class III to Class II and remarkably, some patients from Class III to Class I, which was effectively asymptomatic. That's very compelling. That's very significant. It augurs well for what we should be doing now in testing hypothesis in Phase III. So we look at those data, and we knew about these data, I think we're looking at these data at the end of last year and into Q1. At least some of these data, the complete data set had to be rushed in order to have some data presented at ACC. There's still some data that we're collecting that will be presented, hopefully, in the next few months. There's an opportunity potentially to present it in Q2. But for what we've seen, we're very pleased and for what we expect will be presented in Q2. It's consistent with the same. What we haven't yet presented is the KCCQ data. We haven't yet presented some of the echocardiographic parameters. Those data require more time to curate and to synthesize. That's happening now. And you'll see those data soon enough. And I think you'll similarly see that those data are similarly supportive of what we've already presented.

Okay. And then just in terms of those data and the implications of the class in HFpEF and specifically with the moving 586 into the clinic, I guess, how fast can you move then now that you've got some potential class elevation?

I think we can move fast with 586, Obviously, it has to go through the standard Phase I assessments. But as you're alluding by your question, patients with nHCM offer a bit of a window, a gateway into a subset of patients with heart failure and preserved ejection fraction. Not your obese metabolic syndrome HFpEF patients, but those who may have thickened cardiovascular anatomies and myocardial presentation. That's a significant subset of HFpEF. It could be on the order of 25% to 35% of these patients would resemble those nHCM patients, then we want to study 586. Why 586? It's another myosin inhibitor. It's not aficamten. It has a different structural chemo type, different physiochemical properties, but more importantly, a different mechanism of action. It's indicative again of our continued leadership in this space, and we believe that it is the right molecule to advance in HFpEF as would be distinguished from aficamten in HCM.

Okay. Anything on the dosing in terms of differentiation that you can point to at this point?

Not yet, at this point.

All right. And then I think probably the most common question we get is sort of your expectations or my expectations for the label and really specifically the REMS for apicamten in nonobstructive.

In nonobstructive?

In nonobstructive.

That's way too early to answer.

Sorry, sorry. Excuse me, obstructive. So in obstructive, right, so the range of scenarios and what ultimately do you think FDA will look to, to help guide that?

So we get this question a lot, I mean all our one-on-one meetings. Our base case is that there would be some form of REMS. And just for everybody's edification, there are different kinds of REMS. There is an informational REMS and there's ETASU REMS. And as I'm learning in a [indiscernible] REMS, there's up to 6 different categories of requirements. My understanding is that as it relates to mavacamten, Camzyos, they [indiscernible] all 6. As it relates to aficamten, our hope is that we'll have a much lesser REMS program. But ultimately, that depends on the data. Data from SEQUOIA and also data of the open-label extension. What's encouraging is in the open-label extension of aficamten, a study called FOREST-HCM. These data were presented also at ACC, we saw 0 dose terminations. So it's suggestive that in a real-world experience of an open-label extension, patients can be maintained on their target dose of aficamten without the need for discontinuations. That would hopefully be enabling of us to have a conversation with FDA about what might be a lesser restriction upon its used commercially. But absent the data, this is all just in the abstract. We are preparing for what we hope can be our best foot forward on that. And it could be, at the end of the day, an attestation by physicians regarding safety and no other monitoring or management or it could be that there are monitoring and management requirements, but maybe not as frequently. So you might imagine, instead of ECHOs every 90 days in perpetuity, maybe it that goes every 6 months or every 12 months. just to make sure that patients maintain with EFs at a range where that can be deemed safe and not indicative of risk of heart failure. Those are things that ultimately will only be able to be meaningfully understood when we have the data.

Okay. You've talked about launching the product itself in pretty vocal on that. CV launches generally haven't exactly showered themselves and praise of late. CV launches by nonbig pharma companies have been particularly challenged. And the idea of competing against the big pharmas is not for the faint of heart. So I guess what gives you conviction that a smaller player can successfully compete here? And for front run your rebuttal, are the conditions that existed 20 years ago still applicable today in a more nascent category?

So I think you asked me that question last year and I didn't answer.

It was a little different.

But you're right. Firstly, I don't think there's a good proxy for recent cardiovascular launches here. If you look at the recent cardiovascular launches, they are more typically in markets that are dominated by generics, and where -- with asymptomatic disease, large part, you're putting in place commercial activity and infrastructure that is more direct to primary care or general cardiology versus this specialty cardiology and a symptomatic I do think that with the sales force, roughly 100 to 200 of that range, we'd be able to put in place a commercial infrastructure like that of BMS for what [indiscernible] on mavacamten. But understanding our goal is not to compete with BMS but the way that we're competing for patients. But rather our BMS has done so successfully with [indiscernible] and others have done with [indiscernible] a category beyond those currently being treated. Maybe to elaborate on your question a bit, I think the BMS launch is going well and going according to BMS' expectations, it would seem. Despite what I think was a street consensus of numbers in Q3 that were not met until Q4, where I think the Q4 numbers are more similar to what was expected in Q3. We look at the number of patients going through the hub, the percent of patients on commercial pay versus free goods. We look at the number of repeat prescribers, new scripts, total scripts, the fact that they're taking a price increase, not discounting, all these things to underscore that this launch is going according to plan. And I don't share the view that this launch is struggling. In fact, I think quite the opposite. It's going as one should expect.

Okay. We got 5 minutes left. I think we should move on to reldesemtiv here. So you've -- there was some nuance changes encourage ALS relative to the prior effort you had in ALS. Maybe let's tease out some of that. First off, focusing on these medium to fast progressors, maybe can you talk about the importance of that and to the extent which you've been able to execute in terms of enrollment of it?

Yes. There also enrollment is going very well. We expect to conclude enrollment in the second quarter, unless, as is permitted by the second interim analysis, the data monitoring committee may suggest stopping the study for futility or upsizing the study if there is an effect that could be amplified with an upsizing of the study. And there's a fixed algorithm that's permitted in that case. I believe that what we are doing in COURAGE-ALS is good science, building on what we learned in FORTITUDE-ALS, which was the Phase II study. In that Phase II study, which was a study looking at 3 different doses versus standard of care in patients who received 12 weeks of reldesemtiv, we noted an encouraging effect on both slow vital capacity and ALSFRS change from baseline and where that effect was more pronounced in patients versus placebo when you look at the subset of patients who were medium or fast progressors and with ALSFRS showing a deficit. It's a 48-point scale and we looked at those 44-point below. So not unlike the way Mitsubishi Tanabe [indiscernible] in a subset of patients who were rapid progressors, and they got an approval for all [indiscernible]. We encourage ALS chose to enrich for people who were showing deficit and declining at a higher rate, and we're meeting that objective in our enrollment. And it's suggestive of data that we think would be clinically meaningful and would be supportive of an approval. What you don't want to do as was the case in our Phase II study is dilute the treatment effect versus standard of care by including patients who are stable, not declining in a short duration study. So everybody with ALS ultimately succumbs to the disease, but at different rates. So we're focusing to those patients who are within the window of study more likely to show a deficit where there could be a potential treatment effect.

Okay. As we think about the scenarios coming out of this interim analysis, a couple -- first off clarify, there's no futility component here?

There is.

There is. Okay.

There is a futility component. The study could conceivably stop for futility.

Okay. So I think there's a perception that if there's no change to the enrollment that's a positive sign you're [indiscernible]. And if you look to upsize maybe that affects smaller albeit than how you've got greater power and potentially could have...

That could also be positive.

Right. I guess, is there a scenario in which -- well...

A scenario by which we don't stop the study, and it is still neutral because there's still patients and more data to be collected. So you could imagine the study continues, and it still isn't positive.

Okay. And then in terms of that upsizing, as I recall, it's sort of -- one question is it all probably not the right part, but it's this one on upside.

The data monitoring committee will look at the unblinded data, and they're operating -- they can operate within guidelines that they determine more broadly, but we've included in this adaptive study design, the recommend nature that if there's an effect that would be deemed clinically meaningful, but maybe not consistent with the powering calculations as designed into the statistics of the trial, then they can recommend the upsizing of the study in what is a fixed algorithm of patients, and that would be enabling of the study to continue, but in large.

Okay. And when do you get to this point, you'll top line this?

We'll communicate that by press release.

Perfect. Well, it's going to be an exciting second half of the year. Looking forward to SEQUOIA reading out. Robert and team, thank you very much for coming in.

Thank you.

Best of luck.