Managing Director and Senior Research Analyst, Piper Sandler
All right.Good afternoon, everyone.Thank you so much for joining our healthcare conference here at Piper Sandler.Excited to have the team from Cytokinetics here.What a treat!I mean, we're going to talk about SEQUOIA in a second.This might be, I guess, your last fireside chat before you go into quiet period starting December.So yay, me, getting to ask the last set of questions in a public format.Team, before we go and discuss quite a bit in the next 25 minutes, I think that a lot of investors have been asking us, as you get into top-line data, have you had a chance to connect with the AHA organizers and talk about what type of data you would have the opportunity sharing at top line?So if you could just maybe talk about that, that could be helpful.
Robert Blum
President and CEO, Cytokinetics
Sure.Thank you for inviting us.We are talking to ACC.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Oh, oh, that's right.
Robert Blum
President and CEO, Cytokinetics
ACC, and we're already in dialogue with the American College of Cardiology to understand sort of the ground rules and parameters around which we could be disclosing of top-line results-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
and still be eligible for presentation at the conference.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
-in early April.But also knowing that, this is an evolving situation.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
It's evolving in large part because that which we will be disclosing is that which we are going to then determine is material.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
What would be constituting a significant disclosure for moving the stock price?
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
I think that's a fluid situation.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
We'll want to disclose what could be informative of a best-in-class profile.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
That standard may itself be evolving.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
So if we are needing to disclose something that would be quantitative.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
And, we determine that that is a material disclosure, we'll have to put the ACC presentation even at risk.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Hmm.
Robert Blum
President and CEO, Cytokinetics
We're willing to do that if that is going to be enabling of us to disclose that which is material.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.So it seems like the priority here is really wanting to get the data, have it cleaned up, being able to, if it's material, share as much as you can, even if it-
Robert Blum
President and CEO, Cytokinetics
Yeah
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Jeopardizes your participation at the
Robert Blum
President and CEO, Cytokinetics
Ideally, we would
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
ACC conference
Robert Blum
President and CEO, Cytokinetics
be able to top line what still is permitting us to also present at ACC.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
But we can't refrain from disclosing what our lawyers tell us is material.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
And again, I think that's-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
A n evolving standard.So, you know, we already know certain things about the data.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Fady has been on our earnings calls-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Communicating that we have not had any EF excursions.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
That led to a notification.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
and a dose interruption.So we can assume we've had no EF falls below 40%.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
That which is between 40 and 50 reads on safety.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
And may not matter ultimately to the ACC.So I think it's reasonable to expect that we could be disclosing, that percentage that led to a down titration.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm
Robert Blum
President and CEO, Cytokinetics
Without jeopardizing a presentation.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
At ACC.As it relates to change from baseline and peak VO2.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
The magnitude of effect on the primary endpoint, the p-value, if we determine that that's important.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
As would be deemed material, we'll have to disclose that.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.I mean, given that it's the primary endpoint, I would make the assumption that that would be very material, right?And therefore, would be shared.
Robert Blum
President and CEO, Cytokinetics
It has to be considered in the totality of all the data.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
in terms of whether we think the results for SEQUOIA.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
support a best-in-class profile.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Until we have the full data, I don't know that I can answer.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
But we're keeping an eye on all of that.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
But also the evolving expectations of the street.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
in terms of what would move the stock price.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
That has to factor into our disclosure.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.Well, thank you so much.I know that there are so many moving parts.This means keeping shareholders happy, keeping organizers happy, and making sure that, you know, appreciate that, the thoughtfulness on all those questions.And then in terms of, timing of the actual data as you enter quiet period in December, people leaving for the holidays, I assume, like, starting the week of the twentieth, like, is it fair to assume that data could come after the holidays, before the holidays, or any day in December is fair game?
Robert Blum
President and CEO, Cytokinetics
We're going into a quiet period on December fourth.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.
Robert Blum
President and CEO, Cytokinetics
We've indicated that the data would be available to top line in late December.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
I think we define late December to mean any time after mid-December.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.
Robert Blum
President and CEO, Cytokinetics
And Fady has also made clear that we're not going to disclose data on Christmas.But as to whether it's before or after, it's a function of things we don't know yet.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.
Robert Blum
President and CEO, Cytokinetics
We're proceeding towards database lock.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
But, you know, from database lock to availability of tables, listings, and figures.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
That process can take.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
Weeks.Ultimately, Fady gets the data before he then shares it with me.That process
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
And the socialization of that, all we can know is it's not gonna be early December.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.All right.I know we over exhausted you with the type of data and timing of the data.We appreciate that.I just wanna make sure, Robert alluded to, but Fady wanted to.Since the last earnings call, is it still 0 cases of LV below 40 that has occurred?Okay, nothing has changed in that regard.Okay, good.It's every day -
Robert Blum
President and CEO, Cytokinetics
Yeah.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
We'll be asking you till December fourth.The other question that we get quite a bit is, I think a lot of investors recognize that the differentiation is gonna be on safety, and therefore, the data that we'll see at, from SEQUOIA is gonna be very important.But I think the expectation in terms of peak VO2 and efficacy has been more, it needs to be close to mavacamten.So I get the question: Well, what is close to mavacamten?Is it a plus minus point one, or is it a plus minus point two from peak VO2?Could you maybe talk to us, like, what is being in the ballpark of peak VO2?
Robert Blum
President and CEO, Cytokinetics
Before Fady answers.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
I just wanna make clear, we're not making comparative statements.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
No, no
Robert Blum
President and CEO, Cytokinetics
T o mavacamten.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.
Robert Blum
President and CEO, Cytokinetics
These are different studies-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Right
Robert Blum
President and CEO, Cytokinetics
D ifferent drugs, and we should not be making any comparative statements.But as it relates to absolute effects.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
O bserved in SEQUOIA.
Fady Malik
EVP of Research and Development, Cytokinetics
Yeah, I think, you know, I think if you consider the magnitude of effects on all the parameters.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
T hat we'll be measuring, I think we expect them to tell a story of substantial efficacy.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
F or these patients.I don't think patients can tell the difference, a 5% or 10% difference in one parameter.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
V ersus another, right?And, and physicians can't possibly assess, you know, "Does my patient 10% better.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
F eeling better than on this versus that?
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
I think it's a gestalt.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
You know, do the data all have reasonable magnitudes of effect.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
T hat in this class.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
H ave demonstrated in our clinical studies, as well as those.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
M avacamten, you know, very large.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
T reatment benefit for patients.So we think of, you know, differentiation as efficacy.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
S afety, and ultimately convenience.And I think in all those matters, we have a potentially we'll be able to make a compelling case someday, should the data support all those things.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.Helpful.
Robert Blum
President and CEO, Cytokinetics
That shouldn't be misunderstood to mean that we don't believe that we could see an effect on.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Peak VO2, that is north of where we.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
P owered the study.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
The study was powered with over 90% power.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
T o detect a 1.5.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
We might do appreciably better than that.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.
Robert Blum
President and CEO, Cytokinetics
But I think to Fady's point, ultimately in the marketplace.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
I think physicians' choice will be a function of safety and convenience.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
O ver all else.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.The other question that comes up is just, and this is not related to kinetics, but many recently, especially in 2024, there has been quite a bit of surprises in placebo responses or execution, high discontinuation rates, etc. And so usually, as investors and analysts, we think everything is fine, and suddenly the top-line data becomes, comes in, and it's a big surprise.Could you maybe talk about what you guys have done meticulously in SEQUOIA to really ensure a successful, seamless execution, that there's-
Fady Malik
EVP of Research and Development, Cytokinetics
Mm
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
N ot a surprise that tomorrow we're gonna have?
Fady Malik
EVP of Research and Development, Cytokinetics
Well, the data are blinded, so I can't say there are no surprises in the data yet.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.
Fady Malik
EVP of Research and Development, Cytokinetics
You know, what we do know is overall, the variability.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
A nd the primary measure, peak VO2, is well within what we
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
P owered the study to do.We know that treatment discontinuations.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
O r missing data are within, you know, what we expected.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
A nd powered the study for.Peak VO2 tends to be less prone to placebo effect.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
A s a reproducible measure.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
O f exercise performance.One can't exclude, you know.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
S ome strange placebo effect, but there's no reason to expect it.We train the sites meticulously on how to do that.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.
Fady Malik
EVP of Research and Development, Cytokinetics
Every test is in real time, you know, basically as it's done.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
S ent to the core lab.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
They evaluate them, they provide feedback..
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
T o the sites, if necessary.And so, you know, we think that the attention to detail.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
H aving conducted trials like this before
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
H aving a clinical team that's very experienced
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
I n HCM, conducting the
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
C urrent trials, I think all of that is, you know, the highest quality one can possibly achieve.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Could you remind our investors and the audience on what historical ranges happen in peak VO2 and placebo responses?
Fady Malik
EVP of Research and Development, Cytokinetics
Usually I, you know, when having biopsied the literature, it's plus or minus 0.3.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
I s kind of a typical range.But I would say, you know, that's the expected placebo effect range.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Got it.That's very helpful.Team, the next question, I think after the data becomes available, will be really getting ready for the record filing.So I know that you guys are always well prepared and do your homework and start pre-writing, but how soon post this data could you be in a situation to get the NDA filed?
Robert Blum
President and CEO, Cytokinetics
We've already been drafting major sections.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Of the NDA and the European equivalent.We've scaled up.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
our regulatory teams
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
so that we could be submitting them more or less in parallel.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
We have already been reaching out in order to schedule meetings.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Typically, the way this kind of thing rolls is you have a top-line meeting.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
With FDA, as would be informing of then a subsequent pre-NDA meeting.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
As would then proceed a submission.I expect that we'll have those meetings in the first part of
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
2024, to be enabling of a submission by mid.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Year, mid-year, whether that's June, July or August.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
Or something like that.I'm sure we'll start getting questions, but I think it's premature to provide any more clarity than that.And that's a function of things that are still to be determined-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Once we have those initial meetings.But we're trying to get everything in place so that, the only thing that's
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Left to do is incorporate data from SEQUOIA.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
And other things that are still finalized before we could be submitting.So I imagine we'll be in a better position to provide guidance-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
On when we have the data
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
We have our Q4 earnings call.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Which will be, February.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.It's so from what you just noted, it seems like the EMA filing will be sort of being processed at the same time.Is that right, or is it going to be prioritized, let's file?
Robert Blum
President and CEO, Cytokinetics
It'll be not the same.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
Immediate, but in close proximity.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.
Robert Blum
President and CEO, Cytokinetics
The goal is to get them both on file.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
within, you know, a few weeks to a short few months, if we can.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Great.Numerically, just a question is, given this product profile, what is the possibility you could be granted priority review?Let's say, to show, you know-
Fady Malik
EVP of Research and Development, Cytokinetics
Well, I think, you know, we have Breakthrough Designation.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
We have a means to ask for priority review.It's not our base case assumption.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
We have, obviously, a product in the market already.But I think the data.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
That we generate may make a compelling argument.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.
Fady Malik
EVP of Research and Development, Cytokinetics
For the
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
you know, priority review and their experience with the mechanism.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
Of action, you know, I think
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
also might portend
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
Something like that.But obviously, we'll have to wait and see.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.No, thank you.Another question that also comes up is, you guys have been very thoughtful, educating us that-
Fady Malik
EVP of Research and Development, Cytokinetics
Mm-hmm.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
A REMS program is something that usually a sponsor starts discussing with the FDA.So at what junction post the NDA filing do you start having.Like, when does that occur?Does it occur during the mid-cycle review?Is it towards the end?Like, what's the process behind it?
Robert Blum
President and CEO, Cytokinetics
It's typically socialized.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Even before a submission.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
But where the actual feedback doesn't come until you're engaged around a
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Mid-cycle review and afterwards are negotiating.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
For a label.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
And approval parameters.So we'll have some ability to judge.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Based on our data, but I don't think that will be, in any way validated.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Until we're discussing it with FDA, based on a mid-cycle review.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.And when.What is, in your view.I think, I think investors understand no REMS is obviously not the scenario.So this scenario is there will be a REMS that's maybe less burdensome.They recognize the DDI, not having to do the pharmacy calls is going to be a very big, important aspect of it.The embryonic lethality, at not having that on there for women is going to be important.But like, what is the frequency of an echo that's less burdensome?Like, I don't know, like
Fady Malik
EVP of Research and Development, Cytokinetics
Well, these patients typically.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah, like, what is the perfect echo monitoring scheme?
Fady Malik
EVP of Research and Development, Cytokinetics
You know, these patients typically, as part of their routine care.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
Get an echo every year.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.
Fady Malik
EVP of Research and Development, Cytokinetics
Twice a year is not.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
You know, a large burden compared to once a year.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.
Fady Malik
EVP of Research and Development, Cytokinetics
Ideally, we would,
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
be able to propose a data-driven approach to monitoring
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
you know, that may classify patients based on risk.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.Yeah.
Fady Malik
EVP of Research and Development, Cytokinetics
You're, you know, you're at higher risk, so we should monitor you more frequently.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
You're at low risk.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
We can monitor you less frequently.So, it's not a one.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Size
Fady Malik
EVP of Research and Development, Cytokinetics
Fits all, necessarily.
Robert Blum
President and CEO, Cytokinetics
I think that's where the data from FOREST-HCM.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Maybe even more so than the data from SEQUOIA.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Will be enabling of us to make a case for a REMS program that has, echoes with a frequency not unlike what these patients.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
are doing more normally.We're really encouraged by the FOREST data that we've been presenting.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Already, and they suggest that, as I think we shared at an investor day recently, that
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
As often as we've been doing in FOREST has not contributed to any changes in dose.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Or anything that was informing of a change in clinical.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Practice.But to the extent that continues.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
We can make a case to FDA as rooted in
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
evidence that the frequency of echoes we are performing in SEQUOIA and also
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
FOREST may not be medically necessary.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.But in terms of the early getting the patient on the right dose, that ECHO process is gonna be very similar than what currently is available for mavacamten?Or is there an opportunity to even have some modifications in the early.
Fady Malik
EVP of Research and Development, Cytokinetics
Well, I think.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Getting patient?
Fady Malik
EVP of Research and Development, Cytokinetics
Dosing will be different.You know, I mean, our
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
O ur dosing protocol is quite different.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
We start at the lowest dose of aficamten.We work our way.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
Up in the traditional dose escalation.We have always suggested down titration.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
As opposed to dose interruption.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah.
Fady Malik
EVP of Research and Development, Cytokinetics
So I think dose titration will be distinct to aficamten.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
We can hopefully also make a good case.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
For monitoring phase.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Fady Malik
EVP of Research and Development, Cytokinetics
To be distinct and
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
Other features that are, that are molecule dependent.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
Such as reprotoxicity.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Fady Malik
EVP of Research and Development, Cytokinetics
or, DDIs.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
You know, those will be distinct.I think programs will be quite distinct.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
And what we hope is in, with aficamten.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
The data will provide.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
the means to suggest something that's
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Fady Malik
EVP of Research and Development, Cytokinetics
reasonable for physicians and patients to execute.
Robert Blum
President and CEO, Cytokinetics
There are precedents.I realize that Wall Street is kind of
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Trying to lock in on a narrative around whether there's a category REMS
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
or molecule-specific REMS.And I think there are good precedents.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
for molecule-specific REMS, where the data speak to
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
a different risk.And that's what, hopefully our data will lend support for.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Thank you.I guess the biggest question that we get is, from investors, is there's a very high POS on the success of SEQUOIA and conviction and belief in your team and what you guys have done.No doubt about it.I think the hiccup is in what, how do I predict the differentiated scenarios of the REMS, you know, post that data?And how clear is that gonna be?Do you think once we see.Probably top line might be too early, right?We see some picture.
Robert Blum
President and CEO, Cytokinetics
I think you're already seeing.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
In FOREST data.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
Reasons to believe.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
That the SEQUOIA data will confirm.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
What could be a profile that is not requiring.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
of the same level of ECHO frequency.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
And monitoring.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm.
Robert Blum
President and CEO, Cytokinetics
I think that's already.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
knowable.Hopefully, SEQUOIA doesn't do anything to subtract from that
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
But only adds
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Evidence to that.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
No, that's very helpful.And how do you.I think once the data comes in, the next questions will come into the regulatory discussions.You guys have been very transparent all along the way, but how do you envision sort of the disclosures that you're gonna have into 2024?Obviously, you're gonna announce when NDA and EMA filing has occurred.You're gonna announce, you know, an acceptance and PDUFA date, et cetera.But like, how will you communicate with us and investors as you're starting these early processes of discussing with the FDA, REMS and differentiation, et cetera?Like, are you
Robert Blum
President and CEO, Cytokinetics
So
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Are you gonna be like
Robert Blum
President and CEO, Cytokinetics
We won't be
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Sharing that, or would that
Robert Blum
President and CEO, Cytokinetics
We won't be providing play-by-play-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
Updates, especially if we're in a negotiation-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
With FDA.I don't think that would be appropriate.But when we have something meaningfully definitive-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
to say, we'll say it.More likely concurrent with earnings calls.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
Than in between.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay, that's helpful.The other question that'll come up after the data and after I think SEQUOIA, which is directed to Andrew, but I will let you answer on behalf of Andrew, is pricing, right?I think people recognize the ICER recommendation.People know what the competitor product costs, but let's make the assumption if the data looks win on safety, and let's say it's also further win on efficacy.Would you, as a sponsor, contemplate the idea of pricing higher because the product profile is significantly raised?If you could maybe talk about how you're thinking about scenarios of SEQUOIA in the pricing strategy that-
Robert Blum
President and CEO, Cytokinetics
Yeah.The answer to your question is yes.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
We would contemplate that.Obviously, you'd have to see the data-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Yeah
Robert Blum
President and CEO, Cytokinetics
D o the quant research around pricing-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
budget impact, what this means for-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
payers and discounts.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
But I've been impressed that BMS seems to be getting its price.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
Taking price increases-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
A nd getting the kind of payer coverage-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
That one should want to see for a new cardiovascular
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Drug in a new category, competing with generics.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
So ultimately, we wanna be not just setting price-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
-based on clinical data, but based on HEOR.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
We wanna be a leader in that space.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm.
Robert Blum
President and CEO, Cytokinetics
Already I think we are.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
You mentioned ICER.I don't foresee that the ICER analysis has yet factored meaningfully into pricing of-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Mavacamten.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
They got a higher price.They seem to be having sufficient leverage with payers.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
The price in Europe-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
is higher than I think consensus estimates are
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm
Robert Blum
President and CEO, Cytokinetics
and we'll see how that does in Europe.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm.
Robert Blum
President and CEO, Cytokinetics
But I think BMS is doing a pretty good job of being a price leader-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
Right now, and whether we're coming in at or above-
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Mm-hmm
Robert Blum
President and CEO, Cytokinetics
will be a function of our data.
Yasmeen Rahimi
Managing Director and Senior Research Analyst, Piper Sandler
Okay.Well, team, we have come to 25 minutes, flown by, and I can't, we can't wait for the data.So just wanna say on behalf of all of us here at Piper, thank you for being at this conference, being part of this.It's been just an incredible journey, covering your name and watching what you have done.So we can't wait for SEQUOIA, and wanna say thank you on behalf of all of us.You know?
