Q3 2022 Cytokinetics Inc Earnings Call
Okay.
Yeah.
Good afternoon, and welcome ladies and gentlemen to Cytogenetics third quarter 2022 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 two questions per participant I will now turn the call over to Diane Weiser Cytogenetics Senior Vice President of corporate Communications and Investor Relations. Please go ahead.
Good afternoon, and thanks for joining us on the call today, Robert Blum, President and Chief Executive Officer will begin with a brief overview of the Qatar and recent development that am Alec EVP of R&D will provide updates related to on the Camden Mccarville unhappy Camden, Andrew colors, EVP and chief.
Actual officer will review commercialization planning activities for on the Camden, Mccarville, and our specialty cardiology franchise strategy related to IP Camden.
There were a couple of our SVP and Chief Medical Officer will provide an update on well do something Robert Wong VP and Chief Accounting Officer will provide a financial overview of the past quarter and Ching jaw, SVP and Chief Financial Officer will discuss our financial outlook and corporate development.
Finally, Robert Blum will provide closing comments and reveal expected upcoming key 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 third quarter 2022 financial result filed on form 8-K today, we undertake no obligation to update any forward.
Looking statements. After this call and now I will turn the call over to Robert.
You Diane and thanks for joining us on the call today.
We made good progress in the third quarter and we approached the end of the year in a strong financial position with important progress achieved across the company and for our programs.
Most notably during the quarter, we advanced planning for the potential launch of Omi kept them mccarville subject to FDA approval potentially next year.
Over recent months, we continued productive engagement with FDA as it continues to review of our NDA and we expect the late cycle review to occur later in this quarter in advance of the Advisory Committee meeting.
Engaging constructively with FDA represents a key priority and as such our teams have been very focused on preparations.
That will continue for the next several weeks as we ready for our participation in this important meeting.
We also advanced regulatory preparations for Omi character mccarville outside of the United States. We remain on track to submit a marketing authorization application to the European Medicines agency before the end of the year, which aligns with our go to Europe strategy.
For LC Kimpton, we continued conduct of Sequoia HCM, we completed patient screening in cohort four of Redwood HCM and we furthered our startup activities for the second phase III trial of Alfie Camden as monotherapy, a phase III trial for which we expect to activate sites by year end.
And with enrollment to begin next year.
During the quarter. We also shared results from two analyses of the open label extension trial of Alfie Campton, which both add to our understanding of the potential benefit of longer term treatment without the kimpton and in particular support our rationale for advancing the program to elaborate on the potential for Appy kimpton as could be.
<unk> monotherapy.
For <unk>, we were pleased that the DMC or data monitoring committee recommended that courage AOS continue following their review of unblinded data from the trial.
We are positioned well as we continued to transform and mature our company. We eagerly anticipate next month's Advisory Committee are produced the date in February and numerous other corporate milestones across our early stage and later stage pipeline as you will now hear more with that I'll turn the call over to <unk>.
Eddie.
Thanks Robert.
Robert mentioned top priority for us over the past few months has been preparing for upcoming Advisory Committee meeting for only Campton mccarville.
Our team is conducted mark panels, with experts and rehearsed or presentations Paris.
Paris for potential questions that may be asked at the outcome.
We also are developing supported materials intended to address topics that may arise.
As a reminder, we do not yet have the meeting agenda, nor the specific questions that FDA plans to ask but we believe the advisory committee will be asked to consider questions related to substantial evidence of benefit benefit risk and dosing.
Although our diligent preparation and the dedication of our team we believe that we will be well prepared for the Advisory Committee.
The head of our late cycle review meeting with it anticipated later this quarter. We've continued discussions around dosing of OMA Kempton mccarville, it's benefit risk profile and heart failure patients.
Benefit risk profile, and our affiliate patients at higher risk for that and heart failure events for which the benefit of adding only captain mccarville to standard of care appears larger.
We have also discussed with FDA the potential use of a test to assess plasma concentrations of only captain mccarville to guide dosing.
In Galactic HFF, we employed an assay to assess plasma concentrations of OMA captive mccarville to guide dose titration and with FDA. We're discussing the potential implementation of a test into clinical practice or on the campus of Ah Carbel may be approved.
Turning now to Europe is Robert mentioned, we recently participated in and productive meetings.
With assigned rapid tours in preparation for our expected and MA filing which is planned to occur by the end of the year.
More regulatory developments are also expected and other geographies is will provide further updates.
Regarding Appy Campton, we've also continue to make progress on its development program.
Sequoia HCM is enrolling patients globally, and we now have approximately 70 sites up and running in the U S Europe Israel in China.
The majority of which are team visited in person in recent weeks to facilitate activation in patient enrollment.
We expect that most if not all clinical trial sites will be actively enrolling patients in this fourth quarter.
The trials currently on track to complete enrollment in the first half of 2023.
Which should enable availability of topline results in the second half of next year.
Turning to cohort four of Redwood HCM, we completed screening for patients with Nonobstructive HCM and patient entry into the study should be complete soon.
We anticipate sharing results from cohort four in the first half of next year, which may set us up for advancement into a pivotal phase III clinical trial and Nonobstructive HC him in the second half of 2023.
Finally, we further preparations and study startup activities for our second phase III clinical trial of Ft, Campton, an obstructive HCM.
As a reminder, the goal of this additional trial is to evaluate the safety and efficacy of Appy campton as monotherapy compared to Metopium law common beta blocker used by people with symptomatic obstructive HCM.
This trial should hopefully provide a better understanding of the potential use of appy camp to relative to Kent current standard of care therapy.
The protocol has been finalized site preparations are underway and we expect this trial to have sites ready to go by the end of 2022 with enrolment to start in early 2023.
During the quarter, we announced data from two analyses of the open label extension study of Abby Campton.
Before a recap these findings I'd like to say a word about the name of this study.
Until now we refer to this study is redwood HCM ol Li.
But we have recently renamed it to forest HCM, which stands for five year open label research evaluation of sustained treatment with Abby camped in HCM the.
The name Forrest HCM more accurately reflects the inclusion of patients not only from Redwood HCM, but also from Sequoia HCM and other future trials of Appy campton as it will be open to all patients who complete treatment and all clinical trials of ft Kempton <unk>.
No changes have been made to the protocol related to this name change for the trial.
And now to the findings of these recently presents and analyses.
The first analysis presented at the inaugural meeting of the Hypertrophic Cardiomyopathy society evaluated reduction or withdrawal of background therapy in patients treated with that the captain.
And the 20 patients who completed treatment through we 12 and who were eligible for this analysis 17 achieved successful background therapy reduction or Withdrawl, which was defined as at least one dose reduction of one medication to less than 50% of the baseline dose.
10 patients completely discontinued at least one medication and five withdrew from all standard of care therapies.
Background therapy reduction or Withdrawl was unsuccessful in three patients who reinstituted a beta blockers result of recurrence of symptoms or elevated left ventricular outflow track radiance.
And patients being treated with happy Kempton, who achieved successful reduction or withdrawal of background therapies.
LBO teak radiance and YHA class and Biomarkers remained similar to those who remained on other background therapies.
These data support the rationale for choosing to know investigate appy campton as monotherapy to potentially further elaborate on the next in class profile of Appy Campton.
The second analysis presented at the Heart failure Society of America meeting evaluated patient self reported health status.
And found that as early as week 12 patients treated with Appy campton experienced substantial and significant symptom improvements as measured by the change in Casey C. Q score and suggesting that empty campton is associated not only with improvements in cardiac function, but also symptomatic.
Burden the quality of life improvements.
Cytokinetics presence at medical conferences like HSA, an ATM society.
As grown stronger over the years and is now inclusive not only of our presentations and posters, but also our exhibit booth sponsored symposia support for independent medical education as well as other medical affairs activities.
These conferences represent opportunities to connect with leading researchers in healthcare providers.
Okay, the rigor of our science and clinical trials as.
As well as support health health care professional learning objectives.
Are growing presence signifies just how integral these conferences are as we approached the potential approval and launch of OMA captive mccarville supportive of our franchise strategy and the potential future approval and launch a happy campton.
Aligned with these activities, we continued to expand our headquarters and field based medical affairs team and filled key roles in the medical director Medical Science and medical communications functions.
During the quarter, we also initiated activities with the medical information vendor to begin planning for our medical contact center.
With that I'll turn the call over to Andrew to provide an update on our commercial readiness activities in support of our plan special cardiology specialty cardiology franchise strategy.
Thanks, Patty or commercial readiness activities in the third quarter continue to protocol path to launch Shiroma Captain carve will be approved.
The progress to readiness includes a focus to market access with emphasis to ongoing pair engagement as we continue to meet with top national commercial on Medicare Payors.
We have been meeting with key regional payers as well to discuss evaluate critical data supportive of home a captive mccarville, where the continued our participation a pair conferences as well as medical conferences with the support of our medical affairs and our colleagues.
To adventure awareness of the role of the minutes contractility at heart failure. We are pleased to essentially larger disease State education campaign called the harder contractility during the quarter. The campaign will go the awareness of the ATP community for worsening heart failure and the residual burden that these patients face.
As well as educate professionals about the importance of cardiac contractility and how they fit as a consideration pathogenesis of heart failure.
The campaign currently includes the website digital advertisements finally get medical conferences and more.
Furthermore, we also advanced Mr can get design and development of our patients support and services hub airport element, bringing patient centricity to the forefront of our commercial strategy for OMA captive mccarville.
Turning to distribution and supply of OMA captive Mccarville. We have finished our third party logistics agreement advanced several wholesaler agreements and have successfully completed strategic searching assessment of drug substance and drug product contract manufacturing organizations.
As in previous quarters, our team continued to grow we began hiring our final wave of shall Schwartz leaders with nearly 90% in place against our goal to have all of them onboard by January .
For our initial wave of shelves leaders and those we began recruitment for recently we have received a tremendous response with over 500 applications for just the first 12 positions with top tier candidates, bringing your Chubb shall experience 14 years of cardiovascular experience 13 years of leadership experience in 22 years of farm experience on average.
I am confident they were building a strong team and expect to thrill to fill our roles with similar high caliber talent Hell it.
That approval is granted we will begin hiring on boarding and training Michelle's rush, specifically within a week of approval, we plan to begin nonpersonal and digital promotion.
That time shelves leaders will be deployed in the field.
And medical Affairs team will continue engaged with Hcp's. We also expect to launch our product groups with related education at ATC next year. We are these activities. Many additional element to our voice strategy you are moving forward behind the scenes in preparation for this potentially transform transformational milestone for our company.
Finally, as it relates to advocate and during the quarter, we continued development or go to market strategy in the U S.
Under on trial.
Hire us markedly.
And have initial plans in place by the end of the year.
Building out our commercial readiness plan alongside Lodge planning for both <unk> and <unk> and May afford of key synergies that potential advantages and cross training for all people involved with that I'll turn the call over to Stuart to provide an update on relative shelters.
Thanks, Andrew.
During the third quarter as it relates to rail deceptive, we proceeded with patient enrollment encourage ILS, we now have more than 300 patients enrolled today.
Nearly all of the more than 80 sites are activated globally with robust enrollment three main regions.
U S Europe and Australia.
Enrollment is progressing well and we're on track to complete enrollment in the first half of 2023.
Recently, we announced continuation of courage L. S. Following the first interim analysis conducted by the data monitoring Committee.
Which reviewed unblinded data from the <unk>.
This interim analysis assess from utility and was triggered 12 weeks after approximately one third of the plan number of patients were randomized.
A second enter on analysis is expected to take place in the first half of 2023.
Which will also assessed for futility.
But will also allow for a sixth increase in total enrollment if the unnecessary to augment the statistical power of the trial.
At the same time courage, a L. S open label extension or <unk> <unk>.
Now ongoing for patients who complete courage Alice.
And we are currently finalizing our plans to open a managed to access program in the fourth quarter of this year.
Remind you this program will be available to patients who have completed any of our previous ILS trials, including 40 <unk>.
The phase two trial of <unk>.
And vitality Alice the phase three trial of Tirasemtiv.
<unk> patients are in great need of new therapies. Despite advancements in progress in the treatment landscape include.
Including the recent approval the combination sodium sounds good alright, I'm <unk> for patients with allies.
This approval is not only good news for patients.
That reflects a websites and flexibility on F D A's park to accelerate the pathway to approval.
Patients with a L. S are confronting an <unk> burden of disease and.
And we remain dedicated the thorough evaluation of rail deceptive sports potential allies.
And with that I'll turn it over to Robert long.
Thanks, Stuart we ended the third quarter with approximately $896 million in cash and investments are.
Our revenue in Q3, 2022 came primarily from a vanilla <unk> courage.
Our third quarter of 2022, R&D expenses increased to $62.7 million from $48 $4 million in the third quarter of 2021, primarily due to increases in spending for clinical development activities for encourage <unk> and Sequoia HCM and for other cardiac.
Muscle inhibitor and early research programs.
Our third quarter of 2022, G&A expenses were $48 $2 million up from $26 $2 million in Q3, 2021, due primarily to hire outside outside service spending in anticipation of the potential commercial launch the only camp that mccarville and an increase in personnel relate.
Cause including stock based compensation.
During the quarter, we recognize the loss of $22 $2 million related to the conversion and partial settlement of 2026th convertible notes.
And now Ching will review, our financial outlook and corporate development strategy.
Thanks, Robert we ended the third quarter in a strong financial position was approximately $896 million cash on the balance sheet.
Includes the approximately $523 million in net proceeds raised from a 3.5% convertible senior knows offerings.
The notes have a 30% come version premium and are due in 2027.
In connection with this transaction, we repurchased approximately $117 million in aggregate principal amount of outstanding 2000, 2006 notes through private elite negotiated transactions.
In addition, we completed the unwinding of the cap call instrument, we entered into in 2019 in connection with our 4% comfortable senior note offering of that year.
A transaction that we completed October of this year and net that approximately 26 million of additional cash into cytokinetics.
We are in a strong cash position. Despite our expectation that are burn rate may increase next year with the potential commercialization on we kept on cargo.
In order to importantly, manage our spend as we approach potential commercialization, we have gated majority of lunch related expenses to posted for <unk>.
Furthermore, we have access to additional capital throughout deal was royalty farmer subject to our fulfilling conditions to disbursement.
We feel confident with our cash runway through employing our expense skating strategy, coupled with the option to drill down this capital as needed.
And with that I'll turn the call back over to rubber bulb.
Thank you <unk>.
So as we proceed to close out 2022, a year of progress across our pipeline. We're entering what may be a new era for Cytokinetics. Our company has matured in terms of teams and capabilities and with near term potentially transformative milestones in our future we are accelerating.
<unk> in progress to ready for what we hope will be an even brighter future.
And as we look toward potential commercialization of our first medicine with another just a few years behind that we remain steadfast to advance our earlier stage pipeline. Later this year, we plan to begin a phase one study of C. K 136, another novel cardiac muscle <unk>.
<unk> with the goal of proceeding to potentially phase two studies in specialty cardiovascular indications that would be complementary to that for only camp to mccarville more to come on that exciting expansion of our pipeline soon.
As two business development, we're continuing discussions with potential partners regarding the potential co commercialization of only camp to mccarville in Europe and Japan.
In Japan were also aiming to pair rights for only Kempton mccarville and Alfie Camden together.
Progress with regulatory authorities has informed these discussions at the same time, we're clarifying our own deal interest.
And we look forward to providing further updates and.
And finally during the quarter, we celebrated the opening of our East Coast office, located outside Philadelphia, where certain employees in our commercial or medical affairs in our supply chain teams will be based.
The opening of this office further reflects on our maturation and optimism and I'm pleased to see successes that we're achieving in hiring teams now on both coasts.
With that I'd like to recap our upcoming milestones for only camp to mccarville, we expect to participate in an advisory Committee meeting to review the NDA for only camp to Mccarville on December 13th 2022.
We also expect to launch only camp to mccarville in the U S pending potential FDA approval in Q1 2023 and.
And we expect to submit a marketing authorization application to the European Medicines agency for only camped over carbel by the end of this year 2022.
For <unk> Kempton, we expect to continue enrolling patients with obstructive HTM in Sequoia HCM.
Through the first half of 2023 with results expected in the second half of 2023.
And we are expecting to complete enrollment of patients with Nonobstructive HCM in the cohort four of Redwood HCM with data expected in the first half of 2023, and we expect to begin a second phase three clinical trial of Alfie camped an obstructive HCM in.
Q4 2022.
For C. K 136, we expect to begin a phase one study in Q4 2022 and for road deceptive we expect to.
Proceed through the conduct of the second interim analysis for courage AOS in the first half of 2023 and continue enrolling patients with AOS encourage AOS.
With that expected to completed enrollment in the first half of 2023 and.
And for our ongoing research, we expect to advance new muscle directed compounds as well as conduct IMD, enabling studies for one to two potential drug candidates.
Operator with that we can now open up the call to questions. Please.
Thank you as a reminder to ask a question you don't need to press Star one one on your telephone please stand by when we compile the Q&A roster.
Our first question comes from the line of <unk> Tiwari from Jeffries.
Hello, a college.
Hi, This is Irene <unk>. Thanks, so much for taking our questions I have to if I may the first one is regarding the now I'll try to take.
<unk>. So what you are internal <unk> Friday study in terms I'll spell Microreproduction, Jeremy can shell battle bunker reactions similar to you R. O H T. M trial, and also what say that that <unk> need to shell, which was the jazz at the campaign is clearly differentiated from all I N N a H T M.
Patient My second question is that all I R. A so give it at least now I have to come is approved again that often do this drug will become eligible for <unk> negotiation at the label guess extended so will you be considered west Jordan J, Yeah. When you tried to expand <unk> indications indicate.
<unk>. Thank you.
So let's start with your second question and then the <unk> first and I'll.
Saudi to comment on the first with regard to.
The inflation reduction act and its potential implications for Alfie Camden I do not foresee any implications that would alter our strategy with Alfie Campton, we continued to be focused to the development of Alfie campton.
Four obstructive Anne Nonobstructive, HCM, and we don't foresee that that.
New regulation will change our mind, we do believe now to your first question that we already have seen enough in cohort for to give us confidence of a potential next in class profile for Appy camped in Nonobstructive HCM, we already believe we've seen enough in.
The open label cohort to inform our want to proceed to end of phase two interactions and the start of the phase three study in 2023.
As to the particulars I'll ask fatty may be to comment on what we.
We considered to be the bar here, but please understand will probably not be as specific in light of the fact that this is an open label study is still underway and being conducted and we don't want to do anything to jeopardize the presentation of those data when those data are final.
Yeah, I'll, just say I think.
Without giving any quantitative numbers.
That what we wanted to see with consistency.
Across the different domains that we investigated with kempton and an ATM. So.
That would be consistency of improvements in N Y J class and Casey C Q and Biomarkers and echocardiographic.
Measures of response.
And so I think it's not a specific number but it's really consistency of effect across a range of domains.
Some of which would be part of the of.
The efficacy outcomes in a phase III trial.
The second part of your question was how would that be camped it'd be differentiated and then HCM I think.
We're all the same reasons that we believe it would be differentiated in Oh, HCM apply an ATM and that has to do with.
Rapid dose titration lack of drug drug interactions.
Reverse ability of effect and and.
Several of the other features that we've delineated previously so I think those.
Pharmacokinetic and Pharmacodynamic properties apply to both of <unk> and <unk>.
Really helpful. Thank you [laughter].
Thank you one moment for our next question.
Our next question comes from the line of Carter Gould from Barclays.
Great Carter, Hey, Robert Thank you very much for taking the question. Good afternoon, you guys I guess, maybe a follow up on the on the prior question a bit I'm sure you've seen Bristol sort of phase three design and the Nonobstructive segment there.
In terms of you know the use of the dual endpoints here can you just talk for a second if that sort of consistent was kind of how you're thinking about a potential phase three or any sort of lessons.
As you can kind of hear the design and maybe some of your interactions with <unk> F. D. A and then on I know my campus. If just quickly any change it kind of how you're planning if you get a little bit closer to the to.
To the AD com in terms of points of focus or key topics. Thank you.
Yeah. So we'll start with your second question and then ask Saudi to comment on.
Our views of the.
Study.
Reported by B M S <unk>.
As it relates to the upcoming Advisory Committee we.
We have had.
Several.
Recent FDA interactions and we're getting clarity on what we could expect to be those topics.
For discussion at the outcome, even as we have yet to still have the late cycle meeting and we don't have the formal agenda or formal topics.
But for what has been a very regular dialogue with FDA now over many months.
Certain things are becoming more and more clear and we specifically.
Specifically included some language.
In the press release regarding those matters. So you saw that.
We talked about in the press release that we expect there to be a.
Questions relating to benefit risk leading to dosing and safety. So these are things that we continue to expect will be reading on.
What might be.
The label and how it would be ultimately drafted it is possible that there'd be some other things.
I'm not gonna be able to go into specifics on this call.
For the fact that that wouldn't be appropriate, but I don't think there's going to be surprises in this for us given what has been a very transparent and constructive dialogue, we've been having with FDA.
So.
You know that we.
Are approaching this with the expectation that this is a positive phase III study.
A pivotal study.
Study that was discussed with FDA in great detail before it was conducted in after it was conducted.
While the overall effect was positive we also recognize that the effect is larger.
When considering some of the pre specified subgroups. So I think it's reasonable to expect that there's going to be some conversation about benefit risk and where it may be.
Observed and more pronounced ultra.
Ultimately that's the appropriate thing for advisers to be I think commenting on.
So I hope that's an answer to your question no going back to your first question Alas fatty to comment on.
Our views to the design of the.
Vms study and what it might mean for us.
Hi, Carter I think.
The.
Design of any of these studies needs to take into account.
Finding endpoints that are meaningfully report meaningfully report on patients symptoms and benefit and function.
And similarly, I think as I've said on previous calls all the end points that we examined in <unk>.
C M are applicable Tennessee, meaning.
Nyj class Casey C Q.
Exercise performance and so looking at the design of of the Phase III trial with Mavacamten.
Many of those things are captured there.
And you could expect any clinical trial design in this patient population to have.
Those kinds of endpoints incorporated so it's a little early for me to start providing specifics on our our own thinking and we'll plan to do that down the road, but but in general I think.
Those sorts of endpoints to save doing are clearly meaningful ones and.
Maybe just to add I don't think we were altogether surprised by what we're seeing it's consistent with our expectations.
Thank you.
One moment for our next question.
Our next question comes from the line of <unk> from Piper Sandler.
Hello, Yes.
Hi, Robert and team. Thank you so much for taking my question and congrats on the update maybe.
Maybe the first question is you know we are looking forward to see day Mavacamten Baylor data, but maybe that could you just remind us if that population is captured in Sequoia or would you have to run a similar study to being able to file.
Oh, Oregon accessibility to.
Patients for reducing Steptoe Appalachian City, you could just comment on that for us in terms of your plants and then the second question is you commented that screening has been completed and the non obstructive HTM population. So.
Has your screen failure rates and nonobstructive differ from the Abstractive population, if yes, what does that tell us about these two different populations and thank you again for taking my questions.
Sure. So just to clarify you said looking forward to seeing the <unk> data, we have see those results and perhaps what you meant was seeing whether FDA is going to be.
Expanding the label that time yeah.
Reflect the validate okay, yeah, because they did submit for the supplemental.
And da.
Yeah that'll be interesting to see.
As we have observed in the valor data it's.
I would say.
Revealing but perhaps not really advancing the ball beyond what we thought was already achieved in explorer.
And as you know.
With valor they were able to demonstrate that.
Patients who were eligible for Srt's therapy.
Upon receiving.
Mavacamten.
Several of them were no longer eligible for SRT didn't meet the criteria any longer for that procedure in light of effects observed with the addition of Mavacamten. That's a positive but there are very few.
And they were balance between groups very few events.
Events of SRT.
And as such.
We think a large.
Portion of what was already known about Mavacamten was.
Re affirmed if you will in valor.
As far as your question, specifically about our approach or less value to comment and then you also asked about the screen failure rate in cohort for so fatty if you wouldn't mind addressing those comments.
Sure I mean.
We do have a strategy for how patients and sequoia might contribute to labeling and for reduction.
Reduction of eligibility for SRT.
I won't really.
Further details about that but.
I'll, just remind you that patients eligible for septal reduction therapy.
Are those.
Patients with class three four symptoms that have a high outflow track radiance as are required to get into.
Sequoia in the first place. So I think we have a population that you might consider SRT eligible.
And.
And as May inform potential labeling for that particular aspect of of therapy.
Your other question with regards to.
Cohort four screen failures, we haven't seen screen failure rates to be.
Any meaningfully different I would say then.
And what we see a little bit higher than the cm patients.
In part because one of the parameters.
To get into these trials as the blood tests, it's empty pro BNP.
And people don't always have one of those on on record when they are screened and so the.
The results of that blood test may may or may not determine eligibility.
But all in all we've been pretty pleased with the activity in that trial and and how patients are proceeded from screening to do enrollment.
Thank you team and one last question that I hate to be that annoying analyst, but everyone would love to hear your thoughts on how you are thinking about partnering <unk> <unk> your thoughts around that changed as you were approaching the end of the year.
Increasing enrollment updates just some commentary would be helpful and dropped back into the queue.
Sure So I'll take that.
Our thoughts have not changed we continue to.
Intend to keep.
<unk> for our own account.
Our goal is to be proceeding go to market for Effie Kempton on our own in North America and Europe .
And while we have partnered in China, we continue to seek a partner in Japan otherwise.
Partnering of Alfie Campton is not something that we're pursuing.
Thank you.
Thank you.
Thank you one moment for our next question.
Our next question comes from the line of Joe <unk> from H C. Wainwright.
Hello, Joe everybody could afternoon. So Robert My first question with your New Philadelphia facility I, just wanted to make sure that.
You have them, all still working and not glued to the World series.
So with that said.
Wanted to add a debra.
Exactly [laughter] Oh [laughter] wanted to ask about the dosing test that you alluded alluding to regarding our home a captive is this something or can you clarify is this something you would like to maybe try to put in the initial label as part of your and cycled discussions or is this something that could be worked into clinical <unk>.
Actis later.
Very good questions. So as you know.
An essay was deployed in galactic H to be enabling of.
Those titration and with the goal of getting patients within a target plasma concentration range.
SA worked pretty well.
It's our view that it's useful and therefore, we're going to be doing what we can to make sure that an essay.
Could be available.
The approval of <unk>, whether that makes its way into the labeling or not is something that I think ultimately FDA, we will have to determine if the drug will be approved.
That's.
The subject of dialogue that we've been having with FDA and we'll be prepared for any scenario hopefully that comes our way, but we don't yet have real clarity on that matter yet.
Got it got it and then with regard to the ILS program in the open label extension that you were discussing I know, it's early days here for that but.
What kind of visibility do you have with regard to patient identification for enrollment.
And even example are you getting any prior tirasemtiv patients yet or potential to really get them. As you said you could.
So I'm a little confused by the question so.
We are blinded.
Study encourage AOS as a.
Studied the the open label extinction, Joe there too they're too.
Ways in which.
We provide relative <unk> of the open label extension, it's only for patients that complete encourage all the manage access program.
Accurate, yes, yes, sorry, sorry for the misnomer there, yes, that's what I meant.
That makes more sense then thank you for the clarification so under the advantage access program.
We're seeing patients who have rolled out of August .
And we will be making the manage access program available to patients even.
Some of whom have been on Tirasemtiv for five years, we have patients who have been on tirasemtiv for five plus years, even though we discontinued further development of Tirasemtiv back in 2017 and.
Those are patients who were expressing interest enrolling over into the manage access program for relatives sensitive.
So that will be an option available to them later this year.
Got it very helpful. Thanks, a lot guys.
Thank you.
Thank you one moment for our next question.
Our next question comes from the line of Jason Butler from J M. P Securities.
Hi, Thanks, Hi, Robert Thanks for taking my questions.
I appreciate the the update of details on the commercial prep for for OMA captive could you maybe just speak to some of the items that that will be gated post approval and maybe if you could just give us your updated thoughts on reimbursement and and the the the conversations you've already had and how you think.
About the reimbursement landscape for the drug thanks.
Yeah. Thank you for asking I'm Gonna ask Andrew Carlos to be specific but as you've already heard say and I'll just repeat.
More than a majority of about two thirds of the cost that we might expect would be associated with.
Launch and post launch arcaded.
We're being very careful and prudent about what we invested now print.
Principally long lead time activities.
As would be required to be in place in Q1, if this drug could be launched in the first half of next year, so that speaks to.
In House home office based people, who are going to be doing a lot of the planning work and some of the sales managers not even all of them as you will hear from Andrew and I'll ask Andrew to know elaborate.
Yeah sure and thanks for the question. So in terms of gating were Gabriel things like our sales representatives are patient support programs.
Media and advertising and meeting and events speaker programs and speaker honoraria anything that would be really operational if you will once a product gets approved and those expenses are the majority of expenses for all the candidates Robert alluded to so we have plans in place.
To execute all of those things, but none of those will occur.
If we get approved that's when they would occur in terms of reimbursement in reimbursement landscape as you probably know the heart failure market is.
Has more Medicare than any other kind of <unk>.
<unk> from a pier point of view, followed by commercial and those Medicare and commercial payers are really controlled by.
Handful of Pbms on both sides of those Pbms represent health care plan Blue Cross Blue Shield and made your health care plan, an employer groups. We've been we've been interacting with regional payers light Blue Cross Blue shield as well as national payers like that <unk>.
<unk> or C. B S Express crib. So every major player in the health care <unk> landscape. We've reviewed Cytokinetics, we have meetings plan to go through actual more detailed clinical reviews.
We're planning submissions for reimbursement and Medicare.
Several plans as well so.
We have a very robust plan for access and the access <unk> the customer facing excess pain.
Those that would call needs as customers or one of our first hired well over a year ago or so.
They've been in the field of law onto their medical colleagues and indirectly with each parent for quite some time now.
Great. Thanks for taking my question.
Thank you Jason.
Thank you one moment for our next question.
Our next question comes from the line motto Kumar from Goldman Sachs.
No matter Hey, this is Rob on Friday, and thanks for taking our question I guess our question is really how are you thinking about the subpopulations of Nonobstructive HCM and heart failure with partial injection fraction for <unk>.
Sure. So how are we thinking about subgroups, those who might be.
Be more likely presumably to respond to a cardiac myosin inhibitor fatty do you want to take them.
Sure I mean, I think with regards to an a T M. There are.
It's more rare than the O eight cm patients you Wanna try to be as inclusive as <unk> as possible rather than sort of further subdivide them.
On the other hand, you also won an objective marker.
Of their disease that is.
Indicates.
You know that.
They have a significant burden.
Pathophysiology.
Allergy based on the progression of their.
Of their disease.
So like.
Like many trials.
We would.
Want to have eligibility gated by something objective in terms of a potential biomarker that is reflective of.
Filling pressures.
Overall cardiac function and then also.
They're exercised function or symptoms so.
So when you think about subdividing the population I think less about.
You know specifically excluding space.
[noise] types of an ATM as opposed to ensuring we have symptomatic patients that have significant cardiac dysfunction.
And then the second question and <unk>.
That's a much more heterogeneous.
Population.
Covers everything from.
Jackson fractions of 55% and higher covers.
Covers people with diabetes and obesity and other other issues that may be leading to their symptoms.
So I think there we would tend to be more selective and trying to identify features and have path.
That define a subpopulation that is more like are any cm patients.
And so again without being too specific that's that's how we would approach it.
Thank you.
You're welcome.
Thank you one moment for our next question.
Our next question comes from the line of Jeff Hung from Morgan Stanley .
Thanks for taking my question for Courage Ala can you just remind us what the triggers for the second interim analysis next year, and then I guess for the potential adjustments the size of the city can you just talk about what the powering assumptions are perfect <unk> in terms of also.
What would the considerations b for needing to Justice study size I appreciate it and call you can provide thanks.
Yeah. So the the trigger is.
Based on enrollment.
And when we get to approximately two thirds of the.
Intended.
Enrollment, that's what triggers the second interim with those patients having gotten out to the same time.
With regard to the powering calculations and the potential for Upsized.
Patty to comment on that please.
Yeah, we haven't been I.
Haven't shared really the specifics of the powering.
And how the second interim analysis is constructed.
The.
We do expect to publish a design paper that will have some of those details in it.
But maybe when generalities I think the second interim has two objectives. One is the futility analysis.
That would allow.
Allow the trial to either continue or proceed.
Pending on on.
Whether there is a chance of that trial, having a positive effect so.
The trial really had very little chance of succeeding at the interim analysis.
Then that would be a reason to stop.
In terms of increasing the sample size.
There are.
Scenarios, where there seems to be a positive effect, but we may be under powered to detect us that.
Effect with good statistical confidence and so in that case, the DMC can recommend increasing the number of patients in the trial to give us greater statistical power at the end of the trial.
And that's also some there is some pre defined <unk>.
Limits around that which.
Will be more forthcoming with down the road.
So I think you'll get more of your answers when that design paper publishes but.
For the time being I think thats, where we're comfortable making that.
Disclosure.
Thank you.
Thank you Jeff.
Thank you one moment for our next question.
Our next question comes from the line of <unk> from U B S.
Good afternoon.
Hey, thanks, Thanks for taking our questions I have two one on <unk> M. I K two to four I think he might've seen this update their moving this into obstructive itchy M P.
Presumably this had like a short half life and no D. D. I just don't have the same advantages that'd be have understood and Etsy Camden Me <unk>.
I'll just need the clinical data is gonna be the ultimate deciding factor here, but how do you think about the profile defenses with the <unk> M. I K 224, as we know right now and the second question just don't I'm a captive. So if you are liberal does get PK guided dozing strategy than.
<unk>, how do you see that impacting the commercial opportunity if at all.
So why don't we ask Andrew to comment on your.
Second question how might the.
Inclusion of the PK.
PK guided dose titration essay affect the commercialization.
And then finally can comment on your first question.
Perfect for the questionnaire. So in terms of <unk>, we were planning and expecting all along that pique got a dosing would be in the label as it was in our our clinical studies. So it's not expected to have an impact the way we looked at it and forecasted and when we talk to.
Do you know of.
Cardiologist and clinicians.
The patient is kind of a worsening heart failure patients who could be eligible as an appropriate fit for this medication get a blood test on a regular basis.
Things like kidney function blood sugar et cetera, So and it's only for the titration getting started and getting the right dose is our expectation so those factors and and the fact that.
These types of tests occur often.
Not anticipating it to have an impact on commercialization of the product.
And just.
Ash with regard to your question about M. I K 224.
Think I can't really comment because I haven't seen any data.
Seen any data from that compound I really don't know anything about its properties per se.
I think it's premature for us to make any comments.
I will say that.
We were aware of the existence of this compound for quite a long time.
Cardio used to refer to it also has a compound that might have some preferential properties.
It looks to me like it's reaffirming of what could be next in class profile of Alfie Camden and.
There are other things that obviously distinguish coffee campton from Mavacamten, but.
Until BMS might generate data with 224, it would be premature to comment.
Alright, yeah. Thank you.
Thank you. Thank you one moment for our next question.
Our next question comes from the line of <unk> from his new home.
Great good afternoon.
Good afternoon, Thanks for taking the questions I guess a couple from me if I can one on the camp they've been one an attic Hampton.
So I know you won't give us a peek sales number Robert for for only camped it so perhaps I'll I'll wear the question a little bit differently.
You guys provided a lot of contacts today on the span.
Thanks for that I'm, just curious or grab a little bit of confusion as the gating onyx on expand that associated more with approval and is it is it binary around that or is it more associated with the actual demand of the product.
And as a secondary question to that.
Is it possible for us for you to framework, how you're thinking about.
When only camped it becomes cash flow positive is there a bracket you can give us in terms of years.
On when only captive becomes cash flow positive the way you see it.
And then secondly on an avid camping just curious to get your your read on the overall obstructive hypertrophic cardiomyopathy the market after the Bristol print, obviously put a $5 million, which was significantly below consensus.
Curious how it changes your view of the peak total addressable market there.
And and specifically to Africa, and the revenue opportunity. Thank you.
Sure. So firstly with regard to army camp to mccarville.
Are choosing to gain.
Spending.
Is a function of us recognizing that.
We need to be prudent as it relates to.
Investment and only captive ahead of its approval, but upon approval.
You could expect that we will be committed to what we believe it could be a very.
Effective commercial launch.
In terms of.
Whether we will let other determinants guide the.
Titration of spending I think that's only natural.
We'll look to market access and other things as we might be then upcharge trading spending in accordance with that launch, but we intend.
If the drug is approved to go at it.
In a meaningful way as you would expect for a drug that could generate the kinds of returns that you and other analysts have projected.
So I'm not going to speak to what might be potential peak sales you're right, but we do think that this is a product that under our.
Commercialization in the United States can produce positive.
Net cash flows for the company.
And in terms of how quickly I think as would be not unlike other.
New medicines in this category, it's not gonna happen, where we are producing a profitable product in the first year, but we do expect this product to perform well very well in light of the strategy that Andrew and others are laying out and building on the clinical evidence.
And.
In terms of how soon whether it's you or to your three that kind of thing it depends on pricing it depends on market access market access will be.
Slower in some areas here because this is largely a Medicare population and we have to make sure we get through those Medicare bids that process takes time, but you should expect that we believe that this drug is more than just providing a foot in the door for Effie Kempton.
It's a drug upon commercialization that we think can move the needle for the company and its shareholders.
Probably that's as good as I'm gonna be able to do for you today.
With regard to Africa Kempton.
Let me be very clear.
We have not changed our expectations at all based on the print from BMS, even as I acknowledge.
Sales reported in the most recent quarter came in below Wall Street consensus.
Continued to have every confidence that Vms is doing the right things by the launch of Mavacamten.
And they've already in their own comments reflected on how in October .
A lot of patients were converting from free goods and otherwise the number of physicians trained.
Food, the Rems program and being available to be prescribers and how many are continuing to prescribe unhealth few.
Few if any are <unk>.
Repeat prescribers and dropping off these are all the kinds of things that BMS knows very well and is building a commercial ramp for mavacamten as we expected them to do and.
Hence unless Andrew wants to add any comments I'll just end by saying we continue to believe very significantly in the upside for Mavacamten and also as.
Relates to Effie campton that could have we hope we believe could be next in clash compound.
Andrew anything else you want to say about the.
Launch of Mavacamten and what we're learning.
I mean, I think you covered it will I think it'll be amiss referenced over a thousand patients of which only a third or commercial that Robert alluded to but I think we we know based on claims data there.
Well over 190000 patients who have already been diagnosed in probably three to four times that number on yet diagnosed so it's a pretty big market.
Needs to be addressed and it takes time to develop a market so as Robert alluded to I think.
And it'd be a missed it themselves.
We're very bullish on this market and the opportunity for more than one player.
Great Super helpful. Thanks, So much guys.
Sure.
Thank you one moment for our next question.
Our next question comes from the line of Justin Kim from Oppenheimer.
Hello, Justin.
Hi, Robert Kim Good afternoon, and thanks for taking the question just a quick one on eligibility criteria for the second phase three study of Captain <unk>.
Head to head with Makopo I'll, just you know I'm.
I'm curious whether treatment experience is going to be a criteria there.
Just given the evidence of background withdrawal that was presented recently.
Curious, how you're thinking about investigating this.
Compound against Ah Ah beta blocker, and and whether you envision maybe randomize withdrawl or you know just.
How to think about <unk> wash out that that the campaign or beta blocker.
During during this investigation.
Yeah, So you'll get your answer very soon when this trial design posts.
Clinical trials Dot Gov, but maybe 30, if you wouldn't mind doing what you can to.
Answer.
Yes, and just and I think it's a good question you know.
The child wants to randomize patients too.
Beta blockers is mono therapy versus Appy campton as monotherapy and there are a couple of ways to achieve that you either capture new patients that are not yet on therapy, and and you randomize them and or as you say you potentially have to withdraw patients on existing therapy.
At least for a short time, and then randomize into one of two active therapy. So.
Will be more explicit about how we're going about that but.
Most of these patients can.
Can many of them any way and if the most but many of them can withdraw from their background therapy for a short period of time.
And tolerate that okay.
And that's what we're seeing you open label extension.
That's what's prompted a lot of the investigator enthusiasm for us to do this study.
Okay, great great and maybe just a clarification in terms of.
The end of this study is it is it fair to expect a a wash out at that he can't then in this study as well.
[noise] you know at the end of the study.
We generally do have a washout period, so look for a reversal.
Oh the treatment effect is another indicator of the strength of the.
Of the on treatment effects so.
I would expect a demon study.
Great. Thank you.
Thank you.
Thank you one moment for our next question.
Our next question comes from the line of Jane beyond from Raymond James.
Hello day.
Well.
We're going almost 10 minutes past the Amgen call right now so that's an achievement.
And if itself quick one for me.
If if you guys have have looked at the launch of various o'clock from buyer and Merck is kind of you know something to.
Learn lessons from as you get near to an approval at OMA camped of.
I guess what are some of the takeaways from from you know your your side.
Of how to maybe approach it a new drive that would be in the mix with guideline interactive therapy and in patients that would be maxed out on that therapy.
And is there anything just you know to to make it really simple for all of US 200 very smart.
You know is there anything that's like kind of a red line on this AD com and labeling Oklahoma camp to wear.
To my point on breast acquired Ah getting market share you just when think it's worth it to really go at you know at least a while in in the U S or or pier up you know something that would just be probably the ability of restrictive of access.
Yep.
Yeah. So good questions I will tell you that.
I am studying very carefully the launch of their sick and.
And we have very regular meetings here, where we're looking at data arising from that and it is very telling and informative.
To your point.
Going up against a pillar.
Pillars of standard of care or challenging.
I'm not going to say anything to denigrate very sick with it but I do think that the profile of patients who would benefit from up from only camp Div when added to standard of care is very clear.
And I do think that there are things that we can learn in terms of how to make that.
None.
Through Omnichannel marketing through.
Promotion.
And the.
The number of reps, how they're deployed in position to web centers. These are all things that were learning.
Some of which.
Would be similar diversity, what other things were going to do.
Because it seems that we can and maybe they chose not to.
It is a launch that is benefiting from.
I suspect the expectation that there'll be more data forthcoming they're conducting as you may know a phase for study.
But the patient who my best benefit from when we camp Davis.
A higher risk patient regardless of how you might.
Look at risk, whether that's by ejection fraction, whether that's by.
Blood pressure potassium recent hospitalization BNP any where you might look at it.
The more.
The risk the more likely patients may benefit for a moment captive when added to standard of care.
And that's very much to our benefit.
I guess, there are scenarios around which it's conceivable the labeling would come back where it would be so restrictive that.
It wouldn't be.
Ah launch that we'd want to pursue but those are not probabilistic scenarios based on the conversations were having.
So we really don't have a line in the sand around which we would expect not to go forward. If approved I don't think any of those scenarios are real they are really more in the abstract.
Andrew anything you want to add.
Yeah on that on the second one I think the important.
Element there too is that we expect that the canceling to launch that you know a few years. After all my captive in a big line item of expense It feel force and that's the same fuel for us. So that is an element of kind of cost sharing on the first item I think it's really about.
Four things wanted to focusing on the right patient type and clearly positioning it in explaining that two physicians two that were focused on cardiology and heartfelt treatment centers.
We're deploying where we're going to be focused on that.
That very clearly.
Patient support services in excess so it's Ah.
It's a difficult business, but a pretty simple formula just hard to execute sometimes in it and we're really focused on those four things.
Thank you.
Thank you.
Thank you one moment for our next question.
Our next question comes from the line of Charles Duncan from Cantor Fitzgerald.
Yeah, Hi, Yeah, Robert can team congrats on the progress and good luck with your upcoming add <unk> I had a question that was probably related to last one and that is regarding the puts and takes a pharmacoeconomic value for only captive I guess I'm wondering when you think about the benefits.
Benefit risk calculation, what do you think are the key what is the key element that you think create values for a patient with only captive and the data thus far and and would you use the same element in Europe would that be valued in Europe as well.
Very good questions and yes, both in the U S and Europe . There is a compelling a very persuasive pharmacoeconomic value that accrues when when we camped and mccarville is added to standard of care in the end result is reductions in events those.
Vince being primarily heart failure hospitalizations.
For a population where hospitalization is.
A significant burden and where.
Heart failure.
Hospitalizations as the number one reason for hospitalization and the United States.
So you're getting too I think the crux of where we do see value and hence why we believe we're meeting with such enthusiasm on the part of payers.
Especially.
This is a new medicine that will be positioned for higher risk heart failure patients.
They need not think about this for all of their heart failure patients, but payers are looking for ways to keep people alive and out of the hospital.
And that's exactly where only camped it seems to have its most pronounced effect in galactic, especially for those patients deemed at higher risk of hospitalization.
So.
There is a.
Strong a very solid values story here that you have begun to see us tell <unk>.
Through analyses and presentations and soon those will be publications that will be informing potential.
Use of only camp to <unk> so.
While very often.
These types of <unk>.
Forums, we talk about the clinical safety and efficacy I do believe there is a strong economic and value argument here as well and that'll be a key pillar of our message position.
Very very helpful. If I could just sneak one one more in for <unk> <unk>, but I know, it's been a very substantive call, but could just quickly on that.
Second interim I think you mentioned, it's triggered by enrollment uhm, but I believe it's triggered by two thirds and rolled through and exposed through 12 weeks is is 12 weeks enough really to gauge whether or not the drug might be having activity that could translate task to see and what are your thoughts.
[noise], Oh, Hi, Charles Alaska, Stewart tougher to answer that question and just to be clear.
You're talking about the first interim or the second interim.
Well I'm I'm wondering about the secondhand room I know what what the first syndrome widespread is it similar.
So the first thing Charles.
Third of the patients through 12 weeks.
Afterwards that get from there.
Hi, Charles how are Ya.
Thanks for the question so the.
<unk> just to be clear the the second interim analysis is trigger went at least a third of the patients have reached 24 weeks of treatment.
And this is a sort of a critical analysis.
Analysis because.
Yeah that that that's actually approximates or is consistent with the primary endpoint cause.
The trial changed.
Change from baseline to Alice F. R. S. R at 24 weeks so.
So the second hour announces the more.
Ah line with.
Expectations for for the primary endpoint, that's the first interim.
Was also an important inflection point because that corresponded with the duration of treatment and the place to try out for <unk>.
So that was.
And it's essential benchmark in terms of determining you know for that to utility analysis.
Got it and that makes sense to me thanks for taking my questions.
Thank you. Thank you. Thank you.
[noise]. Thank you one moment for our next question.
Our next question comes from the line of Rohit <unk> from need Hillman company.
I don't really good.
Good afternoon. This is real it on for Sir Thanks for taking our questions for all the captive in terms of the M. A filing for Europe would you wait for the outcome of the outcome of the confirmation to date before submitting.
And then the second question for applicant than.
Is the launch of Mavacamten impacted the awareness and interest in terms of investigator in patient recruitment for Sequoia H B O.
Sure. So with regard to your first question in the submission in Europe of an M. A for only camp to mccarville, we consider those.
Decoupled.
We're not really looking to the outcome is would be guiding are intended submission of an application in Europe . We've already had as I mentioned before enough dialogue with FDA that we kind of have a good sense of what the outcome will be all about we don't know of course the votes, but we know enough about.
Wow.
And we kept a mccarville will be.
Discussed that we are approaching R. M a already with some knowledge of how fda's thinking.
And obviously, we've had interactions with <unk> and Robert tours ourselves.
So we kind of understand what's the temperature in Europe .
So we will proceed there is obviously once you have submitted and the filing is accepted you have day 120, and other opportunities to dialogue with <unk> and it's conceivable that the outcome vote and what might be a <unk> action would inform how we.
Approach a day 120 event.
But not the submission itself.
Your second question related to awareness of Alfie Kempton and <unk>.
<unk> is that right.
Yeah, how is the launch of Mavacamten impacted the awareness and interest in terms of investigator in patient recruitment for <unk>.
Sure I'll ask you to comment on that please.
Yeah. So I mean, I think the field in general is very excited about cardiac mice and inhibitors for the treatment of this disease and.
The enrollment.
Enrollment of Sequoia.
I don't think has been significantly impacted because.
It's an option that some patients may consider.
And relatively.
A good option I think given the accessibility to open label drug after may complete the clinical trial, but importantly, this trial is not just being conducted in the United States is being conducted in Europe is being conducted in China Israel.
And so you know at this point in time I'm sure there's been some impact, but I, but I don't think it has slowed the trial down tremendously.
Okay. Thank you.
Thank you.
Thank you I would not like to turn the conference back to Robert <unk>, President and CEO for closing remarks.
Sure. So thank you operator in light of how long this call is going on I'll be Bruce I, just want to thank all of our participants on the teleconference. Today for your continued support and interest in what we're doing et cetera, kinetics, obviously, a lot going on in big events milestones coming up in the near term and we look forward to keeping you abreast of our progress.
Operator with that we can now conclude the call.
This concludes today's conference call. Thank you for participating you may now disconnect.
The conference will begin shortly to raise your hand doing <unk> you can dial star one one.
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