Q2 2023 Cytokinetics Incorporated Earnings Call

August 3, 2023

Okay.

Good afternoon, and welcome ladies and gentlemen, societal kinetics second quarter 2023 conference call.

At this time I would like to inform you that this call is being recorded and then 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 one question per participant.

Oh, I'll 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.

We will begin with an overview of the quarter and recent developments.

[noise] EVP of R&D will provide updates related to abbvie campton focus to Sequoia HCM Redwood HCM and forests, HCM, Steve Heitner VP clinical research and therapeutic area lead cardiovascular is filling in for Stuart Kupfer today, and we'll provide additional updates for Abbvie Camden.

Relating to Maple HCM and the expected start of Acacia HCM.

And to tell us EVP and Chief commercial officer will speak about commercial readiness activities for Etsy, Camden and its market opportunity, 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 our revised spending guy.

And for 2023 finally, Robert Dawn will provide an update on our early clinical programs in his closing comments and review expected upcoming milestones. Please note that portions of the following discussion, including our responses to questions contain statements that relate to future events and performance rather than historical facts.

And constitute forward looking statements.

Actual results may 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 second quarter 2023 financial results.

Filed on form 8-K that was furnished to the SEC today, we undertake no obligation to update any forward looking statements. After this call and now I will turn the call over to Robert.

You Diane and thanks for joining us on the call today.

Made substantial progress in the second quarter, not only by advancing and broadening the development program for <unk>, but also by making further strides in our earlier stage specialty cardiovascular pipeline.

Sorry, Steve will elaborate our comprehensive clinical trials development program for <unk> Kimpton.

<unk> on all cylinders during the quarter, we completed enrollment in <unk> HCM, we began maple HCM and we prepared to start Acacia HCM the phase III clinical trial of <unk> in patients with non obstructive HCM.

We have accelerated the timeline for this trial and we now expect to open the trial to patient enrollment next month.

It's notable that very soon we will have three ongoing phase III clinical trials for <unk> Kimpton plus the open label extension, which is a testament to our corporate re prioritization and the excellent work of our dedicated regulatory technical operations clinical research and operations teams.

As well as the high level of enthusiasm and diligence of our clinical site investigators and their staffs.

Now that enrollment in Sequoia HCM is complete study conduct is progressing and we remain on track to share top line results by the end of this year.

This trial has progressed through the dose escalation phase for all patients and we're monitoring key metrics and blinded data such as patients randomized baseline characteristics standard deviation around endpoints early terminations and missing data.

And I am pleased to report that across all of these measures Sukhoi HCM is proceeding well and meeting or exceeding our trial design assumptions.

Moreover, alongside our preparations for the reporting on topline results are regulatory supply chain and commercial readiness teams have been actively engaging in numerous activities, including go to market plans that build towards potential approvals and commercialization of <unk>.

Andrew will elaborate on some of those plans shortly.

Well I'll ask the Kimpton may be top of mind in parallel our clinical research activities continued to push forward on other fronts as well in the second quarter, we advanced CK 586, a second cardiac myosin inhibitor into a phase one study we continued the phase one study of CK one three.

Six our cardiac troponin activator, and we continued non clinical research and IND, enabling activities towards our goal of submitting one to two new <unk> over the next one to two years.

Moreover, in response to corporate setbacks earlier in 2023, and as we telegraphed on our last earnings call. We have reduced operating spending by approximately 15% relative to our initial 2023 financial guidance with a heightened focus on our priorities.

<unk> and pipeline, including preparations for the potential approval and commercialization of <unk> campton.

That's all going to enable us to further extend our cash runway Ching will provide more details and updated financial guidance for 2023 later in this call.

As you will hear today, we're moving forward with momentum into the second half of the year with a broad early and late stage pipeline ongoing research in a stronger financial Foundation give.

Giving us conviction and confidence in achieving our goals for the rest of the year as well as setting us up well afterwards with that I'll now turn the call over to <unk>.

Thanks, Robert and the second quarter, we made great progress across the broad development program for <unk> Canton most.

Most importantly, we completed enrollment and randomization in Sequoia HCM, the pivotal phase III clinical trial of FP, Camden with 282 patients randomized.

Surpassing our enrollment target of 270 patients and making it now the largest randomized clinical trial of an investigational therapy ever conducted in patients with obstructive HCM.

Conduct a quiet HCM benefits greatly from our growing experience and learnings related to the use of cardiac myosin inhibitors as well as measures employed in the evaluation of their effectiveness.

<unk>.

And physician preferences.

I am pleased to share that we also met or exceeded our enrollment objectives in terms of geography and patient characteristics. It's quite HCM enrolled in diverse patient population from the U S, China, Europe and Israel patient.

Patients enrolled exhibit a substantial deficit in exercise capacity a key element of the enrollment criteria considering that the primary endpoint assessments for a potential increase in exercise capacity.

Further to this point equates employees and individualized dose titration strategy, which is designed to optimize dose selection and maximize the potential benefit risk profile of Abbvie canton.

In fact at this point all patients have progressed through at least the eight week visit which marks the end of the dose escalation phase.

We're accumulating more and more blinded efficacy and safety data that we monitor closely including things like the standard deviation around the primary endpoint the completeness of endpoint capture the number of early terminations and blinded safety data.

Across all these measures we feel the core HCM is proceeding per plan, certainly matching or exceeding our trial design assumptions.

Our development operations and medical teams are working hard to collect and clean the data as it accumulates as well this program the analyses and tables necessary to report the results expeditiously once we lock the database at the end of the trial.

All of this work has put us on track to report top line results by the end of the year.

Now that all the patients from Sequoia HCM are randomized expect to also present baseline characteristics.

Of these patients at the HCM Society scientific sessions in early October .

Also during the quarter, we presented new data in patients with non obstructive HCM from cohort four of Redwood HCM at the heart failure 2023 Congress built.

Building on initial data presented earlier this year at ACC.

The data showed that following only 10 weeks of treatment.

Camden was associated with an average improvement in the clinical summary score of the Kansas City cardiomyopathy questionnaire or <unk> CSS.

Of 11 points with 58% of the patients experiencing a clinically meaningful reduction in symptom burden of five points or more.

Treatment with Abbvie Kimpton was also associated with improvements in NY. It shape functional class angina frequency high sensitivity cardiac troponin I in NT Pro BNP.

We are pleased to see that most patients were able to achieve the highest available dose of 15 milligrams with no drug discontinuation due to adverse events related to App Camden, no treatment interruptions or down titration events related to <unk> less than 50%.

And no events with Lv eef less than 40%.

We remain confident in the promise of <unk> in non obstructive HCM and look forward to starting a phase III clinical trial in non obstructive HCM soon Steve.

Steve will elaborate on this trial in a moment.

Before I hand, it over to Steve I want to also share an update on forest HCM, which is the open label extension study for patients and complete participation in Redwood HCM, So coy HCM and now Maple HCM as well.

We're pleased to see that nearly all patients elect to continue into the open label extension and we now have patients who have surpassed two years on etsy campton enforced HCM.

In addition to providing data on the efficacy of long term use of <unk> in the treatment of obstructive HCM.

HCM is providing data on both safety and efficacy and a very clinically relevant real world manner with investigators empower to adjust doses in accordance with their clinical judgment and even discontinue other background medical therapy for HCM to simplify their patients' medical regimen.

We will continue to periodically shared data from four its HCM, which we expect to factor importantly into the next in class profile for Camden and shed light on its potential ease of use and safety durability of effect and Tolerability.

With that I'll turn the call over to Steve who is filling in for Stewart, who is unable to join our earnings call today, Steve will speak to the expanding development program for Abbvie Camden.

Thanks Patty.

During the quarter, we announced the start of patient enrollment in Maple HCM.

His III clinical trial of asset Camden, as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM.

We are pleased to report that the first patients have recently been randomized.

While we do not foresee that Maple HCM is critical path to the potential for first FDA approval.

If successful in demonstrating that asset Kempton is superior to mature at all with respect to improvement of exercise capacity heart failure symptoms and New York Heart Association functional to US we would expect to submit the results from this trial as a supplemental NDA for.

For potential label expansion.

<unk> has the potential to meaningfully expand how physicians foresee using epic Hampton.

It would likely be reflected in the treatment guidelines potentially elevating it to first line therapy and potentially expanding the commercial opportunity.

At the same time.

In recent months, we have been continuing preparation for the pivotal phase III clinical trial of <unk> in the non obstructive HCM based on the favorable data arising from cohort four of Redwood HCM.

As noted in today's press release, we are calling this trial, Acacia HCM and keeping with our theme of northern California trees for the program.

Acacia HCM stands for assessment, comparing <unk> to placebo on cardiac endpoints in adults with non obstructive HCM.

This pivotal clinical trial of <unk> in patients with non obstructive HCM is expected to open for patient enrollment next month, which is ahead of schedule.

Underscoring the high level of enthusiasm for this next trial.

And advance I'd like to share a few key points about its design.

<unk> is a phase III multicenter randomized double blind placebo controlled clinical trial expected to enroll approximately 420 patients with symptomatic non obstructive HCM.

I'm Mary endpoint is the change in <unk> clinical summary score from baseline to week 36.

While the primary analysis will take place at 36 weeks patients will continue on treatment with Abbvie Camden or placebo for up to 72 weeks in order to evaluate additional secondary and exploratory analyses, including the time to the first cardiovascular event.

As previously mentioned, we expect to initiate patient dosing.

And Acacia HCM in September .

With that I'll turn the call over to Andrew.

Yes.

Thanks, Steve our commercial readiness team is laser focused on key work streams and supported the potential approval and commercialization of <unk> in both the United States and Europe .

During the quarter, we updated and continue to refine our go to market plans executed against activities outlined within them, including development of a disease State education plan branding positioning patient support programs sales force deployment plans and pricing assessments.

We have also conducted additional market research to gain greater clarity on HCM patient.

Experiences as well as how hep's payers and patients would respond to our potential product profile. Many.

Many of these plans will be augment it once we have results in hand from Sequoia HCM, but our research to date is encouraging in terms of payer patient and physician interest as well as enthusiasm for a next in class cardiac myosin inhibitor.

Our research continues to explore distinguished distinguishing characteristics are actually kept it.

<unk> its potential drug drug interaction profile and dose titration, which will be important to patients and prescribers.

We believe there is and will remain a large unaddressed population of patients with obstructive HCM that may benefit from Matthew Camden, If approved we.

We are fortunate to have been able to redeploy members of our commercial team who had previously been focused on <unk> to now focus on actually Camden, our corporate pivot that has enabled the acceleration of our planning.

An efficient operator operated visualization of our preparations for the potential approval and commercialization of assay captain.

Meanwhile, conversations with payers progressed in accordance with compliant preapproved payer interactions with productive dialogue and education, not only about the HCM landscape and the potential of cardiac myosin inhibitors, but about <unk>, specifically and which they remain highly interested.

We look forward to continuing to develop expanded hone our go to market plans for the potential approval and commercialization of IV, Camden and simultaneously deliver on step wise.

<unk> systematic element of the pre commercial runway.

Toward that end turning to market opportunity in the in Europe . We are pleased to have made our first new hire in Europe , bringing on our head of Europe , who has a proven track record in launching new products delivering growth and exceeding expectations in European and international markets within the rare disease in cardiology space.

Looking forward to having both our European head of access and medical affairs, joining us by the end of Q3.

We are pleased to be attracting top talent, thanks to our strong culture and pipeline.

With that I will turn the call over to Robert Wong.

Thanks, Andrew we ended the second quarter with $592 6 million in cash and investments on our revenue in Q2 2023 came from Astellas and is the remaining amount due to us from there $12 million commitment associated with our conduct.

<unk> ALS are.

Our second quarter 2023, R&D expenses increased to $83 2 million from $57 1 million in the second quarter of 2022, primarily due to increased spending for our cardiac myosin inhibition programs, which represents approximately two thirds of our R&D spend for the quarter our <unk>.

<unk> quarter, 2023, G&A expenses or $39 7 million down from $42 7 million in Q2, 2022, due primarily to reduced outsource spending on commercial readiness activities and now Ching will review, our financial outlook and corporate development strategies.

Thanks Robert.

We ended the quarter was approximately 593 million on the balance sheet, which represents nearly two years of cash runway based on our revised 2023 spending guidance announced today.

I will now elaborate.

Previously we had expected our operating expenses for 2023 to be in the range of $420 million to $450 million and net cash utilization to be approximately $350 million to $375 million.

We have reduced our operating expenses to be in the range of $390 million to $410 million in response to our receipt of a <unk> from the FDA regarding the NDA for omni kept them mccarville.

And the discontinuation of courage AOS.

Our net cash utilization is now expected to be approximately $310 million to $320 million.

This reduction represents savings of approximately 15%.

<unk> demonstrates initiatives to reduce spending and limit head count growth in light of these setbacks.

I will also remind you that as we have outlined in previous and revised guidance. We also expect to receive a $50 million nonrefundable milestone payments from royalty pharma upon the initiation of patient dosing in Acacia HCM, which is expected to start next month.

Through this transaction was royalty pharma. We also remain eligible for two additional tranches of capital if we choose to take them.

$75 million upon our potentially sharing positive results from the <unk> HCM and 100 million upon the acceptance of NDA submission for <unk> in the U S.

We view this transaction as the equivalent to a line of credit, which we can leverage to add to our balance sheet in 2024 if necessary.

Towards that objective, we're in the midst of our annual strategic planning process, which critically evaluate <unk> corporate and pipeline scenarios contingencies and risk mitigation.

And informed investment decisions as we calibrate with board and shareholder alignment and with that I will turn the call back over to Robert Blum.

As you've heard in the second quarter, we made substantial progress across the pipeline.

To add to what my colleagues mentioned during the quarter. We also participated in a type a meeting with the FDA to understand FDA views related to the CRM for <unk>.

And outside the United States, when we camped or <unk> is under review in Europe , and in China and during the quarter. We continued to support these reviews and address questions from regulators.

We also made progress with our earlier stage pipeline.

During the second quarter, we advanced CK 586 into a phase one single ascending dose and multiple ascending dose study and we're pleased with initial progress to date.

CK 586 is a cardiac myosin inhibitor that is mechanistically distinct from Matthew Kimpton and has the potential application for patients with heart failure with preserved ejection fraction or <unk> for which there are few treatment options for some people would have passed their disease in many ways mimics none of.

Give HCM due to their thinking hearts and increased cardiac contractility and symptom burden.

Encouraging data from cohort four of Redwood HCM and patients with non obstructive HCM.

Or potentially a proxy for the therapeutic application of cardiac myosin inhibition in this patient population as we hope to further investigate with CK, 586% in 2024.

At the same time, our consistent commitment to muscle biology research persists. In addition to the ongoing early stage programs for CK 136, and CK 586, we expect to file one to two additional IND for new drug candidates over the next one to two years once these <unk>.

Filed we will have advanced three to four new drug candidates in a relatively short time span and impressive figure for any biopharmaceutical company, which will enable us to expand our pipeline. According to our vision 2025 goals.

There is a great deal of work progressing behind the scenes and I must thank our diligent and dedicated employees for their commitment to our future.

Meanwhile, on the finance and corporate development side, you heard from King how we're doing right by shareholders to prioritize company activities and associated spending while also extending our cash runway. Moreover, we are continuing to advance business development initiatives with focus to Japan and Europe .

As we continue to seek potential partners for <unk>.

Since opening the aperture to partnering for <unk> in Europe . In Q2, we have been actively engaged with potential partners and we are pleased with the progress and level of interest that we've received as well as well as the diligence some deal discussions as it relate to both our <unk> and <unk>.

Our future is only made possible by what came before and this year, we've been celebrating our 25th anniversary with a recent open house held at our headquarters in South San Francisco, We invited our local community of partners former employees investors patients advocates and community leaders and we are.

<unk> been joined by a steam local city and county elected officials as well as staff, representing California State Senators.

We were grateful to celebrate this joyous occasion with our longtime supporters and friends recognizing though that while much is the same as it was when we started Sato kinetics. In 1998. Much has also changed as we've made progress towards our ambitious goals and still the best is yet to come when we hope for.

We bring forward, our first approved medicines to the benefit of patients.

Now I'll recap our upcoming milestones.

For <unk>, we expect to share top line results from Sequoia HCM by the end of the year and we expect to continue enrolling patients in Maple HCM and start Acacia HCM in September 2023.

And we continue to advance our ongoing go to market strategy during 2023.

For <unk>, we expect to continue to pursue potential international approvals for <unk> in Europe , and in China and for CK 136, we expect single ascending dose data from the phase one study in the second half of this year and.

And finally for CK 586, we expect to continue to enroll the phase one study throughout this year.

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

Thank you.

As a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again in.

In the interest of time, we do ask that you. Please kindly limit yourself to one question at this time.

These standby, while we compile the Q&A roster.

And our first question will come from <unk> <unk> from UBS. Your line is open.

Good afternoon.

Hi, good afternoon, its bottom on behalf of Ash watermark from UBS, thanks for taking our questions.

I have a quick one on <unk>.

Just looking at the mechanism is very similar it's distinct from past accounting like you noted.

What's your confidence that this mechanism of action will work for patients.

And why not pursue advanced also in obstructive HCM and just a quick second one like what would be the benchmark for efficacy and what clinical companies are you looking for in this phase one trial.

Sure. So I'll turn this over to Saudi and to Steve, but firstly before I do I'll just say that.

CK 586 is intentionally.

<unk> advanced as would be distinguishable from <unk>, which is being developed as you know in obstructive disease and non obstructive HCM now.

And were we to have identified any issues or liabilities with RC Kimpton, then perhaps CK.

<unk> 586 could be developed in those same indications, but we are not aware of any such issues and hence why we think 586 should stand on its own in a different disease state.

So maybe now I'll turn it over to <unk> to speak to why we believe this mechanism is translatable to that.

Perth.

What we may be looking for both.

It relates to phase one data and ultimately beyond that in half path.

Thanks Robert.

As you mentioned CK 586 and.

And that has a distinct mechanism of action than <unk>, but it's still a cardiac myosin inhibitor and the distinction is really a subtle point of where it binds in.

In what form of the motor protein it inhibits.

Fundamentally it does the same thing and reduces the number of active cross bridges and reduces cardiac contractility and has a shallow exposure response relationship.

Does abbvie campton.

And so fundamentally behaves very similarly.

As Robert said.

Abbvie Camden is doing wonderfully we don't really.

I think we need another drug in HCM, but <unk> is a much different population.

And.

And a very large population at that.

While we are intending with 586 is to focus in a different indication and too.

And do a subset of patients with half pet foods phenotypes mimic some of our NH Sam patients they have.

Larger hearts that can hearts high filling pressures higher biomarkers.

<unk>.

Poorer exercise tolerance in so many ways there are phenocopy.

For those that have genetic.

Non obstructive HCM and.

So we will be advancing $5 86 in that direction, it's really premature for me to discuss what we'll be doing in phase III, rather than focusing I think in that population that most closely mirrors the <unk> population.

I hope that's helpful. Operator, maybe that will move to the next question. Please.

Great.

And our next question will come from row at Basin from Needham <unk> Company. Your line is now open.

Hi, Good afternoon. Good afternoon. This is robin on for Serge. Thanks for taking our questions can you just talk about your expectations for the rate of enrollment for both the maypole indication trials.

And then when do you plan on presenting new data disclosures and medical meetings.

Sure so as it relates to both Maple and soon to start Acacia.

It's too early for us to be guiding us to rate of enrollment by do understand the question and we should get you that answer but it lifts.

See how we get out of this startup phase and these.

Initial enrollments before we might start guiding to enrollment rates in conclusion.

I don't expect that there'll be any data from either of these studies in 2023 of course and as we look to <unk>.

Next year I think it's also premature.

We'll be in a better position to point to what to expect next year. When we do our Q4 earnings in February .

Thank you.

Thank you and as a reminder, we do kindly ask that you. Please limit yourself to one question at this time.

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

Hi, Thanks for taking my question.

Hi, Robert Thanks for taking my question and congrats on the progress.

You said in the prepared comments.

All patients or an acquirer now through the titration phase I was just wondering if you could comment on whether youre seeing what you expected to see in terms of the proportion get to target doses.

So thank you for asking and that's a notable.

Achievement as you highlight that we now are through that dose escalation phase keeping in mind, we're blinded to dose, but maybe I'll ask Steve if he wants to elaborate.

Well, Jason I think Robin just answer to your question.

Obviously, a blinded study and we are in fact blinded to the actual dose administered.

Administered.

So we don't know the proportion of doses.

Patients are being exposed to an in Sequoia.

But do you have already seen some of the data that has been presented with regards to the forest HCM study, which is unblinded.

Where there's a nice balanced shape distribution in doses.

Patients being exposed to.

15, and 10 milligrams for the most part with a smaller proportion getting exposed to five and 20 milligrams.

Okay, great. Thank you.

Thank you Jason.

Thank you.

Our next question comes from Jason Szymanski from Bofa. Your line is open.

Good afternoon afternoon.

Congratulations on the progress and thanks for taking our question I wanted to circle back to some of your comments regarding maple in the possibility of broadening the label with ASIC Camden to include use in the first line setting I'm curious what are you what do you see as the opportunity here I mean, obviously the addressable market is sizable but it seems like there could be.

<unk> potentially logistical or administrative hurdles.

Thinking about pushback from payers or potential capacity issues from community prescribers I mean do you see <unk> Camden is a valid option for all comers with obstructive HCM.

Yes, I think we're following the lead of investigators themselves and forest, who are choosing to take patients off of beta blockers and for reasons that matter importantly to physicians and patients and ultimately I think will be welcomed.

Maple is successful by payers, maybe I'll ask our clinical colleagues if they want to add anything to that and maybe also Andrew if he wants to.

Hi, Jason says fatty I might just add that in the context of a drug that addresses the underlying causes of disease.

There is obviously opportunity for disease modification and so.

April is not addressed not.

Designed to address that point.

Yeah.

In terms of thinking about drug selected.

For patients at least we provide the evidence of which which are the current.

Number one choice since initiated versus the newcomer in the CMI.

There might the best efficacy be found and then over time, we would hope to broaden the case for using CMI early based on the fact that they.

May slow the progression of the disease are stabilized and progression of the disease. So I think this is a beginning of a strategy to establish <unk> as first line therapy.

Okay great.

Anything you want to add.

Maybe one or two things Jason first is that having evidence certainly helps inform guidelines guidelines will then certainly helped kind of a second point.

From a payer point of view.

Maybe get rid of the step at it that we have.

We have I should say as a category through a beta blockers and calcium channel blockers, which from our research seems to be important to physicians as well as patients. If there is evidence that a camden alone.

Treat the disease effectively then we think that will certainly be a good strategy commercially as well.

Great I appreciate the color.

Thank you.

And our next question will come from Joe <unk> from H C. Wainwright Your line is open.

Hello, Joe.

Thanks for all the details.

Looking forward to the start of the case, yes, so Robert I'm going to give you a bit of a run on sentence here with my question.

Give me a little patience here, so with regard to the initiatives.

Cost savings.

Savings and what have you would you consider the company right sized at this point or can we expect any potential additional cost savings and then with regard to app camped in.

Since this is a.

Our broad geographical study are there any particular geographies that might have enhanced focused by you with regard to clinical trial conduct or a treatment regimens that might be different from other regions.

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

So you're right that was a long sentence, but I'm trying to remember the component parts. So let me start with.

I remember to be the first part I do believe and Qing can comment on this too if he likes.

That we went through a very.

Significant cost cutting exercise critically assessing what we need to be doing in 2023 to align better with the new reality, a reality that has us focused on our fee Kimpton and were only <unk> because of the CRO is not.

Part of our near term future.

And recognizing that <unk> was not progressing in phase III, we needed to see where we could redeploy people to have them focused on that which was now our new priority and that's in our fee Kimpton first second and third.

And in order to do that we looked at outsource spending we look at contractors and consultants and we looked at our internal head count. We also looked at plans to grow head count.

And we set some aggressive targets and we met those targets and I think the team here at sort of kinetics did a great job.

Pulling all in the same direction to ensure we could vary meaningfully reduce operating spending not just over the long term, but in the nearer term so as to extend cash runway this year.

And that's what we achieved when we gathered for the Q1 earnings call. We knew we had ambitious targets and we have not yet concluded that exercise. We did conclude that exercise in Q2, and I think people tightened their belt quite substantially.

So I think we are right sized for what our current priorities and knowing where we are today recognizing that kimpton.

Camden is going to be paving the path for this company and we have to be in the best position to capitalize on that as soon as we know more from Sequoia and that'll be end of this year.

So let me see firstly, if king has anything to add to that.

I think Rob will cover so covered it well the only thing I would add is part of our strategic planning process. We are also contemplating different scenarios if.

So clear readout.

Does not meet our expectations then we have scenario planning to address those but obviously you will have to wait for data.

Before executing anything.

I think the next part of your sentence related to geographic.

Variability potentially in where we noting anything or preparing for anything maybe I'll turn to 30 or Steve to speak to that.

Sure. So I'll take that one this is Steve speaking.

Your question alluded to where there is.

Specific geographies that were targeting.

I think that the strategy that cytogenetics is employed has been to cast a wide net.

Capture all geographies you are right that there are treatment.

Strategic differences in how patients are treated in different parts of the world. However, the way that Sequoia was designed.

Captures all patients who have symptomatic obstructive HCM independent.

What medical treatment they have available to them, whether it includes disopyramide or not.

Yes, the exception would be Japan, where they have.

Fabienne between therapy, and we're not running the study in Japan as you know.

<unk>.

Yeah.

But in our independent of the availability of septal reduction therapy, whether it be septal myectomy or alcohol septal ablation.

Seeing that we do have an endpoint that does it.

Measure.

The impact of <unk> on the eligibility of these patients for that and I think.

If you take a step back and look at the strategy that we've employed for HCM at large is that where we have a <unk>.

<unk> program not only is targeting.

Patients with <unk>.

Obstructive HCM independent of geography, but all patients with HCM independent of phenotype, including non obstructive.

Patients patients with Midland Tequila obstruction that you've seen with al.

Redwood HCM cohort four.

As well as.

Hopefully in the future.

Groups.

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

Yes.

Okay.

Yeah, I'll take that I think.

<unk>.

For for Maple Theres, a lot of enthusiasm, giving me a question that we're asking in that study.

And that patient population is a little different than.

Then the other OE Sam populations that have been studied to date.

And obviously there are no.

Large HCM studies ongoing with regards to <unk>.

We think it's the first time a novel therapy has been studied in HCM I think investigator enthusiasm will be high.

Across the board.

Thank you for the answers everyone.

Thank you Joe.

Thank you.

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

Hi, guys.

This is Sean on for Dan Thanks for taking the question can.

Can you talk about the strategic logic behind us sole primary endpoint of GCC Q for Acacia given the parallel novel study you haven't taken into an <unk>.

Primary.

Physician and FDA feedback drove that decision and is the 36 week endpoint versus a 48 week time point and Odyssey.

Entirely driven by the expected duration of the titration period, and if not can you go into that decision making.

Sure I'll ask Steve to speak to those questions. Please.

Okay.

Sure. So this is Steve.

The primary endpoint.

<unk> as I mentioned earlier on is the.

So end point of change in <unk>, and we pick that based on our experience from our phase III study the Redwood code, Florida was presented and you've seen the data.

We also are aware of that.

The majority of patients who.

Have non obstructive HCM are receiving therapy with either a beta blocker or calcium channel blocker actually mostly a beta blocker.

And as you know that impact.

<unk> to achieve a significant change in peak <unk>.

And we felt that if we were to incorporate these two endpoints as us.

Our composite.

Mary endpoint or dual primary endpoints for that matter.

We would hamper.

Likelihood of success.

Obviously exercise capacity is important.

And we have incorporated this.

Bobby mentioned.

As a key secondary endpoint exercise capacity as measured by cardiopulmonary exercise testing.

But in essence, we felt that separating those two would increase the likelihood of technical success for Acacia at Sam.

There was a second part of the question you asked with regards to <unk> 36 versus <unk> 48 weeks of therapy.

I think.

We've chosen 36 weeks.

That gives us I think plenty of time to get to the maximum effects, we have a relatively.

Short titration period in our study.

As <unk> by <unk>.

Executed in Sequoia and.

We've chosen that Youll see as we mentioned later patients will be followed up after that primary endpoint for longer and we will have the opportunity to see if theres any other accumulating efficacy overtime.

Thanks for your question.

Thank you.

And our next question will come from tests from narrow from Jpmorgan. Your line is open.

Hi, Robert and thank you so much for taking our question.

I wanted to ask a question on HCN epidemiology today, if I could.

<unk> historically talked about a patient population of 190000 eus with diagnosed obstructive HCM.

Undiagnosed patient population on top of that.

As I recall.

<unk> had talked about 75000 identified diagnosed obstructive patients that.

We saw them quote around the time of launch.

Can you help us close what the gap might be there, we just really like to get a better understanding of where your latest thinking on epidemiology in obstructive HCM.

Think about diagnose patients here at the time of a potential launch and where you might see that evolving with time. Thanks. So much.

Sure thing I'm going to turn to Andrew.

Who is very focused to these matters and also how the literature is evolving here.

Sure. So thanks for the question Andrew So there are multiple publications some older.

Two lower numbers of epidemiology.

<unk> did a five year longitudinal study on claims data on actual patient on patients that are actually diagnosed and then.

Corroborated that with.

Publications that are more recent around the 190 I can't speak to where BMS gets their number I can only speak to that we're very confident in that 190000 number and that number is growing a little higher than the rate of population on the OE Kim.

And again, that's based on actual data in claims.

<unk>.

We're going from that number.

190 of that 190.

From our research. Furthermore, I think it's important to understand that probably around 60% of those patients are.

Not currently optimized with treatment and still having symptom.

Symptoms and Thats really the target of therapy.

Okay.

Great. Thanks, so much for taking our question.

Thank you.

And our next question will come from Yasmin Rahimi from Piper Sandler Your line is open.

Good afternoon.

Hi, Robert first of all congratulations on the <unk> anniversary and what a wonderful achievement for the entire.

Company.

Two questions that are directed to Steve and fatty and maybe also Andrew could comment on it a question that we're getting from quite a lot of clients right now.

What do we want to see from a safety perspective.

Coming to Korea that could warrant a differentiated echo monitoring.

Would it be a favorable ramp I think a lot of clients understand the absence of DDI.

Want to understand sort of.

How does Sequoia data could maybe just get us really comfortable on the differentiated label.

I really appreciate your thoughtful comments around around these question and I'll jump back in the queue.

Sure I'll turn first to fatty, but I'll underscore of course.

What we're going to share our comments based on what we've seen already in Redwood and forest.

What we hope to and expect to see in Sequoia, but thats still to be known and Camden remains an investigational compound so with that I'll turn to <unk> to answer your question.

Yes.

Thank you.

In terms of.

Echo monitoring we hope to see that the data from forest will support a.

Frequency of Echo monitoring that.

<unk>.

Manageable by patients and their physicians I'm not going to really make any comparative statements as you asked for differentiation, but.

You can imagine.

In forest now monitoring patients for every three months.

We would.

Ultimately those data would support that.

The lack of.

Treatment decisions are safety events that are driven by all of those echos I think everyone recognizes the echocardiograms are a burden to the sites and to the medical system.

<unk> should be a general.

Incentive to minimize the burden on patients and the medical system and so on.

We're very happy with how forest has been proceeding.

As I said.

Earlier, we know patients out to two years.

And we hope that that safety database will lend itself to making a compelling argument for.

Echo monitoring that say might be twice, a year or even yearly at some point.

And in terms of our Rems I think the question really is what physician education is going to be necessary.

In order to use <unk> NAND.

I can't really comment so specifically to your question other than it will be informed by the safety information and the other profiles of Abbvie Campton, which.

To date, we don't think we have any meaningful drug drug interactions.

And in other aspects of the drug that.

That would.

Not require extensive physician education so.

Stay tuned.

Data evolves.

We will hopefully have more to say.

What's been especially reassuring.

In the <unk>.

Clinical trials data that we've seen to date is that.

We haven't observed any early terminations as a result of ejection fractions.

Unexpectedly falling in patients with obstructive HCM.

And we'll be looking to see if that may continue with the unblinded of the Sequoia results, but thats the kind of thing that may ultimately factor into what would be considered a risk that would be mitigated by a potential rems program and that's something that.

We're continuing to be quite hopeful for.

Thank you so much for them.

I'll jump back in the queue.

Thank you.

And our next question comes from Salim Sayed from Mizuho. Your line is open.

Great. Good afternoon, guys. Thanks for the question.

So Robert the number one question, we get obviously I'm sure you get it to you is why is the stock back down at 30 Bucks I think a lot of people are trying to sort out.

Why exactly it's there and nobody really thought it would be there.

At any point in 2023 really.

And then the reasons that we hear from folks it seems.

It seems to be pointing to is the <unk> line.

And then potential deal risk around the assay and I know Theres a one question rule. So we don't really focus on the deal risk piece here.

So given we are.

Four months or so away from Sequoia readout, just curious in your in your discussions with potential partners.

That particular aspect of the story is being perceived.

Do people do you think folks will want to see that data or.

Can you can you make.

The decision to go.

Go it alone or partner.

Prior to that data does give us if you can just.

Set aside some context for us.

Timing of a potential deal if any.

Go it alone or partner decision. Thank you.

So any deal that we might do would have to be a deal that met our expectations to be able to go to Europe on our own but would be supplemented by potential partners involvement and the hurdle is very very high.

We're not looking to do a deal for the deal's sake and were we to do any deal it would be as would be enabling of our continued corporate development with emphasis on our own to go to Europe , you heard Andrew say that we've already hired our head of Europe , we're hiring some other folks there.

Our intention to build out our commercial business in Europe .

So with our last earnings call I did indicate we were opening the aperture.

To partnering <unk> kimpton potentially in Europe , but with focus to Japan and as would only be done if we could make a case that thats better than going it alone and while I won't comment on what we've concluded I will say that we continue to execute on our go to Europe strategy.

And we're looking very critically at.

What might be any alternatives.

That plan, we think it's in the interest of shareholders that we objectively approach that decision. We've done that we're doing that and we continue to execute well on our own plans.

That answers the question.

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

Sure thing.

Thank you.

Our next question comes from Carter Gould from Barclays. Your line is open.

Hello Carter.

Hey, guys you've got on the line for Carter, Thanks for squeezing us in here.

We just have a question on expectations for what you will disclose in the Sequoia topline press release.

What extent does the myocardial level of disclosure.

<unk> is a good benchmark for what to expect and then as a follow up to that.

Considering sequoia out.

On the horizon, what should we anticipate from you and or what will your presence the HSA and <unk> meetings.

Meetings this year. Thank you.

So we're going to be out in full force at Hff's, a and AA.

This year.

As well as the HCM Society meeting in October which falls in between.

What I'll also say is.

And as much as we've guided to results for Sequoia by the end of the year, it's reasonable to expect.

But the full on presentation of those results would occur not at one of those meetings, but perhaps at ACC, which is in April 2024, and ACC has.

Its own guidelines and restrictions as to what would be permitting of our presentation and their scientific sessions.

Which are different from other meetings.

If I recall correctly when myocardial presented its data it was leading into the ESC meeting that year ESC with different restrictions then does ACC.

So I don't know that you can compare what will be our disclosure in a topline release to theirs.

But what I will say is we will disclose that which we determined to be.

Material.

And informative to shareholders without jeopardizing our presentation.

ACC and until we see the data, it's hard to know exactly where that falls.

Thank you.

Our next question comes from Justin Kim from Oppenheimer <unk> Co. Your line is open.

Hello, Justin.

Hi, Robert and good evening everyone.

Maybe just.

A follow up there I just wanted to ask a question with respect to the presence that AJ and and maybe just what we might expect from for it.

Presumably you'd have some experience from sort of Sequoia complete or I'm. Just wondering like is that something we can expect to see how some of those participants of the pivotal did once they were off the drug and re titrated or titrated up from placebo.

And sort of see that.

Shannon.

This year.

Yes, so we're not guiding to any new data from forest at HCA, but rather you heard us referred to baseline demographics from Sequoia The HCM Society.

As it relates to forest, it's not.

Been our practice that we would provide.

<unk> set every medical meeting, but certainly we want to provide meaning.

A meaningful updates when there is.

Significant new data to share and Thats more likely is will be coming at ACC next year.

Okay. Thank you.

Thank you.

And our last question will come from Sri Crippa Devorah Khanda from Cheerless Securities. Your line is open.

Good afternoon.

Good afternoon, Robert and good afternoon <unk>. Thank you so much for taking my question.

Just to follow up on what Robert you mentioned earlier in terms of.

At the end of the.

Drop I think previously you had mentioned that there could be an unblinded event. If the lvs drops were fairly low I was wondering if you can.

What is the bar for barley now and.

We haven't heard about it so far can we assume that it didn't happen. Thank you.

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

Alright, I think.

The protocol is pretty clear that if.

We see a patient as an ejection fraction fall below 40%.

That the investigator and site of kinetics should be informed.

To date, we havent seen we havent been informed of any such events.

And which is quite reassuring, we're not privy to any other drops in ETF. The rest are blinded and will remain so until the study is complete.

Alright, thank you so much.

Yeah.

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

Thank you operator, and thanks to everybody who joined US on this call today.

Obviously quite a lot is going on at our company as we are re prioritizing focusing to <unk>, reducing spending and advancing our pipeline and we think we're doing that very well aligned with what shareholders should expect of us as we come forward to these important milestones.

We look forward to keeping you abreast of our progress we welcome your further questions and look forward to updating you throughout the remainder of this year without operator, we can bring this call to a close.

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

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Good afternoon, and welcome ladies and gentlemen to silo kinetic second quarter 2023 conference call.

At this time I would like to inform you that this call is being recorded and then 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 one question per participant.

I will now turn the call over to Diane Weiser Psychokinetic Senior Vice President of corporate Communications and Investor Relations. Please go ahead.

Good afternoon, and thanks for joining us on the call today.

<unk>, President and Chief Executive Officer.

We will begin with an overview of the quarter and recent developments.

I'd now like EVP of R&D, we will provide updates related to epic Hampton focus to Sequoia HCM Redwood HCM and finance HCN, Steve Heitner VP clinical research and therapeutic area lead cardiovascular is filling in for Stuart Kupfer today, and we'll provide additional updates for etsy Camden.

And relating to Maple HCM and the expected start of Acacia HCN and decal as EVP and Chief commercial officer will speak about commercial readiness activities for ASE campaign.

Market opportunity, 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 revised spending guidance for 2023 finally, Robert Brown will provide an update on our early clinical program and is clear.

<unk> comment and review expected upcoming milestones.

Please note that questions are the following discussion including responses to questions contain statements that relate to future events and performance rather than historical facts and constitute forward looking statements.

Actual results may differ materially from those projected in these forward looking statements.

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 second quarter 2023 financial results filed on form 8-K that was furnished to the SEC today.

They take no obligation to update any forward looking statements. After this call and now I will turn the call over to Robert.

Thank you Diane and thanks for joining us on the call today.

We made substantial progress in the second quarter, not only by advancing and broadening the development program for <unk>, but also by making further strides in our earlier stage specialty cardiovascular pipeline.

Saudi and Steve will elaborate our comprehensive clinical trials development program for <unk> Camden is firing on all cylinders during the quarter, we completed enrollment in Sequoia HCM, we began maple HCM and we prepared to start Acacia HCM the phase II.

<unk> clinical trial of <unk> in patients with non obstructive HCM.

We have accelerated the timeline for this trial and we now expect to open the trial to patient enrollment next month.

It's notable that very soon we will have three ongoing phase III clinical trials for Alfie Campton, plus the open label extension, which is a testament to our corporate re prioritization and the excellent work of our dedicated regulatory technical operations clinical research and operations teams.

As well as the high level of enthusiasm and diligence of our clinical site investigators and their staffs.

Now that enrollment in Sequoia HCM is complete study conduct is progressing and we remain on track to share top line results by the end of this year.

This trial has progressed through the dose escalation phase for all patients and we are monitoring key metrics in blinded data such as patients randomized baseline characteristics standard deviation around endpoints early terminations and missing data and I am pleased to report.

That across all of these measures.

HCM is proceeding well and meeting or exceeding our trial design assumptions. Moreover, alongside our preparations for the reporting on topline results are regulatory supply chain and commercial readiness teams have been actively engaging in numerous activities.

Including go to market plans that build towards potential approvals and commercialization of <unk> Camden.

Andrew will elaborate on some of those plans shortly.

Well I'll ask the Camden may be top of mind in parallel our clinical research activities continued to push forward on other fronts as well in the second quarter, we advanced CK 586.

Cardiac myosin inhibitor into a phase one study we continued the phase one study of CK 136, our cardiac troponin activator and we continued non clinical research and IND, enabling activities towards our goal of submitting one to two new <unk> over the next one to two years.

<unk> on our priorities and pipeline, including preparations for the potential approval and commercialization of <unk>.

That's all going to enable us to further extend our cash runway Ching will provide more details and updated financial guidance for 2023 later in this call.

As you will hear today, we're moving forward with momentum into the second half of the year with a broad early and late stage pipeline ongoing research in a stronger financial Foundation.

Giving us conviction and confidence in achieving our goals for the rest of the year as well as setting us up well afterwards with that I'll now turn the call over to <unk>.

Thanks, Robert and the second quarter, we made great progress across the broad development program for <unk> Camden. Most importantly, we completed enrollment and randomization in Sequoia HCM, the pivotal phase III clinical trial of <unk>, Camden with 282 patients randomized.

Surpassing our enrollment target of 270 patients and making it now the largest randomized clinical trial of an investigational therapy ever conducted in patients with obstructive HCM.

Conduct a quiet HCM benefits greatly from our growing experience and learnings related to the use of cardiac myosin inhibitors as well as measures employed in the evaluation of their effectiveness.

<unk> MK and physician preferences.

I am pleased to share that we also met or exceeded our enrollment objectives in terms of geography and patient characteristics.

It's quite HCM enrolled in diverse patient population from the U S, China, Europe , and Israel patients enrolled exhibit a substantial deficit in exercise capacity a key element of the enrollment criteria considering that the primary endpoint assessments for a potential increase in exercise capacity.

Further to this point equates employees and individualized dose titration strategy, which is designed to optimize dose selection and maximize the potential benefit risk profile of <unk> canton.

In fact at this point all patients have progressed through at least the eight week visit which marks the end of the dose escalation phase.

Cross all these measures we feel Sequoia HCM is preceding per plan, certainly matching or exceeding our trial design assumptions.

All of this work has put us on track to report top line results by the end of the year.

Now that all the patients from Sequoia HCM are randomized we expect to also present baseline characteristics.

Of these patients at the ACM Society scientific sessions in early October .

Also during the quarter, we presented new data in patients with non obstructive HCM from cohort four of Redwood HCM at the heart failure 2023 Congress.

Building on initial data presented earlier this year at ACC.

Data showed that following only 10 weeks of treatment.

Happy Camden was associated with an average improvement in the clinical summary score of the Kansas City cardiomyopathy questionnaire or <unk> CSS.

Of 11 points with 58% of the patients experiencing a clinically meaningful reduction in symptom burden of five points or more.

Treatment with Abbvie Camden was also associated with improvements in NY at Shane functional class angina frequency high sensitivity cardiac troponin I in NT Pro BNP.

We are pleased to see that most patients were able to achieve the highest available dose of 15 milligrams with no drug discontinuation due to adverse events related to App canton, no treatment interruptions or downtown duration events related to LTE up less than 50%.

And no events with LTE up less than 40%.

We remain confident in the promise of <unk> Camden in non obstructive HCM and look forward to starting a phase III clinical trial in non obstructive HCM soon Steve.

Steve will elaborate on this trial in a moment.

We're pleased to see that nearly all patients elect to continue into the open label extension and we now have patients who have surpassed two years on Abbvie campton enforced HCM.

In addition to providing data on the efficacy of long term use of <unk> in the treatment of obstructive HCM.

We will continue to periodically shared data from <unk>, which we expect to factor importantly into the next in class profile for Camden and shed light on its potential ease of use and safety durability of effect and Tolerability.

With that I'll turn the call over to Steve who is filling in for Stewart, who is unable to join our earnings call today, Steve will speak to the expanding development program for Abbvie Captain.

Thanks Patty.

During the quarter, we announced the start of patient enrollment in Maple HCM.

Phase III clinical trial of assay Camden as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM.

We are pleased to report that the first patients have recently been randomized.

While we do not foresee that Maple HCM is critical path to the potential for first FDA approval.

If successful in demonstrating that ASIC kimpton is superior to <unk> at all with respect to improvement of exercise capacity heart failure symptoms and New York Heart Association functional costs, we would expect to submit the results from this trial as a supplemental NDA for potential label expansion.

<unk> has the potential to meaningfully expand how physicians foresee using epic Hampton as would likely be reflected in the treatment guidelines potentially elevating it to first line therapy and potentially expanding the commercial opportunity.

At the same time.

In recent months, we have been continuing preparation for the pivotal phase III clinical trial of <unk> in the non obstructive HCM based on the favorable data arising from cohort four of Redwood HCM.

As noted in today's press release, we are calling this trial, Acacia HCM and keeping with our theme of northern California trees for the program.

Acacia HCM stands for assessment, comparing <unk> to placebo on cardiac endpoints in adults with non obstructive HCM.

This pivotal clinical trial of <unk> in patients with non obstructive HCM is expected to open for patient enrollment next month, which is ahead of schedule underscoring the high level of enthusiasm for this next trial.

You can advance I'd like to share a few key points about its design.

<unk> is a phase III multicenter randomized double blind placebo controlled clinical trial expected to enroll approximately 420 patients with symptomatic non obstructive HCM.

Primary endpoint is the change in <unk> clinical summary score from baseline to week 36.

While the primary analysis will take place at 36 weeks patients will continue on treatment with Abbvie Camden No placebo for up to 72 weeks in order to evaluate additional secondary and exploratory analyses, including the time to the first cardiovascular event.

As previously mentioned, we expect to initiate patient dosing.

Acacia HCM in September .

With that I'll turn the call over to Andrew.

Thanks, Steve our commercial readiness team is laser focused on key work streams in support of the potential approval and commercialization of Etsy Kimpton in both the United States and Europe .

We have also conducted additional market research to gain greater clarity on HCM patient and HCP experiences as well as how hep's payers and patients would respond to our potential product profile.

Any of these plans will be augment it once we have results in hand from Sequoia HCM, but our research to date is encouraging in terms of payer patient and physician interest as well as enthusiasm for a next in class cardiac myosin inhibitor.

Our research continues to explore distinguished distinguishing characteristics of assay candidates, including its potential drug drug interaction profile and dose titration, which will be important to patients and prescribers.

We believe there is and will remain a large unaddressed population of patients with obstructive HCM that may benefit from <unk> if approved.

We are fortunate to have been able to redeploy members of our commercial team who had previously been focused on OMA captive <unk> to now focus on epic Hampton, a corporate pivot that has enabled the acceleration of our planning.

An efficient operator operated visualization of our preparations for the potential approval and commercialization of <unk> Kimpton.

Meanwhile, conversations with payers progressed in accordance with compliant preapproved payer interactions with productive dialogue and education, not only about the HCM landscape and the potential of cardiac myosin inhibitors, but about <unk> Camden, specifically in which they remain highly interested.

We look forward to continuing to develop expanded hone our go to market plans for the potential approval and commercialization of <unk> canton and simultaneously deliver on step wise.

<unk> systematic element of the pre commercial runway.

Toward that end turning to market opportunity in the in Europe . We are pleased to have made our first new hire in Europe , bringing on our head of Europe , who has a proven track record in launching new products delivering growth and achieving expectations in European and international markets within the rare disease in cardiology space.

Looking forward to having both our European head of access and medical affairs join us by the end of Q3.

We are pleased to be attracting top talent, thanks to our strong culture and pipeline.

With that I will turn the call over to Robert Weiner.

<unk> ALS are.

Quarter, 2023, G&A expenses or $39 7 million down from $42 7 million in Q2, 2022, due primarily to reduced outsource spending on commercial readiness activities and now Ching will review, our financial outlook and corporate development strategy.

Thanks Robert.

We ended the quarter was approximately $593 million on the balance sheet, which represents nearly two years of cash runway based on our revised 2023 spending guidance announced today.

I will now elaborate.

Previously we had expected our operating expenses for 2023 to be in the range of $420 million to $450 million and net cash utilization to be approximately $350 million to $375 million.

We have reduced our operating expenses to be in the range of $390 million to $410 million in response to our receipt of a <unk> from the FDA regarding the NDA for <unk> <unk>.

And the discontinuation of courage AOS.

Our net cash utilization is now expected to be approximately 310 to 320 million. This reduction represents savings of approximately 15%.

Which demonstrates initiatives to reduce spending and limit head count growth in light of these setbacks.

Through this transaction was the royalty pharma, we also remain eligible for two additional tranches of capital.

We choose to take them.

$75 million upon our potentially sharing positive results from the Sequoia HCN and 100 million upon the acceptance of NDA submission for <unk> in the U S.

We view this transaction as the equivalent to a line of credit, which we can leverage to add to our balance sheet in 2024 if necessary.

Towards that objective, we're in the midst of our annual strategic planning process, which critically evaluate <unk> corporate and pipeline scenarios contingencies and risk mitigation and.

And informed investment decisions as we calibrate with board and shareholder alignment and with that I will turn the call back over to Robert Blum. Thank.

Thank you Ching.

As you've heard in the second quarter, we made substantial progress across the pipeline.

To add to what my colleagues mentioned during the quarter. We also participated in a type a meeting with the FDA to understand FDA views related to the CRM for <unk>.

And outside the United States <unk> is under review in Europe , and in China and during the quarter. We continued to support these reviews and address questions from regulators.

We also made progress with our earlier stage pipeline during the second quarter, we advanced CK 586 into a phase one single ascending dose and multiple ascending dose study and we're pleased with initial progress to date.

CK, 586% is a cardiac myosin inhibitor that is mechanistically distinct from Matthew Camden and has the potential application for patients with heart failure with preserved ejection fraction or half path for which there are few treatment options for some people would have passed their disease in many ways mimics non obstruct.

<unk> HCM due to their thick and hearts and increased cardiac contractility and symptom burden encouraging data from cohort four of Redwood HCM and patients with non obstructive HCM or potentially a proxy for the therapeutic application of cardiac myosin inhibition in this patient population.

<unk> as we hope to further investigate with CK, 586% in 2024.

Are filed we will have advanced three to four new drug candidates in a relatively short time span and impressive figure for any biopharmaceutical company, which will enable us to expand our pipeline. According to our vision 2025 goals.

There is a great deal of work progressing behind the scenes and I must thank our diligent and dedicated employees for their commitment to our future.

As we continue to seek potential partners for <unk>, <unk> and Nasty campaign.

Since opening the aperture to partnering for <unk> in Europe . In Q2, we have been actively engaged with potential partners and we're pleased with the progress and level of interest that we've received as well as well as the diligence and deal discussions as it relate to both our <unk> and <unk>.

Our future is only made possible by what came before and this year, we've been celebrating our 20 <unk> anniversary with a recent open house held at our headquarters in South San Francisco, We invited our local community of partners former employees investors patients advocates and community leaders and we are.

<unk> been joined by a steam local city and county elected officials as well as staff, representing California State Senators.

We are grateful to celebrate this joyous occasion with our long time supporters and friends, recognizing though that while much is the same as it was when we started Sato kinetics of <unk> 1998. Much has also changed as we've made progress towards our ambitious goals and still the best is yet to come when we hoped.

We bring forward, our first approved medicines to the benefit of patients.

Now I'll recap our upcoming milestones.

For <unk>, we expect to share top line results from Sequoia HCM by the end of the year and we expect to continue enrolling patients in Maple HCM and start Acacia HCM in September 2023.

And we continue to advance our ongoing go to market strategy during 2023.

And finally for CK 586, we expect to continue to enroll the phase one study throughout this year.

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

Thank you.

As a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again in.

In the interest of time, we do ask that you. Please kindly limit yourself to one question at this time please.

Please standby, while we compile the Q&A roster.

And our first question will come from <unk> <unk> from UBS. Your line is open.

Good afternoon.

Hi, good afternoon, its bottom on behalf of ash warm up from UBS. Thanks for taking our questions.

I just have a quick one on its 8586.

Just looking at the mechanism is very similar.

From Pascal and then like you noted.

What gives you confidence that this mechanism of action will work for patients.

Bob.

And why not pursue the ads also in obstructive HCM and just a quick second one like what would be the benchmark for efficacy and what clinical companies are you looking for in this phase one trial.

Sure. So I'll turn this over to Saudi and to Steve, but firstly before I do I'll just say that.

Teekay 586 is intentionally.

Being advanced as would be distinguishable from <unk>, which is being developed as you know in obstructive disease and non obstructive HCM now and.

And were we to have identified any issues or liabilities with Aussie Kimpton then perhaps.

CK 586 could be developed in those same indications, but we are not aware of any such issues and hence why we think 586 should stand on its own in a different disease state. So maybe now I'll turn it over to <unk> to speak to why we believe this mechanism is translatable to have passed.

And what we may be looking for both as it relates to phase one data and ultimately beyond that in half path.

Thanks Robert.

As you mentioned CK 586.

As a distinct mechanism of action than <unk>, but it's still a cardiac myosin inhibitor and the distinction is really a subtle point of where it binds in.

In what form of the motor protein it inhibits.

Fundamentally it does the same thing and reduces the number of active cross bridges and reduces cardiac contractility and has a shallow exposure response relationship.

Does abbvie campton.

And so fundamentally behaves very similarly.

As Robert said.

Abbvie Campton is doing wonderfully we don't really.

I think we need another drug in HCM, but <unk> is a much different population.

And.

And a very large population at that.

Well, we are intending with 586 is to focus in the different indication and to them.

And do a subset of patients with half pet foods phenotypes mimic some of our NH Sam patients they have.

Larger hearts, they can hearts high filling pressures higher biomarkers.

<unk>.

And poorer exercise tolerance in so many ways Theyre Athena copy.

For those that have genetic.

Non obstructive HCM.

So we will be advancing 586 in that direction, it's really premature for me to discuss what we'll be doing in phase III, rather than focusing I think in that population that most closely mirrors the <unk> population.

I hope that's helpful. Operator, maybe that will move to the next question. Please.

Great.

And our next question will come from row at Basin from Needham <unk> Company. Your line is now open.

And then when do you plan on presenting new data disclosures and medical meetings.

Sure so as it relates to both Maple and soon to start Acacia.

It's too early for us to be guiding us to rate of enrollment by do understand the question and we should get you that answer but lifts.

See how we get out of this startup phase and these.

Initial enrollments before we might start guiding to enrollment rates in conclusion.

I don't expect that there'll be any data from either of these studies in 2023 of course and as we look to.

Next year I think it's also premature.

We'll be in a better position to point to what to expect next year. When we do our Q4 earnings in February .

Thank you.

Thank you and as a reminder, we do kindly ask that you. Please limit yourself to one question at this time.

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

Hi, Thanks for taking my question.

Hi, Robert Thanks for taking my question and congrats on the progress.

We said in our prepared comments.

All patients or an acquirer now through the titration phase I was just wondering if you could comment on whether youre seeing what you expected to see in terms of the proportion get to target doses.

So thank you for asking and that's a notable.

Achievement as you highlight that we now are through that dose escalation phase keeping in mind, we're blinded to dose, but maybe I'll ask Steve if he wants to elaborate.

Well, Jason I think Robert just answer your question.

There's obviously a blinded study and we are in fact blinded to the actual dose administered.

Administered.

So we don't know the proportion of doses.

Patients are being exposed to an in Sequoia.

But do you have already seen some of the data that has been presented with regard to the forest HCM study, which is unblinded.

Where there is a nice balance shape distribution and the doses.

Patients being exposed to.

15, and 10 milligrams for the most part with a smaller proportion getting exposed to five and 20 milligrams.

Okay, great. Thank you.

Thank you Jason.

Thank you.

And our next question comes from Jason Szymanski from Bofa. Your line is open.

Good afternoon afternoon.

Congratulations on the progress and thanks for taking our question I wanted to circle back to some of your comments regarding maple in the possibility of broadening the label with ASIC Hampton to include used in the first line setting I'm curious what are you what do you see as the opportunity here I mean, obviously the addressable market is sizable but it seems like there could be.

<unk> potentially logistical or administrative hurdles.

Thinking about pushback from payers or potential capacity issues from community prescribers I mean do you see asset Kimpton is a valid option for all comers with obstructive HCM.

Yes, I think we're following the lead of investigators themselves in forest, who are choosing to take patients off of beta blockers and for reasons that matter importantly to physicians and patients and ultimately I think will be welcomed if may.

<unk> is successful by payers, maybe I will ask our clinical colleagues if they want to add anything to that and maybe also Andrew if he wants to.

Hi, Jason this is fatty I might just add that in the context of a drug that addresses the underlying causes the disease.

There is obviously opportunity for disease modification and so.

April is not addressed.

Designed to address that point.

Yeah.

In terms of thinking about drugs selected.

For patients at least we provide the evidence of which which are the current.

Number one choice since initiated versus a newcomer in the <unk>.

There might the best efficacy be found and then over time, we would hope to broaden the case for using CMI early based on the fact that they.

May slow the progression of the disease are stabilized and progression of the disease. So I think this is a beginning of a strategy to establish <unk> as first line therapy.

Okay, great. Thank you Andrew.

Anything you want to add.

While they may be one or two things Jason first is that having evidence certainly helps inform guidelines guidelines will then certainly help kind of a second point.

From a payer point of view.

Maybe get rid of the step at it that we have.

Camden alone.

Can treat the disease effectively then we think that will certainly be a good strategy commercially as well.

Great I appreciate the color.

Thank you.

And our next question will come from Joe <unk> from H C. Wainwright Your line is open.

Hello, Joe.

Hey, everybody. Thanks for all the details and looking forward to the start of Acacia So Robert I'm going to give you a bit of a run on sentence here with my question.

If you could give me a little patience here, so with regard to the initiatives.

Yes.

Cost savings and what have you would you consider the company right sized at this point or can we expect any potential additional cost savings and then with regard to app camped in.

Since this is a.

Our broad geographical study are there any particular geographies that might have enhanced focused bayou with regard to clinical trial conduct or a treatment regimens that might be different from other regions and lastly, with regard to Acacia are there any external.

<unk> that also assisted with regard to accelerating the start of the study thanks a lot.

So youre right that was a long sentence, but I'm trying to remember the component parts. So let me start with what I remember to be the first part.

I do believe and Qing can comment on this too if he likes.

That we went through a very.

<unk>.

The significant cost cutting exercise critically assessing what we need to be doing in 2023 to align better with the new reality.

<unk> that has us focused on our fee Kimpton and were only <unk> because of the CRO is not part of our near term future.

And in order to do that we looked at outsource spending we look at contractors and consultants and we looked at our internal head count. We also looked at plans to grow head count.

We set some aggressive targets and we met those targets and I think the team here at sort of kinetics did a great job.

Pulling all in the same direction to ensure we could vary meaningfully reduce operating spending not just over the long term, but in the nearer term so as to extend cash runway this year.

And that's what we achieved when we gathered for the Q1 <unk>.

Earnings call.

We knew we had ambitious targets and we have not yet concluded that exercise. We did conclude that exercise in Q2, and I think people tighten their belt quite substantially hence I think we are right sized for what our current priorities and knowing where we are today recognizing that.

Camden is going to be paving the path for this company and we have to be in the best position to capitalize on that as soon as we know more from Sequoia and that'll be end of this year. So let me see firstly, if king has anything to add to that.

I think Rob recover so covered it well the only thing I would add is as part of our strategic planning process. We are also contemplating different scenarios if.

So clear readout.

Does not meet our expectations then we have scenario planning to address those but obviously you will have to wait for data.

Before executing anything.

I think the next part of your sentence related to geographic.

Variability potentially in where we noting anything or preparing for anything maybe I'll turn to fatty or Steve to speak to that.

Sure. So I'll take that one this is Steve speaking.

To your question I alluded to where there is.

Specific geographies that were targeting and I think that the strategy that cytogenetics is employed has been to cast a wide net.

Capture.

All geographies you are right that there are treatment.

Strategic differences in how patients are treated in different parts of the world. However, the way that Sequoia was designed.

<unk>.

Captures all patients who have symptomatic obstructive HCM independent.

Of what medical treatment they have available to them, whether it includes disopyramide or not.

I guess, the exception would be Japan, where they have.

Fabienne <unk> therapy, and we're not running the study in Japan as you know.

But in our independent of the availability of capital reduction therapy, whether it be septal myectomy or alcohol septal ablation.

Seeing that we do have an endpoint that does.

Measure.

The impact of <unk> on the eligibility of these patients for that and I think.

If you take a step back and look at the strategy that we've employed for HCM at large is that where we have a.

Development program not only is targeting.

Patients with <unk>.

Obstructive HCM independent of geography, but all patients with HCM independent Athena type, including non obstructive.

Patients patients with mid ventricular obstruction that you've seen with al.

Redwood HCM cohort four.

As well as.

Hopefully in the future of the subgroups.

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

Yes.

Okay.

Yeah, I'll take that I think.

<unk>.

For for Maple Theres, a lot of enthusiasm, giving me a question that we're asking in that study.

And that patient population is a little different than.

And then the other OE Sam populations that have been studied to date.

And obviously there are no.

Large HCM studies ongoing with regards to <unk>.

We think it's the first time a novel therapy has been studied in HCM I think investigator enthusiasm will be high.

Across the board.

Thank you for the answers everyone.

Thank you Joe.

Thank you.

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

Hi, guys.

This is Sean on for Dan Thanks for taking the question.

Can you talk about the strategic logic behind us sole primary endpoint of GCC Q for Acacia given the parallel novel study you haven't taken in Q2 as co primaries.

Position and FDA feedback drove that decision and is the 36 week endpoint versus a 48 week time point and Odyssey.

Highly driven by the expected duration of the titration period, and if not can you go into that decision making.

Sure I'll ask Steve to speak to those questions. Please.

Sure. So this is Steve.

The primary endpoint for <unk> as we mentioned earlier.

The sole endpoint of change in <unk>, and we pick that based on our experience from our phase III study the Redwood code, Florida was presented and you've seen the data.

We also are aware of that.

The majority of patients who.

Have non obstructive HCM are receiving therapy with either a beta blocker calcium channel blocker actually mostly a beta blocker.

And as you know that impact.

<unk> to achieve a significant change in <unk>.

And we felt that if we were to incorporate these two endpoints.

A composite primary endpoint or dual primary endpoints for that matter and we would hamper.

Likely hood of success.

Obviously exercise capacity is important and we have incorporated this.

Bobby mentioned.

As a key secondary endpoint exercise capacity as measured by cardiopulmonary exercise testing.

But in essence, we felt that separating those two would increase the likelihood of technical success for Acacia its Sam.

There was a second part of the question.

Just you asked with regards to <unk> 36 versus <unk> 48 weeks of therapy.

I think.

We've chosen 36 weeks.

That gives us I think plenty of time to get to the maximum effects, we have a relatively.

Short titration period in our study.

Is mirrored by <unk>.

We executed in Sequoia and.

Thanks for your question.

Thank you.

And our next question will come from tests from narrow from Jpmorgan. Your line is open.

Great great.

Hi, Robert and thanks, so much.

Much for taking our question.

I wanted to ask a question on HCM epidemiology today, if I could.

<unk> historically talked about a patient population of 190000 in the U S with diagnosed obstructive HCM.

Of course, an undiagnosed patient population on top of that.

As I recall.

<unk> had talked about 75000 identified diagnosed obstructive patients that.

We saw them quote around the time of <unk> launch.

Can you help us close what the gap might be there, we just really like to get a better understanding of where your latest thinking on the epidemiology in obstructive HCM.

Do you think about diagnose patients here at the time of a potential launch.

Where you might see that evolving with time, thanks, so much.

Sure thing I'm going to turn to Andrew.

Who is very focused to these matters and also how the literature is evolving here.

Sure. So thanks for the question Andrew So there are multiple publications some older.

Speak to lowered numbers of epidemiology.

We did a five year longitudinal study on claims data on actual patient on patients that are actually diagnosed and then <unk>.

Our operated that with.

Publications that are more recent.

Around the 190, I can't speak to where BMS gets the number I can only speak to that we're very confident in that 190000 number and that number is growing.

Higher than the rate of population on the OE can.

And again, that's based on actual data in claims.

No.

We're going from that number.

190 of that 190.

From our research. Furthermore, I think it's important to understand that probably around 60% of those patients are.

Not currently optimized with treatment and still having simpler.

Symptoms and Thats really the target of therapy.

Okay.

Great. Thanks, so much for taking our question.

Thank you.

And our next question will come from Yasmin Rahimi from Piper Sandler Your line is open.

Good afternoon.

Hi, Robert first of all congratulations on the <unk> anniversary and what a wonderful achievement for the entire.

Company.

Two questions that are directed to Steve and fatty and maybe also Andrew could comment on it a question that we're getting from quite a lot of clients right now.

What do we want to see from a safety perspective, and the upcoming to Korea that could warrant a differentiated echo monitoring and what.

B a favorable ramp I think a lot of clients understand the absence of DDI that may want to understand sort of.

How does Sequoia data could maybe just get us really comfortable on the differentiated label.

And I really appreciate your thoughtful comments around around these question and I'll jump back in the queue.

Sure I'll turn first to fatty, but I'll underscore of course that.

What we're going to share our comments based on what we've seen already in Redwood and forest and what we hope to and expect to see in Sequoia, but thats still to be known.

Camden remains an investigational compound so with that I'll turn to <unk> to answer your question.

Yes.

In terms of.

Echo monitoring we hope to see that the data from forest will support a.

Frequency of Echo monitoring that.

<unk>.

Manageable by patients and their physicians I'm not going to really make any comparative statements as you asked for differentiation, but.

You can imagine.

In forest now monitoring patients for every three months.

We would.

Ultimately those data would support.

A lack of.

Treatment decisions are safety events that are driven by all of those echos I think everyone recognizes the echocardiograms are a burden to the sites and to the medical system.

And I think there should be a general.

Incentive to minimize the burden on patients and the medical system and so.

We're very happy with how forest has been proceeding.

As I said earlier.

Earlier, we know patients out to two years, and we hope that that safety database will lend itself to making a compelling argument for <unk>.

Echo monitoring that say might be twice, a year or even yearly at some point.

And in terms of our Rems I think the question really is what physician education is going to be necessary.

In order to use <unk> NAND.

Yes.

Can't really comment so specifically to your question other than it will be informed by the safety information and the other profiles of Abbvie Campton, which.

Date, we don't think we have any meaningful drug drug interactions and and other aspects of the drug that.

That would.

Not require extensive physician education so.

Stay tuned as the data evolves I think we will hopefully have more to say.

Whats, especially reassuring.

In the clinic.

Clinical trials data that we've seen to date.

We haven't observed any early terminations as a result of ejection fractions.

Unexpectedly falling in patients with obstructive HCM.

And we'll be looking to see if that may continue with the UN blinding of the Sequoia results, but thats the kind of thing that may ultimately factor into what.

It would be considered a risk that would be mitigated by our potential revenue program and that's something that.

We're continuing to be quite hopeful for.

Thank you so much for them Dr. Omar I'll jump back in the queue.

Thank you.

And our next question comes from Salim Sayed from Mizuho. Your line is open.

Great. Good afternoon, guys. Thanks for the question.

So Robert the number one question, we get obviously I'm sure you get it to you is why is the stock back down at 30 Bucks I think a lot of people are trying to sort out.

Why exactly it's there and nobody really thought it would be there.

At any point in 2023 really.

And then the reasons that we hear from folks.

It seems to be pointing to is the <unk> line.

And then potential deal risk around the assay and I know Theres a one question <unk>.

Really focus on the deal risk piece here.

So given we are.

Four months or so away from Sequoia read out just curious in your in your discussions with potential partners, how that particular aspect of the story is being perceived.

Do people do you think folks will want to see that data or.

Can you can you make.

Our decision to <unk>.

Go it alone or partner.

Prior to that data does give us if you can just.

Set aside some context for us.

Timing of a potential deal if any.

Go it alone or partner decision. Thank you.

So any deal that we might do would have to be a deal that met our expectations to be able to go to Europe on our own but would be supplemented by our potential partners involvement and the hurdle is very very high.

Our intention to build out our commercial business in Europe .

So with our last earnings call I did indicate we were opening the aperture.

And we're looking very critically at.

What might be any alternatives.

That plan, we think it's in the interest of shareholders that we objectively approach that decision. We've done that we're doing that and we continue to execute well on our own plans.

That answers the question.

Yes, I think that was helpful. Thanks Darren.

Sure thing.

Thank you Andrew.

Our next question comes from Carter Gould from Barclays. Your line is open.

Hello Carter.

Hey, guys you got on the line for Carter, Thanks for squeezing us in here.

We just have a question on expectations for what you will disclose in the Sequoia topline press release to what extent does the myocardial level of disclosure serve as a good benchmark for what to expect and then as a follow up to that.

Sequoia.

On the horizon, what should we anticipate from you <unk> what will your presence at the HSA and EAA.

Meetings this year. Thank you.

So we're going to be out in full force at Hff's, a and AA.

Sure.

This year.

As well as the HCM Society meeting in October which falls in between.

What I'll also say is.

And as much as we've guided to results for Sequoia by the end of the year, it's reasonable to expect that the full on presentation of those results would occur not at one of those meetings, but perhaps at ACC, which is in April 2020.

<unk> and ACC has.

Its own guidelines and restrictions as to what would be permitting of our presentation and their scientific sessions.

Which are different from other meetings and if I recall correctly when myocardial presented its data it was leading into the ESC meeting that year.

With different restrictions then does ACC.

So I don't know that you can compare what will be our disclosure in a top line release to theirs.

But what I will say is we will disclose that which we determined to be.

Material.

And informative to shareholders without jeopardizing our presentation.

ACC and until we see the data, it's hard to know exactly where that falls.

Thank you.

Our next question comes from Justin Kim from Oppenheimer <unk> Co. Your line is open.

Hello, Justin.

Hi, Robert and good evening everyone.

Maybe just as a.

Follow up there I just wanted to ask a question with respect to the presence that a J and maybe just what we might expect from for it.

Presumably you would have some.

Just from sort of the core complete or I'm. Just wondering like is that something we can expect to see how some of those participants of the pivotal did once they were off the drug and re titrated are titrated up from placebo.

And sort of see that in <unk>.

Chad.

This year.

Yes, so we're not guiding to any new data from forest at AA, but rather you heard us referred to baseline demographics from Sequoia at the HCM Society.

As it relates to forest, it's not.

<unk> been our practice that we would provide updates at every medical meeting, but certainly we want to provide.

Meaningful updates when there is.

Significant new data to share and Thats more likely as we will be coming at ACC next year.

Okay. Thank you.

Thank you.

And our last question will come from Street Crippa Devorah Khanda from Churlish Securities. Your line is open.

Good afternoon.

Good afternoon, Robert and good afternoon to retain thank you so much for taking my question.

Just to follow up on what Robert you mentioned earlier in terms of.

At the end of the.

Drop I think previously you had mentioned that there could be an unblinded event. The lvs drops with fairly low I was wondering if you can.

What is the bar for barley now and.

We haven't heard about it so far can we assume that it didn't happen.

Hello.

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

Alright, I think.

The protocol is pretty clear that if.

We see a patient has an ejection fraction fall below 40%.

That the investigator and site of kinetics should be informed.

To date, we havent seen we havent been informed of any such events.

And which is quite reassuring.

We're not privy to any other drops in ETF. The rest are blinded and will remain so until the study is complete.

Great. Thank you so much.

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

Thank you operator, and thanks to everybody who joined US on this call today.

We look forward to keeping you abreast of our progress we welcome your further questions and look forward to updating you throughout the remainder of this year with that operator, we can bring this call to a close.

Thank you. This concludes today's conference call. Thank you for your participation you may now disconnect good afternoon, and welcome ladies and gentlemen.

<unk> second quarter 2023 conference call.

At this time I would like to inform you that this call is being recorded and then 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 one question 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.

<unk>, President and Chief Executive Officer.

I'll begin with an overview of the quarter and recent developments.

Now like EVP of R&D will provide updates related to Abbvie campton focus to Sequoia HCM Redwood HCM and finance HCM, Steve Heitner, VP clinical research and therapeutic area lead cardiovascular and filling in for Stuart Kupfer today, and we'll provide additional updates for Etsy Camden.

Relating to Maple HCM and speak to the expected start of Acacia HCN and Macau as EVP and Chief commercial officer will speak about commercial readiness activities for ASE campaign, and its market opportunity Robert Wong VP, and Chief Accounting Officer will provide a financial overview of the past quarter.

I am <unk>, SVP, and Chief Financial Officer will discuss our financial outlook and revised spending guidance for 2023, finally, Rob and Brian will provide an update on our lead clinical program in his closing comments and review expected upcoming milestones.

He's now at that question in the following discussion including responses to questions contain statements that relate to future events and performance rather than historical facts and constitute forward looking statements.

Actual results may differ materially from those projected in these forward looking statements additional information concerning factors that could cause our actual results to differ materially any forward looking statement is contained in our SEC filings, including our current report regarding our second quarter 2023 and ancillary.

<unk> filed on form 8-K that was furnished to the SEC today, we undertake no obligation to update any forward looking statements. After this call and now I will turn the call over to Robert.

Thank you Diane and thanks for joining us on the call today.

Saudi and Steve will elaborate our comprehensive clinical trials development program for <unk> Camden is firing on all cylinders during the quarter, we completed enrollment in <unk> HCM, we began maple HCM and we prepared to start Acacia HCM the phase III.

Clinical trial of <unk> in patients with non obstructive HCM.

We have accelerated the timeline for this trial and we now expect to open the trial to patient enrollment next month.

As well as the high level of enthusiasm and diligence of our clinical site investigators and their staffs.

Now that enrollment in Sequoia HCM is complete study conduct is progressing and we remain on track to share top line results by the end of this year.

That across all of these measures.

Including go to market plans that build towards potential approvals and commercialization of Alfie Camden.

Andrew will elaborate on some of those plans shortly.

While <unk> may be top of mind in parallel our clinical research activities continued to push forward on other fronts as well in the second quarter, we advanced CK 586, a second cardiac myosin inhibitor into a phase one study we continued the phase one study of CK 100.

<unk> six our cardiac troponin activator, and we continued non clinical research and IND, enabling activities towards our goal of submitting one to two new <unk> over the next one to two years.

<unk> and pipeline, including preparations for the potential approval and commercialization of <unk>.

That's all going to enable us to further extend our cash runway King will provide more details and updated financial guidance for 2023 later in this call.

As you will hear today, we're moving forward with momentum into the second half of the year with a broad early and late stage pipeline ongoing research in a stronger financial Foundation.

Giving us conviction and confidence in achieving our goals for the rest of the year as well as setting us up well afterwards with that I'll now turn the call over to <unk>.

Thanks, Robert and the second quarter, we made great progress across the broad development program for Abbvie Campton most.

Most importantly, we completed enrollment and randomization in Sequoia HCM, the pivotal phase III clinical trial of <unk>, Camden with 282 patients randomized.

Surpassing our enrollment target of 270 patients and making it now the largest randomized clinical trial of an investigational therapy ever conducted in patients with obstructive HCM.

Conduct a quiet HCM benefits greatly from a growing experience and learnings related to the use of cardiac myosin inhibitors as well as measures employed in the evaluation of their effectiveness.

<unk>.

And physician preferences.

I am pleased to share that we also met or exceeded our enrollment objectives in terms of geography and patient characteristics quite HCM enrolled a diverse patient population from the U S. China, Europe , and Israel patients enrolled exhibit a substantial deficit in exercise capacity a key.

<unk> of the enrollment criteria considering that the primary endpoint assessments for a potential increase in exercise capacity.

Further to this point equates employees and individualized dose titration strategy, which is designed to optimize dose selection and maximize the potential benefit risk profile of Abbvie campton.

In fact at this point all patients have progressed through at least the eight week visit which marks the end of the dose escalation phase.

Across all these measures we feel Sequoia HCM is proceeding per plan, certainly matching or exceeding our trial design assumptions.

All of this work has put us on track to report top line results by the end of the year.

Now that all the patients from Sequoia HCM, a randomized we expect to also present baseline characteristics.

Of these patients at the HCN Society scientific sessions in early October .

Also during the quarter, we presented new data in patients with non obstructive HCM from cohort four of Redwood HCM at the heart failure 2023 Congress builds.

Building on initial data presented earlier this year at ACC.

Data showed that following only 10 weeks of treatment.

Camden was associated with an average improvement in the clinical summary score of the Kansas City cardiomyopathy questionnaire or <unk> CSS.

Of 11 points with 58% of the patients experiencing a clinically meaningful reduction in symptom burden of five points or more.

Treatment with Abbvie Camden was also associated with improvements in NY chain functional class angina frequency high sensitivity cardiac troponin I in NT Pro BNP.

We are pleased to see that most patients were able to achieve the highest available dose of 15 milligrams with no drug discontinuation due to adverse events related to App canton snow treatment interruptions or downtown <unk> events related to <unk> less than 50%.

And no events with Lv eef less than 40%.

We remain confident in the promise of <unk> in non obstructive HCM and look forward to starting a phase III clinical trial in non obstructive HCM soon Steve.

Steve will elaborate on this trial in a moment.

We're pleased to see that nearly all patients elect to continue into the open label extension and we now have patients who have surpassed two years on Abbvie campton enforced HCM.

In addition to providing data on the efficacy of long term use of <unk> in the treatment of obstructive HCM.

With that I'll turn the call over to Steve who is filling in for Stewart, who is unable to join our earnings call today, Steve will speak to the expanding development program for Abbvie Camden.

Thanks Patty.

During the quarter, we announced the start of patient enrollment in Maple HCM.

His III clinical trial of <unk> as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM.

We are pleased to report that the first patients have recently been randomized.

While we do not foresee that Maple HCM is critical path to the potential for first FDA approval.

If successful in demonstrating that assay Camden is superior to <unk> with respect to improvement of exercise capacity heart failure symptoms and Neocart Association functional class, we would expect to submit the results from this trial as a supplemental NDA for potential label expansion.

<unk> has the potential to meaningfully expand how physicians foresee using ASIC Hampton.

We would likely be reflected in the treatment guidelines potentially elevating it to first line therapy and potentially expanding the commercial opportunity.

At the same time.

In recent months, we have been continuing preparation for the pivotal phase III clinical trial of <unk> in the non obstructive HCM based on the favorable data arising from cohort four of Redwood HCM.

As noted in today's press release, we are calling this trial, Acacia HCM and keeping with our theme of northern California trees for the program.

Acacia HCM stands for assessment, comparing <unk> to placebo on cardiac endpoints in adults with non obstructive HCM.

And advance I'd like to share a few key points about its design.

<unk> is a phase III multicenter randomized double blind placebo controlled clinical trial expected to enroll approximately 420 patients with symptomatic non obstructive HCM.

Primary endpoint is the change in <unk> clinical summary score from baseline to week 36.

While the primary analysis will take place at 36 weeks patients will continue on treatment with IV Camden or placebo for up to 72 weeks in order to evaluate additional secondary and exploratory analyses, including the time to the first cardiovascular event.

As previously mentioned, we expect to initiate patient dosing.

And Acacia HCM in September .

With that I will turn the call over to Andrew.

Thanks, Steve our commercial readiness team is laser focused on key work streams in support of a potential approval and commercialization of Etsy Kimpton in both the United States and Europe .

During the quarter, we update it and continue to refine our go to market plans executed against activities outlined within them, including development of the disease State Education plan branding positioning patient support programs sales force deployment plans and pricing assessments.

We have also conducted additional market research to gain greater clarity on HCM patient and HCP experiences as well as how HCP to payers and patients would respond to our potential product profile.

We believe there is and will remain a large unaddressed population of patients with obstructive HCM that may benefit from <unk> if approved.

We are fortunate to have been able to redeploy members of our commercial team who had previously been focused on <unk> to now focus on epic Hampton, a corporate pivot that has enabled the acceleration of our planning and.

An efficient operator operated visualization of our preparations for the potential approval and commercialization of ASIC Hampton.

Meanwhile, conversations with payers progressed in accordance with compliant preapproved payer interactions with productive dialogue and education, not only about the HCM landscape and the potential of cardiac myosin inhibitors, but about abbvie Camden, specifically in which they remain highly interested.

We look forward to continuing to develop expanded hone our go to market plans for the potential approval and commercialization of <unk> canton and simultaneously deliver on step wise.

<unk> systematic element of the pre commercial runway.

Toward that end turning to market opportunity in the in Europe . We are pleased to have made our first new hire in Europe , bringing on our head of Europe , who has a proven track record in launching new products, delivering growth and achieving expectations and European and international markets within the rare disease in cardiology space.

Looking forward to having both our European head of access and medical affairs, joining us by the end of Q3.

We are pleased to be attracting top talent, thanks to our strong culture and pipeline.

With that I will turn the call over to Robert Wong.

Thanks, Andrew we ended the second quarter with $592 6 million in cash and investments our revenue in Q2 2023 came from Astellas and is the remaining amount due to us from there $12 million commitment associated with our conduct.

<unk> ALS are.

Quarter 2023, G&A expenses were $39 7 million down from $42 7 million in Q2, 2022, due primarily to reduced outsource spending on commercial readiness activities and now Ching will review, our financial outlook and corporate development strategy.

Thanks Robert.

We ended the quarter was approximately $593 million on the balance sheet, which represents nearly two years of cash runway based on our revised 2023 spending guidance announced today.

I will now elaborate.

Previously we had expected our operating expenses for 2023 to be in the range of $420 million to $450 million and net cash utilization to be approximately $350 million to $375 million.

We have reduced our operating expenses to be in the range of $390 million to $410 million in response to our receipt of a <unk> from the FDA regarding the NDA for <unk> <unk>.

And the discontinuation of courage AOS.

Our net cash utilization is now expected to be approximately $310 million to $320 million.

This reduction represents savings of approximately 15%.

Which demonstrates initiatives to reduce spending and limit head count growth in light of the setbacks.

I'll also remind you that as we have outlined in previous and revised guidance. We also expect to receive a $50 million nonrefundable milestone payments from royalty pharma upon the initiation of patient dosing in Acacia ACM, which is expected to start next month.

Through this transaction was royalty pharma, we also remain eligible for two additional tranches of capital.

We choose to take them.

$75 million upon our potentially sharing positive results from the Sequoia HCN and 100 million upon the acceptance of NDA submission for <unk> in the U S.

We view this transaction as the equivalent to a line of credit, which you work.

Can leverage to add to our balance sheet in 2024 if necessary.

Towards that objective, we're in the midst of our annual strategic planning process, which critically evaluate <unk> corporate and pipeline scenarios contingencies and risk mitigation and.

And informed investment decisions as we calibrate with board and shareholder alignment and with that I will turn the call back over to Robert Blum.

As you've heard in the second quarter, we made substantial progress across the pipeline.

To add to what my colleagues mentioned during the quarter. We also participated in a type a meeting with the FDA to understand FDA views related to the CRM for <unk>.

And outside the United States <unk> is under review in Europe , and in China and during the quarter. We continued to support these reviews and address questions from regulators.

CK 586 is a cardiac myosin inhibitor that is mechanistically distinct from Matthew Camden and has the potential application for patients with heart failure with preserved ejection fraction or <unk> for which there are few treatment options for some people would have passed their disease in many ways mimics non obstructive.

Give HCM due to their thinking towards an increased cardiac contractility and symptom burden in <unk>.

<unk> data from cohort four of Redwood HCM and patients with non obstructive HCM or potentially a proxy for the therapeutic application of cardiac myosin inhibition in this patient population as we hope to further investigate with CK, 586% in 2024.

At the same time, our consistent commitment to muscle biology research persists. In addition to the ongoing early stage programs for CK 136, and CK 586, we expect to file one to two additional IND.

For new drug candidates over the next one to two years. Once these <unk> are filed we will have advanced three to four new drug candidates in a relatively short time span and impressive figure for any biopharmaceutical company, which will enable us to expand our pipeline according to our <unk>.

<unk> 2025 goals.

There is a great deal of work progressing behind the scenes and I must thank our diligent and dedicated employees for their commitment to our future.

Moreover, we are continuing to advance business development initiatives with focus to Japan, and Europe as we continue to seek potential partners for <unk> Camden.

<unk> been joined by a steam local city and county elected officials as well as staff, representing California State Senators.

We were grateful to celebrate this joyous occasion with our longtime supporters and friends recognizing though that while much is the same as it was when we started Sato kinetics of 1998. Much has also changed as we've made progress towards our ambitious goals and still the best is yet to come when we hope for.

Bring forward, our first approved medicines to the benefit of patients.

Now I'll recap our upcoming milestones.

For <unk>, we expect to share top line results from Sequoia HCM by the end of the year and we expect to continue enrolling patients in Maple HCM and start Acacia HCM in September 2023.

And we continue to advance our ongoing go to market strategy during 2023.

And finally for CK 586, we expect to continue to enroll the phase one study throughout this year.

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

Thank you.

As a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw your question. Please press star one again.

In the interest of time, we do ask that you. Please kindly limit yourself to one question at this time.

Please standby, while we compile the Q&A roster.

And our first question will come from Aswany Varma from UBS. Your line is open.

Good afternoon.

Hi, good afternoon, its bottom on behalf of ash warm up from UBS. Thanks for taking our questions.

I just have a quick one on VK five eight zix.

Just looking at the mechanism is very similar.

After Thompson like you noted.

What gives you confidence that this mechanism of action will work for patients.

And why not pursue advanced also in obstructive HCM and just a quick second one like what would be the benchmark for efficacy and what clinical companies are you looking for in this phase one trial.

Sure. So I'll turn this over to <unk> and to Steve, but firstly before I do I'll just say that.

CK 586 is intentionally.

Being advanced as would be distinguishable from <unk>, which is being developed as you know in obstructive disease and non obstructive HCM now and.

And were we to have identified any issues or liabilities with RC Kimpton then perhaps.

And what we may be looking for both.

As it relates to phase one data and ultimately beyond that in half path.

Thanks Robert.

As you mentioned CK 586.

Has a distinct mechanism of action than <unk>, but it's still a cardiac myosin inhibitor and the distinction is really a subtle point of where it binds in.

In what form of the motor protein it inhibits.

Fundamentally it does the same thing and reduces the number of active cross bridges and reduces cardiac contractility and has a shallow exposure response relationship.

Does abbvie campton.

And so fundamentally behaves very similarly.

As Robert said.

Abbvie Camden is doing wonderfully we don't really.

I think we need another drug in HCM, but <unk> is a much different population.

And.

And a very large population at that.

Well, we are intending with 586 is to focus in a different indication and too.

And do a subset of patients with half pet foods phenotypes mimic some of our Sam patients they have.

Larger hearts, they can hearts high filling pressures higher biomarkers.

<unk>.

Poorer exercise tolerance in so many ways, they're Athena copy.

For those that have genetic.

Non obstructive HCM and.

I hope that's helpful. Operator, maybe that will move to the next question. Please.

Great.

And our next question will come from Rohit Basin from Needham <unk> Company. Your line is now open.

And then when do you plan on presenting new data disclosures and medical meetings.

Sure so as it relates to both Maple and soon to start Acacia.

It's too early for us to be guiding us to rate of enrollment by do understand the question and we should get you that answer but lifts.

See how we get out of this startup phase and these.

Initial enrollments before we might start guiding to enrollment rates in conclusion.

I don't expect that there'll be any data from either of these studies in 2023 of course and as we look to <unk>.

Next year I think it's also premature.

We'll be in a better position to point to what to expect next year. When we do our Q4 earnings in February .

Thank you.

Thank you and as a reminder, we do kindly ask that you. Please limit yourself to one question at this time.

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

Hi, Thanks for taking my question Hi.

Robert Thanks for taking my question and congrats on the progress.

You said in our prepared comments.

Ah patients or an acquirer now through the titration phase I was just wondering if you could comment on whether youre seeing what you expected to see in terms of the proportion get to target doses.

So thank you for asking and that's a notable achievement.

Achievement as you highlight that we now are through that dose escalation phase keeping in mind, we're blinded to dose, but maybe I'll ask Steve if he wants to elaborate.

Well, Jason I think Robin just answer to your question.

Obviously, a blinded study and we are in fact blinded to the actual dose administered.

Administered.

So we don't know the proportion of doses.

Patients are being exposed to an in Sequoia.

But do you have already seen some of the data that has been presented with regard to the forest HCM study, which is unblinded.

Where there's a nice bell shaped distribution and the doses.

Patients are being exposed to.

15, and 10 milligrams for the most part with a smaller proportion getting exposed to five and 20 milligrams.

Okay, great. Thank you.

Thank you Jason.

Thank you.

Our next question comes from Jason Szymanski from Bofa. Your line is open.

Good afternoon afternoon.

Congratulations on the progress and thanks for taking our question I wanted to circle back to some of your comments regarding maple in the possibility of broadening the label with ASIC Camden to include using the first line setting I'm curious what are you what do you see as the opportunity here I mean, obviously the addressable market is sizable but it seems like there could be.

<unk> potentially logistical or administrative hurdles.

Thinking about pushback from payers or potential capacity issues from community prescribers I mean do you see ASIC captain is a valid option for all comers with obstructive HCM.

<unk> is successful by payers, maybe I'll ask our clinical colleagues if they want to add anything to that and maybe also Andrew if he wants to.

Hi, Jason this is fatty I might just add that in the context of a drug that addresses the underlying causes of disease.

There is obviously opportunity for disease modification and so.

April is not addressed not designed to address that point.

But.

In terms of thinking about drug selected.

For patients at least we provide the evidence of which which are the current.

Number one choice.

Initiated versus in the newcomer in the CMI, where might the best efficacy be found and then over time, we would hope to broaden the case for using CMI early based on the fact that they may.

May slow the progression of the disease are stabilized and progression of the disease. So I think this is a beginning of a strategy to establish <unk> as first line therapy.

Great. Thank you Andrew.

Yes, Wally maybe one or two things Jason first is that.

Having evidence certainly helps inform guidelines guidelines will then certainly help kind of a second point from a payer point of view.

Maybe get rid of this step at it that we have will.

We will likely have I should say as a category through a beta blockers and calcium channel blockers, which from our research seems to be important to physicians as well as patients if there's evidence that.

At the campaign alone.

Can treat the disease effectively then we think that will certainly be a good strategy commercially as well.

Great I appreciate the color.

Thank you.

And our next question will come from Joe <unk> from H C. Wainwright Your line is open.

Hello, Joe.

Hey, everybody. Thanks for all the details.

Looking forward to the start of a case here so Robert I'm going to give you a bit of a run on sentence here with my question.

If you could give me a little patience here, so with regard to the initiatives.

<unk>.

Cost savings and what have you would you consider the company right sized at this point or can we expect any potential additional cost savings and then with regard to app camped in.

Since this is a <unk>.

Geographical study are there any particular geographies that might have enhanced focused bayou with regard to clinical trial conduct or a treatment regimens that might be different from other regions.

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

So youre right that was a long sentence, but I'm trying to remember the component parts. So let me start with what I remember to be the first part.

I do believe and Jim can comment on this too if he likes.

We went through a very.

The.

<unk> cost cutting exercise critically assessing what we need to be doing in 2023 to align better with the new reality, a reality that has us focused on our fee Kimpton and were only <unk> because of the CRO is not part of our near term.

Future.

And in order to do that we looked at outsource spending we look at contractors and consultants and we looked at our internal head count. We also looked at plans to grow head count and.

And we set some aggressive targets and we met those targets and I think the team here at sort of kinetics did a great job.

Pulling all in the same direction to ensure we could vary meaningfully reduce operating spending not just over the long term, but in the nearer term so as to extend cash runway this year.

So I think we are right sized for what our current priorities and knowing where we are today recognizing that kimpton.

Camden is going to be paving the path for this company and we have to be in the best position to capitalize on that as soon as we know more from Sequoia and that'll be end of this year.

So let me see firstly, if king has anything to add to that.

I think Rob will cover so covered it well the only thing I would add is part of our strategic planning process. We are also contemplating different scenarios if.

So clear readout.

Does not meet our expectations then we have scenario planning to address those but obviously you will have to wait for data.

Before executing anything.

I think the next part of your sentence related to geographic.

Variability potentially in where we noting anything or preparing for anything maybe I'll turn to 30 or Steve to speak to that.

Sure. So I'll take that one this is Steve speaking.

Your question alluded to where there is.

Specific geographies that were targeting.

I think that the strategy that cytogenetics is employed has been to cast a wide net.

Capture all geographies, you're right that there are treatment.

Strategic differences in how patients are treated in different parts of the world. However, the way that Sequoia was designed.

Captures all patients who have symptomatic obstructive HCM independent.

What medical treatment they have available to them, whether it includes disopyramide or not.

Yes, the exception would be Japan, where they have.

Fabienne between therapy, and we're not running the study in Japan as you know.

<unk>.

Yeah.

But in our independent of the availability of septal reduction therapy, whether it be septal myectomy or alcohol septal ablation.

Seeing that we do have an endpoint that does it.

Measure.

The impact of <unk> on the eligibility of these patients for that and I think.

If you take a step back and look at the strategy that we've employed for HCM at large is that where we have a <unk>.

<unk> program not only is targeting.

Patients with <unk>.

Obstructive HCM independent of geography, but all patients with HCM independent of phenotype, including non obstructive.

Patients patients with met ventricular obstruction that you've seen with al.

Redwood HCM cohort four.

As well as.

Hopefully in the future.

Groups.

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

Yes.

Okay.

Yeah, I'll take that I think.

<unk>.

For for Maple Theres, a lot of enthusiasm, giving me a question that we're asking in that study.

And that patient population is a little different than.

And then the other OE Sam populations that have been studied to date.

And obviously there are no.

Large HCM studies ongoing with regards to <unk>.

We think it's.

The first time a novel therapy has been studied in HCM I think investigator enthusiasm will be high.

Across the board.

Thank you for the answers everyone.

Thank you Joe.

Thank you.

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

Hi, guys.

This is Sean on for Dan Thanks for taking the question.

Can you talk about the strategic logic behind us sole primary endpoint of GCC Q for Acacia given the parallel novel study you haven't taken into an <unk>.

Two as co primaries.

Physician and FDA feedback drove that decision and is the 36 week endpoint versus a 48 week time point and Odyssey.

Entirely driven by the expected duration of the titration period, and if not can you go into that decision making.

Sure I'll ask Steve to speak to those questions. Please.

Okay.

Sure. So this is Steve.

The primary endpoint.

<unk> as I mentioned earlier on is the.

So endpoint of change in <unk>, and we pick that based on our experience from our phase III study the Redwood code, Florida was presented and you've seen the data.

We also are aware of that.

The majority of patients who.

Have non obstructive HCM are receiving therapy with either a beta blocker calcium channel blocker actually mostly a beta blocker.

And as you know that impact.

Tangible to achieve a significant change in peak <unk>.

And we felt that if we were to incorporate these two endpoints as us.

A composite primary endpoint or dual primary endpoints for that matter.

We would hamper.

Likelihood of success.

Obviously exercise capacity is important.

And we have incorporated this.

Bobby mentioned.

As a key secondary endpoint exercise capacity as measured by cardiopulmonary exercise testing.

But in essence, we felt that separating those two would increase the likelihood of technical success for Acacia Sam.

There was a second part of the question you.

You asked with regards to <unk> 36 versus <unk> 48 weeks of therapy.

I think.

We've chosen 36 weeks.

That gives us I think plenty of time to get to the maximum effects, we have a relatively.

Short titration period in our study.

Is mirrored by what we are.

Executed in Sequoia and.

Thanks for your question.

Thank you.

And our next question will come from tests from narrow from Jpmorgan. Your line is open.

Okay, Great Great Hi, Robert Thank you so much for taking our question.

I wanted to ask a question on HCN epidemiology today, if I could.

You've historically talked about a patient population of 190000 eus with diagnosed obstructive HCM, which of course, an undiagnosed patient population on top of that.

As I recall, Bristol had talked about 75000 identified diagnosed obstructive patients.

We saw them quote around the time of <unk> launch.

Can you help us close what the gap might be there, we just really like to get a better understanding of where your latest thinking on the epidemiology in obstructive HCM as you think about diagnose patients here at the time of a potential launch and where you might see that evolving with.

Time, thanks, so much.

Sure thing I'm going to turn to Andrew.

Who is very focused to these matters and also how the literature is evolving here.

Yes.

Sure. So thanks for the question Andrew So there are multiple publications some older.

Speak to lower numbers of epidemiology.

We did a five year longitudinal study on claims data on actual patient on patients that are actually diagnosed and then.

Corroborated that with.

And again, that's based on actual data in claims so.

We're going from that number.

190 of that 190.

From our research. Furthermore, I think it's important to understand that probably around 60% of those patients are.

Not currently optimized with treatment and still having symptom.

Symptoms and Thats really the target of therapy.

Yes.

Great. Thanks, so much for taking our question.

Thank you.

And our next question will come from Yasmin Rahimi from Piper Sandler Your line is open.

Good afternoon.

Hi, Robert first of all congratulations on the <unk> anniversary and what a wonderful achievement for the entire.

Company.

Two questions that are directed to Steve and fatty and maybe also Andrew could comment on it a question that we're getting from quite a lot of clients right now.

What do we want to see from a safety perspective, and the upcoming to Korea that could warrant a differentiated echo monitoring.

Would it be a favorable ramp I think a lot of clients understand the absence of DDI, but may want to understand sort of.

How the Sequoia data could maybe just get us really comfortable on the differentiated label.

Really appreciate your thoughtful comments around around these question and I'll jump back in the queue.

Sure I'll turn first to <unk>, but I'll underscore of.

Of course that.

What we're going to share our comments based on what we've seen already in Redwood and forest and what we hope to and expect to see in Sequoia, but thats still to be known.

Camden remains an investigational compound so with that I'll turn to <unk> to answer your question.

Yes, I mean, I think in terms of.

Echo monitoring we hope to see that the data from forest will support a.

Frequency of Echo monitoring that.

Is.

Manageable by patients and their physicians I'm not going to really make any comparative statements as you asked for differentiation, but.

You can imagine.

In forest now monitoring patients for every three months.

We would.

Ultimately those data would support that.

A lack of.

Treatment decisions are safety events that are driven by all of those echos I think everyone recognizes the echocardiograms are a burden to the sites.

The medical system.

And I think there should be a general.

Incentive to minimize the burden on patients and the medical system and so.

We're very happy with how forest has been proceeding.

As I said.

Earlier, we know patients out to two years, and we hope that that safety database will lend itself to making a compelling argument for <unk>.

Echo monitoring that say might be twice, a year or even yearly at some point.

<unk>.

And in terms of our Rems I think the question really is what physician education is going to be necessary.

In order to use <unk> NAND.

I can't really comment so specifically to your question other than it will be informed by the safety information and the other profiles of Abbvie Campton, which.

To date, we don't think we have any meaningful drug drug interactions and and other aspects of the drug that.

That would.

Not require extensive physician education so.

Stay tuned.

Data evolves I think we will hopefully have more to say.

What's been especially reassuring.

In the <unk>.

Clinical trials data that we've seen to date is that.

We haven't observed any early terminations as a result of ejection fractions.

Unexpectedly falling in patients with obstructive HCM.

And we'll be looking to see if that may continue with the UN blinding of the Sequoia results, but thats the kind of thing that may ultimately factor into what would be considered a risk that would be mitigated by our potential revenue program and that's something that.

We're continuing to be quite hopeful for.

Thank you so much for them.

I'll jump back in the queue.

Thank you.

And our next question comes from Salim Sayed from Mizuho. Your line is open.

Great. Good afternoon, guys. Thanks for the question.

So Robert the number one question, we get obviously I'm sure you get it to us.

Why is the stock back down at 30 Bucks I think a lot of people are trying to sort out.

Why exactly it's there and nobody really thought it would be there.

At any point in 2023 really.

And then the reasons that we hear from folks it seems.

It seems to be pointing to is the <unk> line.

And then potential deal risk around assay and I know Theres a one question rule. So we don't really focus on the deal risk piece here.

So given we are.

Four months or so away from Sequoia readout, just curious in your in your discussions with potential partners, how that particular aspect of the story is being perceived.

Do people do you think folks will want to see that data or can.

Can you make.

The decision to go it alone or partner.

Prior to that data does give us if you can just set.

Set aside some context for us.

Timing of a potential deal if any.

Go it alone or partner decision. Thank you.

So any deal that we might to do would have to be a deal that met our expectations to be able to go to Europe on our own but would be supplemented by potential partners involvement and the hurdle is very very high.

Our intention to build out our commercial business in Europe .

So with our last earnings call I did indicate we were opening the aperture.

And we're looking very critically at what.

It might be any alternatives.

That plan, we think it's in the interest of shareholders that we objectively approach that decision. We've done that we're doing that and we continue to execute well on our own plans.

I hope that answers the question.

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

Sure thing.

Thank you Andrew.

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

Hello Carter.

Hey, guys, you've got Adam on the line for Carter, Thanks for squeezing us in here.

I just have a question on expectations for what you will disclose in the Sequoia topline press release to what extent does the myocardial level of disclosure serve as a good benchmark for what to expect and then as a follow up to that.

Sequoia re out.

On the horizon, what should we anticipate from <unk>, what will your presence at the HSA and DHA.

Meetings this year. Thank you.

So we're going to be out in full force at Hff's, a and AA.

This year.

As well as the HCM Society meeting in October which falls in between.

What I'll also say is.

<unk> and ACC has.

Its own guidelines and restrictions as to what would be permitting of our presentation and their scientific sessions.

Which are different from other meetings and if I recall correctly when myocardial presented its data it was leading into the ESC meeting that year ESC with different restrictions then does ACC.

So I don't know that you can compare what will be our disclosure in a top line release to theirs.

But what I will say is we will disclose that which we determined to be.

Material.

And informative to shareholders without jeopardizing our presentation.

ACC and until we see the data, it's hard to know exactly where that falls.

Thank you.

Our next question comes from Justin Kim from Oppenheimer <unk> Co. Your line is open.

Hello, Justin.

Hi, Robert and good evening everyone.

Maybe just.

A follow up there I just wanted to ask a question with respect to the presence that AJ and and maybe just what we might expect from for it.

Presumably you would have some experience from sort of the core complete or I'm. Just wondering like is that something we can expect to see how some of those participants of the pivotal did once they were off the drug and re titrated are titrated up from placebo.

I'm sorry to see that.

Shannon.

This year.

Yeah. So we're not guiding to any new data from forest at AA, Jay, but rather you heard us referred to baseline demographics from Sequoia The HCM Society.

As it relates to forest, it's not.

Been our practice that we would provide updates at every medical meeting, but certainly we want to provide.

Meaningful updates when there is.

Significant new data to share and Thats more likely is will be coming at ACC next year.

Okay. Thank you.

Thank you.

And our last question will come from Sri Crippa Devorah Khanda from Cheerless Securities. Your line is open.

Good afternoon.

Yeah.

Good afternoon, Robert and good afternoon to retain thank you so much for taking my question.

Just to follow up on what Robert you mentioned earlier in terms of the.

Yes.

Drop I think previously you had mentioned that there could be an unblinded event, if the lvs drop for Burley Noel I was wondering if you can.

What is the bar for Farley <unk> and <unk>.

We haven't heard about it so far can we assume that it didn't happen.

Sure.

Good question and I'll turn it to 30, and maybe Steve if he wants to add.

Alright.

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