Q1 2022 Cytokinetics Inc Earnings Call

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Operator: Good afternoon and welcome, ladies and gentlemen, to the Cytokinetics 1st quarter 2022 conference call. At this time, I'd like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call for questions and answers after the presentation. We will allow for up to two questions per participant. I will now turn the call over to Diane Weiser, Cytokinetics' Senior Vice President of Corporate Communications and Investor Relations. Please go ahead.

Good afternoon, and welcome ladies and gentlemen decide the kinetics first quarter 'twenty to 'twenty two conference call at this time.

I would like to inform you that this call is being recorded and that all participants are in a listen only mode.

At the company's request, we will open the call for questions and answers. After the presentation, we will allow for up to two questions per participant.

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

Diane Weiser: Good afternoon, and thanks for joining us on the call today. Robert Blum, President and Chief Executive Officer, will begin with a brief overview of the quarter and recent developments. Fady Malik, EVP of R&D, will provide updates related to Omicampton-McCarble and AFI-Campton. Andrew Callos, EVP and Chief Commercial Officer, will discuss commercialization planning activities for Omicampton-McCarble and our franchise strategy related to AFI-Campton. Stuart Kupfer, SVP and Chief Medical Officer, will provide an update on Real Deceptive. Robert Wong, VP and Chief Accounting Officer, will provide a financial overview for the past quarter.

Good afternoon, and thanks for joining us on the call today, Robert Blum, President and Chief Executive Officer will begin with a brief overview of the quarter and recent developments fatty Malik EVP of R&D will provide updates related to OMA Campton, Mccarville, NFU, Camden, Andrew Callose, EVP and Chief commercial officer.

Diane Weiser: And Ching Jia, SVP and Chief Financial Officer, will discuss our financial outlook and corporate development strategies. Finally, Robert Blum will provide closing comments and review expected key milestones for 2022. Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our first quarter 2022 financial results filed on Form 8K today. We undertake no obligation to update any forward-looking statements after this call.

We will discuss commercialization planning activities for <unk> and our franchise strategy related to Etsy, Camden, Stuart Kupfer, SVP and Chief Medical Officer will provide an update on rail deceptive, Robert one VP and Chief Accounting Officer will provide a financial overview for the past quarter and Ching jaw.

<unk> SVP and Chief Financial Officer will discuss our financial outlook and corporate development strategies Finally, Robert Blum, who will provide closing comments and review expected key milestones for 2022. Please.

Please note that portions of the following discussion and.

Leading our responses to questions contain statements that relate to future events and performance rather than historical facts and constitute forward looking statements. Our actual results 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.

SEC filings, including our current report regarding our first quarter 2022 financial results filed on form 8-K today, we undertake no obligation to update any forward looking statements. After this call and now I will turn the call over to Robert.

Robert Blum: And now, I will turn the call over to Robert. Thank you, Diane. And thanks again to everyone for joining us on the call today. We had a productive first quarter of the year, and we're moving closer toward our planned transformation to become a fully integrated research, development, and commercial company. Most notably, our NDA for Omicampt and McCarble was accepted for filing by the FDA with a PDUFA date of November 20, or, I'm sorry, November 30, 2022.

Thank you Diane and thanks again to everyone for joining us from the call today.

We had a productive first quarter of the year and we're moving closer toward our planned transformation to become a fully integrated research development and commercial company, most notably our NDA for <unk> was accepted for filing by the FDA with a <unk> date of November 20, I'm, Sorry November 30.

<unk> 2022.

Robert Blum: Since then, we've had ongoing interactions with FDA to address specific queries, and the team at Cytokinetics has worked diligently to prepare timely responses to their requests. We'll soon meet with FDA for a mid-cycle review of our application, as is customary, and for the most part, questions to date have been administrative or have supported additional requested analyses. The NDA acceptance was also a key de-risking milestone that triggered certain spending related to our measured commercial readiness activities.

Since then we've had ongoing interactions with FDA to address specific queries and the team at federal kinetics has worked diligently to prepare timely responses to the request will soon meet with FDA in a mid cycle review of our application.

As customary and for the most part queries to date have been administrative or have supported additional requested analyses.

The NDA acceptance was also a key derisking milestone on gated certain spending related to our measured commercial readiness activities.

Robert Blum: We've continued to build our teams and create a commercial infrastructure to support the potential approval of Omicamptomicarbol in the near term and also the potential commercialization of AfiCampton following completion of our pivotal trial, Sequoia HCM, and subsequently its potential FDA submission for approval. We're pleased to be attracting very high-caliber talent, and we're hiring individuals who bring with them great experience and expertise. From a clinical perspective, we shared additional data from two new analyses from Galactic HF at ACC that add to our understandings of both the clinical and pharmacoeconomic impacts associated with the addition of treatment with Omicamptomacarbal when added to standard of care therapy.

We've continued to build our teams and create a commercial infrastructure to support the potential approval of <unk> in the near term and also the potential commercialization of <unk> Kimpton following completion of our pivotal trials Sequoia HCM and subsequently its potential FDA submission for approval.

We're pleased to be attracting very high caliber talent and we're hiring individuals who bring with them great experience and expertise.

From a clinical perspective, we shared additional data from two new analyses from Galactic eight Jeff at ACC and that add to our understandings of both the clinical and pharma go economic impacts associated with the addition of treatment with <unk> when added to standard of care therapy.

Robert Blum: We continue to believe that Omicamptomacarbal can make a meaningful impact on important outcomes when added to standard of care and for the right patient. And we believe that the clinical opportunity affords a solid business case for establishing commercial capabilities, as well as for serving our cardiac muscle franchise objectives. Building on that theme, during the quarter, we also made significant advances in the development program for Aficamptin, including opening enrollment in Sequoia HCM, the pivotal phase three clinical trial of Aficamptin in patients with symptomatic obstructive HCM. As Fady will elaborate, site startup and activation activities are progressing on schedule, as is the screening and enrollment of patients.

We continue to believe that <unk> can make a meaningful impact on important outcomes.

Added to standard of care and for the right patient.

And we believe that clinical opportunity affords a solid business case for establishing commercial capabilities as well as to serve our cardiac muscle franchise objectives.

Building on that theme during the quarter. We also made significant advances in the development program for <unk> kimpton, including the opening of enrollment in Sequoia HCM, the pivotal phase III clinical trial of <unk> in patients with symptomatic obstructive HCM.

Study will elaborate site startup and activity activation activities are progressing on pace as is.

Is the screening and enrollment of patients.

Fady Malik: Following the positive results from cohort three of Redwood HCM, shared during the quarter, we're now enrolling patients whose background therapy includes disipiramide into Sequoia HCM, a key milestone and opportunity to include the sickest patients in need of new therapeutic options. We've also opened enrollment in Cohort 4 of Redwood HCM for patients with non-obstructive HCM, an important patient segment representing approximately one-third of the prevalent At the end of the first quarter, we remain on strong financial footing with over two years of projected cash runway, even as we expect our operating expenses may increase next year.

Following the positive results from cohort three of Redwood HCM shared during the quarter. We're now enrolling patients whose background therapy includes disopyramide into Sequoia HCM a key milestone in opportunity to include the sickest patients in need of new therapeutic options.

We've also opened enrollment in cohort four of Redwood HCM for patients with non obstructive HCM and important patient segment, representing approximately one third of the prevalent HCM patient population.

At the end of the first quarter, we remain on strong financial footing with over two years of projected cash runway, even as we expect our operating expenses may increase next year.

Fady Malik: This year will be a transformational one for the company, with key milestones across our pipeline, and we're moving closer to making good on our promise to bring forward new muscle-directed medicines for patients with diseases of impaired muscle function. With that, I'll turn the call over to Fady, please. Thanks, Robert.

This year will be a transformational one for the company with key milestones across our pipeline and we're moving closer to making good on our promise to bring forward new muscle directed medicines for patients with diseases of impaired muscle function and with that I'll turn the call over to fatty please.

Thanks Robert.

Fady Malik: While the NDA is under review by FDA, we are continuing to pursue additional learnings from Galactic HF. Last month at ACC, we presented new data from an analysis of Galactic HF showing that the effect of treatment with Omicantin-McCarbol versus placebo on the primary outcome was similar in hospitalized patients and outpatients. This indicates that Omecamtin-McCarbyl similarly reduced the risk of the primary outcome, both when initiated in hospitalized patients and in outpatients. Additionally, this analysis shows that starting treatment with thomacamptomacarbal in the hospital was both safe and well tolerated.

While the NDA is under review by FDA, we are continuing to pursue additional learnings from Galactic HFF.

Last month at ACC, we presented new data from an analysis of Galactic hff's showing that the effect of treatment with <unk> versus placebo on the primary outcome was similar in hospitalized patients and outpatients.

Indicating that <unk> mccarville, similarly reduced the risk of the primary outcome, both one initiated in hospitalized patients and in our patients.

Additionally, this analysis showed that starting treatment with <unk> in the hospital was both safe and well tolerated.

Fady Malik: Speaking to the ability to initiate omecamtiv mecarbil in these patients who are at greater risk for re-hospitalization and cardiovascular death. Importantly, recent public studies have shown that the medications started while patients are in the hospital have some of the best long-term adherence, making these results more significant. Additionally, at ACC, we presented the full results from Meteoric HF, evaluating the effect of 20 weeks of treatment with Omicamptin-McCarbol compared to placebo on exercise capacity.

Speaking to the ability to initiate <unk> in these patients who are at greater risk for re hospitalization and cardiovascular death.

Importantly, recent published studies have shown that the medications started while patients are in the hospital have some of the best long term adherence, making these results more significant.

Additionally, at ACC, we presented the full results for Meteor arcade chef evaluating the effect of 20 weeks of treatment with <unk> compared to placebo on exercise capacity.

Fady Malik: There was no effect on the primary endpoint, which was the change in peak oxygen uptake, or peak VO2, as measured by cardiopulmonary exercise testing from baseline to week 20. This study joins other studies of heart failure therapies that have shown a positive impact on cardiovascular outcomes but have not been successful in impacting exercise performance in patients with heart failure.

There was no effect on the primary endpoint, which was the change in peak oxygen uptake or <unk> as measured by cardiopulmonary exercise testing from baseline to week 20.

This study joins other studies of heart failure therapies that have shown a positive impact on cardiovascular outcomes, but have not been successful in impacting exercise performance in patients with heart failure.

Fady Malik: These data further suggest it may be particularly challenging to impact exercise capacity in this patient population, possibly due to comorbidities or deconditioning associated with heart failure. The results from EDIORC do add to the safety profile of Omecampt and McCarble, showing that under conditions of peak exercise, adverse events, including major cardiac adverse events, were similar between the treatment arms. As we stated previously, we do not expect the results from meteoric HF to have an impact on the NDA currently under review by the FDA.

These data further suggest it may be particularly challenging to impact exercise capacity in this patient population, possibly due to comorbidities are D conditioning associated with heart failure.

The results from meteoric do add to the safety profile of <unk> showing that under conditions of peak exercise adverse events, including major cardiac adverse events were similar between the treatment arms as.

As we stated previously we do not expect the results for Meteor Capes shaft to have an impact on the NDA currently under review by the FDA.

Fady Malik: Also during ACC, new joint guidelines were issued by ACC, AHA, and HFSA, including updates to treatment options for treating patients with heart failure and reduced ejection fractures. In particular, the guidelines outline the characteristics of patients with persistent or worsening heart failure whose risks of adverse cardiovascular outcomes are high.

Also during ACC, new joint guidelines were issued by ACC, a J and H FSA, including updates to treatment options for treating patients with heart failure and reduced ejection fraction.

In particular, the guidelines outlined the characteristics of patients with persistent or worsening heart failure.

Risks of adverse cardiovascular outcomes are high.

Fady Malik: Also, SGLT2 inhibitors were added as a fourth class of medication within guideline-directed medical therapy, or GDMT. We believe these updates augur well for the possibility of future inclusion of omicamptomacarbal in guidelines as an add-on therapy to standard of care therapies, particularly in patients with persistent or worsening heart failure who remain symptomatic and whose risks are elevated despite being on GDMT. We continue to prepare for the potential approval of omicamptomacarbal. On the medical affairs side, we doubled the size of our therapeutic medical scientist team, hired a field director, and began recruiting for our managed health care medical scientist team.

Also <unk> inhibitors were added as a fourth class of medication within guideline directed medical therapy or <unk>.

We believe these updates augur well for the possibility of future inclusion of AUM, a captive mccarville and guidelines as an add on therapy to standard of care therapies, particularly in patients with persistent or worsening heart failure, who remain symptomatic and whose risks are elevated despite being on GMT.

We continue to prepare for the potential approval of <unk> on.

On the medical affairs side, we doubled the size of our therapeutic medical scientists team hired a field director and began recruitment for our managed healthcare medical science team.

Fady Malik: I'm also pleased to announce that we have two abstracts from Galactic HF accepted for presentation at the late-breaking science session at the European Society of Cardiology Heart Failure 2022, taking place in Madrid from May 21st to May 24th. One is an analysis of the effects of Omecamtiv-McCarbyl in patients with lower blood pressure, and the other is an analysis in patients with tricuspid regurgitation at baseline. We look forward to reengaging with our European colleagues whom we've not seen for some time given the pandemic.

I'm also pleased to announce that we have two abstracts from Galactic <unk> accepted for presentation in the late breaking science session at the European Society of Cardiology Heart failure 2022, taking place in Madrid from May 21 to May 24th.

One is an analysis of the effects of <unk> in patients with lower blood pressure and the other is an analysis in patients with tricuspid regurgitation at baseline.

Look forward to re engaging with our European colleagues and we've not seen for some time given the pandemic.

Fady Malik: Turning now to Campton, as Robert mentioned, it was a productive quarter for this multifaceted development program. Notably, we opened enrollment in Sequoyah HCM, the Phase III pivotal trial of apicamptin in patients with symptomatic obstructive HCM. The COI HCM will assess the potential of apicamptin to improve exercise capacity, symptoms, and functional class in patients with obstructive HCM and will employ a personalized dosing scheme to maximize the potential treatment effect and enable patients to reach their target dose quickly.

Turning naphtha campton as Robert mentioned, it was a productive quarter for this multifaceted development program.

Notably we opened enrollment in <unk> HCM, the phase III pivotal trial of <unk> in patients with symptomatic obstructive HCM.

Decoy HCM will assess the potential of Abbvie campton to improve exercise capacity symptoms and functional class in patients with obstructive HCM and we will employ a personalized dosing scheme to maximize the potential treatment effect and enable patients to reach their target dose quickly.

Fady Malik: Following the positive results of cohort 3 of Redwood HCM, we're now including patients whose background therapy includes diazepiramide. Sites across the U.S. are actively screening and enrolling patients, and many others are conducting startup activities. We expect sites outside of the U.S. to begin screening patients in early Q3.

Following the positive results of cohort three of Redwood HCM, we're now including patients whose background therapy includes disopyramide.

Sites across the U S are actively screening and enrolling patients and many others are conducting start up activities. We expect sites outside of the U S to begin screening patients in early Q3.

Fady Malik: Additionally, during the quarter, we opened enrollment in cohort 4 of Redwood HCM for symptomatic patients with non-obstructive HCM. Cohort 4 will enroll 30 to 40 patients in an open-label fashion to escalating doses of apicampin of 5, 10, or 15 mg as informed by echocardiography. While the primary objective is the safety and tolerability of afecamptin, we're also evaluating the effect of afecamptin on left ventricular ejection fraction, New York Heart Association functional class, and cardiac biomarkers, including NT-ProBNP.

Additionally, during the quarter, we opened enrollment in cohort four of Redwood HCM for symptomatic patients with non obstructive HCM.

Cohort four will enroll 30 to 40 patients in an open label fashion to escalating doses of <unk> Camden of 510, or 15 milligrams as informed by Echocardiographer.

While the primary objective is safety and Tolerability of Epic Hampton. We're also evaluating the effect of <unk> Camden on left ventricular ejection fraction, New York Heart Association functional class on cardiac biomarkers, including NT Pro BNP we.

Fady Malik: We expect the data from this cohort to inform the design and conduct of a potential Pivotal Phase III clinical trial in non-obstructive HCM following the completion of Cohort 4. To remind you, last quarter we announced our plan to begin a second Phase 3 clinical trial of affecampin in obstructive HCM in the second half of this year. We've received many questions about this planned trial, so let me provide some clarification. First, this trial was not requested by FDA, and Sequoia HCM remains the sole Pivotal Phase III trial with which we believe we would submit for approval of apicamptin. Second, the goal of this additional phase 3 trial is to better understand and position the use of apicampin relative to standard of care therapy. As such, it will not be a head-to-head trial against Mavicamp.

We expect the data from this cohort to inform the design and conduct of a potential pivotal phase III clinical trial in non obstructive HCM following the completion of cohort four.

To remind you last quarter, we announced our plan to begin a second phase III clinical trial of <unk>, Camden and obstructive HCM in the second half of this year.

We've received many questions about this planned trial. So let me provide some clarifications.

This trial was not requested by FDA and Sequoia HCM remains the sole pivotal phase III trial, with which we believe we would submit for approval of that be captain.

Second the goal of this additional phase III trial is to better understand and position the use of Abbvie Catherine.

Relative to standard of care therapy.

As such it will not be a head to head trial against Mavic Camden.

Andrew Callos: We believe we have an opportunity to advance the field with a next-in-class drug candidate by pursuing important scientific questions, and this trial, along with others we may conduct, may address questions important to understanding the use of a therapy with a new mechanism of action in patients with a spectrum of disease severity and background therapy. Often, these trials await initial drug approval, but we're confident in apicamptin and believe it's advantageous to embark on these studies sooner.

We believe we have an opportunity to advance the field with a next in class drug candidate by pursuing important scientific questions and this trial along with others. We may conduct may address questions important to understanding the use of a therapy with a new mechanism of action and patients with a spectrum of disease severity and.

Background therapy.

Often these trials await initial drug approval, but we're confident in Napa Camden and believe it is advantageous to embark on these studies sooner.

Andrew Callos: We know there's greater interest in the design of this trial, and we plan to share more detail later this year. Towards our goal of sharing longer-term data on the treatment of apicampin in patients with obstructive HCM, we're pleased to announce that the first data cut from the open-label extension of Redwood HCM will be presented at a late-breaking science session at the Heart Failure 2022 meeting in Madrid. This interim look will include data from up to six months of treatment with Aficamp. Patients continue to be treated with Aficamptin and the Open Label Extension, and further analyses of these data are still forthcoming later this year. Looking beyond Aficamptin, we're pleased to see that FDA recently approved Mavicamptin for the treatment of patients with obstructive HCM, making it the first medical therapy for HCM to be approved by the FDA

We know there is greater interest in the design of this trial.

And we plan to share more detail later this year.

Towards our goal of sharing longer term data on the treatment of <unk> in patients with obstructive HCM. We're pleased to announce that the first data cut from the open label extension of Redwood HCM will be presented in a late breaking science session at the heart failure 2022 meeting in Madrid.

This interim look will include data from up to six months of treatment with epic Hampton.

Patients continue to be treated with <unk> Camden in the open label extension and further analysis of these data are still forthcoming later this year.

Looking beyond App you Captain we're pleased to see that FDA recently approved mavic Camden for the treatment of patients with obstructive HCM.

At the first medical therapy for HCM to be approved by the FDA.

Andrew Callos: We'd like to offer our congratulations to the teams who worked to bring this new mechanism of therapy to patients and take pride in this milestone given our discovery role for the program. This is a milestone for patients with HCM who have been in desperate need of new therapies to address the heavy burden of symptoms they endure. We also believe that this milestone approval will provide context for our own potential differentiation of afekampton following results from our pivotal trial. With that, I'll turn the call over to Andrew to provide an update on our commercial writings and activities and planned cardiovascular franchise strategy. Thanks, Fady.

We'd like to offer our congratulations to the teams who work to bring this new mechanism therapy to patients and take pride in this milestone given our discovery role for the program.

This is a milestone for patients with HCM who've been in desperate need for new therapies to address the heavy burden of symptoms they endure.

We also believe this milestone approval will provide context for our own potential differentiation of Appia Kempton following results from our pivotal trial.

With that I'll turn the call over to Andrew to provide an update on our commercial readiness activities and planned cardiovascular franchise strategy.

Andrew Callos: During the first quarter, we continued to build out our commercial capabilities and organization. We began hiring our first-line field-based salesforce leaders, as well as filling key positions across marketing, market access, sales, and commercial operations. We've selected a patient support service partner, and continued payer interactions and activities supportive of deploying our field. As we continue engaging with payers, we are mindful of the critical importance of the potential value proposition for Oma Kempton

Thanks, Patty during the first quarter, we continued to build out our commercial capabilities and organization. We began hiring our first line field based sales force leaders as well as filling key positions across marketing market access sales and commercial operations. We have selected a patient support service part.

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<unk> payer interactions and activity is supportive of deploying our field force.

As we continue engaging with payers, we are mindful of the critical importance of the potential value proposition for OMA captive mccarville.

Andrew Callos: Recently at ACC, we presented data from a health care resource utilization analysis from Galactic HS showing that among a subgroup of patients, treatment with omicamptive maccarbal reduced resource intensity measured by total days in the hospital. The estimated potential cost offset was $3,085, or 19% per patient, and 99% of the cost reductions were due to heart failure hospitalization among those treated with Omecaptive-McCarville. Of course, there are limitations to these data as their relevance will be payer specific.

Recently at ACC, we presented data from our healthcare resource utilization analysis from Galactic Hs showed that among a subgroup of patients treatment with OMA captive mccarville reduced resource intensity measured by total days in the hospital.

The estimated potential cost offset was $385 or 19% per patient and 99% of the cost reductions were due to heart failure hospitalization among those treated with AUM of captain Marvel.

Of course, there are limitations to these data as its relevance will be payer specific.

Andrew Callos: However, considering the payment reduction that hospitals face for 30-day readmission for Medicare and the fact that the prevalence of heart failure is increasing, this potential reduction in hospitalizations and their associated cost underscores the types of potential economic value propositions from the campus of McCarville that we will continue to assess to inform strategy. Also, during this quarter, we signed a master supply agreement for drug supply, initiated several major digital system programs, including enterprise resource planning and serialization, and hired key supply chain leadership roles.

However, if we consider the payment reduction that hospitals face for 30 day readmission for Medicare patients and the fact that the prevalence of heart failure is increasing this potential reduction in hospitalizations and their associated costs underscores the types of potential economic value propositions on the captive mccarville that we will continue to assess to inform strategy.

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Also during this quarter, we signed a master supply agreement for drug supply.

<unk> initiated several major digital system programs, including enterprise resource planning interior elevation and hired key supply chain leadership roles. We also completed a risk assessment of our end to end supply chain and advance appropriate mitigation actions.

Stuart Kupfer: We also completed a risk assessment of our end-to-end supply chain and advanced appropriate mitigation actions. As we have said, our growing cardiovascular commercial infrastructure, supportive of the launch of Omacamptive-McCarbol, will be leveraged for the future potential commercialization of apicampin. With increased awareness in the market of HCM and the clinical utility of cardiac myosin inhibitors, we are confident in the opportunity we have for the future potential launch of our next in-class therapy.

As we have said our growing cardiovascular commercial infrastructure supportive of the launch of OMA captive mccarville will be leveraged for the future potential commercialization of <unk> Catherine.

With increased awareness in the market of HCM and the clinical utility of cardiac myosin inhibitors. We are confident in the opportunity we have for the future potential launch of our next in class therapy.

Stuart Kupfer: With key properties that may impact ease of titration, reversibility, and the ability to reach target concentrations rapidly, we look forward to leveraging our commercial organization and synergies within the treatment community. And with that, I'll turn the call over to Stuart to provide an update on Royal Decepticons. Thanks, Andrew.

With key properties that may impact ease of titration reverse the ability and the ability to reach target concentrate.

Target concentrations rapidly, we look forward to leveraging our commercial organization and synergies within the treatment community and with that I'll turn the call over to Stuart to provide an update on Royal dissenters.

Stuart Kupfer: In the first quarter, we continued enrolling patients in COURAGE-ALS, the phase three clinical trial of rel-deceptive in ALS. Enrollment has been progressing well, with over 70 centers activated in the U.S., Canada, Australia, and Europe, and more than 150 patients enrolled. Support of our ethos and essential to our mission is the conduct of rigorous and disciplined clinical research. We are pleased to have enrolled the most ALS patients into recent clinical trials at any company, even before Courage ALS, which is planned to enroll 555 patients.

Thanks, Andrew.

In the first quarter, we continued enrolling patients encourage ALS the phase III clinical trial around the centers and ALS enrolled.

Enrollment has been progressing well with over 70 centers activated in the U S, Canada, Australia, and Europe and more than 150 patients enrolled.

Core to our hate those and essential to our mission is to conduct a rigorous and disciplined clinical research. We are pleased to have enrolled the most ALS patients into recent clinical trials at any company, even before courage ALS, which is planned to enroll 555 patients.

Stuart Kupfer: The primary endpoint of the trial is a change from baseline to 24 weeks in ALS-FRS-R, an endpoint deemed clinically relevant in both FDA and EMA guidance to evaluate a treatment effect on the function of daily activities in ALS. The main secondary endpoint is a combined assessment of function and survival, which is a joint rank test of the ALSFRS-R total score, time to onset of respiratory insufficiency, and survival time up to 24 weeks.

The primary endpoint of the trial is the change from baseline to 24 weeks and ALS FRS or an endpoint deemed clinically relevant in both FDA and EMA guidance as to evaluated treatment effect on function of daily activities in ALS.

The main secondary endpoint as a combined assessment of function and survival.

As a joint rank test of ALS FRS, our total score time to onset of respiratory insufficiency and survival time up to 2024 weeks.

Stuart Kupfer: Other secondary endpoints include change from baseline to 24 weeks for vital capacity, the patient-reported outcome questionnaire, ALSAC-40, and bilateral hand-grip strength, reflective of our focus on patient centricity. We designed COURAGE-ALS with important input from patients and caregivers to optimize the patient experience and reduce their burden, including many remote. Additionally, to ensure patients can continue therapy with background medicines, patients who are currently taking stable doses of Riluzol and or Adarabone are permitted to enroll, and the randomization is stratified accordingly.

Other secondary endpoints include change from baseline to 24 weeks for a vital capacity the patient reported outcome questionnaire, all sat 40 and bilateral handgrip strength.

Reflective of our focus on patient Centricity.

We designed <unk> with important input from patients and caregivers to optimize the patient experience and reduce the burden, including many remote visits.

Additionally to ensure patients can continue therapy with background medicines patients who are currently taking stable doses of <unk> <unk> are permitted to enroll and the randomization is stratified accordingly.

Stuart Kupfer: We also plan to provide continued access to related symptoms to patients who complete COURAGE-ALS in an open-label extension trial. Furthermore, patients in COURAGE-ALS, as well as patients who participated in our prior ALS trial, will have the opportunity to enroll in a managed access program developed with the objective to ensure safe, ethical, and equitable access to related symptoms. In face-to-face meetings with investigators and patient advocates, we have received enthusiastic support for the patient-friendly protocol in COURAGE-LS, which was built on the solid foundation of our large and robust Phase II trial Fortitude ALS.

We also plan to provide continued access throughout the SMT to patients who complete courage AOS and an open label extension trial.

Furthermore, patients encourage ALS as well as patients who participated in our prior analyst trial will have the opportunity to enroll in our managed access program developed with the objective to ensure it's safe ethical and equitable access to Ralph incentive.

And face to face meetings with investigators and patient advocates we have received enthusiastic support for the patient friendly protocol encourage ALS.

It was built on the solid foundation of our large and robust phase II trial Fortitude ALS.

Stuart Kupfer: Later this year, we expect the Data Monitoring Committee to conduct the first interim analysis in the COURAGE-ALS trial, which will assess for futility and be triggered 12 weeks after approximately one-third of the planned number of patients have been randomized. A second interim analysis will also assess for futility, and there will be an option for a fixed increase in total enrollment, if necessary, to augment statistical power of the trial. ALS is a devastating disease, and no one knows that better than patients and their caregivers.

Later this year, we expect the data monitoring committee to conduct the first interim analysis and the courage AOS trial, which will assess for futility and has triggered 12 weeks. After approximately one third of the planned number of patients is randomized.

A second interim analysis will also assess for futility.

And there will be an option for a fixed increase in total enrollment if necessary to augment the statistical power of the trial.

ALS is a devastating disease and no one knows that better than patients and their caregivers.

Robert Wong: They are desperate for new options and therapies. It is our mission to bring forward a new therapeutic option through high-integrity research and diligent investigation. And with that, I'll turn it over to Robert Wong. Thanks, Stuart. We ended the first quarter with approximately $686 million in cash and investments.

We are desperate for new options and therapies.

It is our mission to bring forward, a new therapeutic option through high integrity research and diligent investigation.

And with that I'll turn it over to Robert Wong.

Sure.

We ended the first quarter with approximately $686 million in cash and investments our revenues in Q1 2022 came from Astellas to co fund courage.

Robert Wong: Our revenues in Q1 2022 came from Estella to co-fund Courage LS. Our first quarter 2022 R&D expenses increased to $45.9 million from $31.6 million in the first quarter of 2021, primarily due to increases in spending on our cardiac myosin inhibitor programs, our new headquarters facility, and our skeletal muscle program. More than 55% of our R&D expenses were attributable to our cardiovascular programs, as expected, given activity for the cardiac myosin inhibitor program, and the remainder of our expenses were attributable to our skeletal and early research activities. Our first quarter 2022 G&A expenses were $33.1 million, up from $15.6 million in Q1 2021, due to higher commercial readiness spending and higher personnel-related costs, including stock-based compensation.

Our first quarter 2022, R&D expenses increased to $45 9 million from $31 6 million in the first quarter of 2021, primarily due to increases in spending on our cardiac cardiac myosin inhibitor programs on the new headquarter facility and our skeletal muscle.

Program.

More than 55% of our R&D expenses were attributable to our cardiovascular programs as expected given activity for the cardiac myosin inhibitor program and the remainder of our expenses were attributable to our skeletal and early research activities.

Our first quarter 2022, G&A expenses were $33 1 million up from $15 6 million in Q1, 2021, due to higher commercial readiness spending and higher personnel related costs, including stock based compensation and now Ching will review, our financial outlook and corporate develop.

Ching Jaw: And now Ching will review our financial outlook and corporate development strategy. Thanks, Robert. Our end-of-quarter cash balance of approximately $686 million is inclusive of the $200 million in payments we received from Zhijing and Royalty Pharma from the transactions announced in December last year and January of this year, respectively. Our balance sheet could be further bolstered by our deal with Royalty Pharma, which affords us access to long-term capital of up to an additional $300 million, subject to certain conditions, primarily to support the potential commercialization Our approach to building a commercial infrastructure will remain prudent, with spending tied to key de-risking milestones.

<unk> strategies.

Thanks Robert.

Our end of the quarter, our cash balance of approximately $686 million is inclusive of the $200 million in payments, we received from <unk> and royalty pharma from the transactions announced in December last year and January of this year respectively.

Our balance sheet could be further bolstered by our deal with royalty pharma, which affords us access to long term capital of up to an additional 300 million subject to certain conditions.

Primarily to support the potential commercialization of <unk> and further development of <unk> in Canada.

Our approach to building a commercial infrastructure will remain prudent with spending tied to key derisking milestone.

Ching Jaw: Given our plans to only hire our sales force after potential NDA approval of Omicam to McCarville, we expect a slower ramp-up in commercial spending in 2022. If Omicantum Accorbo receives approval in late 2022, we expect a more significant post-approval related increase in spending in 2023. Our corporate development strategy remains focused on partnering and longer-term strategies of sensibly building our organization.

Given our plans to only hire our sales force after potential NDA approval Boming chemical mccarville.

Expect a slower ramp up in commercial spending in 2022.

If only cantel Mokobo received approval in late 2022, we expect a more significant post approval related increases in spending in 2023.

Our corporate development strategy and remain focused to partnering and longer term strategies those sensibly building our organization.

Ching Jaw: During the quarter, we continue business development interactions focused on potential partnerships in Asia and Europe. We are seeking a potential partner to facilitate the launch of Omicantum Carbo in Europe. As we focus on our own U.S. launch, having a partner to commercialize Omicantum Carbo in Europe could afford an on-ramp for us to build our own capabilities in Europe in order to support the future commercialization of Apicantum ourselves in

During the quarter, we continue business development interactions focus to potential partnerships in Asia and Europe .

First.

We are seeking a potential partner to facilitate the launch of <unk> in Europe .

As we focus our own U S launch, having a partner to commercialize <unk> in Europe could afford an on ramp for us to build our own capabilities in Europe in order to support the future commercialization of <unk> ourselves.

In Japan, we.

Ching Jaw: We are looking to partner both Omicamptin-McCarbol and Apicamptin together with a partner commercializing both potential medicines, similar to how we partnered both with Xi Jinping and in China. We have a history of strong deal making and look forward to continuing these interactions with potential partners with the objective of closing one or more deals this year. And with that, I'll turn the call back over to Robert Blum. Thank you

We are looking to partner out both <unk> and <unk> together with a partner commercializing both potential medicines.

Similar to how we partners, both with <unk> and in China.

We have a history of strong deal, making and look forward to continuing these interactions with potential partners with the objective to close one or more deals this year.

And with that I'll turn the call back over to Robert Blum.

Robert Blum: So, as you've heard, we began 2022 with important progress across our late stage pipeline, as well as impressive growth across our organization to support the potential approval of Omicam for McCarville later this year. We recently surpassed 300 employees, and I'm pleased with the caliber of talent and the expertise we're building across the organization. Candidates are excited to join our team, given our leadership in muscle biology and the promise of our potential medicines.

King.

As you've heard we began 2022 with important progress across our late stage pipeline as well as impressive growth across our organization to support the potential approval of <unk> later this year.

We recently surpassed 300 employees and I am pleased with the caliber of talent and the expertise we're building across the organization.

<unk> are excited to join our team given our leadership in muscle biology, and the promise of our potential medicines.

Robert Blum: I want to take this opportunity to thank our employees for all that they're doing to build the next great biopharmaceutical company. We recently conducted a comprehensive employee survey and had 98% employee engagement, underscoring our highly committed employees who care deeply about doing impactful work on behalf of patients.

I want to take this opportunity to thank our employees for all that they're doing to build our next great biopharmaceutical company.

We recently conducted a comprehensive employee survey and had 98% employee engagement underscoring our highly committed employees, who care deeply about doing impactful work on behalf of patients.

Robert Blum: During the quarter, we also continued intensive work towards our goal of advancing earlier-stage drug candidates, including CK136, our cardiac troponin activator, as well as other muscle-directed compounds into IND-enabling studies. Our cardiovascular pipeline continues to expand with novel mechanism drug candidates leveraging over two decades of our pioneering leadership in muscle biology and pharmacology, and more to come on those programs soon. At the leadership level, we recently announced changes to our board of directors.

During the quarter. We also continued intensive work towards our goal of advancing earlier stage drug candidates, including CK 136, our cardiac troponin activator as well as other muscle directed compounds into IND, enabling studies.

Our cardiovascular pipeline continues to expand with novel mechanism drug candidates leveraging over two decades of our pioneering leadership in muscle biology, and pharmacology and more to come on those programs soon.

At the leadership level, we recently announced changes to our board of directors.

Robert Blum: Dr. Pat Gage, who served as our Chairman of the Board since 2010, retired from the Board. This was a planned transition announced over a year ago. His retirement was a personal decision, and he departs with our utmost respect and admiration.

Dr. Pat Gage, who served as our chairman of the board since 2010 retired from the board.

This was a planned transition announced over a year ago.

His retirement was a personal decision and he departs with our utmost respect and admiration we.

Robert Blum: We thank him for his many years of service to our board. Upon Pat's retirement, Dr. John Henderson was named the new chairman of the board. John has served as a member of our board since 2009, and we're confident he will lead with discipline and a strong vision for the company in his new position as chairman. Additionally, we have appointed Dr. Bob Harrington to our board. Bob's appointment follows the resignation of Rob Califf from our board, which was prompted by his being named FDA commissioner. Like Rob, Bob is a cardiologist.

We thank him for his many years of service to our board.

Upon patch retirement, Dr. John Henderson was named the New Chairman of the Board. John has served as a member of our board since 2009, and we're confident he will lead with discipline and a strong vision for the company in his new position as chairman.

Additionally, we appointed Dr. Bob Harrington to our board.

Bob Bobs appointment follows the resignation of Rob Calif from our board, which was prompted by his being named FDA Commissioner like Rob Bob as a cardiologist.

Robert Blum: Bob is also Chair of Medicine at Stanford and has a distinguished academic career, bringing broad experience to the company, having overseen dozens of global cardiovascular clinical trials. We're very pleased to welcome Bob to our board. Finally, as Ching elaborated, our recent and second deal with Royalty Pharma not only extends but also expands our partnership and provides ample runway to execute on our commercial and clinical plans in a prudent yet purposeful manner. As we continue to execute against our vision 2025, our ability to monetize our pipeline in order to realize our ambitious goals remains mission critical.

Bob is also chair of medicine at Stanford and with a distinguished academic career, bringing broad experience, having overseen dozens of global cardiovascular clinical trials.

We're very pleased to welcome Bob to our board.

Finally, as Ching elaborated are recent and second deal with royalty pharma not only extends but also expands our partnership and provides ample runway to execute on our commercial and clinical plans in a prudent yet purposeful manner as.

As we continue to execute against our vision 2025, our ability to monetize our pipeline in order to realize our ambitious goals remains mission critical.

Robert Blum: This newer deal is consistent with our corporate development strategies to affordably enable our transformation to a commercial stage company, while also continuing to accelerate our development plans. Now, I'll recap our key milestones for 2022. For Omicamptin-McCarbyl, we expect to launch Omicamptin-McCarbyl in the U.S. pending potential FDA approval in Q4 2022.

This newer deal is consistent with our corporate development strategies to affordably enable our transformation to a commercial stage company, while also continuing to accelerate our development plans.

Now I'll recap our key milestones for 2022 for <unk>, we expect to launch of <unk> in the U S pending potential FDA approval in Q4 2022 for Ft. Campton, we expect to continue enrolling patients with obstructive HCM.

Robert Blum: For Afecamptin, we expect to continue enrolling patients with obstructive HCM in Sequoia HCM throughout 2022. We expect to continue enrolling patients with non-obstructive HCM in Cohort 4 of Redwood HCM, and we expect to begin a second Phase 3 clinical trial of aficamptin in obstructive HCM in the second half of this year. And as you heard from Fady, we expect to share data from Redwood HCM OLE, the Open Label Extension Study of Affey-Campden, at the Heart Failure 2022 meetings later this month, May 23, 2022.

In Sequoia HCM throughout 2022.

We expect to continue enrolling patients with non obstructive HCM in cohort four of Redwood HCM and we expect to begin a second phase III clinical trial of <unk> Kimpton and obstructive HCM in the second half of this year.

And as you heard from <unk>, we expect to share data from Redwood HCM <unk> E. The open label extension study about the kimpton the.

Heart failure 2022 meetings later this month may 23rd 2022 for CK $103 six we expect to reactivate that development program in this year for <unk>, We expect the data monitoring committee to conduct the first interim analysis from courage AOS.

Robert Blum: For CK136, we expect to reactivate that development program this year. For REL-Deceptive, we expect the Data Monitoring Committee to conduct the first interim analysis from COURAGE-ALS in the second half of this year. And for our ongoing research, we expect to advance new muscle-directed compounds and to conduct IND-enabling studies for one to two potential drug candidates.

In the second half of this year and for our ongoing research, we expect to advance new muscle directed compounds and to conduct IND, enabling studies for one to two potential drug candidates.

Operator: An operator With that, we can now open up the call to questions, please. Thank you. Ladies and gentlemen, in order to ask a question, you will need to press star one on your telephone.

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

Thank you, ladies and gentlemen in order to ask a question you will need to press star one on your telephone until we drive question press the pound key please standby, while we compile the Q&A roster.

Operator: And to withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Carter Gould of Barclays. Your line is open. Good afternoon, guys. Hey, great. Maybe good afternoon.

Your first question comes from the line of Carter Gould of Barclays. Your line is open.

Carter Gould: Maybe to start with Robert and Fady, probably an appropriate opportunity to get you guys to comment a bit on the Mavicampton label and pricing, and specifically as you think about implications for differentiation and the market opportunity. I know, Robert, you never kind of explicitly guided on pricing assumptions, but it does appear directionally higher than we and much of the street had expected. We'd love to get your thoughts on those topics.

Good quarter, guys, Hey, great maybe good afternoon, maybe to start with for Robert and fatty.

Probably an appropriate opportunity to get you guys to comment a bit on the mavic Hampton label on pricing and specifically as you think about implications for differentiation and the market opportunity I know Robert never kind of explicitly guided on pricing assumptions, but it does appear directionally higher than than we and much of the street had had expect.

It would love to get your thoughts on those topics.

Robert Blum: Sure, so I'll start and maybe turn to Fady, and also we should ask Andrew to comment, especially as your question related to pricing. First, we want to congratulate BMS and all the colleagues at Myocardia for this approval, but also the HCM patients, the clinical investigators, the advocacy groups, and everyone else that participated. And that includes cytokinetic scientists who conceived of the therapeutic hypothesis for cardiac myosin inhibition and who participated in the discovery of Mavacampton.

Sure So I'll start and maybe turn to Saudi and also we should see.

Andrew to comment, especially as your question pertains to pricing.

Firstly.

We want to congratulate BMS and all the colleagues at myocardium for this approval, but also.

The HCM patients clinical investigators the advocacy groups and everyone else that participated and that includes psychokinetic scientists, who conceived of the therapeutic hypothesis for cardiac myosin inhibition and who participated in the discovery of novel Kimpton.

Robert Blum: This is a meaningful milestone for the fact that it's the first drug approved with an indication of obstructive HCM, and the data from EXPLORER are surely compelling. With that said, as others have commented, the label is now in the public domain, and there are things about that label that we think make sense, and things about that label that enable a next-in-class opportunity to potentially demonstrate differences.

This is a meaningful milestone for the fact that it's the first drug approved with an indication of obstructive HCM and the data from explore are surely compelling.

With that said.

As.

Others have commented the label is now in the public domain.

And there are things about that label that we think makes sense and things about that label that enable a next in class opportunity to potentially.

Demonstrate differences that's why we're doing Sequoia HCM and we hope Sequoia HCM will elaborate on what could be nexgen class properties purposely engineered into <unk> kimpton long ago.

Robert Blum: That's why we're doing Sequoia HCM, and we hope it will elaborate on what could be next-in-class properties purposefully engineered into Affey-Campden long ago. You asked about pricing, and yes, I think the pricing did come in higher than was consensus. And we were within that consensus, expecting prices to be different.

Robert Blum: But with that said, I think pricing is now coming in as more comparable to surgical interventions. When you consider the number of echoes that need to be performed, both to get to a steady state target dose and also a maintenance program for Mavicamton, the costs are even in excess. And we would expect BMS knows what they're doing. They have done their payer research. They've done their work around pharmacoeconomics. And despite what ICER came in with, I expect BMS understands where the market clearing price will be.

You asked about pricing.

And yes, I think the pricing did come in.

Higher than was consensus.

We were within that consensus expecting price to be different but with that said I think pricing is now coming in as is more comparable to surgical interventions.

When you consider the number of echoes that need to be performed both to get to.

Our steady state target dose and also our maintenance program for Maverick Camden.

The costs are even in excess.

And we would expect to BMS knows what theyre doing very have done their payer research they've done their work around the farmer economics.

And despite what ice or came in with I expect BMS understands where the market clearing price will be and at the same time.

Robert Blum: And at the same time, I expect from the standpoint of patient assistance and contracting, there's going to be programs that will be elaborating on how that could still result in lower net costs to patients and also assist in reimbursement. So I think this is all still to be playing out in connection with what I'm sure will be sensible commercial launch plans that BMS is already implementing. So maybe with that, I'll ask Fady or Andrew if there's anything further they want to elaborate on.

I expect from the standpoint of patient assistance and contracting there's going to be programs that will be elaborating on how that could still result in lesser net cost to.

Patients and also as would be assisting in reimbursement. So I think this is all still to be playing out in connection with what I'm sure will be sensible commercial launch plans that BMS is already implementing.

So maybe with that I'll ask Saudi or Andrew if theres anything further they want to elaborate.

Robert Blum: Well, maybe I'll just expand a little bit on Appy Campton and how we have developed it and what we think it may provide in terms of convenience for patients and safety and so forth. You can sort of do your own comparison.

Well, maybe I'll just.

Expand a little bit on on <unk>.

Happy Campton, and how we have developed it and what we think.

It may provide in terms of.

Convenience for patients and safety and so forth.

You can sort of do your own comparison.

Fady Malik: I'll just say, you know, with apicamptin, the way Sequoia is designed, dose escalation should be complete within six to eight weeks. We don't anticipate dose interruptions if EFs are less than 50, as long as they're greater than 40, but merely dose-down titrations. So hopefully, data from Sequoia, as well as from the ongoing open-label extension, would support a simple escalation scheme that's completed within six to eight weeks. Appy Kempton was engineered to avoid drug-drug interactions, and to date, we haven't uncovered any significant drug-drug interactions with Appy Kempton.

Also say.

Would that be Camden.

The way Sequoia is designed.

A dose escalation should be complete within six to eight weeks.

We don't anticipate dose interruptions, if aes are less than 50 as long as they are greater than 40, but merely dose down titrations.

So hopefully those those data from Sequoia as well as from the ongoing open label extension would support a simple escalation scheme, that's completed within six to eight weeks.

<unk> is engineered to avoid drug drug interactions and to date, we haven't uncovered any significant drug drug interactions.

With Abbvie campton.

Fady Malik: We've shown the reversibility of effect in data that we've presented from Redwood, which I think enables its titratability and also provides a means to safely escalate or de-escalate dose. So those are the things I would highlight, you know, that and I think as well as the conduct of sequoia, we're studying it in both monotherapy with other drugs, like beta blockers, calcium channel blockers, dual therapy with those drugs, or with isopyramide and beta blockers as background therapy. So I think we'll have a fairly good understanding of how it performs in those various different conditions. Andrew, anything you want to add? This is maybe very quickly on pricing.

We've shown the reverse ability of effect in data that we presented from Redwood, which I think enable its type trade ability and also provide.

A.

Means to safely escalate or deescalate dose.

So those are the things I would highlight that and I think as well as the.

On the conduct of Sequoia.

We're studying it in both mono therapy with other drugs like beta blockers calcium channel blockers dual therapy with those drugs or with us are paramount and beta blockers as background therapy. So I think we'll have a fairly good understanding of how it performs in those various different conditions.

Andrew anything you want to add.

Andrew Callos: I won't say much about, obviously, BMS's strategy, more that, as Robert stated, maybe came in slightly higher than we were expecting. It'll be interesting, and we'll obviously look how the market reacts, meaning payers, if there are more controls they would put in place, things like prior authorisation to label or step edits through beta blockers or calcium chattel blockers. So those types of things we'll see. It did come in at flat pricing, meaning every dose is the same price, which is as we expected, and there could be further costs in terms of support programs and room to negotiate.

It just maybe very quickly on pricing I won't say much about obviously bms's strategy.

More of that as Robert stated, maybe it came in slightly higher than we were expecting it will be interesting and we'll obviously look how the market reacts meaning payers if theres more controls they would put in place prior things like prior offs to label or step edits through beta blockers or calcium channel blockers for those types of things, we'll see it did.

Come in flat pricing, meaning every dosage that same price, which is as we expected.

And there could be.

<unk> cost in terms of support programs.

Room to negotiate so I think these are all the factors that likely went into it but.

Andrew Callos: So I think these are all the factors that likely went into it, but we have some time. We'll continue to evaluate the market and see how we net out from a labeling point of view as we decide our pricing. Thank you, Carter. Your next question comes from the line of Jason Butler with JMP. Your line is open. Hi, it's Roy on behalf of Jason.

We have some time will continue to evaluate the market and.

See how we net out from a labeling point of view as we decide or pricing.

Future.

Thank you.

Thank you Carter.

Your next question comes from the line of Jason Butler with JMP. Your line is open.

Hi, it's Roy in for Jason Thanks for taking the questions I guess first one a couple of clarification questions.

Jason Butler: Thanks for taking the questions. I got the first one, and there were a couple of clarification questions. Refused by Fady's comments about the second obstructive HCM phase 3 that's going to start in the second half, he said, Not going head-to-head against Mavicampton, but against a drug with a novel mechanism, clarify that, Presumably it's an approved drug, is that correct? That's not exactly what he said, but maybe he can elaborate.

Confused by fatty his comments about the second obstructive HCM phase III, just going to start in the second half. We said, it's not going head to head against some havoc Hampton, but against that drug with a novel mechanism can you just.

Clarify that it presumably it's an approved drug is that correct.

That's not exactly what you said, but maybe he can elaborate okay. Yes.

Fady Malik: OK. Yeah, no worries. What I said was, it would be a standard of care therapy. So I didn't elaborate on the design or of the second trial. I just said that it wouldn't be against Mavicampton, and it could be against standard of care or other aspects of the disease. Got it.

What I said it would be a standard of care therapy. So.

I didn't elaborate.

On the design of the second trial I, just said that.

It wouldn't be against Mavic Hampton.

And it could be against standard of care or other other.

Aspects of the disease.

Got it.

Fady Malik: OK. That made more sense, of course. Alright, is finalizing the trial design all that's preventing us from starting that trial now? I wish starting trials were that easy, but no, once we finalize the trial design, there are operational things such as... IRB submissions and regulatory submissions and so forth. And we probably will also ultimately have regulatory interaction as well. So there are a few things ahead of beginning enrollment, but we've got all those under control. Okay, great. And then on COURAGE-ALS, you mentioned increasing the enrollment size. Can you do that at both of the interims?

With any questions.

Alright.

Finalizing the trial design is that all this gating to starting that trial now.

I wish starting trials were that easy, but no any once we finalize the trial design and other operational things such as IRB submissions and regulatory submissions and so forth then we'd probably will also.

Ultimately.

Have an interaction regulatory interaction as well. So there are few things ahead of.

Beginning enrollment but.

We've got all those under control.

Okay, Great and then I encourage ALS you.

You mentioned, increasing the enrollment.

Can you do that at both of the Interims.

Stuart Kupfer: um... and I guess, in the event of stunningly good data, could the trial be stopped early for efficacy? Hi, this is Stuart Kupfer. Yeah, thanks for the question. So the first interim analysis is for futility only? There's not an option for sizing the trial, but that is an option for the second interim analysis. In terms of stopping for, Unknown Attendee, Steve Smith, Unknown Attendee, Unknown Attendee, Unknown Attendee, Okay, thanks.

And then I guess.

In the event of a stunningly good data because the trial be stopped early for efficacy.

Hi, This is Stuart kupfer.

For the question. So the first interim analysis is.

For futility only.

There is not an option for upsizing the trial, but that is an option for the second interim analysis.

In terms of stopping for.

Efficacy.

The second interim analysis essentially has quite a.

Broader range includes futility and potentially stopping for superiority, but yes, that's a very high bar.

So that's not something we're counting on.

Okay. Okay. Thank you.

Thank you.

Stuart Kupfer: Thank you. Your next question comes from the line of Joe Pantginis of HC1, right? Your line is open.

Your next question comes from the line of Joe <unk> of H C. Wainwright. Your line is open.

Joe Pantginis: Good afternoon, everybody. So I also wanted to stick with courage. Very encouraging the enrollment that you're seeing, but also a bit disquieting. So I just wanted to focus on the interns as well and maybe overall. Are you disclosing or can you remind us what the alpha spend is? Overall, what the hurdle is.

So Jody Hey, there.

Afternoon, everybody. So I also wanted to stick with courage, so very encouraging the enrollment that youre seeing but also a bit disquieting because of the underlying indication that the demand remains high.

So I just wanted to focus on the in terms as well and maybe overall.

Are you disclosing or can you remind us what the alpha spend is for each of the interim analyses and <unk>.

Overall, what the hurdle is.

Stuart Kupfer: Right, we haven't really disclosed those details. What I think we can say is that for this first interim analysis for utility, it's not really a high bar to continue the trial. So we're confident that we'll be proceeding past that interim analysis. Okay, what we've said is that the relative symptom treatment arm would have to do worse. Then the standards of care for us to meet the futility threshold for the first syndrome, and that's, again, as Stuart points out, that's a low bar for what we already know. The second interim does provide for early stopping for futility or otherwise allows us to increase the size if we wanted to amplify on a signal observed, albeit that would be blinded to us.

We havent really disclosed those details.

What I think we can say is that for this first interim analysis for futility.

It's not.

Really a high bar.

To continue the trial. So we're confident that we'll be proceeding past that interim analysis. What we've cited is that.

<unk>.

The <unk> treatment arm would have to do worse.

Then the standard of care for us to meet the futility threshold for the first interim and Thats.

As Stuart points out that's all.

Low bar for what we already know the.

The second interim does provide for early stopping for futility or otherwise allows us to increase the size. If we wanted to amplify on a signal observed, albeit that would be blinded to us.

Robert Blum: And that would be determined by the data monitoring committee. So we have not disclosed to your question any of the alpha spent. Just to be clear, for futility, there's never any alpha spend, so there's no alpha spend on any of the futility analyses; it's only with regard to efficacy if you decide to include that, and then just on Omakam. The quicker part of the question is, and I know, Robert... Pretty much administrative back and forth with the FDA right now. Do you consider, www.youtube.com, New York data? Any learnings that you would point to that allow Paul Absaic, of the population, or the protocol, or is that the House of...

And that would be determined by.

The data monitoring committee. So we have not disclosed to your question any of the alpha spend.

Just to be clear for futility.

There is alpha spend so there's no alpha spend on any of the futility analysis only with regards to efficacy if you decide to <unk>.

Include that got it got it. Thank you for the clarification and then just on OMA captive.

The quicker part of the question is and I know Robert you said, it's pretty much administrative back and forth with the FDA right now do you consider any of the back and forth rate limiting at this moment and then.

Secondly, with regard to <unk> I wanted to focus on just the meteoric data.

Any learnings that you would point to that allow for the potential of say tweaking of the population or the protocol or is that potential path closed at this point.

Robert Blum: I'll take the first one and maybe ask Fady to speak to the second one. Regarding your question about the back and forth, the interactions with FDA, no, I don't consider any of them to be rate-limiting or to affect the timeline for review and approval. These are interactions that I believe are customary for an application of the sort that we submitted. And therefore, I think we remain on the same timeline. And the second question with regard to meteorics.

I will take the first one and maybe a strategy to speak to the second one regarding your question about the back and forth the interactions with FDA.

I don't consider any of them to be rate limiting or to affect the timeline for review and approval.

These are interactions that I believe are customary for an application of the sort that we submitted and therefore I think we remain on the same timeline.

And second question with regards to meteoric.

Fady Malik: You know, I don't think that we haven't really identified a subgroup within the meteoric population where we could confidently say that there is a large treatment effect that would warrant, you know, redoing the trial, per se. That said, within meteoric, we didn't enroll very sick patients. They were really kind of the opposite of what we enrolled in galactic.

I don't think that.

We haven't really identified a subgroup within the meteoric population, where we could confidently say that there is a large treatment effect that would warrant.

Redoing the trial per se.

That said within New York, we Didnt enroll.

Very sick patients they were really kind of.

Opposite of what we've enrolled in galactic and so.

Fady Malik: And so one could ask if you were able to conduct the trial in a much sicker patient population, might you see an improvement in exercise capacity? And I think it's still an open question, but I think it's unlikely we'll pursue it. A lot of cooperative challenges or something like that. Thank you. Thanks, Joe. Your next question comes from the line of Akash Tewari of Jeffries. Your line is open. Good afternoon, Akash. This is Amy.

One could ask if you were able to conduct the trial in much sicker patient population might you see.

An improvement in exercise capacity.

And I think it's still an open question, but.

Think it's unlikely we'll pursue it.

A lot of operational challenges or something like that of course, thanks for the added color guys.

Thank you thanks, Jim.

<unk>.

Your next question comes from the line of a cash story of Jefferies. Your line is open.

Good afternoon.

Akash Tewari: I'm for Akash. Thanks so much for taking our questions. Just a couple.

This is Amy I'm very clear thanks, so much for taking our question.

Fady Malik: So the first one, if we look at MAVA's label, it seems like the benefit from MAVA was smaller in patients on background beta blockers compared to those who weren't. Why do you think we're seeing this type of phenomenon? Can it be that patients on beta blockers at baseline may have lower LVF to begin with, which could potentially limit MAVA's ability to updose? And where do you think AFI could potentially differentiate? And also, what are the implications for physicians when it comes to concomitant use given this phenomenon? These are some of the questions that came out when these data were presented and published. Maybe I'll ask Fady if he wants to comment on that.

Just a couple so the first one if we look at <unk> label.

Right.

That's it from Dabber with smaller in patients on background beta blocker compared to dose the Wang.

Why.

We've seen this type of phenomenon can it be that patients.

On beta blockers that baseline may have lower lvs to begin with which could potentially limit <unk> ability to up dose.

Where do you think you could potentially differentiate.

And also what are the implications for physicians when it comes to concomitant use given this phenomenon.

Good questions. These are some of the observations that came out when these data were presented and published maybe I'll ask Saudi if he wants to comment on that.

Fady Malik: Let me just generally comment on the challenge of beta blockers and trials of exercise performance. You know, Meteoric also had almost 90% of the patients were on beta blockers. And they have two different effects, right? They limit the amount that you can increase your heart rate, which is important to increasing cardiac output, and they also act on skeletal muscle and decrease it.

Let me just generally comment on the challenge of beta blockers and trials of exercise performance.

Meteoric also had they're almost 90% of the patients who are on beta blockers.

And they have two different effects right. They limit the amount that you can increase your heart rate, which is important to increase in cardiac output and they also act on skeletal muscle and decrease its.

Fady Malik: ability to exercise as well. And so, in the context of hypertrophic cardiomyopathy, Mavit Kampton demonstrated improvements in exercise capacity in patients with beta blockers, albeit the effects were attenuated, not surprisingly, because of the combination of those two therapies. You know, I think the real question to ask is, in the context of using a cardiac myosin inhibitor, is beta blocker therapy really needed in HCM? And ultimately, is that something that physicians need to institute in their patients?

Ability to exercise as well.

And so.

In the context of hypertrophic cardiomyopathy.

Mavic campton demonstrated improvements in exercise.

Capacity in patients with beta blockers, albeit the effects were attenuated not surprisingly because of the combination of those two therapies.

I think the real question to ask is is in the context of using a cardiac myosin inhibitors as a beta blocker therapy really needed.

And ultimately.

Is that something that.

Physicians need to institute and their patients and might they maximize their treatment benefit in their quality of life events.

Fady Malik: And might they maximize their treatment benefit and their quality of life eventually by substituting a myosin inhibitor for a beta blocker? So, those are important research questions, as you can imagine, and I think we'll unravel the answers as time goes on. Great, that's super helpful.

Eventually by subset.

Substituting myosin inhibitor for a beta blocker. So those are important research questions. As you can imagine and I think will unfold and the answers will unfold as time goes on.

Fady Malik: And then another one, MAVA seemed to show greater benefit in NYHA Class 3 patients in Explore. Do you think, how does Aficantin compare relatively to MAVA in severe patients? Again, I hate that we're not doing a comparative trial, and so it's going to be very hard to compare, you know, exact numbers from one study to the other, given the populations will be somewhat different. I'll just comment generally that I think sicker patients generally will achieve greater benefits. They have a greater symptomatic burden and a greater exercise burden.

Great. That's super helpful. And then another one Matt that seemed to show a greater benefit.

And why HLA class III patients in explorer.

Ruth Thank Asher how do you think asset Camden can compare relatively to mapping to their patients.

So again.

We're not doing a comparative trial and so it is going to be very hard to compare.

<unk> numbers from one study or the other given the populations will be somewhat different.

I'll just comment generally then I think sicker patients generally will.

Achieved greater benefits they have a greater symptomatic burden greater exercise burden theres more room, if you will for them to improve and so.

Fady Malik: There's more room, if you will, for them to improve. And so it's not surprising, if you will, that the more severely affected patients have a greater treatment effect. Okay, got it. Thanks for having me. Your next question comes from the line of Salim Syed of Mizuho. Hello, Salim. Hey, Robert. Thanks for the questions, guys. Just a couple for me.

It's not surprising if you will that does more severely affected patients have a greater treatment effect.

Yeah.

Okay got it.

<unk> campus.

Your next question comes from the line of Salim Sayed of Mizuho. Your line is open.

Hello Celine.

Hey, Robert.

Thanks for the question guys just a couple from me the first on <unk>. So.

Salim Syed: The first on Mavicamp. Robert, I'd love to know now that we have a price tag in the marketplace for Mavicamp. And if I'm just running some basic math here, when I look at the consensus peak, Navicampton currently has a peak of around $3.5 billion, and Aficampton, the best I can tell, it's closer to around $1.5 billion, so that's about $5 billion, and those are worldwide

Robert I'd Love to know now that we have a price tag in the marketplace for Mavic Camden, If I'm just running some basic math here when I look at consensus peak Mavic Hampton currently has peak around $3 $5 billion.

<unk> campaign, the best I can tell it's closer to around one 5 billion. So that's about 5 billion those are world wide numbers.

Robert Blum: But now that we have a price in the market, just using that $90k price tag and the number you have in your slides for $190k obstructive patients, symptomatic, just in the U.S., obviously, you get to TAMs here that are much larger, even if you assume a 40% growth to net and an 80% compliance, so just curious here, how are you thinking about TAM now that there's of how TAM could mature here on this particular day. If you're asking us if there appear to be discrepancies between those underlying assumptions and the consensus estimates, I think there are, and I think you've pointed that out already in some of your notes.

But now that we have price in the market just using that 90 day price tag and the number you have in your slides for 190, K obstructive patients symptomatic just in the U S. Obviously, you could get to Tim's here that are much larger even if you assume a.

A 40% gross to net.

And 80% compliance. So just curious here how are you thinking about Tam now that theres a price in the marketplace.

How does how timken mature here for this for this particular disease.

If youre asking us if there.

Appear to be discrepancies between those underlying assumptions and the consensus estimates I think there are.

You've pointed that out already in some of your notes.

Robert Blum: I think that now that we have a price set by BMS, it's an opportunity for analysts and investors both, but also for us at cytokinetics to consider how we think about this market opportunity. And we will, but in line with data. And, you know, we're still enrolling patients in sequoias. So it's really premature for me to be too elaborating on what I mean by that. In time, I think this will all play out.

I think that now that we have.

Rice.

By BMS.

An opportunity for analysts and investors, both but also for US it's subtle kinetics to consider.

How we think about this market opportunity and we will but in line with data and we're still enrolling patients in Sequoia. So it's really premature for me to be too.

Elaborating on what I mean by that in time I think this will all play out and we continue to believe that a next in class opportunity can become the category leader.

Robert Blum: And, you know, we continue to believe that a next-in-class opportunity can become the category leader. Do you think there's potential here for this to be a $10 billion plus market worldwide?

Do you think there is potential here for this to be a $10 billion plus market.

Robert Blum: I'm not going to I'm not going to speak to that. But I do think that where this market ultimately will go will benefit from what will be category expansion, patients who are not currently diagnosed and treated getting diagnosed and treated, and ultimately, this mechanism of action should hopefully translate beyond obstructive HCM to non-obstructive diseases, including segments of patients with HFPAF. So ultimately, I think there's an opportunity, a very meaningful opportunity, for this to be a big business.

Worldwide I am not going to.

I'm not going to speak to that.

I do think that.

Where this market ultimately will go we will benefit from.

What will be.

Category expansion patients, who are not currently diagnosed and treated getting diagnosed and treated.

And ultimately this mechanism of action should hopefully translate beyond obstructive HCM to non obstructive disease, including segments of patients would have pest. So ultimately I think there is opportunity a very meaningful opportunity for this to be a big business.

Robert Blum: Okay, and then just a quick one on the REMS and how you guys are thinking about the base case here for bursitis kinetics in Aficamptin. I know it's early, you don't have phase 3 data yet, but based on what you've seen from the profile for Aficamptin in Redwood and the shower PKPD, the shorter half-life, there is a mechanistic rationale as to why you would see less toxic ejection fraction levels.

Okay, and then just a quick one.

Just on the ramp and how you guys are thinking about base case here for four sided kinetics and naphtha kimpton.

I know, it's early you don't have phase III data, yet, but based on what you've seen from the profile for Alpha Camden in Redwood in the shower PK PK PD shorter half life there'll be mechanistic rationale as to why you would see less toxic.

Robert Blum: What is your base case on REMS? Do you guys think that you can? Is there a possibility here that you don't have a REMS? Yes. Here again, I'm not going to make a comparative statement, but, you know, as we think about Aficampin and an independent drug development program, and for the safety data we've already seen in Redwood HCM, one wouldn't necessarily expect a REMS, albeit there are things that we have to demonstrate in Sequoia HCM in order to be able to ensure that.

Injection fraction levels. What is your base case do you guys think that you can is there a possibility here that you don't have a rems.

Yes.

Sure again, I am not going to make a comparative statement, but.

As we think about <unk>, kimpton, and an independent drug development program and for the.

Safety data, we've already seen in Redwood HCM.

I wouldn't necessarily expect to rems, albeit there are things that we have to demonstrate and Sequoia HCM in order to be able to ensure that so where.

Robert Blum: So we're approaching Sequoia HCM with the goal of elaborating on what could be the next in class properties, as well as affording a safety profile that would potentially not require a REMS. You know, Salim, I think it's also important to remember by the time we, hopefully, come to market that this is no longer going to be a new drug class, and physicians will be more familiar with the use of a cardiac myosin inhibitor. Obviously, there would be differences between different drugs and the need to educate on those differences, but You know, it's not a first-in-class entry, and so that may also temper Thank you, Salim.

<unk> Socorro HCM with the goal of elaborating on what could be the next in class properties as could be affording a safety profile that would be.

Essentially not requiring a rems.

So I think it's also important to remember by the time we.

Hopefully come to market. This is no longer going to be a new drug class and physicians will be more familiar with the use of a cardiac myosin inhibitor.

Obviously, there would be differences between different.

Different drugs and the need to educate on those differences but.

It's not a first in class century.

So that May also temporary for the need for a rems.

Super helpful. Thanks, So much guys.

Thank you Celine.

Salim Syed: Your next question comes from the line at Madhukumar of Goldman Sachs. Your line is, Hello everyone, this is Omari Onufrom-Majumdar. So we have a couple questions. First, what kind of data should we expect from the Redwood OU? at Hartfield in 2022 in May.

Your next question comes from the line of Madhu Kumar of Goldman Sachs. Your line is open.

Hello better than that.

Hi, This is Mariano from Ireland.

So we have a couple of questions first what kind of data should we expect from the Redwood oily.

Madhukumar: It says the endpoints and average time to follow up, and then reminds us how the echo monitoring works in both Redwood, Oiley, and Sequoia ATM and how they're similar or different from prior and ongoing trials of other mice and a hindrance in OACM. And then there is a second question after that.

At heart failure, 2000, congratulating me et cetera, endpoint and average time to follow up and then remind us how the echo monitoring works in both.

And so quite ACM and other similar or different from prior and ongoing trials are there might've been a hindrance and OEM.

The second question.

Robert Blum: Sure, so obviously, we don't want to do anything to jeopardize the presentation of the data by elaborating on what you should expect, but this is a study that now enables a longer durability effect to be observed. And our goal is to be able to demonstrate that with AFI-CAMPTN, one can achieve effects that are continuing. So you'll see data pertaining to the use of AFI-CAMPTN, as Fady elaborated, out to six months. And I'll turn to Fady now if there's anything more he wants to add.

Sure. So obviously, we don't want to do anything to jeopardize the presentation of the data by elaborating on what you should expect.

But it is a study that now enables a longer durability effect to be observed and our goal is to be able to demonstrate that with.

As the Kimpton, one can achieve effects that are continuing so youll see data pertaining to the use of <unk>.

Is.

Ah study elaborated out to six months and I will turn to <unk> now if theres anything more he wants to add.

Robert Blum: Yeah, I mean, I think you can expect the kinds of things we've presented in the past, which have to do with gradients and EF and safety, NYHA class, things like that. So I think, you know, as a first presentation, we'll probably focus on the things that are the same themes that we've elaborated on in prior presentations.

Yes, I mean, I think you can.

We expect the kinds of things we presented in the past to have to do with <unk>.

<unk> and safety.

<unk> class things like that so I think.

You'll see that as a fee.

First presentation will probably.

Focus on the things that the same themes that we've.

Elaborated on in prior presentations.

Fady Malik: You know, your second part was to do with echo monitoring, and I'll say that the general scheme in all our trials is the same. Patients come in at least every two weeks for an echo and the potential to be escalated to the next dose. In the OLE right now, we're restricted to doses of 5, 10, and 15 milligrams. In sequoia, the top dose is 20 milligrams, so it's 5, 10, 15,

Your second part was what to do with Echo monitoring.

And ill say that the general scheme in all our trials is the same.

Patients come in.

At least every two week basis.

For an eco and potential to be up.

Escalated to the next dose.

In the OLED right now we are restricted to doses of 510 15 milligrams.

And Sequoia the top dose of 20 milligrams was 510 15 and 20.

Fady Malik: And EOLE is only restricted because of the need to amend the protocol to allow for the higher dose, which we're in the process of doing. So those are the, you know, so the dosing is quite similar amongst all the trials that we're doing. And I'll add an additional data set we will be capturing in OLE, as well as in Sequoia, cardiac MRI data evaluating cardiac structure, function, and fibrosis. So that will give us an opportunity to evaluate for reverse remodeling. It's probably premature to see that at this upcoming Congress, so.

And <unk> only restricted because of the need to amend the protocol to allow for the higher dose which are in the process of doing.

So those are the.

So the dosing is quite similar amongst all of the trials that we're doing.

And an additional.

Data set we will be capturing in the OLED as well as Sequoia is cardiac MRI.

Dana and evaluating cardiac structure function in fibrosis, so that will give us an opportunity to evaluate for reverse remodeling.

But it will be premature to see that at this upcoming Congress. So.

Fady Malik: Great. And then the second question, what kind of patient subsets in HCM will be most amenable to a myosin inhibitor, given the history of the class in MAGATROM? What types of questions, what types of patients would be most amenable to benefiting from a myosin inhibitor?

Great and then second question, what kind of patient subset.

We'll be most amenable to myosin inhibitor, given the history of the class and Mega trial.

What types of questions what types of patients would be most amenable to benefiting from a myosin inhibitor.

Thank you again.

Fady Malik: That's correct. Thank you. In NACM? Oh, in NACM. Okay, I was trying to... SourceFed Outwell. You know, I think there are a few things that define an NHCM patient. One, obviously, is the thickness of their ventricle. Second is the... There are biomarkers that indicate a ventricle under stress, like antipropion P or troponin.

And <unk> is that one and NH Sam Okay, I'm just trying to.

So I set out well.

I think the.

Fady Malik: And the third is a functional and symptomatic domain. How severe are their symptoms, or how impaired is their exercise capacity? I think just an echo that shows that you have a thickened ventricle and maybe a family history of HCM isn't necessarily adequate for, at this point in time, thinking about initiating therapy with a myosin inhibitor or any therapy at this point. Most of the therapies are being studied in symptomatic or functionally limited patients, and so that's, you know, what I would think of as a population that could be studied in Thank you. Your next question comes from the line of Yasmeen Rahimi, from Piper Sandler. Your line is open. Hello, Yasmeen. Hi, this is Swapnil. I'm for Yasmeen.

There are few things that define in HCM patients.

One obviously is the thickness of their ventricle.

<unk> is the.

They are buying with the biomarkers that indicate ventricle under stress like NT pro BNP or proponent.

And the third is.

<unk> functional and symptomatic domains, how severe their symptoms are how imperatives their exercise capacity.

I think just an echo that shows that you have a second ventricle and maybe a family history of HCM.

Necessarily at adequate for at least at this point in time for thinking about initiating therapy with a myosin inhibitor or.

Any therapy at this point most of the therapies are being studied in symptomatic or functionally limited patients and so that's what I would think of as a population that could be studied in future trials.

Great. Thanks for answering the questions.

Thank you.

Your next question comes from the line of Es mean, Brahimi of Piper Sandler Your line is open.

Yasmeen Rahimi: A couple of questions for us. First one is, we see that the Mawa-Campton label has shown that the drug might be related to embryonic and fetal toxicity. So do we know if this is a myosin inhibitor class effect and what work has been done with Effie Campton to rule out this talk?

Hello, Yes.

Hi, This is something that I'm sorry, you asked me in a couple of questions for us.

First one is obviously that the mahwah campus Liberal has shown that the drug might be related.

Embryonic in situ toxicity, so the lean though like if this is a myosin inhibitor class effect.

Work has been done with Etsy Captain rollout this tox.

Robert Blum: And the second question is regarding the second phase 3 trial for AFI-CAMTAN, although it's not a head-to-head MAO-CAMTAN, are you saying that it would be more oriented towards more severe patients who are subject to septal reduction therapy, and the trial would be somewhat similar to the VALOR-HCM trial? Thank you for taking the time to join us. Yeah, so I'd rather talk about Affy Kempton than Mavik Kempton, so with regard to Affy Kempton, if your question is, might we anticipate any of the repro talks, or I'll extend that because we've been asked any of the DDIs, maybe I'll ask Fady to elaborate on what we know and what we still need to learn.

And the second question is regarding the second phase III trial for ASIC Hampton.

Although it's not a head to head Mark Hampton are you seeing like it would be more oriented towards more severe patients.

Subjects are separated.

Third at the end of the client would be somewhat similar to the violent crime. Thank you for taking my questions.

So I'd rather talk about Alfie Kimpton then.

Mavic Kimpton, so with regard to Alfie Kimpton if your question is.

We anticipate any of the <unk>.

Repro tox or.

I'll extend that because we've been asked any of the <unk>, maybe I'll ask <unk> to elaborate on what we know and what we still need to learn.

Robert Blum: Sure, I mean, you know, we've conducted embryo fetal toxicity studies with apicamptin, they don't indicate any direct toxicity of apicamptin on fetal development, you know, any drug that has the potential to make the mother, the maternal host, sick as a cardiac myosin inhibitor can, at higher doses can certainly cause fetal toxicity as a secondary effect, but we don't see any direct fetal toxicity.

Sure.

We've conducted embryo fetal toxicity studies with Abbvie campton.

Don't indicate any direct toxicity of epic Hampton on field development.

Any drug that has the potential to make.

The mother.

Maternal.

Post.

Sick as Annette cardiac myosin inhibitor can.

At highest higher doses.

Certainly cause fetal toxicity is a secondary effect.

But we don't see any direct fetal toxicity.

Fady Malik: And then with regard to your second question, with respect to the profile of patients in Sequoia, we have biased the entry criteria to hopefully enable us to enroll a patient population that is a bit more class three, that's a bit more functional. That's the second trial, phase three. Oh, the second phase three, more severe, okay. Well, we're not really commenting on that particular design, so I can't really answer your question. I could certainly have done that first one, so I'll leave it at that.

And then with regards to your second question.

With respect to the.

The profile of patients in Sequoia.

We have biased the entry criteria to hopefully enable us to.

Enroll a patient population that is a bit more class III, that's a bit more functionally.

Trial.

The second phase III more severe okay, well, we're not really commenting on that particular design. So I can't really answer your question, but.

I could certainly have done that first one so I'll leave it there.

Leave it at that.

Fady Malik: Thanks. Got it. Thank you. Thank you. Your next question comes from the line of Dane Leone of Raymond James. Your line is open. Hello, Dane!

Got it thank you.

Thank you.

Your next question comes from the line of Dane Leone, Raymond James Your line is open.

Good day.

Dane Leone: Hi guys, thanks for the questions. This is Sean on Verdane. Since we're at the end of the call here, just a couple quick ones from us. One, can you comment on the enrollment rate for Sequoia to date and how you would expect that to be impacted by Mavicampton hitting the market? And then second, just a clarification on your OPEX for the year. You previously got it to upwards of $380 million, but it seems like maybe it could be coming down.

Hi, guys. Thanks for the questions. This is Sean on for Dan just on sort of at the end of the call here just a couple of quick ones from US one can you comment on the enrollment rate for Sequoia to date, and how you would expect that to be impacted by lava Camden hitting the market.

And then second just a clarification on your Opex for the year, you've previously guided to upwards of.

<unk> $380 million, but it seems like maybe it could be coming down just a clarification there.

Robert Blum: Just a clarification there. Sure. So with regard to the first, you know, Sequoia HCM just opened. We are in the process of convening investigator meetings, a US meeting recently having been held, and others to follow. It's premature to comment yet on enrollment. It's probably better to ask, you know, how we are doing on activations and initiations, and all that looks good according to plan. I don't know if Fady, you, or Stuart want to add anything to that.

Sure So with regard to the first Sequoia HCM just opened.

We are in the process of convening investigator meetings.

The U S meeting recently, having been held and others to follow.

It's premature to comment yet on enrollment, it's probably better to ask how are we doing on activations and initiations.

All of that looks good according to plan.

I don't know if Saudi your Stewart want to add anything to that.

Robert Blum: Yeah, no, I think it's too early to tell. Well, it's not too early to give you a sense of how fast it's enrolling since enrollment is early. I just will say the investigator enthusiasm has been very high, and obviously people are excited also about the availability of Mavicamten, but the enrollment in Sequoia presents a unique opportunity for the patient to advance the field and ultimately have access to Mavicamten in an open-label extension, and that's going to be attractive to many patients, I think, as well.

I think it's too early to tell to start yet too early to give you a sense of how fast it's enrolling since enrollments early I just will say the investigator enthusiasm has been very high in <unk>.

Obviously people are excited also about the availability of mavic campton, but.

<unk>.

Enrollment in Sequoia presents a unique opportunity for the patient to advance the field and ultimately have.

Axis Taffy Camden in an open label extension.

That's going to be attractive to many many patients do you think is it.

Robert Blum: So we should also emphasize the trial will enroll in regions outside of the U.S. where there is no Mavicamten availability, and ultimately, I think it will enroll quite well. When we indicated that this study could enroll within about a year, it was with full expectation that Mavicamden was going to get approved in the U.S., and the approval doesn't change our view toward that enrollment rate. Your next question was about OPEX. I'll turn to Ching, maybe, to answer that one, please.

We should also emphasize the trial will enroll in regions outside of the U S where there is no magic kimpton availability and ultimately I think we'll enroll quite well.

When we indicated we thought that this study could enroll within about a year. It was with full expectation that amount of Camden was going to get approved in the U S.

The approval doesn't change our view towards that enrollment rate.

Your next question was about Opex I'll turn to Ching maybe to answer that one please sure.

Ching Jaw: Sure. So you're right. We guided that for the year, we expected the cash burn to be in the range of $365 to $385 million.

So you're right we guided that for the year will we expect the cash burn to be in the range of 365% to $385 million.

Ching Jaw: Of course, the first quarter numbers were lower than if you were to just take that number and divide it by four, but that's not really how we planned for OPEX this year. As we elaborated earlier, we're building our commercial organization and capability based on achieving certain milestones throughout the year. And so naturally, as certain people get hired throughout the year, they're going to carry more costs in the second half of the year compared to the first half of the year.

Of course, the first quarter numbers were lower than if you were just take that number and divide it by four but thats not really how we plan for Opex for this year as we elaborated earlier, we're building our commercial organization and capability based on us achieving certain milestones throughout the year.

So naturally a certain people gets hires.

Throughout the year, they're going to carry more costs towards the second half of the year compared to the first half of the year. So do we expect the quarterly spend to ramp up from the first quarter numbers.

Ching Jaw: So do expect the quarterly spend to ramp up from the first quarter numbers. Great, great, thank you. Thank you. Your next question comes from the line of Justin Kim of Oppenheimer. Your line is open. Hello, Justin.

Okay, great. Thank you.

Thank you.

Yeah.

Your next question comes from the line of Justin Kim of Oppenheimer. Your line is open.

Hello, Justin Good afternoon, Hi, Hi, Robert Thanks for taking the questions.

Justin Kim: Good afternoon. Hi Robert. Thanks for taking the questions. You know, maybe just to elaborate a little bit further on some of the questions already asked, but, you know, with the recent approval and labeling of NAVA seeming to suggest the importance of continued development and additional populations, I was wondering whether it's reasonable and maybe even prudent to expect further trials even beyond a second study in symptomatic HCM, just given, you know, the fact that there are a certain number of different

Just maybe just to elaborate a little bit further on some of the questions already asked but.

With the recent approval and labeling of.

Holding to suggest the importance of continued development and additional population.

Curious, whether it's reasonable and maybe even to that.

Further trials, even beyond the second study in symptomatic HCM just given the fact that there are a number of different populations that could see benefit.

Justin Kim: Kutchi Banerjee, Yeah, so Justin, you were at the American College of Cardiology meetings; I saw you there. And as you saw, there's quite a lot of enthusiasm for this new mechanism, and it will likely make a meaningful difference in these patients and how they're treated. And it's not just as explainable by Explorer and Sequoia.

Yes, suggesting you were at the American College of Cardiology meetings I saw you there and as you saw there is quite a lot of enthusiasm for this new mechanism and as we'll likely make a meaningful difference in these patients and how theyre treated and it's not just us would be.

<unk> bye explore and Sequoia and Youre right there should be other studies, even going beyond what we're contemplating with the second phase III study, whether those are pre approval or post approval, it's more likely Theyre post approval, we hope anyway in light of our timelines, but we already are thinking about other studies.

Robert Blum: And you're right, there should be other studies even going beyond what we're contemplating with the second phase three study, whether those are pre-approval or post-approval, it's more likely they're post-approval, we hope anyway, in light of our timelines, but we already are thinking about other studies we might should be doing in connection with Aftecamp and beyond the two phase three studies we're talking about. Great, And maybe just one more on the sort of line of the REMS program requiring, at, You understand anything we might say right now is speculation because of the fact that we're still doing a phase three study.

We might should be doing in connection with <unk>.

Camden beyond the two phase III studies, we're talking about.

Okay, great great.

And maybe just one more on the line of the Rems program requiring.

Echocardiographer every 12 weeks.

Curious any uncertainty mark correct spots in terms of how the team thinks that may change the property for myosin inhibitor or maybe specifically designed.

Designed for Athene, and how that might change in the long run.

You understand anything we might say right now is speculation for the fact that we're still doing a phase III study.

Robert Blum: But, you know, we haven't been requiring the number of ECHOs as is currently contemplated by the Mavicampton label. While it does take a couple of ECHOs to get to a starting dose for AfiCampton, that can happen within a few weeks as opposed to a much longer period of time.

But.

We haven't.

Been requiring of the number of echoes is.

Currently contemplated by the amount of Camden label.

It does take a couple of echos to get to a starting dose for kimpton.

That can happen within.

A few weeks as opposed to a much longer period of time and therefore.

Robert Blum: And therefore, we haven't had any dose discontinuations or interruptions. Our expectation is that if we continue to develop AfiCampton the way we have, one shouldn't require the kind of frequent ECHO monitoring. But that's still to be determined, and we haven't done the trial yet, and we have to demonstrate that with clinical evidence. Fady, I don't know if there's anything more you want to add.

We haven't had any of the dose.

Discontinuation or interruptions.

Our expectation is if we continue to develop the kimpton the way we have.

One shouldn't require the kind of frequent echo monitoring, but thats still to be determined and we haven't done the trial, yet and we have to demonstrate that with clinical evidence.

If there's anything more you want to.

Fady Malik: You know, I just think it again, it's going to be looking at the need for continued monitoring in the context of long-term treatment with Aficamptin and the open label extension, as well as what emerges from Sequoia. So, you know, as Robert said, data will eventually inform what the label will look like. Great, thanks. Thank you. Your next question comes from the line of Charles Duncan of Cantor Fitzgerald. Your line is open. Hi, this is Robert.

I, just think again, it's going to be.

Looking at the.

Need for continued monitoring in the context of long term treatment with <unk> campaign and the open label extension.

As well as what emerges from Sequoia so.

As Robert said data will inform eventually what the label will look like.

Great. Thanks, so much.

Thank you.

Your next question comes from the line of Charles Duncan of Cantor.

Charles Your line is open.

Charles Duncan: Good afternoon. Good afternoon, Robert. This is Pete at the Robles Fund on behalf of Charles.

Hi, good afternoon, good afternoon Robert.

This is because Rob was on for Charles Congrats on all the progress this past quarter. So.

Robert Blum: Congratulations on all the progress. So, one of our questions is, you know, what are the plans or expectations for an OMI ad com, and what would you expect the key points of debate to be, especially with regard to the burden of disease in patients with the injection fraction, say, less than. As we've communicated previously, we're not anticipating an adcom for Omicamptive in connection with the NDA as submitted and now on file.

One of our questions.

What are the plans or expectations for an ad.

<unk> Com and what would you expect the key points of debate to be especially with regards to the burden of disease in patients with ejection fraction less than 30%.

Okay.

So as we've communicated previously.

We're not anticipating an AD com for Omi captive in connection with the NDA.

It was submitted and now on file.

Robert Blum: And that's what was communicated to us by FDA and as reflected in our public announcement. That's not to say it won't happen, and, in fact, it possibly could, but we don't expect it, and we have no reason to assume it will occur based on anything that's transpired since then.

And Thats.

It was communicated to us by FDA.

Reflected in our public announcement, that's not to say it won't happen and in fact, it possibly could but we don't expect it and we have no reason to assume it will occur based on anything Thats transpired. Since then so we continue to believe that.

Robert Blum: So we continue to believe that this application will be reviewed absent an adcom, and we're focused on the PDUFA date later this year. And your second question? The second question is, you know, with the PDUFA date coming up in November, what do you think is required to be in the product label for when we do sort of become part of the treatment guide? That's a very good question.

This application will be reviewed absent an AD com and we're focused on the <unk> date later this year.

And your second question in a.

Second question is with a <unk> date coming up in November .

What do you think is required to be in the product label for when we do sort of become part of the treatment guidelines.

Robert Blum: The treatment guidelines are providing for both foundational treatments but others that could be added on therapy. And maybe I'll ask Fady and Stuart to speak about what came out in the guidelines and what that could foretell if Omicam to McCarble should be included in guidelines. Yeah, I think the guidelines certainly specified foundational therapy with four classes of medication, beta blockers, a RAS inhibitor, an MRA, and an SGLT2 inhibitor. But not all patients can tolerate all four classes. Not all patients are adequately treated, and they may still have symptoms. However, they may still end up in the hospital.

So it's a very good question the treatment guidelines are providing for both foundational treatments, but others that could be add on therapy, and maybe I'll ask fatty and Stuart to speak about.

What came out in the guidelines and what that could foretell.

<unk> to be included in guidelines.

Yes, I think.

Within guidelines, certainly specify foundational therapy with.

Four classes of medications beta blockers.

A ras inhibitor and MRA and <unk> two inhibitor.

But not all patients can tolerate all four classes not all patients are.

Our adequately treated they may still have symptoms.

Fady Malik: And so the guidelines also specify a number of add-on therapies or therapies that may be supplemental to those. In certain scenarios, and I think Omicampto should be one of those, and the data that we've generated in Galactic and, subsequently, in the analyses that we've published, you know, indicate that sicker patients benefit even to a larger extent from Mappy Campton, and presumably the guidelines would reflect that. All right, thank you. Thanks for taking our questions. Thank you. Your next question comes from the line of Serge Belanger of Neidham & Company. Your line is... Oh, Serge.

It may still end up in the hospital and so the guidelines also specify a number.

Add on therapies or therapies that may be supplemental to those.

In certain scenarios and I think.

The captive should be one of those and the data that we've generated in galactic and and subsequently in the analyses that we've published indicate that sicker patients.

<unk>, even to a larger extent traumatic Hampton and presumably the guidelines would reflect that.

Alright, thank you.

Thanks for taking my question.

Thank you.

Your next question comes from the line of searches and Langer of meat.

<unk> Company your line is open.

So serge.

Serge Belanger: Good afternoon, Robert. Just a couple questions regarding plans for a European partnership. I think you reiterated your willingness to partner Olmec-Campbell's and kind of hold on to Ashwakantan rights.

Good afternoon Robert.

Just a couple of questions regarding plans for European partnership.

You reiterated your willingness to partner <unk>.

And kind of.

Hold onto asset Camden rights.

Robert Blum: I just want to make sure that I got that right and then maybe just highlight for us the timelines for European approval of Olmec-Hampton and how you see that market opportunity relative to the U.S. opportunity. Thanks. Sure, so I'll speak to this and maybe ask Andrew also to address the latter part of your question. Yeah, we continue to focus on the partnering of Omicampton-McCarble in Europe. It's in part because we're going to be plenty busy with our focus on Omicampton-McCarble in the United States and our development of Aficampton.

Just want to make sure that I got that right and then maybe just highlight for us.

Timelines for European approval of <unk> and.

And how you see that market opportunity.

Relative to the U S opportunity.

Yeah.

Sure. So I'll speak to this and maybe ask Andrew also to address the latter part of your question yes.

Yes, we continue to focus to the partnering of <unk> in Europe , it's in part because.

We're going to be plenty busy with our focused <unk> in the United States and our development of <unk>.

Robert Blum: And we're sober to the reality of what it takes to be successful in Europe, and we've done, under Andrew's supervision, exercises and planning to understand what peer group companies have done and what we think is practical from our standpoint. And you've got to walk before you can run.

And we are sober to the reality of what it takes to be successful in Europe .

We've done under Andrew supervision exercises and planning to understand what peer group companies have done and what we think is practical from our standpoint and you got to walk before you can run with that said there is a compelling opportunity for <unk> in Europe like in the United States, but it's obviously a lesser one.

Robert Blum: With that said, there's a compelling opportunity for Omicampton-McCarble in Europe, like in the United States, but it's obviously a lesser one in light of what we imagine would be some of the market access challenges and also pricing. With that, maybe I'll turn it to you, Andrew. Yeah, yeah, Robert, I think, From an opportunity point of view, the prevalence in Europe is slightly higher in terms of total number, not by much, so it's similar to U.S., but obviously price is a good bit lower, so that's really what affects the overall opportunity from a European point of view, but when you consider, like the U.S., when you consider APICAMP and OMACAMP and the synergies across an organization, it could become more interesting from a timing point of view.

In light of what we imagine would be some of the market access challenges and also pricing with that maybe I'll turn it to you Andrew.

Yes, Robert I think.

From an opportunity point of view of the prevalence in Europe .

Slightly slightly higher in terms of total number not by much.

The U S, but obviously price is a good bit lower.

So thats really what affects the overall opportunity from a European point of view, but when you consider like the U S. When you consider at Camden Noma captive in the synergies across an organization it could become more interesting from a timing point of view, so but I think to answer your question directly certainly the opportune.

Robert Blum: So I think to answer your question directly, certainly the opportunity is less, and it's really factored due to price. We've been very clear that one of the reasons why we're so compelled to go to market with Omicamptive in the United States is what we foresee to be both the concentrated customer segments around which we can build a good business here in the U.S. and also what that affords us in the way of synergies as we intend to go to market with Affie Kampden. The same thing holds true in Europe, but to a different magnitude.

<unk> has lessened its really factored due to pricing.

We've been very clear that one of the reasons why were so compelled to go to market with <unk> in the United States is what we foresee to be.

Both the concentrated customer segments around which we can build a good business here in the U S and also what that affords us in the way of synergies as we intend to go to market without the kimpton the.

The same thing holds true in Europe , but.

In a different magnitude and we have to be pragmatic about what we can do in the same timeframe. So our interest in partnering <unk> is not to exclusively license seeded away, but rather to seek a partner around which we could build an on ramp.

Andrew Callos: And we have to be pragmatic about what we can do in the same time frame. So our interest in partnering Omicamp to McCarble is not to exclusively license it away, but rather to seek a partner around whom we could build an on-ramp for a business for Affie Kampden and where that would provide us with some sharing of responsibilities for Omicamp. So that's the way we're approaching partnering. And potential European approval of Omicamp is expected in 2023. Or do we have a timeline? Yeah, so we haven't spoken to that explicitly yet. It's going to obviously be a function of when we file an MAA and seek approval, and that has not yet happened.

For our business for <unk> Kimpton.

And that would provide us some sharing of responsibilities for <unk>. So that's the way we're approaching partnering.

Okay and potential European approval expected in 2023 or do we have a timeline at this point.

Robert Blum: Here again, we're focusing on the US, but we're also pursuing those interactions with EMA and in Europe. And we'll give an update on that once we have something more concrete to speak to. Okay, let me squeeze in one more. Is it too early to talk about a potential timeline for a readout of cohort four of the Redwood trough? Maybe just a bit.

Yes, so we haven't spoken to that explicitly yet.

Can obviously be a function of when we file an MAA and seek approval and that has not yet happened.

Here again, we're focusing on the U S. But we're also pursuing those interactions with EMA.

And in Europe , and we will give an update on that once we have something more concrete to speak to.

Okay. Let me squeeze in one more is it too early to talk about a potential timeline for a readout of our cohort for the Redwood trial.

Maybe just a bit.

Robert Blum: It's something that we could maybe talk about on the next call. Let's see how the enrollment goes. As you know, it's an open-label cohort, 30 to 40 patients, and I do expect this will enroll well, so it might be something we can talk about on the next call. Dickens McGrath, Thank you.

It's something that we could maybe talk about what the next call, let's see how the enrollment goes as you know.

An open label cohort 30 to 40 patients.

I do expect this will enroll well so it might be something we can talk about on the next call.

Okay. Thanks.

Thanks for taking my question.

Thank you.

Yeah.

Operator: There are no further questions at this time. I'd like to turn the call back over to Speaker Robert Blum for closing remarks. Please go ahead.

There are no further questions at this time I'd like to turn the call back over to speakers Robinson for closing remarks. Please go ahead.

Robert Blum: Thank you, Operator, and thanks to all the participants in our teleconference today. Thank you for your continued support and interest in cytokinetics. Obviously, this first quarter was a very, very busy and productive one, and at the same time, we covered a lot of ground on this call, so I'll just be brief in my concluding remarks. We look forward to sharing with you the open label extension data from Redwood OLE soon and also continuing to update you on our progress with Omicampton, McCarville, and Afikampton and, as we move into the second half of the year, first interim analysis with Courage ALS.

Thank you operator.

Thanks to all the participants on our teleconference. Today. Thank you for your continued support and interest in Sato kinetics. Obviously this first quarter was a very very busy and productive one and at the same time, we covered a lot of ground on this call. So I'll just be brief in my concluding remarks, we look forward to share.

Robert Blum: So, with those as key milestones for the remainder of the year, we thank you for your attention today, and with that, we can conclude the call, please. This concludes today's conference call. Thank you for participating. You may now disconnect.

<unk> with you the open label extension data from.

Redwood OLED soon and also continuing to update you on our progress both with <unk> and <unk> Kimpton and as we move into the second half of the year, a first interim analysis with courage AOS, so with those as key milestones for the remainder of the year.

We thank you for your attention today and with that we can conclude the call. Please.

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

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