Q3 2021 Cytokinetics Inc Earnings Call

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Operator: Good afternoon, and welcome ladies and gentlemen to Cytokinetics' third quarter 2021 conference call. At this time, I would like to inform you that this call is being recorded and that all participants are in the 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 Joanna Siegel, Cytokinetics Senior Manager of Corporate Communications and Investor Relations. Please go ahead. Good afternoon, and thanks for joining us on the call today. Robert Blum, our President and Chief Executive Officer, will begin with an overview of the quarter and recent developments. Then

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Good afternoon, and welcome ladies and gentlemen, this hydrokinetics third quarter 2021 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 Joanna legal Battle kinetics senior manager of corporate Communications and Investor Relations. Please go ahead.

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

Robert Blum, our President and Chief Executive Officer will begin with an overview of the quarter and recent development then <unk> Malik our EVP of research and development will provide an update on all the kimpton mccargo, including recently presented additional analyses from Galactic Asia as long as an update on our ongoing next steps with the FDA next.

Joanna Siegel: Fady Malik, our EVP of Research and Development, will provide an

Robert I. Blum: https://www.nasa.gov

Fady Ibraham Malik: https://www.cdc.gov.au

Stuart Kupfer: Our SVP and Chief Medical Officer will provide an update on our development program for AFI-CAMPTN by recapping the results from Cohorts 1 and 2 of Redwood HCM, elaborating on continuing activities in Redwood HCM, and reviewing the design of Sequoia HCM, our planned Phase 3 clinical trial of AFI-CAMPTN in patients with obstructive heart failure. He will also speak to initial progress in COURAGE-ALS, our ongoing Phase 3 clinical trial of rel-deceptive in patients with ALS. Then, Andrew Callos, our EVP and Chief Commercial Officer, will discuss our go-to-market strategy for Omacamptin-McCarbol and our cardiovascular franchise development plans.

Copper, our SVP and Chief Medical Officer will provide an update on our development program for IV Campton by recapping the results from cohort, one and two of Redwood HCM elaborating on continuing activities in Redwood HCM and reviewing the designer the quiet HCM, our planned phase III clinical trial of AB Camden in patients with obstructive.

<unk> HCM.

He will also speak to initial progress encourage our ongoing phase III clinical trial, a real disruptive in patients with a lot.

Then Andrew Carlos our EVP and Chief commercial Officer will discuss our go to market strategy for OMA kept them, a carbo and our cardiovascular franchise development plan for the commercialization of IV Kimpton.

Andrew Callos: for the Commercialization of Affy Campton. Robert Wong, our VP and Chief Accounting Officer, will provide a financial overview for the past quarter.

Robert C. Wong: Ching Jaw, our SVP and Chief Financial Officer, will discuss strategic planning, our financial outlook, and corporate development strategies before Robert.

Robert Wong, our VP and Chief Accounting Officer will provide a financial overview for the past quarter and Ching jaw, our SVP and Chief Financial Officer will discuss strategic planning, our financial outlook and corporate development strategies before Robert Blum will provide concluding thought unexpected key milestones for the remainder of 2021.

Ching W. Jaw: Before Robert Blum provides concluding thoughts and expected key milestones for the remainder of 2021. 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.

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.

Robert I. Blum: Our actual results might differ materially from those projected in these forward-looking statements.

Robert I. Blum: Additional information concerning factors that could cause our actual results to differ may be found

Information concerning factors that could cause our actual results to differ material leave from those in these forward looking statements is contained in our SEC filings, including our current report regarding our third quarter 'twenty 'twenty. One financial result filed on form 8-K today, we undertake no obligation to update any forward looking statements after.

Robert I. Blum: https://www.youtube.com.uk Now, I will turn the call over to... Thank you, Joanna. And thanks again to everyone for joining us on the call today. We had a very productive third quarter marked by meaningful progress across all of our later stage programs. Most notably, we are sharing positive results from our Phase 2 clinical trial, Redwood HCM, which demonstrated the efficacy and safety of aficamptin, our next-in-class drug candidate, in patients with obstructive hypertrophic cardiomyopathy. As we've said, these results met our high expectations for this trial, and we received positive feedback from the physician community. Stuart will elaborate more on these results in a moment.

This call now I will turn the call over to Robert.

Thank you Joanna and thanks again to everyone for joining us on the call today.

We had a very productive third quarter marked by meaningful progress across all of our later stage programs, most notably our sharing positive results from our phase II clinical trial, Redwood HCM, which demonstrated the efficacy and safety of <unk> Kimpton, our next in class drug candidate.

In patients with obstructive hypertrophic cardiomyopathy.

As we've said these results met our high expectations for this trial and we received positive feedback from the physician community.

Robert I. Blum: During the third quarter, we were also pleased to complete enrollment in Cohort 3 of Redwood HCM, which, as you recall, enrolled patients also on Desipiramide, a medication often prescribed to patients with more severe HCM. We expect to share the results from Cohort 3 in the first quarter of 2022. Following previous interactions with FDA from which we received feedback on our planned trial design, we've continued to advance activities in preparation for Sequoia HCM, a Phase III clinical trial of aficampin in patients with obstructive HCM.

Stuart will elaborate more on these results in a moment.

During the third quarter. We were also pleased to complete enrollment in cohort three of Redwood HCM, which as Youll recall enrolled patients also on just the pyramid of medication often prescribed to patients with more severe HCM, we expect to share the results from cohort three in the first quarter of <unk>.

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Following previous interactions with FDA for which we receive feedback on our planned trial design. We've continued to advance activities in preparation for Sequoia HCM the phase III clinical trial without the Camden in patients with obstructive HCM.

Robert I. Blum: As we recently presented, and as Stuart will elaborate, this trial was designed to potentially demonstrate a significant improvement in exercise capacity and evaluate safety in a broad population of patients with symptomatic obstructive HCM. We're working with sites around the world, including many who participated in Redwood HCM who are enthusiastic about also participating in Sequoia HCM, and we look forward to starting this trial soon. Moving now to our heart failure program, we continued activities supportive of our plans to submit an NDA for Omicamp to McCarble, and we remain on track towards our goal of submission in the fourth quarter of this year. Fady will have more to say about that in a moment.

As we recently presented it as Stuart will elaborate this trial was designed to potentially demonstrate.

A significant improvement in exercise capacity and evaluate safety in a broad population of patients with symptomatic obstructive HCM.

We are working with sites around the world, including many who participated in Redwood HCM, who are enthusiastic about also participating in Sequoia HCM and we look forward to starting this trial soon.

Moving now to our heart failure program, we continued activity supportive of our plans to submit an NDA for <unk> and we remain on track towards our goal of submission in this fourth quarter of this year Faddy will have more to say about that in a moment.

Andrew Callos: Additionally, as outlined in our recent Analyst and Investor Day, we're making significant progress in refining and executing our go-to-market strategies for Omicamp to McCarble across several work streams that Andrew will elaborate on in a moment. These commercial readiness activities represent a tremendous scope of work from our growing commercial organization and supporting our go-to-market strategy. As well as our intention to build a cardiovascular business franchise by leveraging common denominators and synergies across our business, inclusive of our plans, both for the potential launch of Omicamptomacarbal and a potential future launch of Athicamptomacarbal, As Fady will discuss, in the third quarter, we presented additional results from GALACTIC-HF highlighted by an analysis of black patients enrolled in GALACTIC-HF, showing that the treatment effect of omicamptomacarbal in black patients was consistent with the treatment effect in the overall population, and also similar to the effect observed in white patients in the trial.

Additionally, as outlined in our recent analyst and Investor Day, we're making significant progress in refining and executing our go to market strategies for Omi captive mccarville across several work streams that Andrew will elaborate on in a moment.

These commercial readiness activities represent a tremendous scope of work from our growing commercial organization and supporting our go to market strategies as well as our intention to build a cardiovascular business franchise by leveraging common denominators and synergies across our business inclusive of.

Our plans both for the potential launch of <unk> and a potential future launch about the kimpton.

As Saudi will discuss in the third quarter, we presented additional results from Galactic eight Jeff highlighted by an analysis of black patients enrolled in Galactic HFF showing that the treatment effect of <unk> in black patients was consistent with the treatment effect in the overall population and also similar.

To the effect observed in white patients in the trial.

This finding is important due to the fact that black patients.

Andrew Callos: This finding is important due to the fact that black patients tend to have a higher risk of heart failure and often have worse outcomes. Additionally, an analysis of the severe heart failure subgroup in Galactic HF was published in the Journal of the American Medical Association, Cardiology, illuminating a larger treatment effect when compared to the overall population of patients studied. This important manuscript was accompanied by an editorial suggesting recognition of a new classification for a group of severe heart failure patients whose still prevailing high unmet need represents an increasing patient population with heart failure that contributes more and more to the clinical and the economic burden of this disease.

<unk> tend to have a higher risk of heart failure, and often have worse outcomes.

Additionally, an analysis of the severe heart failure subgroup in Galactic <unk>, Jeff was published in the journal of the American Medical Association Cardiology.

Illuminating a larger treatment effect when compared to the overall population of patients studied.

This important menu script was accompanied by an editorial suggesting recognition of a new classification for group a severe heart failure patients, who still prevailing higher unmet need represents an increasing patient population with heart failure that contributes more and more to the clinical and the.

Economic burden of this disease.

Finally, we were pleased in the most recent quarter to begin enrolling patients encourage ALS, our phase III clinical trial of rail deceptive in patients with ALS.

The results from the phase II clinical trial for the two day, Alice we're deemed compelling by investigators and physicians, who treat patients with ALS and our advancement to phase III is an exciting and an important step forward for this program as is aligned with our dedication to the AOS communities.

Andrew Callos: Finally, we were pleased in the most recent quarter to begin enrolling patients in COURAGE-ALS, our Phase 3 clinical trial of rel-deceptive in patients with ALS. The results from the Phase 2 clinical trial, Fortitude ALS, were deemed compelling by investigators and physicians who treat patients with ALS, and our advancement to Phase 3 is an exciting and important step forward for this program, as is aligned with our dedication to the ALS community. The ALS communities are more assertively seeking new medicine, and the FDA and public policy makers seem to be increasingly responding to these louder calls for action. It is an incredibly important time for our company.

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The airlift communities are more assertively, seeking new medicines, and the FDA and public policymakers seem to be increasingly responding to these louder calls for action.

It is an incredibly important time for our company. We are building our teams and capabilities. As we are now on the precipice of a powerful transformation from an R&D company into one that is also a commercial organization.

It has always been our strategic vision to ourselves deliver on the promise of our science and we're closer now to that than ever before.

These are exciting times to be sure, but how we execute on those plans will matter.

Robert I. Blum: We're building our teams and capabilities as we're now in the precipice of a powerful transformation from an R&D company into one that is also a commercial organization. It has always been our strategic vision to ourselves deliver on the promise of our science, and we're closer to that now than ever before. These are exciting times, to be sure, but how we execute on those plans will matter.

Robert will speak to our current financials, and Jim will comment on our progress and prospects and continuation of our long standing practice to diversify our access to capital through both partnering and structured financings as is informed by annual strategic planning.

With that I'll turn the call over now to <unk> to elaborate on developments related to <unk>.

Fady Ibraham Malik: Robert will speak to our current financials, and Ching will comment on our progress and prospects in continuation of our long-standing practice to diversify our access to capital through both partnering and structured financings as informed by annual strategic planning. With that, I'll turn the call over now to Fady to elaborate on developments related to Omicamptive McCarver. Thanks, Robert.

Thanks, Robert as you mentioned results from additional analyses of Galactic HFF presented during the quarter at the heart failure Society of America annual scientific meeting reinforced that outcomes with <unk> and black patients enrolled in Galactic H.

We're consistent with the overall population and like the overall study results were driven primarily by a reduction in heart failure hospitalizations and heart failure events.

Fady Ibraham Malik: As you mentioned, results from additional analyses of galactic HF presented during the quarter at the Heart Failure Society of America annual scientific meeting reinforced that outcomes with Omicantin, McCarville, and Black patients enrolled in Galactic HS were consistent with the overall population. And like the overall study results, we're driven primarily by a reduction in heart failure hospitalizations and heart failure events. The treatment effect in black patients was also similar compared to white patients.

The treatment effect and black patients was also similar compared to white patient.

Galactic HFF enrolled the most back black patients among recent heart failure trial and have patients enrolled in the U S. 29% were black which is important not only because black patients have historically been under represented and clinical research, but also because they have a higher risk of heart failure and suffer worse outcome.

This disparity and outcomes is complex, but it is encouraging to see that the potential benefit of treatment, although I'm a captive mccarville remains consistent in this group.

Expanding on the theme of higher risk patients with heart failure, three weeks ago, a manuscript entitled assessment of OMA captive <unk> for the treatment of patients with severe heart failure was published in Jama cardiology. Following on the heels of the initial data presentation in late June at heart failure 2002.

Fady Ibraham Malik: Galactic HF enrolled the most black patients among recent heart failure trials, and of patients enrolled in the U.S., 29% were black, which is important not only because black patients have historically been underrepresented in clinical research but also because they have a higher risk of heart failure and suffer worse outcomes. This disparity in outcomes is complex, but it's encouraging to see that the potential benefit of treatment with Omicamptive Mecarbil remains consistent in this group.

One and international Congress of the European Society of Cardiology.

The analysis by Dr. Michael Felker and co authors looked at the treatment effect of <unk> on the primary composite endpoint in patients from Galactic HFF classified as having severe heart failure based on modified criteria from the heart failure Association of the European Society of Cardiology Advanced Heart.

Failure position statement.

Patients in this subgroup had nyj class III for symptoms.

Fady Ibraham Malik: Expanding on the theme of higher-risk patients with heart failure, three weeks ago, a manuscript entitled Assessment of Omicamptive Mecarbil for the Treatment of Patients with Severe Heart Failure was published in JAMA Cardiology. Following on the heels of the initial data presentation in late June at Heart Failure 2021, an international congress of the European Society of Cardiology, the analysis by Dr. Michael Felker and co-authors looked at the treatment effect of omicamptomacarbal on the primary composite endpoint in patients with galactic HF. Classified as having severe heart failure based on modified criteria from the Heart Failure Association of the European Society of Cardiology (Advanced Heart Failure Position Statement). Patients in this subgroup had NYHA Class 3-4 symptoms.

Of less than or equal to 30% and hospitalization for heart failure within the prior six months.

Approximately 30% of patients enrolled in Galactic <unk> met these criteria and head event rates are approximately twice those patients without severe heart failure and.

This post hoc analysis.

Those with severe heart failure, who received <unk> experienced a significant treatment benefit for the primary endpoint with a hazard ratio of 0.80.

Whereas patients without severe heart failure had no significant treatment benefit with a hazard ratio of <unk> 99.

Results for cardiovascular death, or qualitatively similar patients with heart failure that was severe experienced a trend towards treatment benefit for a moment Camden mccarville, while patients without severe heart failure did not.

OMA Camden Mccarville was equally well tolerated in patients with and without severe heart failure with no significant changes in blood pressure renal function or potassium compared to placebo.

Accompanying this manuscript was an editorial authored by doctors Clyde Yancy, Adrian Hernandez, and Greg Panaro titled identifying treatments for stage two heart failure.

Fady Ibraham Malik: EF of less than or equal to 30% and hospitalization for heart failure within the prior six months. Approximately 30% of patients enrolled in GALACTIC-HF met these criteria and had event rates that were approximately twice those of patients without severe heart failure. In this post-hoc analysis, those with severe heart failure who received Omicamptive Mecarbil experienced a significant treatment benefit for the primary endpoint with a hazard ratio of 0.80, whereas patients without severe heart failure had no significant treatment benefit with a hazard ratio of 0.99. The results for cardiovascular death were qualitatively similar.

And which states see too is proposed as a new addition to the currently defined four stages of heart failure, <unk> and as would encapsulate these severe heart failure patients.

So may be a priority for additional impactful therapy.

This high unmet need with a focus of our panel discussion at our recent analyst and Investor day.

Spite, the availability and adherence to guideline directed medical therapy, our GMT.

Patients with worsening heart failure is still have high event rate as we heard from doctors Morris and Toric Ahmad who are both specialists and heart failure major academic medical centers. It can be a challenge to get patients on GMT, because many are unable to tolerate their medications due to side effects.

Andrew Callos: Patients with heart failure that was severe experienced a trend toward treatment benefits from omacamptin and macabol, while patients without severe heart failure did not. Omecamtiv-McCarville was equally well tolerated in patients with and without severe heart failure, with no significant changes in blood pressure, renal function, or potassium compared to placebo. Accompanying this manuscript was an editorial authored by Drs. Clyde Yancey, Adrian Hernandez, and Greg Fonaro titled, Identifying Treatments for Stage C-2 Heart Failure.

With <unk> with a potential add on therapy with a novel mechanism of action that could be used as a complement to and alongside existing therapies without increasing cardiac mortality.

Physician feedback has indicated that their view is positive towards the clinical utility of AUM, a captive mccarville as an additional therapeutic option with a good safety and Tolerability profile and that there is a clear need for therapy like home and Camden mccarville to fit into regular practice.

Moving on we completed enrollment in meteoric <unk> at the end of the second quarter and we continued conduct of the trial in the third quarter.

Andrew Callos: In which stage C2 is proposed as a new addition to the currently defined four stages of heart failure, A through D, and as would encapsulate these severe heart failure patients, who may be a priority for additional impactful therapy. This high unmet need was the focus of our panel discussion at our recent Analyst and Investor Day. Despite the availability and adherence to Guideline-Directed Medical Therapy, or GDMT, patients with worsening heart failure still have high event rates. As we heard from Drs.

This trial will provide insight as to how mckesson mccarville could benefit another key aspect of improving the lives of people with heart failure, which is to improve their exercise capacity.

A common concern of patients with heart failure is their inability or difficulty with everyday task.

But current treatments have little to no impact on exercise capacity and stamina we.

We expect to complete meteoric HFF this year and look forward to reporting results in early 2022.

Fady Ibraham Malik: Alana Morris and Tariq Hamad, who are both specialists in heart failure at major academic medical centers, it can be a challenge to get patients on GDMT because many are unable to tolerate their medications due to side effects. With Omicam of McCarble, we have a potential add-on therapy with a novel mechanism of action that could be used as a complement to and alongside existing therapies without increasing cardiac mortality. Physician feedback has indicated that their view is positive towards the clinical utility of vomicamptomacarbal as an additional therapeutic option.

Also in the third quarter, we conducted meetings with FDA to support the preparation and submission of our new drug application or NDA for <unk>.

We completed a pre NDA meeting, which confirm the suitability for submission of content related to chemistry manufacturing and control clinical pharmacology and the non clinical program as well as the format of dataset <unk> integrated summary of safety and other components of the NDA.

We also had a meeting with FDA to discuss the assay for plasma concentrations of <unk> in terms of its potential need to guide dosing as well as the regulatory pathway for its implementation.

Fady Ibraham Malik: With a good safety and tolerability profile, and that there is a clear need for therapy like Omicamptomacarbal to fit into regular practice. Moving on, we completed enrollment in METEORIC-HF at the end of the second quarter, and we continued conduct of the trial in the third quarter. This trial will provide insight as to how Omicamptin-McCarville could benefit another key aspect of improving the lives of people with heart failure, which is to improve their exercise capacity. A common concern of patients with heart failure is their inability or difficulty with everyday tasks. But current treatments have little to no impact on exercise capacity and stamina.

In sum these meetings provided guidance to some of the content of our NDA, which is on track for submission this quarter.

As we approach our goal of submitting our NDA to the FDA. We also continued simultaneously growing the scope and reach of our medical affairs activities by hiring therapeutics area lead medical directors and deploying additional field based medical scientists.

We have developed a compliant.

<unk> for an investigator sponsored studies program, which is timely as we have started to receive requests for potential collaborative activities.

The team is working on finalizing their scientific platform or on the captive mccarville, which forms the basis for communications with medical professionals.

We also initiated vendor selection for the development of the medical contact center to be prepared to respond to requests for medical information our direct questions to the proper personnel for a response.

Stuart Kupfer: We expect to complete METEORIC-HF this year and look forward to reporting results in early 2022. Also, in the third quarter, we conducted meetings with FDA to support the preparation and submission of our new drug application, or NDA, for Omicamptin-McCarbol. We completed a pre-NDA meeting that confirmed the suitability for submission of content related to chemistry, manufacturing, and control, clinical pharmacology, and the non-clinical program, as well as the format of datasets, the integrated summary of safety, and other components of the NDA.

With that I'll turn the call over to Stuart to provide an update on naphtha campton enroll deceptive.

Thanks Patty.

During the third quarter in September we presented the full results from cohorts, one and two of Redwood HCM the phase II clinical trial of IV Camden at the Heart failure Society of America annual scientific meeting in Denver as.

As we've mentioned the results were positive and support our advancing <unk> into phase III, which I'll touch on in a moment.

As we previously shared and Redwood HCM treatment with Abbvie Camden for 10 weeks resulted in statistically significant reductions from baseline compared to placebo.

Stuart Kupfer: We also had a meeting with FDA to discuss the assay for plasma concentrations of omicamptomacarbal in terms of its potential need to guide dosing, as well as the regulatory pathway for its implementation. In sum, these meetings provided guidance for some of the content of our NDA, which is on track for submission this quarter. As we approach our goal of submitting our NDA to the FDA, we have also continued simultaneously growing the scope and reach of our medical affairs activities by hiring Therapeutic Area Lead Medical Directors and deploying additional field-based medical science.

And the average resting left ventricular outflow tract or <unk>.

Pressure gradient and the average post now Sal de <unk> great.

Majority of patients treated with that be Camden.

79% in cohort, one and 93% in cohort two achieved.

To achieve the target goal of treatment defined as resting gradient less than 30 millimeters of Mercury and post valsalva gradient less than 50 millimeters of Mercury at week 10.

Compared to 8% for placebo.

These reductions in <unk> gradient were dose dependent with.

With patients achieving greater reductions of LDL gradient with increasing doses of IV Camden.

The reductions in LDL C grading occurred within two weeks of initiating treatment were maximized within two to six weeks of the start with dose titration and were sustained until the end of treatment at 10 weeks.

Stuart Kupfer: We have developed a compliant framework for an investigator-sponsored studies program, which is timely as we have started to receive requests for potential collaborative activities. The team is working on finalizing their scientific platform for Omicamp to McCarble, which forms the basis for communications with medical professionals. We also initiated vendor selection for the development of a medical contact center to be prepared to respond to requests for medical information or direct questions to the proper personnel for a response. With that, I'll turn the call over to Stuart to provide an update on Affie Kampton and Roald Assembly. Thanks, Fady. During the third quarter,

Reverse ability of LD, Ot gradient and there'll be ejection fraction reductions were observed after discontinuation of Abbvie Camden.

With levels returned to baseline at the end of the two week washout period.

Patients also experienced statistically significant reductions in empty pro BNP.

And treatment would that be Camden was associated with an improvement in New York Heart Association functional class.

With a substantial number of patients improving by at least one class.

As previously stated treatment with Abbvie Camden was well tolerated.

Incidents of adverse events were similar between treatment arms and there were no treatment related serious adverse event.

Importantly, there were no treatment interruptions or discontinuation.

Dr. Marty Marin director of Hypertrophic Cardiomyopathy Center at Tufts University School of Medicine.

Stuart Kupfer: Redwood HCM, Phase 2 Clinical Trial, at the Heart Failure Society of America Annual Scientific Meeting in Denver. As we've mentioned, the results were positive and support our advancing at the camp into phase three, which I'll touch on in a moment.

Who presented the results of Redwood, HCM and <unk> and <unk>.

Toward the potential clinical utility of anti Camden based on the elimination of arresting LD Ot gradients in nearly all patients.

Dr. Marin further commented on the substantial improvement in heart failure symptoms.

Stuart Kupfer: As we previously shared, in Redwood HCM, treatment with afecamtin for 10 weeks resulted in statistically significant reductions from baseline compared to placebo, and the Average Resting Left Ventricular Outflow Tract, or LVOT, Pressure Gradient, and the Average Post-Val Salve at LVOT Grading. Additionally, the majority of patients treated with apicanthus. 79% in cohort 1 and 93% in cohort 2 achieved the target goal of treatment defined as a resting gradient less than 30 millimeters of mercury and a post-valsalva gradient less than 50 millimeters of mercury at week 10, compared to 8% for placebo. These reductions in LBOT gradient were dose dependent. Patients Achieving Greater Reductions of the LVOT Gradient with Increasing Doses of Abucamp; Reductions in LVOT

<unk> onset and reverse ability of effect.

The ability to use precise echo guided titration and the lack of dosing interruptions for low ejection fraction.

At the conference. We also received a positive reaction from physicians, who manage patients with HCM and expressing their enthusiasm about the results.

And for a medication that potentially could be used for patients who have symptomatic obstructive HCM and.

And were not responding to current standard of care therapies.

Overall, we're very encouraged by the results so far and their potential translation to clinical practice.

During the quarter. We also completed enrollment in cohort three of Redwood, HCM, and which patients with obstructive HCM.

While receiving disopyramide as background therapy are treated with Abbvie, Camden and an open label manner.

This cohort will further inform the potential inclusion of this small but important patient population.

Our planned phase III trial.

In addition, during the third quarter, we continued enrolling patients in Redwood HCM O L E. The open label extension trial of Redwood HCM.

Stuart Kupfer: [inaudible] reversibility of the LVOT gradient and

Stuart Kupfer: with levels returning to baseline at the end of the two-week washout period. Patients also experienced statistically significant reductions in end

With a positive result in hand from Redwood HCM, we have been actively engaging in startup activities for Sequoia HCM.

Our planned phase III clinical trial of Athey Camden in patients with obstructive HCM.

Stuart Kupfer: And treatment with naphecamtin was associated with an improvement in New York Heart Association functional class, with a substantial number of patients improving by at least one class. As previously stated, treatment with apicampin was well-tolerated, the incidence of adverse events was similar between treatment arms, and there were no treatment-related serious adverse events. Importantly, there were no treatment interruptions or discontinuations. Dr. Marty Marin, Director of the Hypertrophic Cardiomyopathy Center at Tufts University School of Medicine, who presented the results of Redwood HCM at HFSA, Underscored the potential clinical utility of Ampucampton based on the elimination of arresting LVOT gradients in nearly all patients. Dr. Marin further commented on the substantial improvement in heart failure symptoms. Rapid onset and reversibility of effect. The ability to use precise echoguided titration, and the lack of dosing interruptions for low ejection.

At our analyst and Investor Day meeting in October we presented the design of the trial, which I'll recap at a high level now.

Sequoia HCM is a randomized double blind placebo controlled international clinical trial designed to evaluate abbvie Camden in patients with symptomatic obstructive HCM on background medical therapy for 24 weeks.

The primary objective is to evaluate the change from baseline to week 24, and peak oxygen uptake or peak the O two.

Measured by cardiopulmonary exercise testing or see pet.

As a measure of exercise capacity.

Among the secondary objectives, we are investigating the change in Kansas City Cardiomyopathy questionnaire clinical symptom score.

And New York Heart Association functional class at week 12 to evaluate a potentially early improvement in heart failure symptoms.

And again at week 24.

We plan to randomize 270 patients in a one to one ratio to Abbvie Camden or placebo. In addition to standard of care.

Each patient will receive up to four escalating doses of that be Camden or placebo with dose optimization based on achievement of echocardiographic targets.

Stuart Kupfer: At the conference, we also

Stuart Kupfer: www.hcm.hcm.org and for medication that potentially could be used for patients who have symptomatic obstructive HCM and are not responding to current treatments

Starting dose will be five milligrams once daily escalating to 10, 15, or 20 milligrams once daily as needed to achieve target gradients.

These four doses were selected based on the results from Redwood HCM to facilitate selection of the optimal dose for each patient and maximize the individual benefit risk profile.

Stuart Kupfer: Overall, we're very encouraged.

Stuart Kupfer: I'm very encouraged by the results so far and their potential translation to clinical practice. During the quarter, we also completed enrollment in Cohort 3 of Redwood HCM, in which patients with obstructive HCM who are receiving dicepiramide as background therapy are treated with apicampin in an open-label manner.

Study start up activities regulatory filings and IRB submissions are underway with the first site initiations already completed.

Drug product availability in early 2022 will enable the commencement of screening and enrollment of the first patient in this trial.

In anticipation of enrolling patients with obstructive HCM from China, and Sequoia HCM, we continue to collaborate closely with our partner <unk> Pharmaceuticals.

Stuart Kupfer: This cohort will further inform the potential inclusion of small but important interventions.

Stuart Kupfer: This is a small but important patient population in our planned phase 3 trial. In addition, during the third quarter, we continued enrolling patients in Redwood HCM OLE, the open-label extension trial of Redwood HCM. With the positive results in hand from Redwood HCM, we have been actively engaging in startup activities for Sequoia HCM, our planned phase 3 clinical trial of apicampin in patients with obstructive heart failure. At our Analyst and Investor Day meeting in October, we presented the design of the trial, which I'll recap at a high level now. Sequoia HCM is a randomized, double-blind, placebo-controlled international clinical trial designed to evaluate apicampin in patients with symptomatic obstructive HCM on background medical therapy for 24 weeks.

<unk> recently completed a phase one study evaluating single and multiple doses of <unk> Hampton and healthy Chinese subjects.

Pharmacokinetic results were similar to those observed in the Caucasian populations in.

We enrolled in our phase one study of happy Camden conducted in the U S and.

And similarly showed a dose proportional pharmacokinetics with a safety and tolerability profile comparable to placebo.

The results of this study supports submission of a clinical trial application and enrollment of patients with obstructive HCM in China.

On the neuromuscular front.

As Robert mentioned during the third quarter, we began enrolling patients encourage ALS the phase III clinical trial of rail defensive in ALS.

Courage ALS will enroll approximately 555 patients with ALS randomized two to one to receive rather sensitive or placebo for 24 weeks.

Stuart Kupfer: The primary objective is to evaluate the change from baseline to week 24 in peak oxygen uptake, or peak VO2.

Solid by a 24 week period in which all patients will receive around incentives.

Stuart Kupfer: Measured by Cardiopulmonary Exercise Testing or CPET, which is a measure of exercise capacity. Among the secondary objectives, we are investigating the change in the Kansas City cardiomyopathy questionnaire clinical symptom score and New York Heart Association Functional Class at Week 12 to evaluate a potentially early improvement in heart failure symptoms, and again at week 24. We plan to randomize 270 patients in a 1-to-1 ratio to apicampin or placebo in addition

The primary endpoint is the change from baseline to 24 weeks in ALS FRS or.

Functional rating scale that indicates the progression of ALS.

As we design courage analyst, we incorporated feedback from patients and caregivers.

To renewed key barriers to clinical trial participation.

To help make the patient experience less burdensome.

We are also working to provide continued access to rail deceptive for all patients who complete courage ALS.

As well as patients who have previously participated in our ALS trial.

Reflective of our goal to ensure ethical and equitable access for patients who are in need.

With that I will turn the call over to Andrew to discuss our progress against that go to market strategy for on the captive mccarville.

Stuart Kupfer: Each patient will receive up to four escalating doses of apicampin or placebo, with dose optimization based on achievement of echocardiographic targets. The starting dose will be 5 mg once daily, escalating to 10, 15, or 20 mg once daily, as needed to achieve target ratings.

Yes.

Thanks Stuart.

During the third quarter, we advanced our go to market strategy for OMA captive Mccarville and we were pleased to presented at our recent analyst and Investor Day. There are a few highlights to the strategy I'd like to review on today's call.

First our go to market strategy is based on a gated build with a planned total investment to be titrated overtime as de risking events occur such as NDA submission NDA filing and approval by the FDA to illustrate we have around 10% to 15% of our planned commercial ftes in place today, and we will have less than one third.

Stuart Kupfer: Thank you. Study startup activities, regulatory filings, and IRB submissions are underway, with the first

Of the total number.

In place post NDA submission.

Stuart Kupfer: The first site initiation has already

This level of commercial hires are sufficient for launch preparation.

Stuart Kupfer: Drug product availability in early 2022 will enable the commencement of screening and enrollment of the first patients in this trial. In anticipation of enrolling patients with obstructive HCM from China in the sequoia HCM trial, we continue to collaborate closely with our partner, Bixin Pharmaceuticals. Jixing recently completed a Phase I study evaluating single and multiple doses of apicampin in healthy Chinese subjects. The pharmacokinetic results were similar to those observed in the Caucasian population enrolled in our phase one study of apicampin conducted in the U.S. and similarly showed dose-proportional pharmacokinetics with safety and tolerability.

As Robert mentioned, we hired a seasoned team to implement this go to market strategy.

And we now have our full leadership team in place as well as our account manager team who call on payers and nearly all of our marketing organization.

The go to market strategy is based on four key pillars insights education access and support.

It speaks to having a very deep understanding of who the worsening heart failure patient is.

Where are they are accretive and who the cardiologists are who treat them.

Education means that if <unk> is approved then we need to ensure the cardiologist clearly understand the data supporting our label, including evidence supporting <unk> potential benefit for the subset of patients who have worsening heart failure.

Stuart Kupfer: The results of this study support the submission of a clinical trial.

Stuart Kupfer: This concludes the presentation of the Clinical Trial Application and Enrollment of Patients with Obstructive HVM in China. As Robert mentioned, during the third quarter, we began enrolling patients in COURAGE-ALS, the phase 3 clinical trial of rel-deceptive in ALS. Courage ALS will enroll approximately 555 patients with ALS, randomized 2-to-1, to receive reldeceptive or placebo for 24 weeks.

Stuart Kupfer: followed by a 24-week period in which all patients will receive

Stuart Kupfer: All of these are candidates. We'll receive her all the time.

Stuart Kupfer: The primary endpoint is a change from baseline to 24 weeks and an ALSFRSR Functional Rating Scale that indicates the progression of ALS. As we designed COURAGE-ALS, we incorporated feedback from patients and caregivers to remove key barriers to clinical trial participation and to help make the patient experience less burdensome.

Well sure fueled sales fueled medical shared services and systems across the entire organization.

Once we have established relationships and built system to support the launch of OMA captive mccarville, we are well positioned to accelerate and streamline the potential launch of Akron canton.

It is an incredibly exciting time to be working at cytogenetics as we continue to grow our team and advance our plans. It remains an important for us to remember the driving force behind this motivation patients and the clear unmet need in ballpark failure in HCM.

Stuart Kupfer: We are also working to provide continued access to related symptoms for all patients who complete COURAGE-ALS, as well as patients who have previously participated in our ALS trials.

And with that I'll turn it over to Robert Wong, who will provide an update to our financials.

Thanks, Andrew.

I had an update on cash revenue and spending and then Ching will review, our financial outlook and corporate development strategies more details on our actual results for the third quarter 2021 are included in the press release, which we released earlier this afternoon we.

Andrew Callos: Reflecting our goal to ensure ethical and equitable access for patients who are in need. With that, I will turn the call over to Andrew to discuss our progress against the go-to-market strategy for Omicamptive Macargo.

We ended the third quarter with approximately $668 9 million in cash and investments.

Andrew Callos: Thank you. Thank you. Thank you.

Andrew Callos: During the third quarter, we advanced our go-to-market strategy for Omicamptive McCarville, and we were pleased to present it at our recent analyst invest— There are a few highlights to this strategy I'd like to review on today's call. First, our go-to-market strategy is based on a gated build. For more information, please visit www.fda.gov, in place post NDA submission. This level of commercial hires is sufficient for launch preparation.

Our revenue in third quarter of 2021 came primarily from our recognizing a 5 million dollar milestone from <unk> pharmaceuticals in anticipation of the start of Sequoia HCM.

Our third quarter 2021, R&D expenses increased to $48 4 million from $24 2 million in the third quarter of 2020.

Andrew Callos: As Robert mentioned, we've hired a CG team to implement this go-to-market strategy. And we now have our full leadership team in place, as well as our account manager team, who call them payers, and nearly all of our market. The go-to-market strategy is based on four key pillars, insights, education, access, and support. Insight speaks to having a very deep understanding of who the worsening heart failure patient is, where they are treated, and who the cardiologists are who treat them.

Andrew Callos: Education means that if Omacamptin-McCarville is approved, then we need to ensure that cardiologists clearly understand the data supporting our label, including the evidence supporting Omacamptin-McCarville's potential benefit for the subset of patients who have worsening heart failure. Access B2R plans have affordable co-pays for most patients as soon as possible after launch.

Andrew Callos: And finally, www.ncbi.nlm.nih.gov, My copay support for commercial patients, patient assistance program, and educational services. To support our goal of affordable access, our payer account management team met with every major payer in the third quarter. We have introduced our team and our company while engaging payers in a mutual understanding of the unmet need in our society. For further support access, our health, economics, and outcome research colleagues continue to advance outcomes research with a goal of multiple publications in 2022.

Despite spending in anticipation of war potential commercial launch a former captain mccarville in 2022 personnel related costs, including stock based compensation and facilities costs related to our new building and.

And now Ching will review, our financial outlook and corporate development strategies.

Thanks Robert.

As in our annual practice, we recently conducted a comprehensive strategic planning process with subsequent presentation and discussion with our board.

This year the strategic plan was focus to prioritizing are expanding clinical pipeline.

To ensure that we focus on R&D programs that leverage our core competencies and competitive advantages in muscle biology, and also address hi, unmet need opportunities that may have for high return on investment potential.

Andrew Callos: These publications are targeted at documenting the value of Omicamp and McCarville as illustrated by meaningful reductions in resource utilization, intensity, and cost. And we are preparing for the potential launch of Omicantin-McCarville. We are simultaneously building our cardiovascular franchise strategy towards our plans for the potential launch of FEC. Keeping in mind our corporate goal of bringing multiple medicines to market in the next several years, this strategy relies on several synergies. First, among the cardiologists who treat these patients, there is an 85% overlap between the cardiologists who treat patients with heart failure and those who treat patients with HCM.

In addition.

We pressure tested plans to enrich our research pipeline with external collaborations that could complement and strengthen our internal innovation.

Lastly, refocused in this year strategic planning process to critically evaluating and it'd be formulating our cardiovascular and your muscular business franchise strategies that should continue or the capitalized on lifecycle management of our most advanced struck candidates only.

Kenton Mccarville, EPPY, Kempton and Robeson too.

To recap our cash position. We ended the third quarter was approximately $669 million in cash which includes 297 million raced in Q3 through inactivity offering net of expenses.

Therefore, our poor form a cash at year end 2021 is expected to be in the range of 600 to 610 million, which represents more than three years, so cash runway using our revised net cashew realization guidance.

Robert C. Wong: Cost efficiency is another area where we will share field sales, field medical, shared services, and systems across the entire organization. Once we have established relationships and built systems to support the launch of Omicamptive McCarville, we are well-positioned to accelerate and streamline the potential launch of apicamp. It is an incredibly exciting time to be working at Cytokinetics. As we continue to grow our team and advance our plans, it remains important for us to remember the driving force behind this motivation, patience, and the clear unmet need for both heart failure and HCM.

All of 195 to 215 million in 2021.

With the potential commercial launch elbow me cancel carbel.

And the funding of two phase three clinical trials.

Mccoy is Yan and courage allies we.

We do expect our 2022 and 2023 cash burn rate to increase south of 2021 spending.

And we will provide guidance on this in our fourth quarter earnings call.

<unk> occurred in early 2022.

As we have stated.

Robert C. Wong: And with that, I'll turn it over to Robert Wong, who will provide an update on our Thanks, Andrew. I'll provide an update on cash, revenue, and spending, and then Ching will review our financial outlook and corporate development strategy. More details on our actual results for the third quarter of 2021 are included in the press release, which we released earlier this afternoon. We ended the third quarter with approximately $668.9 million in cash and investments.

We continue to seek ways to strengthen our balance sheet and in the third quarter, we have been advanced partnering a structure financing discussions align with our corporate development strategy.

During the quarter, we continue our discussions with potential co development and cold commercialization partners for let me cancel them carbel as well as at the Captain with party attention to business development in Asia, and other a complementary geographies, where we don't intend to go to market ourselves.

Our plan is to preserve north American and potentially European rights for development and commercialization proposed only cancel mccarville in ft Camden.

Robert C. Wong: Our revenue in the third quarter of 2021 came primarily from our recognizing a $5 million milestone from Zhijing Pharmaceuticals in anticipation of the start of Sequoia HCM. Our third quarter 2021 R&D expenses increased to $48.4 million from $24.2 million in the third quarter of 2020, primarily due to increases in spending for our clinical development activities for our cardiac muscle inhibitor program. In addition, we incurred transition costs related to the termination of our collaboration with Amber.

In parallel we have also being a dancing discussions with multiple entities and fun.

Was shared interest related to structure financings, including royalty monetization and a structure that deals.

To further support the commercial launch album, we kept in Kabul, and our continued and expanded development objectives four EPPY Kempton.

Our goal is to complete these deals in the fourth quarter, which could enable us to the end of the year was two to three years. So full of cash one way even as we expect the spending in 2022 and 2023 to be higher than are expected spending this year.

Robert C. Wong: And our purchase from Angen of approximately 7.3 million of materials, including manufactured quantities of the active pharmaceutical ingredients for Omecantin-McCarmel, thereby completing our purchase. More than 70% of our R&D expenses were attributable to our cardiovascular programs, as expected, given activity related to transitions from our collaborations with Amgen, the purchase of manufactured quantities of active pharmaceutical ingredients, ongoing activities associated with Meteoric HF, and also our The remainder of our expenses were attributable to our early research and skeletal muscle program activities.

As you know we have always build our business on a strong financial foundation and we have an established history of making non equity diluted deals to support our continued growth and progress.

Which transactions expected to close this quarter. We believe we are positioned financially and strategically to ask that you the potential lunch over let me cancel the carbel and continue to advance our pipeline and business franchise strategies.

And with that I'll return the call back over to Robert Bun.

Thank you Ching.

Within our vision 2025 that we set forth in 2020, we laid out several goals, including achieving regulatory approvals for at least two drugs arising from our pipeline and expanding our discovery platforms.

Over the past quarter. In addition to the clinical regulatory and commercial progress. We made we also engaged in activities to broaden our research footprint in the years to come.

Robert C. Wong: Our third quarter 2021 G&A expenses were $26.2 million, up from $12.3 million in the third quarter of 2020. Due primarily to an increase in outside spending in anticipation of our potential commercial launch of Omicant and McCarble in 2022, as well as personnel-related costs including stock-based compensation and facilities costs related to our new building. And now, Ching will review our financial outlook and corporate development strategy. Thanks, Robert.

Thinking even beyond 2025, we continue to forge ahead as leaders in muscle biology with focus to populations of high unmet need in the next year, you'll be hearing more about our activities as we've extended our muscle biology focus from the bio mechanics of muscle contractility too.

The energetics growth and metabolism of muscle with novel mechanism drug candidates advancing in development.

While much of our focus has been on our programs in cardiovascular disease.

Ching W. Jaw: As is our annual practice, we recently conducted a comprehensive strategic planning process with subsequent presentation and discussion with our board. This year, the strategic plan was focused on prioritizing our expanding clinical pipeline to ensure that we focus on R&D programs that leverage our core competencies and competitive advantages in muscle biology and also address high unmet need opportunities that may afford high return on investment potential. In addition,

You heard with our stirred encourage AOS our commitment to the AOS communities remains strong.

Along these lines. We also recently donated data from our completed clinical trials and AOS to the Proact database, which stands for pooled resource open access AOS clinical trials.

Proact is available to members of the research community and it contains over 10000 D identified clinical patient records from multiple completed clinical trials, providing a powerful tool to advanced research in the AOS field and also together observations related to disease progression.

<unk> and <unk> do you have any logic data.

We will be donating data from three completed trials in AOS benefit AOS vitality, LLS and fortitude AOS, which represents data from almost 600 patients.

Ching W. Jaw: We pressure-tested plans to enrich our research pipeline with external collaborations that could complement and strengthen our internal innovation. Lastly, we focused in this year's strategic planning process on critically evaluating and reformulating our cardiovascular and neuromuscular business franchise strategies that should continually capitalize on lifecycle management of our most advanced drug candidates, Omikensha McCarble, Effie Kempton, and Rowdy Sanchez. To recap our cash position, we ended the third quarter with approximately $669 million in cash, which includes $297 million raised in Q3 through an equity offering, net of expense. Therefore, our pro forma cash at year end 2021 is expected to be in the range of 600 to 610 million, which represents more than three years of cash runway using our revised net cash utilization guidance of $195 to $215 million in 2021.

We're pleased to be working with the AOS Association with price for life and with the Neurologic Clinical Research Institute at mass General to share. These data with the AOS communities to which were altogether. So importantly dedicated.

Further demonstrating our commitment to patient communities during the quarter, we renewed our partnership with curious to me to increase education awareness public policy in fund raising for spinal muscular atrophy and we also announced the fourth annual Cytokinetics Communications Fellowship grants program.

Which will award a total of $100000 in grants to patient advocacy organizations in heart failure, and HCM in Alice and S. M. A to support increased capacity and communications and outreach.

As we near the end of 2021, we look back on our very gratifying progress at achievements and we look ahead to what may be a watershed year for our company. We expect to end 2021 with two distinct programs advancing in phase three clinical trials with our.

First potential medication moving towards a potential approval and commercial launch and all of that happening on the foundation of continued innovations in muscle biology, directed to patients who rely upon us and in areas for which our leadership offers hope for diseases associated.

Ching W. Jaw: With the potential commercial launch of mecanthum carbol and the funding of two phase three clinical trials and Koya HCM and Courage ALS, we do expect our 2022 and 2023 cash burn rate to increase relative to 2021 spending, and we will provide guidance on this in our fourth quarter earnings call planned to occur in early 2022. As we have stated, we continue to seek ways to strengthen our balance sheet.

With muscle dysfunction, and weakness, we look forward to providing more updates on our continued progress and we welcome your questions and feedback.

Now let me recap are expected milestones for the remainder of 2021 for OMA captive mccarville, we expect to submit an NDA to the F. D. A in this fourth quarter of this year.

We also expect to complete the conduct a meteoric H F by year end with results expected in early 2022.

Ching W. Jaw: And in the third quarter, we advanced partnering and structure financing discussions aligned with our corporate development strategy. During the quarter, we continued our discussions with potential co-development and co-commercialization partners for Omicampton Carbon, as well as Epicampton, with priority attention to business development in Asia and other complementary geographies where we don't intend to go to market ourselves. Our plan is to preserve North American and, potentially, European rights for development and commercialization of both Omicantin-McCarville and epichemicals.

For Alfie Campton, we expect to continue with studies startup with regulatory filings with IRB submissions in sight readiness activities altogether for Sequoia HCM and with availability of drug product and early 20, twenty-two we anticipate commencement of screening and enrollment of the first.

Patients in that trial.

And for real deceptive, we expect to complete enrollment of courage, Alice say well the remainder of this year.

And for our ongoing research, we expect to advanced new muscle directed compounds and to conduct IMD, enabling studies.

And to potentially advanced one to two potential drug candidates into clinical development over the next year.

Ching W. Jaw: In parallel, we have also been advancing discussions with multiple entities and funds with shared interests related to structure financing, including royalty monetization and structured debt deals, to further support the commercial launch of Omicantin-McCarbol and our continued and expanded development objectives for epichemical. Our goal is to complete these deals in the fourth quarter, which could enable us to end the year with two to three years of forward cash runway, even as we expect the spending in 2022 and 2023 to be higher than our expected spending this year.

Operator with that update we can now open the call up to questions. Please.

To ask a question you want me to press Star one on your telephone.

Try your question past the pound key please stand battle, we can pal to Q&A roster.

Your first question comes from that line of gain Leon with Raymond James.

Hello day, Great Hi, Robert and team. Thank you for taking our questions and congratulations on all the updates just two for me if you will firstly.

Can you give us any more color in terms of the scale and scope of the Sequoia HCM study as we think about one modeling expenses and two time to run. The study is it fair to use the explore HCM study as a similar proxy in scale and scope for the patience required and enroll.

Ching W. Jaw: As you know, we have always built our business on a strong financial foundation, and we have an established history of making non-equity diluted deals to support our continued growth and progress. With transactions expected to close this quarter, we believe we are positioned financially and strategically to execute on the potential launch of Omicantum Carbo and continue to advance our pipeline and business franchise strategy. And with that, I'll turn the call back over to Robert Wong. Thank you, Ching.

And then my second question would be just a drill down a little bit more on the.

Submission for OMA captive.

I know, it's been asked before but in terms of updating your communications back and forth, but the F D. A.

Any additional color in terms of the scope or scale of the label as it relates to baseline.

Less in particular ejection fraction. Thank you.

Sure good questions. So I'll start and turn it over to Saudi He May also ask Stuart to elaborate I don't think we're going to provide any specific financial guidance with regard to Sequoia. It may be premature to do that until we start dosing patients, but certainly we can give you some things to hold onto with regard to your <unk>.

Robert I. Blum: Within our Vision 2025, which we set forth in 2020, we laid out several goals, including achieving regulatory approval for at least two drugs arising from our pipeline and expanding our discovery platform. Over the past quarter, in addition to the clinical regulatory and commercial progress we made, we also engaged in activities to broaden our research footprint in the years to come. Thinking even beyond 2025, we continue to forge ahead as leaders in muscle biology with focus on populations of high unmet need.

Projections for instance, what might be our expectations in terms of time for enrollment and duration of the study I hope that can be helpful. And certainly you know already the number of patients we aim to enroll.

So why don't I turn it over to the 31st to talk to you about how we think it's going to enroll the number of sites. The number of countries things like that and then most likely once we start dosing.

Presumably that'll be in early 2022 will be in a better position to a point to how we think it's going to be affecting our spending.

Robert I. Blum: In the next year, you'll be hearing more about our activities as we've extended our muscle biology focus from the biomechanics of muscle contractility to the energetics, growth, and metabolism of muscle, with novel mechanism drug candidates advancing in development. While much of our focus has been on our programs in cardiovascular disease, as you heard, with our Start. Encourage.

And then we'll come back to your second question.

Alright, Thanks Robert.

Thank God, we plan to enroll approximately 270 patients.

In two Sequoia, which is a little bit more than wasn't an old and explore.

Think the.

The size and scope are comparable and.

Certainly the number of sites and things like that we will probably go to a few more sites and they did and explore.

Robert I. Blum: ALS, our commitment to the ALS communities remains strong. Along these lines, we also recently donated data from our completed clinical trials in ALS to the PROACT database, which stands for Pooled Resource Open Access ALS Clinical Trials. ProAct is available to members of the research community, and it contains over 10,000 de-identified clinical patient records from multiple completed clinical trials, providing a powerful tool to advance research in the ALS field and also to gather observations related to disease progression and epidemiologic data.

Or <unk>.

Nearly a dozen countries.

And well over north of 80 sites I think ultimately when we get to study fully up and going.

So our plan is to.

Push art and too and.

And roll this as quickly as possible.

But there are certain I think limitations in terms of this study startup and things like that that are hard to press. Once once we have sites up and going I think of actual enrolled very rapidly.

So then your second question related to the.

N D a and how we're approaching.

What could be.

That which is contained within the NDA indication statement it otherwise in particular round ejection fraction and.

Robert I. Blum: We will be donating data from three completed trials in ALS, Benefit ALS, Vitality ALS, and Fortitude ALS, which represents data from almost 600 patients. We're pleased to be working with the ALS Association, with Prize for Life, and with the Neurologic Clinical Research Institute at Mass General to share these data with the ALS communities to which we are all together so important dedicated. Furthermore, demonstrating our commitment to patient communities, during the quarter, we renewed our partnership with CureSMA to increase education, awareness, public policy, and fundraising for spinal muscular atrophy, and we also announced the fourth annual Cytokinetics Communications Fellowship Grants Program, which will award a total of $100,000 in grants to patient advocacy organizations in heart failure, in HCM, in ALS, and in SMA to support increased capacity in communications and outreach.

As we've stated we do believe that patients with ef's less than 30%.

Are seemingly benefiting a great deal more than other patients.

In Galactic and we do think that it's in the interests of Omi Campton mccarville in patients with heart failure that that's where the.

Labels should point.

So we are hopeful that that data, including graphics could be included in the label ultimately upon potential approval, but that's obviously going to be subject to F. D. A review, but based on conversations we've been having in Saudi can elaborate we do feel encouraged that that would be supportive.

And consistent with other things the FDA is done.

Saudi anything you want to add.

I think we've had those discussions with FDA, obviously, what ends up in the label will be the outcome of the negotiations at the time.

That we negotiate the label, but in general I think they're supportive of the concept that the label should indicate.

Where the benefit of the drug is concentrated and that provides.

Physicians with the information needed Tibet use the drug.

And and that contact the <unk>, an important obviously an important indicator.

Robert I. Blum: As we near the end of 2021, we look back on our very gratifying progress and achievements, and we look ahead to what may be a watershed year for our company. We expect to end 2021 with two distinct programs advancing in phase three clinical trials, with our first potential medication moving towards potential approval and commercial launch, and all of that happening on the foundation of continued innovations in muscle biology directed to patients who rely upon us and in areas for which our leadership offers hope for diseases associated with muscle dysfunction and weakness. We look forward to providing more updates on our continued progress, and we welcome your questions and feedback.

Not only the label it might suspect that that could ultimately inform how only kempton mccarville could be incorporated into guidelines also and you got a sense of that from some of the publications that Saudi referred to in his statements.

Excellent. Thank you very much and congratulations.

Thanks thing.

You know our next question comes from that line of Japan, Guinness with H C. Wainwright.

Hello, Joe Hey, everybody. Good afternoon, thanks for taking the questions I.

Wanted to focus my first question on the concept that you guys are really.

Important execution and logistics.

Time for the company so with that said I'll, even go off of one of Stewart's comments and Robert you said it to about drug availability for Sequoia early next year.

And executing courage as well do you feel you've had to plan anything above and beyond for these studies you know no matter, what it is including drug availability based on any.

Robert I. Blum: Now let me recap our expected milestones for the remainder of 2021. For Omicampt of McCarble, we expect to submit an NDA to the FDA in the fourth quarter of this year. We also expect to complete the conduct of Meteoric HF by year end, with results expected in early 2022. For Athecampton, we expect to continue with study startup, regulatory filings, IRB submissions, and site readiness activities. Altogether, for Sequoia HCM, and with the availability of the drug product in early 2022, we anticipate commencement of screening and enrollment of the first patients in that trial.

Anticipated issues around the global supply chain problems that we're seeing right now.

Very good question I think that might be the first time on one of these earnings call that we really did get a question about the supply chain. It's an area of intense focus for US right now as we are not only embarking on these large phase three studies, but were readying for the supply of them, we camped up into the marketplace.

Obviously had we still been partner do them, John that would be something we'd have relied on them for but now it's our responsibility and we are executing well on contracts as well as conversion of drug substance to drug product and the like.

The study's startup activities for Sequoia are proceeding nicely, we move very swiftly from having completed cohorts went into reading up the results having meetings with F D a and readying to start Sequoia.

Robert I. Blum: And for Real Deceptive, we expect a complete enrollment of Courage ALS throughout the remainder of this year. And for our ongoing research, we expect to advance new muscle-directed compounds and to conduct IND-enabling studies, and to potentially advance one to two potential drug candidates into clinical development over the next year. Operator, with that update, we can now open the call to questions, please.

All of that occurring in a relatively short timeframe. So it seems like things are going well that way both in support of clinical trials and also commercialization.

But we are building the supply chains.

At the same time, we're executing on how the delivery of drug product into.

Operator: To ask a question, you will need to press star 1 on your telephone. 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 Dane Leone with Raymond James. Hello, Dave. Good. Hi, Robert and team. Thank you for taking the questions and congratulations on all the updates.

Clinical trials is occurring so it's something that I think is going to be continuing to be a focus for senior management as that is enabling of our success.

To this point the good news is we're working with some of the same contract manufacturing organizations with whom we have long standing relationships with and there may also be opportunities to.

Consolidate programs amongst them so that we're working.

Dane Vincent Leone: Just two for me, if you will. Firstly, can you give us any more color in terms of the scale and scope of the Sequoia HCM study? As we think about, one, modeling expenses, and two, time to run the study, is it fair to use the Explorer HCM study as a similar proxy in scale and scope for the patients required for enrollment? And then my second question would be just to drill down a little bit more on the submission for OMACAMPTIV.

With them for more than one program and.

We're we're focused a small molecule.

Drug candidates and in that way.

It's not like we're dealing with an incredibly.

Novel way of approaching supply, but at the same time, we have to ensure capacity and deliverable timelines and that's what we're focused towards Saudi anything you want to add to that.

No I think you summed it up I think we've been able to continue to advance.

Drug supplies for our studies and things like that I think the the real.

Dane Vincent Leone: I know it's been asked before, but in terms of updating your communications back and forth with the FDA, any additional color in terms of the scope or scale of the label as it relates to baseline left ventricular ejection fraction? Thank you.

And a major constraint is has to do with the spare capacity in the supply chain.

There's just a lot of it's been squeezed out. So you have to be careful about how you plan thing and what I might also say is Andrew and his team are very focus to the handoff between the manufacturers and then the logistics associated with distribution and all of the activities in connection with ensuring P.

Robert I. Blum: Sure, good questions. So I'll start and turn it over to Fady. She may also ask Stuart to elaborate. I don't think we're going to provide any specific financial guidance with regard to Sierra.

<unk> get reliable sources of drug as well that speaks to potential patient hub services and other things like that over time, I expect you'll hear more about that from Andrew too.

Robert I. Blum: It may be premature to do that until we start dosing patients, but certainly, we can give you some things to hold on to with regard to your projections. For instance, what might be our expectations in terms of time for enrollment and duration of the study? I hope that can be helpful, and I'm sure you already know the number of patients we aim to enroll. So why don't I turn it over to Fady first to talk to you about how we think it's going to enroll, the number of sites, the number of countries, things like that, and then most likely once we start dosing, presumably that'll be in early 2022, we'll be in a better position to point to how we think it's going to be affecting our spending. And then we'll come back to your All right, thanks, Robert.

That's very very helpful. Thank you and then I guess two smaller questions. One maybe for King on the financial side. You. We had this 7.3 million dollar cost to pay Amgen for drug drug product for all the captive just curious what might still be outstanding they're going.

Going into the future or if that expense is essentially done and then second if I heard fatty correct. When he was disc discussed.

Discussing the future from a captive as well I could've sworn I heard him say potential iced teas, so that sounded like an interesting teased there. So I'm curious what kind of studies who might be looking at thank you.

Yeah, I mean I have to like.

Oh go ahead you go first.

Yeah I'll I'll go I'll go for studies, so in regards to the.

Payment that we pay Amgen.

Fady Ibraham Malik: You know, I think we plan to enroll approximately 270 patients in Sequoia, which is a little bit more than was enrolled in Explore. I think, you know, this, the size and scope are comparable. Certainly the number of sites and things like that. We will probably go to a few more sites than they did in... Explore nearly a dozen countries and well over north of 80 sites, I think, ultimately, when we get the study fully up and going.

$7.3 million. This corner is the last of those payment says we stay that in our press release.

For the nine months ended September 30th plenty plenty, one we have pay them $14 6 million. So that was the total amount and there's some point see was the last of the payments.

Thanks.

And I think just in regards to investigator sponsor.

<unk> Oh, sorry.

Yes.

We began to receive proposals, obviously will that them and decide which ones. We can support things like that they all under a fairly.

Fady Ibraham Malik: So our plan is to push hard and to enroll this as quickly as possible. But there are certain, I think, limitations in terms of study startup and things like that that are hard to press. Once we have sites up and going, I think it will actually enroll very rapidly.

Broad range of of interests.

The people have out really outside some of them outside of the heart failure.

Population that we studied in galactic some of them within.

But I think we will we will elaborate more on those as we begin to.

To see them through.

[noise] understood. Thank you very much.

Robert I. Blum: So then your second question related to the NDA and how we're approaching what could be that which is contained within the NDA, the indication statement, and otherwise, in particular around ejection fraction. As we've stated, we do believe that patients with EFs less than 30% are seemingly benefiting a great deal more than other patients in Galactic, and we do think that it's in the interest of Omicampt of McCarble and patients with heart failure that that's where the labels should point.

Thank you.

Your next question comes from the line of gas Meanwhile, hobby with Piper Sandler.

Hello, Yes.

Okay alright. Thank you so much for taking my questions that I have two questions <unk>, maybe the first place to start it.

You.

You know I can that can happen.

<unk> F E recently by some of the actions that were taken clean it sort of a nervous Nellie situation.

The question for you is especially over the last few months and you have been interacting with the F. D. A what sort of their tone their body language enthusiasm to eight P. M and you could just elaborate so that.

Robert I. Blum: So we are hopeful that that data, including graphics, could be included in the label ultimately upon potential approval. But that's obviously going to be subject to FDA review. But based on conversations we've been having, and Fady can elaborate, we do feel encouraged that that would be supportive and consistent with other things the FDA has done. Fady, anything you want to add?

How does discussion when I think that could be really at in question and then I have a follow up question.

Sure. So what I'll say is often times in these situations biotech companies talk about having a pre NDA meeting they submit an NDA. It gets filed or doesn't get filed and then they await approval.

Fady Ibraham Malik: I think we've had those discussions with FDA, and obviously, what ends up in the label will be the outcome of the negotiations at the time that we negotiate the label, but in general, I think they're supportive of the concept that the label should indicate where the benefit of the drug is concentrated, and that provides physicians with the information needed to best use the drug. And in that context, the EF is obviously an important indicator.

In our case over the last year, we've had many interactions with FDA both in person before Covid shut that down and then also.

Subsequently by zoom.

Zoom interactions and otherwise through written exchange of documents.

I've found FDA to be very accessible and very interactive with us and providing guidance that informs both the formatting and the content of our planned NDA submission.

Fady Ibraham Malik: And not only the label; I might suspect that it could ultimately inform how Omicampt and McCarville could be incorporated into guidelines also, and you get a sense of that from some of the publications that Fady referred to in his statement.

So I'm very encouraged by the level of engagement should hopefully support our submission that would hopefully align with interest for approval.

Operator: Your next question comes from the line of Joe Pantginis with HC Wainwright.

Joseph Pantginis: Hey, everybody. Good afternoon.

Joseph Pantginis: Thanks for taking the questions. I wanted to focus my first question on, you know, the concept that you guys are really in an important execution and logistics time for the company. So with that said, you know, I'll even go off of one of Stuart's comments, and Robert, you said it too, about drug availability for Sequoia, early next year, and executing courage as well. Do you feel you've had to plan anything above and beyond for these studies?

We've had.

All of our questions satisfactorily answered in order to provide for US now to go through the final mechanics of an NDA submission in order to get that.

Done this quarter.

Mm. Thank you bye bye.

<unk>, Okay, and maybe a follow up question.

Maybe giving me an inside when you speak with cardiologists, whether I decide to private packet whether it is in the hospital setting sort of the level of <unk> were only can cat in terms of a novel mechanism of action does it click right away when they know that it's the first my child being able.

Robert I. Blum: https://www.youtube.com.uk Transcribed by https://otter.ai Very good question, and I think that might be the first time on one of these earnings calls that we really did get a question about the supply chain. It's an area of intense focus for us right now, as we're not only embarking on these large Phase III studies, but we're readying for the supply of Omicamptive into the marketplace. And obviously, had we still been partnered with Amgen, that would be something we'd have relied on them for, but now it's our responsibility, and we are executing well on contracts, as well as the conversion of drug substance to drug product, and the like. The study startup activities for Sequoia are proceeding nicely.

To really being able to <unk> <unk> I think I need that might be really important like how long appointment is the novelty that's mode of action for driving adoption and their intent to add them beyond obviously that outstanding Dia back to nature.

So it's a little too early to talk about adoption of course and that as much as not approved but certainly based on.

Headboards and interactions with.

Key opinion leaders that have been driven out of medical affairs and also a market research.

It is driven out of our commercial group, we're getting very positive vibes about how the novelty of the mechanism may translate into potential future adoption, maybe I'll turn it over to Saudi first to speak about some of those activities that he has overseen and then I'll turn to Andrew as well.

Robert I. Blum: We move very swiftly from having completed cohorts 1 and 2, reading out the results, having meetings with FDA, and getting ready to start Sequoia. All of that is occurring in a relatively short time frame, so it seems like things are going well that way, both in support of clinical trials and also commercialization, but we are building the supply chains at the same time we're executing on how the delivery of the drug product into clinical trials is occurring.

Yeah, I mean, I think in the physician community certainly understand where this could play a role and it's been Ah.

Finding a drug that can improve cardiac function safely and have benefits for patients has been a long standing goal in this field.

If you listen to our Investor Day presentation, I think you might hear some of the enthusiasm and the to discuss since we had but.

But it was similar amongst many add board that we conducted both in the us and in Europe.

Robert I. Blum: So it's something that I think is going to be, and will continue to be a focus for senior management as that is an enabler of our success. And to this point, the good news is we're working with some of the same contract manufacturing organizations with whom we have longstanding relationships. And there may also be opportunities to consolidate programs amongst them so that we're working with them on more than one program. You know, we're focused on small molecule drug candidates. And in that way, it's not like we're dealing with an incredibly novel way of approaching supply.

And I think even as we go out to other stake holders in the process. We're sensing their enthusiasm for something that is new but on the other hand, we understand how it works and it and it's rational rationalist, Hawaii might might use it.

Alright.

The only thing I would add is that when we talk with physicians.

There were excited by the mechanism not for the mechanism alone, but it's a reason to believe relative to the data and the evidence that we produced.

So when they look at the mechanism and the evidence and the unmet need are very well aligned they are running out of options when patients can't tolerate guideline directed medical therapy.

We're running out of options when they need products that could be an add on the neutral and kidney neutral on blood.

Fady Ibraham Malik: But at the same time, we have to ensure capacity and deliverable timelines. And that's what we're focused on. Fady, anything you want to add to that? No, I think you summed it up.

Blood pressure and working patients and when you talk about the add on and those type of effects. They get very excited and a good reason to believe then kind of closing as a mechanism. So we're getting a lot of enthusiasm for a very specific subset of patients relative to the product.

Fady Ibraham Malik: But I think, you know, we've been able to continue to advance. Drugs supplies for our studies and things like that. I think the real, you know, major constraint has to do with the, you know, spare capacity in the supply chain. There's just a lot of it that's been squeezed out.

Thank you for Indiana K.

Thank you.

Your next question comes from the line at the calf Huh with Morgan Stanley.

Hey, Jeff Thanks for taking me Hey, Robert Thanks for taking the question Ah previously indicated that Ah meetings with payers on a Mckenzie mccardell had been largely introductory just curious if you've had any updates that you can provide on peer feedback.

Fady Ibraham Malik: So you have to be, you know, careful about how you plan things. And what I might also say is Andrew and his team are very focused on the handoff between the manufacturers and then the logistics associated with distribution and all of the activities in connection with ensuring patients get reliable sources of drugs as well. And that speaks to potential patient hub services and other things like that. Over time, I expect you'll hear more about that from Andrew too. Very, very helpful.

Sure I'll turn it over to Andrew to address that.

Sure so quickly.

The question, so we've interacted with.

As I mentioned with hired all of our account managers as well as the leader of that team.

Many of them have existing relationships with all the major payors, we've interacted with a major payer then it's really more about and production who was Cytokinetics and then making sure we align well on how they think about heart failure, how do they manage heart failure.

What are their challenges and what are their needs. So we've had those kind of baseline discussions and then where will go next is.

Joseph Pantginis: Thank you. And then I have two smaller questions. One, maybe for Ching, you know, on the financial side, you would have this $7.3 million cost to pay Amgen for the drug product for Omicamptive. Just curious what might still be outstanding there going into the future, or if that expense is essentially done. And then second, if I heard Fady correctly, when he was discussing the future of Omicamptive as well, I could have sworn I heard him say potential ISE. So that sounded like it. So I'm curious what kind of study... Yeah, I mean, go ahead, Ching, you go. Yeah, I'll go. I'll go first, Fady.

<unk> Riggs is kind of a pre.

Approval information exchange.

We'll start doing that in coming weeks. So the feedback has been.

They do like that we can clearly identify those patients.

Relative to benefit and E. S. So then therefore that could indicate.

They would target us from a prior authorization point of view, which is <unk>, which is acceptable to us because that gives us access to a very specific population that greatly benefits for a moment captain. So hopefully that gives you a color of our interactions in the third quarter.

The other thing to add is there's there's a lot more forthcoming that you'll see in the published literature in 2022 that underscores the economic burden of heart failure, especially for those with worsening heart failure, and where there could be opportunity for a new mechanism therapy like when we can.

Ching W. Jaw: So in regards to the payment that we pay Amgen, the $7.3 million this quarter is the last of those payments. As we stated in our press release, for the nine months ended September 30, 2021, we paid them $14.6 million. So that was the total amount, and this $7.3 was the last payment.

To the Carbel based on results from Galactic to make a dent in that four payers and payers are clearly aware of the economic burden associated with their management of heart failure patients there were especially at the high Medicare percentage of these patients for which there are often times penalised when these.

Patients are readmitted.

Fady Ibraham Malik: And I think just in regards to investigator-sponsored studies. You know, we began to receive proposals. Obviously, we'll vet them and decide which ones we can support, things like that. They fall under a fairly broad range of interests that people have, you know, really outside, some of them outside of the heart failure population that we studied in Galactic, some of them within, but I think we'll elaborate more on those as we begin to see them through.

So a novel mechanism therapy that could reduce heart failure related events, primarily hospitalizations would be something that would catch their attention and that's something that we will continue to investigate.

Investigators could be supportive of our plans for them we camped.

Great. Thanks, and I think I may have misheard, but did you say that you expect.

Enrollment of courage to be completed this year.

Why's any updates on this may timing or when you might be better able to gauge the paste enrollment to estimate that Tanya. Thanks.

Operator: Your next question comes from the line of Yasmeen Rahimi with Piper Sandler.

Yeah, what I, what I said or meant to say was that <unk>.

Yasmeen Rahimi: Hello Yasmeen,

Moment continues through this year, but also intended next year also.

Yasmeen Rahimi: Hi Robert, thank you so much for taking my questions, but I have two questions for you.

We expect that.

Will enrolled patients sufficient to enable.

Robert I. Blum: Two questions for you. Maybe the first place to start is, Uh, a lot of our investors have been sort of surprised by the FDA recently with some of the actions that were taken and created sort of a nervous Nelly situation. So I guess the question for you is, especially over the last few months, as you've been interacting with the FDA, what sort of their tone, their body language, their enthusiasm towards you. If you could just elaborate on the, you know, how this discussion went. I think that could be really uh important, and then I have a follow-up question.

Ah first interim analysis next year, the timing of which is still to be defined but we expect that were it to pass through that interim analysis. Hopefully it will this study would continue through next year. So no. It's not intended to complete enrollment this year.

Okay. Thank you.

Thank you Jeff.

Your next question comes from the line as I cashed, Hawaii with caffeine.

Hello cash.

Hey, Robert Uhm. So thanks, so much for taking my questions can you talk about what drove your decision to look at exercise capacity as your primary endpoint person call you and not the combo that appointment madder hat why may exercise capacity and be a more youthful and point both for the agency and clinicians and Additionally have you heard any feedback.

Robert I. Blum: Sure, so what I'll say is that often in these situations, biotech companies talk about having a pre-NDA meeting, they submit an NDA, it gets filed or doesn't get filed, and then they await approval. In our case, over the last year, we've had many interactions with FDA, both in person before COVID shut that down, and then also, subsequently, through Zoom interactions and otherwise, through written exchange of documents. I found FDA to be very accessible and very interactive with us, providing guidance that informs both the formatting and the content of our planned NDA submission.

From either the S. T. A R K O L on the need for longterm outcomes data post approval for applicant then thank you.

Why don't we turn first to Stewart to address the first question and then maybe fatty in steward the second question.

Thank you Robert.

So we focused on.

Uhm functional improvement.

And patients with destructive HCM compare gnathic Hampton versus placebo and.

With respect to the fact that these patients had a very poor exercise tolerance.

Robert I. Blum: So I'm very encouraged by the level of engagement that should hopefully support our submission that would hopefully align with interest for approval. We've had all of our questions satisfactorily answered in order to provide for us now to go through the final mechanics of an NDA submission in order to get that done this quarter.

We focus on one of the most rigorous objective.

Measurements of exercise capacity and and that is clearly.

P P O two.

As well as other parameters using cardiopulmonary exercise testing.

And.

So without rather than.

The mining this with.

Robert I. Blum: Thank you, Robert, for the answer.

More subjective.

Yasmeen Rahimi: Maybe you could give me some insight when you speak with cardiologists, whether these are in private.

Conant of a composite endpoint.

We really wanted to zero in on what we thought was the most sort of critical.

Robert I. Blum: sort of the level of appreciation they have for Omicamtiv in terms of a novel mechanism of action. Does it click right away when they know that it's the first myotrope, being able to really improve cardiac contractility? I think that might be really important, like how important the novelty of its mode of action is for driving adoption in their enthusiasm, beyond obviously the outstanding data from Galactin HS.

And quantitative measurement and objective measurement of exercise capacity and.

Having said that we will be evaluating.

Other endpoints is secondary endpoints that.

Evaluate uhm symptomatic improvements such as the Kansas City Cardiomyopathy questionnaire.

New York Heart Association functional class et cetera. So.

Those other kind of I'll say more.

Fady Ibraham Malik: So it's a little too early to talk about adoption, of course, in that as much as it has not been approved, but certainly based on advertising boards and interactions with key opinion leaders that have been driven out of medical affairs and also market research. As is the case with our commercial group, we're getting very positive vibes about how the novelty of the mechanism may translate into potential future adoption. Maybe I'll turn it over to Fady first to speak about some of those activities that she's overseen, and then I'll turn to Andrew as well.

More traditional and points, we will be evaluated.

And Sequoia.

[laughter].

And your second question.

What you wanted to repeat that for me a cash.

Yeah, absolutely have you heard any feedback either from the F. D. A R. K O L on the need for outcomes data post approval for a C. K 274.

Yeah outcome.

The regulators and Kols appreciate that outcome data are very hard to come by in it.

<unk> matic, although very.

Heavily burdened patient population.

Fady Ibraham Malik: Yeah, I mean, I think the physician community certainly understands where this could play a role. And it's been a long-standing goal in this field to find a drug that can improve cardiac function safely and have benefits for patients. If you listen to our Investor Day presentation, I think you might hear some of the enthusiasm and the two discussions we had. But it was similar amongst many ad boards that we conducted, both in the U.S. and in Europe.

These patients unlike traditional heart failure patients don't get hospitalized.

Their mortality rates are are usually quite low in lesson.

Well well under 5% per year so.

You can't really doing it outcomes based trial per se and I think that's well understood based on the event right.

That said I think that there's also a recognition that the therapy that.

Is being developed for these patients as a lifelong therapy and so.

Andrew Callos: And I think even as we go out to other stakeholders in the process, we're sensing their enthusiasm for something that is new. But on the other hand, we understand how it works, and it's rational. It's rational as to why you might use it. This is Andrew.

A good understanding of it.

Safety Longterm is important and that's why.

We're conducting the open label extension and plan at least five years of follow up in patients that we enroll in that that rollout of either redwood or sequoia to enable us to better characterize the course of these patients who are being treated with that the campton.

Andrew Callos: The only thing I would add is that when we talk with physicians, they're excited by the mechanism, not for the mechanism alone, but it's a reason to believe relative to the data and the evidence. So when they look at the mechanism, and the evidence, and the unmet need, they are very well aligned. They are running out of options when patients can't tolerate guideline-directed medical therapy. They are running out of options when they, Products that could be an add-on that can neutralize kidney, and blood pressure in working, and when you talk about the add-on and those type of effects, they get very excited and have a good reason to believe then that kind of closing is a mechanism, so we're getting a lot of enthusiasm for a very specific subset of patients relative to the problem

I think the advent of new Pharmaceuticals is gonna drive a better awareness of the outcomes associated with a diagnosis of HCM cause could be.

Modified with.

Add on therapy, Kempton or Mavacamten.

You're going to see I think increasingly publications arising out of registries.

Week to the real world evidence associated with these longitudinal studies.

Studies, so we will be in a position to better understand.

What might be possible, but I do suspect that will play into ultimately the adoption of the category, but to your original question as to whether regulators are pushing for it.

Yasmeen Rahimi: Thank you for the answers,

I don't think that's likely going to factor into the.

Operator: Your next question comes from the line of Jeff Hung with Morgan Stanley.

The registration of these new medicines at least not from what we've heard from FDA.

Jeff Hung: Good job. Thanks for taking the time.

That's super helpful and if I if I may just follow up here can you talk about the.

Jeff Hung: Hey Robert, thanks for taking the question. Previously, you indicated that meetings with payers were like a MacKenzie-McCartney concert.

The importance of showing that patients are able to get stabilized onto a state goes for this class of drugs. If that's something that the agency is focused on from a regulatory perspective. Thanks. So much.

Robert I. Blum: Previously, you indicated that meetings with payers on Omakens and McCarble have been largely introductory. Just curious if you have any updates that you can provide on payer feedback. Sure, I'll turn it over to Andrew to address that. Thank you.

It's certainly something that we think is possible it achievable with Alfie campton.

Andrew Callos: So we've interacted with, you know, as I mentioned, we hired all of our account managers, as well as a leader of that team. Many of them have existing relationships with all the major payers. We've interacted with the major payers, and it's really more about introductions: who is Cytokinetics, and then making sure we align well on how they think about heart failure, how do they manage heart failure? What are their challenges

And we hope to be able to demonstrate that with Sequoia.

If your question is pointed to is that something FDA is pushing for because of their review of.

Other product that would not be appropriate for FDA to be signaling anything like that to us.

Understood. Thanks, so much I appreciate it.

Yeah. Our next question comes from their line of selling side with a man with nursing home.

Closely.

Good good afternoon, Robert and team and congrats on all the progress just a couple for me one on to some foreign one on actually real deceptive.

Andrew Callos: And what are their So we've had those kind of baseline discussions, and then where we'll go next is, you know, per FDA regulations, kind of a pre-approval information exchange. And we will start doing that in the coming weeks. So the feedback has been, well, they do like that we can clearly identify those patients relative to benefit in ES. So then, therefore, that could indicate where they would target us from a prior authorization point of view, which is exactly acceptable to us because that gives us access to a very specific population that greatly benefits from all the captains.

So on 274 looks and Robert always seen the.

The fetus here has gotten a lot more comfortable for a lot of long only investors right and I'm curious in your mind what are the gating factors. When you think about the story what are they gaining factors here for two some for that are really stopping you from turning on the afterburners and starting to develop.

Have passed fortunate you know, it's a large indication more aggressively.

We can also asked the same question for Nonobstructive hypertrophic cardiomyopathy.

And then the second question on rolled Assumptive. So let me start to dig in here on the current design you guys are enrolling looks like Alice F. R. US total score 44 or less when when you look at the the.

Andrew Callos: So hopefully, that gives you a flavor of our interactions in the third. The other thing to add is there's a lot more coming that you'll see in the published literature in 2022 that underscores the economic burden of heart failure, especially for those with worsening heart failure and where there could be opportunity for a new mechanism therapy like Omicam to Bicarbol based on results from Galactic to make a dent in that for payers.

The face to data.

The slow progress or turnstile, which had a.

A score of 41, they didn't really show much of a difference between drug and placebo. Some curious and you guys are thinking about courage are you going to limit somehow this slow progressors that are entering the trial or.

Or how are you insuring that you know when when we got to futility that you haven't in over enrolled slow progression. So I guess, it's one way to ask it or how are you controlling but they're going to actually have enough medium or fast progressors that would show a larger benefit potentially according to the fence to Dana. Thank you.

Andrew Callos: And payers are clearly aware of the economic burden associated with their management of heart failure patients. They're aware, especially of the high Medicare percentage of these patients for which they're oftentimes penalized when these patients are readmitted. So a novel mechanism therapy that could reduce heart failure-related events, primarily hospitalizations, would be something that would catch their attention. And that's something that we'll continue to investigate as it could be supportive of our plans for Omicamp. Great, thanks.

Sure both very good questions, let's start with your first one around the development program for half the Kempton we've.

We've spent quite a bit of time over these last several months once we saw the redwood results.

Considering what might be our next steps beyond Sequoia HCM for ft, Campton in Saudi in Steward, and Steve and others here et cetera genetics are considering a number of different.

Trial designs as we would be expected.

To expand the development program, and Nonobstructive, HCM and and help them, it's premature for us to elaborate on them, but you should expect in 2022 to hear more about our plans that way.

Jeff Hung: I think I may have misheard, but did you say that you expected enrollment in COURAGE to be completed this year? Otherwise, any updates on estimated timing or when you might be better able to gauge the pace of enrollment to estimate that timing? Thanks.

We intend to be pursuing the development of Alfie Kempton, along both those lines and not in a linear way per se, but in parallel ways that would be enabling of us to build on what we know four ft campton.

Robert I. Blum: Yeah, what I said or meant to say was that enrollment continues through this year but also intended next year also. We expect that we'll enroll patients sufficient to enable a first interim analysis next year, the timing of which is still to be defined, but we expect that were it to pass through that interim analysis, hopefully it will, the study would continue through next year. So, no, it's not intended to complete enrollment this year.

I'm just not in a position to do that on today's call.

But certainly as we plan for budgets for 2022 and goals and consider a resources that we need to align in order to make that happen that's very much in the forefront of our planning.

Your second question related to courage AOS in Alaska, Saudi and Stuart to address I think you might.

Operator: Your next question comes from the line of Akash Tewari with Jeffreys.

The misunderstanding a bit how we are designing the study we are going to be prioritizing for those patients who are progressing but they can elaborate.

Akash Tewari: Hey Robert, So

Robert I. Blum: Thanks so much for taking my questions. Can you talk about what drove you?

Operator: https://www.youtube.com.au

Yeah, I think it's really an enrichment strategy filling in so they an entry criteria designed in such a way to enrich for the medium and after Progressors.

Operator: Transcribed by https://otter.ai

And Ah can turnovers turtle, but describe how that works but.

Robert I. Blum: And finally, have you heard any feedback from either the FDA or KOLs on the need for long-term outcomes data post-approval for Aficantin? Thank you.

But ultimately it's also something that we can monitor because.

And you can look at progressive you can look at the.

Calculate the early progression rates in the study and ensure that you're enrolling the right patients and blinded way uhm.

Stuart Kupfer: Why don't we turn first to Stuart to address the first question and then maybe Fady and Stuart to address the second question. Thank you, Robert. So we focused on Evaluating Functional Improvement.

Sure.

So selenite I think you're referring to the post hoc analyses that were conducted with the fortitude Alice database and.

Stuart Kupfer: in patients with destructive HEM, comparing apicampin versus placebo, and

While we observed transit benefit.

In slow Progressors we.

Stuart Kupfer: With respect to the fact that these patients have very poor, you know, exercise tolerance.

We observed greater magnitude benefit with respect to Alice F. R. S R and a medium and fast progressing patients.

Stuart Kupfer: exercise tolerance. We focus on one of the most rigorous, objective measurements of exercise capacity, and that is clearly peak PO2 as well as other parameters using cardiopulmonary exercise testing. And so, you know, we thought rather than

And what.

What we did with map that progression rate two critical entry criteria, particularly a maximum Alice F or S. R.

A 44.

Stuart Kupfer: Combining this with, let's say, a more subjective... This is one component of a composite endpoint. We really wanted to zero in on what we thought was the most critical and quantitative measurement, an objective measurement of exercise capacity. Having said that, we will be evaluating other endpoints, these secondary endpoints that evaluate symptomatic improvements, such as the Kansas City Cardiomyopathy Questionnaire, New York Heart Association Functional Class, et cetera. Those other kind of, I'll say, more traditional endpoints we will be evaluating, and Sequoia.

As well as time from symptom onset.

Two.

Years, and so if.

If we apply to fly there's two main criteria.

That enriches is that he mentioned for population.

Faster progressing patients.

While not excluding slow progressors, but we will have a larger proportion of medium and faster progressing patience and that.

That strategy.

We anticipate that this will increase the sensitivity.

Detecting a beneficial treatment effect was around the symptom.

Okay got it. So this is this is more you will be able to in your view.

Stuart Kupfer: and you're the second question. What? Do you want to repeat that for me, Akash?

Do this based on entry criteria not having to calculate during the trial based on blind and data.

Akash Tewari: Yeah, absolutely. Have you heard any feedback, either from the FDA or KOLs, on the need for outcomes data post-approval for CK274? Yeah, you know, outcomes data, I think the regulators and KOLs appreciate that outcomes data are very hard to come by, symptomatic, although, you know, a very heavily burdened patient population. These patients, unlike traditional heart failure patients, don't get hospitalized. Um, their mortality rates are usually quite low and, you know, less. Well, you know, well under 5% per year.

That's correct exactly.

Thank you.

Thank you so.

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

Good afternoon, Jason.

Hi, Robert Thanks for taking my questions could you just wondering if you could talk a little bit more about the past four African person in China is that data that you need beyond the completed PK study to open up the Sequoia trial to China, and then just to give us a sense of <unk>.

What proportion of patients as to <unk>, you think could come from from China and then.

Could could sequoia as a standalone support registration in China or would you need additional data oriented additional trial beyond that that trial. Thanks.

[noise], yeah, so very good questions were.

Fady Ibraham Malik: And so, you can't really do an outcomes-based trial, per se, and I think that's well understood based on the event rate. That said, I think that there's also a recognition that the therapy that is being developed for these patients is a lifelong therapy. And so, you know, having a good understanding of the sites that we enroll in that roll out of either Redwood or Koya to enable us to, you know, better characterize the course of these patients who are being treated with apicampin.

Still learning about what might be required, but it's our assumption.

That we're going to be in a position to start Sequoia.

In China.

And based on the phase one data via enrolling China patients into the same study and as could be supportive of registration in China as well as outside of China U S. Europe elsewhere. So that's the intention and the plan, obviously that subject to regulatory unit.

Actions that are still to be hard.

But our partners regime is very much on top of these things and we're working very very well stewardess, leading much of that activity for Cytokinetics Stuart anything more you want to add.

I think you've summarized it very well.

Fady Ibraham Malik: You know, I think the advent of new pharmaceuticals is going to drive a better awareness of the outcomes associated with a diagnosis of HCM, as could be modified with add-on therapy of afecamptin or mavicamptin. You're going to see, I think, more publications arising out of registries that speak to the real-world evidence associated with these longitudinal studies. So we will be in a position to better understand what might be possible, and I do suspect that'll play into the adoption of the category in the end. But to your original question as to whether regulators are pushing for it, I don't think that's likely going to factor into the registration of these new medicines, at least not from what we've heard from FDA.

We certainly rely on N G shake or for guidance they have more expertise in China regarding the regulatory requirements.

But as you as it has been.

Laid out we expect the phase one data to support enrollment of patients in China in Sequoia HCM and.

That trial to support registration in China.

Great. Thanks for taking my questions.

Thank you.

Your next question comes from their lineup Charles Duncan with Cantor Fitzgerald.

Charles.

Hello, Robert and team congratulations on good year of Prime crafts. Thanks for taking my question had a couple of questions why nine only camden's and then another on it roll deceptive with regard to only captive and da Sein Lane I guess I'm wondering are you are.

Are you planning on press releases, the submission or the acceptance for review our filing and then I guess I just need to clarify something I think it was two two Danes question would you be filing for a broad labor.

Akash Tewari: That's super helpful. And if I may just follow up here, can you talk about the importance of showing the FDA that patients are able to get stabilized onto a safe dose for this class of drugs? Is that something that the agency is focused on from a regulatory perspective?

Robert I. Blum: That's something that the agency is focused on from a regulatory perspective. Thanks so much. It's certainly something that we think is possible and achievable with AFI Camp. And we hope to be able to demonstrate that with Sequoia. If your question is pointed to, is that something FDA is pushing for because of their review of another product, that would not be appropriate for FDA to be signaling anything like that to us.

Will claim with data pointing to the patient cohort that had the greatest benefit or would you limit the filing claim to that cohort.

Yeah, So I'll take those and how do you may want to elaborate with regard to the communications and the press release, we expect to be.

Submitting an NDA in this quarter and we probably would not be communicating anything until such time as we have a read on its final ability, whether it's filed or not filed by FDA.

Operator: Your next question comes from the line of Salim Syed with Mazzuho. Hello, Salim.

And then as to your second question last Friday to speak.

Salim Qader Syed: Hello Salim. Good afternoon Robert and team, and congrats on all the progress. Just a couple from me, one on 274 and one on the actual Real Decentive. So on 274: Robert, obviously, the thesis here has gotten a lot more comfortable for a lot of long-only investors, right? And I'm curious in your mind, what are the gating factors when you think about the story, what are the gating factors here for 274? The slope progressor per trial, which had a score of 41, didn't really show much of a difference between the drug and placebo. So I'm curious how you guys are thinking about courage.

Regarding how we might approach the indication statement and where might be the information containing the.

Patients that benefited the most.

Yeah I can.

You'll get different indications statements, even recent ones, they're different approaches, but and generally they reflect the patient population that was studied in the clinical trial at large.

You can see in the.

Entresto label after the the Paragon data were added that there was an additional statement with regards to where the benefit was concentrated E in patients with below normal ejection fraction.

So it may.

It may be that you could end up with modifying statement an indication.

Salim Qader Syed: Are you going to limit somehow the slope progressors that are entering the trial? Or how are you ensuring that when we get to futility, you know you have an over-enrolled slow progression, I guess is one way to ask it, or how are you ensuring that you're going to actually have enough medium or fast progressors that would show a larger benefit here, potentially according to the phase two data? Thank you.

You certainly will have data in the clinical trials section that show.

The Prespecified subgroups, which one of which was ejection fraction as you know and showed a the.

The benefit in the lower ejection fraction group the Nyj three four group.

And.

And in others and across the.

Subgroups that we had pre specified so there are different places in the label where the information may be contained.

Robert I. Blum: Sure, both very good questions. Let's start with your first one about the development program for AFI-CAM. We've spent quite a bit of time over these last several months once we saw the Redwood results. Considering what might be our next steps beyond Sequoia HCM for Affy Campton and Fady and Stuart and Steve and others here at Cytokinetics are considering a number of different trial designs, as we would be expected, to expand the development program in non-obstructive HCM and in HFPAF.

And ultimately you know it's hard to predict where we will end up until we go through those discussion.

Okay. That's helpful I consistent with what I kind of thought regarding media are okay. Thank you mentioned that you complete the conduct of it yet this year can you give us some sense on timing to data could that be in the first half of the first quarter.

And then can you confirm whether or not you think that that data would then be submitted to the agency and have any potential for impacting the review it seems like it'd be pretty early in the review psychos, So so likely not.

Robert I. Blum: It's premature for us to elaborate on them, but you should expect in 2022 to hear more about our plans that way. We intend to be pursuing the development of AFI-CAMPTN along both those lines, and not in a linear way per se, but in parallel ways that would be enabling us to build on what we know for AFI-CAMPTN. I'm just not in a position to do that on today's call. But certainly, as we plan for budgets for 2022 and goals and consider resources that we need to align in order to make that happen, that's very much at the forefront of our planning.

Yeah, I think what.

And we will probably aren't going to give guidance with regards to first half a second half of the quarter with regards to meteoric.

Conduct will wrap up this year, but it's really going to wrap up pretty late in the quarter.

And then of course, there's a complicated study because there's a lot of central lab.

Work in terms of the sea pet evaluations, and so forth and and the datasets are relatively complex to integrate.

Fady Ibraham Malik: Your second question related to COURAGE-ALS, and I'll ask Fady and Stuart to address it. I think you might be misunderstanding a bit how we are designing the study. We are going to be prioritizing those patients who are progressing, but they can elaborate. Yeah, I think, you know, it's really an enrichment strategy, Salim. And so the entry criteria were designed in such a way to enrich for the medium and faster progressors. And I can turn to Stuart a little bit to describe how that works.

Tightened database lock maybe.

Swift as you might have an event based trial.

Okay.

But I think.

The.

Other aspect of your question that you're going to have to remind me of again now got lost track of it.

Just just the impact on you.

View Psycho tiny.

Yeah, No I think having the results in hand in early in the quarter is not going to you know obviously, the FDA will see them as we release them in and.

Fady Ibraham Malik: But ultimately, you know, it's also something that we can monitor because Stuart Kupfer, Akash Tewari, Paul Choi, Sean McCutcheon, Adhiraj Chauhan, Cameron Bozdog, So Salim, I think you're referring to the post hoc analyses that were conducted with the Fortitude ALS database.

And hope to see them presented.

But they will we think impact your view.

Safety data will be probably.

Part of an update during the review cycle, but that's it.

Stuart Kupfer: Why we observed trends of benefit in slow progressors, we observed greater magnitudes of benefit with respect to ALS-FRS-R in medium and fast-progressing patients. And what we did was map that progression rate to critical entry criteria, you know, particularly a maximum ALS-FRS-R of 44, as well as time from symptom onset.

Okay, and then going on to around the centre of just one quick question regarding the conduct of that trial in it and I think you mentioned in the previous set of questions or a couple of the floor that you're kind of them reaching for faster progressing patience.

And so I guess I'm wondering are you explicitly asking for more balls are onset versus limb onset patient seemed like become system with that given that under two years since symptom presentation.

Stuart Kupfer: So if we apply those two main criteria that enrich, as Fady mentioned, the population of faster-progressing patients,

Stuart Kupfer: Progressing Patients Well, I'm not excluding slow progressors, but we'll have a large proportion of medium and faster progressing patients. And, you know, with that strategy. We anticipate that this will increase the sensitivity of detecting a beneficial treatment effect with relative symptoms.

Stuart taken out now.

That we were not being that restricted in terms of our enrollment we're certainly.

Uhm enrolling patients uhm in both categories, but.

As I mentioned before major criteria.

Yeah to enrich for faster progressing patients based on that.

Salim Qader Syed: Okay, got it. So this is more, you will be able to, in your view, do this based on entry criteria, not having to calculate during the trial based on blinded data? That's correct, exactly. Okay, thank you.

Alice FRS score.

Baseline in time since it's a nonsense.

Okay. Thanks for taking the questions.

Thank you Charles.

Your next question comes from their line of work.

With a medium and company.

Operator: Your next question comes from the line of Jason Butler with JMP Securities. Good afternoon.

Good afternoon.

Hi, Good afternoon. This is rove it on for search. Thanks for taking my question can you talk a bit about how the meteoric H F trial fits with the gold market strategy for OMA captive do you expect a label expansion or better pair reimbursement.

Jason Nicholas Butler: Hi Robert. Thanks for taking the questions. I'm just wondering if you could talk a little bit more about the path for Africantin in China. Is there data that you need beyond the completed PK study to open up the Sequoia trial in China? And then, you know, just to give us a sense of what proportion of patients in Sequoia you think could come from China. And then, you know, could Sequoia be sold as a standalone support registration in China? Or would you need additional data or an additional trial beyond that trial? Thanks.

Sure all are starting to speak to that and maybe Andrew might want to add.

At.

Yeah, I think if me New York is positive we would at some point submit for a supplemental NDA.

Filing an expansion of the label that would include the results meteoric.

The clinical benefit there is important patience and certainly would be worth having in the label that wouldn't come until after primary approval of 'em Captain Carbel.

And I think.

Being.

Then proving exercise capacity is something that is rarely shown with drugs that improve.

Robert I. Blum: Yeah, so very good questions. We're still learning about what might be required, but it's our assumption that we're going to be in a position to start Sequoia. And based on the phase one data, enrolling Chinese patients into the same study could be supportive of registration in China, as well as outside of China, the US, Europe, elsewhere. So that's the intention in the plan. Obviously, that's subject to regulatory interactions that are still to be had.

That would be a unique feature of them captive mccarville said the trial will be positive.

Turn it over to Andrew <unk> anything else you want to add that.

Sure I mean, we're going to be negotiating access.

Preapproval post approval and largely will be using the data from galactic. If we have a positive New York trial, that's certainly will enhance the benefit we could bring the patient expressing capacity could enhance our value argument if patients feel better or it could be more productive so.

It depends on how the data retail and what the adjustments or for the label, but I wouldn't expect it to have a major impact on our overall access strategy your excess levels.

Stuart Kupfer: But our partner, Zhijing, is very much on top of these things, and we're working very, very well. Stuart is leading much of that activity for cytokinetics. Stuart, anything more you want to add? I think you've summarized it very well. We certainly rely on G-Shane for guidance, http://www.ncbi.nlm.nih.gov. We expect the Phase 1 data to support enrollment of patients in China and Sequoia HCM that trial to support registration.

What it does do is it reinforces the mechanism as provides.

What could be differentiating.

Benefits to patients beyond outcomes, this being a functional outcome and in that way it could reinforce.

The use of only came to book horrible, but I agree with Andrew it's not likely to drive.

View things.

Operator: Your next question comes from the line of Charles Duncan with Cantor Fitzgerald.

Very much have.

Have the effect of things like adherence in compliance of patients and also how physicians might ultimately view the category.

Charles Cliff Duncan: [inaudible]

Charles Cliff Duncan: Hello, Robert, and team. Congratulations on

Great. Thank you.

Charles Cliff Duncan: And a good year of progress. Thanks for taking my question.

And there are no further questions in queue at this time.

Charles Cliff Duncan: A couple of questions, one on Omicamtiv and then another on Relative Ascentive. With regard to the Omicamtiv NDA filing, I guess I'm wondering, are you planning on press-releasing the submission or not?

Alright, your closing remarks please.

Thank you thanks, very much to all of the participants.

On our teleconference. Today. Thanks for your continued support and your interest in Cytokinetics. We're pleased to be able to provide you updates with respect to our progress as well as our prospects.

Charles Cliff Duncan: or filing, and then I guess I just need to clarify some things.

Charles Cliff Duncan: I think it was to Dane's question, would you be filing for a broad label claim?

Obviously, a lot is going on at our company and we're looking forward to continuing to execute well on our key milestones through the remainder of this year and then peering into next year as mentioned it could be quite a transformational year 2022, we look forward to sharing with you all of those updates.

Charles Cliff Duncan: If you could label a claim with data pointing to the patient, the cohort that had the greatest benefit, or would you limit the filing of the claim to that cohort?

Robert I. Blum: Yeah, so I'll take those, and Fady may want to elaborate with regard to the communications and the press release. We expect to be submitting an NDA in this quarter, and we probably would not be communicating anything until such time as we have a read on its fileability, whether it's filed or not filed by FDA. And then as to your second question, I'll ask Fady to speak regarding how we might approach the indication statement and where it might be information containing the patients that benefited the most.

And with that operator, we can conclude the call.

Thank you. This does conclude today's conference you may now disconnect.

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Robert I. Blum: Yeah, you know, I think if you look at different indication statements, even recent ones, there are different approaches, but in general, they reflect the patient population that was studied in the clinical trial at large. For example, you can see on the Entresto label after the Paragon data were added that there was an additional statement with regard to where the benefit was concentrated, i.e., in patients with below normal ejection fraction.

Robert I. Blum: So it may be that you could end up with a modifying statement in the indication. You certainly will have data in the clinical trial section that show the pre-specified subgroups, one of which was ejection fraction, as you know, and showed the benefit in the lower ejection fraction group, the NYHA 3-4 group, and others across the subgroups that we had pre-specified. So there are different places in the label where the information may be contained. And ultimately, it's hard to predict where we'll end up until we go through those discussions.

Charles Cliff Duncan: Okay, that's helpful. Consistent with what I kind of thought.

Fady Ibraham Malik: Regarding Meteoric, I think you mentioned that you'd complete the conduct of it this year. Can you give us some sense on timing for data? Could that be in the first half of the first quarter? And then can you confirm whether or not you think that that data would then be submitted to the agency and have any potential for impacting the review? It seems like it'd be pretty early in the review cycle, so probably not.

Fady Ibraham Malik: Yeah, you know, I think what we probably aren't going to give guidance with regard to the first half or second half of the quarter with regard to meteorics. Its conduct will wrap up this year, but it's really going to wrap up pretty late in the quarter. And then, of course, it's a complicated study because there's a lot of central lab work in terms of the CPET evaluations and so forth, and the data sets are relatively complex to integrate, so time database lock may be, You don't know how to SWIFT as you might in an event-based trial.

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Fady Ibraham Malik: The, Um, but I think, um, the, the, uh, other aspect of your question. You're going to have to remind me of it again now. I think I lost track of it.

Charles Cliff Duncan: Just to impact on the review cycle timing.

Fady Ibraham Malik: Yeah, no, I think, you know, having the results in hand and early in the quarter is not going to, obviously, the FDA will see them as we release them and hope to see them presented, but they won't, we think, impact the review. There will be safety data that will probably be part of an update during the review cycle. But that's it.

Charles Cliff Duncan: Okay, and then going on to Routless Temptive, just one quick question regarding the conduct of that trial. And I think you mentioned in the previous set of questions, or a couple of the four, that you're kind.

Charles Cliff Duncan: You're kind of enriching for faster progressing.

Charles Cliff Duncan: And so I guess I'm wondering, are you?

Operator: Transcribed by https://otter.ai

Charles Cliff Duncan: This presentation seemed like it would be consistent with that given that it was under two years since the symptom presentation.

Stuart Kupfer: Stuart, do you want to take that? No. Yeah, no. We're not being that restrictive.

Stuart Kupfer: We're not being that restrictive in terms of our enrollment. We're certainly enrolling patients, you know, in both categories, but as I mentioned before, major criteria to enrich for faster progressing patients based on that LSFRS score at baseline and the time since Zemansky.

Charles Cliff Duncan: Okay, thanks for taking the questions. Thank you.

Operator: Your next question comes from the line of Rohit Bhasin with Needham & Company. Good afternoon...

Rohit Bhasin: Hi, good afternoon. This is Rohit on for Surge.

Rohit Bhasin: Thanks for taking my question. Can you talk a bit about how the Meteoric HF trial fits with the gold market strategy for Olmec Amtiv? Do you expect a label expansion or better payer reimbursement? Sure, I'll ask Fady to speak to that, and maybe Andrew might want to add.

Fady Ibraham Malik: I think if METEORIC is positive, we would at some point submit for a supplemental NDA filing, an expansion of the label that would include the results of METEORIC. You know, the clinical benefit there is important to patients, because improving exercise capacity is something that is rarely shown with drugs that improve heart health. That would be a unique feature of Omicamptive McCarville should the trial be positive. Maybe I'll ask to turn it over to Andrew to see if he has anything else he wants to add. Sure.

Andrew Callos: I mean, we're going to be negotiating access. Pre-approval, post-approval, and largely, we'll be using the data from Galactic. If we have a positive meteoric trial, that certainly will enhance the benefit. We could bring the patient to specialty incapacity.

Andrew Callos: It could enhance our value argument. Patients feel better, and they could be more productive. So it's really going to depend on how the data read out and what the adjustments are to the label. But I wouldn't expect it to have a major impact on our overall access strategy or access. What it does do is it reinforces the mechanism as provided. What could be differentiating benefits to patients beyond outcomes, this being a functional outcome?

Andrew Callos: And in that way, it could reinforce the use of Omicam to Bacarbol, but I agree with Andrew, it's not likely to drive sales. But it might very much have an effect on things like adherence and compliance of patients, and also how physicians might ultimately view the category.

Operator: And there are no further questions in queue at this time. Robert, your closing remarks, please. Thank you.

Robert I. Blum: Thank you. Thanks very much to all the participants in our teleconference today. Thanks for your continued support and your interest in cytokinetics.

Operator: We're pleased to be able to provide you with updates with respect to our progress as well as our prospects. Obviously, a lot is going on at our company, and we're looking forward to continuing to execute well on our key milestones through the remainder of this year and then looking into next year. As mentioned, it could be quite a transformational year in 2022.

Operator: We look forward to sharing with you all of those updates, and with that, Operator, we can conclude the call. Thank you. This does conclude today's conference call. You may now disconnect.

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Operator: Thank you. This does conclude today's conference call. You may now disconnect. Thanks for watching!

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Operator: No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. Good afternoon, and welcome, ladies and gentlemen, to Cytokinetics' third quarter 2021 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 Joanna Siegel, Cytokinetics' Senior Manager of Corporate Communications and Investor Relations. Please go ahead.

Robert I. Blum: Good afternoon, and thanks for joining us on the call today. Robert Blum, our President and Chief Executive Officer, will begin with an overview of the quarter and recent developments. Then, Fady Malik, our EVP of Research and Development, will provide an update on Omicamp.

Stuart Kupfer: Stuart Kupfer, our SVP and Chief Medical Officer, will provide an update on our development program for AFI Campton by recapping the results from Cohorts 1 and 2 of Redwood HVM, and elaborating on

Stuart Kupfer: Collaborating on continuing activities in Redwood HCM and reviewing the design of Sequoia HCM, our planned Phase 3 clinical trial of afecamptin in patients with obstructive HCM. He will also speak to initial progress in COURAGE-ALS, our ongoing Phase 3 clinical trial of rel-dissemptive in patients with ALS.

Andrew Callos: Then, Andrew Callos, our EVP and Chief Commercial Officer, will discuss our go-to-market strategy for Omacampton McCarble and our cardiovascular franchise development plans for the commercialization of Affie Campton. Robert Wong, our VP and Chief Accounting Officer, will provide a financial overview for the past quarter. And Ching Jaw, our...

Ching W. Jaw: SCP and the Chief Financial Officer will discuss strategic planning.

Robert I. Blum: Our financial outlook and corporate development strategies before Robert Blum will provide

Robert I. Blum: will provide concluding thoughts and expected key milestones for the remainder of 2021.

Unknown Executive: Please note that portions of the following discussion, including our responses to questions, contain statements that

Unknown Executive: [inaudible] Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our third quarter 2021 financial results filed on Form 8K today. We undertake no obligation to update any forward-looking statements after the, Now I will turn the call over to you, Joanna.

[music].

Robert I. Blum: And thanks again to everyone for joining us on the call today. We had a very productive third quarter marked by meaningful progress across all of our later stage programs. Most notably, we are sharing positive results from our Phase 2 clinical trial, Redwood HCM, which demonstrated the efficacy and safety of aficamptin, our next-in-class drug candidate, in patients with obstructive hypertrophic cardiomyopathy. As we've said, these results met our high expectations for this trial, and we received positive feedback from the physician community. Stuart will elaborate more on these results in a moment.

Robert I. Blum: During the third quarter, we were also pleased to complete enrollment in Cohort 3 of Redwood HCM, which, as you recall, enrolled patients also on Desipiramide, a medication often prescribed to patients with more severe HCM. We expect to share the results from Cohort 3 in the first quarter of 2022. Following previous interactions with FDA from which we received feedback on our planned trial design, we've continued to advance activities in preparation for Sequoia HCM, a Phase III clinical trial of aficampin in patients with obstructive HCM.

Robert I. Blum: As we recently presented, and as Stuart will elaborate, this trial was designed to potentially demonstrate a significant improvement in exercise capacity and evaluate safety in a broad population of patients with symptomatic obstructive HCM. We're working with sites around the world, including many who participated in Redwood HCM, who are enthusiastic about also participating in Sequoia HCM, and we look forward to starting this trial soon. Moving now to our heart failure program, we continued activities supportive of our plans to submit an NDA for Omicamptive McCarble, and we remain on track towards our goal of submission in the fourth quarter of this year. Fady will have more to say about that in a moment.

Robert I. Blum: Additionally, as outlined in our recent Analyst and Investor Day, we're making significant progress in refining and executing our go-to-market strategies for Omicampt and McCarble across several work streams that Andrew will elaborate on in a moment. These commercial readiness activities represent a tremendous scope of work from our growing commercial organization and support our go-to-market strategy. As well as our intention to build a cardiovascular business franchise by leveraging common denominators and synergies across our business, including our plans for the potential launch of Omicamptomacarbal and a potential future launch of Athicamptomacarbal.

Robert I. Blum: As Fady will discuss, in the third quarter, we presented additional results from GalacticHF, highlighted by an analysis of black patients enrolled in GalacticHF, showing that the treatment effect of Omicamptomacarbal in black patients was consistent with the treatment effect in the overall population and also similar to the effect observed in white patients in the trial. This finding is important due to the fact that black patients tend to have a higher risk of heart failure and often have worse outcomes.

Good afternoon, and welcome ladies and gentlemen to Cytogenetics third quarter 2021 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 Joanna Segal that'll come that ex senior manager of corporate Communications and Investor Relations. Please go ahead.

Robert I. Blum: Additionally, an analysis of the severe heart failure subgroup in Galactic HF was published in the Journal of the American Medical Association Cardiology, illuminating a larger treatment effect when compared to the overall population of patients studied. This important manuscript was accompanied by an editorial suggesting recognition of a new classification for a group of severe heart failure patients whose still prevailing high unmet need represents an increasing patient population with heart failure that contributes more and more to the clinical and the economic burden of this disease.

Good afternoon, and thanks for joining us on the call today, Robert Blum, our President and Chief Executive Officer will begin with an overview of the quarter and recent developments.

<unk> Malik our EVP of research and development will provide an update on all mcham from a carbo, including recently presented additional analyses from Galactic H F. As long as an update on our ongoing next steps with the FDA.

Stuart Kupfer, our SVP and Chief Medical Officer will provide an update on our development program for IV Camden by Recapping the results from cohort, one and two of Redwood HCM elaborating on continuing activities in Redwood HCM and reviewing the design of the quiet HCM, our planned phase III clinical trial of Appia Camden in.

Robert I. Blum: Finally, we were pleased in the most recent quarter to begin enrolling patients in CURID-ALS, our Phase 3 clinical trial of rel-deceptive in patients with ALS. The results from the Phase 2 clinical trial, Fortitude ALS, were deemed compelling by investigators and physicians who treat patients with ALS, and our advancement to Phase 3 is an exciting and important step forward for this program, as is aligned with our dedication to the ALS community. The ALS communities are more assertively seeking new medicine, and the FDA and public policy makers seem to be increasingly responding to these louder calls for action. It is an incredibly important time for our company.

With obstructive HCM he.

He will also speak to initial progress encourage our ongoing phase III clinical trial, a rubber stamped it in patients with ALS.

And then Andrew Carlos our EVP and Chief Commercial Officer will discuss our go to market strategy for OMA kept him a carbo and our cardiovascular franchise development plans for the commercialization of IV Kempton.

One our VP and Chief Accounting Officer will provide a financial overview for the past quarter and Ching jaw, our SVP and Chief Financial Officer will discuss strategic planning, our financial outlook and corporate development strategies before Robert Blum will provide concluding thought unexpected key milestones for the remainder of 2021.

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.

Robert I. Blum: We're building our teams and capabilities as we're now in the precipice of a powerful transformation from an R&D company into one that is also a commercial organization. It has always been our strategic vision to ourselves deliver on the promise of our science, and we're closer to that now than ever before. These are exciting times, to be sure, but how we execute on those plans will matter.

Our actual results might differ materially from those projected in these forward looking statements additional information.

Information concerning factors that could cause our actual results to differ material from those in these forward looking statements is contained in our SEC filings, including our current report regarding our third quarter 2021 financial result filed on form 8-K today, we undertake no obligation to update any forward looking statements after.

Robert I. Blum: Robert will speak to our current financials, and Ching will comment on our progress and prospects in continuation of our long-standing practice to diversify our access to capital through both partnering and structured financings as informed by annual strategic planning. With that, I'll turn the call over now to Fady to elaborate on developments related to Omicampt of McCarble. Thanks, Robert.

This call now I will turn the call over to Robert.

Thank you Joanna and thanks again to everyone for joining us on the call today.

We had a very productive third quarter marked by meaningful progress across all of our later stage programs, most notably our sharing positive results from our phase II clinical trial, Redwood HCM, which demonstrated the efficacy and safety of Abbvie Kimpton, our next in class drug candidate.

Fady Ibraham Malik: As you mentioned, results from additional analyses of galactic HF presented during the quarter at the Heart Failure Society of America annual scientific meeting reinforced that outcomes with omicantin, macarbol, and black patients enrolled in galactic HF were consistent with the overall population. And like the overall study results, we're driven primarily by a reduction in heart failure hospitalizations and heart failure events. The treatment effect in black patients was also similar compared to white patients.

In patients with obstructive hypertrophic cardiomyopathy.

As we've said these results met our high expectations for this trial and we received positive feedback from the physician community.

Stuart will elaborate more on these results in a moment.

During the third quarter. We were also pleased to complete enrollment in cohort three of Redwood HCM, which as Youll recall enrolled patients also on just the pyramid of medication often prescribed to patients with more severe HCM.

Fady Ibraham Malik: Galactic HF enrolled the most black patients among recent heart failure trials, and of patients enrolled in the U.S., 29% were black, which is important not only because black patients have historically been underrepresented in clinical research but also because they have a higher risk of heart failure and suffer worse outcomes. This disparity in outcomes is complex, but it's encouraging to see that the potential benefit of treatment with Omicaptive Mecarbil remains consistent in this group.

We expect to share the results from cohort three in the first quarter of 2022.

Following previous interactions with FDA from which we receive feedback on our planned trial design. We've continued to advance activities in preparation for Sequoia HCM the phase III clinical trial without the kimpton in patients with obstructive HCM.

As we recently presented it as Stuart will elaborate this trial was designed to potentially demonstrate.

A significant improvement in exercise capacity and evaluate safety in a broad population of patients with symptomatic obstructive HCM.

Fady Ibraham Malik: Expanding on the theme of higher-risk patients with heart failure, three weeks ago, a manuscript entitled Assessment of Omicamptomacarbal for the Treatment of Patients with Severe Heart Failure was published in JAMA Cardiology. Following on the heels of the initial data presentation in late June at Heart Failure 2021, an International Congress of the European Society of Cardiology, the analysis by Dr. Michael Felker and co-authors looked at the treatment effect of omicamptomacarbal on the primary composite endpoint in patients with galactic HF. Classified as having severe heart failure based on modified criteria from the Heart Failure Association of the European Society of Cardiology (Advanced Heart Failure Position Statement).

We're working with sites around the world, including many who participated in Redwood HCM, who are enthusiastic about also participating in Sequoia HCM and we look forward to starting this trial soon.

Moving now to our heart failure program, we continued activity supportive of our plans to submit an NDA for <unk> and we remain on track towards our goal of submission in this fourth quarter of this year Faddy will have more to say about that in a moment.

Additionally, as outlined in our recent analyst and Investor Day, we're making significant progress in refining and executing our go to market strategies for Omi captive mccarville across several work streams that Andrew will elaborate on in a moment.

These commercial readiness activities represent a tremendous scope of work from our growing commercial organization and supporting our go to market strategies as well as our intention to build a cardiovascular business franchise by leveraging common denominators and synergies across our business inclusive of.

Fady Ibraham Malik: Patients in this subgroup had NYHA Class 3-4 symptoms, EFs of less than or equal to 30%, and hospitalization for heart failure within the prior six months. Approximately 30% of patients enrolled in GALACTIC-HF met these criteria and had event rates through approximately twice those of patients without severe heart failure. In this post-talk analysis, those with severe heart failure who received Omacamptive-McCarble experienced a significant treatment benefit for the primary endpoint with a hazard ratio of 0.80, whereas patients without severe heart failure had no significant treatment benefit with a hazard ratio of 0.99. The results for cardiovascular death were qualitatively similar.

Our plans both for the potential launch of <unk> and a potential future launch of Ft Kimpton.

As Barry will discuss in the third quarter, we presented additional results from Galactic HFF highlighted by an analysis of black patients enrolled in Galactic HFF showing that the treatment effect of <unk> in black patients was consistent with the treatment effect in the overall population and also Sim.

Alert to the effects observed in white patients in the trial.

This finding is important due to the fact that black patients.

<unk> tend to have a higher risk of heart failure, and often have worse outcomes.

Additionally, an analysis of the severe heart failure subgroup in Galactic eight Jeff was published in the journal of the American Medical Association Cardiology.

Fady Ibraham Malik: Patients with heart failure that was severe experienced a trend towards treatment benefits from Omecamtiv-McCarville, while patients without severe heart failure did not. Omecansin-McCarville was equally well tolerated in patients with and without severe heart failure, with no significant changes in blood pressure, renal function, or potassium compared to placebo. Accompanying this manuscript was an editorial authored by Drs. Clyde Yancey, Adrian Hernandez, and Greg Fonaro titled, Identifying Treatments for Stage C-2 Heart Failure. In which stage C2 is proposed as a new addition to the currently defined four stages of heart failure, A through D, and as would encapsulate these severe heart failure patients, who may be a priority for additional impactful therapy.

Illuminating a larger treatment effect when compared to the overall population of patients studied.

This important manuscript was accompanied by an editorial suggesting recognition of a new classification for group a severe heart failure patients who is still prevailing higher unmet need represents an increasing patient population with heart failure that contributes more and more to the clinical and the.

Economic burden of this disease.

Finally, we were pleased in the most recent quarter to begin enrolling patients encourage ALS, our phase III clinical trial of rail deceptive in patients with ALS.

The results from the phase II clinical trial, Fortitude ALS were deemed compelling by investigators and physicians, who treat patients with ALS and our advancement to phase III is an exciting and an important step forward for this program as is aligned with our dedication to the AOS communities.

Fady Ibraham Malik: This high unmet need was a focus of our panel discussion at our recent Analyst and Investor Day. Despite the availability and adherence to Guideline-Directed Medical Therapy, or GDMT, patients with worsening heart failure still have high event rates. As we heard from Drs.

The airlift communities are more assertively, seeking new medicines, and the FDA and public policymakers seem to be increasingly responding to these louder calls for action.

Fady Ibraham Malik: Alana Morris and Tariq Hamad, who are both specialists in heart failure at major academic medical centers, say it can be a challenge to get patients on GDMT because many are unable to tolerate their medications due to side effects. With Omicam to McCarville, we have the potential add-on therapy with a novel mechanism of action that could be used as a complement to and alongside existing therapies. Without Increasing Cardiac Mortality, Physician feedback has indicated that their view is positive about the clinical utility of vomicamptomacarbal as an additional therapeutic option, with a good safety and tolerability profile, and that there is a clear need for therapy like omicamptomacarbal to fit into regular practice.

It is an incredibly important time for our company. We are building our teams and capabilities. As we are now on the precipice of a powerful transformation from an R&D company into one that is also a commercial organization.

It has always been our strategic vision to ourselves deliver on the promise of our science and we're closer now to that than ever before.

These are exciting times to be sure, but how we execute on those plans will matter.

Robert will speak to our current financials, and Shane will comment on our progress and prospects and continuation of our long standing practice to diversify our access to capital through both partnering and structured financings as is informed by annual strategic planning.

Fady Ibraham Malik: Moving on, we completed enrollment in METEORIC-HF at the end of the second quarter, and we continued conduct of the trial in the third quarter. This trial will provide insight as to how Omicamptin-McCarville could benefit another key aspect of improving the lives of people with heart failure, which is to improve their exercise capacity. A common concern of patients with heart failure is their inability or difficulty with everyday tasks. However, current treatments have little to no impact on exercise capacity and stamina.

With that I'll turn the call over now to <unk> to elaborate on developments related to Omi captive mccarville.

Thanks, Robert as you mentioned results from additional analyses of Galactic HFF presented during the quarter at the heart failure Society of America annual scientific meeting reinforce that outcomes with Camden Mccarville black patients enrolled in Galactic <unk>.

Consistent with the overall population and like the overall study results were driven primarily by a reduction in heart failure hospitalizations and heart failure events.

Fady Ibraham Malik: We expect to complete METEORIC-HF this year and look forward to reporting results in early 2022. Also, in the third quarter, we conducted meetings with FDA to support the preparation and submission of our new drug application, or NDA, for Omicamptin-McCarbol. We completed a pre-NDA meeting that confirmed the suitability for submission of content related to chemistry, manufacturing, and control, clinical pharmacology, and the non-clinical program as well as the format of datasets, the integrated summary of safety, and other components of the NDA.

The treatment effect and black patients was also similar compared to white patient.

Galactic HFF enrolled the most back black patients among recent heart failure trial and have patients enrolled in the U S. 29% were black which is important not only because black patients have historically been underrepresented in clinical research, but also because they have a higher risk of heart failure and suffer worse outcome.

This disparity and outcomes is complex, but it is encouraging to see that the potential benefit of treatment phenomenon captive mccarville remains consistent in this group.

Expanding on the theme of higher risk patients with heart failure, three weeks ago, a manuscript entitled assessment of only <unk> <unk> for the treatment of patients with severe heart failure was published in Jama cardiology. Following on the heels of the initial data presentation in late June at heart failure 2000.

Fady Ibraham Malik: We also had a meeting with FDA to discuss the assay for plasma concentrations of Omicamptive Mecarbil in terms of its potential need to guide dosing, as well as the regulatory pathway for its implementation. In sum, these meetings provided guidance on some of the content of our NDA, which is on track for submission this quarter. As we approach our goal of submitting our NDA to the FBA, we have also continued simultaneously growing the scope and reach of our medical affairs activities by hiring Therapeutic Area Lead Medical Directors and deploying additional field-based medical science.

One and international Congress of the European Society of Cardiology.

The analysis by Dr. Michael Felker and co authors looked at the treatment effect of <unk> on the primary composite endpoint in patients from Galactic HFF classified as having severe heart failure based on modified criteria from the heart failure Association of the European Society of Cardiology adverse.

<unk> heart failure or position statement.

Patients in this subgroup had nyj class III for symptoms es of less than or equal to 30% and hospitalization for heart failure within the prior six months.

Fady Ibraham Malik: We have developed a compliant framework for an investigator-sponsored studies program, which is timely as we have started to receive requests for potential collaborative activities. The team is working on finalizing their scientific platform for Omicamptive McCarville, which forms the basis for communications with medical professionals. We also initiated vendor selection for the development of a medical contact center to be prepared to respond to requests for medical information or direct questions to the proper personnel for a response. With that, I'll turn the call over to Stuart to provide an update on Affie Kampton and Roald Assembly. Thanks, Fady. During the third quarter of September, we present

Approximately 30% of patients enrolled in Galactic HFF met these criteria and had event rates are approximately twice those patients without severe heart failure.

In this post hoc analysis.

And those with severe heart failure, who received <unk> experienced a significant treatment benefit for the primary endpoint with a hazard ratio of 080, whereas patients without severe heart failure had no significant treatment benefit with a hazard ratio of <unk> 99.

Our results for cardiovascular death, or qualitatively similar patients with heart failure that was severe experienced a trend towards treatment benefit for a moment Camden mccarville, while patients without severe heart failure did not.

Stuart Kupfer: We presented the full results from cohorts 1 and 2 of Redwood HDM, the phase 2 clinical trial of apicampin, at the Heart Failure Society of America annual scientific meeting in Denver. As we've mentioned, the results were positive and support our advancing at the camp into phase three, which I'll touch on in a moment.

OMA Camden Mccarville was equally well tolerated in patients with and without severe heart failure with no significant changes in blood pressure renal function or potassium compared to placebo.

Accompanying this manuscript was an editorial authored by doctors Clyde Yancy, Adrian Hernandez, and Greg Panaro titled identifying treatments for stage C to heart failure.

Stuart Kupfer: As we previously shared, in Redwood,

Stuart Kupfer: [inaudible] and the average resting left ventricle.

And which states seek to as proposed is a new addition to the currently defined four stages of heart failure, <unk> and as would encapsulate these severe heart failure patients.

Stuart Kupfer: Particular Outflow Tract, or LVOT, Pressure

Stuart Kupfer: Pressure Gradient, and the average post-valve salivate LVOT gradient in the majority of patients treated with apicampus. 79% in cohort 1 and 93% in cohort 2 achieved the target goal of treatment defined as a resting gradient less than 30 millimeters of mercury and a post-valsalva gradient less than 50 millimeters of mercury at week 10, compared to 8% for placebo. These reductions in LBOT gradient were dose-dependent, with patients achieving greater reductions of LVOT gradient with increasing doses of abicampin.

Well, maybe a priority for additional impactful therapy.

This high unmet need was a focus of our panel discussion at our recent analyst and Investor day.

Despite the availability and adherence to guideline directed medical therapy, our GMT.

Patients with worsening heart failure is still have high event rate as.

As we heard from doctors Morris and Toric Ahmad.

Both specialists and heart failure major academic medical centers and it can be a challenge to get patients on GMT, because many are unable to tolerate their medications due to side effects.

With <unk>, we have the potential add on therapy with a novel mechanism of action that could be used as a complement to and alongside existing therapies without increase in cardiac mortality.

Stuart Kupfer: Reductions in LVOT gradient occurred within two weeks of initiating treatment and were maximized.

Physician feedback has indicated that their view is positive towards the clinical utility of OMA captive mccarville as an additional therapeutic option with.

Stuart Kupfer: The end of treatment is two to six weeks of the start of dose titration and were sustained until the end of treatment at 10 weeks. Reversibility of LBOT gradient and LBHX infraction reductions were observed after discontinuation of AFI-CAMP-1, with levels returning to baseline at the end of the two-week washout period. Patients also experienced statistically significant reductions in NT Pro BMP, and treatment with Aficampin was associated with an improvement in New York Heart Association functional class, with a substantial number of patients improving by at least one class.

Good safety and Tolerability profile and that there is a clear need for therapy, Lycoming Camden mccarville to fit into regular practice.

Moving on we completed enrollment in meteoric <unk> at the end of the second quarter and we continued conduct of the trial in the third quarter.

This trial will provide insight as to how mckesson mccarville could benefit another key aspect of improving the lives of people with heart failure, which is to improve their exercise capacity.

A common concern of patients with heart failure is their inability or difficulty with everyday task.

Stuart Kupfer: As previously stated, treatment with apicampin was well-tolerated, the incidence of adverse events was similar between treatment arms, and there were no treatment-related serious adverse events. Additionally, there were no treatment interruptions or discontinuations. Dr. Marty Marin, Director of the Hypertrophic Cardiomyopathy Center at Tufts University School of Medicine, who presented the results of Redwood HCM at HFSA, Underscored the potential clinical utility of anticampin based on the elimination of arresting LVOT gradients in nearly all patients. Dr. Mehran further commented on the substantial improvement in heart failure symptoms, as well as the rapid onset and reversibility of effects.

But current treatments have little to no impact on exercise capacity and stamina.

We expect to complete meteoric HFF this year and look forward to reporting results in early 2022.

Also in the third quarter, we conducted meetings with FDA to support the preparation and submission of our new drug application or NDA for OMA Captain Carnival.

We completed our pre NDA meeting, which confirm the suitability for submission of content related to chemistry manufacturing and control clinical pharmacology and the non clinical program as well as the format of dataset Ina granted integrated summary of safety and other components of the NDA.

We also had a meeting with FDA to discuss the assay for plasma concentrations of <unk> captive mccarville in terms of its potential need to guide dosing as well as the regulatory pathway for its implementation.

Stuart Kupfer: The ability to use precise echoguided titration, and the Lack of Dosing Interruptions for Low Ejection Practice. At the conference, we also received a positive reaction from physicians who manage patients with HCM, expressing their enthusiasm about the results and for medication that potentially could be used for patients who have symptomatic obstructive HCM and are not responding to current standard of care therapy. Overall, we're very encouraged by the results so far and their potential translation to clinical practice. During the quarter, we also completed enrollment in Cohort 3 of Redwood HCM, in which patients with obstructive HCM who are receiving disupiramide as background therapy are treated with aficampin in an open-label manner.

In sum these meetings provided guidance to some of the content of our NDA, which is on track for submission this quarter.

As we approach our goal of submitting our NDA to the FDA. We also continued simultaneously growing the scope and reach of our medical affairs activities by hiring therapeutic area lead medical directors and deploying additional field based medical scientists.

We have developed a compliant framework for an investigator sponsored studies program, which is timely as we have started to receive requests for potential collaborative activities.

The team is working on finalizing their scientific platform here on the captive mccarville, which forms the basis for communications with medical professionals.

We also initiated vendor selection for the development of our medical contact center to be prepared to respond to requests for medical information our direct questions to the proper personnel for a response.

Stuart Kupfer: This cohort will further inform the potential inclusion of small but important patients.

Stuart Kupfer: Thank you very much. In addition, during the third quarter, we continued enrolling patients in Redwood HCM OLE, the open-label extension trial of Redwood HCM. With the positive results in hand from Redwood HCM, we have been actively engaging in startup activities for Sequoia HCM, our planned phase 3 clinical trial of apicampin in patients with obstructive heart failure. At our Analyst and Investor Day meeting in October, we presented the design of the trial, which I'll recap at a high level now. Sequoia HDM is a randomized, double-blind, placebo-controlled, international clinical trial designed to evaluate apicampin in patients with symptomatic obstructive HDM on background medical therapy for 24 weeks.

With that I'll turn the call over to Stuart to provide an update on epic Hampton enrolled attempted.

Thanks Patty.

During the third quarter in September we presented the full results from cohorts, one and two of Redwood HCM the phase II clinical trial of that be Camden.

Heart failure Society of America annual scientific meeting in Denver.

As we've mentioned the results were positive and support our advancing <unk> into phase III, which I'll touch on in a moment.

As we previously shared and Redwood HCM treatment with Abbvie Camden for 10 weeks resulted in statistically significant reductions from baseline compared to placebo.

And the average resting left ventricular outflow tract or LDL T pressure gradient.

And the average post now Sal de <unk> great.

Stuart Kupfer: The primary objective is to evaluate the change from baseline to week 24 in peak oxygen uptake, or peak VO2.

The majority of patients treated with that be Camden.

79% in cohort, one and 93% in cohort two achieved.

Stuart Kupfer: Measured by Cardiopulmonary Exercise Testing or CPET, which is a measure of exercise capacity. Among the secondary objectives, we are investigating the change in the Kansas City cardiomyopathy questionnaire clinical symptom score and New York Heart Association Functional Class at Week 12 to evaluate a potentially early improvement in heart failure symptoms, and again at week 24. We plan to randomize 270 patients in a one-to-one ratio to apicampin or placebo in addition to standard of care.

Achieved the target goal of treatment defined as resting gradient less than 30 millimeters of Mercury and post valsalva gradient less than 50 millimeters of Mercury at week 10.

Compared to 8% for placebo.

These reductions in LDL T gradient were dose dependent with.

With patients achieving greater reductions of Lv Ot gradient with increasing doses of happy campus.

The reductions in ldlc gradient occurred within two weeks of initiating treatment with <unk>.

<unk> within two to six weeks of the start with dose titration and were sustained until the end of treatment at 10 weeks.

Reverse ability of ELV, Ot gradient and there'll be ejection fraction reductions were observed after discontinuation of athey Camden with levels returned to baseline at the end of the two week washout period.

Stuart Kupfer: Each patient will receive up to four escalating doses of apicampin or placebo with dose optimization based on achievement of echocardiographic targets. The starting dose will be 5mg once daily, escalating to 10, 15 or 20mg once daily, as needed.

Patients also experienced statistically significant reductions in empty pro BNP.

And treatment would that be Camden was associated with an improvement in New York Heart Association functional class.

Stuart Kupfer: Achieved Target Rate These four doses were selected based on the results from Redwood HCM to facilitate selection of the optimal dose for each patient and maximize the individual benefit-risk profile. Study startup activities, regulatory filings, and IRB submissions are underway, with the first site initiations already underway.

With a substantial number of patients improving by at least one class.

As previously stated treatment with Abbvie Camden was well tolerated.

Incidents of adverse events were similar between treatment arms and there were no treatment related serious adverse event.

Importantly, there were no treatment interruptions or discontinuation.

Stuart Kupfer: Drug product availability in early 2022 will enable the commencement of screening and enrollment of the first patients in this trial. In anticipation of enrolling patients with obstructive HCM from China in the sequoia HCM trial, we continue to collaborate closely with our partner, Jixing Pharmaceuticals. Jixing recently completed a phase one study evaluating single and multiple doses of apicampin in healthy Chinese subjects. The pharmacokinetic results were similar to those observed in the Caucasian population enrolled in our phase one study of apicampin conducted in the U.S. and similarly showed dose-proportional pharmacokinetics with a safety and tolerability profile comparable to

Dr. Marty Marin director of Hypertrophic Cardiomyopathy Center at Tufts University School of Medicine.

We presented the results of Redwood HCM and HSA.

Underscore the potential clinical utility of anti Camden based on the elimination of arresting LVL ingredients in nearly all patients.

Dr. Myron further commented on the substantial improvement in heart failure symptoms.

Rapid onset and reverse ability of effect.

The ability to use precise echo guided titration and the lack of dosing interruptions for low ejection fraction.

At the conference. We also received a positive reaction from physicians, who manage patients with HCM and expressing their enthusiasm about the results.

Stuart Kupfer: The results of this study support the submission of a clinical trial application and enrollment of patients with obstructive HCM in China.

And for a medication that potentially could be used for patients who have symptomatic obstructive HCM.

And are not responding to current standard of care therapies.

Stuart Kupfer: on the neuromuscular front. As Robert mentioned, during the third quarter, we began enrolling patients in COURAGE-ALS, the phase 3 clinical trial of rel-dissemptive in ALS. Courage ALS will enroll approximately 555 patients with ALS, randomized 2 to 1, to receive raldecentive or placebo for

Overall, we're very encouraged by the results so far and their potential translation to clinical practice.

During the quarter. We also completed enrollment in cohort three of Redwood, HCM, and which patients with obstructive HCM.

While receiving disopyramide as background therapy are treated with Abbvie, Camden and an open label manner.

Stuart Kupfer: followed by a 24-week period in which all patients will receive raw data. The primary endpoint is a change from baseline to 24 weeks and ALSFRSR, which is a functional rating scale that indicates the progression of ALS.

This cohort will further inform the potential inclusion of this small but important patient population and our planned phase III trial.

In addition, during the third quarter, we continued enrolling patients in Redwood HCM OLED. The open label extension trial of Redwood HCM.

Stuart Kupfer: As we designed Courage ALS, we incorporated feedback from patients and caregivers to remove key barriers to clinical trial participation and to help improve the patient experience.

With a positive result in hand from Redwood HCM, we have been actively engaging in startup activities for Sequoia HCM.

Our planned phase III clinical trial of <unk> in patients with obstructive HCM.

Stuart Kupfer: We are also working to provide continued access to Relda Semptive for all patients who complete COURAGE-ALS, as well as patients who have previously participated in our ALS trial, reflective of our goal to ensure ethical and

At our analyst and Investor Day meeting in October we presented the design of the trial, which I'll recap at a high level now.

So Korea HCM is a randomized double blind placebo controlled international clinical trial designed to evaluate <unk> Camden in patients with symptomatic obstructive HCM on background medical therapy for 24 weeks.

Andrew Callos: Thank you. With that, I will turn the call over to Andrew to discuss our progress against the go-to-market strategy for Omicamptive Macargo.

The primary objective is to evaluate the change from baseline to week 24, and peak oxygen uptake or peak the O two.

Andrew Callos: or. During the third quarter, we advanced our go-to-market strategy for Omicamptive McCarville, and we were pleased to present it at our recent analyst investigation. There are a few highlights of this strategy I'd like to review on today's call. First, our go-to-market strategy is based on a gated bill. For more information, please visit www. FEMA.gov, in place post NDA submission.

Measured by cardiopulmonary exercise testing or CPAP.

Which is a measure of exercise capacity.

Among the secondary objectives, we are investigating the change in Kansas City Cardiomyopathy questionnaire clinical symptom score.

In New York Heart Association functional class at week 12 to evaluate a potentially early improvement in heart failure symptoms and <unk>.

Again at week 24.

We plan to randomize 270 patients in a one to one ratio to Abbvie Camden or placebo. In addition to standard of care.

Andrew Callos: This level of commercial hires is sufficient for launch preparation. As Robert mentioned, we've hired a CG team to implement this go-to-market strategy. And we now have our full leadership team in place, as well as our account manager team, who call them payers, and nearly all of our market. The Grow2Market strategy is based on four key pillars, insights, education, access, and support. Insight speaks to having a very deep understanding of who the worsening heart failure patient is, where they are treated, and who the cardiologists are who treat them.

Each patient will receive up to four escalating doses that'd be camden or placebo with dose optimization based on achievement of echocardiographic targets the.

The starting dose will be five milligrams once daily escalating to 10, 15, or 20 milligrams once daily as needed to achieve target gradients.

These four doses were selected based on the results from Redwood HCM to facilitate selection of the optimal dose for each patient and maximize the individual benefit risk profile.

Study start up activities regulatory filings and IRB submissions are underway with the first site initiation is already completed.

Andrew Callos: Education means that if Omacamptin-McCarville is approved, then we need to ensure that cardiologists clearly understand the data supporting our label, including the evidence supporting Omacamptin-McCarville's potential benefit for the subset of patients who have worsening heart failure.

Drug product availability in early 2022 will enable the commencement of screening and enrollment of the first patient in this trial.

In anticipation of enrolling patients with obstructive HCM from China, and Sequoia HCM, we continue to collaborate closely with our partner <unk> Pharmaceuticals.

Andrew Callos: Access speaks to our plans to have affordable co-pays for most patients as soon as possible after launch. And finally, things like copay support for commercial patients, patient assistance programs, and educational services. To support our goal of affordable access, our payer account management team met with every major payer in the third quarter. We introduced our team and our company while engaging payers in a mutual understanding of the unmet need in our society.

<unk> recently completed a phase one study evaluating single and multiple doses of IV Hampton and healthy Chinese subjects.

The pharmacokinetic results were similar to those observed in the Caucasian populations.

Enrolled in our phase one study of happy Camden conducted in the U S.

And similarly showed dose proportional pharmacokinetics with a safety and tolerability profile comparable to placebo.

The results of this study supports submission of a clinical trial application and enrollment of patients with obstructive HCM in China.

On the neuromuscular front.

Andrew Callos: For further support access, our Health, Economics, and Outcomes Research colleagues continue to advance outcomes research with a goal of multiple publications in 2022. These publications are targeted at documenting the value of Omecaptan-McCarville as illustrated by meaningful reductions in resource utilization, intensity, and cost.

As Robert mentioned during the third quarter, we began enrolling patients encourage ALS the phase III clinical trial of <unk> in ALS.

Courage ALS will enroll approximately 555 patients with ALS randomized two to one to receive rather sensitive or placebo for 24 weeks.

Led by a 24 week period in which all patients will receive rather sensitive.

Andrew Callos: And we are preparing for the potential launch of Omicantin-McCarville. We are simultaneously building our cardiovascular franchise strategy towards our plans for the potential launch of Keeping in mind our corporate goal of bringing multiple medicines to market in the next several years, this strategy relies on several synergies. First, among the cardiologists who treat these patients, there is an 85% overlap between the cardiologists who treat patients with heart failure and HCM.

The primary endpoint is the change from baseline to 24 weeks in ALS FRS or.

The functional rating scale that indicates the progression of ALS.

As we design courage, Alice we incorporated feedback from patients and caregivers.

If you remove key barriers to clinical trial participation.

And to help make the patient experience less burdensome.

We are also working to provide continued access to <unk> for all patients who complete courage a L. S.

As well as patients who have previously participated in our trials.

Reflective of our goal to ensure ethical and equitable access for patients who are in need.

Andrew Callos: Cost efficiency is another area where we will share field sales, field medical, shared services, and systems across the entire organization. Once we have established relationships and built systems to support the launch of Omicamptive McCarville, we are well positioned to accelerate and streamline the potential launch of Apicamptive. It is an incredibly exciting time to be working at Cytokinetics. As we continue to grow our team and advance our plans, it remains important for us to remember the driving force behind this motivation, patience, and the clear unmet need for both heart failure and HCM. And with that, I'll turn it over to Robert Wong, who will provide an update on our finances. Thanks, Andrew.

With that I will turn the call over to Andrew to discuss our progress against that go to market strategy for on the captive mccarville.

Yes.

Thanks Stuart.

The third quarter, we advanced our go to market strategy for OMA captive Mccarville, and we were pleased to presented at our recent analyst and Investor day.

There are a few highlights to the strategy I would like to review on today's call.

First our go to market strategy is based on a gated build with a planned total investment to be titrated overtime as de risking events occur such as NDA submission NDA filing and approval by the FDA to illustrate we have around 10% to 15% of our planned commercial ftes in place today, and we will have less than one third.

Of the total number of.

In place post NDA submission.

This level of commercial hires are sufficient for launch preparation.

As Robert mentioned, we hired a seasoned team to implement this go to market strategy.

And we now have our full leadership team in place as well as our account manager team who call on payers and nearly all of our marketing organization.

The go to market strategy is based on four key pillars insights education access and support.

This speaks to having a very deep understanding of who the worsening heart failure patient is.

Where are they are accretive and who the cardiologists are who treat them.

Robert C. Wong: I'll provide an update on cash, revenue, and spending, and then Ching will review our financial outlook and corporate development strategy. More details on our actual results for the third quarter 2021 are included in the press release, which we released earlier this afternoon. We ended the third quarter with approximately $668.9 million in cash and investments.

Education means that if <unk> is approved then we need to ensure that cardiologist clearly understand the data supporting our label, including the evidence supporting <unk> potential benefit for the subset of patients who have worsening heart failure.

<unk> speak to our plans to have affordable co pays for most patients as soon as possible after launch and finally <unk>.

Support and tells the program that we will have and provide for patients like co pay support for commercial patients patient assistance program and educational services.

To support our goal of commercial of affordable access our payer account management team has met with every major payer in the third quarter, we have introduced our team and our company, while engaging payers and a mutual understanding of the unmet need in heart failure.

Robert C. Wong: Our revenue in the third quarter of 2021 came primarily from our recognizing a $5 million milestone from Zhijing Pharmaceuticals in anticipation of the start of Sequoia HCM. Our third quarter 2021 R&D expenses increased to $48.4 million from $24.2 million in the third quarter of 2020, primarily due to increases in spending for our clinical development activities for our cardiac muscle inhibitor program. In addition, we incurred transition costs related to the termination of our collaboration with AMI.

Further support access our health economics outcome research colleagues continue to advance outcomes research with the goal of multiple publications in 2022.

Publications are targeted documenting the value of OMA cabinet mccarville as illustrated by meaningful reductions in research utilization intensity and cost.

And we are preparing for the potential launch of our Mckesson Mccarville, we are simultaneously building, our cardiovascular franchise strategy towards our plans for the potential launch of Patty Kimpton, keeping in mind, our corporate goal of bringing multiple medicines to market in the next several years.

This strategy relies on several synergies FERC.

Robert C. Wong: And our purchase from Angen of approximately 7.3 million units of materials, including manufactured quantities of the active pharmaceutical ingredients for omacamptin-micarbol, thereby completing our purchase. More than 70% of our R&D expenses were attributable to our cardiovascular programs, as expected, given activity related to transitions from our collaborations with Amgen, the purchase of manufactured quantities of active pharmaceutical ingredients, ongoing activities associated with Meteoric HF, and also our cardiac myosin inhibitor programs, including the ongoing activities associated with Redwood HCM and startup activities related to Sequoia.

And the cardiologists, who treat these patients there was an 85% overlap between the cardiologist, who treat patients with heart failure and HCM.

Cost efficiency is another synergy where we will share fueled sales fueled medical shared services and systems across the entire organization.

Once we have established relationships and built system to support the launch of OMA captive mccarville, we are well positioned to accelerate and streamline the potential launch of Abbvie kimpton.

It is an incredibly exciting time to be working our cytogenetics as we continue to grow our team and advance our plans. It remains an important for us to remember the driving force behind this motivation patients and the clear unmet need in ballpark failure in HCM and with that I'll turn it over to Robert Wong, who will provide an update to our financials.

Thanks, Andrew I'll provide an update on cash revenue and spending and then Ching will review, our financial outlook and corporate development strategies.

Details on our actual results for the third quarter 2021 are included in the press release, which we released earlier this afternoon.

Robert C. Wong: The remainder of our expenses were attributable to our early research in skeletal muscle programming. Our third quarter 2021 G&A expenses were $26.2 million, up from $12.3 million in the third quarter of 2020. Due primarily to an increase in outside spending in anticipation of our potential commercial launch of Omicant and McCarble in 2022, as well as personnel-related costs, including stock-based compensation, and facilities costs related to our new building. And now, Ching will review our financial outlook and corporate development strategy. Thanks, Robert.

We ended the third quarter with approximately $668 9 million in cash and investments.

Our revenue in third quarter of 2021 came primarily from our recognizing a 5 million dollar milestone from <unk> pharmaceuticals in anticipation of the start of Sequoia HCM.

Our third quarter 2021, R&D expenses increased to $48 4 million from $24 2 million in the third quarter of 2020.

Primarily due to increases in spending for our clinical development activities for our cardiac muscle inhibitor programs. In addition, we incurred transition costs related to the termination of our collaboration with Amgen and our purchase from Amgen of approximately $7 3 million of materials, including.

Quantities of the active pharmaceutical ingredient for OMA campton, mccarville, thereby completing our purchase commitment.

Ching W. Jaw: As is our annual practice, we recently conducted a comprehensive strategic planning process with subsequent presentation and discussion with our board. This year, the strategic plan was focused on prioritizing our expanding clinical pipeline to ensure that we focus on R&D programs that leverage our core competencies and competitive advantages in muscle biology and also address high unmet need opportunities that may afford high return on investment potential. In addition,

More than 70% of our R&D expenses were attributable to our cardiovascular program as expected given activity related to transitions from our collaborations with Amgen. The purchased manufactured quantities of active pharmaceutical ingredient ongoing activities associated with meteoric H F and Alt.

So our cardiac myosin myosin inhibitor program, including the ongoing activities associated with Redwood HCM and startup activities related to Sequoia HCM.

The remainder of our expenses were attributable to our early research and research in skeletal muscle program activity.

Our third quarter 2021, G&A expenses were $26 2 million up from $12 3 million in the third quarter of 2020.

Due primarily to an increase in outside spending in anticipation of our potential commercial launch of <unk> in 2022.

Ching W. Jaw: We pressure-tested plans to enrich our research pipeline with external collaborations that could complement and strengthen our internal innovation. Lastly, we focused in this year's strategic planning process on critically evaluating and reformulating our cardiovascular and neuromuscular business franchise strategies that should continually capitalize on lifecycle management of our most advanced drug candidates, Omikanta McCarble, Effie Kempton, and Rowdy Sanchez. To recap our cash position, we ended the third quarter with approximately $669 million in cash, which includes $297 million raised in Q3 through an equity offering, net of expense. Therefore, our pro forma cash at year-end 2021 is expected to be in the range of $600 to $610 million, which represents more than three years of cash runway using our revised Net Cash Uralization Guiding of $195 to $215 million in 2021, with the potential commercial launch of Victoria HGM and Courage ALS.

Personnel related costs, including stock based compensation and facilities costs related to our new building.

And now Ching will review, our financial outlook and corporate development strategy.

Thanks Robert.

Our annual practice, we recently conducted a comprehensive strategic planning process with subsequent presentation and discussion with our board.

This year the strategic plan was focus to acquire typing.

Expanding clinical pipeline.

We ensure that we focus on R&D programs that leverage our core competencies and competitive advantages in muscle biology, and also address high unmet need.

<unk> that may have poor high return on investment potential.

In addition, we.

We pressure test it plans to enrich our research pipeline with external collaborations that could complement and strengthen our internal innovation.

Lastly, we focused in this year strategic planning process to critically evaluating every formulating our cardiovascular and neuromuscular business franchise strategy that should continually capitalize on lifecycle management of.

Our most advanced drug candidate.

Paul Mckenzie Mccarville epic Kimpton and routed centers.

To recap our cash position we ended the third quarter was approximately $669 million in cash.

It includes $297 million late in Q3 through an equity offering net of expenses.

Ching W. Jaw: We do expect our 2022 and 2023 cash burn rates to increase relative to 2021 spending. And we will provide guidance on this in our fourth-quarter earnings call planned to occur in early 2022. As we have stated, we continue to seek ways to strengthen our balance sheet, and in the third quarter, we had advanced partnering and structured financing discussions aligned with our corporate development strategy. During the quarter, we continued our discussions with potential co-development and co-commercialization partners for Omicantum Carbyl, as well as Aficantum, with priority attention to business development in Asia and other complementary geographies where we don't intend to go to market ourselves.

Therefore, our pro forma cash at year end 2021 is expected to be in the range of $600 million to $610 million.

Which represents more than three years of cash runway using our revised net cash utilization guidance Paul.

Paul the $195 million to $215 million in 2021.

What's the potential commercial launch of Omnicare Carnival.

And the funding of two phase III clinical trials.

Deploy SDN and encourage all that we.

We do expect our 2022 and 2023 cash burn rate to increase relative to 2021 spending.

And we will provide guidance on this in our fourth quarter earnings call and Tau occurred in early 2022.

As we have stated.

We continue to seek ways to strengthen our balance sheet and in the third quarter, we have beds events partnering structure financing discussions aligns with our corporate development strategy.

During the quarter, we continue our discussions with potential co development and co commercialization partners for <unk> as well as at the Kimpton.

Ching W. Jaw: Our plan is to preserve North American and potentially European rights for development and commercialization of both omicantin, maccabo, and epichemicals. In parallel, we have also been advancing discussions with multiple entities and funds with shared interests related to structure financing, including royalty monetization and structure debt deals, to further support the commercial launch of Omicantin-Li-Carbo and our continued and expanded development objectives for Epi-Chem. Our goal is to complete these deals in the fourth quarter, which could enable us to end the year with two to three years of forward cash runway, even as we expect the spending in 2022 and 2023 to be higher than our expected spending this year.

With priority attention to business development in Asia, and other complementary geographies, where we don't intend to go to market ourselves.

Our plan is to preserve north American and potentially European rights for development and commercialization for both <unk> and ft Camden.

In parallel we have also been advancing discussions with multiple entities in funds with share of interest related to the structure of financings, including royalty monetization and a structure that deals.

So further support the commercial launch telephone we kept them in Kabul, and our continued and expanded development objectives or at the Kempton.

Our goal is to complete these deals in the fourth quarter, which could enable us to end. The year was two to three years of forward cash runway, even as we expect the spending in 2022 and 2023 to be higher than our expected spending this year.

Ching W. Jaw: As you know, we have always built our business on a strong financial foundation, and we have an established history of making non-equity diluted deals to support our continued growth and progress. With transactions expected to close this quarter, we believe we are positioned financially and strategically to execute on the potential launch of Omicantum Carbo and continue to advance our pipeline and business franchise strategy. And with that, I'll turn the call back over to Robert Wong. Thank you, Ching.

As you know we have always built our business on a strong financial foundation and we have an established history of making non equity dilutive deals to support our continued growth and progress.

With transactions expected to close this quarter, we believe we are positioned financially and strategically to execute.

The potential launch of <unk> and continued to advance our pipeline and business franchise strategies.

Robert C. Wong: Within our Vision 2025, which we set forth in 2020, we laid out several goals, including achieving regulatory approval for at least two drugs arising from our pipeline and expanding our discovery platform. Over the past quarter, in addition to the clinical, regulatory, and commercial progress we made, we also engaged in activities to broaden our research footprint in the years to come. Thinking even beyond 2025, we continue to forge ahead as leaders in muscle biology with focus on populations of high unmet need.

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

Thank you Ching.

Within our vision 2025 that we set forth in 2020, we laid out several goals, including achieving regulatory approvals for at least two drugs arising from our pipeline and expanding our discovery platforms.

Over the past quarter. In addition to the clinical regulatory and commercial progress. We've made we also engaged in activities to broaden our research footprint in the years to come.

Thinking even beyond 2025, we continue to forge ahead as leaders in muscle biology with focus to populations of high unmet need in the next year, you'll be hearing more about our activities as we've extended our muscle biology focused from the bio mechanics of muscle contractility too.

Robert C. Wong: In the next year, you'll be hearing more about our activities as we've extended our muscle biology focus from the biomechanics of muscle contractility to the energetics, growth, and metabolism of muscle, with novel mechanism drug candidates advancing in development.

Energetics growth and metabolism of muscle with novel mechanism drug candidates advancing in development.

Robert I. Blum: While much of our focus has been on our programs in cardiovascular disease, as you heard, with our Start and Encourage ALS programs, our commitment to the ALS communities remains strong. Along these lines, we also recently donated data from our completed clinical trials in ALS to the PROACT database, which stands for Pooled Resource Open Access ALS Clinical Trials. ProAct is available to members of the research community, and it contains over 10,000 de-identified clinical patient records from multiple completed clinical trials, providing a powerful tool to advance research in the ALS field and also to gather observations related to disease progression and epidemiologic data.

While much of our focus has been on our programs in cardiovascular disease as you heard with our started encourage AOS our commitment to the AOS communities remains strong.

Long. These lines. We also recently donated data from our completed clinical trials in AOS to the Pro Act database, which stands for pooled resource open access ALS clinical trials proactive is available to members of the research community and it contains over 10.

D identified clinical patient records from multiple completed clinical trials.

Abiding a powerful tool to advance research in the AOS field and also together observations related to disease progression and that'd be a dealogic data.

Robert I. Blum: We will be donating data from three completed trials in ALS, Benefit ALS, Vitality ALS, and Fortitude ALS, which represents data from almost 600 patients. We're pleased to be working with the ALS Association, with Prize for Life, and with the Neurologic Clinical Research Institute at Mass General to share these data with the ALS communities to which we are all together so important dedicated. Furthermore, demonstrating our commitment to patient communities, during the quarter, we renewed our partnership with CureSMA to increase education, awareness, public policy, and fundraising for spinal muscular atrophy, and we also announced the fourth annual Cytokinetics Communications Fellowship Grants Program, which will award a total of $100,000 in grants to patient advocacy organizations in heart failure, in HCM, in ALS, and in SMA to support increased capacity in communications and outreach.

We will be donating data from three completed trials in AOS benefit ALS vitality, ALS and fortitude ALS, which represents data from almost 600 patients.

We're pleased to be working with the ALS Association with price for life and with the Neurologic Clinical Research Institute at mass General to share. These data with the AOS communities to which we were altogether. So importantly dedicated.

Further demonstrating our commitment to patient communities during the quarter, we renewed our partnership with cure SMA to increase education awareness public policy and fund raising for spinal muscular atrophy and we also announced the fourth annual subtle kinetics Communications Fellowship Grant program.

<unk>, which will award a total of $100000 in grants to patient advocacy organizations in heart failure, and HCM in ALS and SMA to support increased capacity and communications and outreach.

Robert I. Blum: As we near the end of 2021, we look back on our very gratifying progress and achievements, and we look ahead to what may be a watershed year for our company. We expect to end 2021 with two distinct programs advancing in phase three clinical trials, with our first potential medication moving towards potential approval and commercial launch, and all of that happening on the foundation of continued innovations in muscle biology directed to patients who rely upon us and in areas for which our leadership offers hope for diseases associated with muscle dysfunction.

As we near the end of 2021, we look back on our very gratifying progress and achievements and we look ahead to what may be a watershed year for our company.

We expect to end 2021 with two distinct programs advancing in phase III clinical trials with our first potential medication moving towards a potential approval and commercial launch and all of that happening on the foundation of continued innovations in muscle biology directed.

Patients, who rely upon us and in areas for which our leadership offers hope for diseases associated with muscle dysfunction and weakness, we look forward to providing more updates on our continued progress and we welcome your questions and feedback.

Robert I. Blum: We look forward to providing more updates on our continued progress, and we welcome your questions and feedback. Now, let me recap our expected milestones for the remainder of 2021. For Omicampt of McCarble, we expect to submit an NDA to the FDA in the fourth quarter of this year. We also expect to complete the conduct of meteoric HF by year end, with results expected in early 2022. For Athecampton, we expect to continue with study startup, regulatory filings, IRB submissions, and site readiness activities; all together for Sequoia HCM, and with the availability of the drug product in early 2022, we anticipate commencement of screening and enrollment of the first patients in that trial.

Now, let me recap our expected milestones for the remainder of 2021 for <unk>, we expect to submit an NDA to the FDA in this fourth quarter of this year.

We also expect to complete the conduct of meteoric HFF by year end with results expected in early 2022 for.

<unk> Kimpton, we expect to continue with study startup with regulatory filings with IRB submissions and site readiness activities altogether for Sequoia HCM and with availability of drug product in early 2022 we anticipate commencement of screening and enrollment of the first page.

Robert I. Blum: And for Real Deceptive, we expect a complete enrollment of Courage ALS throughout the remainder of this year. And for our ongoing research, we expect to advance new muscle-directed compounds and to conduct IND-enabling studies, and to potentially advance one to two potential drug candidates into clinical development over the next year. Operator, with that update, we can now open the call to questions, please.

<unk> in that trial.

And for real disruptive, we expect to complete enrollment of courage ALS C well.

The remainder of this year.

And for our ongoing research, we expect to advance new muscle directed compounds and to conduct IND, enabling studies.

And to potentially advanced 1% to two potential drug candidates into clinical development over the next year.

Robert I. Blum: To ask a question, you will need to press star 1 on your telephone. 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 Dane Leone with Raymond James. Hello Dane. Good. Hi, Robert and team. Thank you for taking the questions and congratulations on all the updates.

Operator with that update we can now open the call up to questions. Please.

To ask a question you will need to press star one on your telephone to withdraw your question question Palanquin. Please standby, while we compile the Q&A roster.

Your first question comes from the line of Dane Leon with Raymond James.

Hello, Doug Great Hi, Robert and team. Thank you for taking my questions and congratulations on all the updates.

Dane Vincent Leone: And then my second question would be just to drill down a little bit more on the submission for OMACAMPTIV. I know it's been asked before, but in terms of updating your communications back and forth with the FDA, any additional color in terms of the scope or scale of the label as it relates to baseline left ventricular ejection fraction? Thank you.

Just two for me if you will firstly can.

Can you give us any more color in terms of the scale and scope of the Sequoia HCM study as we think about one modeling expenses and two time to run. The study is it fair to use the explorer HCM study as a similar proxy in scale and scope for the patients required in <unk>.

Robert I. Blum: Sure, good questions. So I'll start and turn it over to Fady. She may also ask Stuart to elaborate. I don't think we're going to provide any specific financial guidance with regard to Sierra.

<unk>.

And then my second question would be just to drill down a little bit more on the submission for OMA captive.

I know, it's been asked before but in terms of updating your communications back and forth with the FDA.

Robert I. Blum: It may be premature to do that until we start dosing patients, but certainly, we could give you some things to hold on to with regard to your projections. For instance, what might be our expectations in terms of time for enrollment and duration of the study? I hope that can be helpful, and I'm sure you already know the number of patients we aim to enroll. So why don't I turn it over to Fady first to talk to you about how we think it's going to enroll, the number of sites, the number of countries, things like that, and then most likely once we start dosing, presumably that'll be in early 2022, we'll be in a better position to point to how we think it's going to be affecting our spending. And then we'll come back to your All right, thanks, Robert.

Any additional color in terms of the scope or scale of the label as it relates to baseline left ventricular ejection fraction. Thank you.

Sure. Good question, so I'll start and turn it over to Saudi He May also ask Stuart to elaborate I don't think were going to provide any specific financial guidance with regard to sequoia. It may be premature to do that until we start dosing patients.

Certainly we could give you some things to hold on to with regard to your projections for instance, what might be our expectations in terms of time for enrollment and duration of the study I hope that can be helpful. And certainly you know already the number of patients we aim to enroll.

So why don't I turn it over to a fatty first to talk to you about how we think it's going to enroll the number of sites the number of countries things like that.

Then most likely once we start dosing.

Presumably that'll be in early 2022 will be at a better position to a point to how we think it's going to be affecting our spending.

Fady Ibraham Malik: You know, I think we plan to enroll approximately 270 patients in Sequoia, which is a little bit more than was enrolled in Explorer. I think, you know, this, the size and scope are comparable, um... certainly the number of sites and things like that we will probably go to a few more sites than they did in Explore nearly a dozen countries and well over north of 80 sites, I think, ultimately, when we get the study fully up and going.

And then we'll come back to your second question.

Alright, Thanks, Robert I think we plan to enroll approximately 270 patients and two Sequoia, which is a little bit more than wasn't enrolled and explore.

I think the.

The size and scope of our comparable and.

Certainly the number of sites and things like that we will probably go to a few more sites and they did and explore.

Nearly a dozen countries.

And well over north of 80 sites I think ultimately when we get the study fully up and going.

Fady Ibraham Malik: So our plan is to push hard and to enroll this as quickly as possible, but there are certain, I think, limitations in terms of study startup and things like that that are hard to press. Once we have sites up and going, I think it will actually enroll very rapidly.

So our plan is to.

Push hard end to end.

Enroll this as quickly as possible.

But there are certain I think limitations in terms of study start up and things like that that are hard to press. One once we have sites up and going I think it would actually will enroll very rapidly.

Fady Ibraham Malik: So then your second question related to the NDA and how we're approaching what could be that which is contained within the NDA, the indication statement, and otherwise, in particular around ejection fraction. As we've stated, we do believe that patients with EFs less than 30% are seemingly benefiting a great deal more than other patients In Galactic, and we do think that it's in the interest of Omicampt of McCarble and patients with heart failure that that's where the label should point.

So then your second question related to the.

N D E and how we're approaching.

What could be.

That which is contained within the M D. A indication statement it otherwise in particular around ejection fraction.

As we've stated we do believe that patients with <unk> less than 30%.

Our seemingly benefiting a great deal more than other patients.

In Galactic and we do think that it's in the interest of <unk> in patients with heart failure that that's where the.

Fady Ibraham Malik: So we are hopeful that that data, including graphics, could be included in the label ultimately upon potential approval. But that's obviously going to be subject to FDA review. But based on conversations we've been having, and Fady can elaborate, we do feel encouraged that that would be supportive and consistent with other things the FDA has done. Fady, anything you want to add?

Label should point.

So we are hopeful that that data, including graphics could be included in the label ultimately upon potential approval, but that's obviously going to be subject to FDA review, but based on conversations we've been having and fatty can elaborate.

We do feel encouraged that that would be supportive and consistent with other things. The FDA has done study.

Fady Ibraham Malik: I think we've had those discussions with FDA, and obviously, what ends up in the label will be the outcome of the negotiations at the time that we negotiate the label, but in general, I think they're supportive of the concept that the label should indicate where the benefit of the drug is concentrated, and that provides physicians with the information needed to best use the drug. And in that context, the EF is obviously an important indicator.

<unk> anything you want to add.

No I mean, I think we've had those discussions with FDA and obviously what ends up in the label will be the outcome of the negotiations at the time.

We negotiate the label, but in general I think they are supportive of the concept that the label should.

Indicate where the benefit of the drug is concentrated and that provides.

Physicians with the information needed to best use the drug.

Fady Ibraham Malik: And not only the label; I might suspect that it could ultimately inform how Omicampt and McCarville could be incorporated into guidelines also, and you get a sense of that from some of the publications that Fady referred to in his statement.

And in that context, DFS and important obviously an important indicator.

Not only the label I might suspect that that could ultimately inform how <unk> could be incorporated into guidelines also and you got a sense of that from some of the publications that fatty referred to in his statements.

Operator: Your next question comes from the line of Joe Pantginis with HC Wainwright.

Okay.

Excellent. Thank you very much and congratulations.

Thanks, Dan.

Joseph Pantginis: Hey, everybody. Good afternoon.

Your next question comes from the line of Joe <unk> with HC Wainwright.

Joseph Pantginis: Thanks for taking the questions. I wanted to focus my first question on, you know, the concept that you guys are really in an important execution and logistics time for the company. So with that said, you know, I'll even go off of one of Stuart's comments, and Robert, you said it too, about drug availability for Sequoia, early next year, and executing courage as well. Do you feel you've had to plan anything above and beyond for these studies?

Hello, Joe.

Yeah. Good afternoon, thanks for taking the questions.

Wanted to focus my first question.

Concept that you guys are really in a important execution and logistics.

Time for the company so with that said I'll, even go off of Stuart's comments and Robert you said it too about drug availability for Sequoia.

Early next year.

And executing courage as well.

Robert I. Blum: No matter what it is, including drug availability based on any. Very good question, and I think that might be the first time on one of these earnings calls that we really did get a question about the supply chain. It's an area of intense focus for us right now, as we're not only embarking on these large Phase III studies, but we're readying for the supply of Omicamptive into the marketplace. And obviously, had we still been partnered with Amgen, that would be something we'd have relied on them for, but now it's our responsibility. And we are executing well on contracts, as well as conversion of drug substance to drug product, and the like. The study startup activities for Sequoia are proceeding nicely.

Do you feel you've had to plan anything above and beyond for these studies no matter, what it is including drug availability based on any.

Anticipated issues around the global supply chain problems that we're seeing right now.

Very good question and I think that might be the first time on one of these earnings call that we really did get a question about the supply chain is an area of intense focus for US right now as we're not only embarking on these large phase III studies, but we are readying for the supply of <unk> into the marketplace.

Obviously had we still been partnered with Amgen that would be something we would have relied on them for but now it's our responsibility and we are executing well on contracts.

Well as conversion of drug substance to drug product.

And the like.

Robert I. Blum: We move very swiftly from having completed cohorts 1 and 2, reading out the results, having meetings with FDA, and getting ready to start Sequoia. All of that is occurring in a relatively short time frame, so it seems like things are going well that way, both in support of clinical trials and also commercialization, but we are building the supply chains at the same time we're executing on how the delivery of the drug product into clinical trials is occurring.

The study startup activities for Sequoia are proceeding nicely, we move very swiftly from having completed cohorts, one and two reading out the results, having meetings with FDA and readying to start Sequoia.

All of that occurring in a relatively short timeframe. So it seems like things are going well that way both in support of clinical trials and also commercialization.

But we are building the supply chains.

At the same time, we are executing on how the delivery of drug product into.

Robert I. Blum: So it's something that I think is going to continue to be a focus for senior management as that is an enabler of our success. And to this point, the good news is we're working with some of the same contract manufacturing organizations with whom we have longstanding relationships, and there may also be opportunities to consolidate programs amongst them so that we're working with them for more. You know, we're focused on small molecule drug candidates. And in that way, it's not like we're dealing with an incredibly novel way of approaching supply.

Clinical trials is occurring so it's something that I think is going to be continuing to be a focus for senior management.

That is enabling of our success.

To this point the good news is we're working with some of the same contract manufacturing organizations with whom we have long standing relationships with and there may also be opportunities to consol.

Consolidate programs amongst them so that we're working.

With them for more than one program.

We're focused to small molecule.

Drug candidates in that way.

It's not like we're dealing with an incredibly.

Fady Ibraham Malik: But at the same time, we have to ensure capacity and deliverable timelines. And that's what we're focused on. Fady, anything you want to add to that? No, I think you summed it up.

Novel way of approaching supply, but at the same time, we have to ensure capacity and deliverable timelines and thats what were focused towards <unk>.

Fady Ibraham Malik: But I think, you know, we've been able to continue to advance. Drugs supplies for our studies and things like that. I think the real, you know, major constraint has to do with the, you know, spare capacity in the supply chain. There's just a lot of it that's been squeezed out.

Saudi anything you want to add to that.

No I think you summed it up I think we've been able to continue to advance.

Drug supplies of our studies and things like that I think.

The real major constraints this has to do with the.

Joseph Pantginis: So you have to be, you know, careful about how you plan things. And what I might also say is Andrew and his team are very focused on the handoff between the manufacturers and then the logistics associated with distribution and all of the activities in connection with ensuring patients get reliable sources of drugs as well. And that speaks to potential patient hub services and other things like that. Over time, I expect you'll hear more about that from Andrew too.

Spare capacity in the supply chain.

There's just a lot of it has been squeezed out so you have to be careful about how you plan things.

What I might also say as Andrew and his team are very focused to the handoff between the manufacturers and then the logistics associated with distribution.

And all of the activities in connection with ensuring patients get reliable sources of drug as well that speaks to the potential patient hub services and other things like that over time, I expect youll hear more about that from Andrew too.

Joseph Pantginis: Very, very helpful. Thank you. And then, I guess, two smaller questions. One, maybe for Ching, you know, on the financial side, we had this $7.3 million cost to pay Amgen for the drug product for Omicamptive. Just curious what might still be outstanding there going into the future, or if that expense is essentially done. And then, second, if I had heard Fady correctly when he was discussing the future for Omicamptive, as well, I could have sworn I heard him say potential IS. So that sounded like. So I'm curious about what kind of study... Yeah, I mean, I don't know.

That's very very helpful. Thank you and then I guess two smaller questions. One maybe for <unk> on the financial side, you would have this seven $3 million cost to pay Amgen for drug drug product for OMA captive just curious what might still be outstanding they're going towards it.

Going into the future or is that expense is essentially done and then second.

If I heard fatty correct when he was <unk> <unk>.

Discussing the future from a captive as well.

A sworn I heard him say potential ISO ts so that sounded like an interesting ts there. So I'm curious what kind of studies you might be looking at thank you.

Ching W. Jaw: Oh, go ahead, Shing. Yeah, I'll go. I'll go first, Fady.

Yes, I mean I have no idea.

Oh go ahead sing to go first.

Ching W. Jaw: The payment that we pay Amgen, the $7.3 million this quarter, is the last of those payments. As we stated in our press release, for the nine months ended September 30, 2021, we paid them $14.6 million. So that was the total amount, and this $7.3 was the last payment.

Yeah, I'll I'll go.

I'll go for a study so.

In regards to <unk>.

Payment that we paid Amgen does.

$7 $3 million.

Quarter is the last of those payments as we stated in our press release for.

For the nine months.

Ended September 30th 'twenty or 'twenty, one we have pay down $14 6 million. So that was the total amount and the seven point C was the last of the payments.

Fady Ibraham Malik: And I think just in regards to the investigator, sponsor, or initiated study. You know, we began to receive proposals. Obviously, we'll vet them and decide which ones we can support, things like that. They fall under a fairly broad range of interests that people have, you know, really outside, some of them outside of the heart failure population that we studied in Galactic, some of them within, but I think we'll elaborate more on those as we begin to see them through.

Yes.

Thanks.

I think just in regards to investigator sponsor.

Initiated.

Yes.

We began to receive proposals, obviously, we'll vet them and decide which ones we can support things like that.

All under a fairly.

Broad range of interest.

The people have really outside some of them outside of the heart failure.

Population that we studied in galactic some of them within.

But I think we will.

Operator: Thank you very much.

We will elaborate more on those as we begin to.

Yasmeen Rahimi: Your next question comes from the line of Yasmeen Rahimi with the Piper Family.

To see them through.

Sure understood. Thank you very much.

Thank you.

Yasmeen Rahimi: Hello Yasmeen, and Hi Robert, thank you so much for taking my questions, but I have two questions for you. Maybe the first place to start is, a lot of you know, our investors have been sort of surprised by the FDA recently with some of the actions that were taken and created sort of a nervous Nelly situation. So I guess the question for you is, especially over the last few months, as you've been interacting with the FDA, what sort of their tone, their body language, their enthusiasm towards you, if you could just elaborate on the, um,

Your next question comes from the line of Yasmin Rahimi with Piper Sandler.

Hello, Yes.

Hi, Robert Thank you so much for taking my questions, but I have two questions maybe the first place to start it.

A lot.

Investors have been surprised by the FDA recently by some of the actions that we've taken are created sort of a nervous Nellie situation.

Just a question for you is especially over the last few months that you've been interacting with the FDA, what's sort of their cone their body language there into the eye.

Robert I. Blum: How does this discussion blend? I think that could be really important. And then I have a follow-up question.

Adam maybe you could just elaborate sort of depth.

How does discussion and I think that could be really in question and then I have a follow up question.

Robert I. Blum: Sure, so what I'll say is that often in these situations, biotech companies talk about having a pre-NDA meeting, they submit an NDA, it gets filed or doesn't get filed, and then they await approval. In our case, over the last year, we've had many interactions with FDA, both in person before COVID shut that down, and then also, subsequently, through Zoom interactions and otherwise, through written exchange of documents. I found FDA to be very accessible and very interactive with us, providing guidance that informs both the formatting and the content of our planned NDA submission.

Sure. So what I'll say is oftentimes in these situations biotech companies talk about having a pre NDA meeting they submit an NDA it gets filed or doesn't get filed and then they await approval.

In our case.

Over the last year, we've had many interactions with FDA both in person before Covid shut that down and then also sub.

Subsequently by.

Zoom interactions and otherwise through written exchange of documents.

I found the FDA to be very accessible and very interactive with us.

And providing guidance that.

Robert I. Blum: So I'm very encouraged by the level of engagement that should hopefully support our submission that would hopefully align with interest for approval. We've had all of our questions satisfactorily answered in order to provide for us now to go through the final mechanics of an NDA submission in order to get that done this quarter.

Informs both the format and the content of our planned NDA submission.

So I'm very encouraged by the level of engagement should hopefully support our submission that would hopefully align with interest for approval.

We've had.

All of our questions satisfactorily answered in order to provide for US now to go through the final mechanics of an NDA submission in order to get that.

Robert I. Blum: Thank you, Robert, for the answer. And maybe a follow-up question.

<unk> done this quarter.

Robert I. Blum: Maybe giving me some insight when you speak with...

Thank you Robert.

Sure.

Operator: Transcribed by https://otter.ai

Maybe a follow up question is.

Maybe giving me some insight when you speak with cardiologists, whether it'd be private practice, whether it is at the hospital setting.

Robert I. Blum: sort of the level of appreciation

Operator: https://www.globalonenessproject.org

Sort of the level of depreciation they have where omi Cam cats in terms of a novel mechanism of action does it click right away when they know that it's the first <unk> being able to really being able to improve cardiac country.

Robert I. Blum: and their enthusiasm beyond, obviously, the outstanding data from Black2Nature.

Kelly I think maybe that might be really important like how important is the novelty of its mode of action point driving adoption and their enthusiasm.

Fady Ibraham Malik: So it's a little too early to talk about adoption, of course, in that much is not approved, but certainly, based on advertising boards and interactions with Key Opinion Leaders That Have Been Driven Out Of Medical Affairs And Also Market Research, As is driven out of our commercial group, we're getting very positive vibes about how the novelty of the mechanism may translate into potential future adoption. Maybe I'll turn it over to Fady first to speak about some of those activities that she's overseen, and then I'll turn to Andrew as well.

Beyond obviously, the outstanding data from black to nature.

So it's a little too early to talk about adoption of course.

And that as much as not approved but certainly based on AD boards and interactions with.

Key opinion leaders that have been driven out of medical affairs and also market research.

It's driven out of our commercial group, we're getting very positive vibes about how the novelty of the mechanism may translate into potential future adoption, maybe I'll turn it over to <unk> to speak about some of those activities that he has overseen and then I'll turn to Andrew as well.

Andrew Callos: Yeah, I mean, I think the physician community certainly understands where this could play a role. And it's been a long-standing goal in this field to find a drug that can improve cardiac function safely and have benefits for patients. If you listen to our Investor Day presentation, I think you might hear some of the enthusiasm and the two discussions we had. But it was similar amongst many ad boards that we conducted, both in the U.S. and in Europe.

Yes, I mean, I think in the physician community certainly understand where this could play a role and it's been a.

Finding a drug that can improve cardiac function safely and have benefit for patients has been a long standing goal in this field.

If you listen to our Investor Day presentation, I think you might hear some of the enthusiasm in the to discuss since we had.

But it was similar amongst many AD boards that we conducted.

Andrew Callos: And I think even as we go out to other stakeholders in the process, you know, we're sensing that there's a lot of interest. Their enthusiasm for something that is new. But on the other hand, we understand how it works. And it's, and it's rational as to why you might, you might use

And in the U S and in Europe.

And I think even as we go out too.

Other stakeholders in the process, we're sensing their enthusiasm for something that is new but on the other hand, we understand how it works in it and its rational rationale as to why you might might use it.

Andrew Callos: This is Andrew. The only thing I would add is that...

Andrew Callos: The only thing I would add is that when we talk with physicians... They're excited by the mechanism, not for the mechanism alone, but it's a reason to believe relative to the data and the evidence that we have. So when they look at the mechanism, and the evidence and the unmet need are very well aligned, they are running out of options when patients can't tolerate guideline-directed medical therapy. They are running out of options when they need products that could be an add-on that's neutral on kidney, and blood pressure in worsening patients, and when you talk about the add-on and those type of effects, they get very excited, and it's a good reason to believe that kind of closing is a mechanism, so we're getting a lot of enthusiasm for a very specific subset of patients relative to the product.

This is Andrew the only thing I would add is that when we talk with physicians.

We're excited by the mechanism not for the mechanism alone, but it's a reasonable lead relative to the data and the evidence that we produced.

So when they look at the mechanism.

The evidence and the unmet need are very well aligned.

We are running out of options when patients can't tolerate guideline directed medical therapy.

We are running out of options when they need products that could be an add on net neutral on kidney neutral.

<unk> pressure and worsening patients.

When you talk about the add on and those type of effects. They get very excited and have good reason to believe then kind of closing as a mechanism. So we're getting a lot of enthusiasm for a very specific subset of patients relative to the product.

Yasmeen Rahimi: Thank you for the answers,

Operator: Your next question comes from the line of Jeff Hung with Morgan Stanley. Hey Jeff. Thanks for taking the time. Hey Robert.

Thank you Randy I'm sorry.

Thank you.

Your next question comes from the line of Jeff Hung with Morgan Stanley.

Jeff Hung: Robert, thanks for taking the questions. Previously, you indicated that meetings with payers on McKenzie-McCarble have been largely introductory. Just curious if you have any updates that you can provide on payer feedback. Sure, I'll turn it over to Andrew to address that. Thank you.

Hey, Jeff Thanks for taking me.

Hey, Robert Thanks for taking the question.

We indicated that our meetings with payers on in Mckenzie Mccarville had been largely introductory just curious if you have any updates that you can provide on payer feedback.

Robert I. Blum: So we've interacted with, you know, as I mentioned, we hired all of our account managers, as well as a leader of that team. Many of them have existing relationships with all the major payers. We've interacted with the major payers, and it's really more about introductions: who is Cytokinetics, and then making sure we align well on how they think about heart failure, how do they manage heart failure? What are their challenges

Sure I'll turn it over to Andrew to address that.

Sure.

Appreciate the questions.

Market with.

As I mentioned, we've hired all of our account managers as well as the leader of that team many of them have existing relationships with all the major payers, we've interacted with the major payers and its really more about introduction, who is side of kinetics, and then making sure we align well on how they think about heart failure, how do they manage her.

Andrew Callos: And what are their So we've had those kind of baseline discussions, and then where we'll go next is, you know, per FDA regulations, kind of a pre-approval information exchange. We will start doing that in the coming weeks. So the feedback has been, well, they do like that we can clearly identify those patients relative to benefit in ES. So then, you know, that could indicate where they would target us from a prior authorization point of view, which is exactly acceptable to us because that gives us access to a very specific population that greatly benefits from all the captains. So hopefully, that gives you a flavor of our interactions in the third dimension.

Failure, what are their challenges and what are their needs. So we've had those kind of baseline discussions and then where we will go next is.

Our FDA regs as a kind of a pre approve.

Approval information exchange.

We will start doing that in coming weeks. So the feedback has been.

They do like that we can clearly identify those patients rare.

Relative to benefit in Es.

And therefore that could indicate where they would target us from a prior authorization point of view, which exact which is acceptable to us because that gives us access to a very specific population that greatly benefits from moment captain. So hopefully that gives you a color of our interactions in the third quarter.

Andrew Callos: The other thing to add is there's a lot more coming that you'll see in the published literature in 2022 that underscores the economic burden of heart failure, especially for those with worsening heart failure and where there could be opportunity for a new mechanism therapy like Omicam to Bicarbol based on results from Galactic to make a dent in that for payers. And payers are clearly aware of the economic burden associated with their management of heart failure patients.

The other thing to add is theres a lot more forthcoming that youll see in the published literature in 2020 to that.

Underscores the economic burden of heart failure, especially for those with worsening heart failure, and where there could be opportunity for a new mechanism therapy like <unk> based on results from galactic to make a dent in that for payers and payers are clearly aware.

Andrew Callos: They're aware, especially of the high Medicare percentage of these patients for which they're oftentimes penalized when these patients are readmitted. So a novel mechanism therapy that could reduce heart failure-related events, primarily hospitalizations, would be something that would catch their attention. And that's something that we'll continue to investigate as could be supportive of our plans for Omicamp. Great, thanks.

<unk> of the economic burden associated with their management of heart failure patients there were especially of the high Medicare percentage of these patients for which there are oftentimes penalized when these patients are readmitted.

A novel mechanism therapy that could reduce heart failure related events, primarily hospitalizations.

Would be something that would catch the attention and thats something that we will continue to.

Jeff Hung: I think I may have misheard, but did you say that you expected enrollment in COURAGE to be completed this year? Otherwise, any updates on estimated timing or when you might be better able to gauge the pace of enrollment to estimate that timing? Thanks.

Investigators could be supportive of our plans for Omi campus.

Great. Thanks.

I think I may have misheard, but did you say that you expect.

Enrolment of courage to be completed this year, otherwise any updates on that made timing or when you might be better able to gauge the pace of enrollment to estimate that time, yes, yes.

Robert I. Blum: Yeah, what I said or meant to say was that enrollment continues through this year but also intended next year also. We expect that we'll enroll patients sufficient to enable a first interim analysis next year, the timing of which is still to be defined, but we expect that were it to pass through that interim analysis, hopefully it will, the study would continue through next year. So, no, it's not intended to complete enrollment this year.

What I do what I said or I meant to say was that enrolment continues through this year, but also intended next year also.

We expect that we will enroll patients sufficient to enable.

Our first interim analysis next year, the timing of which is still to be.

Define but we expect that we're it's a pass through that interim analysis hopefully it will the study would continue through next year. So no. It's not intended to complete enrollment this year.

Operator: Your next question comes from the line of Akash Tewari with Jeffreys.

Okay. Thank you.

Thank you Jeff.

Akash Tewari: Hey Robert, so thanks so much for taking my questions.

Your next question comes from the line of a cash <unk> with Jefferies.

Hello, Josh.

Hey, Robert.

Robert I. Blum: Can you talk about what drove you?

So thanks, so much for taking my questions.

Operator: [inaudible]

Operator: Transcribed by https://otter.ai

Can you talk about what drove your decision to look at exercise capacity as your primary endpoint for Sequoia and not the composite endpoint that matter hat Y may exercise capacity would be a more youthful endpoint both for the agency and clinicians and Additionally have you heard any feedback from either the FDA or kols on the need for long term outcome data posted.

Robert I. Blum: And finally, have you heard any feedback from either the FDA or KOLs on the need for long-term outcomes data post-approval for Aficantin?

Ruble for epic Camden. Thank you.

Stuart Kupfer: Why don't we turn first to Stuart to address the first question and then maybe Fady and Stuart to address the second question. Thank you, Robert.

Why don't we turn first to Stuart to address the first question and then maybe body of steward the second question.

Thank you Robert.

So we focused on.

Stuart Kupfer: So we focused on Evaluating Functional Improvement in Patients with Destructive HCM, Comparing Aficampin vs. Placebo. With respect to the fact that these patients have very poor exercise tolerance, we focused on one of the most rigorous...

Evaluating functional improvement.

In patients with destructive HCM, comparing at that Camden versus placebo and.

With respect to the fact that these patients have very poor exercise tolerance.

We focus on one of the most rigorous objective.

Measurements of.

Exercise capacity in and that is clearly <unk>.

Stuart Kupfer: And so, yeah, we thought rather than combining this with, let's say, a more subjective..., https://www.kenhub.com

<unk>.

As well as other parameters using cardiopulmonary exercise testing.

And.

So we thought rather than <unk>.

In mining this with.

Let's say a more subjective.

Components of a composite endpoint.

Operator: And your second question. What? Do you want to repeat that for me, Akash? Absolutely.

We really wanted to zero in on what we thought was the most sort of critical.

And quantitative measurement and objective measurement of exercise capacity.

Akash Tewari: Have you heard any feedback, either from the FDA or KOLs, on the need for outcomes data post-COVID?

Having said that we will be evaluating other.

Other endpoints secondary endpoints that.

Evaluate.

Symptomatic improvements such as the <unk>.

The city cardiomyopathy questionnaire.

Fady Ibraham Malik: for Outcomes Data Post-Approval for CK274. You know, outcomes data, I think the regulators and KOLs appreciate that outcomes data are very hard to come by, symptomatic, although, you know, a very heavily burdened patient population. These patients, unlike traditional heart failure patients, don't get hospitalized, um... their mortality rates are usually quite low, and you know that Well, you know, well under 5% per year. And so, you can't really do an outcomes-based trial, per se, and I think that's well understood based on the event rate.

New York Heart Association functional class et cetera. So.

Those other kind of I'll say more more traditional endpoints, we will be evaluating.

And Sequoia.

Okay.

And your second question.

<unk>.

What you wanted to repeat that for me.

Yeah absolutely.

Have you heard any feedback either from the FDA or kols on the need for outcomes data post approval for CK 274, Okay.

Yes outcomes data I think that the regulators and Kols appreciate that outcomes data are very hard to come by in it.

Symptomatic, although very heavily.

Heavily burdened patient population.

These patients unlike traditional heart failure patients don't get hospitalized.

Their mortality rates are usually quite low and lessen.

Well, well under 5% per year and so.

You can't really doing an outcomes based trial per se and I think that's well understood based on the event rate.

Fady Ibraham Malik: That said, I think that there is also a recognition that the therapy that is being developed for these patients is a lifelong therapy. And so, you know, I mean, having a good understanding of the long term is important, and that's why we're conducting the Open Label Extension and plan at least five years of follow-up and patients that we enroll in that roll out of either Redwood or Koya to enable us to, you know, better characterize the course of these patients who are being treated with apicampin.

That said I think the there's.

There is also a recognition that the therapy that.

<unk> is being developed for these patients is a lifelong therapy and so.

Having a good understanding of it.

Safety long term is important and that's why we're conducting the open label extension and plan at least five years of follow up in patients that we enroll in that that rollout of the redwood or sequoia to enable us to better characterize the course.

Fady Ibraham Malik: You know, I think the advent of new pharmaceuticals is going to drive a better awareness of the outcomes associated with a diagnosis of HCM, as could be modified with add-on therapy such as Affy Kempton or Mavvy Kempton and you're going to see, I think, more publications arising out of registries that speak to the real-world evidence associated with these longitudinal studies. So we will be in a position to better understand what might be possible, and I do suspect that'll play into the adoption of the category in the end. But to your original question as to whether regulators are pushing for it, I don't think that's likely going to factor into the registration of these new medicines, at least not from what we've heard from FDA.

These patients who are being treated with alpha Camden.

Yes.

I think the advent of new pharmaceuticals is going to drive a better awareness of the outcomes associated with a diagnosis of HCM.

Could be.

Modified with.

Add on therapy of Ft, Kimpton or magic counted and.

Youre going to see I think increasingly publications are rising out of registries that speak to the real world evidence associated with these longitudinal.

Studies, so we will be in a position to better understand.

What might be possible, because I do suspect that will play into ultimately the adoption of the category.

But to your original question as to whether regulators are pushing for it.

I don't think thats likely going to factor into.

Fady Ibraham Malik: That's super helpful. And if I may just follow up here, can you talk about the importance of showing the FDA that patients are able to get stabilized onto a safe dose for this class of drugs? Is that something that the agency is focused on from a regulatory perspective? Thanks so much; it's certainly very helpful.

The registration of these new medicines at least not from what we've heard from FDA.

That's super helpful and if I, if I may just follow up here.

Can you talk about.

The importance of showing.

That patients are able to get stabilized onto a safe dose for this class of drugs is that something that the agency is focused on from a regulatory perspective. Thanks. So much.

Robert I. Blum: It's certainly something that we think is possible and achievable with AppyCAM, and we hope to be able to demonstrate that with Sequoia. If your question is pointed to, is that something FDA is pushing for because of their review of another product? That would not be appropriate for FDA to be signaling anything like that to us.

It's certainly something that we think is possible and achievable with RP Kempton.

We hope to be able to demonstrate that with Sequoia.

If your question is pointed to is that something FDA is pushing for because of their review of another product that would not be appropriate for FDA to be signaling anything like that to us.

Operator: Your next question comes from the line of Salim Syed with Mazzuho.

Understood. Thanks, so much.

Salim Qader Syed: Good afternoon, Robert and team, and congrats on all the progress. Just a couple for me, one on 274 and one on actually relative incentive. So on 274, look, Robert, obviously, the thesis here has gotten a lot more comfortable for a lot of long-only investors, right? And I'm curious in your mind, what are the gating factors when you think about the story?

Your next question comes from the line of Salim Syed with.

With Mizuho.

Hello, Sir.

Good afternoon, Robert and team and congrats on all the progress just a couple from me one on 274 and one on actually rather sensitive.

So on to some in for Robert.

The thesis here has gotten a lot more comfortable for a lot of long only investors right and I'm curious in your mind what are the gating factors when you think about the story.

Salim Qader Syed: What are the gating factors here for 274 that are really stopping you from turning on the afterburners and starting to develop HEF-PEF, which, as you know, is a major indication, more aggressively? And I guess we could also ask the same question for non-obstructive hypertrophic cardiomyopathy. And the second question on relative incentives. So as we start to dig in here on the courage design, you guys are enrolling, looks like ALS, FRS, total score of 44 or less.

What are the gating factors here for to some for that.

Early stopping you from turning on the afterburners and starting to develop have Pat Fortunately, it's a large indication.

More aggressively I.

And I guess, we could also asked the same question for non obstructive hypertrophic cardiomyopathy.

And then the second question on <unk>, So as we start to dig in here on the current design.

You guys aren't enrolling it looks like ALS FRS.

Salim Qader Syed: But when we look at the Phase 2 data, the slope progressor per tile, which had a score of 41, didn't really show much of a difference between the drug and placebo. So I'm curious how you guys are thinking about courage.

Total score 44 or less but when we look at the.

The phase two data.

<unk> slow progress our tile and wood.

Score of 41 didn't really show much of a difference between drug and placebo.

Robert I. Blum: Are you going to limit somehow the slope progressors that are entering the trial or... or how are you ensuring that when we get to futility, you know you have an over-enrolled slow progression, I guess is one way to ask it, or how are you ensuring that you're going to actually have enough medium or fast progressors that would show a larger benefit here potentially according to the phase two data? Thank you. Both very good questions. Let's start with your first one on the development program for AFI-CAM. We've spent quite a bit of time over these last several months since we saw the Redwood results.

Curious how you guys are thinking about courage are you going to limit somehow this slow progressive that are entering the trial or.

Or how are you ensuring that you know when when.

When we got to futility that you haven't it over enrolled slow progression I guess, that's one way to ask it or how are you controlling but theyre going to actually have enough medium or fast progressing that wouldn't show a larger benefit here potentially.

Going to the phase two data thank you.

Sure both very good questions, let's start with your first one around the development program for <unk> Kimpton.

Robert I. Blum: Considering what might be our next steps beyond Sequoia HCM for Affy Kampton, Fady, Stuart, and Steve, and others here at Cytokinetics are considering a number of different trial designs, as we would be expected, to expand the development program in non-obstructive HCM and in HFPAF. It's premature for us to elaborate on them, but you should expect in 2022 to hear more about our plans that way We intend to be pursuing the development of AFI-CAMPTN along both those lines and not in a linear way per se, but in parallel ways that would be enabling us to build on what we know for AFI-CAMPTN. I'm just not in a position to do that on today's call.

We've spent quite a bit of time over these last several months once we saw the redwood results.

Considering what might be our next steps beyond Sequoia HCM for ft, Kimpton in Saudi and Stewart, and Steve and others here et cetera, kinetics are considering a number of different.

Trial designs, we would be expected.

To expand the development program in non obstructive HCM and and help them.

It's premature for us to elaborate on them, but you should expect in 2022 to hear more about our plans that way.

We intend to be pursuing the development of Alfa Kimpton, along both of those lines.

Not in a linear way per se, but in parallel ways that would be enabling of us to build on what we know for <unk>.

Robert I. Blum: But certainly, as we plan for budgets for 2022 and goals and consider resources that we need to align in order to make that happen, that's very much in the forefront of our planning. Your second question related to COURAGE-ALS, I'll ask Fady and Stuart to address. I think you might be misunderstanding a bit how we are designing the study. We are going to be prioritizing those patients who are progressing, but they can elaborate.

Kimpton.

I'm just not in a position to do that on today's call.

But certainly as we plan for budgets for 2022 and goals and.

Consider a resources that we need to align in order to make that happen that's very much in the forefront of our planning.

Your second question related to courage AOS in Alaska, Saudi and Stewart to address I think you might.

The misunderstanding a bit how we are designing the study we are.

Going to be prioritizing for those patients who are progressing but they can elaborate.

Robert I. Blum: Yeah, I think, you know, it's really an enrichment strategy, Salim. And so the entry criteria are designed in such a way to enrich for the medium and faster progressors. And I can turn it over to Stuart a little bit to describe how that works. But ultimately, you know, it's also something that we can monitor because Stuart Kupfer, Akash Tewari, Paul Choi, Sean McCutcheon, Adhiraj Chauhan, Cameron Bozdog, Yeah, so Salim, I think you're referring to

Yes, I think it's really an enrichment strategy filling them and so the entry criteria designed in such a way to enrich for the medium and faster progresses.

And I can turn it over to Stuart little bit describe how that works.

But ultimately it's also something that we can monitor because.

And you can look at progress you can look at the.

Calculate the early progression rates in the study and ensure that you are enrolling the right patients in a blinded way.

Sure.

So Celine I think you're referring to the post hoc analyses that were conducted with fortitude ALS database and.

While we observed trends would benefit.

In slow progresses, we.

We observed greater.

It's a benefit with respect to ALS FRS or in the medium and fast progressing patients.

Operator: (inaudible) and what we did was map that out.

Operator: https://www.kenhub.com

And.

What we did with map that.

Progression rate to critical entry criteria, particularly a max in ALS FRS or.

Stuart Kupfer: as well as time from symptom onset of two years. And so, if we apply those two main criteria, it enriches, as Fady mentioned, for a population of faster-progressing patients. Well, I'm not excluding slow progressors, but we'll have a large proportion of medium and faster progressing patients with this strategy. And, you know, with that strategy. We anticipate that this will increase the sensitivity of detecting a beneficial treatment effect with related symptoms.

A 44.

As well as time from symptom onset.

Two years and so.

If we apply those apply those two main criteria.

That enriches us that he mentioned for population faster progressing.

Progressing patients.

While not excluding slow progresses, but we'll have a larger proportion of medium and faster progressing patients and that.

That strategy.

We anticipate that this will increase the sensitivity.

Salim Qader Syed: Okay, got it. So this is more, you will be able to, in your view, do this based on entry criteria, not having to calculate during the trial based on blinded data? That's correct, exactly. Okay, thank you.

Detecting a beneficial treatment effects throughout the symptoms.

Okay got it. So this is this is more you.

We'll be able to in your view.

Do this based on entry criteria not having to calculate during the trial based on blinded data.

Operator: Your next question comes from the line of Jason Butler with JMP Security. Good afternoon, Jason.

Correct exactly right okay. Thank you.

Thank you Sue.

Jason Nicholas Butler: Hi Robert, thanks for taking the questions. I was just wondering if you could talk a little bit more about the path for Aficantin in China. Is there data that you need beyond the completed PK study to open up the Sequoia trial to China? And then, you know, just give us a sense of what proportion of patients in the trial you think could come from China. And then, you know, could Sequoia be a standalone support registration in China, or would you need additional data or an additional trial beyond that trial? Thanks.

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

Good afternoon, Jason.

Hi, Robert Thanks for taking my questions.

Just wondering if you could talk a little bit more about the path for <unk> in China.

Is there data that you need beyond the completed PK study to open up the Sequoia trial to China, and then just give us a sense of what proportion of patients since the corner you think could come from China and then.

Could could sequoia as a standalone support registration in China or would you need additional data or additional trial.

Robert I. Blum: Yes, a very good question. We're still learning about what might be required, but it's our assumption that we're going to be in a position to start Sequoia. And based on the phase one data, be enrolling Chinese patients into the same study, and as could be supportive of registration in China, as well as outside of China, the US, and Europe, also. So that's the intention and the plan. Obviously, that's subject to regulatory interactions that are still to be had.

Beyond that that trial. Thanks.

Yes, so very good questions. We're.

Still.

Learning about what might be required, but it is our assumption.

We're going to be in a position to start Sequoia.

In China.

And based on the phase one data via enrolling China patients into the same study and as could be supportive of registration in China as well as outside of China U S. Europe elsewhere, So thats the intention and the plan obviously, that's subject to regulatory.

Robert I. Blum: But our partner, Zhijing, is very much on top of these things, and we're working very, very well. Stuart is leading much of that activity for cytokinetics. Stuart, anything more you want to add? I think you've summarized it very well, certainly rely on G-Stream for guidance.

<unk> that are still to be had but our partners regime is very much on top of these things and we're working very very well Stuart is leading much of that activity for cytogenetics Stuart anything more you want to add.

I think you've summarized it very well.

We certainly rely on angi shame or four guidance they have more expertise in China regarding the regulatory requirements.

Stuart Kupfer: Please see the Phase 1 data to support enrollment of patients in China and Sequoia HCM.

But as you've been.

Been laid out we expect the phase one data to support enrollment of patients in China, and Sequoia HCM and that.

Operator: That trial to support registration in China. Great. Thanks for taking the questions. Thank you.

In that trial to support registration in China.

Charles Cliff Duncan: Your next question comes from the line of Charles Duncan with Cantor Fitzgerald.

Great. Thanks for taking the questions.

Thank you.

Charles Cliff Duncan: Hello Robert and team, congratulations on a good year of progress.

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

Hello Charles.

Charles Cliff Duncan: Thanks for taking my question. I had a couple of questions, one on Omicamdiv and then another on Relative Assentive. With regard to the Omicamdiv NDA filing, I guess I'm wondering, are you planning on press releasing the submission or the acceptance?

Hello, Robert and team congratulations on good year of progress. Thanks for taking my question had a couple of questions.

One on the Omi captive and then another on <unk> with regard to the only captive NDA filing I guess I'm wondering are you are you planning on press, releasing the submission or the acceptance for.

Charles Cliff Duncan: or filing, and then I guess I just need to clarify.

Charles Cliff Duncan: I think it was to Dane's question, would you be filing for a broad label claim?

Review, our filing and then I guess.

I just need to clarify something I think it was to the Danes question would you be filing for a broad label claim with data pointing to the patient cohort that had.

Charles Cliff Duncan: Do you have a broad label claim with data pointing to the patient, the cohort that had the greatest benefit, or would you limit the filing claim to that cohort?

Robert I. Blum: Yeah, so I'll take those, and Fady may want to elaborate with regard to the communications and the press release. We expect to be submitting an NDA in this quarter, and we probably would not be communicating anything until such time as we have a read on its fileability, whether it's filed or not filed by FDA. And then as to your second question, I'll ask Fady to speak regarding how we might approach the indication statement and where it might be information containing the patients that benefited the most.

Greatest benefit or would you limit the filing claim to that cohort.

Yeah. So I'll take those in that he may want to elaborate with regard to the communications and the press release, we expect to be.

Submitting an NDA in this quarter and we probably would not be communicating anything until such time as we have a read on its final ability, whether it's filed or not filed by FDA.

And then as to your second question I'll ask study to speak.

Regarding how we might approach the indication statement and where it might be the information containing the.

Robert I. Blum: Yeah, you know, I think if you look at different indication statements, even recent ones, there are different approaches, but in general, they reflect the patient population that was studied in the clinical trial at large. For example, you can see on the Entresto label, after the Paragon data were added, that there was an additional statement with regard to where the benefit was concentrated, i.e., in patients with below normal ejection fraction.

Patients that benefited the most.

Yes, I can.

I think if you don't get different indication statement, even recent ones there are different approaches, but and generally they reflect the patient population that was studied in a clinical trial at large.

You can see in the.

Entresto label after the the Paragon data were added that there was an additional statement with regards to where the benefit was.

Robert I. Blum: So it may, it may be that you could end up with a modifying statement in the indication. You certainly will have data in the clinical trial section that show the pre-specified subgroups, one of which was ejection fraction, as you know, and showed a benefit in a lower ejection fraction group, the NYJ34 group, and others across the subgroups that we had pre-specified. So there are different places.

Johnson traded I E in patients with below normal ejection fraction.

So if I may.

It may be that you could end up with modifying statement in the indication.

We will have data in the clinical trial section that show.

The pre specified subgroups, which one of which was ejection fraction as you know and showed a.

The benefit in the lower ejection fraction group the NY Chase III for group.

And.

<unk>.

And in the others and across the.

Charles Cliff Duncan: Okay, that's helpful. It kind of fits what I kind of thought regarding meteorics. I think you mentioned that you would complete the conduct of it this year. Can you give us some sense on timing for data? Could that be in the first half of the first quarter? And then can you confirm?

Subgroups that we had pre specified so there are different places in the label where the information may be contained.

And ultimately you know, it's hard to predict where we'll end up until we go through those discussions.

Okay, that's helpful and consistent with what I kind of thought regarding meteoric I think you mentioned that you complete the conduct of it yet this year.

Can you.

Give us some sense on timing to data could that be in the first half of the first quarter and then can you confirm whether or not you think that that data would then be submitted to the agency and have any potential for impacting the review it seems like it could be pretty early in the review cycle.

Fady Ibraham Malik: Yeah, you know, I think what we probably aren't going to give guidance with regard to the first half or second half of the quarter with regard to Meteoric. Its conduct will wrap up this year, but it's really going to wrap up pretty late in the quarter.

So likely not.

Yes, I think.

What.

<unk>.

We probably aren't going to give guidance with regards to first half or second half of the quarter with regards to meteoric.

Fady Ibraham Malik: And then, of course, it's a complicated study because there's a lot of central lab work in terms of the CPET evaluations and so forth. And the data sets are relatively complex to integrate. You don't know how to SWIFT as you might in an event-based trial.

Its conduct will wrap up this year, but it's really going to wrap up pretty late in the quarter.

And then of course there is.

A complicated study because theres a lot of central lab.

Work in terms of the C pet evaluations and so forth.

And the datasets are relatively complex to integrate.

Fady Ibraham Malik: The, Um, but I think, um, the, the, uh, other aspect of your question. You're going to have to remind me of it again now. I've got a lot of it messed up.

Time and database lock, maybe not as Swift as you might have in an event based trial.

Okay.

But I think.

The.

Other aspect of your question.

Charles Cliff Duncan: Just to impact on the review cycle timing.

Youre going to have to remind me of again now got lost track of it.

Fady Ibraham Malik: Yeah, no, I think, you know, having the results in hand and early in the quarter is not going to, obviously, the FDA will see them as we release them and hope to see them presented, but they won't, we think, impact the review. There will be safety data that will probably be part of an update during the review cycle. But that's it.

Just the impact on.

View cycle timing, yes.

Yes, no I think having the results.

Hand in early in the quarter is not going to obviously, the FDA will see them as we release them in.

And hope to see them presented.

Well, we think impacted reviewed safety data will be probably.

Charles Cliff Duncan: Okay, and then going on

Part of an update during the review cycle.

Charles Cliff Duncan: Welcome to Routless Semptive. Just one quick question regarding the conduct of that trial, and I think you mentioned in the previous set of questions, or a couple of the four that

That's it.

Okay, and then going onto <unk>, just one quick question regarding.

The conduct of that trial and I think you mentioned in the previous set of questions or a couple of the floor.

Charles Cliff Duncan: that you're kind of enriching for faster progressing patients, and so I guess I'm wondering are you explicitly asking for more bulbar onset versus limb onset patients, which would seem to be consistent with that given

At your kind of them, reaching for faster progressing patients.

And so I guess I'm wondering are you explicitly asking for more vault, our onset versus limb onset patients seem like beacon system with that given that.

Operator: https://www.kenhub.com

Stuart Kupfer: Stuart, do you want to take that? No. Yeah, no. We're not being that restrictive in terms of our...

There are two year since symptom presentation.

Stuart you want to take that.

We're not seeing that restricted.

Stuart Kupfer: We are certainly enrolling patients in both categories, but as I mentioned before, major criteria to enrich for faster progressing patients based on that ALSFRS score at baseline and time since Zemansky.

In terms of our enrollment we're certainly.

Enrolling patients.

In both categories, but.

As I mentioned before the major criteria.

To enrich for faster progressing patients based on that.

Charles Cliff Duncan: Okay, thanks for taking the questions. Thank you.

Thats FRS score at.

At baseline and time since symptom onset.

Operator: Your next question comes from the line of Rohit Bhasin with Needham & Company. Good afternoon. Hi, good afternoon. This is

Okay. Thanks for taking the questions. Thank you. Thank you Paul.

Your next question comes from the line of Rohit Jansen with Needham <unk> company.

Rohit Bhasin: Hi, good afternoon. This is Rohit on for Surge.

Rohit Bhasin: Thanks for taking my question. Can you talk a bit about how the Meteoric HF trial fits with the gold market strategy for OMICAMTIV? Do you expect a label expansion or better payer reimbursement? Sure, I'll ask Fady to speak to that, and maybe Andrew might want to add.

Good afternoon.

Hi, Good afternoon. This is rohit on for Serge. Thanks for taking my question can.

Can you talk a bit about how the meteoric H F trials fits with the go market strategy for <unk>.

Do you expect the label expansion or better payer reimbursement.

Fady Ibraham Malik: I think if METEORIC is positive, we would at some point submit a supplemental NDA filing, an expansion of the label that would include the results of METEORIC. You know, the clinical benefit there is important to patients, especially since improving exercise capacity is something that is rarely shown with drugs that improve heart health. That would be a unique feature of homuncampsid macarbol should the trial be positive. Maybe I'll ask to turn it over to Andrew to see if he has anything else he wants to add. Sure. I mean, we're going to be negotiating access.

Sure I'll ask Scott to speak to that and maybe Andrew might want to add.

Yes, I think if new York is positive we would at some point submit for a supplemental NDA file.

Filing an expansion of the label that would include the results in New York.

The clinical benefit there is important patients and certainly would be worth having in the label that wouldn't come until after the primary approval of them captive mccarville.

And I think.

Being that improving exercise capacity is something that is rarely shown with drugs that improve.

That would be a unique feature of AUM captive mccarville should the trial be positive.

Alaska turn it over to Andrew anything else he wants to add.

Andrew Callos: Pre-approval, post-approval, and largely, we'll be using the data from Galactic. If we have a positive meteoric trial, that certainly will enhance the benefit. We could bring the patient to specialty incapacity.

Sure I mean, we're going to be negotiating access.

Pre approval post approval and largely will be using the data from galactic. If we have a positive New York trial that certainly will enhance the benefit we could bring to patients, especially in capacity it could enhance our value argument if patients feel better or it could be more productive so it really.

Andrew Callos: It could enhance our value argument. Patients feel better, and they could be more productive. So it really does depend on how the data reads out and what the adjustments are to the label. But I wouldn't expect it to have a major impact on our overall access strategy or access. What it does do is it reinforces the mechanism as provided. What could be differentiating benefits to patients beyond outcomes, this being a functional outcome? And in that way, it could reinforce the use of Omicam to Bacarbal, but I agree with Andrew, it's not likely to drive. It might very much have an effect on things like adherence and compliance of patients and also how physicians might ultimately view the category.

It depends on how the data readout and what the adjustments are to the label, but I wouldn't expect it to have a major impact on our overall access strategy your access models.

What it does do is it reinforces the mechanism as provides.

What could be differentiating.

Benefits to patients beyond outcomes this being a functional outcome.

And that way it could reinforce.

The use of <unk> of the carnival, but I agree with Andrew it's not likely to drive.

So we view things and Mike very much have the effect of things like adherence and compliance of patients and also how physicians might ultimately view the category.

Operator: And there are no further questions in queue at this time. Robert, your closing remarks, please. Thank you.

Great. Thank you.

Robert I. Blum: Thank you. Thanks very much to all the participants in our teleconference today. Thanks for your continued support and your interest in cytokinetics.

And there are no further questions in queue at this time, Robert your closing remarks. Please.

Thank you thanks very much to all the participants on our teleconference. Today. Thanks for your continued support and your interest in Cytogenetics, we're pleased to be able to provide you updates with respect to our progress as well as our prospects.

Operator: We're pleased to be able to provide you with updates on our progress as well as our prospects. Obviously, a lot is going on at our company, and we're looking forward to continuing to execute well on our key milestones through the remainder of this year and then looking forward to next year. As mentioned, it could be quite a transformational year 2022. We look forward to sharing with you all of those updates, and with that, Operator, we can conclude the call.

Obviously, a lot is going on at our company and we're looking forward to continuing to execute well on our key milestones through the remainder of this year and then peering into next year as mentioned it could be quite a transformational year 2022, we look forward to sharing with you all of those updates.

Operator: Thank you. This does conclude today's conference call. You may now disconnect.

And with that operator, we can conclude the call.

Yes.

Thank you. This does conclude today's conference call you may now disconnect.