Q1 2021 Cytokinetics Inc Earnings Call

[music].

Good afternoon, and welcome ladies and gentlemen to Cytogenetics first 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.

Operator: Good afternoon and welcome, ladies and gentlemen, to Cytokinetics' first quarter 2021 conference call. At this time, I'd like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call for questions and answers after the presentation. I'd now like to turn the call over to Diane Weiser, Cytokinetics' Senior Vice President of Corporate Communications and Investor Relations. Please go ahead.

I'll now like to turn the call over to Diane Weiser Cyberkinetics Senior Vice President of corporate Communications and Investor Relations. Please go ahead.

Good afternoon, and thanks for joining us on the call today, Robert Blum, our President and Chief Executive Officer will kick off the call with an overview of the quarter and recent developments then 30 Malik our EVP of research and development will provide an update on <unk> included including progress following our recent meeting with FDA.

Diane Weiser: Good afternoon, and thanks for joining us on the call today. Robert Blum, our President and Chief Executive Officer, will kick off the call with an overview of the quarter and recent developments. Then, Fady Malik, our EVP of Research and Development, will provide an update on Omicamptin-McCarbyl, including progress following a recent meeting with FDA and what to expect from upcoming analyses from Galactic HF, the positive Phase III clinical trial of Omicamptin-McCarbyl, as well as recent activities related to Meteoric HF, the second Phase III clinical trial of Omicamp

And what to expect from upcoming analyses from Galactic H F. The positive phase III clinical trials on the camp and mccarville as well as recent activities related to meteoric H F. The second phase III clinical trial of OMA Camden Mccarville next Stuart Kupfer, our SVP and Chief Medical Officer will provide an update on our.

Diane Weiser: Next, Stuart Kupfer, our SVP and Chief Medical Officer, will provide an update on our Cardiac Myosin Inhibitor Program with focus on Redwood HCM, the Phase II clinical trial of CK274. Then, Robert Wong, our VP and Chief Accounting Officer, will provide a financial overview for the past quarter, and Ching Jia, our SVP and Chief Financial Officer, will discuss our financial outlook and corporate development strategies before Robert Blum then returns to provide concluding thoughts and expected key milestones for the remainder of 2021. We also have a new team member on today's call, Andrew Callos, our Chief Commercial Officer, who joined Cytokinetics during the quarter and who you will hear from on upcoming calls.

Cardiac myosin inhibitor program with focus to Redwood HCM the phase II clinical trial of CK, two seven and four then 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 our financial outlook and corporate develop.

And and strategies before Robert Blum, then return to provide concluding thoughts and expected key milestones for the remainder of 2021.

We also have a new team member on today's call Andrew Carlos Our Chief Commercial officer, who joined Cytogenetics during the quarter and who you will hear in upcoming calls.

Diane Weiser: Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance, rather than historical facts, and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our Q1 2021 financial results filed on Form 8K today. We undertake no obligation to update any forward-looking statements after this call. And now, I will turn the call over to Rob.

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 may differ materially from those projected and these forward looking statements additional information concerning factors that could.

Cause our actual results to differ materially from those and these forward looking statements is contained in our SEC filings, including our current report regarding our first quarter 2021 financial results filed on form 8-K. Each day, we undertake no obligation to update any forward looking statements. After this call and now I will turn the call.

Over to Robert.

Robert I. Blum: Thank you, Diane, and thanks again to everyone for joining us on the call today. We had a productive first quarter and are feeling increasingly more optimistic as our nation reemerges into new normalities in the coming months with widespread vaccinations for COVID-19. We continue to wish you and your families good health and well-being.

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

We had a productive first quarter and are feeling increasingly more optimistic as our nation reemerged towards new normal she used in the coming months with widespread vaccinations for COVID-19, we continue to wish you and your families good health and wellbeing.

We're also optimistic about sort of kinetics, and our pipeline our progress and our prospects.

Robert I. Blum: We're also optimistic about cytokinetics in our pipeline, our progress, and our prospects. In the first quarter, we executed well against our plans and are firing on all cylinders, with priority to advancing our industry-leading cardiovascular drug candidates directed to muscle, Focusing on both Redwood HCM and Meteoric HF, as well as advancing regulatory and commercial readiness workstreams in support of Omicampta McCarble. Toward that end, I'm very pleased to introduce the newest member of our leadership team.

And the first quarter, we executed well against our plans and are firing on all cylinders with priority to advancing our industry, leading cardiovascular drug candidates directed to muscle focusing to both redwood HCM and meteoric HFF.

And as advancing regulatory and commercial readiness work streams and support of Omi kept them mccarville.

Toward that and I'm very pleased to introduce the newest member of our leadership team.

Robert I. Blum: Andrew Callos, Andrew joined us as our Chief Commercial Officer, and we're thrilled to have him on board at a key time for our company as we turn the corner towards commercialization and transition to be a forward integrated biopharmaceutical company. Andrew brings relevant commercial and operational experience from cardiovascular specialty care and rare disease marketing. He had a long and successful career at Pfizer and at Wyeth Pharmaceuticals, where he oversaw U.S. and international pharmaceutical business franchises. Most recently, Andrew served as regional president and general manager of North America for Pfizer's Upjohn business unit. And prior to that role, and during his over 20 years at Pfizer and its predecessor companies.

Andrew Carlos Andrew joined US as our Chief commercial officer, and we're thrilled to have him on board and a key time for our company as we turned the corner towards commercialization and transition to be a forward integrated biopharmaceutical company.

Andrew brings relevant commercial and operational experience from cardiovascular specialty care and rare disease markets. He had a long tenured and successful career at Pfizer and Wyeth Pharmaceuticals, where he oversaw U S and international pharmaceutical business franchises.

Recently, Andrew served as regional President and General manager and North America for Pfizer's, Upjohn business unit and prior to that role and during his over 20 years at Pfizer and predecessor companies. He held leadership positions, including as Vice President U S cardiology and.

Robert I. Blum: He held leadership positions, including as Vice President, U.S. Cardiology and Metabolic Marketing, overseeing the commercialization of Eliquis in the United States. Andrew also served as Vice President and Head of Inflammation Marketing Europe and Vice President, Global Commercial Development for Rare Diseases. As you can see, his experience is a perfect fit for cytokinetics, and he has quickly come up to speed and contributed to the many commercial planning work streams that had already been underway prior to his arrival.

Metabolic marketing overseeing the commercialization of <unk> and the United States.

And you also served as vice President and head of inflammation marketing Europe, and Vice President Global commercial development for rare diseases.

As you can see his experience is a perfect fit for subtle kinetics and he has quickly come up to speed and contributed to the many commercial planning work streams that had already been underway prior to his arrival.

Robert I. Blum: Andrew joins us to lead a team of similarly expert commercial colleagues at Cytokinetics who are experienced in cardiovascular and neuromuscular specialty care markets. And as we proceed to finalize our go-to-market planning for Omicamptive McCarble and CK274, you'll be hearing more from Andrew and his team about our plans, including at an investor day to be scheduled later this year. On the regulatory front, as previously communicated, during the first quarter, we convened an FDA meeting to review the Phase III clinical trial results from GalacticHF, and we're now proceeding towards additional interactions with FDA and other regulatory authorities.

And Andrew joins us to lead a team of similarly expert commercial colleagues, it's subtle kinetics, who are experienced and cardiovascular and neuromuscular specialty care markets.

And as we proceed to finalize our go to market planning for Omi captive Mccarville AMC K, two seven and four youll be hearing more from Andrew and his team.

About our plans, including out and Investor day to be scheduled later this year.

On the regulatory front as previously communicated during the first quarter, we convened and FDA meeting to review the phase III clinical trial results from Galactic HFF and were now proceeding towards additional interactions with FDA and other regulatory authorities, Saudi will elaborate in a moment, but some.

Robert I. Blum: Fady will elaborate in a moment, but suffice it to say, we're pleased with the level of engagement and the feedback that we received from FDA, and we believe GalacticHF can stand on its own as a pivotal trial in a planned NDA submission. We're now proceeding towards our goal of an NDA submission for Omicamp to McCarble in the second half of 2021. We also advanced our go-to-market planning with workstreams focused on market research, brand positioning, supply chain manufacturing and logistics, market access, health economics and outcomes research, customer engagement, and other commercial infrastructure to inform our future investment and execution strategies in anticipation of a potential commercial launch of Omicampta McCarble in the United States in 2022. Ching will elaborate later in this call on our financials, our cash runway, and our deal objectives to support our go-to-market strategy.

Price it to say, we're pleased with the level of engagement and the feedback that we received from FDA and we believe galactic HFF can stand on its own as a pivotal trial and a planned NDA submission.

We're now proceeding towards our goal of an NDA submission for <unk> and the second half of 2021.

We also advanced our go to market planning with work streams focused on market research brand positioning supply chain manufacturing and logistics market access health economics, and outcomes research customer engagement and other commercial infrastructure to inform our future investment.

And execution strategies and anticipation of a potential commercial launch of <unk> and the United States in 2022 Ching.

Ching will elaborate later in this call on our financials, our cash runway and our deal objectives to support our go to market strategy.

We also made significant strides advancing our cardiac myosin inhibitor program during the quarter.

Focusing on the completion of Redwood HCM, our ongoing phase II clinical trial of CK, two seven and four in patients with symptomatic obstructive hypertrophic cardiomyopathy.

Stuart will elaborate in the first quarter, we opened and promptly completed enrollment in cohort two and more recently opened enrollment to cohort. Three. In addition, this morning, we announced that we also activated the first site and the open label extension study for patients who completed.

Robert I. Blum: We also made significant strides advancing our cardiac myosin inhibitor program during the quarter. Focusing on the completion of Redwood HCM, our ongoing Phase 2 clinical trial of CK274 in patients with symptomatic obstructive hypertrophic cardiomyopathy, as Stuart will elaborate, in the first quarter, we opened and promptly completed enrollment in Cohort 2 and more recently opened enrollment in Cohort 3. In addition, this morning, we announced that we have activated the first site in the Open Label Extension Study for patients who have completed Redwood HCM.

Redwood HCM.

This high proficiency execution underscores the urgency of our activities and this program given the high unmet need among patients with hypertrophic cardiomyopathy based.

Based on data from the interim analysis of cohort one that we announced in December we plan to engage FDA in this quarter and prepare for a phase III clinical trial expected to begin before year end.

We're also advancing medical and.

And new product planning activities directed to specialty care cardiologists and high volume heart failure hospitals that overlap with high volume HCM centers of excellence given the many synergies between our cardiac myosin modulators and planning.

Robert I. Blum: This high-proficiency execution underscores the urgency of our activities in this program given the high unmet need among patients with hypertrophic cardiomyopathy. Based on data from the interim analysis of Cohort 1 that we announced in December, we plan to engage FDA in this quarter and prepare for a Phase 3 clinical trial expected to begin before year-end. We're also advancing medical and new product planning activities directed to specialty care cardiologists in high-volume heart failure hospitals that overlap with high-volume HCM centers of expertise, given the many synergies between our cardiac myosin modulators and planning. And with that, I'll turn the call over now to Fady to elaborate on developments related to Omicamptive McCarver. Thanks, Robert.

And with that I'll turn the call over now to 30 to elaborate on developments related to <unk>.

Thanks Robert.

During the first quarter, we advanced film a captive mccarville forward and several important ways.

We met with FDA to review the topline results of Galactic HFF.

And that type C meeting met our expectations in terms of engagement and feedback.

We now intend to proceed to file an NDA later this year based on results from Galactic HFF and the rest of the development program.

We had an opportunity to hear from FDA at those matters that we should be prepared to address and finalizing the NDA filing and we're now preparing for additional discussions with FDA during the second quarter, including and other planned type C meeting that we expect to further inform our filing strategy.

At this next meeting we plan to share additional analyses of Galactic HFF and request FDA feedback that can inform labeling and our NDA submission.

Fady Ibraham Malik: During the first quarter, we advanced Doma Campes Macabre forward in several important ways. First, we met with FDA to review the top-line results of Galactic HF. That type C meeting met our expectations in terms of engagement and feedback. We now intend to proceed to file an NDA later this year based on results from Galactic HF and the rest of the development program. We had an opportunity to hear from FDA as to those matters that we should be prepared to address in finalizing the NDA filing.

We expect still further interactions, including a potential pre NDA meeting.

To have multiple opportunities to engage the FDA ahead of our goal to submit an NDA and the second half of the year.

I'll remind you that our planned NDA submission will be based on the results of Galactic HFF and combination with the rest of the development program comprising over 30 clinical trials and as informed by prior regulatory discussions.

In parallel with these activities, we continue to conduct meteoric HFF, our second phase III clinical trial of OMA captive mccarville and patients with heart failure with reduced ejection fraction.

Fady Ibraham Malik: We are now preparing for additional discussions with FDA during the second quarter, including another Plan Type C meeting that we expect to further inform our filing strategy. At this next meeting, we plan to share additional analyses of Galactic HF and request FDA feedback that can inform labeling and our NDA submission. We expect further interactions, including a potential pre-NDA meeting, and are pleased to have multiple opportunities to engage FDA ahead of our goal to submit an NDA in the second half of the year.

And meteoric HFF, we're investigating the potential effects of AUM and Camden mccarville to improve exercise tolerance in patients with heart failure, which may provide a benefit for these patients struggling to perform daily activities.

Screening is now nearly closed and we're on track to complete randomization of patients and the meteoric and this second quarter.

We expect top line results to be available in early 2022.

And the findings from meteoric are positive we expect that data from that trial would be submitted and a supplemental filing as would be expected to follow a potential FDA approval and commercial launch.

I'd like to acknowledge the efforts of the study team investigators and study coordinators for their successful commitment to accomplish this milestone during an unprecedented pandemic.

Fady Ibraham Malik: I'll remind you that our planned NDA submission will be based on the results of GALACTIC-HF in combination with the rest of the development program comprising over 30 clinical trials and as informed by prior regulatory discussions. In parallel with these activities, we continue to conduct METEORIC-HF, our second Phase III clinical trial of Omicamptive Mercarbol in patients with heart failure with a reduced ejection fraction. In METEORIC-HF, we're investigating the potential effects of omacamptin-micarbol to improve exercise tolerance in patients with heart failure, which may provide a benefit for these patients struggling to perform daily activities. Screening is now nearly closed, and we're on track to complete randomization of patients into Meteoric in this second quarter. We expect top-line results to be available in early 2022.

During the quarter, we received confirmation that data from a secondary analysis of Galactic HFF assessing the effect of OMA, Camden, Mccargo, and clinical outcomes and relationship to ejection fraction at baseline.

And will be presented by Dr. John <unk> and a late breaking clinical trial session at the American College of Cardiology, 17th annual scientific sessions.

And we can't say more about these data so as not to break embargo policies, but suffice it to say and we believe it will further advance the understanding of which patients in galactic <unk> achieve the greatest benefit from treatment with AUM of Camden Mccarville on top of standard of care.

The executive committee of Galactic HFF and collaboration with cider kinetics.

And that's been working on several additional secondary analyses from which data will be forthcoming later this year at medical meetings and and manuscripts to further elaborate on the results of Galactic HFF and inform its potential use.

Fady Ibraham Malik: If the findings from EDIORC are positive, we expect that data from that trial would be submitted in a supplemental filing as would be expected to follow a potential FDA approval and commercial launch. I'd like to acknowledge the efforts of the study team, investigators, and study coordinators for their successful commitment to accomplish this milestone during an unprecedented pandemic. During the quarter, we received confirmation that data from a secondary analysis of galactic HF assessing the effect of Omicamptin-Micarbyl on clinical outcomes in relationship to ejection fraction at baseline will be presented by Dr. John Tierlink in a late-breaking clinical trial session at the American College of Cardiology 70th Annual Scientific Session.

We believe that these additional analyses will be very informative as to how on the captive mccarville performed and galactic and illuminate key learnings.

Given the dynamics of the heart failure treatment setting it's incumbent on us to best understand how to frame. These data and what can hopefully be and approval submission for this first in class cardiac myosin activator, which reduced the risk of heart failure events and its pivotal trial.

To that point and the last quarter, we continued market research activities to better define and refine.

Potential target product profile of OMA captive mccarville, and understand where it may best fit and the treatment armamentarium, particularly given the new entries available to clinicians and their patients.

As we've said before it's an exciting time and the treatment of heart failure, where there is still tremendous unmet need and we remain enthusiastic that AUM and captive mccarville may provide a welcome addition, and the battle to better manage this high prevalence progressive disease.

Fady Ibraham Malik: We can't say more about these data, so as not to break embargo policies, but suffice it to say, we believe it will further advance the understanding of which patients in GALACTIC-HF achieve the greatest benefit from treatment with Omicamptive Mecarbil on top of standard of care. The Executive Committee of Galactic HF, in collaboration with Cytokinetics, has been working on several additional secondary analyses from which data will be forthcoming later this year at medical meetings and in manuscripts to further elaborate on the results of Galactic HF and inform its potential use. We believe that these additional analyses will be very informative as to how Omicamptive Macarble performed in Galactic and illuminate key learnings.

Particularly among more severe patients who have exhausted guideline directed therapy and still suffered debilitating symptoms are at high risk for heart failure hospitalization.

We also have had opportunity to engage with a large number of kols during the quarter with a significant majority of them providing positive views regarding on the campus and mccarville and importantly, pointing out that it could potentially fill a key need among more severely ill patient population that is more at risk.

Of hospitalization and re hospitalization.

Common themes included and understanding that biologically it stands to reason that those patients with more impaired cardiac systolic function may benefit more from this novel mechanism therapy is designed to act directly on muscle and improve cardiac function and performance.

Fady Ibraham Malik: Given the dynamics of the heart failure treatment setting, it's incumbent on us to best understand how to frame these data and what can hopefully be an approvable submission for this first-in-class cardiac myosin activator, which reduced the risk of heart failure events in its pivotal trial. To that point, in the last quarter, we continued market research activities to better define and refine the potential target product profile of Omicamptive Mecarbil and understand where it may best fit in the treatment arsenal.

As well as the potential to add <unk> to the standard of care given its favorable tolerability and safety profile as we observed and Galactic HFF.

And which is addition to standard of care did not adversely affect blood pressure of renal function.

And finally during the past quarter were pleased to conduct and inaugural meeting of our heart failure patient Advisory Council.

This is a group of passionate patients and caregivers with whom we've been meeting regularly to inform understandings of the patient experience disease journey and unmet needs.

Fady Ibraham Malik: Particularly given the new entries available to clinicians and their patients. As we've said before, it's an exciting time in the treatment of heart failure, where there are still tremendous unmet needs. And we remain enthusiastic that Omicamps of McCarble may provide a welcome addition in the battle to better manage this high-prevalence progressive disease, particularly among more severe patients who have exhausted guideline-directed therapy and still suffer debilitating symptoms or are at high risk for heart failure hospitalization.

These insights will be instrumental and designing patient support services educational materials and guiding the development of our heart failure directed pipeline.

We're grateful to the participants and from our first engagement. We are confident this group will be valuable to our patient centric activities.

As we've indicated cytogenetics is committed to advancing <unk> as a key priority in 2021.

Doing that has required extensive attention to wind down activities and our collaboration with Amgen and.

Fady Ibraham Malik: We also had the opportunity to engage with a large number of KOLs during the quarter, with a significant majority of them providing positive views regarding Omicamptomocarbal and importantly, pointing out that it could potentially fill a key need among a more severely ill Asian population that is more at risk of hospitalization and re-hospitalization. Common themes included an understanding that biologically, it stands to reason that those patients with more impaired cardiac systolic function may benefit more from this novel mechanism therapy that's designed to act directly on muscle and improve cardiac function and performance, as well as the potential to add Omecamtiv mecarbil to standard of care given its favorable tolerability and safety profile, as we observed in galactic HF. In which its addition of the standard of care did not adversely affect blood pressure or renal function.

Included amongst these projects are managing the transfer of the integrated safety database and reported related reporting obligations.

Receipt of regulatory documents and assuming responsibility for manufacturing.

Transitioning these many work streams from a 15 year collaboration is not trivial and our team at Scioto kinetics has been very busily attempting to these issues to ensure smooth and orderly handoffs.

Naturally we have prioritized OMA captive mccarville and are therefore day prioritizing the further development of our cardiac troponin activator CK 136, formerly referred to as AMG 594, which will be deferred for the rest of 2021.

We plan to continue its development and the future as we continue to build out and advance our pipeline.

And look to expand our emerging cardiovascular product franchise.

And with that I'll turn the call over to Stuart.

Thanks Patty.

Fady Ibraham Malik: And finally, during the past quarter, we're pleased to conduct the inaugural meeting of our Heart Failure Patient Advisory Council. This is a group of passionate patients and caregivers with whom we've been meeting regularly to inform understandings of the patient experience, disease journey, and unmet needs. These insights will be instrumental in designing patient support services, educational materials, and guiding the development of a Heart Failure Directed Pipeline.

During the quarter, we made significant progress within our cardiac myosin inhibitor program.

On the advancement of CK 274.

I'll begin with an update on Redwood HCM, the phase II clinical trial of CK 274, and patients with obstructive HCM <unk>.

Including highlighting recent and upcoming regulatory interactions and then touch on preclinical data recently presented at the American Chemical Society annual meeting.

During the first quarter and Redwood HCM, we dosed the first patient and also completed full enrollment in cohort two.

Fady Ibraham Malik: We're grateful to the participants. From our first engagement, we are confident this group will be valuable to our patient-centric activities. As we have indicated, cytokinetics is committed to advancing Omicamptin-McCarbyl as a key priority in 2021. However, doing that has required extensive attention to wind down activities in our collaboration with Amgen. Included amongst these projects are managing the transfer of the Integrated Safety Database and related reporting obligations, the seat of regulatory documents, and assuming responsibility for manufacturing.

Which is examining the safety and Tolerability of doses of 10, 20, and 30 milligrams of CK 274 versus placebo.

Dosing of CK 274 is individually titrated by Echocardiographer at weeks, two four and six with dosing and optimize on the basis of targeted reductions and L. D O T gradients, while maintaining a normal ejection fraction.

Overall, the treatment duration is 10 weeks with and echocardiogram to examine reverse ability of effect two weeks after the last dose.

Fady Ibraham Malik: Transitioning these many work streams from a 15-year collaboration is not trivial, and our team at Cytokinetics has been very busy attending to these issues to ensure smooth and orderly handoffs. Naturally, we have prioritized omicamptomacarbal and are therefore deprioritizing the further development of our cardiac troponin activator, CK136, formerly referred to as AMG594, which will be deferred for the We plan to continue its development in the future as we continue to build out and advance our pipeline and look to expand our emerging cardiovascular product franchise. And with that, I'll turn the call over to Stuart. Thanks, Fady. During the quarter, we made significant progress with our cardiac patients.

We remain on track to report topline results from both cohort one and cohort two mid year.

And as well and to begin a planned phase III clinical trial by year end.

Earlier this week, we announced the opening of cohort three of Redwood HCM.

<unk> III is intended to examine the safety and Tolerability of CK 274, and patients whose background therapy includes <unk> at Paramount.

And medications that are sometimes used in patients with symptoms refractory to first line non oral therapy.

And that has been excluded and most trials and of HCM intervention to date.

And cohort three patients will receive CK 274, and open label fashion over a 10 week period with individualized dose titration or 510 or 15 milligrams once daily.

This cohort is not being conducted to further refine the dosing strategy that we intend to study and phase III and <unk>.

Stuart Kupfer: Myosin Inhibitor Program Focus on the Advancement

Stuart Kupfer: of CK274. I'll begin with an update on Redwood HCM, the Phase 2 clinical trial of CK274 in patients with obstructive HCM, including highlights

Instead cohort three is expected to provide important data to inform the potential inclusion and <unk>.

<unk> treated patients and our planned phase III clinical trial.

Additionally, this morning, we announced that we have activated the first site and Redwood HCM O L D.

Stuart Kupfer: and then touch on preclinical data recently presented at the American Chemical Society Annual Meeting. During the first quarter of Redwood HCM, we dosed the first patient and also completed full enrollment in cohort two, which is examining the safety and tolerability of doses of

The open label extension study that is designed to assess the long term safety and Tolerability of CK 274, and patients with symptomatic obstructive HCM.

Eligible patients will have completed their participation and Redwood HCM.

Primarily we will evaluate long term safety as assessed by the incidence of adverse events and left ventricular infection.

Stuart Kupfer: This is 10, 20, and 30 milligrams of CK274 versus placebo. Dosing of CK274 is individually titrated by echocardiography at weeks 2, 4, and 6.

Section and less than 50 per cent.

Secondary endpoints include measures of the long term effects of CK 274 on left ventricular outflow tract gradient.

And assessments.

Okay.

Yes.

Alright, and assessments and steady state pharmacokinetics.

Stuart Kupfer: with dosing optimized on the basis of target reduction and LVOT gradients while maintaining a normal ejection process.

The open label extension study will also include a cardiac MRI sub study to assess changes and cardiac morphology function and fibrosis.

All enrolled patients will receive CK 207, and four and use a similar echocardiographer guided dose titration to individually optimized dose and it has been employed and Redwood HCM.

Stuart Kupfer: Overall, the treatment duration is 10 weeks with an echocardiogram to examine reversibility of effect two weeks after the last dose. We remain on track to report top-line results from both Cohort 1 and Cohort 2 by mid-year, as well as to begin a planned Phase 3 clinical trial by year-end. Earlier this week, we announced the opening of Cohort 3 of Redwood HCM. Cohort 3 is intended to examine the safety and tolerability of CK274 in patients whose background therapy includes disipiramide, a medication that is sometimes used in patients with symptoms refractory to first-line medical therapy and that has been excluded in most trials of HCM interventions to date. In Cohort 3, patients will receive CK274 in an open-label fashion over a 10-week period with individualized dose titration of five

During the last quarter. We also made progress under our collaboration with <unk> pharmaceuticals with initiation of a phase one clinical study of CK 274, and healthy participants and China.

This aligns with our share and objective for the inclusion of China, and a global phase III clinical trial planned to begin later this year.

We are pleased to see that our colleagues and you're seeing our operating with the same sense of urgency as we are to enable the advancement of CK, two seven and four into a global registration program.

From a regulatory perspective.

We were also pleased to recently received orphan drug designation from the FDA.

For CK, 274, and symptomatic HCM encompassing both obstructive and non obstructive patients.

This underscores the significant unmet need and patients who continue to suffer symptoms that can severely impact their quality of life and.

Stuart Kupfer: 10 or 15 milligrams once daily. However, this cohort is not being conducted.

Few treatment options available to them and no currently approved medical therapies.

Operator: http://www.cdc.gov.au

And the first quarter, we also prepared for regulatory interactions including type C.

Stuart Kupfer: Thank you for joining us to inform the potential inclusion of disoperamide-treated patients in our planned Phase III clinical trial. Additionally, this morning, we announced that we have activated the first site in the Redwood HCM OLD Open Label Extension Study that is designed to assess the long-term effects of COVID-19.

And and the phase two meetings with the FDA as well as with E N a per scientific advice.

The first of these next level meetings is planned to occur in the second quarter and will inform how we approach and end of phase two meeting that is expected to occur and the third quarter.

Finally last month data related to the optimization of CK, two seven and four including the first disclosure and if its chemical structure.

Stuart Kupfer: for the Long-Term Safety and Tolerability of CK274 in Patients with Symptomatic Obstructive HCM. Eligible patients will have completed their participation at Redwood HCM. Primarily, we will evaluate long-term safety as assessed by the incidence of adverse events and left ventricular infection less than 50%. Secondary endpoints include measures of the long-term effects of CK274 on left ventricular outflow tract radiance, and Assessment

And were presented at the American Chemical Society Spring 2021 virtual meeting.

This scientific presentations highlighted the preclinical characterization of CK 274.

And focused on key compound characteristics, including including the top line.

The shallow dose response relationship and.

And lack of meaningful cytochromes people or 50 interactions.

Furthermore, data were presented from genetic models of HCM and with CK 274 reduced fractional shortening.

And L D O T peak gradient and a dose related manner.

These results highlight the success of the chemical optimization program conducted aside and kinetics, which was intentionally focused on designing key compound characteristics to enable flexible safe and timely dosing adjustments and clinical practice.

Stuart Kupfer: and Assessments of Steady, Safe Pharmacokinetics. The Open Label Extension Study will also include a cardiac MRI sub-study to assess changes in cardiac morphology, function, and fibrosis.

And I look forward to results from both cohorts, one and two with Redwood HCM.

Stuart Kupfer: All enrolled patients will receive CK274 and use a similar echocardiography-guided dose.

Which will elucidate how these next generation the geochemical properties of CK, two seven and four may translate into important clinical effects and patients with obstructive HCM.

Stuart Kupfer: This is a biography-guided dose titration to individually optimized dose as has been employed in Redwood HCM. During the last quarter, we also made progress under our collaboration with Jixing Pharmaceuticals, with initiation of a

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

Thanks Stuart.

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

Stuart Kupfer: This concludes today's one clinical study of CK274 in healthy participants in China. This aligns with our shared objective for the inclusion of China in a global phase three clinical trial planned to begin later this year. We are pleased to see that our colleagues at Yixing are operating with the same sense of urgency as we are to enable advancement of CK274 into a global registration program from a regulatory perspective. We were also pleased to recently receive Orphan Drug Designation from the FDA for CK274 in symptomatic HCM encompassing both obstructive and non-obstructive patients.

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

And we ended the first quarter with approximately $460 million and cash and investments.

Our revenues in Q1, 2020, one came primarily from our strategic alliances with Amgen and Astellas.

Our first quarter 2021, R&D expenses increased to $31 6 million from $21 7 million in the first quarter of 2020, primarily due to increases in spending on our skeletal muscle programs and clinical development activities for our cardiac myosin inhibitor program.

More than 50% of our R&D expenses were attributable to our cardiovascular programs as expected given activity for meteoric and Sarah and the cardiac myosin inhibitor program and the remainder of our expenses were attributable to our skeletal and early research activities.

Stuart Kupfer: This underscores a significant unmet need in patients who continue to suffer symptoms that can severely impact their quality of life. There are a few treatment options available to them and no currently approved medical therapy. In the first quarter, we also prepared for regulatory interactions, including type C and end of phase two meetings with the FDA, as well as with the EMA for scientific advice.

Our first quarter 2021 and G&A expenses were $15 6 million up from $12 4 million and Q1, and 2020 due to higher personnel related costs, including stock based compensation and higher commercial readiness spending.

And now Ching will review, our planning and corporate development strategy.

Thanks Robert.

As we ended the first quarter was approximately $460 million in cash.

And look to our financial guidance for 2020, one and believe we have over two years old flow of cash runway.

We have also indicated that we may revise financial guidance based on finalizing commercial planning activities.

Stuart Kupfer: The first of these next level meetings is planned to occur in...

Operator: Page PAGE of NUMPAGES www.verbalink.com Page PAGE of NUMPAGES

And it only came from Kabul and a potential product launch in 2022.

unknown: The Bulletproof Executive 2013 Finally, last month, data related to the

During the quarter, we delve deeply into commercial planning and art developing a comprehensive go to market strategy, which will be presented to our board took and alignment on the overall approach and investment requirements.

unknown: Data related to the optimization of CK274, including the first disclosure of its chemical structure, were presented at the American Chemical Society Spring 2021 virtual meeting. This scientific presentation highlighted its preclinical characterization.

The strategy comprises key elements such as market assessment brand strategy market access.

Commercial organizational structure.

Customer facing and digital engagement strategy supply chain and information systems and.

And projected sales spending and return on investment.

unknown: Sour, and focused on key compound characteristics, including its haploidity, Shallow Dose Response Relationship, and Lack of Meaningful Cytokines

As we advance these strategies in support of potential launch of Omi counts and mccarville, we are focusing on the most efficient and high yield investments to enable the commercialization of <unk> and we kept them carbo in 2020 two.

unknown: Any Full Cytochrome P450 Interactions

unknown: Furthermore, data were presented from...

Stuart Kupfer: and LBOT Peak Gradient in a dose-related manner. These results highlight the success of the chemical optimization program conducted at Cytokinetics, which was intentionally focused on designing key compound characteristics to enable flexible, safe, and timely dosing adjustments in clinical practice.

But also you could settle kinetics to be best prepared for a potential expansion of our cardiovascular pipeline and the commercialization of CK two seven and four.

The foundation, we built for Omi, Tencent and Cardinal will be leveraged to support the planned product launch for CK, two seven and floor, which will soon follow.

As part of this planning process.

We are engaging and industry benchmarking exercises to understand best practices to optimize our approach to franchise debarment and especially in a post pandemic world.

Stuart Kupfer: We now look forward to results from both Cohorts 1 and 2 of Redwood HCM, which will elucidate how these next-generation physiochemical properties of CK274 may

Executing on our commercial strategies and plans May result, and are incurring significant additional expenses that were not included in our current financial guidance.

We expect that some or all of those potential expenses could be covered by our accessing additional capital through strategic partnerships with near term cash infusions or by equity and or debt financing if deemed appropriate.

Robert C. Wong: May translate into important clinical effects in patients with obstructive HCM. And with that, I'll turn it over to Robert Wong, who will provide an update on our finances.

Robert C. Wong: Thanks, Stuart. I'll first provide an update on cash, revenue, and spending. And then Ching will review our financial outlook and corporate development strategies for the future. More details on our actual results for the first quarter of 2021 are included in the press release, which we released earlier this afternoon. We ended the first quarter with approximately $460 million in cash and investments.

Finally.

As we have previously discussed we are advancing a twofold corporate development strategy in 2021 firstly.

To seek a development and commercialization partner for all intents and Mokobo and CK two some floor in complementary geographies to that where we intended to go to market and ourselves.

For those additional geographies. We are currently engaged in potential partnering discussions in Japan and Europe.

Secondly.

To seek potential royalty monetization and or structure financing deals in order to support the commercial launch of Omi Kingdom mccarville.

Robert C. Wong: Our revenues in Q1 2021 came primarily from our strategic alliances with Amgen and Estelle. Our first quarter 2021 R&D expenses increased to $31.6 million from $21.7 million in the first quarter of 2020, primarily due to increases in spending on our skeletal muscle programs and clinical development activities for our cardiac myosin inhibitor program. More than 50% of our R&D expenses were attributable to our cardiovascular programs, as expected, given activity for meteoric HF and the cardiac myosin inhibitor program, and the remainder of our expenses were attributable to our skeletal and early research activities. Our first quarter 2021 G&A expenses were $15.6 million, up from $12.4 million in Q1 2020 due to higher personnel-related costs, including stock-based compensation, and higher commercial readiness. Now Thanks, Robert.

CK 2004.

During the first quarter.

We've had encouraging and productive interactions with potential partners to advance this strategy and we look forward to continuing those discussions as May result in a deal or deals in the second half of the year.

Subtle kinetics has always gain access to capital through a diverse array of transaction types and we continue to believe that our path to commercialization will be served by our continuing monetization of our leadership and muscle pharmacology.

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

Thank you Ching.

Before I provide an update on our expected milestones for the remainder of the year.

I'd like to take a moment to remind you of the landscape upon which subtle kinetics as operating especially as it relates to the overall clinical and economic burden of cardiovascular disease today.

Despite COVID-19, taking well over 500000 American lives cardiovascular disease remains the leading killer of Americans, taking even more lives over the same timeframe.

Clearly.

The impact of cardiovascular disease to patients caregivers and our health care system remains unacceptable.

We're gratified to be and are positioned to have the opportunity to make a meaningful impact with novel mechanism therapies that work. Unlike other available therapies and as may benefit millions of patients with various forms of heart failure.

Ching W. Jaw: As we ended the first quarter with approximately $460 million in cash, we look to our financial guidance for 2021 and believe we have over two years of forward cash runway. We have also indicated that we may revise financial guidance based on finalizing commercial planning activities related to omicantin carbyl and a potential product launch in 2022. During the quarter, we delved deeply into commercial planning and are developing a comprehensive go-to-market strategy, which will be presented to our board to gain alignment on the overall approach and investment requirements. The strategy comprises key elements, such as market assessment, brand strategy, market access, Commercial Organizational Structure, Customer Facing and Digital Engagement Strategies, Supply Chain, Information Systems, and Projected Sales, Spending, and Return on Investment.

Phase III trials have demonstrated that modulating cardiac myosin either by its activation or inhibition can translate into clinically meaningful effects on highly relevant registration endpoints and we're pleased to have pioneered the biopharmaceutical.

<unk> sciences directed to cardiac muscle and we're excited to be preparing for commercialization activities and the same comprehensive and expert way and which we are defining and entirely new cardiovascular pharmacology.

Ching W. Jaw: As we advance these strategies in support of the potential launch of omicans and macarons, we are focusing on the most efficient and high yield investments to enable the commercialization of omicans and macarons in 2022, but also equipping cytokinetics to be best prepared for potential expansion of our cardiovascular pipeline and the commercialization of CK274. The foundation we built for Omicantin Carbol will be leveraged to support the planned product launch for CK274, which will soon follow.

Ching W. Jaw: As part of this planning process, we are engaging in industry benchmarking exercises to understand best practices to optimize our approach to franchise development, especially in a post-pandemic world. Experiencing on our commercial strategies and plans may result in our incurring significant additional expenses that are not included in our current financial guidance. We expect that some or all of those potential expenses could be covered by our accessing additional capital through strategic partnerships, with near-term cash infusions, or by equity and or debt financing if deemed appropriate. Finally,

Close in mind as we are intent to capitalize on our franchise approach to our business much like we prioritized our portfolio approach to our focus to muscle biology.

I want to emphasize the high degree of overlap and high volume centers that specialize in both heart failure and HCM, both geographically as well as institutionally the investments, we're making and sales and marketing infrastructure to support the potential commercialization of <unk>.

Ching W. Jaw: As we have previously discussed, we are advancing a two-fold corporate development strategy in 2021. Firstly, to become a CK Development and Commercialization Partner for Omicantin-McCarville and CK274 in complementary geographies to that where we intend to go to market ourselves for those additional geographies.

We will be amortized over time and set the table for advancement and potential commercialization of CK 274, and other words, the economies of scale and the synergies we've seen and R&D over many years. It's autokinetic should also serve us well from a commercial standpoint.

As we expect to build a cardiovascular drug franchise established on sustainable and growing revenues.

Ching W. Jaw: We are currently engaged in potential partnering discussions in Japan and Europe. Secondly, to seek potential royalty monetization and or structure financing deals in order to support the commercial launch of Omicantum Carbo and CK274 during the first quarter.

While our priorities in 2021 are clearly focused on our cardiovascular programs.

We're also mindful that we need to continue to prepare for courage AOS the phase III clinical trial of <unk> in patients with ALS.

AOS is another major area of high unmet need for patients and we maintain our commitment to opening this trial to potential enrollment once we have clarity on our go to market strategy with <unk> and progression of CK $2, seven and four to phase III.

Ching W. Jaw: We've had encouraging and productive interactions with potential partners to advance this strategy, and we look forward to continuing those discussions, which may result in a deal or deals in the second half of the year. Cytokinetics has always gained access to capital through a diverse array of transaction types. And we continue to believe that our path to commercialization will be served by our continuing modernization of our leadership in muscle pharmacology. And with that, I'll turn the call back over to Robert Blum. Thank you. Thank you, Ching.

During the quarter, we initiated clinical trial startup activities, including regulatory and institutional review boards submissions for courage AOS and.

<unk> for the potential start of the trial and the second half of the year.

In summary, as we round out the second quarter of 2021, we remain enthusiastic about our prospects across the pipeline and our transformation to a fully integrated biopharmaceutical company. The second half of the year has us turning over several cards, it's subtle genetics most notably.

Robert I. Blum: Before I provide an update on our expected milestones for the remainder of the year, I'd like to take a moment to remind you of the landscape upon which cytokinetics is operating, especially as it relates to the overall clinical and economic burden of cardiovascular disease today. Despite COVID taking well over 500,000 American lives, cardiovascular disease remains the leading killer of Americans, taking even more lives over the same time frame.

And the upcoming results from Redwood HCM and the potential regulatory advancement of OMA <unk> and mccarville.

And with what we believe could be amongst the most promising cardiovascular pipelines, we're taking strides to realize our mission of bringing potential medicines to people living with cardiovascular diseases of impaired muscle function and that may improve their health span.

Robert I. Blum: The impact of cardiovascular disease on patients, caregivers, and our health care system remains unacceptable. We're gratified to be in a position to have the opportunity to make a meaningful impact with novel mechanism therapies that work unlike other available therapies and may benefit millions of patients with various forms of heart failure. Phase 3 trials have demonstrated that modulating cardiac myosin, either by its activation or its inhibition, can translate into clinically meaningful effects on highly relevant registrations. We're pleased to have pioneered the biopharmaceutical sciences directed to cardiac muscle, and we're excited to be preparing for commercialization activities in the same comprehensive and expert way in which we're defining an entirely new cardiovascular pharmacology.

At the same time ingenuity and innovation remain a core focus of our research activities, which are also a key component of our vision 2025, and the next few years to remind you we expect to double our development pipeline to 10 therapeutic programs as well as to expand our <unk>.

Discovery platform from the bio machinery of muscle contractility to muscle energetics growth and metabolism. We're.

We're making good progress already and expect to select up to two more development compounds over the next year across our cardiac and skeletal programs to enter IND, enabling studies and we look forward to elaborating on these promising R&D programs and our future calls.

Robert I. Blum: As you've heard, it's been a productive quarter, and we're energized by the transformation taking place at the company as we advance plans for a first potential FDA approval and commercial launch, which we believe will set the table for achievement of our Vision 2025, one goal of which is to secure two to three approvals for our potential medicines over the next few years. Ching reviewed components and work streams related to our go-to-market strategy in support of the commercialization of Omicamptive McCarble.

Now, let me recap our expected milestones for 2021 for <unk>, we expect to meet with the FDA and this second quarter to continue discussions related to our goal of an NDA submission and the second half of 2021.

We expect randomization of patients with heart failure, and meteoric H F to be completed in the second quarter of 2021, and we expect to refine our go to market strategy and our potential commercial launch plans and the second quarter of 2021 and through the remainder of this year.

Robert I. Blum: During the quarter, we continued to conduct market research with physicians and payers to refine our target product profile and our understanding of patient journeys and treatment patterns related to the severe heart failure patient who may benefit most from treatment with Omecamptin-McCarbol. We also began in earnest to lay down the design strategy for our commercial organization and our potential launch of Omicamptin-McCarbol.

For CK, two seven and four we expect to announce results from cohorts, one and two and Redwood HCM by mid year 2021, we plan to engage regulatory authorities regarding our phase III trial and development program and this second quarter and also continuing into the second half.

2021, and we expect to begin a potential phase III clinical trial of CK, two seven and four by the end of 2021.

Robert I. Blum: These activities had begun under our collaboration with Amgen and now are being refined with that collaboration coming to an end later this month. As we develop the structure and customer engagement strategy for Omicampta McCarble, we're keeping CK274 close in mind as we are intent to capitalize on a franchise approach to our business, much like we prioritized a portfolio approach to our focus on muscle biology. I want to emphasize the high degree of overlap in high-volume centers that specialize in both heart failure and HCM, both geographically as well as institutionally.

Sorel deceptive, we expect to continue conducting startup activities for courage AOS and we may open the trial to enrollment and second half 2021, again subject to our plans relating to advancing <unk> towards commercialization and CK 207, and four two.

A potential phase III clinical trial and patients with obstructive HCM and.

And for our ongoing research and we expect to advanced programs and conduct IND, enabling studies to potentially advanced 1% to two potential drug candidates in development in 2022 opt.

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

Robert I. Blum: The investments we're making in sales and marketing infrastructure to support the potential commercialization of Omicamptomicarbol will be amortized over time and set the table for the advancement and potential commercialization of CK274. In other words, the economies of scale and the synergies we've seen in R&D over many years at Cytokinetics should also serve us well from a commercial standpoint as we expect to build a cardiovascular drug franchise established on sustainable and growing revenue. While our priorities in 2021 are clearly focused on our cardiovascular program,

Ladies and gentlemen, just as a reminder, if you'd like to ask a question. Please press star and then and number one on your telephone keypad. Once again that is star and the number one.

Your first question comes from the line of Manuela and Chatty with H C. Wainwright.

Hello, Juan Manuel and good.

Good afternoon, guys and thank you for taking my question.

Congratulations on the gas and oil program.

Discussion will be FDA and Mccann.

Feedback going as expected and could you.

You think provide more color on what elements were discussed with the FDA and what still needs to be discussed before and Jason.

Mission.

Sure I'm not sure we're going to be able to do more than that which we already mentioned on this call, but perhaps in summary.

Robert I. Blum: We're also mindful that we need to continue to prepare for COURAGE-ALS, the Phase 3 clinical trial of rel-deceptive in patients with ALS. ALS is another major area of high unmet need for patients, and we maintain an commitment to opening this trial to potential enrollment once we have clarity on our go-to-market strategy with Omicamptomacarbal and progression of CK274 to Phase III. During the quarter, we initiated clinical trial startup activities, including regulatory and Institutional Review Board submissions for COURAGE-ALS, in preparation for the potential start of the trial in the second half of the year.

I'll say that the first meeting.

Specifically intended to.

Understand if galactic H F by itself without any other phase III clinical trial could stand alone and support of an NDA filing and we ask questions that had discussion and we believe coming out of that call that we got the answer that we were looking for which is that we can pursue.

<unk> this way.

And to file an NDA based.

Based on Galactic by itself.

But thats just the beginning of a series of FDA interactions that we had intended and with that I'll turn it over to Saudi to speak about some of the things we expect to be discussing in other FDA interactions, including and upcoming type C meeting.

Robert I. Blum: In summary, as we round out the second quarter of 2021, we remain enthusiastic about our prospects across the pipeline and our transformation to a fully integrated biopharmaceutical company. The second half of the year has us turning over several cards at Cytokinetics, most notably the upcoming results of Redwood HCM and the potential regulatory advancement of Omecampton macarbonate. With what we believe could be amongst the most promising cardiovascular pipelines, we're taking strides to realize our mission of bringing potential medicines to people living with cardiovascular diseases of impaired muscle function that may improve their health. At the same time, ingenuity and innovation remain a core focus of our research activities, which are also a key component of our Vision 2025.

Yes.

Maybe just tackle that at a high level I think there are many aspects of filing and NDA.

To try to get FDA input on before you go ahead and file the NDA in terms of.

Approaching labeling in terms of approaches too.

And dosing and other things that we.

We'll examine with them in terms of.

Net program.

That way, we can put together a filing that I think helps to align.

And what their feedback might be with our objectives.

Finally, there are a number of technical matters that one assets settle with them in terms of.

Data standards and.

Other aspects of the program is one submits a filing an NDA.

NDA filing and.

Robert I. Blum: In the next few years, to remind you, we expect to double our development pipeline to 10 therapeutic programs, as well as to expand our discovery platform from the biomachinery of muscle contractility to muscle energetics, growth, and metabolism. We're making good progress already and expect to select up to two more development compounds over the next year across our cardiac and skeletal programs to enter IND-enabling studies. And we look forward to elaborating on these promising R&D programs in our future calls. Now, let me recap our expected milestones for 2021.

Large undertaking and there are many details, which sometimes it helps to align on before you submit the documentation so that youre not having to sort through those things later.

Got it got it. Thank you that's very helpful and.

And this will go back to <unk>.

And can you help us maybe frame.

Yes.

And what's the specific any farquhar dawn, especially when comfortable and potential comparable sales.

And with how thing that telecom from.

Sure. So again I'll start and then turn it over to Saudi and Stuart.

As you know we already reported on interim results from cohort one we did that back at the end of last year, we had some pretty high expectations going into that and I think admittedly we believe that.

Robert I. Blum: For Omicamp to McCarble, we expect to meet with the FDA in this second quarter to continue discussions related to our goal of an NDA submission in the second half of 2021. We expect randomization of patients with heart failure in meteoric HF to be completed in the second quarter of 2021, and we expect to refine our go-to-market strategy and our potential commercial launch plans in the second quarter of 2021 and through the remainder of this year.

The interim cohort one data exceeded those expectations and that a majority of patients achieved clinically meaningful responses at the low end of the planned dose response curve and we did not have.

Any of those patients.

Have <unk> fall below 50%, so we see that as auguring well for the completion of the study both cohorts one and cohort two.

And as we are now completed with enrollment in cohort two.

We'll be proceeding towards the database lock and the readout of those results but.

Robert I. Blum: For CK274, we expect to announce results from cohorts 1 and 2 in Redwood HCM by mid-year 2021. We plan to engage regulatory authorities regarding our phase 3 trial and development program in this second quarter and also into the second half of 2021. And we expect to begin a potential phase 3 clinical trial of CK274 by the end of 2021. For RelDeceptive, we expect to continue conducting startup activities for Courage ALS, and we may open the trial to enrollment in the second half of 2021, again, subject to our plans relating to advancing Omicamptin-McCarbol towards commercialization and CK274 to a potential Phase III clinical trial in patients with

But as far as how that compares to another compound.

Keep in mind. Please that we're running a different study we're not doing a head to head comparison. We are however, looking at what we think are real world.

Practice Pat.

Robert I. Blum: And for our ongoing research, we expect to advance programs and conduct IND-enabling studies to potentially advance one to two potential drug candidates in development in 2022. Operator. With that, we can now open the call to questions, please.

Operator: Ladies and gentlemen, just as a reminder, if you'd like to ask a question, please press star and then the number one on your telephone keypad. Once again, that is star and the number one. Your first question comes from a line from Emanuela Branchetti with HC Wainwright.

And the and broadening from the third core and in fact with HCM.

HCM and.

And the beginning of this course and boys at auction.

Emanuela Branchetti: Thank you for taking my questions. Congratulations on the progress on all programs. You mentioned the discussion with the FDA on how the counties are going as expected. Could you please provide more color on what elements were discussed with the FDA and what still needs to be discussed before NDA submission?

And if I remember correctly.

Could you elaborate from the rationale behind combining CK 274 with disappeared and wide.

I'll turn that over to Saudi or Stuart whoever wants to answer that.

Alright, and wants to take that question from me.

Alright, so the rationale.

Robert I. Blum: Sure. I'm not sure we're going to be able to do more than that which we already mentioned on this call, but perhaps, in summary, I'll say that the first meeting was specifically intended to understand if Galactic HF, by itself, without any other Phase III clinical trial, could stand alone in support of an NDA filing. And we asked questions and had discussion, and we believe coming out of that call that we got the answer that we were looking for, which is that we can proceed this way, readying to file an NDA based on Galactic by itself.

And as we've noted as debt.

And <unk> patients.

And with more advanced.

Symptomatic obstructive HCM or sometimes treated.

With Disopyramide.

And which can.

Reduced cardiac contractility to some extent, but.

If there are patients.

And it being treated with some of the standard therapy, including guidance per month.

Who still are suffering.

From symptoms related to HCA and they could benefit.

From a drug like CK, two seven and for which of course is specifically designed to inhibit <unk>.

Robert I. Blum: But that's just the beginning of a series of FDA interactions that we had intended. And with that, I'll turn it over to Fady to speak about some of the things we expect to be discussing in other FDA interactions, including an upcoming type C meeting. Yeah, I'll maybe just tackle that at a high level.

Reduced cardiac contractility.

Hum.

The debt.

There there really is a potential advantage here for patients with.

And what sort of run out of options.

To speak and are.

Further along and and.

Natural history of the disease.

Fady Ibraham Malik: I think, you know, there are many aspects of filing an NDA to try to get FDA input on before you go ahead and file the NDA in terms of approaching labeling in terms of approaches to Dosing and other things that we will examine with them in terms of the program. That way, we can put together a filing that I think helps align what their feedback might be with our objectives. Finally, there are a number of technical matters that one has to settle with them in terms of data standards and other aspects of the program as one submits a filing. NDA filing is a very large undertaking, and there are many details which sometimes it helps to agree on before you submit the documentation so that you're not having to sort through those things later.

In terms of their disease severity, they they could benefit from another medical intervention.

Such a secret to seven four and that's so that's really our objective to explore them.

And that more severe patient population.

By adding to Disopyramide treated patient.

Got it thank you for that and.

It's simple items.

From a low ball would you expect to and it means both as the Thai and advances cut off before.

Yeah.

Okay.

I'm, sorry, Stuart could you take that.

Right well the.

I'm sorry, if I understood. The question was about releasing data for cohort three was ethical and yeah, yeah, what's the timeline for that.

Well the the well let me say first of all.

The the the results from cohort one and two.

And essentially you're willing to form our planning for phase III. So I just wanted to be very clear that.

Those are the cohorts that are focused on our dose finding and.

unknown: Got it, got it. Thank you, that's very helpful. And switching over to Redwood HCM, can you help us maybe frame the expectation around the upcoming data? What should we specifically focus on, especially when considering potential comparisons with phase two data obtained with Bava Camtas?

<unk> objectives.

And that will.

Potentially feed into our phase II trial design and we plan to start that study by the end of the year.

Cohort the conduct of cohort three or the start of phase III is not contingent on completion of cohort three and.

So having said that the we will release the results of essentially when we and we get to the point of completing.

Robert I. Blum: Sure, so again, I'll start and then turn it over to Fady and Stuart. As you know, we already reported on interim results from Cohort 1. We did that back at the end of last year.

And completing that cohort.

And it will be likely later in the year, but again, it's it's a we don't have a specific you know meeting or timeline at the moment and again, it's not tied to starting.

Robert I. Blum: We had some pretty high expectations going into that, and I think, admittedly, we believe that the interim Cohort 1 data exceeded those expectations in that a majority of patients achieved clinically meaningful responses at the low end of the planned dose response curve. And we did not have any of those patients have their EFs fall below 50%. So we see that as auguring well for the completion of this study, both in Cohorts 1 and Cohort 2.

Our phase III trial.

And most likely this open label extension will be generating data for a while and will be periodically reporting on its progress.

Got it thank you very much.

Thank you.

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

Hey, Charles.

Hey, Robert and team Thanks for taking our question and congrats and afford progress, they're telling me captive.

Robert I. Blum: And as we have now completed enrollment in Cohort 2, we'll be proceeding towards the database lock and the readout of those results. But as far as how that compares to another compound, you know, keep in mind, please, that we're running a different study. We're not doing a head-to-head comparison. We are, however, looking at what we think are real-world practice patterns here in this trial on top of background therapy compared to placebo, where we think this can best inform phase three. And with that, I'll turn it over to Fady and Stuart.

Very good productivity this quarter and wanted to ask you question about that recent FDA meeting.

Know that you probably can't give us details, but I'm just wondering first of all if you've received the meeting minutes, yet and secondly.

Do you feel like the FTA was most compelled by the efficacy and we've seen or by the identification of the high burden and relatively underserved patient population likely both but.

Fady Ibraham Malik: I think Robert covered most of it. I think I'll just be brief in that we were quite pleased with the cohort 1 results. I think, as we've said, the majority of the patients in that cohort reached the target of where we would stop escalating drug therapy, but not everybody. And that was why we embarked on cohort 2 to study somewhat higher doses and see if we could ensure that we had covered the top of the dose range.

And where do you think their real interest Smith.

So good question, firstly with regard to the minutes yes.

And we have received them.

With regard to your second question I don't think I can speak for F. D. A.

But I think as you know.

With a program that comprises over 30 clinical trials and our phase III pivotal trial that has over 8000 patients and 35 countries, it's a rather robust dataset that.

Fady Ibraham Malik: So the data from cohort one and two will, you know, inform the starting dose and, obviously, the top dose as well. And we'll report those data in July. But, you know, I think the most important data are the effect of the drug on the left ventricular outflow track gradient, the timing of its reduction, and the extent of its reduction. And all of those things should be pretty well laid out for you all when we report the data in the middle of the year.

We have generated in connection with Omi capped and mccarville over 15 years.

And I don't think the FDA is newly realizing the unmet need and heart failure, and you've seen how they've been leaning forward and connection with approvals and that space.

Albeit not medicines that directly impact cardiac muscle.

And I think.

Well I can't speak for F. D. A we have had many many many listening sessions with opinion leaders.

And the Galactic results have been provided.

unknown: And in regards to the enrollment of the third cohort in Redwood HCM, the beginning of this cohort was optional, if I remember correctly. Could you elaborate on the rationale behind combining CK274 with disopyramide?

And.

There is a very consistent theme running across those conversations which is this is.

And opportunity that we've been looking for in connection with.

unknown: I'll turn that over to Fady or Stuart, whoever wants to answer that. Stuart, why don't you take that question?

And the new mechanism therapy that binds directly to cardiac muscle enhances cardiac function improves cardiac performance and can do so safely without risk of arrhythmia is heart rate and where blood pressure and renal function are not compromised.

Stuart Kupfer: Right, so the rationale is, as we've noted, that patients with more advanced symptomatic obstructive ACM are sometimes treated with disopiramide, which can reduce cardiac contractility.

unknown: www.cdc.gov.au who still are suffering from symptoms related to HCM. They could benefit from a drug like CK 274, which, of course, is specifically designed to inhibit, you know, reduced cardiac contractility. So, there really is a potential advantage here for patients who have sort of run out of options, so to speak, and are further along in the natural history of the disease in terms

So that's what we believe <unk> represents.

And could be complementary to standard of care and keep in mind. The results, we saw and Galactic we're on top of standard of care and we believe that.

That speaks to and opportunity set for only kept from a carnival and we discussed that with FDA and we were pleased with the feedback I hope that answers your question.

Yeah, absolutely. So it's kind of the entire and can stop but it does seem like a day certainly considered the differentiated mechanism of action and potentially target product profile.

unknown: https://www.kenhub.com

unknown: That's really our objective, to explore that more severe patient population by adding to Disappear My Treated Patients.

I think it's important that you know the FDA has been involved and a lot of.

Public meetings with academics and Biopharma.

Cardiovascular heart failure researchers and.

And trying to advance the field you saw you know a couple of years ago, our guidance came out to reiterate their position on what approve ability for drugs and heart failure and looks like.

unknown: Got it. Thank you for that. And since the army's an open label, would you expect to release data as the trial advances, perhaps before all patients are done?

unknown: I'm sorry, Stuart, can you take that? Right. Well, the question, as I understood it, was about releasing data for cohort three. Was that the question?

And that you see many senior members of the FDA involved in these and <unk>.

These meetings and I.

I think that just reflects on a recognition that there is a tremendous unmet need here. Despite the fact that we have existing therapies and.

unknown: Well, let me say first of all that the results from Cohort 1 and 2 essentially will inform our planning for Phase 3. So I just want to make it very clear that those are the cohorts that are focused on our dose-finding objectives. So that will... We plan to start that study by the end of the year. The conduct of cohort 3 or the start of phase 3 is not contingent on completion of cohort 3.

You can just even look at the event rates from Galactic.

And there they exceed 30% and even higher than that and some sub population. So.

Still a tremendous need despite the therapies that we have.

And it makes sense I know there'll be a lot of questions on <unk>.

Seven and four from other analysts so I'll leave that to them, but I wanted to ask you about courage, Alan you mentioned being in a position to start that phase III.

unknown: So having said that, we will release the results essentially when we get to the point of completing that cohort. It will be likely later in the year. But again, we don't have a specific meeting or timeline at the moment. And again, it's not tied to starting.

Once you nailed down and only captive and go to market and and then potential moving to seven four into phase three and I guess I'm kind of wondering.

What are the trigger points with regard to encourage AOS. If you can if you can share them with us that you are waiting for it and be able to operationalize that net study.

Stuart Kupfer: Our phase three trial. Yeah, most likely, this open-label extension will be generating data for a while, and we will be periodically reporting on its progress.

Sure. Good question. So firstly as you may recall, we presented the design for courage AOS.

unknown: Got it, thank you very much. Thank you.

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

Last year and.

Charles Cliff Duncan: Hey, Robert, and team. Thanks for taking our call.

And we've also commented on additional secondary analyses.

Charles Cliff Duncan: Our question and congrats on the forward progress with Omicamptive.

Lead and support for ways, we think we can and rich the response seen in fortitude AOS and <unk>.

Charles Cliff Duncan: Very good productivity this quarter. I wanted to ask you a question about that recent FDA meeting. I know that you probably can't give us any details, but I'm

Designed into that phase III trial courage, AOS and we've also announced that.

Charles Cliff Duncan: I'm just wondering, first of all, if you've received the meeting minutes yet.

Astellas has agreed to provide co funding of courage AOS and <unk>.

And connection with their receipt of a low single digit royalty on sales and certain countries. We've also announced that courage.

Robert I. Blum: Do you feel like the FDA was most compelled by the efficacy that was seen or by the identification of the high burden and relatively underserved patient population? Probably both, but where do you think their real interest was? So, good question.

<unk> is designed with interim analyses so that we can see if it is.

Affirming the kind of activity that we designed and powered the study for based on what we saw and phase two so we took certain.

Robert I. Blum: Firstly, with regard to the minutes, yes, and we have received them. With regard to your second question, I don't think I can speak for FDA, but I think, as you know, with a program that comprises over 30 clinical trials and a phase three pivotal trial that involves over 8,000 patients in 35 countries. It's a rather robust data set that we have generated in connection with Omicamptomocarbal over 15 years. I don't think the FDA is just now realizing the unmet need in heart failure, and you've seen how they've been leaning forward in connection with approvals in that space.

Steps to ready for the potential start of courage AOS.

But we're a small company and we have to maintain priority and focus. So we wanted to make certain that we understood what would be the path forward for <unk> and CK, two seven and four.

Before we commit to operationalize encourage AOS and we laid out a couple of objectives or milestones. Firstly, we wanted to see the galactic results. We've seen them. We wanted to understand if they could support an NDA filing and we believe that we have that feedback and that they do and we.

We expect to file in second half of the year, but we also want to understand the go to market strategy and how that can.

Robert I. Blum: All be it not medicines that directly impact cardiac muscle. And I think, while I can't speak for FDA, we have had many, many, many listening sessions with opinion leaders since the Galactic results were provided. There is a very consistent theme running across those conversations, which is, this is an opportunity that we've been looking for in connection with new mechanism therapy that binds directly to cardiac muscle, enhances cardiac function, improves cardiac performance, and can do so safely without risk of arrhythmias, heart rate, and where blood pressure and renal function are not compromised.

Return on investment the timelines the expenses and the activities and make certain that we've got our arms around that and where and the process of making that happen. We also wanted to understand CK, two seven and four and what could be its path to phase three.

So that's partly answered by the fact that we've seen interim data from cohort, one and we're engaging regulatory authorities and we are.

Preparing for potential phase III later, this year, but we haven't seen enough yet from Redwood and order to be committal to courage AOS.

Robert I. Blum: So, that's what we believe Omicamptomacarbal represents, as something that could be complementary to standard of care, and keep in mind, the results we saw in Galactic were on top of standard of care. And we believe that that speaks to an opportunity set for Omicampt of McCarble, and we discussed that with FDA, and we were pleased with the feedback. I hope that answers your question.

We want to see those data in order to be able to be and the best position to know that CK $2 seven and four has a path forward to phase III and that can be moving forward potentially in parallel with rail dissented.

Encourage AOS in phase III.

Imagine that will then be a company with a profile and we camped or going to market potentially in 2022 and two programs one from each of our verticals in phase three and 2022, we like that complexion, and we think that's in the interest of shareholders and and the interest of our science.

Charles Cliff Duncan: Yeah, absolutely. So it's kind of the entire gestalt.

Robert I. Blum: The entire Gestalt, but it does seem like they certainly consider the differentiated mechanism of action and potentially target product profile. I think it's important that, you know, the FDA has been involved in a lot of public meetings with academics and biopharmaceutical heart failure researchers and trying to advance the field. You know, a couple of years ago, guidance came out to reiterate their position on what approvability for drugs and heart failure looks like.

That's what we've been building towards and if Theres anything that we've learned from the course of over 20 years that sort of kinetics is that theres always advantage to having one up next.

Program up is and the interest of building a sustainable and durable company managing a portfolio enables us to build a franchise.

<unk>, both cardiac and skeletal muscle so we're not there yet with courage AOS, we still have to turnover a few cards, but we're getting there in the meantime, we've been conducting startup activities and getting mobilized and I hope that helps.

Robert I. Blum: You see, you know, many senior members of the FDA involved in these meetings, and I think that just reflects the recognition that there's tremendous unmet need here, despite the fact that we have existing therapies. You can even look at the event rates in Galactic; they exceed 30% and even higher than that in some subpopulations, still a tremendous need despite the therapies that we have.

That does help Robert Thank you for the thoughtful.

And Sir and strategy and appreciate you taking our questions.

Sure thing.

Your next question comes from the line of Salim Syed with Mizuho.

Hello, it's really great.

Hey, Robert Hey, guys. Thanks for all the color and congrats on the progress.

Just a couple from me if I can.

Charles Cliff Duncan: Yeah, that makes sense. I know there'll be a lot of questions on 274 from other analysts, so I'll leave that to them. But I wanted to ask you about COURAGE-ALS. You mentioned being in a position to start that phase 3. Once you nail down Omicamptive, go to market, and then potentially move 274 into Phase 3. And I guess I'm kind of wondering, what are the trigger points with regard to COURAGE-ALS, if you can, if you can share them with us that you're waiting for to be able to operationalize that, that study. Sure.

Fatty did I hear you right that did you think were getting the data from Redwood and July.

I think I said mid year and July to mid year.

It is but I thought you mentioned the month is that I just want make sure I did.

Didn't Mishear, Inc.

I might have mentioned the month I think we expect that data given the completion of enrollment and the completion of.

And anticipated study duration and thanks for it to readout sometime in July.

And given that.

We still havent locked the database, we still are conducting the study.

I've senior notes and you've made certain calculations and projections on timing what I can say is that.

Robert I. Blum: Sure, good question. First of all, as you may recall, we presented the design for CourageALS late last year. And we've also commented on additional secondary analyses that lend support for ways we think we can enrich the response seen in Fortitude ALS as designed into that phase three trial, Courage ALS. We've also announced that Astellas has agreed to provide co-funding of Courage ALS in connection with their receipt of a low single-digit royalty on sales in certain countries.

We're looking to mid year, and that's still to be determined based on things still to happen.

Okay got it.

To clarify and that though I mean, if you guys had finished enrollment for cohort two.

In February I believe and things you guys announced that on the 25th specifically.

Why wouldn't you be able to lock the database.

Two weeks from post the 10 treatment duration zone at the <unk>.

Echo why wouldn't you be able to lock. It then for cohort two and present the data earlier in the Senate curiosity.

Robert I. Blum: We've also announced that Courage ALS is designed with interim analysis, so that we can see if it is, confirming the kind of activity that we designed and powered the study for based on what we saw in phase two. So we took certain steps to prepare for the potential start of COURAGE-ALS. But we're a small company, and we have to maintain priority and focus.

So theres actually a four week period. After we turn so there's a two week echo at week 12, and then Theres a two week follow up a week 14.

You know Theres a period of time when all of the echoes has to be centrally read and adjudicated and the data needs to be cleaned and all that sort of stuff. So.

The timeline is something that requires.

And and includes database lock and core lab activities and so forth.

Robert I. Blum: So we wanted to make certain that we understood what the path forward for Omicamptomecarbol and CK274 is before we commit to operationalizing Courage ALS, and we laid out a couple of objectives or milestones. Firstly, we wanted to see the galactic results. We've seen them.

Okay got it and then just secondly.

And you guys are just starting to discuss the phase III for CK 274, and I'm just wondering.

And you guys are planning to.

Do this with <unk> on the market.

And it's a pretty efficient in January and 2022.

Robert I. Blum: We wanted to understand if they could support an NDA filing, and we believe that we have that feedback and that they can. And we expect to file in the second half of the year.

Are you guys contemplating the head to head versus <unk> or.

Or how are you guys exactly you're thinking about this with another eight CMS and <unk>.

And on the market and early part of 'twenty two.

Robert I. Blum: But we also want to understand the go-to-market strategy and how that can return on investment, The Timelines, the Expenses, and the Activities, and make certain that we've got our arms around that and we're in the process of making that happen. We also wanted to understand CK274 and what its path to Phase 3 could be. So that's partly answered by the fact that we've seen interim data from Cohort 1, and we're engaging regulatory authorities, and we are preparing for potential Phase 3 later this year.

It's a good question, but I don't think it would be reasonable for us to be responding about that from the competitive positioning standpoint, recognizing that there could be a <unk>.

Single pivotal trial, there could be more than one we're ultimately going to be.

Deciding how best to position and frame CK 274, and what will be.

A dynamic space.

We do.

Expect BMS should get approval from Maverick camped and in 2022, but we also believe that.

The trial that we expect to conduct at least the phase III trial that we've been focused towards is one that.

Robert I. Blum: But we haven't seen enough yet from Redwood in order to be committal to Courage ALS, so we want to see the data in order to be able to be in the best position to know that CK274 has a path forward to phase 3.

Should enroll well not only in the United States, but outside the United States. Our plan is to make this a global registration program.

So I think it has the potential then to still enroll rapidly even as mavic campton may be approved in 2022 as far as the head to head or anything like that I think it would be premature for us to speak to any of those issues.

Robert I. Blum: And that can be moving forward potentially in parallel with rel-deceptive in Courage ALS in phase 3. Imagine that we'll then be a company with a profile, Omicamptive going to market potentially in 2022, and two programs, one from each of our verticals in phase three, in 2022. We like that complexion; we think that's in the interest of shareholders and in the interest of our science. That's what we've been building towards. And if there's anything that we've learned from the course of over 20 years at cytokinetics, it's that there's always an advantage to having one up. The next program up is in the interest of building a sustainable and durable company. Managing a portfolio enables us to build a franchise across both cardiac and skeletal muscle.

Got it thanks, so much guys.

Thank you.

Your next question comes from the line of Ted <unk> with Piper Sandler.

Hey, Terry and thank you very much hi, guys. How are you and thanks for the thorough update.

And just one question would be with respect to Omi Kimpton cabos hurt by that update and.

One of those sort of and maybe its a little bit early to talk about this but what do you see as sort of the market opportunity based on the results that were reported.

From from clock, but thanks very much.

Robert I. Blum: So we're not there yet with Courage ALS. We still have to turn over a few cards, but we're getting there. In the meantime, we've been conducting startup activities and getting mobilized. I hope that helps. That does help, Robert. Thank you for the thoughtful answer and strategy and appreciate you taking our questions.

Sure Good question I'm going to.

Tackle that but I'll also ask Andrew Who's joined this call to speak about it also at a high level because he brings a different perspective and some of US. It's hydrokinetics. We've been at this for 15 years on <unk> and the clinic and we admittedly are pretty close to the trees, but he can look at this from.

Operator: Your next question comes from the line of Salim Syed with Mizuho.

Forrest viewpoint, as well and given his expertise and specialty care cardiology markets I think it would be helpful. For you to hear from him at least this first time.

Salim Qader Syed: Hello Salim. Hey, hey Robert.

Salim Qader Syed: Hey guys, thanks for all the color and congrats on the progress. Just a couple for me if I can.

Salim Qader Syed: Fady, did I hear you right that we're getting the data for Redwood in July? I think I said mid-year, isn't July mid-year? It is, but I thought you mentioned the month. I just want to make sure I didn't mishear you. I might have mentioned the month.

And I will tell you is that.

There are over 6 million patients today, and the United States with heart failure that number looks to be growing to $8 million to $9 million by 2030, if you consider that roughly half of those have heart failure with reduced ejection fraction and you look at data cuts how many have ejection fractions.

Fady Ibraham Malik: I think we expect the data given the completion of enrollment and the completion of, you know, the anticipated study duration and things for it to read out sometime in July. Given that we still haven't locked the database, we're still conducting the study, I've seen your notes, and you've made certain calculations and projections on timing, what I can say is that we're looking to mid-year, and that's still to be determined based on things still to happen. Okay, I got it.

Below 40 below 35 below 30 below 25, and you can get this from real world evidence.

There are a large number of patients who fit the bill for that which is comparable to how we pre specified in galactic.

Patients above and below the median the median and galactic was 28% ejection fraction at 28%.

There are over 4000 of those patients in galactic and they are.

Salim Qader Syed: Just to clarify on that, though, if you guys had finished enrollment for cohort two, in February, I believe, I think you guys announced that on the 25th, specifically, why wouldn't you be able to lock the database? Two weeks post the week 10 treatment duration, so at the last echo, why wouldn't you be able to lock it then for a cohort too and present the data earlier? Just out of curiosity.

Symbolic if you will of patients with more severe heart failure and other risk factors and we're looking at a combination of these risk factors is defines a patient population, that's and high unmet need of new therapy. Despite.

Standard of care.

Because this is cardiology, you're talking about thousands or tens of thousands, but hundreds of thousands of patients and even over a million such patients and that's where we need to be smart about positioning and knowing where omi captive mccarville.

Salim Qader Syed: Salim, there's actually a four-week period after week 10, so there's a two-week echo at week 12, and then there's a two-week follow-up at week 14. There's a period of time when all the echoes have to be centrally read. Adjudicated, Data need to be cleaned, and all that sort of stuff, so, you know, the timeline is something that requires, includes, you know, database lock, and core lab activities and so forth.

May play a role and guideline and directed therapy, but maybe I'll stop there and turn it over to Andrew to provide some of his perspective.

Thank you Robert.

And maybe just to build on what Robert said web and fair.

And we knew the team we've been spending a lot of time on our go to market strategy and.

And given the profile that fatty and Robert described and and add on therapy. We are concluding that there given the unmet need and the net to the profile of him a captive that there are a numerous amount of patients that could benefit from the emerging profile of <unk> and that we could be very successful and.

Salim Qader Syed: Okay, got it. And then just secondly, you guys are starting to discuss phase three for CK274. And I'm just wondering how you guys are planning to do this with Mavicampton on the market. I guess the PDUF is in January 2022. Are you guys contemplating the head-to-head versus NAFA or not? How are you guys exactly thinking about this with another HCM acid?

Commercializing it as well.

And we're currently designing and building what we think is the right size commercial organization and infrastructure that will enable us to focus on care settings, where the majority of heart failure patients and accretive are both both.

Robert I. Blum: Potentially on the market, early part of 22. It's a good question, but I don't think it would be reasonable for us to be responding to that from the competitive positioning standpoint, recognizing that there could be a single pivotal trial, or there could be more than one. We're ultimately going to be deciding how best to position and frame CK274 in what will be a dynamic space. We do expect BMS to get approval for Mavicampton in 2022.

Both community cardiology and hospitals, so getting those cardiologist and those two care settings and activate it on on the campaign for the subset of patients is really what's going to be critical to our success and we feel again rightsize their organization and the right Rois that we felt that it can be successful and this market.

Hello.

Awesome. Thank you guys.

Thank you Ted.

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

Hello, Jeff.

Sure.

And Jeff.

Okay.

Can you hear me.

Yes, we can hear you now, okay, hey, everyone and thanks for taking the question and and welcome Andrew.

Robert I. Blum: But we also believe that the trial that we expect to conduct, at least the phase three trial that we've been focused on, is one that should enroll well not only in the United States but outside the United States. Our plan is to make this a global registration program. So I think it has the potential then to still enroll rapidly, even as Mavicampton may be approved in 2022. As far as a head-to-head or anything like that, I think it'd be premature for us to speak to any of those issues. Got it. Thanks so much, guys.

And so actually this is for Andrew if he's on the line.

And I guess before you joined cytogenetics, what aspects of OMA captive mccargo or black or did you find those compelling and now that you're at the company. What are some of the improvements that you envision for the commercial efforts.

Sure. Thanks for the welcome.

And then the the biggest thing really is the science the focus of the company has on science and mess with the unmet need from a patient point of view really focusing on the muscle biology.

Cardiac myosin inhibitor Hamburger cardio and.

Activators that really massive science and unmet need.

Really the foundation of what I thought was.

Operator: Your next question comes from the line with Ted Tantoff and Piper Sandler.

Great for patients and great for an organization to be successful.

Ted Tantoff: Great, thank you very much. Hi guys, how are you?

Coming to the company and now for a few months.

Ted Tantoff: And thanks for the thorough update. I guess my question would be with respect to Omi Kempton-McCarver. I was encouraged by that update and want to know sort of, and maybe it's a little bit early to talk about this, but what do you see as sort of the market opportunity based on the results that were reported from Galactic? Thanks very much.

I think what we really learned is that you have to make sure that you get access to drugs and you get cardiologists. They really understand the evidence produced by a clinical trial like Galactic HFF and.

Using this evidence really painting a picture for with a clear patient is that can benefit most from that.

And then bringing the organization and the infrastructure in place.

Robert I. Blum: Sure, good question. I'm going to tackle that, but I'll also ask Andrew, who's joined this call, to speak about it at a high level because he brings a different perspective than some of us at Cytokinetics. We've been at this for 15 years with Omicamptomacarbal in the clinic, and we admittedly are pretty close to the trees, but he can look at this from a forest viewpoint as well, and given his expertise in specialty care cardiology markets, I think it'd be helpful for you to hear from him, at least this first time. What I'll tell you is that...

And with the right ROI and the right sizing and structure for a company our size.

Kind of marrying these things together access drug profile, given the evidenced and science and kind of our go to market strategy I think that formula together, we'll certainly make us successful.

Thank you for the question question wasn't directed to me, but we will have an opportunity not only to hear from Andrew but also members of his team as we will have an investor day later this year and we intend to lay out our go to market strategy and significant detail, we're not going to <unk>.

Try to be.

That company that competes on every front, but rather instead, where do we think the mechanistic science the evidence and our ability to achieve a high ROI could district distinguish sutter kinetics in a marketplace with a high unmet need both clinically and economically and.

Robert I. Blum: There are over 6 million patients today in the United States with heart failure, and that number looks to be growing to 8 to 9 million by 2030. If you consider that roughly half of those have heart failure with reduced ejection fraction, and you look at data cuts, how many have ejection fractions below 40, below 35, below 30, below 25, and you can get this from real world evidence. There are a large number of patients who fit the bill for that, which is comparable to how we pre-specified in GALACTIC patients above and below the median. The median in GALACTIC was 28%, and the ejection fraction was 28%.

Don't forget the economic piece of this because as you've already seen and Galactic HFF.

Only captive on top of standard of care translated into significant reductions and hospitalizations and re hospitalizations and those hospitals are having to eat those costs on patients readmitted within 30, and 60 days and there is a very compelling.

The opportunity for a farmer coed gnomic argument here that we think makes a lot of sense to institutions and cardiologists to treat patients in those institutions.

Robert I. Blum: There are over 4,000 of those patients in GALACTIC, and they are symbolic, if you will, of patients with more severe heart failure and other risk factors. And we're looking at a combination of these risk factors as a patient population that's in high unmet need of new therapy despite a standard of care. So, you know, because this is cardiology, you're talking about not thousands or tens of thousands but hundreds of thousands of patients and even over a million such patients.

And more to follow on that but recognizing that when we go forward to hopefully a launch of only captive mccarville will have laid out our rationale for others to also understand.

Great. Thanks.

Thank you.

Your next question comes from the line of Dane Leone with Raymond James.

Good day.

Hi, How's it going and congrats on all the progress.

Just one from me because it's getting a bit late.

And the call the.

Could you maybe just parse out because we've got a lot of questions in terms of what you've disclosed around redwood today with cohort one and vs cohort two.

Robert I. Blum: And that's where we need to be smart about positioning and knowing where Omicamptive McCarble may play a role in guideline-directed therapy. But maybe I'll stop there and turn it over to Andrew to provide some of his perspective.

And then the opening of cohort three which is a paramount.

Is.

Maybe just to stay clearly it is the purpose of the cohort three combination study with and they are paramount to satisfy what.

Andrew Callos: Thanks, Robert. So, you know, maybe just to build on what Robert said, you know, I've been fairly new to the team, and we've been spending a lot of time on our go-to-market strategy. And, Given the profile that Fady and Robert described and an add-on therapy, we conclude that given the unmet need and the match to the profile of OMACAMPTIV, there are a numerous amount of patients that could benefit from the emerging profile of OMACAMPTIV and that we could be very successful in commercializing it as well.

A lot of the clinical community highlight is potentially a deficiency of what was generated with mom and camps and dataset.

Or is there some angle that maybe you can get more efficacy out of the cohort one dosing.

On and combination with desert pyramid that would you know.

<unk> necessity from dosing 274 higher to the doses that were used in cohort two.

Yeah.

That's an interesting way of thinking about it I haven't even thought about it that way.

It very.

Very much as an order to inform the possible inclusion of other patients in phase III, but maybe fatty can speak more to that or Stuart.

Andrew Callos: So, you know, getting those cardiologists in those two care settings activated on omacamta for that subset of patients is really what's going to be critical to our success. And we feel, again, on the right side of their organization and the right ROI, that we certainly can be successful in this market. Thank you, guys. Thank you, Ted.

Yes, I think.

And I can't really speak to you know the whole investigative communities thinking about this other than and these are patients that have not had the opportunity to participate and Ah.

Trials, we're about to conduct a.

Fairly sizeable trial and this area and if there isn't a need to exclude them.

And then why not include them and so I think cohort three is designed to give us the.

And you know the information regarding the safety of combining those two drugs. So that we can do so and and informed manner.

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

Great. Thank you guys.

Thank you.

Your next question comes from the line of Greg Savannah with Goldman Sachs.

Jeff Hung: Jeff, you might be on mute.

Jeff Hung: Here you go. Okay. Well, hey, everyone. Thanks for taking the question and welcome in. So actually, this is for Andrew, if he's on the line. I guess, before you joined Cytokinetics, what aspects of Omacampus, McCarble, or Galactic did you find most compelling? And now that you're at the company, what are some of the improvements that you envision for the commercial efforts?

Hey, Greg. Thank you Hi team. This is Anna on for Greg Just one quick question from US on two seven and four cohort three and the chosen dose doesn't appear to be and slightly lower than the other doses and explore.

And if you could just provide some color on the decision around the doses chosen from cohort three and perhaps if you can give us some color on whats.

Whats the magnitude of the effect size that you're hoping to see with cohort three versus my T stop previously and in cohort one and things.

Andrew Callos: Sure. Thanks for the welcome.

Andrew Callos: I mean, the biggest thing really is the science, the focus the company has on science, and, you know, matching it with the unmet need, from a patient point of view, really focusing on the muscle biology, you know, cardiac myosin inhibitor, cardio myosin activators, that really massive science and unmet need is really the foundation of what I thought was great for patients and great for an organization to be successful. You know, coming to the company now for a few months.

Stewart why don't you go and I'll take that.

Okay.

So the you know that and as we've been discussing disopyramide has some impact on reducing cardiac contractility.

And.

Given that effect.

And we want to.

Essentially evaluate that patient population.

Cautiously and now as a as you might expect and so you know as.

As we.

And described in our December press release, and the interim results of cohort one.

Andrew Callos: I think what we really learned is that you have to make sure that you get access to drugs and that you get cardiologists to really understand the evidence produced by a clinical trial like Galactic HS and, you know, using this evidence, really paint a picture of who the clearest patient is that can benefit most from that. And then bringing the organization and the infrastructure in place, you know, with the right ROI and, you know, the right sizing and structure for a company our size, kind of marrying these things together, the access drug profile, given the evidence and science and kind of our go-to-market strategy.

And we determined that the those a lot of that lower dose range was safe tolerable and.

And.

So it is reasonable to us.

Evaluate their disopyramide treated patients you know using those doses that had already been qualified and so to speak we're known to be safe and well tolerated and.

And then.

And additional point is and just as a just to reinforce the point is that CK two seven and four.

And dosing as individualized for each patient.

Alright, so and based on achieving target gradients and.

Andrew Callos: I think that formula together will certainly make us. I know the question wasn't directed to me, but you'll have an opportunity not only to hear from Andrew but also members of his team, as we'll have an investor day later this year, and we intend to lay out our go-to-market strategy in significant detail.

While maintaining.

Reasonably normal ejection fraction and so.

It could be very well be that some patients.

Dice up here and I will be.

Well controlled achieving they're probably gradients and the lower dose range and.

Still some patients may require higher doses, but.

Robert I. Blum: We're not going to try to be that company that competes on every front, but rather, instead, where do we think the mechanistic science, the evidence, and our ability to achieve a high ROI could distinguish cytokinetics in a marketplace with a high unmet need, both clinically and economically? And don't forget the economic piece of this, because as you've already seen in Galactic HF, Omicamptive, on top of standard of care, translated into significant reductions in hospitalizations and re-hospitalizations.

And the end and we'll learn this and our phase III trial.

And then.

And what what type of the for the most part.

Doses will be required.

Given the full dose range and phase III and these are times that PMI treated patients.

Yeah.

Okay, great. Thanks, so much.

Thank you.

And your last question comes from the line of of cash Tomorrow with Wolfe Research.

So our cash.

Hey, guys. This is Andrew on for cash just had a couple if I can.

First can you kind of talk to us about how much relative reduction and contractility, you guys need to alleviate kind of the outflow gradient and this is something that I believe we're targeting for fairly low on a day dosing per call. It I see 15, or so could you speak to that and then secondly in terms of average.

Robert I. Blum: And those hospitals are having to eat those costs on patients readmitting within 30 and 60 days. And there's a very compelling opportunity for a pharmacoeconomic argument here that we think makes a lot of sense to institutions. So, more to follow on that, but recognizing that when we go forward with, hopefully, a launch of Omicampt and McCarble, we'll have laid out our rationale for others to also understand.

<unk> LD eef drops across the cohorts and across like any dose that you might bring forward. When we look at the average is from the <unk> trials. If you guys are able to dose relatively higher up the dosing curve given the shallower relationship is it fair to say that we could see a slightly high.

Operator: Your next question comes from the line of Dane Leone with Raymond J. Hello, Dane. Hey, how's it going? Congratulations on all the progress.

Dane Vincent Leone: Just one for me because it's getting a bit late on the call. Could you maybe just parse out, because we've got a lot of questions in terms of what you've disclosed around Redwood to date with Cohort 1 versus Cohort 2, and then the opening of Cohort 3 with Disipiramide. Maybe just to state clearly, is the purpose of the Cohort 3 combination study with dizzopyramide to satisfy what a lot of the clinical community highlighted as potentially a deficiency of what was generated with the Mavikampton dataset?

Here average drop and E F and then lastly, while.

No we do.

Don't want to everybody's going to look at the phase II results and trying to pare it back to back and given the design of the trial and the titration scheme is it fair to say that the better comparator is really the explorer trial versus the phase two pioneer thanks.

All good questions I'll turn it over to fatty and fatty and Stuart can probably handle these better than I could.

Dane Vincent Leone: Or is there some angle that maybe you can get more efficacy out of the Cohort 1 doses in combination with dizzopyramide that would preclude the necessity from dosing 274 higher for the doses that were used in Cohort 2? Thank you. That's an interesting way of thinking about it. I hadn't even thought about it that way.

So I'll try and tackle them quickly as we are.

And a shorter on time I think you know in regards to your first question, it's a little bit of and open matter.

Section fraction you need to.

Drop in order to.

Maximize the effect and the gradient and I think it depends on the patient. These patients in general have ejection fractions that are 70, 75%. So they have quite a ways and they are a significant.

Dane Vincent Leone: It is very much in order to inform the possible inclusion of other patients in phase three, but maybe Fady can speak more to that or Stuart. Yeah, I think I can't really speak to the whole investigative community's thinking about this other than that these are patients that have not had the opportunity to participate in trials. We're about to conduct a, you know, fairly sizable trial in this area, and if there isn't a need to exclude them, then why not include them? And so I think cohort three is designed to give us information regarding the safety of combining those two drugs so that we can do so in an informed manner.

Room to move in terms of trying to maximize the effect on the gradient.

But it's kind of sum it up I think we were anticipating.

Drops of five to 15.

Range, depending on the patient and the severity of their their gradient.

I think the second question in terms of.

And remembering third question now, but the second question had to do with.

I want to remind me.

Yeah.

And if the shallower PK PD plays out is it fair to say the average yes.

Could be relatively higher is that suggestive that we could get relatively higher on the dosing curve.

Operator: Your next question comes from the line of Greg Savanova with Goldman Sachs.

Right Yeah, no I think that's a net.

Greg Savanova: Hey Greg, Hi Sean. Hi team, this is Anna for Greg. Just one quick question from us on 274 Cohort 3 and the chosen doses, which appear to be slightly lower than the other doses that have been explored. If you could just provide some color on the decision around the doses chosen for Cohort 3 and perhaps if you could give us some color on, you know, what's the magnitude of the effect size that you're hoping to see.

<unk> observation.

The fall and injection.

345% on average is pretty.

Minimal in terms of again, where these patients start and so you know as I alluded to and the first question. If you can.

Predictably push the dose a bit higher maybe even potentially lower the ejection fraction a bit more and you're still well and the normal range, but you may be able to achieve a greater effect in patients that have.

Anna: And that's what you're hoping to see with Cohort 3 versus what you saw previously in Cohort 1. Thanks.

More severe gradient.

And that's something that will hopefully have some read on when we see the fullness of the data from Redwood eight share.

Stuart Kupfer: Stuart, why don't you go ahead and take... Right, so as you know, we've been discussing, disipiramide has some impact on reducing cardiac contractility.

HCM, rather and then I think and the last question.

The answer is I think the explorer data in some ways.

And the echocardiographic data from explorer, probably a better comparator.

Stuart Kupfer: And, you know, given that effect, we want to essentially evaluate that patient population cautiously, as you might expect.

Redwood HCM.

And in a sense that.

It's a placebo controlled trial patients are on background therapy.

And in their phase III trial, there they had withdrawn patients from background therapy.

Stuart Kupfer: You know, as we, you know, describe.

Stuart Kupfer: and our.

Stuart Kupfer: December Press Release and the Interim Results of Cohort 1

And open label trial I think there are certainly differences between the two trials that really preclude a head to head count.

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Stuart Kupfer: Page PAGE of NUMPAGES www.verbalink.com Page PAGE of NUMPAGES So, you know, it was reasonable to, you know, evaluate the diaspiramide-treated patients using those doses that had already been qualified, so to speak.

We caution people from you know.

We're always trying to draw those comparisons and the absence of understanding the underlying.

Variables, but.

But in essence, I think probably explore would be more relevant to the redwood experience.

Okay.

Thank you.

Thank you.

And there are no further questions at this time.

Okay. It looks like we covered quite a lot of ground here and the presentation and the Q&A. So I'll be brief I want to thank everybody for their attention and for participation.

Stuart Kupfer: But an additional point is, and just as a reminder, just to

Stuart Kupfer: CK274 dosing is individualized for each patient, right so and based on achieving target radiance.

Operator: http://www.cdc.gov.au

And 2021 earnings call.

A lot of good things going on et cetera, kinetics were approaching the remainder of the year with clear I'd focus to execution on getting.

Stuart Kupfer: And we'll learn this in our Phase 3 trial, what type of, for the most part, what sort of doses will be required given the full dose range in Phase 3 in these di-supermitreated patients.

Getting to the results of Redwood HCM and mid year, putting.

Operator: And your last question comes from the line of Akash Tewari with Wolf Research.

Okay and strategy for <unk> and readying to build what we think can be a transformational time that subtle kinetics as we transition to our commercial phase with a potential.

Andrew: Hey guys, this is Andrew on behalf of Akash. I just had a couple if I could. But first, can you kind of talk to us about how much relative reduction in contractility you guys need to alleviate kind of the outflow gradient? This is something that I believe, you know, we're targeting fairly low on a dosing curve, call it IC15 or so. Could you speak to that?

The 22 that is happening at the same time, we're doubling down on research and development, both our research platform expansion and a doubling of our pipeline and clinical research and we hope to be one of those companies that is establishing a franchise business at the <unk>.

Fady Ibraham Malik: And then secondly, like in terms of average LVEF drops across the cohorts and across like any dose that you might bring forward, when we look at, you know, the averages from the Mavikanton trials, if you guys are able to dose relatively higher up the dosing curve, given the shallower relationship, is it fair to say that we could see a slightly higher average drop in EF? And then lastly, while I know, you know, we don't want to, everybody's going to look at these phase two results and try and compare them back to Mavikanton.

Same time, we continue to innovate in science and bring forward, a sustainable pipeline and make for a durable business.

So look forward to keeping you updated on our progress and we look forward to responding to other comments and questions overtime with that operator, we can bring this call to a close.

Ladies and gentlemen, this does conclude today's conference call. We thank you for your participation you may now disconnect.

Fady Ibraham Malik: Given the design of the trial and the titration scheme, is it fair to say that the better comparator is really the Explorer trial versus the phase two Pioneer? Thanks. All good questions. I'll turn it over to Fady, and Fady and Stuart can probably handle these better than I could.

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Fady Ibraham Malik: So I'll try and tackle them quickly as we're getting shorter on time. I think, you know, in regards to your first question, it's a little bit of an open matter as to what... injection fraction you need to drop in order to, you know, maximize the effect on the gradient. I think it depends on the patient. These patients, in general, have ejection fractions that are 70 or 75 percent. So they have quite a ways to go, you know, they have significant... uh... room to move in terms of trying to maximize the effect on the gradient, uh... you know, but it's kind of summed it up. I think we were anticipating drops of 5 to range depending on the patient and the severity of their gradient. I think the second question in terms of, I'm remembering the third question now, but the second question had to do with... You want to remind me?

Fady Ibraham Malik: Yeah, like, if the shallower PK PD plays out, is it fair to say the average EF drop could be relatively higher? Is that suggestive that we could get relatively higher on the dosing curve? Right. Yeah, no, I think that's an astute observation.

Fady Ibraham Malik: You know, the fall and ejection, of 3, 4, 5% on average, is pretty minimal in terms of, again, where these patients start. And so, you know, as I alluded to in the first question, if you can predictably push the dose a bit higher, maybe even potentially lower the ejection fraction a bit more, you're still well within the normal range, but you may be able to achieve a greater effect in patients that have more severe gradients. That's something that we'll hopefully have some reading on when we see the fullness of the data from Redwood HF. HCM rather

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Fady Ibraham Malik: And then I think in the last question, you know, the answer is I think the Explorer data in some ways, the echocardiographic data from Explorer, are probably a better comparator to Redwood HCM in the sense that it's a placebo-controlled trial, and patients are on background therapy. In their Phase II trial, they withdrawn patients from background therapy. It's an open-label trial. I think there are certainly differences between the two trials that really preclude a head-to-head comparison,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

Operator: And There are no further questions at this time.

Robert I. Blum: Okay, looks like we covered quite a lot of ground here in the presentation and the Q&A, so I'll be brief. I want to thank everybody for their attention and for participating in the 2021 earnings call. Obviously, a lot of good things are going on at cytokinetics. We're approaching the remainder of the year with clear eyes on execution on getting to the results of Redwood HCM mid year, putting Strategy for Omicamp into McCarble, and readying to build what we think can be a transformational time at cytokinetics as we transition to our commercial phase with a potential 2022.

Robert I. Blum: That is happening at the same time we're doubling down on research and development, both our research platform expansion and a doubling of our pipeline in clinical research. And we hope to be one of those companies that is establishing a franchise business. At the same time, we continue to innovate in science and bring forward a sustainable pipeline and make for a durable business.

Operator: I look forward to keeping you updated on our progress, and we look forward to responding to other comments and questions over time. With that, operator, we can bring this call to a close. Ladies and gentlemen, this does conclude today's conference call. We thank you for your participation. You may now disconnect.

Operator: [inaudible]...........

Operator: Ladies and gentlemen, this does conclude today's conference call. We thank you for your participation. You may now disconnect.

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Operator: Good afternoon, and welcome ladies and gentlemen to Cytokinetics' first quarter 2021 conference call. At this time, I'd like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call for questions and answers after the presentation. I'd now like to turn the call over to Diane Weiser, Cytokinetics' Senior Vice President of Corporate Communications and Investor Relations. Please go ahead.

Diane Weiser: Good afternoon, and thanks for joining us on the call today. Robert Blum, our President and Chief Executive Officer, will kick off the call with an overview of the quarter and recent developments. Then, Fady Malik, our EVP of Research and Development, will provide an update on Omicamptin-McCarbyl, including progress following a recent meeting with FDA and what to expect from upcoming analyses from Galactic HF, the positive Phase III clinical trial of Omicamptin-McCarbyl, as well as recent activities related to Meteoric HF, the second Phase III clinical trial of Omicamp

Diane Weiser: Next, Stuart Kupfer, our SVP and Chief Medical Officer, will provide an update on our Cardiac Myosin Inhibitor Program with focus on Redwood HCM, the Phase II clinical trial of CK274. Then, Robert Wong, our VP and Chief Accounting Officer, will provide a financial overview for the past quarter, and Ching Jia, our SVP and Chief Financial Officer, will discuss our financial outlook and corporate development strategies before Robert Blum then returns to provide concluding thoughts and expected key milestones for the remainder of 2021. We also have a new team member on today's call, Andrew Callos, our Chief Commercial Officer, who joined Cytokinetics during the quarter and who you will hear about on an upcoming call.

Diane Weiser: Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our first quarter 2021 financial results filed on Form 8K today. We undertake no obligation to update any forward-looking statements after this call. And now, I will turn the call over to Robert.

[music].

Robert I. Blum: Thank you, Diane, and thanks again to everyone for joining us on the call today. We had a productive first quarter and are feeling increasingly more optimistic as our nation reemerges into new normalities in the coming months with widespread vaccinations for COVID-19. We continue to wish you and your families good health and well-being.

Robert I. Blum: We're also optimistic about cytokinetics in our pipeline, our progress, and our prospects. In the first quarter, we executed well against our plans and were firing on all cylinders, with priority to advancing our industry-leading cardiovascular drug candidates directed to muscle, Focusing on both Redwood HCM and Meteoric HF, as well as advancing regulatory and commercial readiness workstreams in support of Omicampta McCarble. Toward that end, I'm very pleased to introduce the newest member of our leadership team.

Good afternoon, and welcome ladies and gentlemen to set of genetics first quarter 2021 conference call. At this time I'd like to inform you that this call is being recorded and that all participants are in a listen only mode at the company's request, we will open the call for questions and answers after the presentation.

Robert I. Blum: Andrew Callos, Andrew joined us as our Chief Commercial Officer, and we're thrilled to have him on board at a key time for our company as we turn the corner towards commercialization and transition to be a forward integrated biopharmaceutical company. Andrew brings relevant commercial and operational experience from cardiovascular specialty care and rare disease marketing. He had a long and successful career at Pfizer and at Wyeth Pharmaceuticals, where he oversaw U.S. and international pharmaceutical business franchises. Most recently, Andrew served as regional president and general manager of North America for Pfizer's Upjohn business unit. And prior to that role, and during his over 20 years at Pfizer and its predecessor companies.

I'll now like to turn the call over to Diane Weiser Cyberkinetics Senior Vice President of corporate Communications and Investor Relations. Please go ahead.

Good afternoon, and thanks for joining us on the call today, Robert Blum, our President and Chief Executive Officer will kick off the call with an overview of the court of Cologuard and recent developments then 30 Malik our EVP of research and development will provide an update on AUM accounts and Macquarie ball included including progress following our recent meeting with M D.

And what to expect from upcoming analyses from Galactic H F. The positive phase III clinical trials on the Camden Mccarville as well as recent activities related to meteoric H F. The second phase III clinical trial upon the Kimpton and Powerball next Stuart Kupfer, our SVP and Chief Medical Officer will provide an update on our.

Robert I. Blum: He held leadership positions, including as Vice President, U.S. Cardiology and Metabolic Marketing, overseeing the commercialization of Eliquis in the United States. Andrew also served as Vice President and Head of Inflammation Marketing Europe and Vice President, Global Commercial Development for Rare Diseases. As you can see, his experience is a perfect fit for cytokinetics, and he has quickly come up to speed and contributed to the many commercial planning work streams that had already been underway prior to his arrival.

Cardiac myosin inhibitor program with focus to Redwood HCM the phase II clinical trial of CK 274, and then 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 our financial outlook and corporate development.

And and strategies before Robert Blum, then return to provide concluding thoughts and expected key milestones for the remainder of 2021.

We also have a new team member on today's call Andrew Carlos Our Chief Commercial officer, who joined subtle kinetics during the quarter and who you will hear and upcoming calls.

Robert I. Blum: Andrew joins us to lead a team of similarly expert commercial colleagues at Cytokinetics who are experienced in cardiovascular and neuromuscular specialty care markets. And as we proceed to finalize our go-to-market planning for Omicamptive McCarble and CK274, you'll be hearing more from Andrew and his team about our plans, including at an investor day to be scheduled later this year. On the regulatory front, as previously communicated, during the first quarter, we convened an FDA meeting to review the Phase III clinical trial results from GalacticHF, and we're now proceeding towards additional interactions with FDA and other regulatory authorities.

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 may differ materially from those projected and these forward looking statements additional information concerning factors that could.

Cause our actual results to differ materially from those and these forward looking statements is contained in our SEC filings, including our current report regarding our first quarter 2021 financial results filed on form 8-K. Each day, we undertake no obligation to update any forward looking statements. After this call and now I will turn the call.

Over to Robert.

Robert I. Blum: Fady will elaborate in a moment, but suffice it to say, we're pleased with the level of engagement and the feedback that we received from FDA, and we believe Galactic HF can stand on its own as a pivotal trial in a planned NDA submission. We're now proceeding towards our goal of an NDA submission for Omicamp to McCarble in the second half of 2021. We also advanced our go-to-market planning with workstreams focused on market research, brand positioning, supply chain manufacturing and logistics, market access, health economics and outcomes research, customer engagement, and other commercial infrastructure to inform our future investment and execution strategies in anticipation of a potential commercial launch of Omicampta McCarble in the United States in 2022. Ching will elaborate later in this call on our financials, our cash runway, and our deal objectives to support our go-to-market strategy.

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

We had a productive first quarter and are feeling increasingly more optimistic as our nation re emerges towards new normal she used in the coming months with widespread vaccinations for COVID-19, we continue to wish you and your families good health and wellbeing.

We're also optimistic about subtle kinetics, and our pipeline, our progress and our prospects and the first quarter, we executed well against our plans and are firing on all cylinders with priority to advancing our industry, leading cardiovascular drug candidates directed to muscle folk.

Kissing to both Redwood HCM and meteoric HFF.

Well as advancing regulatory and commercial readiness work streams and support of Omi Camden Mccarville.

Toward that and I'm very pleased to introduce the newest member of our leadership team.

And Andrew Carlos Andrew joined US as our Chief commercial officer, and we're thrilled to have him on board and a key time for our company as we turned the corner towards commercialization and transition to be a forward integrated biopharmaceutical company.

Robert I. Blum: We also made significant strides advancing our cardiac myosin inhibitor program during the quarter. Focusing on the completion of Redwood HCM, our ongoing Phase 2 clinical trial of CK274 in patients with symptomatic obstructive hypertrophic cardiomyopathy, as Stuart will elaborate, in the first quarter, we opened and promptly completed enrollment in Cohort 2, and more recently opened enrollment in Cohort 3.

Andrew brings relevant commercial and operational experience from cardiovascular specialty care and rare disease markets. He had a long tenured and successful career at Pfizer and Wyeth Pharmaceuticals, where he oversaw U S and international pharmaceutical business franchises.

Most recently, Andrew served as regional President and General manager and North America for Pfizer's, Upjohn business unit and prior to that role and during his over 20 years at Pfizer and predecessor companies.

Robert I. Blum: In addition, this morning, we announced that we have activated the first site in the Open Label Extension Study for patients who have completed Redwood HCM. This high-proficiency execution underscores the urgency of our activities in this program given the high unmet need among patients with hypertrophic cardiomyopathy. Based on data from the interim analysis of Cohort 1 that we announced in December, we plan to engage FDA this quarter and prepare for a Phase 3 clinical trial expected to begin before year-end.

Held leadership positions, including as Vice President U S cardiology, and metabolic marketing overseeing the commercialization of <unk> and the United States.

And you also served as vice President and head of inflammation marketing Europe, and Vice President Global commercial development for rare diseases.

As you can see his experience is a perfect fit for Sato kinetics, and he has quickly come up to speed and contributed to the many commercial planning work streams that had already been underway prior to his arrival.

Robert I. Blum: We're also advancing medical and new product planning activities directed to specialty care cardiologists in high-volume heart failure hospitals that overlap with high-volume HCM centers of expertise, given the many synergies between our cardiac myosin modulators and planning. And with that, I'll turn the call over now to Fady to elaborate on developments related to Omicamptive McCarver. Thanks, Robert.

Andrew joins us to lead a team of similarly expert commercial colleagues at startup kinetics, who are experienced and cardiovascular and neuromuscular specialty care markets and.

And as we proceed to finalize our go to market planning for Omi captive Mccarville, AMC <unk>, seven and four youll be hearing more from Andrew and his team and.

About our plans, including other and Investor day to be scheduled later this year.

Fady Ibraham Malik: During the first quarter, we advanced omicamp of macarbo forward in several important ways. First, we met with FDA to review the top-line results of GALACTIC-HF. That type C meeting met our expectations in terms of engagement and feedback. We now intend to proceed to file an NDA later this year based on results from Galactic HF and the rest of the development program. We had an opportunity to hear from FDA as to those matters that we should be prepared to address in finalizing the NDA filing.

On the regulatory front as previously communicated during the first quarter, we convenient and FDA meeting to review the phase III clinical trial results from Galactic HFF and we're now proceeding towards additional interactions with FDA and other regulatory authorities.

Saudi will elaborate in a moment, but suffice it to say, we're pleased with the level of engagement and the feedback that we received from FDA and we believe galactic HFF can stand on its own as a pivotal trial and a planned NDA submission. We're now proceeding towards our goal of an NDA submission for <unk>.

Fady Ibraham Malik: We're now preparing for additional discussions with FDA during the second quarter, including another Plan Type C meeting that we expect to further inform our filing strategy. At this next meeting, we plan to share additional analyses of Galactic HF and request FDA feedback that can inform labeling and our NDA submission. We expect further interactions, including a potential pre-NDA meeting, and are pleased to have multiple opportunities to engage FDA ahead of our goal to submit an NDA in the second half of the year.

<unk> and mccarville and the second half of 2021.

We also advanced our go to market planning with work streams focused on market research brand positioning supply chain manufacturing and logistics market access health economics, and outcomes research customer engagement and other commercial infrastructure to inform our future investment.

And and execution strategies and anticipation of a potential commercial launch of <unk> and the United States in 2022 Ching.

Fady Ibraham Malik: I'll remind you that our planned NDA submission will be based on the results of GALACTIC-HF in combination with the rest of the development program comprising over 30 clinical trials and as informed by prior regulatory discussions. In parallel with these activities, we continue to conduct METEORIC-HF, our second Phase III clinical trial of Omicamptive Mercarbol in patients with heart failure with a reduced ejection fraction. In METEORIC-HF, we're investigating the potential effects of Omicamptin-McCarbol to improve exercise tolerance in patients with heart failure, which may provide a benefit for these patients struggling to perform daily activities. Screening is now nearly closed, and we're on track to complete randomization of patients into meteoric in this second quarter. We expect top-line results to be available in early 2022.

<unk> will elaborate later in this call on our financials, our cash runway and our deal objectives to support our go to market strategy.

We also made significant strides advancing our cardiac myosin inhibitor program during the quarter focusing on the completion of Redwood HCM, our ongoing phase II clinical trial of CK 274, and patients with symptomatic obstructive hypertrophic cardiomyopathy.

Stuart will elaborate in the first quarter, we opened and promptly completed enrollment in cohort two and more recently opened enrollment to cohort. Three. In addition, this morning, we announced that we also activated the first site and the open label extension study for patients who completed.

Redwood HCM.

Fady Ibraham Malik: If the findings from EDIORC are positive, we expect that data from that trial would be submitted in a supplemental filing as would be expected to follow a potential FDA approval and commercial launch. I'd like to acknowledge the efforts of the study team, investigators, and study coordinators for their successful commitment to accomplish this milestone during an unprecedented pandemic. During the quarter, we received confirmation that data from a secondary analysis of galactic HF assessing the effect of Omicamptin-Micarbyl on clinical outcomes in relationship to ejection fraction at baseline will be presented by Dr. John Tierlink in a late-breaking clinical trial session at the American College of Cardiology 70th Annual Scientific Session.

This high proficiency execution underscores the urgency of our activities and this program given the high unmet need among patients with hypertrophic cardiomyopathy.

Based on data from the interim analysis of cohort one that we announced in December we plan to engage FDA in this quarter and prepare for a phase III clinical trial expected to begin before year end.

We're also advancing medical and new product planning activities directed to specialty care cardiologists and high volume heart failure hospitals that overlap with high volume HCM centers of excellence given the many synergies between our cardiac myosin modulators and planning.

And with that I'll turn the call over now to 30 to elaborate on developments related to <unk>.

Thanks, Robert during the first quarter, we advanced film and captive mccargo forward and several important ways.

Fady Ibraham Malik: We can't say more about these data, so as not to break embargo policies, but suffice it to say we believe it will further advance the understanding of which patients in Galactic HF achieve the greatest benefit from treatment with Omicamptive Mecarbil on top of standard of care. The Executive Committee of GalacticHF, in collaboration with Cytokinetics, has been working on several additional secondary analyses from which data will be forthcoming later this year at medical meetings and in manuscripts to further elaborate on the results of Galactic HF and inform its potential use. We believe that these additional analyses will be very informative as to how Omicamptive Macarble performed in Galactic and illuminate key learnings.

We met with FDA to review the topline results from Galactic HFF.

That type C meeting met our expectations in terms of engagement and feedback.

And we now intend to proceed to file an NDA later this year based on results from Galactic HFF and the rest of the development program.

We had an opportunity to hear from FDA at those matters that we should be prepared to address and finalizing the NDA filing.

And we're now preparing for additional discussions with FDA during the second quarter, including another plant type C meeting that we expect to further inform our filing strategy.

At this next meeting we plan to share additional analyses of Galactic HFF and request FDA feedback that can inform labeling and our NDA submission.

We expect still further interactions, including a potential pre NDA meeting and are pleased to have multiple opportunities to engage the FDA ahead of our goal to submit an NDA and the second half of the year.

Fady Ibraham Malik: Given the dynamics of the heart failure treatment setting, it's incumbent on us to best understand how to frame these data and what can hopefully be an approvable submission for this first-in-class cardiac myosin activator, which reduced the risk of heart failure events in its pivotal trial. To that point, in the last quarter, we continued market research activities to better define and refine the potential target product profile of Omicamptive McCarville and understand where it may best fit in the treatment arsenal.

I'll remind you that our planned NDA submission will be based on the results of Galactic HFF and combination with the rest of the development program comprising over 30 clinical trials and as informed by prior regulatory discussions.

In parallel with these activities, we continue to conduct meteoric HFF, our second phase III clinical trial of only captive mccarville and patients with heart failure with reduced ejection fraction.

And meteoric HFF, we're investigating the potential effects of OMA, Camden mccarville to improve exercise tolerant and patients with heart failure, which may provide a benefit for these patients struggling to perform daily activities.

Fady Ibraham Malik: Particularly given the new entries available to clinicians and their patients. As we've said before, it's an exciting time in the treatment of heart failure, where there are still tremendous unmet needs. And we remain enthusiastic that Omicamps of McCarble may provide a welcome addition in the battle to better manage this high-prevalence, progressive disease, particularly among more severe patients who have exhausted guideline-directed therapy and still suffer debilitating symptoms or are at high risk for heart failure hospitalization.

Screening is now nearly closed and we're on track to complete randomization of patients and the meteoric and this second quarter.

We expect topline results to be available in early 2022.

And the findings from meteoric are positive we expect that data from that trial would be submitted and a supplemental filing as would be expected to follow a potential FDA approval and commercial launch.

I'd like to acknowledge the efforts of the study team investigators and study coordinators for their successful commitment to accomplish this milestone during an unprecedented pandemic.

Fady Ibraham Malik: We also had the opportunity to engage with a large number of KOLs during the quarter, with a significant majority of them providing positive views regarding Omicamptomocarbal and importantly, pointing out that it could potentially fill a key need among a more severely ill Asian population that is more at risk of hospitalization and re-hospitalization. Common themes included an understanding that biologically, it stands to reason that those patients with more impaired cardiac systolic function may benefit more from this novel mechanism therapy that's designed to act directly on muscle and improve cardiac function and performance, as well as the potential to add Omecamtiv mecarbil to standard of care given its favorable tolerability and safety profile, as we observed in galactic HF. In which its addition to standard of care did not adversely affect blood pressure or renal function.

During the quarter, we received confirmation that data from a secondary analysis of Galactic HFF assessing the effect of OMA, <unk> and clinical outcomes and relationship to injection fraction at baseline.

And we presented by Dr. John <unk> and a late breaking clinical trial session at the American College of Cardiology, 70th annual scientific sessions.

We can't say more about these data so as not to break embargo policies, but suffice it to say and we believe it will further advance the understanding of which patients in galactic <unk> achieve the greatest benefit from treatment with AUM of Camden Mccarville on top of standard of care.

The executive committee of Galactic HFF and collaboration with SATA kinetics has.

And that's been working on several additional secondary analyses from which data will be forthcoming later this year at medical meetings and and manuscripts to further elaborate on the results of Galactic HFF and inform its potential use.

Fady Ibraham Malik: And finally, during the past quarter, we're pleased to conduct the inaugural meeting of our Heart Failure Patient Advisory Council. This is a group of passionate patients and caregivers with whom we have been meeting regularly to inform understandings of the patient experience, disease journey, and unmet needs. These insights will be instrumental in designing patient support services. Educational Materials and Guiding the Development of a Heart Failure Directed Pipeline. We're grateful to the participants.

We believe that these additional analyses will be very informative as to how on the captive mccarville performed and galactic and illuminate key learning gives.

Given the dynamics of the heart failure treatment setting it's incumbent on us to best understand how to frame. These data and what can hopefully be and approval submission for this first in class cardiac myosin activator, which reduced the risk of heart failure events and its pivotal trial.

To that point and the last quarter, we continued market research activities to better define and refine.

Fady Ibraham Malik: From our first engagement, we are confident this group will be valuable to our patient-centric activities. As we've indicated, Cytokinetics is committed to advancing Omicamptin-McCarbyl as a key priority in 2021. Doing that has required extensive attention to wind down activities in our collaboration with Amgen. Included amongst these projects are managing the transfer of the Integrated Safety Database and related reporting obligations, the seat of regulatory documents, and assuming responsibility for manufacturing.

<unk> target product profile of OMA captive mccarville.

And understand where it may best fit and the treatment armamentarium, particularly given the new entries available to clinicians and their patients.

As we've said before it's an exciting time and the treatment of heart failure, where there is still tremendous unmet need and we remain enthusiastic that <unk> may provide a welcome addition, and the battle to better manage this high prevalence progressive disease.

And particularly among more severe patients who've exhausted guideline directed therapy and still suffered debilitating symptoms are at high risk for heart failure hospitalization.

We also have had opportunity to engage with a large number of kols during the quarter with a significant majority of them providing positive views regarding home and kept them a carnival and importantly, pointing out that it could potentially fill a key need among more severely ill patient population that.

Fady Ibraham Malik: Transitioning these many work streams from a 15-year collaboration is not trivial, and our team at Cytokinetics has been very busy attending to these issues to ensure smooth and orderly handoffs. Naturally, we have prioritized omecamptomacarbal and are therefore deprioritizing the further development of our cardiac troponin activator, CK136, formerly referred to as AMG594, which will be deferred for the rest We plan to continue its development in the future as we continue to build out and advance our pipeline and look to expand our emerging cardiovascular product franchise.

That is more at risk of hospitalization and re hospitalization.

Common themes included and understanding that biologically it stands to reason that those patients with more impaired cardiac systolic function may benefit more from this novel mechanism therapy is designed to act directly on muscle and improve cardiac function and performance as.

And as well as the potential to add <unk> to standard of care, given its favorable tolerability and safety profile as we observed and Galactic HFF.

Fady Ibraham Malik: And with that, I'll turn the call over to Stuart. Thanks, Fady. During the quarter, we made significant progress within our cardiac myosin inhibitor program, focused on the advancement of CK274. I'll begin with an update on Redwood HCM, the Phase 2 clinical trial of CK274 in patients with obstructive hypertension, including highlighting recent and

And which is addition to standard of care did not adversely affect blood pressure and renal function.

And finally during the past quarter were pleased to conduct and inaugural meeting of our heart failure patient Advisory Council.

This is a group of passionate patients and caregivers with whom we have been meeting regularly to inform understandings of the patient experience disease journey and unmet needs.

These insights will be instrumental and designing patient support services educational materials and guiding the development of our heart failure directed pipeline.

Stuart Kupfer: upcoming regulatory interactions and then touch on preclinical data recently presented at the American Chemical Society Annual Meeting. During the first quarter of Redwood HCM, we dosed the first patient and also completed full enrollment in cohort two, which is examining the safety and tolerability of doses of 10, 20, and 30 milligrams of

And grateful to the participants and from our first engagement. We are confident this group will be valuable to our patient centric activities.

As we've indicated cytogenetics is committed to advancing <unk> as a key priority in 2021.

Doing that has required extensive attention to wind down activities and our collaboration with Amgen and.

Included amongst these projects are managing the transfer of the integrated safety database and reported related reporting obligations and receipt of regulatory documents and assuming responsibility for manufacturing <unk>.

Stuart Kupfer: CK274 versus placebo. Dosing of CK274 is individually titrated by echocardiography at weeks 2, 4, and 6, with dosing optimized on the basis of target reductions and LVOT gradients.

Transitioning these many work streams from a 15 year collaboration is not trivial and our team at Scioto kinetics has been very busily attempting to these issues to ensure a smooth and orderly handoffs.

Naturally we have prioritized OMA captive mccarville and are therefore day prioritizing the further development of our cardiac troponin activator CK 136, formerly referred to as AMG 594, which will be deferred for the rest of 2021.

unknown: Edited by: https://otter.ai

Stuart Kupfer: Overall, the treatment duration is 10 weeks with an echocardiogram to examine reversibility of effect two weeks after the last dose.

Stuart Kupfer: We remain on track to report top-line results from both Cohort 1 and Cohort 2.

We plan to continue its development and the future as we continue to build out and advance our pipeline.

And look to expand our emerging cardiovascular product franchise.

Stuart Kupfer: As well as to begin a planned phase 3 clinical trial by year end. Earlier this week, we announced the opening of Cohort 3 of Redwood HDM.

And with that I'll turn the call over to Stuart.

Thanks Patty.

During the quarter, we made significant progress within our cardiac myosin inhibitor program.

Stuart Kupfer: Cohort 3 is intended to examine the safety and tolerability of CK274 in patients whose background therapy includes disoperamide, a medication that is sometimes used in patients with symptoms refractory to first-line medical therapy and that has been excluded in most trials of HCM interventions to date. In Cohort 3, patients will receive CK274 in an open-label fashion over a 10-week period with individualized dose titration of 5, 10, or 15 milligrams once daily. This cohort is not being conducted to further refine the dosing strategy that we intend to study in Phase 3, but instead, Cohort 3 is expected to provide important data to inform the potential inclusion of disoperamide-treated patients in our planned Phase 3 clinical trial. Additionally, this morning, we announced that we

And so on the advancement of CK 274.

I'll begin with an update on Redwood HCM, the phase II clinical trial of CK 274, and patients with obstructive HCM income.

Including highlighting recent and upcoming regulatory interactions and then touch on preclinical data recently presented at the American Chemical Society annual meeting.

During the first quarter and Redwood HCM, we dosed the first patient and also completed full enrollment in cohort two.

Which is examining the safety and Tolerability of doses 10, 20, and 30 milligrams of CK 274 versus placebo.

Dosing and CK 274 is individually titrated by Echocardiographer at weeks, two four and six with dosing and optimize on the basis of targeted reductions and ldlc gradients, while maintaining a normal ejection fraction.

Overall, the treatment duration, and 10 weeks with and echocardiogram to examine reverse ability of effect two weeks after the last dose.

Stuart Kupfer: An Open Label Extension Study that is designed to assess long-term safety

We remain on track to report top line results from both cohort one and cohort two mid year.

Stuart Kupfer: tolerability of CK274 in patients with symptomatic obstructive HCM. Eligible patients will have completed their participation at Redwood HCM. Primarily, we will evaluate long-term safety as assessed by the

And as well and to begin a planned phase III clinical trial by year end.

Earlier this week, we announced the opening of cohort three of Redwood HCM.

<unk> III is intended to examine the safety and Tolerability of CK 274, and patients whose background therapy includes guidance at Paramount and.

Stuart Kupfer: Project Inspection, less than 50%. Secondary endpoints include measures of the long-term effects of CK274 on left ventricular outflow tract gradients.

Medication that are sometimes use in patients with symptoms refractory to first line medical therapy.

And that has been excluded and most trials of HCM intervention to date.

Stuart Kupfer: and Trickerla Outflow Track Radiance, and Assessments, and Assessments of Steady State Pharmacokinetics. The Open Label Extension Study will also include a cardiac MRI sub-study to assess changes in cardiac morphology, function, and fibrosis.

And cohort three patients will receive CK 274, and open label fashion over a 10 week period with individualized dose titration or 510 or 15 milligrams once daily.

And this cohort is not being conducted to further refine the dosing strategy that we intend to study and phase III and <unk>.

Stuart Kupfer: All enrolled patients will receive CK274 and use a similar echocardiography-guided dose titration.

Ted cohort three is expected to provide important data to inform the potential inclusion and disopyramide treated patients and our planned phase III clinical trial.

Stuart Kupfer: Unlimited Dose Titration to Individually Optimized Dose as has been employed in Redwood HCM. During the last quarter, we also made progress in our collaboration with Ji Xing Pharmaceuticals, with an

Additionally, this morning, we announced that we have activated the first site and Redwood HCM O L D and <unk>.

Open label extension study that is designed to assess the long term safety and Tolerability of CK 274, and patients with symptomatic obstructive HCM.

Stuart Kupfer: Initiation of a Phase 1 Clinical Study of CK274 in Healthy Participants in China This aligns with our shared objective for the inclusion of China in a global phase three clinical trial planned to begin later this year. We are pleased to see that our colleagues at Jisheng are operating with the same sense of urgency as we are to enable advancement of CK274 into a global registration program from a regulatory perspective. We were also pleased to recently receive Orphan Drug Designation from the FDA for CK274 in symptomatic HCM, encompassing both obstructive and non-obstructive patients.

Eligible patients will have completed their participation and Redwood HCM.

Primarily we will evaluate long term safety as assessed by the incidence of adverse events and left ventricular infection.

Section and less than 50%.

Secondary endpoints include measures of the long term effects of CK 207, and four <unk>.

And trigger a outflow tract gradient.

And assessments.

Yes.

Alright, and assessments and steady state pharmacokinetics.

The open label extension study will also include a cardiac MRI sub study to assess changes and cardiac mythology function and fibrosis.

All enrolled patients will receive CK 274 and use a similar.

Stuart Kupfer: This underscores a significant unmet need in patients who continue to suffer symptoms that can severely impact their quality of life. There are a few treatment options available to them, and no currently approved medical therapy.

<unk> guided dose titration to individually optimized dose and it has been employed and Redwood HCM.

During the last quarter. We also made progress under our collaboration with <unk> pharmaceuticals with initiation of a phase one clinical study of CK 274, and healthy participants and China.

Stuart Kupfer: In the first quarter, we also prepared for regulatory interactions, including type C and end of phase two meetings with the FDA, as well as with the EMA for scientific advice. The first of these next-level meetings is planned to occur in the second quarter and will inform how we approach an end of phase two meeting that is expected to occur in the third quarter. Finally, last month.

And this aligns with our share and objective for the inclusion of China, and a global phase III clinical trial planned to begin later this year.

We are pleased to see that our colleagues as you're seeing are operating with the same sense of urgency as we are to enable the advancement of CK, two seven and four into a global registration program.

From a regulatory perspective.

We were also pleased to recently received orphan drug designation from the FDA for CK 274, and symptomatic HCM encompassing both obstructive and non obstructive patients.

Stuart Kupfer: Data related to the optimization of CK274.

Stuart Kupfer: Including the first disclosure of its chemical structure, were presented at the American Chemical Society Spring 2021 virtual meeting. This scientific presentation

This underscores the significant unmet need and patients who continue to suffer symptoms that can severely impact their quality of life.

And few treatment options available to them and.

Stuart Kupfer: This slide highlighted the preclinical characterization of CK274 and focused on key compound characteristics, including its half-life, the shallow dose-response relationship, and lack of meaningful cytochrome P450 interactions. Furthermore, data were presented from genetic models of HCM, in which CK274 reduced fractional shortening.

And no currently approved medical therapies.

And the first quarter, we also prepared for regulatory interactions, including type C and and the phase two meetings with the FDA as well as with DNA for scientific advice.

The first of these next level meetings is planned to occur and the second quarter and will inform how we approach and end of phase two meeting that is expected to occur and the third quarter.

Finally last month day.

Related to the optimization of CK, two set and board, including the first disclosure and if its chemical structure were.

And were presented at the American Chemical Society Spring 2021 virtual meeting.

Stuart Kupfer: and LVOT Peak Gradient in a Dose-Related Manifest

This scientific presentations highlighted the preclinical characterization of CK 274.

Stuart Kupfer: These results highlight the success of the chemical optimization program conducted at Cytokinetics Inc.

And focused on key compound characteristics, including including the top line.

unknown: Transcript by Transcription Outsourcing, LLC.

And the shallow dose response relationship and.

Stuart Kupfer: We now look forward to results from both cohorts 1 and 2 of the Redwood HCM study, which will elucidate how these next-generation physiochemical properties of CK274 may translate into important clinical effects in patients with obstructive HCM.

And lack of meaningful cytochrome <unk> hundred 50 interactions.

Furthermore, data were presented from genetic models of HCM and with CK 274 reduced fractional shortening.

And L D O T peak gradient and a dose related manner.

These results highlight the success of the chemical optimization program conducted at Cytogenetics, which was intentionally focused on designing key compound characteristics to enable flexible safe and timely dosing adjustments and clinical practice.

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

Robert C. Wong: Thanks Stuart. I'll first provide an update on cash, revenue, and spending, and then Ching will review our financial outlook and corporate development strategies looking forward. More details on our actual results for the first quarter of 2021 are included in the press release, which we released earlier this afternoon. We ended the first quarter with approximately $460 million in cash and investments.

We now look forward to results from both cohorts, one and two with Redwood HCM.

Which will elucidate how these next generation is geochemical properties of CK, two seven and four may translate into important clinical effects and patients with obstructive HCM.

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

Thanks Stuart.

I'll first provide an update on cash revenue and spending and then Ching will review, our financial outlook and corporate development strategy looking forward.

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

Robert C. Wong: Our revenues in Q1 2021 came primarily from our strategic alliances with Amgen and Estella. Our first quarter 2021 R&D expenses increased to $31.6 million from $21.7 million in the first quarter of 2020, primarily due to increases in spending on our skeletal muscle programs and clinical development activities for our cardiac myosin inhibitor program. More than 50% of our R&D expenses were attributable to our cardiovascular programs, as expected, given activity for meteoric HF and the cardiac myosin inhibitor program, and the remainder of our expenses were attributable to our skeletal and early research activities. Our first quarter 2021 G&A expenses were $15.6 million, up from $12.4 million in Q1 2020, due to higher personnel-related costs, including stock-based compensation and higher commercial readiness. Now Thanks, Robert.

And we ended the first quarter with approximately $460 million and cash and investments.

Our revenues in Q1, 2021 came primarily from our strategic alliances with Amgen and Astellas.

Our first quarter 2021, R&D expenses increased to $31 6 million from $21 7 million in the first quarter of 2020, primarily due to increases in spending on our skeletal muscle program and clinical development activities for our cardiac myosin inhibitor programs.

More than 50% of our R&D expenses were attributable to our cardiovascular programs as expected given activity for meteoric HFF and the cardiac myosin inhibitor program and the remainder of our expenses were attributable to our skeletal and early research activities.

Our first quarter 2021 and G&A expenses were $15 6 million up from $12 4 million and Q1, and 2020 due to higher personnel related costs, including stock based compensation and higher commercial readiness.

And now Ching will review, our planning and corporate development strategy.

Thanks Robert.

Ching W. Jaw: As we ended the first quarter with approximately $460 million in cash, we look to our financial guidance for 2021 and believe we have over two years of forward cash runway. We have also indicated that we may revise financial guidance based on finalizing commercial planning activities related to Omicantin Carbyl and a potential product launch in 2022. During the quarter, we delved deeply into commercial planning and are developing a comprehensive go-to-market strategy, which will be presented to our board to gain alignment on the overall approach and investment requirements. The strategy comprises key elements such as market assessment, brand strategy, market access, Commercial Organizational Structure, Customer Facing and Digital Engagement Strategies, Supply Chain, Information Systems, and Projected Sales, Spending, and Return on Investment.

As we ended the first quarter was approximately $460 million and cash we.

Look to our financial guidance for 2020, one and believe we have over two years old flow of cash runway.

We have also indicated that we may revise financial guidance based on finalizing commercial planning activities.

And it only came from Kabul and a potential product launch in 2022.

During the quarter, we delve deeply into commercial planning and <unk> a comprehensive go to market strategy, which will be presented to our board to gain alignment on the overall approach and investment requirements.

The strategy comprises key elements such as the market assessment brand strategy market access.

Commercial organizational structure.

Customer facing and digital engagement strategy supply chain and information systems and.

And projected sales spending and return on the investment.

Ching W. Jaw: As we advance these strategies in support of the potential launch of Omicantum Carbo, we are focusing on the most efficient and high-yield investments to enable the commercialization of Omicantum Carbo in 2022, but also equipping Cytokinetics to be best prepared for potential expansion of our cardiovascular pipeline and the commercialization of CK274. The foundation we built for Omicantin Carbol will be leveraged to support the planned product launch for CK274, which will soon follow, as part of this planning process.

As we advance these strategies in support of potential launch, Oklahoma cancer Mccarville, we are focusing on the most efficient and high yield investments to enable the commercialization and we kept some cargo in 2022.

But also you could settle kinetics to be best prepared for a potential expansion of our cardiovascular pipeline and the commercialization of CK two seven and four.

The foundation, we built for army tensile and Cardinal will be leveraged to support the planned product launch for CK 2004, which will soon follow.

As part of this planning process.

Ching W. Jaw: We are engaging in industry benchmarking exercises to understand best practices to optimize our approach to franchise development, especially in a post-pandemic world. Moreover, executing on our commercial strategies and plans may result in our incurring significant additional expenses that were not included in our current financial guidance.

We are engaging and industry benchmarking exercises to understand best practices to optimize our approach to franchise debarment and especially in a post pandemic world.

Executing on our commercial strategies and plans May result in our incurring significant additional expenses that were not included in our current financial guidance.

Ching W. Jaw: We expect that some or all of those potential expenses could be covered by our accessing additional capital through strategic partnerships, with near-term cash infusions or by equity and or debt financing if deemed appropriate. Finally, as we have previously discussed, we are advancing a two-fold corporate development strategy in 2021. Firstly, to seek a development and commercialization partner for Omicantin-McCarville and CK274 in complementary geographies to that where we intend to go to market ourselves. For those additional geographies

We expect that some or all of those potential expenses could be covered by our accessing additional capital through strategic partnerships with near term cash infusions or by equity and or debt financing if deemed appropriate.

Finally as.

As we have previously discussed we are advancing a twofold corporate development strategy in 2021 firstly.

To seek a development and commercialization partner for all intensive mccargo and CK, two seven and four in complementary geographies to that where we intended to go to market ourselves.

For those additional geographies. We are currently engaged in potential partnering discussions and Japan and Europe.

Ching W. Jaw: We are currently engaged in potential partnering discussions in Japan and Europe. Secondly, to seek potential royalty monetization and or structure financing deals in order to support the commercial launch of Omicantum Carbo and CK274 during the first quarter.

Secondly.

To seek potential royalty monetization and or structured financing deals in order to support the commercial launch of Omi Kingdom mccarville.

CK, two seven and four <unk>.

During the first quarter.

Ching W. Jaw: We've had encouraging and productive interactions with potential partners to advance this strategy, and we look forward to continuing those discussions, which may result in a deal or deals in the second half of the year. Cytokinetics has always gained access to capital through a diverse array of transaction types, and we continue to believe that our path to commercialization will be served by our continuing modernization of our leadership in muscle pharmacology. And with that, I'll turn the call back over to Robert Blum. Thank you. Thank you, Ching.

We've had encouraging and productive interactions with potential partners to advance this strategy and we look forward to continuing those discussions as May result in a deal or deals in the second half of the year.

So I don't say that ex has always gain access to capital through a diverse array of transaction types and we continue to believe that our path to commercialization will be served by our continuing monetization of our leadership and muscle pharmacology.

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

Thank you Ching.

Robert I. Blum: Before I provide an update on our expected milestones for the remainder of the year, I'd like to take a moment to remind you of the landscape upon which cytokinetics is operating, especially as it relates to the overall clinical and economic burden of cardiovascular disease today. Despite COVID taking well over 500,000 American lives, cardiovascular disease remains the leading killer of Americans, taking even more lives over the same time frame.

And I'll provide an update on our expected milestones for the remainder of the year.

Like to take a moment to remind you of the landscape upon which subtle kinetics as operating especially as it relates to the overall clinical and economic burden of cardiovascular disease today.

Despite COVID-19, taking well over 500000 American lives cardiovascular disease remains the leading killer of Americans, taking even more lives over the same timeframe.

Clearly the impact of cardiovascular disease to patients caregivers and our health care system remains unacceptable.

Robert I. Blum: The impact of cardiovascular disease on patients, caregivers, and our health care system remains unacceptable. We're gratified to be in a position to have the opportunity to make a meaningful impact with novel mechanism therapies that work unlike other available therapies and may benefit millions of patients with various forms of heart failure. Phase 3 trials have demonstrated that modulating cardiac myosin, either by its activation or its inhibition, can translate into clinically meaningful effects on highly relevant registration, and we're pleased to have pioneered the biopharmaceutical sciences directed to cardiac muscle.

We're gratified to be and are positioned to have the opportunity to make a meaningful impact with novel mechanism therapies that work. Unlike other available therapies and as may benefit millions of patients with various forms of heart failure.

Phase III trials have demonstrated that modulating cardiac myosin.

Neither by its activation or inhibition can translate into clinically meaningful effects on highly relevant registration endpoints. We're pleased to have pioneered the biopharmaceutical sciences directed to cardiac muscle and we're excited to be preparing for commercialization.

Robert I. Blum: And we're excited to be preparing for commercialization activities in the same comprehensive and expert way in which we're defining an entirely new cardiovascular pharmacology. As you've heard, it's been a productive quarter, and we're energized by the transformation taking place at the company as we advance plans for a first potential FDA approval and commercial launch, which we believe will set the table for achievement of our Vision 2025. One goal of which is to secure two to three approvals for our potential medicines over the next few years.

<unk> activities and the same comprehensive and expert way and which we are defining and entirely new cardiovascular pharmacology.

And as you've heard it's been a productive quarter and we're energized by the transformation taking place at the company as we advanced plans for our first potential FDA approval and commercial launch, which we believe will set the table for achievement of our vision 2025.

One goal of which is to secure two to three approvals for our potential medicines over the next few years.

Robert I. Blum: Ching reviewed components and work streams related to our go-to-market strategy in support of the commercialization of Omicamptive McCarble. During the quarter, we continued to conduct market research with physicians and payers to refine our target product profile and our understanding of patient journeys and treatment patterns related to the severe heart failure patient who may benefit most from treatment with Omicamptomacarbons. We also began in earnest to lay down the design strategy for our commercial organization and our potential launch of Omicamptive McCarble.

Ching reviewed components and work streams related to our go to market strategy and supportive the commercialization of <unk> <unk> during.

During the quarter, we continued to conduct and market research with physicians and payers to refine our target product profile and our understanding of patient journeys and treatment patterns related to the severe heart failure patients who may benefit most from treatment with <unk>.

We also began in earnest to lay down the design strategy for our commercial organization and our potential launch of <unk>.

Robert I. Blum: These activities had begun under our collaboration with Amgen and now are being refined with that collaboration coming to an end later this month. As we develop the structure and customer engagement strategy for Omicamptomacarbal, we're keeping CK274 close in mind as we are intent to capitalize on a franchise approach to our business, much like we prioritized a portfolio approach to our focus on muscle biology. I want to emphasize the high degree of overlap in high-volume centers that specialize in both heart failure and HCM, both geographically as well as institutionally.

These activities had begun under our collaboration with Amgen and now are being refined with that collaboration coming to an and later this month.

As we develop the structure and customer engagement strategy for <unk>, we're keeping CK $2 seven and four close and mind as we are intent to capitalize on our franchise approach to our business much like we prioritized our portfolio approach to our focus.

And to muscle biology.

I want to emphasize the high degree of overlap and high volume centers that specialize and both heart failure and HCM, both geographically as well as institutionally the and.

Robert I. Blum: The investments we're making in sales and marketing infrastructure to support the potential commercialization of Omicamptomicarbol will be amortized over time and set the table for the advancement and potential commercialization of CK274. In other words, the economies of scale and the synergies we've seen in R&D over many years at Cytokinetics should also serve us well from a commercial standpoint as we expect to build a cardiovascular drug franchise established on sustainable and growing revenue. While our priorities in 2021 are clearly focused on our cardiovascular program,

<unk>, we are making and sales and marketing infrastructure to support the potential commercialization of <unk> will be amortized over time and set the table for advancement and potential commercialization of CK 274 and.

In other words, the economies of scale and the synergies we've seen and R&D over many years. It's subtle kinetics should also serve us well from a commercial standpoint, as we expect to build a cardiovascular drug franchise established on sustainable and growing revenues.

While our priorities in 2021 are clearly focused on our cardiovascular programs. We're also mindful that we need to continue to prepare for current J O less the phase III clinical trial of rail dissented and patients with AOS.

Robert I. Blum: We're also mindful that we need to continue to prepare for COURAGE-ALS, the Phase 3 clinical trial of rel-deceptive in patients with ALS. ALS is another major area of high unmet need for patients, and we maintain an commitment to opening this trial to potential enrollment once we have clarity on our go-to-market strategy with Omicamptomacarbal and progression of CK274 to Phase III. During the quarter, we initiated clinical trial startup activities, including regulatory and institutional review board submissions for COURAGE-ALS, in preparation for the potential start of the trial in the second half of the year.

<unk> is another major area of high unmet need for patients and we maintain our commitment to opening this trial to potential enrollment once we have clarity on our go to market strategy with AUM and <unk> and progression of CK 207, and forward to phase III.

During the quarter, we initiated clinical trial startup activities, including regulatory and institutional review board submissions for courage AOS and preparation for the potential start of the trial and the second half of the year.

Robert I. Blum: In summary, as we round out the second quarter of 2021, we remain enthusiastic about our prospects across the pipeline and our transformation to a fully integrated biopharmaceutical company. The second half of the year has us turning over several cards at Cytokinetics, most notably the upcoming results of Redwood HCM and the potential regulatory advancement of Omecampt and McCarble. With what we believe could be amongst the most promising cardiovascular pipelines, we're taking strides to realize our mission of bringing potential medicines to people living with cardiovascular diseases of impaired muscle function that may improve their health. At the same time, ingenuity and innovation remain a core focus of our research activities, which are also a key component of our Vision 2025.

In summary, as we round out the second quarter of 2021, we remain enthusiastic about our prospects across the pipeline and our transformation to a fully integrated biopharmaceutical company. The second half of the year has us turning over several cards and startup genetics most notably.

The upcoming results of Redwood HCM, and the potential regulatory advancement of AUM and <unk>.

And with what we believe could be amongst the most promising cardiovascular pipelines and we're taking strides to realize our mission of bringing potential medicines to people living with cardiovascular diseases of impaired muscle function and that may improve their health span.

At the same time ingenuity and innovation remain a core focus of our research activities, which are also a key component of our vision 2025, and the next few years to remind you we expect to double our development pipeline to 10 therapeutic programs as well as to expand our disc.

Robert I. Blum: In the next few years, to remind you, we expect to double our development pipeline to 10 therapeutic programs, as well as to expand our discovery platform from the biomachinery of muscle contractility to muscle energetics, growth, and metabolism. We're making good progress already and expect to select up to two more development compounds over the next year across our cardiac and skeletal programs to enter IND-enabling studies. And we look forward to elaborating on these promising R&D programs in our future calls. Now, let me recap our expected milestones for 2021.

<unk> platform from the bio machinery of muscle contractility to muscle energetics growth and metabolism.

We're making good progress already and expect to select up to two more development compounds over the next year across our cardiac and skeletal programs to enter R&D, enabling studies and we look forward to elaborating on these promising R&D programs and our future calls.

Now, let me recap our expected milestones for 2021 for <unk>, we expect to meet with the FDA and this second quarter to continue discussions related to our goal of an NDA submission and the second half of 2021.

Robert I. Blum: For Omicamp to McCarble, we expect to meet with the FDA in this second quarter to continue discussions related to our goal of an NDA submission in the second half of 2021. We expect randomization of patients with heart failure in meteoric HF to be completed in the second quarter of 2021, and we expect to refine our go-to-market strategy and our potential commercial launch plans in the second quarter of 2021 and through the remainder of this year.

We expect randomization of patients with heart failure, and meteoric HFF to be completed in this second quarter of 2021, and we expect to refine our go to market strategy and our potential commercial launch plans and the second quarter of 2021 and through the remainder of this year.

Robert I. Blum: For CK274, we expect to announce results from cohorts 1 and 2 in Redwood HCM by mid-year 2021. We plan to engage regulatory authorities regarding our phase 3 trial and development program in this second quarter and also into the second half of 2021. And we expect to begin a potential phase 3 clinical trial of CK274 by the end of 2021. For RelDeceptive, we expect to continue conducting startup activities for Courage ALS, and we may open the trial to enrollment in the second half of 2021, again, subject to our plans relating to advancing Omicamptin-McCarbol towards commercialization and CK274 to a potential Phase III clinical trial in patients with

For CK 207, and four we expect to announce results from cohorts, one and two and Redwood HCM by mid year 2021, we plan to engage regulatory authorities regarding our phase III trial and development program and this second quarter and also continuing into the second half.

2021, and we expect to begin a potential phase III clinical trial of CK 207, and four by the end of 2021.

Sorel disruptive we expect to continue conducting startup activities for courage AOS and we may open the trial to enrollment and second half 2021, again subject to our plans relating to advancing <unk> towards commercialization and CK 207, and four two.

Potential phase III clinical trial and patients with obstructive HCM.

Robert I. Blum: And for our ongoing research, we expect to advance programs and conduct IND-enabling studies to potentially advance one to two potential drug candidates in development in 2022. Operator. With that, we can now open the call to questions, please.

And for our ongoing research, we expect to advance programs and conduct IND, enabling studies to potentially advanced 1% to two potential drug candidates in development in 2022.

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

Ladies and gentlemen, just as a reminder, if you'd like to ask a question. Please press star and then the number one on your telephone keypad. Once again that is star and the number one.

Operator: Ladies and gentlemen, just as a reminder, if you'd like to ask a question, please press star and then the number one on your telephone keypad. Once again, that is star and the number one. Your first question comes from a line from Emanuela Branchetti with HC Wainwright.

Your first question comes from the line of Emmanuel I'll, let Bren chatty with HC Wainwright.

Emanuela Branchetti: Good afternoon, guys, and thank you for taking my questions. Congratulations on the progress on all programs. You mentioned the discussions with the FDA on Omicantiv are going as expected. Could you please provide more color on what elements were discussed with the FDA and what still needs to be discussed before the NDA submission?

Hello, Juan Manuel.

Good afternoon, guys and thank you for taking my question.

Congratulations on the call gas and oil program.

And you mentioned that discussion with the FDA feedback.

Feedback going as expected and could.

Could you. Please provide more color on what elements were discussed with the FDA and what's the and needs to be discussed before NDA submission.

Robert I. Blum: Sure, I'm not sure we're going to be able to do more than that which we've already mentioned on this call, but perhaps, in summary, I'll say that the first meeting was specifically intended to understand if Galactic, HF, by itself, without any other phase 3 clinical trial could stand alone in support of an NDA filing. And we asked questions and had discussion, and we believe coming out of that call that we got the answer that we were looking for, which is that we can proceed this way, readying to file an NDA based on Galactic by itself.

Sure I'm not sure we're going to be able to do more than that which we already mentioned on this call, but perhaps in summary, I will say that the first meeting was specifically intended to.

Understand if galactic HFF by itself without any other phase III clinical trial could stand alone and support of an NDA filing and we ask questions that had discussion and we believe coming out of that call that we got the answer that we were looking for which is that we can pursue.

<unk> this way.

Readying to file an NDA.

Based on Galactic by itself.

Robert I. Blum: But that's just the beginning of a series of FDA interactions that we had intended. And with that, I'll turn it over to Fady to speak about some of the things we expect to be discussing in other FDA interactions, including an upcoming type C meeting. Yeah, I'll maybe just tackle that at a high level. I think, you know, there are many aspects of filing an NDA to try to get FDA input on before you go ahead and file the NDA, in terms of approaching labeling, in terms of approaches to, those things and other things that we will examine with them in terms of the program. That way, we can put together a filing that I think helps to align what their feedback might be with our

But that's just the beginning of a series of FDA interactions that we had intended and with that I'll turn it over to Saudi to speak about some of the things we expect to be discussing in other FDA interactions, including and upcoming type C meeting.

Yes.

Maybe just tackle that at a high level I think there are many aspects of filing and NDA.

To try to get FDA input on before you go ahead and file the NDA in terms of.

Approaching labeling in terms of approaches too.

Hum.

And on dosing and other things that we.

We will examine with them in terms of.

Program.

That way, we can put together a filing that I think helps to align.

What their feedback might be with our objectives.

Robert I. Blum: Finally, there are a number of technical matters that one has to settle with them in terms of data standards and other aspects of the program as one submits a filing. NDA filing is a very large undertaking, and there are many details which sometimes it helps to agree on before you submit the documentation so that you're not having to sort through those things later.

And finally, there are number of technical matters that one assets settle with them in terms of.

Data standards and.

Other aspects of the program is one submits a filing.

NDA filing is a very large undertaking and there are many details which sometimes it helps to align on before you submit the documentation so that you're not having to sort through those things later.

Robert I. Blum: Thank you. That's very helpful. And switching over to Redwood HCM, can you help us maybe frame the expectation around the upcoming data? What should we specifically focus on, especially when considering potential comparisons with phase two data obtained with Bava Camtas?

Got it got it. Thank you that's very helpful and.

This will go back to the HCN.

And I suppose maybe right.

Non-GAAP coming data, what should we specifically farquhar dawn, especially when considering potential comparison faithful volatile thing with telecom volume.

Sure. So again I'll start and then turn it over to Saudi and Stuart.

Robert I. Blum: Sure. So again, I'll start and then turn it over to Fady and Stuart. As you know, we already reported on interim results from Cohort 1. We did that back at the end of last year.

As you know we already reported on interim results from cohort one we did that back at the end of last year, we had some pretty high expectations going into that and.

Robert I. Blum: We had some pretty high expectations going into that, and I think, admittedly, we believe that the interim Cohort 1 data exceeded those expectations in that a majority of patients achieved clinically meaningful responses at the low end of the planned dose-response curve, and we did not have any of those patients have EFs fall below 50%. So we see that as auguring well for the completion of this study, both Cohorts 1 and Cohort 2, and as we have now completed enrollment in Cohort 2, we'll be proceeding towards the database lock and the readout of those results.

I think admittedly we believe that.

The interim cohort one data exceeded those expectations and that a majority of patients achieved clinically meaningful responses at the low end of the planned dose response curve and we did not have.

Any of those patients.

Have ef's fall below 50%, so we see that as auguring well for the completion of this study both cohorts one and cohort two.

And as we are now completed with enrollment in cohort two.

We will be proceeding towards the database lock and the readout of those results but.

Robert I. Blum: But as far as how that compares to another compound, you know, keep in mind, please, that we're running a different study. We're not doing a head-to-head comparison. We are, however, looking at what we think are real-world practice patterns here in this trial on top of background therapy compared to placebo, where we think this can best inform phase three. And with that, I'll turn it over to Fady and

But as far as how that compares to another compound.

Keep in mind pleased that we're running a different study we're not doing a head to head comparison. We are however, looking at what we think are real world.

Practice Pat.

Patterns here in this trial on top of background therapy compared to placebo, where we think this can best and form phase III and with that.

Turn it over to fatty and Stuart.

Fady Ibraham Malik: I think Robert covered most of it. I think I'll just be brief in that we were quite pleased with the cohort 1 results. I think, as we've said, the majority of the patients in that cohort reached the target of where we would stop escalating drug therapy, but not everybody. And that was why we embarked on cohort 2 to study somewhat higher doses and see if we could ensure that we had covered the top of the dose range.

And I think Robert covered most of it I think I'll just be brief and that the.

We were quite pleased with the cohort one results I think as we've said the majority of the patients and that cohort reached the <unk>.

Target of where we would stop escalating.

Drug therapy, but not everybody and that was why we embarked on cohort two study somewhat higher doses and see if we could ensure that we had covered the top of the dose range.

Fady Ibraham Malik: So the data from cohort one and two will, you know, inform the starting dose and, obviously, the top dose as well. And we'll report those data in July. But, you know, I think the most important data are the effect of the drug on the left ventricular outflow track gradient, the timing of its reduction, and the extent of its reduction. And all of those things should be pretty well laid out for you all when we report the data in the middle of the year.

So the data from cohort, one and two will inform the starting dose and obviously the top dose as well.

And we'll report those data in July.

I think the most important data are the effect of the drug on the left ventricular outflow tract gradient.

And the timing of its reduction and the extent of its reduction.

And all of those things should be.

<unk>.

Well laid out for you all when we when we report the data and the middle of the year.

unknown: Thank you. And in regards to the enrollment of the third cohort in Redwood HCM, the beginning of this cohort was optional, if I remember correctly. Could you elaborate on the rationale behind combining CK2-74 with disopyramide?

Got it thank you and.

And then from the third cohort and Evangelists HCN.

Ooh Ooh and Ah.

This collectible is the option.

Yeah.

And I remember correctly and could you.

You elaborated on that rationale behind combining two henkel for example for PMI.

Yeah.

I'll turn that over to Saudi or Stuart whoever wants to answer that.

Stuart Kupfer: I'll turn that over to Fady or Stuart, whoever wants to answer that. Stuart, why don't you take that question?

Alright, and wants to take that question from there.

Right so.

And the rationale is.

unknown: Right, so the rationale is, you know, as we've noted, that patients with more advanced symptomatic obstructive ACM are sometimes treated with disopiramide, which can reduce cardiac contractility to stomach acid.

We've noted is that patients.

With more advanced.

Symptomatic obstructive HCM or sometimes treated with.

And with Disopyramide.

And which can.

Reduced cardiac contractility to some extent, but.

If there are patients despite being treated with some of the standard therapy, including <unk>.

unknown: https://www.globalonenessproject.org who are still suffering.

Who still are suffering from.

unknown: https://www.youtube.com or www.youtube.com

And from symptoms related to HCM they could benefit.

From a drug like CK, two seven and four.

<unk>, which of course is specifically designed to inhibit <unk>.

unknown: https://www.kenhub.com

Reduced cardiac contractility.

<unk>.

The net debt.

unknown: So there really is a potential advantage here for patients who have sort of run out of options, so to speak, and are further along in the natural history of the disease. In terms of their disease severity, they could benefit from another medical intervention, such as CK274. And that's really our objective, to explore

There really is a potential advantage here for patients with.

Good sort of run out of options.

To speak and are.

And further along and and.

Natural history of the disease.

In terms of their disease severity, they could benefit from another medical intervention.

Such a ckc's and floor and that's so that's really our objective to explore.

unknown: to explore that more severe patient population by adding to disappear my treated patient.

And that more severe patient population.

And by adding to Disopyramide treated patient.

unknown: Got it, thank you for that. And since the army's an open label, would you expect to release data as the trial advances, perhaps before all patients are dosed?

Got it thank you for that and.

It's simple.

All right and we'll go from low ball would be ex.

Back to I think Inc.

<unk> Italia and advances that obstacle.

And with that dog.

Stuart Kupfer: I'm sorry, Stuart, can you take that? Right, well, the I'm sorry, but I just said the question was about releasing data for cohort three. Was that the question? Yeah.

Okay.

I'm, sorry, Stuart and you take that.

Alright.

And I'm, sorry, if I understood. The question was it not releasing data from cohort three was that the current yeah yeah.

And in line for that.

Well the the.

unknown: Well, let me say first of all that the results from Cohort 1 and 2 essentially will inform our planning for Phase 3. So I just want to make it very clear that those are the cohorts that are focused on our dose finding objectives. So that will...

Well, let me say first of all.

And the the results from cohort one and two.

Essentially it will inform our planning for phase III. So I just wanted to be very clear.

That.

Those are the cohorts that are focused on our dose finding.

Objectives.

And that will.

Stuart Kupfer: We plan to start that study by the end of the year, so the conduct of Cohort 3 or the start of Phase 3 is not contingent on the completion of Cohort 3.

Potentially feed into our phase III trial design and we plan to start that study by the end of the year.

Cohort the conduct of cohort three or the start of phase III is not contingent on completion of cohort three.

And so.

Stuart Kupfer: So, having said that, we will release the results essentially when we get to the point of completing that cohort. It will be likely later in the year, but again, we don't have a specific meeting or timeline at the moment, and again, it's not tied to starting.

Having said that we.

We will release the results of essentially when we.

And at the point of completing.

Completing that cohort.

And it will be.

Later in the year.

But again, it's we don't have a specific need.

Meaning are your timeline at the moment and again, it's not tied to starting our <unk>.

Stuart Kupfer: Our phase three trial. Yeah, most likely, this open-label extension will be generating data for a while, and we will be periodically reporting on its progress.

Phase III trial.

Yes, and most likely this open label extension will be generating data for a while and we will be periodically reporting on its progress.

unknown: Got it, thank you very much. Thank you.

Got it thank you very much.

Q.

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

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

Charles.

Charles Cliff Duncan: Hey, Robert, and team. Thanks for taking our question and congratulations on the forward progress with Omicaptive. Very good productivity this quarter. I wanted to ask you a question about that recent FDA meeting. I know that you probably can't give us any details, but

Hey, Robert and team and thanks for taking our question and congrats on the forward progress and has helped me captive.

Very good productivity this quarter I wanted to ask you question about that recent FDA meeting I know that you probably can't give us details but.

Charles Cliff Duncan: I'm just wondering, first of all, if you've received the meeting minutes.

Just wondering first of all if you've received the meeting minutes, yet and secondly.

unknown: Unknown Speaker, Unknown Speaker, Unknown Speaker, the

unknown: Do you feel like the FDA was most compelled by efficacy?

Do you feel like to FTE was most compelled by the efficacy and we've seen or by the identification of the high burden and relatively underserved patient population likely Bose.

unknown: I was seen or by the identification of the high burden and relatively underserved

Robert I. Blum: Under-served patient population, likely both, but where do you think their real interest lies? So, good question. Firstly, with regard to the minutes, yes.

Or do you think they're real and interest months.

And so good question, firstly with regard to the minutes, yes and.

Robert I. Blum: And we have received them. With regard to your second question, I don't think I can speak for FDA. But I think, as you know, with a program that comprises over 30 clinical trials and a phase three pivotal trial that involves over 8,000 patients in 35 countries, it's a rather robust data set that we have generated in connection with Omicamp to McCarble over 15 years. I don't think the FDA is newly realizing the unmet need in heart failure, and you've seen how they've been leaning forward in connection with approvals in that space, all be it for medicines that directly impact cardiac muscle.

And we have received them.

With regard to your second question I don't think I can speak for FDA.

But I think as you know.

With a program that comprises over 30 clinical trials and our phase III pivotal trial that has over 8000 patients and 35 countries. It's a rather robust dataset that we have generated in connection with AUM and <unk>.

Mccarville over 15 years.

And I don't think the FDA is newly realizing the unmet need and heart failure, and you've seen how they've been leaning forward and connection with approvals and that space.

Albeit not medicines that directly impact cardiac muscle.

Robert I. Blum: And I think, while I can't speak for FDA, we have had many, many, many listening sessions with opinion leaders since the Galactic results were provided. And, There is a very consistent theme running across those conversations, which is, this is an opportunity that we've been looking for in connection with a new mechanism therapy that binds directly to cardiac muscle, enhances cardiac function, improves cardiac performance, and can do so safely without risk of arrhythmias, heart rate, and where blood pressure and renal function are not compromised.

And I think.

Well I can't speak for FDA, we have had many many many listening sessions with opinion leaders since the galactic results have been provided.

And.

There is a very consistent theme running across those conversations.

Which is this is.

And opportunity that we've been looking for in connection with.

The new mechanism therapy that binds directly to cardiac muscle enhances cardiac function improves cardiac performance and can do so safely without risk of arrhythmia is heart rate and blood pressure and renal function are not compromised. So that's what we bill.

Robert I. Blum: So that's what we believe Omicamptomacarbal represents, as something that could be complementary to standard of care. And keep in mind, the results we saw in Galactic were on top of standard of care. And we believe that that speaks to an opportunity set for Omicampt of McCarble. And we discussed that with FDA, and we were pleased with the feedback. I hope that answers your question.

Please <unk> represents.

And could be complementary to standard of care and keep in mind. The results, we saw and Galactic we're on top of standard of care.

And we believe that.

That speaks to and opportunity set for <unk>, and we discussed that with FDA and we were pleased with the feedback I hope that answers your question.

Charles Cliff Duncan: Yeah, absolutely. So it's kind of the...

Yeah, absolutely. So it's kind of the entire and can stop but it does seem like they certainly considered the differentiated mechanism of action and potentially target product profile.

Robert I. Blum: So it's kind of the entire gestalt, but it does seem like they certainly consider the differentiated mechanism of action and potentially target product profile. I think it's important that, you know, the FDA has been involved in a lot of public meetings with academics and biopharmaceuticals, cardiovascular, and heart failure researchers, and trying to advance the field. You know, a couple of years ago, guidance came out to reiterate their position on, you know, what approvability for drugs and heart failure looks like, and you see, you know, many senior members of the FDA involved in these meetings.

I think it's important that the FDA has been involved and a lot of.

Public meetings with academics and Biopharma.

Cardiovascular heart failure researchers.

And trying to advance the field.

A couple of years ago, our guidance came out to reiterate their position on what approve ability for drugs and heart failure looks like.

And that you see many senior members of the FDA involved and these.

Robert I. Blum: And I think that just reflects the recognition that there's tremendous unmet need here, despite the fact that we have existing therapies. You know, you can just even look at the event rates in Galactic; they exceed 30% and even higher than that in some subpopulations. That's still a tremendous need despite the therapies that we have.

And these meetings and.

I think that just reflects on.

A recognition that there is a tremendous unmet need here. Despite the fact that we have existing therapies and.

You can just even look at the event rates from Galactic.

And there they exceed 30% and even higher than that and some sub population. So.

Still a tremendous need despite the therapies that we have.

Charles Cliff Duncan: I know there will be a lot of questions on 274 from other analysts, so I'll leave that to them. But I wanted to ask you about COURAGE-ALS. You mentioned being in a position to start that Phase 3. Once you nail down Omicamptive, Go-To-Market, and then potential...

And it makes sense I know there'll be a lot of questions and $2 seven and four from their analysts so I'll leave that to them, but and wanted to ask you about courage AOS and you mentioned being in a position to start that phase III.

<unk> nailed down and only captive go to market and then potential moving to seven four into phase three and I guess.

Charles Cliff Duncan: Moving 274 into Phase 3, and I guess I'm kind of wondering what the trigger points are with regard to Courage ALS, if you can, if you can share them with us.

And I'm wondering.

What are the trigger points.

With regard to encourage AOS, if Houston, if you can share them with us that you are waiting towards being able to operationalize that net study.

unknown: That you're waiting for to be able to operationalize that study. Sure.

Robert I. Blum: Sure, good question. First of all, as you may recall, we presented the design for CourageALS late last year. And we've also commented on additional secondary analyses that lend support for ways we think we can enrich the response seen in Fortitude ALS as designed into that phase three trial, Courage ALS. We've also announced that Astellas has agreed to provide co-funding of Courage ALS in connection with their receipt of a low single-digit royalty on sales in certain countries.

Sure. Good question. So firstly as you may recall, we presented the design for courage AOS late last year.

And we've also commented on additional secondary analyses that lead and support for ways. We think we can enrich the response seen in fortitude ALS as designed into that phase III trial courage AOS and we've also announced.

And that <unk>.

Telus has agreed to provide co funding of courage.

And.

Connection with their receipt of a low single digit royalty on sales in certain countries. We've also announced that courage AOS is designed with interim analyses. So that we can see if it is.

Robert I. Blum: We've also announced that Courage ALS is designed with interim analysis, so that we can see if it is. Affirming the kind of activity that we designed and powered the study for based on what we saw in phase two. So we took certain Steps to Prepare for the Potential Start of COURAGE-ALS. But we're a small company, and we have to maintain priority and focus.

Affirming the kind of activity that we designed and powered the study for based on what we saw and phase two so we took certain step.

Steps to ready for the potential start of courage AOS.

But we're a small company and we have to maintain priority and focus. So we wanted to make certain that we understood what would be the path forward for <unk> and CK, two seven and four.

Robert I. Blum: So we wanted to make certain that we understood what the path forward for Omicamptomecarbol and CK274 is before we commit to operationalizing Courage ALS, and we laid out a couple of objectives or milestones. Firstly, we wanted to see the galactic results. We've seen them.

Before we commit to operationalize encourage AOS and we laid out a couple of objectives or milestones. Firstly, we wanted to see the galactic results. We've seen them. We wanted to understand if they could support an NDA filing and we believe that we have that feedback and that they do and we.

Robert I. Blum: We wanted to understand if they could support an NDA filing, and we believe that we have that feedback and that they can. And we expect to file in the second half of the year.

To file in second half of the year, but we also want to understand the go to market strategy and how that can.

Robert I. Blum: But we also want to understand the go-to-market strategy and how that can return on investment, The Timelines, the Expenses, and the Activities, and make certain that we've got our arms around that and we're in the process of making that happen. We also wanted to understand CK274 and what its path to Phase 3 could be. So that's partly answered by the fact that we've seen interim data from Cohort 1, and we're engaging regulatory authorities, and we are preparing for potential Phase 3 later this year.

Return on investment the timelines the expenses and the activities and make certain that we've got our arms around that and where and the process of making that happen. We also wanted to understand CK $2, seven and four and what could be its path to phase III. So that's partly answered.

And by the fact that we've seen interim data from cohort, one and we're engaging regulatory authorities and we are.

Preparing for potential phase III later, this year, but we haven't seen enough yet from Redwood and order to be committal to courage AOS. So we want to see those data in order to be able to be and the best position to know that CK 207, and four has a path forward to phase III and.

Robert I. Blum: But we haven't seen enough yet from Redwood in order to be committal to Courage ALS, so we want to see the data in order to be able to be in the best position to know that CK274 has a path forward to phase 3. And that can be moving forward potentially in parallel with rel-deceptive in Courage ALS in phase 3. Imagine that we'll then be a company with a profile, Omicamptive going to market potentially in 2022, and two programs, one from each of our verticals in phase three, in 2022.

That can be.

Moving forward potentially in parallel with rail dissented.

Encourage AOS and phase III.

Imagine that will then be a company with a profile <unk> going to market potentially in 2022 and two programs one from each of our verticals in phase III and 2022, we like that complexion, we think that's in the interest of shareholders and and the interest of our science.

Robert I. Blum: We like that complexion; we think that's in the interest of shareholders and in the interest of our science. That's what we've been building towards. And if there's anything that we've learned from the course of over 20 years at cytokinetics, it's that there's always an advantage to having one up. The next program up is in the interest of building a sustainable and durable company. Managing a portfolio enables us to build a franchise.

And that's what we've been building towards and if Theres anything that we've learned from the course of over 20 years that sort of kinetics is that theres always advantage to having one up next.

Program up is and the interest of building a sustainable and durable company managing a portfolio enables us to build a franchise.

Across both cardiac and skeletal muscle and so we're not there yet with courage AOS, we still have to turn it over a few cards, but we're getting there in the meantime, we've been conducting start up activities and getting mobilized and I hope that helps.

Charles Cliff Duncan: That does help, Robert. Thank you for the thoughtful answer and strategy, and I appreciate you taking the time to answer our questions.

Salim Qader Syed: Your next question comes from the line of Salim Syed with Mizuho.

That does help Robert Thank you for the thoughtful.

And Sir and strategy and I appreciate you taking our questions.

Salim Qader Syed: Hello, Salim. Great. Hey, hey, Robert.

Sure thing.

Your next question comes from the line of Salim Syed with Mizuho.

Salim Qader Syed: Hey guys, thanks for all the color and congrats on the progress. Just a couple for me if I can.

Hello Celine.

Hey, Robert Hey, guys. Thanks for all the color and congrats on the progress.

Just a couple from me if I can.

Salim Qader Syed: Fady, did I hear you right that we're getting the data for Redwood in July? I think I said mid-year, isn't July mid-year? It is, but I thought you mentioned the month. I just want to make sure I didn't mishear you. I might have mentioned the month.

Fatty did I hear you right.

Did you think were getting the data from Redwood in July.

I think I said mid year and July to mid year.

It is but I thought you mentioned the month is that I just want to make sure I did.

Mishear, Inc.

I might have mentioned the month I think we expect that data given the completion of enrollment and the completion of.

Fady Ibraham Malik: I think we expect the data given the completion of enrollment and the completion of, you know, the anticipated study duration and things for it to read out sometime in July. Given that we still haven't locked the database, we are still conducting the study, I've seen your notes, and you've made certain calculations and projections on timing. What I can say is that we're looking to mid-year, and that's still to be determined based on things still to happen. Okay, I got it.

The anticipated study duration and things for it to read out sometime in July.

Given that.

We still havent locked the database, we still are conducting the study.

I've seen your notes and you've made certain calculations and projections on timing what I.

I can say is that.

We're looking to mid year, and that's still to be determined based on things still to happen.

Okay got it just just to clarify and that so I mean, if you guys had finished enrollment for cohort two.

Salim Qader Syed: Just to clarify on that, though, if you guys had finished enrollment for cohort two, in February, I believe, I think you guys announced that on the 25th, specifically, why wouldn't you be able to lock the database? Two weeks post the Week 10 treatment duration, so at the last echo, why wouldn't you be able to lock it then for a cohort too and present the data earlier? Just out of curiosity.

In February I believe and things you guys announced that on the 2000 and specifically.

Why wouldn't you be able to lock the database.

Two weeks from post the 10 treatment duration, so that the lost Echo why wouldn't you be able to lock. It then for cohort two and present the data earlier and this any curiosity.

Salim Qader Syed: Salim, there's actually a four-week period after week 10, so there's a two-week echo at week 12, and then there's a two-week follow-up at week 14. Um, you know, there's a period of time when all the echoes have to be centrally read. Page PAGE of NUMPAGES www.verbalink.com Page PAGE of NUMPAGES Okay, got it.

So theres actually a four week period. After we turn so there is a two week echo at week 12, and then Theres a two week follow up a week 14.

Theres a period of time when all of the echoes has to be centrally read and adjudicated and the data needs to be cleaned and all that sort of stuff. So.

The timeline is something that requires.

And includes database lock and core lab activities and so forth.

Salim Qader Syed: And then, just secondly, you guys are starting to discuss phase three for CK274, and I'm just wondering how you guys are planning to do this with Mavicampton on the market. I guess PDUFA is in January 2022. Are you guys contemplating the head-to-head versus MAFA, or not? How are you guys exactly thinking about this with another HCM asset? Potentially on the market, early part of 22. It's a good question, but I don't think it would be reasonable for us to be responding to that from the competitive positioning standpoint, recognizing that there could be a single pivotal trial, or there could be more than one. We are ultimately going to be deciding how best to position and frame CK274 in what will be a dynamic space. We do expect BMS to get approval for Mavicampton in 2022. But we also believe that the trial that we expect to conduct, at least the

Okay got it and then just secondly.

And you guys are just starting to discuss the phase III for CK, two four and and just wondering.

And you guys are planning to.

Do this with <unk> on the market.

And that's a pity.

And January 2022.

Are you guys contemplating the head to head vs Mappa or.

Or how are you guys exactly you're thinking about this with another HCM asset.

And the market and early part of 'twenty two.

It's a good question, but I don't think so.

It would be reasonable for us to be responding about that from the competitive positioning standpoint, recognizing that there could be a single pivotal trial, there could be more than one we're ultimately going to be <unk>.

Deciding how best to position and frame CK 274, and what will be.

A dynamic space.

And do.

Expect BMS should get approval from Abbott camped in 2022, but we also believe that.

The trial that we expect to conduct at least.