Q4 2021 Cytokinetics Inc Earnings Call

Unknown Executive: Good afternoon and welcome, ladies and gentlemen, to Cytokinetics' fourth 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.

Good afternoon, and welcome ladies and gentlemen, two sided kinetics fourth quarter 2021 conference call at this time I would like to inform you that this call is being recorded and that all participants are in a listen only mode at the company's request, we will open the call for questions and answers. After the presentation, we will allow for up to two questions.

Unknown Executive: At the company's request, we will open the call for questions and answers after the We will allow for up to two questions per participant. I will now turn the call over to Joanna Segal. Cytokinetics, Senior Manager of Corporate Communications and Investor Relations. Please go ahead.

<unk> per participant I will now turn the call over to Joanna to Gal.

Zero kinetics senior manager of corporate Communications and Investor Relations. Please go ahead.

Joanna Segal: Thanks. Good afternoon, and thanks for joining us on the call today. Robert Blum, President and Chief Executive Officer, will begin with a brief overview of the quarter and recent developments. Fady Malik, EVP of R&D, will then provide updates related to omicans of McCarville and CK136. Stuart Kupfer, SVP and Chief Medical Officer, will provide an update on Appicampton and Royal Decentive. Andrew Callos, EVP and Chief Commercial Officer, will discuss commercialization planning activities for Omacamptic McCarville. Robert Wong, VP and Chief Accounting Officer, will provide a financial overview for the past quarter.

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

Robert Blum, President and Chief Executive Officer will begin with a brief overview of the quarter and recent development, Saudi Malik EVP of R&D will then provide updates related to own Mccann <unk> and CK 136, Stuart Kupfer, SVP and Chief Medical Officer will provide an update on Outback Hampton and rather center.

Andrew Carlos EVP, and Chief commercial officer will discuss commercialization planning activities for our mechanical Mccarville, Robert Wong VP, and Chief Accounting Officer will provide a financial overview for the past quarter and Ching jaw, SVP and Chief Financial Officer will discuss our 2020 to financial guidance and corporate development strategies.

Robert Blum: And Ching Jaw, SVP and Chief Financial Officer, will discuss our 2022 financial guidance and corporate development strategies. Finally, Robert Blum will provide closing comments and review expected key milestones for 2022. Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements.

Robert Brian will provide closing comments and review of expected key milestones for 2022.

Robert Blum: 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 fourth quarter 2021 financial results filed on Form 8K today. We undertake no obligation to update any forward-looking statements after this call.

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 fourth quarter 2021 financial results filed on form 8-K today, we undertake no obligation to update any forward looking statements. After this call now I will turn the call over to Robert.

Robert Blum: Now, I will turn the call over to Robert. Thank you, Joanna. And thanks again to everyone for joining us on the call today. We had a very productive fourth quarter, with additional positives and progress continuing into the early part of this year. Most notably, we recently announced that the FDA accepted for filing our NDA for Omicamptomacarbal, assigning a PDUFA date of November 30, 2022. This is an exciting milestone for our company, which has been made possible by dozens of clinical trials, thousands of clinical trial participants, and years of dedication from employees of Cytokinetics.

Okay.

Robert Blum: We also announced the results of METEORIC-HF, which did not show an effect of treatment with omicamptomacarbal compared to placebo on exercise capacity in patients being treated with standard of care medical therapy. While we are of course disappointed in this result, the NDA on file with the FDA is based on the results from Galactic HF, and we do not expect the results from Meteoric HF to read on the potential approval of Omicamptomicarbol, given the safety profile was consistent with prior clinical trials. Turning to AFI-CAM.

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

We had a very productive fourth quarter with additional positives in progress continuing into the early part of this year.

Most notably we recently announced that the FDA accepted for filing our NDA for <unk> assigning a <unk> date of November 32022.

This is an exciting milestone for our company, which has been made possible by dozens of clinical trials.

A clinical trial participants and years of dedication from employees of subtle kinetics.

We also announced the results of meteoric HFF, which did not show an effect of treatment with Omi captive mccarville compared to placebo on exercise capacity in patients being treated with standard of care medical therapy.

While we are of course disappointed in this result, the NDA on file with the FDA is based on the results from Galactic HFF and we do not expect the results for meteoric HFF to read on the potential approval of <unk> given the safety profile was consistent with prior clinical trials.

Turning to Africa Hampton, we've made substantial progress in this program throughout 2021 and again already this year during the quarter. We received breakthrough therapy designation from the FDA for Alfie Kimpton The center for drug evaluation of the National metals, a medical products administration.

Robert Blum: We've made substantial progress in this program throughout 2021, and again, already this year. During the quarter, we received breakthrough therapy designation from the FDA for Afecamptin. The Center for Drug Evaluation of the National Medical Products Administration also granted breakthrough therapy designation for Afecamptin for the treatment of symptomatic obstructive HCM in China.

Also granted breakthrough therapy designation for Alfie Camden for the treatment of symptomatic obstructive HCM in China.

Robert Blum: Additionally, just yesterday, we announced that Sequoia HCM, the phase 3 clinical trial of aficamptin in patients with symptomatic obstructive HCM, has opened to enrollment. We also recently shared top-line results from cohort 3 of Redwood HCM in patients treated with disipiramide, which is supportive of including this patient population in Sequoia HCM. Later in this call, Stuart will detail our plans for expanding the development program for Affey-Campden with additional trials to be underway this year.

Additionally, just yesterday, we announced that Sequoia HCM.

<unk> three clinical trial of Alfie Kimpton in patients with symptomatic obstructive HCM has opened to enrollment. We also recently shared top line results from cohort three of Redwood HCM in patients treated with Disopyramide, which is supportive of including this patient population in <unk>.

H C M.

Later in this call Stuart will detail our plans for expanding the development program for Alfie Campton with additional trials to be underway. This year.

Robert Blum: During Q4, we also progressed earlier stage research programs to IND-enabling studies, and we are also planning to advance the clinical development of CK136, our cardiac troponin activator. Fady will speak more to our objectives for this novel mechanism program in a moment. Underpinning our recent successes and support of our ambitious goals this year is our strong balance sheet and funding commitments that together represent over two years of cash runway, bolstered by two recent transactions on which Ching will elaborate further.

During Q4, we also progressed earlier stage research programs to R&D, enabling studies and we are also planning to advance the clinical development of CK 136, our cardiac troponin activator, Saudi will speak more to our objectives for this novel mechanism program in a moment.

Underpinning underpinning our recent successes and supportive of our ambitious goals. This year is our strong balance sheet and funding commitments that together represent over two years of cash runway bolstered by two recent transactions on which Jim will elaborate further.

Robert Blum: We are entering an exciting new phase for our company. We've continued to expand our team, and we're building new capabilities leading up to the potential approval and expected launch of Omicampt and McCarvel. At the same time, we've continued to work across our pipeline of late-stage programs with Affy Campton and Rel Decentive, as well as earlier-stage programs, including CK136 and our preclinical activities, all progressing, Today, we look forward to sharing updates with you from all of these programs, as well as our expected milestones for the year. And with that, I'll turn the call over to Fady to elaborate firstly on recent developments related to Omicamptomacarbal and CK136. Thanks, Robert.

We are entering an exciting new phase for our company. We've continued to expand our team and we're building new capabilities, leading up to the potential approval and expected launch of Omi captive mccarville.

At the same time, we've continued to work across our pipeline of late stage programs with Abbvie, Kimpton and real deceptive as well as earlier stage programs, including CK 136, and our preclinical activities all progressing.

Today, we look forward to sharing updates with you from all of these programs as well as our expected milestones for the year.

And with that I'll turn the call over to Saudi to elaborate firstly on recent developments related to <unk> and CK 136.

Fady Malik: Last week, we announced the top-line results of METEORIC-HF, evaluating the effect of 20 weeks of treatment with Omacamptin-McCarbol compared to placebo on exercise capacity. In this trial consisting of 276 participants, there was no effect on the primary endpoint, which was the change in peak oxygen uptake, or peak VO2, as measured by cardiopulmonary exercise testing from baseline to week 20. Adverse events were similar between the treatment arms, and it's important to note in this trial that we enrolled a lower risk patient population than galactic HF and investigated a different hypothesis, namely increasing exercise capacity as opposed to reducing the risk of clinical outcomes.

Great. Thanks, Robert.

Last week, we announced the topline results of meteoric HFF evaluating the effect of 20 weeks of treatment with AUM of Camden mccarville compared to placebo on exercise capacity.

And this trial consisting of 276 participants there was no effect on the primary endpoint, which was the change in peak oxygen uptake or <unk> as measured by cardiopulmonary exercise testing from baseline to week 20.

Adverse events were similar between the treatment arms and its important to note in this trial that we enrolled a lower risk patient population than galactic HFF and investigated a different hypothesis, namely increasing exercise capacity as opposed to reducing the risk of clinical outcomes.

Fady Malik: While medical therapies have demonstrated significant reductions in the risk of adverse clinical outcomes in heart failure patients with reduced ejection fraction, as was also observed with Omicamptin, McCarvel, and Galactic HF, Demonstrating an improvement in exercise capacity with these same medical therapies has been elusive.

Well medical therapies have demonstrated significant reductions in the risk of adverse clinical outcomes in heart failure patients with reduced ejection fraction as was also observed with AUM of Camden Mccarville in Galactic HFF.

Demonstrating an improvement in exercise capacity with the same medical therapies has been elusive.

Fady Malik: METEORIC-HF was an extremely well-conducted trial, performed under challenging circumstances given the pandemic. I want to congratulate the study team and the investigators for completing this trial, as well as to thank the patients for their participation. The full results, which are embargoed for now, will be presented at the ACC Scientific Session as a late-breaking clinical trial in April. We're continuing to pursue additional learnings from GALACTIC-HF. In the fourth quarter, we presented the results from post-hoc analyses showing that treatment with omicamptomacarbal was associated with a significant reduction in the risk of stroke.

Meteoric HFF was an extremely well conducted trial performing and performed under challenging circumstances, given the pandemic.

I congratulate the study team and the investigators for completing this trial as well as to thank the patients for their participation.

Full results, which are embargoed for now will be presented at the ACC scientific session as a late breaking clinical trial in April .

We're continuing to pursue additional learnings from Galactic H F. In the fourth quarter, we presented the results from post hoc analysis, showing that treatment with <unk> was associated with a significant reduction in the risk of stroke. This reduction may be related to the reduction in adverse events of atrial fibrillation or <unk>.

Fady Malik: This reduction may be related to the reduction in adverse events of atrial fibrillation or flutter, as well as improvements in atrial and ventricular function that have been observed in GALACTIC-HF and previous clinical trials for vomicamptive macarbal. At the upcoming ACC Scientific Sessions in April, we look forward to presenting new analyses from GALACTIC-HF, comparing the effect of Omicamptomacarbal on the pre-specified subgroups of hospitalized patients versus outpatients. Plus, our Health Economics and Outcomes Research colleagues, in collaboration with Dr. Nihar Desai of the Yale School of Medicine and others, will be presenting data on the heart care, the health care resource utilization, as well as the associated intensity and cost of patients from galactic HF.

As well as improvements in atrial and ventricular function that had been observed in galactic <unk> in previous clinical trials, Oklahoma captive mccarville.

At the upcoming ACC scientific session in April we look forward to presenting new analyses from Galactic HFF comparing the effect of <unk> on the pre specified subgroups of hospitalized patients versus outpatient plus.

Plus our health economics and outcomes research colleagues in collaboration with Dr. Knee hard to sigh of the Yale School of Medicine, and others will be presenting data on the heart failure heart care, the healthcare resource utilization as well as the associated intensity and cost of patients from Galactic <unk>.

Yeah.

Fady Malik: As Robert mentioned, the NDA for Omicamptomocarbal is under review by FDA with a PDUFA date of November 30, 2022. I want to take a moment to congratulate and thank all the contributors to this filing, as it represents many years of dedication in the pursuit of an innovative hypothesis for the potential benefit of patients with heart failure. Now back to pre-commercialization activities for Omicamp and McCarble. On the medical affairs side, in the fourth quarter, we continued to expand the size and leadership of our therapeutic medical scientist team and began development of our managed health care medical science team as well. We also completed vendor selection for the Medical Contact Center.

As Robert mentioned, the NDA for <unk> <unk> is under review by FDA with a <unk> date of November 32022.

I want to take a moment to congratulate and thank all of the contributors to this filing as it represents many years of dedication and the pursuit of an innovative hypothesis.

And for the potential benefit of patients with heart failure.

Now back to pre commercialization activities for <unk>.

On the medical affairs side in the fourth quarter, we continued to expand the size and leadership of our therapeutic medical scientists team and began development of our managed health care medical science team as well.

We also completed vendor selection for the medical contact center.

Unknown Executive: And finalize the governance and design of our investigator-sponsored study program. The medical affairs team will continue important education activities supportive of the potential launch of Omicamptomicarbals, driven by our 2022 strategic plan. Switching gears to CK136, our investigational novel cardiac troponin activator.

And finalize the governance and design of our investigator sponsored study program.

Medical Affairs team will continue important education activities supportive of the potential launch of AUM in Campton Mccarville, driven by our 2022 strategic plan.

Switching gears to CK 136, our investigational novel cardiac troponin activator during.

Fady Malik: During the quarter, we presented preclinical data relating to its discovery and optimization. We also presented and published preclinical data on an analog of CK136, showing that it increases contractility without negative impacts on myocardial energetics. We have started our planning to enable advancing the development program for CK136 before the end of the year. CK136 has the potential to be differentiated from Omicantin-McCarbyl, given its mechanism of action and our plans to investigate its potential safety and efficacy in adjacent populations of unmet need, such as heart failure with right ventricular dysfunction. With that, I'll turn the call over to Stuart to provide an update on AFI-CAMPTEN and REL-DECEMTIV. Thanks, Fady.

During the quarter, we presented preclinical data relating to its discovery and optimization. We also presented and published preclinical data on an analog of CK 136, showing that and increases contractility without negative impacts on myocardial energetics.

We have started our planning to enable advancing the development program for CK 136, before the end of the year.

CK 136 has the potential to be differentiated from them, we can't do mccarville, given its mechanism of action and our plans to investigate its potential safety and efficacy and adjacent populations of unmet need such as heart failure with right ventricular dysfunction.

With that I'll turn the call over to Stuart to provide an update on <unk> and rail deceptive.

Thanks Patty.

Stuart Kupfer: During the quarter, we were pleased to announce that the FDA granted breakthrough therapy designation for abbey cancer. The treatment of symptomatic obstructive HCM is based largely on the data generated from the Phase II clinical trial, Redwood HCM. ACM remains an area of high in the mid, Few treatment options for patients who often experience many symptoms that impact their daily quality of life. A few weeks ago, we also shared top-line results from Cohort 3 of Redwood HCM conducted in patients with obstructive HCM who were refractory.

During the quarter, we were pleased to announce that the FDA granted breakthrough therapy designation, perhaps you can't.

With the treatment of symptomatic obstructive HCM based largely on the data generated from the phase II clinical trial Redwood HCM.

Hey, Sam remains an area of high unmet need.

Few treatment options for patients, who often experience many symptoms that impact their daily quality of life.

A few weeks ago. We also shared top line results from cohort three at Redwood HCM conducted in patients with obstructive HCM double refractory despite treatment with the last line of therapy Disopyramide.

Stuart Kupfer: Despite treatment with the last line of medical therapy, Results showed that substantial reductions were achieved in the average resting and post-foul salvo, left ventricular outflow tract, These decreases were achieved with only modest decreases in average LV ejection practice, with no patients whose ejection fraction fell below the pre-specified safety threshold of 50%.

<unk> showed that substantial reductions were achieved in the average resting and post valsalva.

Left ventricular outflow tract ratings.

Decreases were achieved with only modest decreases in average Lv ejection fraction.

With no patients, whose ejection fraction fell below the pre specified safety threshold of 50%.

Stuart Kupfer: The pharmacokinetics and safety and tolerability profile of athamcanthin were consistent with prior experience in Redwood HCM, and there were no treatment in a, We look forward to presenting the full results of Cohort 3 at the ACC Annual Scientific Sessions in April. Yesterday, we were pleased to announce the opening of enrollment in Sequoia HCN. Phase 3 Registrational Trial of Athlete Cancer.

The pharmacokinetics and safety and Tolerability profile of that in Canada and were consistent with prior experience in Redwood HCM.

And there were no treatment interruptions.

We look forward to presenting the full results of cohort three at the ACC annual scientific session in April .

Yesterday, we were pleased to announce the opening of enrollment in Sequoia HCM the phase III Registrational trial I'm happy Camden.

Stuart Kupfer: Sequoia HCM is a randomized, double-blind, placebo-controlled international clinical trial designed to compare 24 weeks of treatment with apicampin or placebo in patients with symptomatic obstructive HCM, who has substantial outflow tract gradients despite background medical therapy. The primary objective is to evaluate the change from baseline to week 24 in peak VO2 measured by CPET as a measure of exercise capacity. We expect to enroll 270 patients to apicampin or placebo, in addition to standard of care, randomized in a one-to-one ratio.

HCM is a randomized double blind placebo controlled international clinical trial designed to compare at 24 weeks of treatment with Abbvie canton or placebo in patients with symptomatic obstructive HCM.

Who has substantial outflow tract gradient despite background medical therapy.

The primary objective is to evaluate the change from baseline to week 24, and <unk> measured by C pet as a measure of exercise capacity.

We expect to enroll 270 patients to Abbvie Camden or placebo in.

In addition to standard of care randomized in a one to one ratio.

Stuart Kupfer: Following the positive results of Cohort 3 of Redwood HVM, Patients whose background therapy includes disipiramide will also be eligible to enroll. Each patient will receive up to four escalating doses of apicampin or matching placebo. Beginning with 5 mg once daily and escalating to 10, 15, or 20 mg once daily, as needed to achieve target outflow track rating.

Following the positive results of cohort three of Redwood HCM.

Patients, whose background therapy includes disopyramide will also be eligible to enroll.

Each patient will receive up to four escalating doses of anti canton or matching placebo.

Beginning with five milligrams once daily and escalating to 10, 15 or 20 milligrams once daily.

As needed to achieve target outflow tract gradient.

Stuart Kupfer: This escalation is based on echocardiography alone. Secondary objectives include evaluations of the change in KCCQ clinical symptom score, and New York Heart Association functional class at week 12 and week 24. While the inclusion and exclusion criteria are summarized in yesterday's press, One of the key criteria I want to call out is that we'll be enrolling patients with peak CO2, less than 80% of that predicted for each patient. Indicating a clear and objective reduction in exercise performance.

This escalation is based on Echocardiographer alone.

Secondary objectives include evaluation of the change in case in CQ clinical symptom score.

In New York Heart Association functional class at week, 12, and week 24.

While the inclusion and exclusion criteria are summarized in yesterday's press release.

One of the key criteria I want to call out is that we will be enrolling patients with P. C O two less than 80% of that predicted for each patient and.

Indicating a clear and objective reduction and exercise performance.

Stuart Kupfer: Therefore, we do expect to enroll a patient population whose decreased functional capacity is characterized by an objective, rigorous measure. We anticipate enrollment of Sequoia HCM to take roughly one year, and therefore expect to enroll through the duration of this. Meanwhile, we're continuing to enroll prior patients from Redwood HCM into the Open Label Extension Study, Redwood HCM OLE. The great majority of patients from Redwood HCM are choosing to continue into the Open Label Extension, with 37% with 37 patients so far included, at sites that are open to enrollment. We look forward to sharing the first data cut from the Open Label Extension of Redwood HCM later this year.

Therefore, we do expect to enroll a patient population whose decreased functional capacity is characterized by an objective rigorous measurement.

We anticipate enrollment of Sequoia HCM to take roughly one year.

And therefore expect to enroll through the duration of this year.

Meanwhile, we're continuing to enroll prior patients from Redwood HCM into the open label extension study Redwood HCM OLED.

Great majority of patients from Redwood HCM are choosing to continue went to the open label extension with 37% with 37 patients. So far included.

Sites that are open to enrollment.

We look forward to sharing the first data cut from the open label extension of Redwood HCM later this year.

Stuart Kupfer: This year we also plan to expand the development program for, First, we plan to add a Cohort 4 to Redwood HCM to enroll symptomatic patients with non-obstructive, This approach will enable us to move more expeditiously into a potential pivotal clinical trial in non-obstructive HCM thereafter. We expect to begin enrolling Cohort 4 at several sites starting in the United States very soon. It will include approximately 30 to 40 patients with non-obstructive HCM enrolled in an open-label fashion, to escalating doses of aficampin of 5, 10, or 15 milligrams as informed by echocardiography. The primary objective will be safety and tolerability of apicampin in this patient population.

This year, we also plan to expand the development program for happy Campbell.

Stuart Kupfer: But we'll also evaluate their biomarker and symptom response. Further details of the design of Cohort 4 will be provided when we announce that it's open to enrollment. Later in 2022, we plan to start an additional phase 3 clinical trial of apicamp and obstructive HCM. To better understand its use relative to the current standard of care therapy.

First we plan to add a cohort four to redwood HCM to enroll symptomatic patients with non obstructive HCM.

This approach will enable us to move more expeditiously into a potential pivotal clinical trial in non obstructive HCM thereafter.

We expect to begin enrolling cohort four at several sites starting in the United States very soon.

It will include approximately 30% to 40 patients with non obstructive HCM enrolled in an open label fashion to escalating doses of basket Camden 510, or 15 milligrams is informed by Echocardiographer.

The primary objective will be safety and Tolerability of Matthew Camden in this patient population.

But we will also evaluate their biomarker and symptom responses.

Further details of the design of cohort four we provided more you announced that it's opened to enrollment.

Second.

Later in 2022, we plan to start an additional phase III clinical trial of App at Canton and obstructive HCM.

To better understand its use relative to the current standard of care therapy.

Stuart Kupfer: The results from this trial may be incorporated into treatment guidelines or an expansion of the label of a, following its potential initial approval that may be based on the results of Sequoia HCM. Our planning to conduct a second phase 3 clinical trial of apicanthin is further testament to our confidence in the next-in-class profile of apicanthin. We look forward to sharing more details about the expansion of this important development program for AfriCanton throughout the year. Turning now to...

The results from this trial may be incorporated into treatment guidelines for an expansion of the label of happy camping.

All in its potential initial approval that may be based on the results of Sequoia HCM.

Our planning to conduct a second phase III clinical trial of epic Camden is further testament to our confidence in the next in class profile of that in canton.

We look forward to sharing more details about the expansion of this important development program for <unk> cancer throughout the year.

Turning now to <unk>.

Stuart Kupfer: Continued enrolling patients in COURAGE-ALS, the phase 3 clinical trial of rel-deceptive in ALS. As a reminder, this is a large international trial that will enroll 555 patients with ALS in the U.S., Canada, Australia and Europe, and it builds on the results from Fortitude AL. Phase 2 clinical trial would show that patients on all those groups of relative symptoms experience less disease progression. Patients on Placebo, Larger and clinically meaningful differences emerging over time. During the past quarter, we presented data from our ALS program at the International Symposium on ALS MND. Among the presentations was an analysis of the baseline characteristics of the first 27 patients enrolled in Courage ALS.

Continued enrolling patients encourage ALS phase.

Phase III clinical trial of <unk> in ALS.

Stuart Kupfer: Which shows that the majority of patients enrolled at the time of the analysis were middle progressors or fast progressors, as was intended by the inclusion criteria of COURAGE-ALS to increase the sensitivity of detecting a treatment effect. As we continue to enroll in this potentially pivotal clinical trial this year, we expect the Data Monitoring Committee to conduct a first interim analysis in the trial, which will assess for futility, and is triggered 12 weeks after approximately one-third or more of the planned number of patients is randomized. We remain enthusiastic about what Courage ALS may deliver for patients with ALS. These patients and their advocacy organizations are fighting tirelessly.

As a reminder, this is a large international trial that will enroll 555 patients with ALS in U S, Canada, Australia and Europe .

And it builds on the results from Fortitude ALS, the phase II clinical trial, which showed that patients on all dose groups of rather sensitive experienced less disease progression in patients on placebo.

With larger and clinically meaningful differences emerging over time.

During the past quarter, we presented data from our ALS program at the International Symposium on <unk>.

Among the presentations with an analysis of the baseline characteristics of the first 27 patients enrolled encourage a L. S.

Which showed that the majority of patients enrolled at the time of the analysis, where middle progresses or fast progresses as was intended by the inclusion criteria of courage allies to increase the sensitivity in detecting a treatment effect.

As we continue to enroll the potentially pivotal clinical trial. This year, we expect the data monitoring committee to conduct the first interim analysis in the trial.

Which will assess for futility and.

And as trigger 12 weeks after approximately one third or more of the planned number of patients is randomized.

We remain enthusiastic about what courage AOS may deliver for patients with ALS.

These patients and their advocacy organizations are fighting tirelessly to support the development of new therapies for what is truly a terrible disease.

Unknown Executive: To support the development of new therapies for what is truly a terrible disease. These patients continue to inspire us every day. With that, I'll turn the call over.

These patients continue to inspire us every day.

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

Andrew Callos: Thanks Stuart. During the fourth quarter, we continued to build our commercial capabilities, systems, organization and infrastructure, while executing against our go to market strategy in the US for Omicant and McCarvel, across market access, sales and market, First, market access progress includes furthering our pricing strategy and distribution approach while we continue to engage with all major payers with plans to expand our payer interactions to include the results from Galactic HS in the coming months.

Thats store during the fourth quarter, we continued to build our commercial capabilities systems organization and infrastructure, while executing against our go to market strategy in the U S for OMA captive mccarville across market access sales and marketing.

First market access progress include furthering our pricing strategy and distribution approach, while we continue to engage with all major payers with plans to expand our payer interactions to include results from Galactic <unk> in the coming months.

Andrew Callos: Second, with our marketing team in place, the brand strategy, as well as the product positioning that highlights the benefits of Olmecantib mecarbil and how it addresses unmet needs in the treatment of heart fire with reduced ejection fraction has been finalized, and we continue to progress the development of our launch campaign. Finally, activities supportive of building and deploying our Salesforce for the potential launch continues. We have finalized Salesforce size and structure.

With our marketing team in place the brand strategy as well as the product positioning that highlights the benefits of <unk> and how it addresses unmet needs in the treatment of heart failure with reduced ejection fraction has been finalized and we continue to progress the development of our launch campaign.

Finally activity is supportive of building and deploying our sales force for the potential launch continues we have finalized sales force size and structure. Furthermore, key customers have been identified across hospitals and cardiologists and fueled territory boundaries have been designed we expect our sales force size to be around 200 ftes.

Andrew Callos: Furthermore, key customers have been identified across hospitals and cardiologists, and field territory boundaries have been designed. We expect our Salesforce size to be around 200 FTEs, and consistent with our gated approach, the hiring of Salesforce representatives will occur after approval of the drug by the FDA. As we have stated previously, our strategy has been based on this gated build, remaining prudent of spend and initiating activities in line with key de-risking events.

And consistent with our gated approach the hiring of sales force Representatives will occur after approval of the drug by the FDA.

As we have stated previously our strategy has been based on mitigated build remaining prudent of spend and initiating activities in line with key de risking events.

Andrew Callos: The recent announcement of acceptance of our NDA by the FDA is one of those events, which has triggered the start of certain activities and some additional hiring and key longer lead time positions including first line field managers, sales operations, commercial learning and development, and further expansion of our HEOR, patient services, access distribution and access distribution, Still, our overall team will only be about one-third of our expected post-approval headcount, as the majority of our spending and FTEs will not occur until approval. Including hiring our field representatives, media purchases, and patient support programs.

Announcement of acceptance of our NDA by the FDA as one of those events.

Triggered the start of certain activities and some additional hiring in key longer lead time positions, including first line field managers shelves operations commercial learning and development and further expansion of our <unk> patient services access distributions in excess distribution teams.

Our overall team will only be about one third of our expected post approval head count as the majority of our spending and Ftes will not occur until approval.

Including hiring of our field representatives media purchases and patient support programs.

Andrew Callos: For Aficampton, we've engaged with global health technology assessment organizations during the past quarter to better understand value drivers that would be supportive of access in key European markets. In 2022, we will complete our U.S. go-to-market strategy for affected and continue to conduct market research with payers, physicians, and patients to inform its potential entry as a new treatment for hypertrophic cardiomyopathy. And with that, I will turn the call over to Robert Wong.

For ASE campaign, we've engaged with global health technology assessment organizations during the past quarter to better understand value drivers that would be supportive of accessing key European markets.

2022, we will compete complete our U S go to market strategy for Ashford Captain and continue to conduct market research with payers physicians and patients to inform potential entry as a new treatment for hypertrophic cardiomyopathy.

I will turn the call over to Robert Wong.

Andrew Callos: Thanks, Andrew. I'll review our cash revenue and spending for the fourth quarter 2021. We end at the fourth quarter with $623.7 million in cash and investments. This cash balance does not include $150 million in proceeds received from transactions executed in late 2021 and early 2022.

Thanks, Andrew I'll review, our cash revenue and spending for the fourth quarter 2021, we.

We ended the fourth quarter with $623 7 million in cash and investments. This cash balance does not include $150 million in proceeds received from transactions executed in late 2021 in early 2022.

Robert Wong: Our revenue in the fourth quarter of 2021 came primarily from $54.9 million of licensed revenue recognized from the transaction with Zhijie, Our fourth quarter 2021 R&D expenses increased to $43.5 million from $29.2 million in the fourth quarter of 2020, primarily due to increases in spending for clinical development activities, for our cardiac muscle inhibitor programs, COURAGE-ALS, facility expenses, and for regulatory filing costs. More than 60% of our R&D expenses were attributable to our cardiovascular programs and the remainder of our expenses were attributable to our skeletal muscle programs and early research activities.

Our revenue in the fourth quarter of 2021 came primarily from $54 9 million of license revenue recognized from the transaction with <unk>.

Our fourth quarter 2021, R&D expenses increased to $43 5 million from $29 2 million in the fourth quarter of 2020, primarily due to increases in spending for clinical development activities for <unk>.

Cardiac muscle inhibitor programs.

Bridge facility.

Facility expenses and for regulatory filing cost.

More than 60% of our R&D expenses were attributable to our cardiovascular programs and the remainder of our expenses were attributable to our skeletal muscle programs and early research activity.

Robert Wong: Our fourth quarter 2021 G&A expenses were $33.8 million, up from $13.9 million in the fourth quarter of 2020, due primarily to higher outside service spending in anticipation of the potential commercial launch of Omecamp to McCarville, an increase in personnel-related costs, including stock-based compensation, and facility expenses for our new headquarters.

Our fourth quarter 2021, G&A expenses were $33 8 million up from $13 9 million in the fourth quarter of 2020, due primarily to higher outside service spending in anticipation of the potential commercial launch of <unk>, an increase in personnel related costs, including stock.

Compensation and facility expenses for our new headquarters.

Ching Jaw: And now Ching will review our Financial Outlook and Corporate Development Strategy. Thanks, Robert. Today we announce our financial guidance for 2022. The company anticipates 2022 revenue will be in the range of $20 to $25 million. Operating expenses will be in the range of $380 to $400 million, and Net Cash Utilization will be approximately $365 to $385 million.

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

Thanks Robert.

We announced our financial guidance for 2022.

The company anticipates 2022 revenue will be in the range of 20% to 25 million.

Operating expenses will be in the range of $380 million to $400 million.

And net cash utilization will be approximately $365 million to $385 million.

Ching Jaw: Our current cash balance of approximately $724 million, Plus additional committed capital expected to be earned from Royalty Pharma upon the dosing of the first patient in Sequoia HDM represents more than two years of forward cash based on our projected operating expenses and net cash utilization range for 2022. Given the PDUFA date of November 30th for Omicantum Carbo and our approach to only hire the majority of the sales force post-NDA approval, I expect a relatively slow ramp up in commercial spending in 2022.

Our current cash balance of approximately $724 million plus.

Plus additional committed capital expected to be earned from royalty pharma upon the dosing of the first patient in Sequoia HCM represents more than two years. So for test based on our projected operating expenses and net cash utilization range for 2022.

Given the Paducah date of November 30th for home and kept them with carbo and our approach to only hire the majority of the sales force post NDA approval.

I expect a relatively slow ramp up in commercial spending in 2022.

Ching Jaw: Most of the sales and marketing spend for the commercial launch of Omicamp and Carbo, For example, related to Salesforce. Media Purchases and Patient Support Program Spending will not occur until 2023 if only Campylobacillus macabra receives approval in late 2022. And therefore, we do not expect significant post-approval related increases in spending until 2023.

Most of the sales and marketing spend for the commercial launch, Oklahoma Kimco Mccarville.

For example related to Salesforce.

Media purchases and patient support program spending will.

We will not occur until 2023.

<unk> received approval in late 2022.

And therefore, we do not expect significant post approval.

Related increases in spending until 2023.

Ching Jaw: Our strong balance sheet is supported by two recent transactions. During the fourth quarter, we announced the extension of our collaboration with Eugene Pharmaceuticals, by entering into an exclusive license and collaboration agreement to develop and commercialize omicantin macabre for HapRap in Greater China. Cytokinetics also entered into common stock purchase agreements that provided for sales, provided for the sale and issuance to entities affiliated with RTW Investments, LP, of shares of cytokinetics common stock with an aggregate purchase price of $20 million at a price per share of $39.125.

Our strong balance sheet is supported by two recent transactions.

During the fourth quarter, we announced the expansion of our collaboration with <unk> Pharmaceuticals.

By entering into an exclusive license and collaboration agreement to develop and commercialize the only sensible in Kabul for Hep wrapped in greater China.

So I look at that also.

<unk> entered into a common stock purchase agreement that provides a poor sales.

Provider for the sale and issuance to entities affiliated with RTW investments L. P of share yourself subtle can ask common stock with an aggregate purchase price of $20 million.

Price per share of 39.1 to $5.

Ching Jaw: In January 2022, we announced that Royalty Pharma will provide Cytokinetics long-term capital of up to $300 million, primarily to support the potential commercialization of Omicantin-McCarbol and further development of African, It will be available to us in five tranches, including an initial tranche of $50 million, which was received upon closing of the deal, and four additional tranches, Those four additional tranches totaling $250 million will be accessible in $25 million increments, subject to certain conditions. Upon the Occurrence of Certain Milestones Related to Omicantum Acarbo and Africam, Each tranche that Cytokinetics draws down will be followed by an interest-free, payment-free period of six calendar quarters. After which equal installment repayments will be required over the following 34 calendar quarters. The total amount of interest and principal repayment will total 1.9 times the amount drawn.

In January 2022, we announced that royalty pharma will provide cytogenetics long term capital of up to $300 million, primarily to support the potential commercialization of only kept them with carbo and.

Further development of epic Kimpton.

It will be available to us in five tranches, including an initial tranche of $50 million, which was received upon closing of the deal.

For additional context.

For additional tranches totaling $250 million will be accessible in $25 million increments subject to certain conditions.

Upon the occurrence of certain milestones related to only kingdom with carbo and epic Kimpton.

Each tranche that set up the next gross down.

I'll be followed by an interest free payment for a period of six calendar quarters. After.

Equally.

Installment repayments will be required over the following 34 calendar quarters.

The total amount of interest and principal repayments will total one nine times the amount drawn.

Ching Jaw: Additionally... Wealthy Pharma purchased from Cytokinetics a revenue participation rate on Africamtum of 4.5% on sales up to $1 billion and 3.5% for sales above $1 billion. Subject to certain step down. In exchange, Rotifarma will pay to Cytokinetics a total of up to $150 million, including $50 million at closing and two additional $50 million tranches, each conditional upon the initiation of potential pivotal clinical trials for obstructive HCM and non-obstructive HCM, respectively. Consistent with our past practices, we will aim to end 2022 with more than two years of forward cast runway.

Additionally.

Royalty pharma purchase from subtle kinetics revenue participation right.

<unk> kept them up four 5%.

Sales up to $1 billion, and three 5% core sales above $1 billion.

Subject to certain step downs.

In exchange royalty pharma will pay to southern can I have a total of up to $150 million, including $50 million at closing and two additional 50 million conscious.

Conditional upon the initiation of a potential pivotal clinical trials for obstructive HCM and now obstructive HCM respectively.

Consistent with our past practices, we will aim to end 2022 with more than two years, so for cash runway.

Ching Jaw: Given the potential for increased spending in 2023 and 2024 to support the planned commercial launch of Omicantum Carbo and our expanded R&D pipeline. We expect to pursue additional business development as well as potential financing and or other corporate development deals again in 2022. And with that, I'll turn the call back over to Robert Blum. Thank you, Ching.

Given the potential for increased spending in 2023 and 2024 to support the planned commercial launch of <unk> and our expanded R&D pipeline.

We expect to pursue additional business development as well as potential financing <unk> other corporate development deals again in 2022.

And with that I will turn the call back over to Robert bump.

Thank you Ching.

Robert Blum: We expect that 2022 will be another transformational year for our company. The work we've engaged in during the fourth quarter of 2021 and the early part of this year has set us up well to execute against ambitious goals set forth in our vision 2025, beginning with what may be the regulatory approval of our first potential medicine, as well as the expansion of our development programs for Aficamptin, alongside of progress with Reldeceptive and the advancement into the clinic of earlier stage candidates and advancement through the clinic of CK136.

We expect that 2022 will be another transformational year for our company.

The work we've engaged in during the fourth quarter of 2021 and the early part of this year.

Set us up well to execute against the ambitious goals set forth in our vision 2025.

Beginning with what may be the regulatory approval of our first potential medicine.

What was the expansion of our development programs for Alpha Campton.

Alongside of progress with <unk> and the advancement into the clinic of earlier stage candidates and advancement through the clinic of CK 103 six.

Robert Blum: Additionally, as Ching mentioned, we're pleased with the recent licensing agreement from McCampton McCarble in China. As we stated, it's our intention to launch Omicamp to McCarble in the U.S. and do that alone, but we're actively pursuing opportunities to potentially partner Omicamp to McCarble in Europe as well as in Japan, and we're remaining focused on long-term strategies of sensibly building out our organization.

Additionally, as Ching mentioned, we're pleased with our recent licensing agreement for <unk> in China.

As we stated.

Our intention to launch <unk> in the U S and do that alone, but we're actively pursuing opportunities to potentially partner <unk> in Europe as well as in Japan, and we're remaining focused on long term strategies of some slowly building out our organization.

Robert Blum: We look forward to sharing more about those corporate development strategies later and throughout this year. And now I'll recap our expected milestones for 2022. For Omicamptomacarbal, we expect to launch Omicamptomacarbal in the United States pending potential FDA approval, which may come in Q4 2022.

Look forward to sharing more about those corporate development strategies later and say well this year.

And now I'll recap our expected milestones for 2022.

For <unk>, we expect to launch of <unk> in the United States pending potential FDA approval, which may come in Q4 2022.

Robert Blum: For AFI Campton, we expect to continue enrollment in Sequoia HCM throughout 2022. We expect to begin enrolling patients with non-obstructive HCM in a Cohort 4 of Redwood HCM, that to occur in this first quarter, 2022. And we expect to begin a second Phase 3 clinical trial of aficamptin in obstructive HCM later in the second half, 2022. And we expect to share data from the Open Label Extension Study for patients who are completing Redwood HCM throughout 2022. For CK1.3.6, we expect to reactivate the development program in this year, 2022.

For <unk> Kimpton, we expect to continue enrollment in Sequoia HCM throughout 2022.

We expect to begin enrolling patients with non obstructive HCM.

<unk> four of Redwood HCM that to occur in this first quarter 2022.

And we expect to begin a second phase III clinical trial of <unk> in obstructive HCM later in the second half 2022.

And we expect to share data from the open label extension study for patients who are completing redwood HCM throughout 2022.

For CK 136, we expect to reactivate the development program in this year 2022 for <unk>, we expect the data monitoring committee to conduct its first interim analysis from courage AOS.

Unknown Executive: For REL-Deceptive, we expect the Data Monitoring Committee to conduct its first interim analysis from COURAGE-ALS in 2022. And for ongoing research, we expect to advance new muscle-directed compounds and conduct IND-enabling studies for one to two potential drug candidates, in this calendar year. Operator, with that, we can now open up the call to questions. We will now begin our question and answer session. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key.

2022, and for ongoing research, we expect to advance new muscle directed compounds and conduct IND, enabling studies for one to two potential drug candidates.

In this calendar year.

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

We will now begin our question and answer session. As a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound key at the company's request, we will allow for up to two questions per participant. Our first question will come from the line of Carter Gould with Barclays. Please proceed with your.

Unknown Executive: At the company's request, we will allow for up to two questions per participant. Our first question will come from the line of Carter Gould with Barclays, please proceed with your question. Good afternoon, Carter. Hello, Carter. Carter, your line may be on mute. Please unmute yourself. Your line is open on our end. Hi, can you hear me?

Jen.

Good afternoon Carter.

Hello to remain with us.

Part of your line maybe on mute. Please UN mute yourself. Your line is open on our end.

Hi can you hear me.

Yes, Hello, I hear you.

Unknown Executive: Yes. Hello. Hi, you've got Edwin on the line for Carter.

Hi, you've got everyone on the line for Carter, we just have a question on the decision to launch the second phase III study for at the Canton.

If you could talk about how this trial will be.

Different versus Sequoia and second is this a result of an ask from the FDA or EMA.

Unknown Executive: We just have a question on the decision to launch the second phase 3 study for at the Hampton. If you could talk about how this trial will be, you know, different versus Sequoia and second, is this a result of an ask from the FDA or EMA? Thanks.

So I'll start and then turn it over to fabby and Stuart, but firstly it is not in response to any request we received from FDA, rather instead, it's underscoring our confidence in a next in class candidate that we think.

Robert Blum: So I'll start and then turn it over to Fady and Stuart. But firstly, it is not in response to any request we receive from FDA. Rather, instead, it's underscoring a confidence in a next-in-class candidate that we think it's incumbent upon us to advance the field, as could ultimately speak to broader labeling. And we think that AFI-CAMPBIN affords us that opportunity.

It's incumbent upon us to advance the field could ultimately speak to broader labeling and we think that Alfie kimpton affords us that opportunity we're.

Fady Malik: We're not going to elaborate too much on its design right now. But I will ask Fady and Stuart if there's anything further they want to add. I'll just maybe add that, you know, there are lots of important scientific questions with regards to therapeutic intervention in this patient population. They all aren't answered by Sequoia, but additional studies may contribute to understanding where therapy may be positioned in guidelines or may be effective under different situations. And as Robert said, we'll provide more details as we get closer to initiating this phase three trial. But we'll emphasize it wasn't in response to any particular feedback from regulators.

We're not going to elaborate too much on its design right now, but I will ask Saudi and Stuart if theres anything further they want to.

I'll, just maybe add that there are lots of important scientific questions with regards to.

Therapeutic intervention in this patient population they all all arent answered by Sequoia.

But they are but.

Additional studies may contribute to.

Understanding where therapy may be positioned in guidelines or maybe.

Effective under different situations.

As Robert said, we will provide more details as we get closer to initiating this phase III trial.

But we will emphasize it wasn't in response to any particular feedback from regulators.

Unknown Executive: Your next question will come from the line of Justin Kim with Oppenheimer. Please proceed with your question. Hello, Justin.

Your next question will come from the line of Justin Kim with Oppenheimer. Please proceed with your question.

Unknown Executive: Hi, uh... Hi, Robert. Thanks for taking the question. Just a couple from me.

Hello, Justin Hi.

Robert Blum: I know the METEORQ data are still fresh in the hands of the team, but was curious if there's any observations on Peak VO2's reliability as an endpoint, particularly during COVID-19, just trying to sort of understand whether there was sort of any variability observed based on patients' enrollment before or during the pandemic. You know, it's a tough question to answer absent being able to share the data, as we will soon enough at ACC, but maybe Fady, do you want to speak to that?

Hi, good.

Good afternoon, and thanks for taking the question.

Just a couple from me.

I know the meteoric data are still fresh in the hands of the team but was curious if there was any observations on peak <unk> reliability as an end point, particularly during COVID-19.

Trying to sort of understand whether there was sort of any variability observed.

Just on patient enrollment before or during the pandemic.

It's a tough question to answer absent being able to share the data as we will soon enough at ACC, but maybe deciding do you want to speak to that.

Robert Blum: Yeah, I think it's a good question, because we obviously conducted this trial during a challenging time. I will say, I think that the quality of the data are surprisingly good in that respect, and that there are very few missing CPET tests, and the quality, the variability, and so forth, was pretty close to what we expected. You know, cardiopulmonary exercise testing in general seems to be a very objective means of assessing exercise capacity, and it is not really, it's not much of a placebo effect there either, so I think the, Overall, the modality in the pandemic, despite the pandemic, was still a meaningful outcome in this trial. Great. And maybe just one on the fourth cohort.

Yes, I think it's a good question because we obviously conducted this trial during a challenging time I will say I think that the quality of the data are surprisingly good in that respect and that.

There are very few missing.

C Pap tests.

And the quality.

Variability and so forth it was pretty close to what we expected.

Cardiopulmonary exercise testing in general.

It seems to be a very objective means of assessing exercise capacity and not really.

Not much of a placebo effect there either so I think the.

Overall, the modality and the <unk>.

Pandemic.

Despite the pandemic was still is still meaningful.

Outcome in this trial.

Okay, great great.

Fady Malik: Given the lack of eventual options for symptomatic non-obstructive disease, would you anticipate these patients to skew maybe more towards the severe side in non-obstructive patients? I'm just kind of curious to know what the specific clinical activity measures might advance the programs to broader, larger studies. Sadi, do you want to take that?

And maybe just one on the.

Fourth cohort given the lack of eventual options for synthetic non obstructive disease would you anticipate these patients to skew maybe more towards the severe side.

In non obstructive patients and just kind of curious to know what the.

Specific clinical activity and measures might advance programs to broader larger studies.

So how do you do you want take that.

Stuart Kupfer: I'll turn it over to Stuart. I think it's still to be seen. I think you see a spectrum of symptoms that you see in the obstructive patients as well. They're going to be less severe and more severely affected patients. We'll skew based on our enrollment criteria a little bit towards the more symptomatic, Patient population, but I don't think that there's reason to per se think they're different. Ehm.

I'll start and I'll turn it over to Stuart I think.

I think it's still to be seen I think youll see the spectrum of.

Symptoms that you see in the.

Struck give patients as well theyre going to be less severe more severe.

We affected patients.

We.

We will skew based on our enrollment criteria, a little bit towards the more symptomatic.

Patient population, but.

I don't think that there is reason that per se I think theyre different.

Stuart Kupfer: Stuart, anything you want to add to that or? Yeah, I mean, I agree. It's certainly just by the fact they're symptomatic indicates a certain degree of disease progression. And, you know, we'll be tracking circulating biomarkers, to sort of characterize Severity of the disease and so that that will, Thank you. Your next question will come from the line of Anupam Rama with J.P. Morgan. Please proceed for the question. Chai Anupam.

Stuart.

Anything you want to add to that or.

Yes.

I agree it certainly just like the fact they are symptomatic.

Somatic indicates a certainty.

Degree of disease progression, and we will be tracking circulating biomarkers as well.

To further characterize.

<unk>.

Disease, and so that will.

Essentially inform us.

We proceed.

And how these patients perform with the safety profile looks in terms of the.

The next next study.

Great. Thanks, so much.

Your next question will come from the line of Andrew Palm Rama with J P. Morgan. Please proceed with your question.

Hi, Aldo pump.

Unknown Executive: Hey, hey, thanks so much for taking the question. Maybe just following on Carter's question on the second Apicampton obstructive study, I know you're not talking about the trial designs too much, but are these going to be kind of two independent or completely different populations that you'll be enrolling, say, in Sequoia versus the second phase three, or will there be some overlap in patient phenotype? Thanks so much.

Hey, Thanks for so much for taking the question maybe just following on Carter's question.

The second <unk> in obstructive study I know youre not talking about the trial designs too much but are these going to be kind of two independent are completely different populations that youll be enrolling say in sequoia versus the second phase III or will there be some overlapping.

Patient phenotype. Thanks, so much.

Robert Blum: That's a good question. Obviously, in light of the fact that they're both going to be directed to patients with obstructive HCM, there's going to be some overlap, but they're really intended to ask and answer different questions. One should not be codependent on the other.

That's a good question.

Obviously in light of the fact that they are both going to be directed to patients with obstructive HCM theres going to be some.

Overlap, but they are really intended to ask and answer different questions. One should not be co dependent on the other and as we've already indicated we expect Sequoia HCM to be alone is sufficient and pivotal for potential registration.

Fady Malik: And as we've already indicated, we expect sequoia HCM to be alone sufficient and pivotal for potential registration. Perhaps that's the best I can do right now without elaborating on the design, which we don't intend to do today. But Fady, anything you want to add?

Perhaps that's the best I can do right now without elaborating on the design, which we don't intend to do today, but Saudi anything you want to add.

Fady Malik: No, I think that, to be clear, I think we are going to, it will be an obstructive HCM patient. And I think, again, to say that, You know, there are lots of scientific questions, you could probably think of several yourself that you'd like to know in terms of how to implement therapy in these patients and what might be expected as a result of therapy. And we don't want to, we want to indicate that we're planning to pursue some of those to better inform the field. But we're just not ready to tip our hand at this point in the process.

No I think thats to.

To be clear I think we are going to pursue.

It will be in obstructive HCM patients and I think.

Again to say that.

There are lots of scientific questions you could probably think of several yourself.

To know in terms of how to implement therapy in these patients.

What might be expected as a result of therapy.

We don't want to.

One indicate that we're planning to pursue some of those to better inform the field.

But we're just not ready to tip, our hand at this point.

And the process.

Unknown Executive: We're not trying to be coy. All we're trying to do is make certain that we get it organized before we start describing it in its design for the fact that we do want to get Sequoia HCM off and running, and then we'll soon enough be able to elaborate on what this next trial will look like. Okay, cool. Thanks so much for taking our questions. Your next question will come from Akash Tewari with Jeffries. Please proceed with your question. Hi, this is Leo Bokash.

We're not trying to be coy.

We're trying to do is make certain that we get it organized before we close.

Describing it in its design.

For the fact that.

We do want to get Sequoia HCM, often running and then we will soon enough be able to elaborate on what this next trial will look like.

Okay cool thanks, so much for taking our question.

Thank you.

Next question will come from our cash to worry with Jefferies. Please proceed with your question.

Unknown Executive: Thank you for answering our question. So could you give us more color on why the team's enrolled in another phase three of the Kempton study? Would you perhaps do a Hatch-for-Hatch study versus MARVA? Also, how much would this trial cost?

Hi.

Hi, This is <unk>. Thank you for that.

No question, so could you give us some more color on why that same thing eroded another phase III Captain study, which are perhaps to hatch the house study, but the smarts Nava.

How much what its trial costs.

Second question is previously noted it's not that the long term extension for obstructive HCM, despite being on a stable dose.

1% patient, it's not a long term extension had there al.

Unknown Executive: And our second question is, previously we noticed MARVA's long-term extension for non-obstructed HCM, despite being on a stable dose, 21% patients on long-term extension, had their LVEF drop below 50%. Is there any color that you could give us on the stability of LVEF for Redwood, for patients in Cohort 1 and 2? Have any of these patients needed dose adjusted after 10 weeks, and they have seen their LVEF drop below 50%?

Yes, chop below 50% is there any color that you could give us on the stability of Lv app for rapidly.

If a patient in cohort one and two have had any of these patients need a dose adjusted after 10 week and they had seen and they have seen their LDF choppy low 50%. Thank you.

Robert Blum: Thank you. So I'll take the first one and maybe ask Fady and Stuart to speak to the data from open label extension. Again, we're not going to speak to the specific design of this second phase 3 study.

So I'll take the first one and maybe ask Saudi and Stuart.

Stuart to speak to the data from open label extension.

Again, we're not going to speak to the specific design of this second phase III study I can tell you the cost associated with that study or more likely going to be borne in 2023. Then 2022, we do expect to start the second phase III study this year, but.

Robert Blum: I can tell you that the costs associated with that study are more likely going to be borne in 2023 than 2022. We do expect to start the second phase 3 study this year. The majority of that spending will not hit our P&L this year.

The majority of that spending will not hit our.

P&L this year.

Robert Blum: I won't comment on whether it's going to be a head-to-head comparison with another drug or not for the fact that that's not our intention today. Instead, our intention is to say that for the fact that now we've raised additional capital and for our confidence in its next-in-class profile, we do believe that it's our obligation to advance the category as should be enabling of potential further expansions in labeling in accordance with standard of care. And I think that's the best we're going to be able to do today. Fady or Stuart, do you want to talk about LVEF and the Open Label Extension?

I won't comment on whether it's going to be a head to head comparison with another.

Drug or not for the fact that.

That's not.

Our.

Intention today instead, our intention is to say that for the fact that now we've raised additional capital and for our confidence in its next in class profile, we do believe that it's.

Our obligation to advance the category should be enabling of potential.

Further expansions in labeling in accordance with standard of care and I think that's the best we're going to be able to do today.

Saudi or Stewart do you want to talk about <unk> and the open label extension.

Stuart Kupfer: Sure, well, you know, we we are planning to present data from an open label extension, you know, in the coming year. So we're not going to elaborate on details, any details right now. What I can say is that I think the data from the first three cohorts of Redwood HCM are really informative. In terms of what we might expect in the longer, So you may recall that there were no patients who required any treatment interruptions.

Sure well.

We are planning to present data from our open label extension.

In the coming year.

So we're not going to elaborate on details any details right now.

What I can say is that I think the data from the first three cohorts Redwood HCM I really formative.

What we might expect in the longer term.

So you may recall that there were no patients required any.

<unk> interruptions.

Stuart Kupfer: Ashwani Verma, Srikripa Devarakonda, Jason Butler, John Henderson, Robert Wong, Steve, And, you know, that's something that, again, we'll just have to sort of continue to follow with, you know, Logger term experience that we'll gain. The Open Label Extension of Redwood, as well as the Sequoia HCM, which is a 24-week trial.

During any of those cohorts and.

I think that sort of speaks to the.

Relatively wide therapeutic index of Appia Hampton and.

That's something that.

Again, we will just have to sort of continue to follow with you.

Longer term experience symbol gain.

You know the open label extension Redwood.

As well as the sequester HCM, which is a 24 week trial.

Stuart Kupfer: It's not for us to comment on another company's drug candidate and how it's performing in a clinical study. What I can tell you is what Stuart just said is we're pretty comfortable that the dosing and the dose regimen, Vermeen, That is echo guided, demonstrated in cohorts one, two, and three, that it was producing predictable exposures that could be maintained. Thank you. Thank you.

It's not for us to comment on another company's drug candidate and how it's performing.

In a clinical study what I can tell you is what Stuart just said as well.

We're pretty comfortable that the dosing and the dose regimen.

That is echo guided.

Demonstrated in cohorts, one two and three that it was producing predictable exposures that could be maintained.

Thank you.

Thank you. Your next question will come from Charles Duncan with Cantor Fitzgerald. Please proceed with your question.

Charles Duncan: Your next question will come from Charles Duncan with Cantor Fitzgerald. Please proceed with your question. Hello Charles.

Charles Duncan: Hey Robert, congrats to you and the team on that OMI NDA acceptance as well as the core start. I have, I'm thinking exercise capacity and so I kind of have a two part question for Fady and then had a follow up that I wanted to ask for Ching. So regarding the two part question on exercise capacity, given the meteoric results, I guess I'm wondering how can you, how do you reconcile that relative to, you know, the mechanism that we've talked about in the past and do you think that that could impact in any way the perception of clinical value for OMI?

Hello Charles.

Hey, Robert Congrats to you and the team on that Omi NDA acceptance as well as it could start.

Half.

We can exercise capacity and so I kind of have a two part question.

For Fannie and then had a follow up that I wanted to ask for Cheng.

Regarding the two part question on exercise capacity.

Even the meteoric.

Results I guess I'm wondering how can you how do you reconcile that relative to.

The mechanism that we've talked about in the past and do you think that that could impact in any way the perception of clinical value for Omi and then the second part is.

Charles Duncan: And then the second part is relative to the conduct of the meteoric study, was there any takeaways that you had from that study that would impact or help you conduct this study better for sequoia with affie cancer? Good questions, Fady.

Relative to the conduct of the meteoric study was there any takeaways that you.

That you have from that that study that would impact or help you conduct this study better for Sequoia with Saffy match.

And so you can't do it.

Good question study.

Fady Malik: Yeah, thanks, Charles. But I think, you know, I think with regards to the results that we saw in New York, the lack of effect on exercise tolerance, I think there are a couple of potential explanations. And admittedly, they're conjectures and shouldn't be taken on as any read on the results. But when you see, we clearly know that omicantin-micarbol increases exercise performance. I mean, that's cardiac performance.

Yes, Thanks, Charles I think.

I think with regards to the results that we.

<unk> New York.

<unk> has an effect on exercise.

I think there are a couple of potential explanations and admittedly there conjectures and shouldnt be taken.

As any.

Read on the results.

But when you see we clearly know that <unk> increases exercise performance.

I mean extra cardiac performance, we've shown that in other clinical trials.

Fady Malik: We've shown that in other clinical trials. But in these patients that we enrolled in New York, relatively stable. You know, the question is, how much is their cardiac performance limiting to their exercise performance? You know, recall, these patients have the heart failure results in a lot of skeletal muscle dysfunction. You see energetic deficits in the skeletal muscle that go a long way, along with cardiac muscle.

But in these patients that we enrolled in New York relatively stable.

The question is how much is their cardiac performance limiting to their exercise performance.

Recall these patients have.

The heart failure results in a lot of skeletal muscle dysfunction.

Dysfunction, you see energetic deficits in skeletal muscle and go along with cardiac muscle and the relative contributions of the two I think are.

Fady Malik: And, you know, the relative contributions of the two, I think, are not very well understood. We clearly see with other drugs, or rather, I should say, mechanical means or device-related means that improve cardiac function, proven in some exercise performance. You know, they generally have much larger impacts on cardiac performance. And so it could just be that the, you know, the magnitude of increase in cardiac performance produced by a drug is not large enough to... You know, to see an improvement in skeletal muscle performance in these patients, or rather exercise performance in these patients.

Not very well understood.

We clearly see with other drugs.

Our other rather I should say mechanical means or device related means that improve cardiac function proven in some exercise performance.

They generally have much larger impacts on cardiac performance and so it could just be that the the magnitude of increase in cardiac performance produced by drug is not large enough to.

To see an improvement in skeletal muscle performance in these patients.

Their exercise performance in these patients.

Fady Malik: That makes sense. And then the risk on AFI, on the conduct of that study, or? Yeah, yeah, I, I think the, well, just the other part was whether it impacts the clinical value of OMACAMPTIV. And I think, you know, there, I think it doesn't really.

That makes sense and then the risk.

On the conduct of that study or yes, yes.

Fady Malik: Most of the focus has been on clinical outcomes. It would have been a nice to have to see, you know, a positive study, obviously, and would have distinguished OMACAMPTIV from other heart failure therapies where you have impacts on clinical outcomes. But, you know, like, like those therapies, you don't have actually impacts on exercise capacity.

I think the just to your other part with whether it impacts the clinical value of only captive and I think.

There I think it doesn't really most of the <unk>.

Focus has been clinical outcomes it would've been a nice to have to see positive study, obviously and would've distinguished only captive from other heart failure therapies, where.

You have impacts on clinical outcomes, but.

Like like those therapies, you don't have actually impacts on exercise capacity. So.

We don't we at least in our market research and things haven't seen a large negative impact of not having.

Benefit there.

Fady Malik: So, you know, we don't, we, at least in our market research and things, haven't seen a large negative impact of not having a benefit there. In terms of takeaways for Sequoia, there's certainly a big advantage to having conducted a large international Phase III trial using an endpoint that's measured the same way as the endpoint we're going to conduct Sequoia with. And so, you know, we have a lot of experience now in terms of how the test can go wrong, how should you train sites, what should you be looking for, and how do you qualify sites, all those things.

In terms of takeaways for Sequoia.

It's certainly a big advantage to having conducted a large international.

Phase III trial, using an endpoint that's measured the same way as the endpoint, we're going to conduct.

Sequoia with and so.

Fady Malik: And I would say, you know, meteoric when you look at the data quality and all that was really an excellently conducted study. And I think that reads well on our ability to do the same in Sequoia.

We haven't had a lot of experience now in terms of how the test can go wrong. How should you trained sites what should you be looking for.

And how do you qualify sites all of those things and I would say meteoric when you look at the data quality and all of that was really an excellent. We conducted study and I think that re dwell on our ability to do the same same in Sequoia.

Ching Jaw: Okay, thank you. And then quickly moving to Ching, regarding expense guidance, appreciate you providing full year guidance and for this year, probably not ready to do that for next year. But I guess I'm just kind of wondering in terms of the expense this year, would you anticipate a step function or incremental increase for next year? And then out of the 365 to 385, you know, expenses, what percentage of that will be spent on omicamptive marketing up, you know, approximately?

Okay. Thank you.

And then quickly moving to Chang.

Regarding expense guidance I appreciate you providing full year guidance.

For this year.

Not ready to do that for next year, but I guess I'm just kind of wondering in terms of the expense. This year would you anticipate a step function or incremental increase for next year.

And then.

Out of the $3 65 to $3 85.

Expenses, what percentage of that will be spent on omi captive marketing hub.

Approximately.

Ching Jaw: Hey Charles, thank you for your question. So first part of your question, as Andrew outlined during the call, we don't expect to begin hiring the sales force until after we receive NDA approval, which is now looking likely to be end of November.

Hey, Charles Thank you for your question so.

The first part of your question.

As Andrew outlined during the call.

We expect to begin hiring the sales force until after we receive FDA approval, which is now looking likely to be end of November .

Ching Jaw: So if you look at 2022, I don't expect significant increases in 2022 relative to the range we gave today. In 2023, those sales force that we hired in 2022 will accrue four-year expenses. So I do expect. Significant headcount expense increase in 2023, in addition to all the marketing spend, media buys, and patient support program, et cetera. So we're not ready to give 2023 guidance, but I think it's safe to say that the expenses in 2023 are expected to be higher than 2022. And in terms of percent of the range, we're not breaking.

So if you look at 2022.

I don't expect expect significant increases.

In 2022 relative to the range, we gave today in 2023.

Those sales force that we hired in 2022 will accrue full year expenses, So I do expect.

A significant headcount increase.

<unk> expense increase in 2023 in addition to all the marketing spend media buys and patients.

Patient support program et cetera. So.

We're not ready to give 2023 guidance, but I think it's safe to say that the expenses in 2023.

<unk> to be higher than 2022.

And.

In terms of percent of the range, but we're not breaking it down.

Robert Blum: Now today, but as Andrew outlined, the spending in 2022 in commercial for Omicamtips and Carbo is roughly a third of the total spend that we will anticipate once Omicamtips is launched and the commercial spending reaches steady state. So I hope that answers. Charles, you asked about whether in 2022 what percent was marketing, and the marketing spend is really quite modern. If you mean commercial, and inclusive of that is supply chain, distribution, logistics, as well as other commercial expenses beyond marketing, then it starts to become a bit more notable, but it's still quite significantly smaller than that which is going to even one of our clinical trials.

Down today.

And to all line.

Spending in 2022.

And commercial for all New Kingdom Carbo is roughly a third of the total spend that we will anticipate once <unk> is launched and.

Commercial spending we just steady state so I hope that answers your question.

And Sir Robert whether in 'twenty.

2022, what percent was marketing and the marketing spend is really quite modest.

If you mean commercial and inclusive of that is supply chain.

Distribution logistics.

As well as other commercial expenses beyond marketing then it starts to become a bit more notable but it still.

Quite significantly.

Smaller than that which is going to even one of our clinical trials.

Robert Blum: So I wouldn't be focused on the marketing spend in 2022 as a big driver of increased spending. Much of that increased spending in 2022 versus 2021, for instance, relates to the fact that it's a full year of Courage ALS, a full year of Sequoia, as well as the additional clinical trials that you heard about today. Why did we choose to do the deals that we did in December and January?

So I wouldn't be focused on the marketing spend in 2022 is a big driver of increased spending much of that increased spending in 2022 versus 2021 for instance relates to the fact that it's a full year of courage AOS a full year of Sequoia.

As well as the additional clinical trials that you heard about today.

Why did we choose to do the deals that we did in December and January a large part it's in order to be able to be in a position to substantially expand the development program for <unk> Kimpton as we announced today.

Charles Duncan: In large part, it's in order to be able to be in a position to substantially expand the development program for AFI Campton, as we announced today. That's helpful, Robert. Appreciate it.

Charles Duncan: Not all that concerned about expenses and look forward to additional BizDev activity out of you folks. Thanks for taking the question. Thanks so much.

That's helpful. Robert appreciate it not all that concerned about expenses and look forward to additional biz Dev activity out of you folks thanks for taking the questions.

Thanks, so much.

Madhu Kumar: Your next question will come from Madhu Kumar with Goldman Sachs. Please proceed with your question. Good afternoon. Hey guys, thanks for taking my question. This is Rob on for MADU.

Next question will come from Madhu Kumar with Goldman Sachs. Please proceed with your question.

Good afternoon.

Unknown Executive: I was just wondering, can you please remind us of what the futility analysis criteria for the potential second half look into Courage ALS is? Sure, I'll turn to Fady and Stuart for that. So the question is about the upcoming futility now. Uh, yeah, correct. What's the criteria?

Hey, guys. Thanks for taking my question. This is Rob on for <unk>. I was just wondering can you. Please remind us of what the futility analysis criteria for potential second half look into courage Oss.

Sure I'll turn to study and Stuart for that.

So the question is about the.

Upcoming futility analysis.

Yes, correct, what's the criteria.

Fady Malik: Well, as we mentioned in the call, you know, we won't conduct that until, We have about a third of the patients who have reached 12 weeks treatment. It's a pretty straightforward utility analysis. It, you know, essentially we're assessing whether a relative sensitive is showing a trend of greater benefit versus placebo. And that's kind of the base. That's sort of the bottom line. So not such a high bar.

Well as we mentioned in the call.

We won't conduct that until.

We have about a third of the patients who have reached 12 weeks treatment, it's a pretty straightforward.

Utility analysis.

It.

Essentially we're assessing whether all.

All of the centers is.

Showing a trend of greater benefit versus placebo.

Fady Malik: But we certainly want to have some level of confidence before we, you know, continue to advance the trial. So that's really the objective of the first interim. You know, this first futility, in keeping in mind the study design provides for a second interim analysis as well, but this futility analysis is really designed to ensure that there's no adverse consequence of the addition of relative deceptive to standard of care, and therefore, to Stuart's point, it's not a particularly high bar we expect to be able to proceed through.

The base, that's sort of the bottom line.

So.

Not such a high bar.

But we certainly want to have some level of confidence before we continue to advance the trial. So thats really the objective of the first interim.

This first futility and keeping in mind. The study design provides for a second interim analysis as well, but this futility analysis is really designed to ensure that there is no adverse consequence of the addition of relative jumped up to standard of care.

And therefore to Stuart's point, it's not a particularly high bar.

We expect to be able to proceed through.

Fady Malik: Our goal is to be able to know that we're doing at least as well as we saw in Fortitude ALS, and then seeing those effects as could be amplified over longer periods of time. So the first utility will be a lower bar.

Our goal is to be able to know that we're doing at least as well as we saw in fortitude ALS and then.

Seeing those effects could be amplified over longer periods of time. So the first futility will be a lower bar. The next interim could provide for a higher bar.

Fady Malik: The next interim could provide for a higher bar. Okay, thank you very much. Thank you. Operator Your next question will come from Jeff Hung with Morgan Stanley. Please proceed with your question. Good afternoon, Jeff. Hi, this is Milano, I'm for Jeff.

Okay. Thank you very much.

Thank you.

Your next question will come from Jeff Hung with Morgan Stanley . Please proceed with your question.

Good afternoon, Joe.

Jeff Hung: Thanks for taking our questions. So I guess it's falling up for courage. In addition to sample size, can you talk a little bit more about the things you're doing and elements of the study design that will help increase the chances for success? And then our second question, just a quick one for CK136. Was it kind of a question of reprioritization that you're now reacting the program later this year, or what was kind of a decision to now reactivate the program? Thank you. Sure, I'll start with the second question.

Hi, This is <unk> on for Geoff Thanks for taking our questions.

So I guess just following up for courage. In addition to sample size can you talk a little bit more about the things we're doing in elements of the study design that will help increase the chances for success.

And then our second question just a quick one first CK 136.

Was it kind of a question every priority prioritization that you are now reacting. The program later this year or what was kind of a decision to now reactivate the program. Thank you.

Sure I'll start with the second question.

Robert Blum: We wanted to make sure we had the additional resources, cash and otherwise, to be able to advance CK136. To remind you, this was a compound previously that was partnered with Amgen, and we needed to provide for the transition under our collaboration with Amgen to be able to fully independently progress it forward, and that's what we're doing now. But in the second half of 2021... We were readying for this in part to ensure that we could finish what we started.

We wanted to make sure we had the additional resources cash and otherwise to be able to advance CK 136 to remind you. This was a compound previously that was partnered with Amgen.

And we needed to provide for the transition under our collaboration with Amgen to be able to fully independently progress. It forward and that's what we're doing now but in the second half of 2021.

We were readying for this in part to ensure that we could finish what we started.

Robert Blum: And our intention is to pick up where CK136 left off under our Amgen collaboration, advance it forward in phase one and be in a position to make a decision about potential phase two as soon as we can. So you'll see more about CK136. We're pretty excited about this molecule.

And our intention is to pick up where CK 136 left off under our Amgen collaboration advance it forward in phase one can be in a position to make a decision about potential phase two as soon as we can so you'll see more about CK 136 were pretty.

Cited about this molecule its novel mechanism, we think affords it opportunities will be studied in some key indications with high unmet need and therefore youll hear more about that this year.

Robert Blum: It's novel mechanism. We think affords it opportunity to be studied in some key indications with high unmet need. And therefore, you'll hear more about that this year. With respect to Courage ALS in your first question, I'll turn to Stuart and Fadi. But I'll start by saying sample size is just one of the things that we're looking at based on learnings from Fortitude ALS and in discussions with regulatory authorities. We've designed Courage ALS to enrich for what we hope will be a treatment effect based on things that we have previously observed. Stuart and Fadi, perhaps you can elaborate.

With respect to encourage AOS and your first question first and I'll turn to steward in Saudi but I'll start by saying sample size is just one of the things that we're looking at based on learnings from Fortitude ALS and in discussions with regulatory authorities. We've designed courage AOS to enrich for what we hope will be a treatment effect.

Just on things that we have previously observed Stewart in Saudi perhaps you can elaborate.

Stuart Kupfer: You know, that's exactly right. What we learned from Forge today, and what's really, I think, strengthens study design and increases probability of success, and not the least of which is the dose. We selected a dose of 300mg BID. We thought that was optimal in terms of the benefit-risk profile.

Yeah, that's exactly right.

What we learned from Ford to today unless really.

I think strengthened.

Design and increases profitability.

Success.

Not the least of which is the dose selection.

We selected a dose 300 milligrams B I D.

And we thought that was optimal in terms of the benefit risk profile.

Stuart Kupfer: Another major element which Robert was alluding to is enriching the population for patients that are, Medium or fast progressors and I mentioned this in the call during the call. And the reason for that is based on, you know, again, results from the Fortitude, showing that those patients that are actually demonstrating the largest magnitude of treatment benefit. So with that patient population where there were, Leith Progression, Dr. Prima, Dr. Prima, Dr. Prima, Dr. Prima compared to placebo. You know, the this, you know, kind of what you might expect.

Another major element, which.

Robert was alluding to is enriching the population for.

Ah patients that are meet.

Medium or fast progresses, and I mentioned this on the call during the call.

And the reason for that is based on again results from Fortitude I'm showing that those patients that are actually demonstrating the.

The largest magnitude.

Treatment benefit so.

Was that the patient population, where there was.

Less progression.

Compared to placebo and.

The this.

Yes.

Kind of what you might expect.

Stuart Kupfer: The Gregor Ability Detective Treatment Effect, https://www.kenhub.com For more information visit www. FEMA.gov, of Demonstrating a Treatment Benefit. There, there are other elements as well. I won't go into a lot of detail.

B Gregor.

Gregor ability to detect a treatment effect.

<unk> population that is progressing more rapidly so.

Sort of increasing the sensitivity of the likelihood.

Demonstrating a treatment benefit.

Stuart Kupfer: But you know, we we put a lot of thought into the design of the study in terms of the, um, The ability of patients to actually engage and participate, you know, obviously these patients have a lot of difficulty with mobility, and just being through transportation to the clinic was very difficult. So, you know, most of our visits are actually remote. And so I think compared to other trials that have been conducted in ALS, this one is relatively easy for patients to participate in. So it has, you know, significantly less burden and hopefully that will improve patient retention and engagement. Great.

There are there are other elements as well I won't go into a lot of detail.

We put a lot of thought into.

The design of the study in terms of the.

The ability of patients to actually.

Engage and participate.

Obviously these patients have a lot of difficulty with mobility.

And just being.

Transportation to the clinic is very difficult so.

Most of our visits are actually remote visits.

Hum.

And so.

I think compared to other trials that have been conducted in ALS. This one is relatively easy.

Patients to participate in so.

Significantly less burden and.

Hopefully that will.

Improved patient retention and engagement.

Great. Thank you.

Thank you.

Andrew Callos: Thank you. Thank you. Your next question will come from Dane Leone with Raymond James. Please proceed with your question. Hi guys, this is Sean on for Dane.

Your next question will come from Dane Leone with Raymond James. Please proceed with your question.

Dane Leone: Thanks for taking the questions. I'm just kind of a... Um, maybe a little bit of detail would be good on the endpoints for the Redwood Cohort 4. Um, how do they compare and contrast to the Mavericks study?

Hi, guys. This is Shawn on for Dan Thanks for taking the questions.

Just kind of a.

Maybe.

Little bit of detail would be good on the endpoints for the Redwood cohort four.

How do they compare and contrast.

To the Maverick study.

Robert Blum: Um, and then kind of how do those secondary endpoints, maybe functional endpoints, point you to a potential pivotal? Yeah, I think the Maverick study taught us some things. I thought it was a good study, and it demonstrates that BNP is an effective biomarker for this mechanism of action in this population. But we can also go farther, as we intend to do in Cohort 4, and, Pretty soon we'll be posting on clinicaltrials.gov the design and endpoints for this study, but Fady or Stuart, do you want to say anything else at this time?

And then kind of how do those secondary endpoints, maybe functional endpoints point.

Point, you to a potential pivotal.

Yeah.

I think the Maverick study taught us some things I thought it was a good study and.

This demonstrates that the BNP is it effective biomarker.

This mechanism of action in this population, but we can also.

Go further as we intend to do in cohort four in <unk>.

Pretty soon we will be posting on clinical trials dot Gov, the design and endpoints for this study but.

Stewart do you want to say anything else at this time.

Robert Blum: Now I was just going to basically say, reflecting on what Robert said, we'll elaborate in detail when we're ready to start, but, you know, in terms of the objectives, As far as safety and tolerability and dose finding, I think you can get a sense of the end points we will be incorporating. Great, thank you.

No.

Oh go ahead.

Go ahead Stuart.

We're just going to basically say, reflecting what Robert said will elaborate in detail already start but.

In terms of the objectives.

<unk> safety and Tolerability in some dose finding.

I think you can get some sensitive.

What kind of endpoints will be incorporating.

Yeah.

Great. Thank you.

Jason Butler: Your next question will come from Jason Butler with JMP Securities. Please proceed with your question. Hey Robert, thanks for taking the question. Just one on Omicamtiv for me.

Your next question will come from Jason Butler with JMP Securities. Please proceed with your question.

Robert Blum: Just in terms of the 200 person sales force, can you speak to what proportion of the target audience that allows you to focus on from the start and how that breaks down between hospitals or physicians that spend a lot of time in hospitals versus outpatient heart failure clinics? Thanks. Sure, we'll turn to Andrew to answer that please. Sure. Thanks for the question. So relative to Salesforce, we're focused on the majority of cardiologists who treat worsening heart failure. You know, I would, you know, say it's probably in the 60 to 70% range.

Alright. Thanks.

Hey, Robert Thanks for taking the question just one on <unk> for me.

Just in terms of a 200 person sales force can you speak to.

What proportion of the target audience that allows you to focus on from the start and.

How that breaks down between hospitals or physicians that spent a lot of time in hospitals versus outpatient heart failure clinics.

Sure, we'll turn to Andrew to answer that please.

Andrew Callos: And, you know, there are there is some overlap, obviously, between cardiologists who treat in hospital and as compared to just spend time in hospital. So there will be kind of duplicate coverage for those cardiologists who cover both. And then your kind of final point of your question in terms of relative sizing, we're probably about 60-65% focused on just in terms of headcount focused on outpatient cardiologists, and the balance of them focused on hospital, A lot easier to cover, you know, the hospitals, there's probably about, you know, there's a little less than 1,000 hospitals we're focused on and less than 10,000 cardiologists. So maybe that's just another way to think about it.

Sure. Thanks for the question so relative to the sales force.

Focused on the majority of cardiologists to treat worsening heart failure.

I would say, it's probably in the 60% to 70% range.

And.

There is some overlap obviously between cardiologists, who are treated in hospital and as compared to just spend time in the hospital. So there will be.

Duplicate coverage for those cardiologists to cover both and then you are kind of a final point of your question in terms of relative sizing.

We're probably about 60, 65% focused on just in terms of head count focused on outpatient cardiologist and the balance of them focused on hospitals, a lot easier to cover.

The hospitals are probably about a little less than a 1000 hospitals were focused on and less than 10000 cardiologists have maybe that's just another way to think about it.

Andrew Callos: Yep, great, that's helpful, thanks. Thank you, Jason. Your next question will come from Salim Syed with Mizzou Hope. Please proceed with your question. Hello Salim.

Great that's helpful. Thanks.

Thank you Jason.

Your next question will come from selling Salim Sayed with Mizuho. Please proceed with your question.

Salim Syed: Hi, this is, it's Mike Linden on for Salim. Thanks so much for taking our questions. Appreciate it. A couple on Afrikampton, if I may.

Closely.

Hi, This is Mike on for Celine. Thanks.

Thanks, so much for taking my questions I appreciate it.

A couple on <unk>, if I may.

Andrew Callos: First on Sequoia, I know it's early on with enrollment just getting started, what is the comfort level for Sequoia's enrollment in the U.S.? With Mavicampton possibly approved in April, or maybe what are some of the drivers that might push patients to actually enroll, knowing there's a possibility of being on placebo versus Mavicampton availability? And then the second question, also on Mavicampton, I know you can't speak on price, and it's pretty early here, but just... Generally, on the obstructive HCM market, there seems to be a little bit of discrepancy between how people are modeling peak sales for Mavikampton versus modeling for Afrikampton. And one of the key drivers there is obviously price.

First on Sequoia I know, it's early on with enrollment just setting started.

What what is the comfort level for.

Enrollment in the U S.

With Maverick Hampton, possibly approved in April .

Or maybe what are some of the drivers that might put patient push patients to actually enroll.

Knowing there's a possibility of being on placebo.

Since kimpton availability.

And then the second question also on Epic Hampton.

Aye.

I know you can't speak on price and it's pretty early here, but just.

Generally in the obstructive HCM market.

There seems to be a little bit of discrepancy between how people are modeling peak sales for <unk> versus <unk>.

Modeling for epic Hampton.

And one of the key drivers there is obviously price so.

Andrew Callos: So, debate over where the ballpark price comes in seems to be kind of a wide range that people focus on. With ICER having come in talking about Mavikampton at $12,000 to $15,000 a year, I believe Myocardia's numbers were previously a lot higher than that. So, just generally speaking, just to help us understand the dollar size of the market for obstructive, what market comp should we be looking at or what framework?

State over where the ballpark price comes in.

Seems to be kind of a wide range that people focus on with ICU or having some and talking about <unk>.

At 12 months to 15000, a year I believe myocardial numbers were previously a lot higher than that so just generally speaking just to help us understand the dollar size of the market for obstructive.

What market comp.

Should we be looking at or what framework.

Robert Blum: Sure, so why don't we start with your second question first and I'll turn to Andrew. I will tell you for quite a long time we've been pointing to... Price and Value in this category, as was different than sometimes put forward by Myocardia and echoed by Wall Street analysts, We're taking note of the ICER commentary. We also expect BMS is pretty savvy about these things and knows what it's doing in terms of how it's ultimately going to be pricing in accordance with expected demand as well as value assumptions, where that ultimately sorts out in terms of gross to net, I think is something that we'll be observing.

Sure. So why don't we start with your second question first and I'll turn to Andrew.

I will tell you for quite a long time, we've been pointing to.

Price and value in this category.

<unk> different than sometimes put forward by myocardial <unk> and <unk>.

Echoed by Wall Street analysts.

We're taking note of the ice are common.

Commentary, we also expect BMS is pretty savvy about these things and knows what it's doing in terms of how it's ultimately going to be pricing in a <unk>.

Gordon's with expected demand.

Well as Val.

Value assumptions were.

Robert Blum: We obviously have our own scenarios, but for a product that's just entering phase three, you'll please forgive us if we'll be not disclosing anything about how we intend to ultimately be pricing. Andrew, anything you want to add to that? Yeah, I mean, probably the only thing maybe to add to think about forecasting is certainly not going to be in the ICER price range, I would guess it's not going to be in that top range you've seen either. You know, so you probably somewhere in the middle, there's always a good analogy, just to look at price prevalence relationships.

Where that ultimately sorts out in terms of gross to net I think as well.

Something that we will be observing we obviously have our own scenarios, but for a product. That's just entering phase III youll. Please forgive us if it will be.

Not disclosing anything about how we intend to ultimately be pricing, Andrew anything you want to add to that.

Andrew Callos: This is, you know, a rare disease right now, there's diagnosed less than 200,000 patients in the US. So I think, you know, maybe that could give you another hint or clue in terms of maybe pricing to try to look at. When you consider forecasting, over time, there's really, there's symptomatic treatments, there's, there's obviously, Part-Time Resident Question of the Day Part-Time Resident Question of the Day, To your first question, which spoke to enrollment, you know, the projection that Stuart put forward of approximately a year, give or take, that's with the full knowledge that we expect Mavicamton to be approved in Q2, and I do think that that drug should likely be embraced and will be launched successfully.

Yes, I mean, probably the only thing maybe to add.

To think about.

Forecasting is certainly not going to be in the ICU or price range I would guess, it's not going to be in that top range you've seen either.

So you're probably somewhere in the middle there is always a good analogy is to look at price privilege relationships. This is.

Our rare disease right now.

Diagnosed less than 200000 patients in the U S. So I think maybe that could give you another hint or clue in terms of maybe pricing to try to look at.

When you consider forecasting overtime.

There is really there.

Symptomatic treatments or Theres obviously.

Surgery as well so there's really not a good effective pharmaceutical treatment that treat the underlying condition until these and if these products would get approved.

Look at that 190000 prevalence if you believe that the prevalence is three to four times that just because of diagnosis rates be increasing over time and you kind of look at that price point I'm imagining that over time, you're going to get the majority of patients treated so.

Hopefully there are some inputs or some thoughts for modeling, but beyond that I'm not going to really comment.

To your first question, which spoke to enrollment.

The.

Projection that Stewart put forward of approximately a year give or take.

With the full knowledge that we expect Maverick kimpton to be approved in Q2.

And I do think that.

That drug should likely be embraced and will be launched successfully I think BMS will be effective at commercializing that.

Andrew Callos: I think BMS will be effective at commercializing that first-in-class compound, but at the same time, we feel pretty good about our projections for how we expect Sequoia to enroll, both because Afikampton affords a next-in-class profile because of the fact that in a clinical trial, patients are afforded access to care and resource intensity that isn't always available. Outside of a clinical trial, especially as would be through an open-label extension. But we're not banking on the U.S. alone. Obviously, we're enrolling patients in other geographies, too. Fady or Stuart, anything you want to add to that?

First in class compound, but at the same time.

We feel pretty good about our projections for how we expect sequoia to enroll both because of Kimpton affords a next in class profile because of the fact that.

In a clinical trial patients are afforded access to care and resource intensity that isn't always available outside of a clinical trial, especially because it would be through an open label extension.

But we're not banking on the U S alone.

We're enrolling patients.

Other geographies too.

Saturday or Stuart anything you want to add to that.

Fady Malik: Yeah, well, I will add that, you know, patients who enroll in Sequoia will, of course, have the opportunity to enroll in the Open Label Extension. So it's an advantage to having, you know, at the Campton for long term treatment at no cost. And I think that that can be appealing as well.

Yes.

I will add that pace.

Patients who enroll in Sequoia will of course have the opportunity to enroll in the open label extension.

So as an advantage to having.

At Camden.

For long term treatment at no cost and I think that that can be appealing as well.

Stuart Kupfer: I think the other thing to keep in mind is that we're not we're not talking about a disease that's rapidly progressive and fatal, which, you know, makes it very difficult to obviously enroll if there's an available drug out there. But, you know, these patients have lived with their symptoms often for years. And whether they may choose to go into a clinical trial or begin another drug, obviously, is their choice. But we think it's, Stuart said it's still pretty attractive to be able to enter a clinical trial and receive long-term open-label treatment at the end of that study at no cost to them, so. We'll see how that how that goes.

I think the other thing to keep in mind is that we're not we're not talking about a disease that is rapidly progressive and fatal which makes it very difficult to obviously enroll.

There's an available drug out there but.

These patients who live with their symptoms often for years.

Whether they may choose to go into a clinical trial or Ken another drug obviously their choice, but we think it's Stuart.

Pretty attractive to be able to.

Enter clinical trial.

Receive long term.

The open label treatment at the end of that study.

Cost to them.

We'll see how that goes.

Stuart Kupfer: You know, Sequoia is going to be enrolling in a very large number of clinical trial centers. So that goes a long way towards enabling of us to be confident in what will be roughly one year to enroll the full complement of patients. Got it.

Sequoia is going to be enrolling at a very large number of clinical trial centers.

So that goes a long way towards enabling of us to be confident in.

What will be roughly one year to enroll the full complement of patients.

Okay.

Got it thank you.

Yasmeen Rahimi: Thank you. Your next question will come from Yasmeen Rahimi with Piper Sandler. Please proceed with your question. Hello Yasmeen. Hi, hi Robert.

Thank you.

Next question will come from Yasmin Rahimi with Piper Sandler. Please proceed with your question.

Robert Blum: Thank you so much for the great updates. So two questions, I absolutely respect your decision on, you know, providing more color on the design of the second Abbey Campton HCM study, but I would like to understand, Fady, from you, can you maybe help us understand obstructive HCM patient populations better? Like, how do we segment these patients? Like, I know you alluded to mild to moderate in terms of symptoms, but if you could speak a little bit more granularly in regards to the spectrum of disease, that could be helpful.

Hello.

Hi, Hi, Robert Thank you so much for the great updates.

Two question I, absolutely respect here does it does.

Susanne on providing more color on the design of the second Ivy Canton.

Oh, HCM study, but I would like to understand from you can you maybe help us understand obstructive HCM patient populations better like how do we segment. These patients like I know you alluded to mild to moderate in terms of sometimes but if you could speak a little bit more granularly.

In regards to the spectrum of disease that could be helpful. And then the second question is about.

Fady Malik: And then the second question is about non-obstructive HCM study. You know, given that we have seen the failure with another myosin binding inhibitor in non-obstructive HCM, what confidence do you have that you should be able to see, you know, success in this population? And I really appreciate you answering my questions. Sure, Yasmeen.

Attractive HCM study.

Given that we have seen the failure with another binding inhibitor in non obstructive HCM what confidence do you have that you should be able to see success in this population.

I really appreciate you answering my question.

Fady Malik: Good to talk to you. I think, you know, in terms of OHCM, There's a whole spectrum of disease. You have patients who have fairly mild obstruction, but may have other stiffer parts of their ventricle that contribute to abnormal filling and potentially symptoms. You have patients that have high levels of obstruction but maybe not very much symptoms. Obviously, you have patients with high levels of obstruction and significant symptoms. And then finally, you have patients in whom medical therapy isn't really controlling their disease, and they have to consider surgical or invasive options in terms of septal ablation.

Sure, Yes, I mean, good talk to you I think.

In terms of O HCM.

There is a whole spectrum of disease, you have patients who have fairly mild obstruction.

But may have other.

Different parts of their ventricle that contribute to abnormal filling and potentially symptoms.

You have patients that have high levels of obstruction, but maybe not very many symptoms. Obviously, you have patients with high levels of obstruction and.

And significant symptoms and then finally, you have patients in whom.

Medical therapy isn't really controlling there.

Disease, and they have to considered surgical or invasive options in terms of.

Septal ablation.

Fady Malik: You know, so I think in a nutshell, that is sort of the spectrum of patients and we're, you know, focused really on the symptomatic patients with a significant degree of obstruction for studies of apicamptin and in this field in general. There are other populations to consider as well.

So I think in a nutshell that is sort of the spectrum of patients.

Focus really on the symptomatic patients with a significant degree of obstruction for studies of anti campton.

And in this field in general.

But there are other populations to consider as well.

Fady Malik: You know, in terms of your your second question with regards to NHCM, non obstructive HCM, you know, by definition, these patients don't have, Obstruction to blood flow leaving their heart, you know, but they have thickened, stiff ventricles, problems with filling, you know, you viewed Maverick as a failure, but I think, I think you have to be cautious in the way you think about that. You know, Maverick was a study that was relatively small, not very long, and it had a lot of clinical endpoints, which probably were underpowered with regards to assessing clinical, clinical events, or rather clinical outcomes, you know, symptoms or exercise performance.

In terms of your second question with regards to MHC, a non obstructive HCM.

Bye.

Definition of these patients don't have.

Obstruction of blood flow, leaving their heart.

They have thickened stiff ventricles problems with filling.

You viewed maverick is a failure, but I think I think you have to be cautious in the way you think about that.

Maverick was a study that was relatively small not very long.

And have a lot of clinical endpoints, which are probably we're underpowered with regards to assessing clinical.

Clinical events.

Alright, clinical outcomes symptoms or exercise performance.

Fady Malik: You know, if you could measure exercise performance in a study of 50 people, we wouldn't need to do sequoia in a study of, you know, 270 people. And, you know, do you know in this population, whether treatment is sufficient for. 16 weeks versus do you need much longer treatment, six months to 12 months, for instance, so.

If you could measure exercise performance in a study of 50 people, we wouldnt need to do Sequoia in the study of 270 people.

And do.

Do you know in this population whether treatment is sufficient for <unk>.

16 weeks versus do you need much longer treatment.

Six months to 12 months for instance, so.

Fady Malik: You know, I think the key in a phase two study of NHCM is asking whether there are signals that... Read on the potential in a Phase III trial to impact a more clinically relevant outcome. You know, might you see indications of reverse remodeling? Might you see biomarker changes and other things?

I think the key is in a phase III study of HCM is asking.

Whether there are signals that.

Read on the potential in a phase III trial to impact a more clinically relevant outcome.

Might you see indications of reverse for modeling.

Might you see biomarker changes.

And other things and then move into phase III to better design and implement a phase III trial, where you test that test the impact of those things on clinical meaningful endpoints.

Fady Malik: And then, you know, moving to Phase III to better design and implement a Phase III trial where you test the impact of those things on clinically meaningful endpoints. So I don't view, I think Maverick pointed to the impact of the mechanism of action on, you know, on certain biomarkers which are potentially predictive of long-term benefit in the area. But obviously, we still have to build that bridge from Phase II to Phase III. Thank you so much, Fady, for that thoughtful answer. Thank you. Your next question will come from Rohit Bhasin with Needham and Company. Please proceed with your question. Hurry!

So I don't view I think maverick pointed to the impact of the mechanism of action on.

Certain biomarkers, which are are potentially.

Potentially predictive of long term Benny.

Benefit in the area.

But obviously, we still have to build that bridge from phase II to phase III.

Thank you so much batting cleanup thoughtful answer.

Okay.

Your next question will come from Rohit <unk> with Needham and company. Please proceed with your question.

Alright.

Rohit Bhasin: Hi, this is Rohit on for Serge. Thanks for taking my question. Just in regards to the meteoric HF trial, does this trial change the way you think about potential investments for marketing Olmec Antiv upon approval? I'll start and maybe turn to Andrew, but I'll say definitely not.

Hi, This is Ryan on for <unk>. Thanks for taking my question just in regards to the meteoric trial does this trial change the way you think about a potential investments for marketing Oba captive upon approval.

I'll start and maybe turn to Andrew, but I will say definitely not.

Robert Blum: We made the decisions to do what we're doing based on Galactic and Galactic alone. And while we had hoped to see effects from meteoric that would be additive to what we saw with galactic, the fact that the results are neutral in meteoric don't subtract from what has us excited about Omicamptive from galactic. I will tell you that Omicamptive joins a long list of heart failure drugs that have not demonstrated improvement in exercise stamina.

We made the decisions to do what we're doing based on Galactic in Galactic alone.

And while we had hoped to see effects.

For me the work that would be additive to what we saw with galactic.

The fact that the results are neutral in <unk>.

Do you work don't subtract from what has us excited about what <unk> from Galactic.

I will tell you that omi.

From a captive joins a long list of heart failure drugs that have not demonstrated improvement in exercise stamina.

Robert Blum: And while we thought we had a good therapeutic hypothesis that warranted testing, we feel confident that the meteoric results are telling us that this drug candidate, much like many others, isn't translating into effect on exercise stamina. But however, it has already demonstrated in the substantially larger clinical trial, GALACTIC, much, much larger, much longer treatments that it had effect on hard clinical outcomes, including a composite of death and heart failure related events.

And while we thought we had a good therapeutic hypothesis that warranted testing.

We feel confident that the meteoric results are telling us that.

This drug candidate much like many others isn't translating into effect on exercise stamina.

Robert Blum: And our investment decisions are predicated on that. Andrew, anything you want to add to that? You covered it really well, Robert. The only thing maybe I would add is that we had done some market research as well with physicians to get their feeling on, you know, meteoric, had it been positive, neutral, or negative. And had it been positive, then it certainly would have been additive, as Robert described, but given where it netted out, we're not really anticipating any impact at all, and it changed, Nothing on our positioning, nothing in our overall strategy, nothing in our investment in field force size. I mean all continues as planned.

However, it has already demonstrated in a substantially larger clinical trial galactic much much larger much longer treatments that have affect on hard clinical outcomes, including a composite of death and heart failure related events.

Our investment decisions are predicated on that.

Andrew anything you want to add to that.

You covered it really well Robert the only thing maybe I would add is that we have done some market research as well with physicians to get their feeling on.

New York had it been positive neutral or negative.

And.

Had it been positive and that certainly would have been additive as Robert described but given where it netted out we're not really anticipating any impact at all and it changes nothing on our positioning nothing in our overall strategy and nothing in our investment in field force size.

I mean, all continues as planned.

Andrew Callos: And to that effect, it's not just investments in commercialization, but investments in lifecycle management. As we think about the potential approval for Omicamptive down the road, we are already contemplating what would be other studies that we think we would be wanting to initiate in 2023 and 2024. That's very helpful. Thank you. Your next question will come from Emanuela Branchetti with H.C. Wainwright, please proceed with your question. Hello, Emmanuella.

And to that effect, it's not just investments in commercialization, but investments in lifecycle management as we think about the potential approval for <unk> down the road.

<unk> already contemplating what would be other studies that we think we would be wanting to initiate in 2023 and 2024.

Okay.

That's very helpful. Thank you.

Thank you.

Your next question will come from Emmanuel I'll, let Bren chatty with H C. Wainwright. Please proceed with your question.

Hello, a menu Ella.

Emanuela Branchetti: Good afternoon, guys, and thank you for taking my question. I was wondering if you can help us gauge the awareness around Omicamtiv in the clinical community, and what do you envision will be important in driving the adoption if the drug will be approved? How long do you think we will have to wait to see Omicamtiv inclusion in the American guidelines, for example, and do you think this will constitute a key point post-approval? Good questions.

Good afternoon. Good afternoon, guys and thank you for taking my question and so wondering if you can help us gauge the awareness around when they come to us in the clinical community and what do you envision within part time team driving the adoption you said that will be approved.

How long do you think we will have to wait to see him accounted inclusion you can get Madigan guidelines for example, and do you think this will constitute a key point post approval.

Robert Blum: So awareness, is a function of a number of things, including the activity associated with clinical research and to what extent those investigators are themselves engaged actively in the management of patients with heart failure. And for the fact that Omicamptomacarbal was being developed in the United States and also globally for so many years across so many studies, awareness is reasonably high. Andrew can speak to that in more quantitative ways from market research.

Good question so awareness.

As a function of a number of things including the.

The activity associated with clinical research and to what extent those investigators are themselves.

<unk> engaged actively in the management of patients with heart failure and for the fact that <unk> was being developed in.

In the United States.

So globally for so many years across so many studies awareness is a reasonably high Andrew can speak to.

That in more quantitative ways for market research I'll also point out that.

Robert Blum: I'll also point out that As we're intending to go to market with Omicamptive McCarble, the guidelines will matter importantly, and guidelines, as Fady can speak to, are being updated now with more frequency, and we do expect that Omicamptive is going to be reflective, in guidelines shortly post approval. And that's one contributor to what could be early adoption. Another one is market access. And that's where we're going to be a bit more conservative, as Andrew can speak. So why don't we start with Andrew asking him to comment first, and then Fady afterwards.

As we are intending to go to market with Omi came to <unk>. The guidelines will better importantly guidelines as fatty can speak to are being updated now with more frequency and.

And we do expect that Omi captive is gonna be reflective.

And guidelines shortly post approval.

And.

That's one contributor to what could be early adoption. Another one is market access and that's where we're going to be a bit more conservative.

Andrew can speak so why don't we start with Andrew asking him to comment first and then Saudi afterwards.

Andrew Callos: So on awareness, there's actually really good awareness relative to where Omecampus macarbulus is in the registration status. You know, unaided, we're about one in, Cardiologists are aware of Omicamptib which is actually very high for unaided awareness when you don't have a commercial presence. In the marketplace, and over half of cardiologists, you know, when aided when you just talk about mechanism, etc, are certainly aware of it.

Sure. So on awareness theres that actually really good awareness relative to where on the captive mccarville.

And the registration status unaided, where about one in 10 cardiologists are aware of all the captive which is actually very high for unaided awareness. When you don't have a commercial presence in the marketplace and over half of cardiologist.

When aided when you just talk about mechanism et cetera are certainly aware of it. So we have really good awareness going into awards relative to adoption.

Andrew Callos: So we have really good awareness going in. A launch relative to adoption, you know, one of the things you see across, Adoption is generally slow in the beginning. Some of that is due to awareness, as you've asked, and others is due to just uptake by payers over time. So we're expecting broad payer access probably 12 to 14 months after launch, but we certainly know that uptake will be slow maybe for the first 12 to 14 months as we start to build more of that payer access and patient access, especially with Medicare, where the majority of patients are, and there's a very defined timeline to get Medicare access. Hopefully that helps. Fady.

One of the things you see across.

Pretty much all launches.

Adoption is generally slow in the beginning some of that is due to awareness as you've asked that others can do to get uptake by payers over time so.

We're expecting broad payer access probably 12 to 14 months after launch, but we certainly know that uptake will be slow maybe for the first 12 months to 14 months as we start to build more of.

That payer access and patient access, especially with Medicare.

Where the majority of patients are and there's a very defined timeline to get Medicare access so hopefully that helps.

Fady Malik: Yeah, thanks, Andrew. I think with regards to guidelines, you know, as Robert indicated, The Guideline Committees have acknowledged the more rapid pace of heart failure research and the availability of new data that may drive heart failure care, and in parallel, the need to potentially update guidelines to incorporate new evidence as it's generated. While they may go through a process of a complete rewrite of the guidelines every few years, I think they, particularly in the U.S., are beginning to think about smaller updates to the guidelines in the intermediate periods.

Yes, Thanks, Andrew I think with regards to guidelines.

Robert indicated.

The guideline committees.

Acknowledged the more rapid pace of heart failure research and the.

Availability of new data that made.

Drive heart failure care.

And then.

Parallel the need to potentially update guidelines to incorporate new evidence as it generated so.

While they may go through a process of a complete rewrite of the guidelines every few years I think.

Particularly in the U S are beginning to think about.

Smaller updates to the guidelines in the intermediate periods.

Fady Malik: And so we would hope with the data that we have, and particularly with an approval, that Guideline Committees may look to see where to incorporate Omicamptin-McCarbol into the standard of care. Very helpful, thank you. Thank you. And at this time, there are no further questions in queue. I would now like to turn it back over to Robert Blum for closing remarks. Thank you, operator. And thanks to everybody on the call today. I'll make my concluding comments brief.

So we would hope with.

The data that we have and particularly with an approval.

Guideline committees may look to see where to incorporate <unk> into the standard of care.

Thank you.

Thank you.

And at this time there are no further questions in queue I would now like to turn it back over to Robert <unk> for closing remarks.

Robert Blum: We ended 2021 on a high note. Lots of progress in our R&D pipeline as well as in preparations for 2022. We executed at the end of the year and early part of this year on some key transactions that afford us a stronger balance sheet as well as a more forward cash runway. And we started this year already on a high note with regard to designation of the NDA for Omicamtiv under standard review and our expected QDUFA date later this year, as well as with the Cohort 3 of Redwood HCM and the start of Sequoia HCM.

Thank you operator, and thanks to everybody on the call today, all backed by <unk>.

Concluding comments brief.

We ended 2021 on a high note.

So lots of progress in our R&D pipeline as well as in preparations for 2022, well we executed at the end of the year and early part of this year on some key transactions.

Afford us a stronger balance sheet as well as more forward cash runway.

We started this year already on a high note with regard to.

Designation of the.

The NDA for only captive under standard review and are expected <unk> date later this year.

Well as with the cohort three of Redwood HCM and the start of Sequoia HCM. So we're firing on all cylinders and we're feeling pretty good about how this could be another transformational year. We appreciate everybody's interest in the company and the progress we're making we look forward to keeping you abreast of that progress and prospects throughout this year.

Robert Blum: So we're firing on all cylinders and we're feeling pretty good about how this can be another transformational year. We appreciate everybody's interest in the company and the progress we're making. We look forward to keeping you abreast of that progress and prospects throughout this year. With that, Operator, we can now conclude the call. Thanks very much. This concludes today's conference call. Thank you for participating. You may now disconnect. [music]

With that operator, we can now conclude the call thanks very much.

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

[music].

[music].

[music].