Q3 2019 Earnings Call

Good afternoon, and welcome ladies and gentlemen, Kinda Cytokinetics third quarter 2019 conference call at this time I'd like to inform you that this call is being recorded and that all participants are any listen only mode.

Unknown Executive: Good afternoon and welcome, ladies and gentlemen, to the Cytokinetics 3rd Quarter 2019 conference call. At this time, I'd like to inform you that this call is being recorded and that all participants are in a listen-only mode.

Unknown Executive: At the request of the company, we will open the call for questions and answers. When the pre-after the presentation, I will now turn the call over to Diane Weiser, Cytokinetics Vice President of Corporate Communications and Investor Relations. Please go ahead.

At the request of the company, we will open the call for question and answers when the <unk> after the presentation.

I'll now turn the call ever Kim Diane Wiser, Cytokinetics, Vice President of corporate Communications and Investor Relations. Please go ahead.

Happy Halloween everyone. Thanks for joining us on the cost of that Robert Flamm, Our President and Chief Executive Officer will kick off the call, but the growth you up our key priority then study Malik our SVP of research and development will provide update on key developments from accounts in the horrible cardiac myosin activator under a lot.

Diane Weiser: Happy Halloween, everyone, and thanks for joining us on the call today. Robert Blum, our President and Chief Executive Officer, will kick off the call with a review of our key priorities. Then, Fady Malik, our EVP of Research and Development, will provide updates on key developments for Omacampin-McCarbyl, our cardiac myosin activator, under our collaboration with Amgen, as well as for CK274, our wholly-owned cardiac myosin inhibitor, now proceeding from Phase I to Phase II development. Then Robert Wong, our VP and Chief Accounting Officer, will provide a financial overview for the quarter, and Ching Jaw, our SVP and Chief Financial Officer, will discuss corporate development strategies.

And with Amgen as well for 67 for our wholly on cardiac myosin inhibitor now proceeding from phase one phase to develop.

Then Robert on our VP and Chief Accounting Officer will provide a financial overview for the quarter unleashing, our SVP and Chief Financial Officer will discuss corporate development strategies and he wants our SVP and Chief Medical Officer Canfield calls today. So Robert will then cover Austin updates relating throughout the something.

Robert I. Blum: Andy Wolf, our SVP and Chief Medical Officer, can't be on the call today, so Robert will then cover off on updates relating to RelDeceptive, our fast skeletal muscle troponin activator, in our collaboration with Astellas, before concluding with thoughts on the company's outlook and expected milestones for the remainder of the year. 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 filing. We undertake no obligation to update any forward-looking statements after the call.

Our fast skeletal muscle to pony taxes, either under our collaboration with seller before concluding with back from the company's outlook and expected milestones for the remainder of the.

Please note that portions are falling discussion, including our responses to questions contains statements that relate to future events it before rather than historical facts constitute forward looking statements.

Actual results may differ materially from those projected to these forward looking statements additional information concerning factors that could cause our actual results could differ materially American. These forward looking statements contain a SBC science, we undertake no obligation to update any forward looking statements. After the call and now I'll turn the call or rather.

Robert I. Blum: And now, I'll turn the call over to Robert. Thank you, Diane. And thanks again to everyone for joining us on the call today. We continue to make good progress against our priorities in the third quarter. And to begin today's call, I'd like to remind everyone what those priorities are in order to provide some context for the updates you'll be hearing about from the team. Priority number one remains the advancement of Omicamptor maccabum, our cardiac myosin activator, currently the subject of two ongoing phase three clinical trials under our collaboration with Amgen. As you may know, enrollment in GALACTIC-HF was completed in July.

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

We continue to make good progress against our priorities during the third quarter.

And to begin todays call I'd like to remind everyone what those properties or in order to provide some context for the updates you'll be hearing about from the team.

Kurt number one remains the advancement of Omecamtiv mecarbil or cardiac myosin activator currently the subject of two ongoing phase three clinical trial.

Our collaboration with after.

As you May know, but im glad to take true completed in July .

Robert I. Blum: That, in and of itself, is a big achievement, considering the number of patients, sites, and countries that participated in this important clinical trial. Looking forward, based on the accrual of clinical endpoint events in the trial, we expect the second planned interim analysis to occur in the first quarter of 2020. While we certainly don't expect the trial to conclude as a result of that analysis, we do recognize that that is a possibility and we need to be ready. With that said, both Galactic HF and Meteoric HF continue to be on track to read out results in 2021. Given the proximity to the results of these key trials, Amgen and Cytokinetics have stepped up commercial readiness activities, including work streams focused on matters such as market access, health economics, and medical affairs. And we'll elaborate on that in a moment.

That's the shelf is a big achieved but considering the number of patients sites in countries that participated in this important clinical trial.

Looking forward based on the accrual of clinical endpoint events in the true.

We expect the second planned interim analysis to occur in the first quarter of 2020 .

Well, we certainly don't expect to try to conclude.

But that analysis, we do recognize that as a possibility and we'd need to be ready.

With that said, both Galactic HF and you do you work Asia continued to be on track to read out so 2021.

Given the proximity to the results of these key trials and Jordan Sadler kinetics of stepped up commercial readiness activities, including work streams focused on matters, such as market access health economics, and medical affairs and will elaborate on that in a moment.

Robert I. Blum: Priority number two is the advancement of CK274, our wholly owned cardiac myosin inhibitor, for the potential treatment of hypertrophic cardiomyopathy, or HCF, and we expect to begin phase two by year end. As we said, we believe CK274 represents a potential next-in-class drug candidate that has now demonstrated a distinct clinical profile in healthy subjects, consistent with that which we observed in our preclinical work, and we hope to translate it into a therapy with optimized dosing, ease of titration, and symptom relief for HCM patients. In a moment, Fady will discuss the significance of the Phase 1 data in Healthy Volunteers and how the properties we've confirmed will shape our approach to Phase 2 and beyond. Priority number three is the advancement of Reldesemta, our fast skeletal muscle troponin activator, and we expect to potentially begin a pivotal phase three clinical trial in patients with ALS no sooner but still in the latter part of 2020.

Priority number two is the advancement of CK juice for portfolio cardiac myosin inhibitor for the potential treatment of hypertrophic cardiomyopathy work together.

And we expect to but good things to bite you're in.

As we said we believe CK two seven Ford represents a potential next in class drug candidate. That's now demonstrated a distinct clinical profile in healthy subjects consistent with that which we observed in our preclinical work and we hope to translate with therapy with optimized dosing.

Ease of choice ration M. symptom relief for HCM patients.

Both Saudi will discuss the significance of the phase one data in healthy volunteers and how the properties. We have confirmed will shape our approach to phase two and beyond.

Priority number three is the advancement of real just.

Our shops skeletal mostly to coated activator, and we expect to potentially but given a pivotal phase three clinical trial in patients with less no sooner, but still in the latter part of 2020 .

Robert I. Blum: In the last quarter, we presented additional results from Fortitude ALS, which provide further support for advancement of this drug candidate as a potential new therapy for patients suffering with ALS, especially in light of the FDA guidance which was recently published. I just returned from productive meetings with our partners at Astellas, and I'll share an update regarding this program and our collaboration later in today's call.

In the last quarter, we presented additional results from four to two less which provides further support for advancement of this drug candidates as a potential new therapy for patients suffering with ailments, especially in light of the FDA guidance, which recently published I.

I just returned from productive meetings with our partners that are still.

Sure uptake regarding this program and our collaboration later in today's call.

Robert I. Blum: So the company is well positioned with the advancement of our three lead drug candidates in later stages of clinical development. In addition, we're also encouraged by recent developments relating to our cardiac troponin activator, partnered with Amgen, in Phase I, and now two more potential drug candidates advancing an IND-enabling study. Given the opportunities to impact a wide array of cardiovascular and neuromuscular diseases associated with impaired muscle function and muscle weakness, with our industry-leading pipeline of muscle activators and inhibitors, it's especially rewarding to note that the company does not pivot on any single program and is in an excellent position to deliver on the promise of our biology and its related pharmacology for patients. With that, I'll turn the call over to Fady to elaborate on key developments in Thanks, Robert.

So the company is well positioned with the advancement of our Threed lead drug candidates in later stages of clinical development.

In addition, we're also encouraged by recent developments relating to our cardiac chipotle and activator part to revamp Gen phase, one and now to more potential drug candidates advancing an idea enabling studies.

Given the opportunities to impact a wide array of cardiovascular add neuromuscular diseases associated with impaired muscle function and muscle weakness.

With our industry leading pipeline.

Activators inhibitors, it's especially rewarding to note that the company does not pivot on any one single program that is an excellent position to deliver on the promise of our biology and its related pharmacology for patients with that I'll turn the call over to Saudi to elaborate on key developments.

And our cardiovascular program.

Thanks Robert.

Fady Ibraham Malik: One of the most important developments in our cardiovascular programs this quarter centered around completing enrollment in Galactic HF and beginning to advance DK274 into Phase II clinical development as a result of supportive and encouraging data coming out of the Phase I study in Healthy Volunteer. I'll address both of these developments starting with Omicamptive and Galactic HF. On our last call, we discussed the breadth of enrollment of more than 8,200 heart failure patients in Galactic HF and that this now represents one of the largest outcome trials ever conducted in heart failure. So why is this important, and how is the treatment landscape in heart disease changing as zombie cancer in McCargill gets closer to the finish line in this trial? Well, it's an exciting time in the treatment of heart failure, with newer medicines like Entresto being added to the standard of care, and existing medicines... like the SGLT2 inhibitors, recently demonstrating a reduced risk for worsening heart failure and cardiovascular death when added to the standard of care.

The most important developments in our cardiovascular program this quarter centered around completing enrollment in black allocate Jeff and beginning to advance DKK four into phase two clinical development as a result of supported encouraging data coming out in phase one study in healthy volunteer.

I'll address both of these developments starting with him accounts and Galactic HF.

On our last call, we discuss the breadth of enrollment of more than 8200 heart failure patients in Galactic HF and this that's it now represents one of the largest outcome trial ever conducted in heart failure. So.

So why is this important and how is the treatment landscape and arc is changing.

Answered Mcarthur gets closer to the finish line in this trial.

Well, it's an exciting time the treatment of heart failure with newer medicines like trust so being added standard of care in existing medicines like the SCLC two inhibitor recently, that's demonstrating reduced risk for worsening heart failure and cardiovascular death when added to the standard of care.

Fady Ibraham Malik: These developments underscore the continuing burden of heart failure and the opportunity to improve patient outcomes with new approaches to treatment. With this backdrop, and given our having enrolled over 8,200 patients in GALACTIC-HF, we are hearing increased enthusiasm from the clinical community and thought leaders for the important potential that cancer macabre may represent for heart failure therapy. Therapeutic rationale and development make it the first and only heart failure medicine specifically developed to treat the fundamental problems in these patients, that is, the inability of their hearts to pump effectively.

These developments underscore the continuing burden of heart failure, and the opportunity to improve patient outcomes with new approaches treatment.

With this backdrop and given our having enrolled over 8200 patients and Galactic HF.

We are hearing increase enthusiasm for the clinical community and its thought leaders for the important potential omecamtiv Mecarbil may represent a heart failure therapy.

It's therapeutic rationale in development make it the first and only heart failure medicine, specifically developed the treat the fundamental problem for these patients.

That is the inability their hearts to compete effectively.

Fady Ibraham Malik: As such, Omicamton McCarble has the opportunity to become foundational in treating heart failure with reduced ejection fraction, and the Galaxy K-Chip. We now have over 10,000 patient years of cumulative exposure with a number of patients having been on therapy for over two years. The DMC recently held one of their regular meetings and again recommended continuing the trial without changes.

As shown on the captive mecarbil has the opportunity to become foundational and treating heart failure with reduced ejection fraction.

And Galactic HF.

We've now enrolled we now have over 10000 patient years cumulative exposure with a number of patients having been on therapy.

For over two years.

The DMC recently held one of the regular meetings and again recommended continuing the trial without changes.

Fady Ibraham Malik: We now look forward to the second interim analysis, which we expect to occur in the first quarter of 2020. As a reminder, this analysis will include an assessment of potential superiority as well as for futility. The Fertility Boundary allows stopping the trial if there is no chance of success were it to continue, while the criteria for superiority are conservative. Unless we think there's a small chance that the trial will stop for efficacy at this interim analysis, even if the benefit of Omicamp's McCarble is consistent with the planning assumption. Additionally, it's important to note that the stopping boundaries provide guidance to the DMC, and they do not represent binding rules.

We now look forward to the second interim analysis, which we expect to occur in the first quarter 2020 .

As a reminder, this analysis will include an assessment for potential superiority as well as for futility.

The futility boundary enabled stopping the trial, there's no chance of success were to continue well the criteria for superiority or conservative.

Let's we think there's a small chance of the trial the stock for efficacy at this interim analysis, even if the benefit of Omecamtiv Mecarbil is consistent with the planning assumption.

Additionally, it's important to note that the staffing boundaries to provide guidance the DMC and they do not represent finding rule.

Fady Ibraham Malik: The DMC considers all available evidence in its recommendations regarding child conduct, and other considerations may support the consideration of galactic HF, even if numerical superiority boundaries are met in the planned analysis. Should the trial stop early, we certainly want to be prepared for next steps, and so, as Robert mentioned, together with Amgen, we're engaging in a diverse range of pre-commercial, medical, and regulatory readiness activities. To minimize time for the submission of marketing applications,

The DMC considers all available evidence and his recommendations regarding trial conduct another consideration may support that consideration nickel aggregate, Jeff even if numerical superiority boundaries are met the primary planned analysis.

Should the trials fairly certainly want to be prepared next step and so as Robert mentioned together with Amgen, we're engaging and diverse range of three commercial medical and regulatory readiness activities.

Minimize time that a submission of marketing application.

Fady Ibraham Malik: Towards its end, our medical affairs activities are ramping up. Implementation of our field-based medical strategies has begun with the successful deployment of our first medical science liaisons, or MSLs. As you may know, MSLs are seen as the medical face of the company, and they'll often be the first representatives of cytokinetics with whom a healthcare provider is contacted, particularly Key Opinion Leaders, Investigators, and Academics.

Towards this end our medical affairs activities are ramping up.

Implementation of our field based medical strategies began with the successful deployment or first medical science liaisons or myself.

As you May note and the sales we've seen as the medicine faces the company and there will be the first representatives of Cytokinetics with whom the healthcare providers contact.

Particularly key opinion leaders investigators and academic.

The cells, we focused on scientific exchange medical and disease State education that support our ongoing clinical trial.

Fady Ibraham Malik: The MSLs will be focused on scientific exchange, medical and disease, state education, and support of our ongoing clinical trials. In addition, Cytokinetics in Amsterdam ramped up commercial readiness activities in critical areas, including brand development and market research, to prepare for a successful global launch of Omicamp for McCarver. Importantly, the companies are also implementing multiple strategies to generate real-world evidence in targeted health care systems to complement expected clinical trial data and to support planned discussions with payers regarding the economic value of treatment with Omicampr and McCarver. Now moving to our Cardiac Myosin Inhibitor Program, we are pleased to recently present data from a completed Phase I study looking at escalating single and multiple ascending doses of CK274 in healthy subjects at the Heart Failure Society of America's 23rd Annual Scientific Meeting in Philadelphia.

In addition, cytokinetics and Amgen that ramped up commercial readiness activities in critical areas, including brand development and market research to prepare for a successful global launch of Omecamtiv Mecarbil.

Importantly, the companies are also implementing multiple strategies to generate real world evidence and targeted healthcare systems to complement expected clinical trial data and to support plan discussion with payers regarding the economic value treatment with them after mecarbil.

Now moving to our cardiac myosin inhibitor program. We're pleased to recently presented data from the completed phase one study looking at escalating single and multiple ascending doses of CK 274 in healthy subjects at the heart failure societies Americas 20, Threerd annual scientific meeting.

Philadelphia.

The data were encouraging and consistent with what we've seen preclinically.

He met its primary and secondary objectives to assess safety and tolerability of single and multiple or oral doses of CK two seven for.

Fady Ibraham Malik: The data were encouraging and consistent with what we've seen preclinically. This study met its primary and secondary objectives to assess the safety and tolerability of single and multiple oral doses of CK274. Describe the pharmacokinetics of CK274 and its pharmacodynamics as measured by a cardiography. We also characterize the pharmacokinetic and pharmacodynamic relationship, or PK-PD relationship, of OQF-274 with regard to cardiac function and healthy participants. To quickly recap, the study demonstrated that CK274 was safe and well-tolerated in healthy participants. No serious adverse events and no clinically meaningful changes in vital signs, ECGs, or laboratory tests were observed. The pharmacokinetics of CK274 were generally dose-linear, and steady-state appeared evident within 14 days of dose.

Described the pharmacokinetics of CK two seven forward as Pharmacodynamic.

As measured by a few cardiomyopathy.

We also characterized pharmacokinetic and pharmacodynamic relationship or PK PD relationship between.

With two some teekays use them for with regards to cardiac function and healthy participant.

To quickly recap the study demonstrated the CK 274 was safe and well tolerated and healthy participant.

No serious adverse events and no clinically meaningful changes and vital signs DCG or laboratory tests were observed.

Pharmacokinetics of CK, two some forward generally dose linear and steady state appeared evident within 14 days dosing.

Left ventricular ejection fraction decrease in exposure dependent manner in the PK PD relationship.

Okay to some four observed in humans was similar to that ups or three clinically when adjusted for differences in protein binding.

Specifically the shallow exposure response relationship observe preclinically appears to translate to healthy participant and when combined with the drug PK may enable flexible dose optimization human.

Importantly, steady state was achieved within two weeks of daily dosing and reversibility.

Fady Ibraham Malik: Left Ventricular Ejection Fraction Decreased in Exposure-Dependent Manner in the PK-PD Relationship, K274 observed in humans was similar to that observed pre-clinically when adjusted for differences in protein binding. Specifically, the shallow exposure-response relationship observed preclinically appears to translate to healthy participants, and when combined with the drug's PK, may enable flexible dose optimization in humans. More importantly, steady state was achieved within two weeks of daily dosing, and reversibility of effects was observed within 24-48 hours following 14 days of dosing. We are really pleased to see that these properties enable us to include a two-week dose titration schedule in the upcoming Phase 2 clinical trial and may ultimately translate to rapid onset, ease of titration, and rapid symptom relief for patients with obstructive HCM So with that, I'll now share more details about the Plan Phase 2 trial, which we expect to begin by year end. The trial is called Redwood HCM.

Other effects was observed within 24 to 48 hours following 14 days of dose.

We're really pleased to see that these properties enable us to include a two week dose titration schedule in the upcoming phase two clinical trial and May ultimately translate to rapid onset ease of type transaction and rapid symptom relief for patients with obstructive ATM in the clinical practice setting.

So with that I will now share more details about the planned phase two trial, which we expect to begin by year end.

Trial is called Redwood.

Which stands for randomized devaluation of dosing with Casey said before in a constructive outflow disease and ATM.

We're excited to have selected for the name of the trial. This magnificent an enduring tree assembled in northern California.

As it not only reflects cytokinetics roots in the region, but importantly reflects the strength independence and then during qualities, we aspire to deliver to patients who are living with obstructive ATM as may eventually benefit from our novel investigational therapy.

Redwood HCM will be a multicenter randomized placebo controlled double blind dose finding study in patients with symptomatic obstructive HCM.

Fady Ibraham Malik: This stands for Randomized Evaluation of Dosing with CK274 in Obstructive Outflow Disease in HCM. We're excited to have selected, for the name of the trial, this magnificent and enduring tree, a symbol of Northern California, as it not only reflects Cytokinetics' roots in the region but importantly reflects the strength, independence, and enduring qualities we aspire to deliver to patients who are living with obstructive HCM and may eventually benefit from our novel investigational therapy. Redwood HCM will be a multi-center, randomized, placebo-controlled, double-blind, dose-finding study in patients with symptomatic obstructive HCM. The primary objective of the trial is to determine the safety and tolerability of TK274. Secondary objectives are to describe the concentration-response relationship of CK274 on the resting and post-bell cells of the left ventricular outflow gradient as measured by echocardiography during 10 weeks of treatment.

Primary objective of the trials to determine the safety and Tolerability of Teekay Q4.

Secondary objectives are to describe the concentration response relationship of CK two some for on the resting and post bell sales of left ventricular outflow gration as measured by AFFO cardiomyopathy during 10 weeks of treatment.

Well get into more details regarding specific endpoints the redwood HCM when we announced the started the trial expected later this quarter.

Two sequential cohorts with an option for a third or will be enrolled within each cohort 18 patients will be randomized two to one to active or placebo treatment and receive up to three escalating doses of CK Q4, or placebo based on echocardiographic guidance.

Importantly, given the half licensee cases, some for patients will receive an echocardiogram. After two weeks of treatment at each dose to determine whether they will be uptight trade.

The schedule should contribute to optimize the dosing and potential efficacy quickly.

In the trial and ideally in the clinical setting.

Fady Ibraham Malik: We'll get into more details regarding specific endpoints of Redwood HCM when we announce the start of the trial, expected later this quarter. Two sequential cohorts, with an option for a third cohort, will be enrolled. Within each cohort, 18 patients will be randomized 2 to 1 to active or placebo treatment and receive up to 3 escalating doses of CK274 or placebo based on echocardiographic guidance. Importantly, given the half-life of CK274, patients will receive an echocardiogram after two weeks of treatment at each dose to determine whether they will be experiencing uptight training. The schedule should contribute to optimizing dosing and potential efficacy quickly, both in the trial and, ideally, in the clinical setting. Overall, the treatment duration will be 10 weeks with an echocardiogram to confirm reversibility of effect two weeks after the last dose.

Overall, the treatment duration will be 10 week with an echocardiogram to confirm ribbit reversibility of affect two weeks after the last do.

Redwood HCM is expected to enroll patients in around 20 investigative sites North America in Europe .

Currently finalizing operational plans to initiate the trial and expected to open to enrollment in this fourth quarter.

Thank you get the trial up and running and continue to receive positive feedback with similar enthusiasm from our investigative sites.

And now Robert.

Yet you on our financials for the quarter.

Thanks Betty.

Ill first provide an update on cash revenue and spending and then Chang will review our corporate development strategy.

Or details of our actual results for the third quarter 2019 are included in the press release, which we released earlier this afternoon.

We ended the third quarter with 166 million in cash and investments.

Our revenue in Q3 2019 came from our strategic alliances with Amgen and Astellas.

Fady Ibraham Malik: Redwood ACM is expected to enroll patients in around 20 investigative sites in North America and Europe. We're currently finalizing operational plans to initiate the trial and expect it to open to enrollment in this fourth quarter. We're enthusiastic to get the trial up and running and continue to receive positive feedback with similar enthusiasm from our investigative sites. And now Robert Wong will update you on our financials for the quarter. Thanks, Fady.

And we recognize revenue associated with their reimbursement of our development expenses related to meteoric HM for a seller, we recognize revenue for reimbursement of our research activity as well, that's where development expenses incurred related to our closing out fortitude ale that.

Our third quarter 2019, R&D expenses decreased to 20.2 billion from 21.7 billion in the third quarter of 24, primarily due to lower spending related to our neuromuscular development activities offset by increased activities related to meteoric HF and seek.

Robert C. Wong: I'll first provide an update on cash, revenue, and spending, and then Ching will review our corporate development strategy. More details of our actual results for the third quarter 2019 are included in the press release which we released earlier this afternoon. We ended the third quarter with $166 million in cash and investments.

Seven for.

More than half of our R&D expenses were attributable to our cardiovascular programs as expected given activity for meteoric, Hey, Jeff and the cardiac myosin inhibitor program and the remainder of our expenses were attributable primarily to our early research activity.

Robert C. Wong: Our revenue in Q3 2019 came from our strategic alliances with Amgen and Estella. For Amgen, we recognize revenue associated with their reimbursement of our development expenses related to Meteoric HF. For Estella, we recognize revenue for reimbursement of our research activities, as well as for development expenses incurred related to our closing out of Fortitude ALS. Our third quarter 2019 R&D expenses decreased to $20.2 million from $21.7 million in the third quarter of 2018.

Our third quarter 2019, DNA extensive were 9.8 billion up from 7.2 million in Q3, 2018, due primarily to increase outside legal expenses and higher personnel related costs, including stock based compensation.

And now Chang will review, our corporate development strategy.

Thanks Robert.

As Robert mentioned, we ended the third quarter was 166 million in cash.

Which represent nearly 24 months of lower cash based on our 2019 guidance of 85 90 million that cash burn.

Robert C. Wong: This was primarily due to lower spending related to our neuromuscular development activities, offset by increased activities related to meteoric HF and CK274. More than half of our R&D expenses were attributable to our cardiovascular programs, as expected, given activities for meteoric HF and the cardiac myosin inhibitor program, and the remainder of our expenses were attributable primarily to our early research activities. Our third quarter 2019 G&A expenses were $9.8 million, up from $7.2 million in Q3 2018.

As we have previously stated our strategy remains to manage our cash prudently through the expected readout of results from Galactic HF in 2021.

Towards that objective in September we presented our strategic plan to our board, which focused on prioritizing near term spending to position the company for long term growth.

Prior to the board meeting.

Engage the company's middle management and senior leadership team.

Broadband prioritization exercise.

And then we did the same without for members.

We consider and scientific and clinical validation.

Our abilities of technical success.

Robert C. Wong: Due primarily to increased outside legal expenses and higher personnel-related costs, including stock-based compensation. And now Ching will review our corporate development strategy. Thanks Robert. As Robert mentioned, we ended the third quarter with $166 million in cash, which represents nearly 24 months of forward cash based on our 2019 guidance of $85 to $90 million net cash burn.

Regulatory path to approval and market access and commercial potential.

We also assessed on may patient needs.

And potential quite impact.

The results from all three groups were remarkably similar and echo what Robert outlined at the start of the call. We consider only tempted cargo to be our top priority.

Okay to seven four in Oh, I seem to be our second priority and rod incentive.

To be our third priority.

As such near term spending will be allocated based on this rank order.

What's that also means is that others of our programs in development and research will not receive.

Ching W. Jaw: As we have previously stated, our strategy remains to manage our cash prudently through the expected readout of results from Galactic HF in 2021. Toward that objective, in September, we presented our strategic plan to our board, which focused on prioritizing near-term spending to position the company for long-term growth. Prior to the board meeting, we engaged the company's middle management and senior leadership team in a program prioritization exercise. And then we did the same with our four members.

Comparable funding until such time.

We have access to more capital.

For loan growth.

We also discussed with the board our approach to broaden our reach certain platform and to strengthen our commercial capability.

In anticipation of potentially multiple commercial product launches.

Few years.

As we look towards year end, our balance sheet remains strong.

We also are continuing to seek additional capital to extend our cash runway through a recent expense.

Ching W. Jaw: We consider scientific and clinical validation, probabilities of technical success, regulatory Path to Approval, and Market Access and Commercial Potential. We also assess on-med patient needs and Potential for Impact. The results from all three groups were remarkably similar and echo what Robert outlined at the start of the call.

Activity inclusive of potential business development in collaboration and or project financing.

In the third quarter, we've made progress towards our potentially executing multiple transactions some of which can foresee occurring in the current fourth quarter.

We remain confident in our ability to vigilantly deploy capital against our prioritized programs to deliver optimal patient care and return on investment for our shareholders.

Ching W. Jaw: We consider Omicampium Carbo to be our top priority, CK274 in OHDM to be our second priority, and Radacentive in ALS to be our third priority. As such, near-term spending will be allocated based on this ranking order. What that also means is that others of our programs in development and research will not receive comparable funding until such time as we have access to more capital for a long time. We also discussed with the board our approach to broaden our research platform and to strengthen our commercial capabilities in anticipation of potentially multiple commercial product launches in the next few years. As we look towards year-end, our balance sheet remains strong, but we also are continuing to seek additional capital to extend our cash runway through a recent expansion of activity inclusive of potential business development collaborations and or project financing. In the third quarter, we made progress towards potentially executing on multiple transactions, some of which we can foresee occurring in this current quarter.

With that I'll turn the call back over to Rob.

Thank you check.

To pick up on Cigs comments regarding prioritization of R&D programs and spending.

The exercise we went through with our management team and board was especially instructive and based on conversations. We've had many of you. We believe our terminal priorities are well aligned with feedback we've received from external stakeholders as well.

As we execute on these priorities, we do so with an eye towards initiating commercialization of what could be our first approved there will be kept at carpe.

As you heard were substantially dialing up pre commercial activities specifically in the areas of health economic outcomes research market access and commercial plan.

And we've added key new hires to our teams alongside those of counterparts at Amgen.

A number of concurrent work streams in support of touch lunch ready. This is impressive and underscores the significant opportunity that omecamtiv mecarbil represents to patients with historic dysfunction heart failure with a clinical and economic burden, that's only growing given the aging demographics.

Ching W. Jaw: We remain confident in our ability to vigilantly deploy capital against our prioritized programs to deliver optimal patient care and return on investment for our shareholders. And with that, I'll turn the call back over to Robert. Thank you, Ching.

I also want to emphasize our third of Tuesday, guys have an urgency to initiate redwood HCM. The phase two clinical trial of CK 274 in patients with obstructive HCM.

Robert I. Blum: To pick up on Ching's comments regarding prioritization of R&D programs and spending, the exercise we went through with our management team and board was especially instructive. And based on conversations we've had with many of you, we believe our internal priorities are well aligned with feedback we've received from external stakeholders as well. As we execute on these priorities, we do so with an eye towards initiating commercialization of what could be our first approved therapy, Omicab to McCarver. As you know, we're substantially ramping up pre-commercial activities, specifically in the areas of health economics and outcomes research, market access, and commercial planning. And we've added key new hires to our teams alongside those of our counterparts at Amgen.

This is the patient population great need of novel therapies to treat both the symptoms of HCM, which impact everyday light and the ability to do some of the things that we take for granted like walking up a flood steroids are going food shopping as well as the underlying contractual dysfunction in fibrosis.

Aside you discussed the data from our phase one study augur well for what we see in the phase two trial and ultimately what physicians can look forward to in terms of ease of use tightrail should and potential safety and efficacy in the clinical setting.

Finally, we're continuing to delve deeply and critically to evaluate the results from our recent phase two clinical trials of relative subs.

HLS at an empty SMS.

Robert I. Blum: The number of concurrent work streams in support of potential launch readiness.., is impressive and underscores the significant opportunity that Omicab to McCarville represents to patients with systolic dysfunction heart failure with a clinical and economic burden that's only growing given the aging demographic. I also want to emphasize our enthusiasm and urgency to initiate Redwood HCM, the Phase 2 clinical trial of CK274 in patients with obstructive HCM. This is a patient population in great need of novel therapies to treat both the symptoms of HCM, which impact everyday life, and the ability to do some of the things that we take for granted, like walking up a flight of stairs or going food shopping, as well as the underlying contractile dysfunction and fibrosis, As Fady discussed, the data from our Phase 1 study augured well for what we may see in the Phase 2 trial and ultimately what physicians can look forward to in terms of ease of use, titration, and potential safety and efficacy in the clinical setting.

In parallel we're working with regulatory authorities and payers to assess various approaches we may consider to advance rate sensitive into later stage clinical development.

Most recently at the Nielsen meeting last month, Jeremy Schupfner. The principal investigator from four to two they called US presented additional post talk analysis from the trial that showed faster progressing patients who received any dose of rail deceptive experienced a statistically significant and clinically meaningful lesser <expletive> .

Clearly npls FRS as measured from baseline to week 12 that did their counterparts, who received placebo. In addition ads in both cases to standard of care.

These results are important because it real deceptive can have a positive impact on faster progressing patients over just 12 weeks, it's reasonable to hypothesize that we may see an impact on function and disease progression for slower progressing patients over a longer time horizon and thus we have a compelling.

Opportunity to potentially demonstrate that a treatment benefit of future clinical trial by either evaluating a broader set of patients to be studied over longer time horizon or otherwise by Richard the trial with faster progressing patients, but in both scenarios in order to show potentially clinically meaningful and statistics.

Robert I. Blum: Finally, we're continuing to delve deeply and critically to evaluate the results from our recent Phase II clinical trials of Reldaceptive in ALS and in SMA. In parallel, we're working with regulatory authorities and payers to assess various approaches we may consider to advance relative incentive into later stage clinical development. Most recently, at the NEALS meeting last month, Jeremy Scheffner, the principal investigator for Fortitude ALS, presented additional post-talk analyses from the trial that showed faster-progressing patients who received any dose of Reldaceptive experienced a statistically significant and clinically meaningful lesser decline in ALS-FRS, as measured from baseline to Week 12, than did their counterparts who received placebo in addition, and in both cases, to standard of care. These results are important because if rel-deceptive can have a positive impact on faster-progressing patients over just 12 weeks, it's reasonable to hypothesize that we may see an impact on function and disease progression for slower-progressing patients over a longer time horizon, and thus we have a compelling opportunity to potentially demonstrate that a treatment benefit of a future clinical trial by either evaluating a broader set of patients to be studied over a longer time horizon or otherwise by enriching the trial with faster-progressing patients, but in both scenarios, in order to show a potentially clinically meaningful and statistically valid therapeutic effect of rel-deceptive in patients with ALS.

Leave outlets therapeutic effect of rail deceptive in patients with a less.

Towards that objective. We recently received from feedback from FDA in response to questions relating to a draft registration trial protocol and we're pleased to see the responses were construction and supportive more planes. Moreover, we're especially pleased that our plans seems to resonate with recently published FDA.

Pertaining to drug development in a lot less.

As previously mentioned, we can't anticipate getting a phase three trial until soonest. The latter how quick 2020 and between now and then we'll finalize the protocol obtained additional investigator and regulatory feedback and operationalize. The study plan before committing to do so.

We also need to restructure and clarified the economics and respective roles and responsibilities under our collaboration with the steps.

Towards that objective, we had previously communicated our want to renegotiate certain terms of our collaboration agreement.

I'm pleased to report that we in the still US have agreed in principle to revised turns of our collaboration agreement. So thats Cytokinetics would have the exclusive right to develop and commercialize all fast skeletal which are prone and activators, including relative symptoms and CK six so one.

In that case of Stellus as future contributions would be to provide partial co funding for certain phase three clinical trial costs were relative sensitive in a 11.

Robert I. Blum: Towards that objective, we recently received feedback from FDA in response to questions relating to a draft registration trial protocol, and we're pleased to see the responses were constructive and supportive of our plan. Moreover, we're especially pleased that our plans seem to resonate with recently published FDA guidance pertaining to drug development in ALS. As previously mentioned, we can't anticipate beginning a Phase III trial until the latter half of 2020, and between now and then, we'll finalize the protocol, obtain additional investigator and regulatory feedback, and operationalize a study plan before committing to do so. We also need to restructure and clarify the economics and respective roles and responsibilities under our collaboration with Estelle.

To provide other kinds support.

If exchange, let's start with would receive a low to mid single digit royalty on rail deceptive to be payable by Cytokinetics.

We also agreed in principle to extend our joint research program for another year with Astellas sponsoring research cytokinetics through 2020 .

Of course, these agreements in principle or non binding and there continue to put our vitalizing amendments to our collaboration agreement and absent that agreement the terms of the existing agreement remain in place.

In the meantime, however, we continue to plan for the potential advancement of rail deceptive into a phase three trial again later in 2020.

We also remain dedicated to advanced research education support and awareness for the patient populations we start.

Robert I. Blum: Towards that objective, we had previously communicated our desire to renegotiate certain terms of our collaboration agreement. I'm pleased to report that we and Astellas have agreed, in principle, to revise the terms of our collaboration agreement so that Cytokinetics would have the exclusive right to develop and commercialize all fast skeletal troponin activators, including rel-deceptive and CK601. In that case, Astellas' future contributions would be to provide partial co-funding for certain Phase III clinical trial costs for rel-deceptive in ALS and to provide other in-kind support. And, in exchange, the Stelits would receive a load of mid-single-digit royalties on Reld Assemptive to be payable by Cytokinetics. We also agreed in principle to extend our joint research program for another year with Estella Sponsoring Research in Cytokinetics through 2020. Of course, these agreements in principle are non-binding, and they're contingent upon our finalizing amendments to our collaboration agreement, and absent that agreement, the terms of the existing agreement remain in place.

During the quarter, we announced a continuation of our partnership with your estimate to increase education awareness public policy at fundraising for spinal muscular atrophy. We're also very pleased to recently announced a call for proposals for the second annual Cytokinetics Communications Fellowship Grant program, which provides.

To select patient advocacy organizations that are serving the HLS heart failure HCM or estimate communities. These grants would be intended to support increased capacity in communications awareness building and community engagement.

Activities, we've identified a gap for AG advocacy organizations, who are need of support.

Given that now let me recap or expected milestones for the remainder of 2019.

For Omecamtiv Mecarbil, we expect to continue to get to conduct Galactic HF add meteoric HF in patients with heart failure through well 2019.

For CK 274, we expect to begin Redwood HCM or planned phase two clinical trials in patients with obstructive HCM This fourth quarter.

Robert I. Blum: In the meantime, however, we continue to plan for the potential advancement of REL-Deceptive into a Phase III trial again later in 2020. We also remain dedicated to advancing research, education, support, and awareness for the patient populations we serve. During the quarter, we announced the continuation of our partnership with CureSMA to increase education, awareness, public policy, and fundraising for spinal muscular atrophy. We're also very pleased to recently announce a call for proposals for the second annual Cytokinetics Communications Fellowship Grant Program, which provides grants to select patient advocacy organizations that are serving the ALS heart failure, HCM, or SMA community. These grants would be intended to support increased capacity in communications, awareness building, and community engagement.

For AMG Fivenine for we expect Amgen, we will continue the phase one study of HFG fivenine for throughout 2019 and for rail deceptive, we'll continue to advance planning for potential future trials in HLS and estimate.

For preclinical research, we expect to continue research activities under our joint Research program with the Stellus directed to the discovery of next generation skeletal muscle activators again throughout 2019, we also expect to continue our other muscle biology focused research, including the expand.

One of our research activities beyond the contractility of muscle to the energetics of muscle.

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

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

Robert I. Blum: Key Activities We've identified a gap for advocacy organizations who are in need of support. Given that, now, let me recap our expected milestones for the remainder of 2019. For Omicamptin-McCarville, we expect to continue to conduct galactic HF and meteoric HF in patients with heart failure throughout 2019. For CK274, we expect to begin Redwood HCM, our planned Phase 2 clinical trial in patients with obstructive HCM, in this fourth quarter. For AMG-594, we expect Amgen will continue the Phase I study of AMG-594 throughout 2019, and for Rel-Deceptive, we'll continue to advance planning for potential future trials in ALS and SMA. For preclinical research, we expect to continue research activities under our joint research program with Astellas directed to the discovery of next-generation skeletal muscle activators again throughout 2019.

Once again that is star and the number one.

And we'll we'll take your first question from Jason Butler with JMP Securities.

Hi, Jason Hi.

Thanks for taking the questions and congrats on all the progress across the pipeline in the quarter.

Had a couple on 274, and then a follow up 100 MCAM Tim.

So the phase two Redwood trial, Saudi I think you said that youre going to be assessing the.

The LDL C gradient, both at rest and post exercise if that's correct can you talk about those two measures and how how we should think about those data points and how informative. Each is in terms of say three planning and then.

Can you just speak to how you think about opportunities for CK two seven for the on obstructive HCM for example, and most obviously a non obstructive patients.

Yes, sure all let's take the first question so just to.

Be clear, but we will be assessing is.

The effective to seven for on the left ventricular outflow grading at rest and post bellsouth not not post exercise of outsell the is the.

Breathing, the new or where are you fair down against the close.

Unknown Executive: We also expect to continue our other muscle biology-focused research, including the expansion of our research activities beyond the contractility of muscle to the energetics of muscle. Operator, with that, we can now open up the call, please, to questions. Ladies and gentlemen, just as a reminder, if you'd like to ask a question, please press star and then the number one on your telephone keypad. Once again, that is star and then the number one.

Got it.

That you're.

Generating into drastic pressure.

Increasing.

The gradient through that mean.

Common maneuver that's done in HCM patients to look at maximum gradient.

And so those two maneuvers, we'll look at that.

That the about salvage rating in the resting great yet in this trial there won't be an exercise assess and this trial is think.

Our experience and other domain Jess really to be confident in a placebo controlled trial of.

The effect of of any driven exercise, we need a much larger studies and we have plans right now or this them.

Unknown Executive: And we'll take your first question from Jason Butler with JNP Security. Hi, thanks for taking the questions and congratulations on all the progress across the pipeline in the quarter. I had a couple on 274 and then a follow-up on Omicantive.

For the safety trial.

The second question you asked.

You can remind me what I wanted to know that impact of that is basically flat right. So the him the relationship the phase three planning is that.

The effective.

Q4 on the Radian is the most sensitive way by which we can establish dose and it dosing regimen.

Fady Ibraham Malik: For the Phase 2 Redwood trial, Fady, I think you said that you're going to be assessing the LVOT gradient both at rest and post-exercise. If that's correct, can you just talk about those two measures and how we should think about those data points and how informative each is in terms of Phase 3 planning, and then can you just speak to how you think about opportunities for CK274 beyond obstructive HCM Yeah, sure. I'll take the first question.

The highly sensitive biomarker.

Have a cardiac myosin akt inhibitors sac and.

It will enable us really to characterize exposure response relationship and set.

Properly for phase three.

So that I think was the main objective of our phase two study is to ensure that we are dosing patients that are similar to those that we would wynnewood enrollment phase three and then the them with.

Similar dosing regimen as we would employ phase three.

Fady Ibraham Malik: So just to be clear, what we will be assessing is the effect of 274 on the left ventricular outflow gradient at rest and post-Valsalva, not post-exercise. Blot it, you know, so that you're generating interthoracic pressure and increasing the gradient through that means. It's a common maneuver that's done in HCM patients to look at maximum gradients. And so, those two maneuvers will look at both the valsalva gradient and the resting gradient in this trial. There won't be an exercise assessment in this trial. I think, you know, our experience in other domains suggests really to be confident in a placebo-controlled trial of the effect of any drug on exercise, you need a much larger study than we have planned right now for this phase 2 trial. The second question you asked. Unknown Speaker Can you remind me what...

So Jason you also asked about next steps that could include other indications.

I think we're putting those on pause right now to better understand the landscape around which.

Cardiac myosin inhibitor may have effect in non obstructive HCM, but also in other indications where we have ambition.

So as you heard our priorities laid out those are certainly potential priorities down the road, but given our current capital and how we're thinking about our business right now we're going to.

Focus to those things that we underscored in this call.

Great.

And then just wondering how many campuses.

Can you provide any color around the upcoming interim in terms of.

Whether the stopping boundaries are focused.

On the primary endpoint versus key secondary endpoints, such as cardiovascular death, and then do you have any plans to present republish baseline characteristics or the statistical analysis plan at any point. Thanks.

Fady Ibraham Malik: Unknown Speaker Wanted to know the impact of that on phase three planning. Unknown Speaker Right. So the relationship to phase three planning is that... The effect of TK274 on the gradient is the most sensitive way by which we can establish the dose and a dosing regimen.

Yes, I can't really comments on the specifics of what the criteria are.

Clearly obviously they would involve the primary endpoint being met.

But I really comment beyond that.

The.

The baseline characteristics of the trial will be something that will come out.

Robert I. Blum: It's a highly sensitive biomarker of a cardiac myosin inhibitor's effect, and it'll enable us to really characterize the exposure-response relationship and set the dose properly for phase three. So that, I think, was the main objective of our phase two study, to ensure that we are dosing patients that are similar to those that we would enroll in phase three, and then we dose them with a similar dosing regimen as we would employ in phase three. So Jason, you also asked about next steps that could include other indications. And I think we're putting those on hold right now to better understand the landscape around them. Cardiac Bias and Inhibitor may have an effect in non-obstructive HCM but also in other indications where we have ambition.

Appropriate academic forum.

The next few months and the.

Our planning to publish paper on the designed for lactic that will.

Hopefully also.

In the public domain the next few months as well.

I think in many respects, having that information will elaborate on some of things you've been asking about Jason.

That will be forthcoming.

Great appreciate all the will of the additional details thanks for taking questions.

Thank you thanks.

Your next question comes from the line of Cho Pitkanen with H.C. Wainwright.

Hey, guys. Good afternoon, thanks for taking the questions.

Couple of questions actually it's nice to get the visibility on the us stellus.

Fady Ibraham Malik: So as you heard our priorities laid out, those are certainly potential priorities down the road, but given our current capital and how we're thinking about our business right now, we're gonna focus on those things that we underlined in this call. Great. And then just one on Omicamptive.

Collaboration for relative symptoms and.

Reaching almost the ultimate end point here of having these negotiations virtually complete. So my first question is I guess, there's somewhat related is can you give any indication of the level of co funding that a stellus might provide for the phase threes and also I guess it impacts what you're the overall impact on milestone.

Fady Ibraham Malik: Can you provide any color around the upcoming interim in terms of whether the stopping boundaries are focused, you know, on the primary endpoint versus key secondary endpoints such as cardiovascular death? And then do you have any plans to present or publish baseline characteristics or the statistical analysis plan at any point? Thanks. Yeah, so I can't really comment on the specifics of what the criteria are. Obviously, obviously, they would involve the primary endpoint being met, but I won't really comment beyond that. The baseline characteristics of the trial will be something that will come out in an appropriate academic forum in the next few months. We are planning to publish a paper on the design of GoLACTIC that will hopefully also be in the public domain in the next few months as well.

Revenue is for the next 24 months.

Yes so.

Obviously this is still matters that is.

Dynamic and at this stage, we have agreement in principle, but theres still a number of other things that have to be agreed and finalize before we could really answer your question, but I think you should expect that were we to make a final agreement this would be a program that.

Cytokinetics would be advancing where the majority of development cost nonclinical in clinical would be board by Cytokinetics.

Stellus would provide co funding, but it would not be a majority, but rather a minority co fund.

Fady Ibraham Malik: I think in many respects, having that information will elaborate on some of the things you've been asking about, Jason. That will be fourth coverage. Great. I appreciate all of the additional details. Thanks again for taking questions. Thank you. Thank you. Your next question- Hello Joe. Hey guys, good afternoon.

And in exchange for royalty the flip side of that as Cytokinetics would be retaining the exclusive.

Commercial rights in order to enable a substantially bigger piece of the economics on the other side and with regard to milestones and royalties I think that we'll have to stay.

So for now.

Unknown Executive: Thanks for taking the questions. A couple of questions, actually. It's nice to get the visibility on the Estellas collaboration, Pharrell Decemtive, and reach almost the ultimate end point here of having these negotiations virtually complete. So my first question is, I guess they're somewhat related, can you give any indication of the level of co-funding that Estellas might provide for the phase threes, and also, I guess it impacts, what the overall impact on milestone revenue is for the next 24 months?

Comment like we havent before on what would be potential milestones and royalties only that which is our.

I understand thanks for that and then I guess the question is is the drug or open for re partnering is something you want to consider or wait until you have some.

Finalized phase three protocols and then secondly, a question for fatty maybe I just wanted to see if there was any update regarding meteoric. Thanks.

Robert I. Blum: Yeah, so obviously, this is still a matter that is dynamic. And at this stage, we have agreement in principle, but there's still a number of other things that have to be agreed and finalized before we can really answer your question. But I think you should expect that were we to make a final agreement, this would be a program that Cytokinetics would be advancing where the majority of development costs, non-clinical and clinical, would be borne by Cytokinetics, and Astellas would provide co-funding, but it would not be a majority but rather a minority of that co-funding, and in exchange for royalties. The flip side of that is cytokinetics would be retaining the exclusive commercial rights in order to enable a substantially bigger piece of the economics on the other side.

Yes, so I'll start turnover to Saudi regard to partnering.

The reason, we approached us tell us the way we did is very much because we have the conviction ourselves to be leading the development and commercialization of relative to some to the nail less ADESA may so.

I think partnering is not right now something that we're giving much thought too.

As much as were rather instead of trying to figure out how we ourselves on a go forward and what kind of timing protocol budget et cetera.

Spectrum, you, our CFO turn it back to Saudi.

Yes, very pleased without meteoric gets going we've.

Continue at sites to the study regularly.

Sites enrolling well the sites that are open.

We have I think we're on.

Track.

Robert I. Blum: And with regard to milestones and royalties, I think that'll have to stay silent for now. We'll not comment like we haven't before on what would be potential milestones and royalties, only that which is earned. I understand. No, thanks for that.

In terms of enrollment that study.

Types of patients who are getting very please see sort of.

These are the kind of basis I think we can have impact.

On their exercise performance just based on the initial characteristics of their exercise testing so.

Unknown Executive: And then I guess the question is, is the drug or open to repartnering? Is this something you want to consider or wait until you have some, you know, finalized phase three protocols? And then secondly, a question for Fady, I just wanted to see if there was any update regarding Meteoric. Thank you.

Yes, David is going smoothly there.

Thanks, a lot guys.

Thank you Joe.

Thanks, Rob.

Your next question comes from the line of Chad Messer with Needham and company.

Hello, Jeff.

Hello, Good evening, and happy Halloween and thanks for taking my my questions.

First I I had one on the neil's data that those results make a lot of logical sense to me.

Robert I. Blum: Yeah, so I'll start and then turn it over to Fady regarding partnering. The reason we approached Estella the way we did is very much because we have the conviction ourselves to be leading the development and commercialization of relative assentive in ALS and SMA. So I think partnering is not right now something that we're giving much thought to as much as we're instead trying to figure out how we ourselves want to go forward and with what kind of timing, protocol, budget, etc. And with respect to meteoric, I'll turn it back to Fady.

With that something you also looked at with with real deceptive in anyway.

So this is with relevant sometimes those days are mix I was curious aftermarket my apologies.

Your question just did we look at the effects of Tirasemtiv.

Parsing slow progress through some faster progress theirs.

Ill, let study answer that question, but before he does so I'll say one of the things that prompted us to do this is increasingly momentum in the lift community to look at slope aggressors distinctly from faster progress years in clinical research in general.

Fady Ibraham Malik: Yeah, we're very pleased with how Meteoric is going. We're, you know, continuing to add sites to the study regularly, sites are enrolling well, the sites that are open that we have, you know, I think we're on track in terms of enrollment in that study. Types of patients we're getting, and I'm very pleased to see sort of, you know, these are the kinds of patients I think we can have an impact on their exercise performance just based on the initial characteristics of their exercise testing, so. I'd say everything's going smoothly there. Great, thanks a lot guys. Thank you, Jeff. Your next question comes from the line of Chad Messer with NATO. Hello, Chad. Hello, good evening, and happy Halloween.

And as you may know.

The FDA recently approved drug called a durable that was.

And then all comers population and was demonstrated no effect in that first phase three study, but then based on a post talk analysis identified a clinically meaningful effect in the group a faster progressing patients and that studied that group again in another phase three trial only 100.

29 patients in that second phase III trial salt in a meaningful effect on the other assets.

Six months and submitted that FDA approval FDA approved for all patients faster and slower progressing patients so that was remarkable and very.

Unknown Executive: Um, first, I had one on the Niels data that those results make a lot of logical sense. Was that something you also looked at with Rel Decemtive in any way? So this is with relative symptoms, those data that we... I meant with a pure symptom, my... Your question is, did we look at the effects of tear assemptive parsing slow progressors from faster progressors? I'll let Fady answer that question, but before he does, I'll say one of the things that prompted us to do this is the increasing momentum in the ALS community to look at slow progressors distinctly from faster progressors in clinical research in general. And as you may know, the FDA recently approved a drug called Adarabone that was studied in an all-comers population and demonstrated no effect in that first phase 3 study.

Portal and informing the way we want to approach some of these analyses and some of our thinking but ill now turn to Fady to answer your direct question.

Yes, the we did look at those sorts of things and in the vitality study as well and.

The I think our conclusions were very similar.

In that close the slowest for aggressors.

Benefit elite than they dilute the signal that you see with the faster progress years. So.

Makes sense, if you will having taken a look at it fortitude to do that we saw the same thing.

Yes to receive notice the therapeutic hypothesis for an investigational medicines this to slow the decline of disease progression, it's difficult to separate.

Unknown Executive: But then, based on a post hoc analysis, identified a clinically meaningful effect in a group of faster progressing patients and then studied that group again in another phase 3 trial. Only 129 patients in that second phase 3 trial saw a meaningful effect on ALSFRS at 6 months and submitted that for FDA approval. FDA approved it for all patients, faster and slower progressing patients.

Potential effect out.

Absent some measure of progression in park in a patient populations. So it's going one way and enrichment strategy to enroll those patients who are faster progress, but it's also a practical one.

Yes, so that that all makes sense to me and you've kind of.

Almost completely precluded might might might follow up to that which is.

Robert I. Blum: So that was remarkable and very important in informing the way we wanted to approach some of these analyses and some of our thinking. Yeah, no, I mean, we did look at those sorts of things in the vitality study as well. The, you know, I think our conclusions were very similar in that the slowest progressors benefit the least, and they dilute the signal that you see with the faster progressors.

Whether looking at for faster progress reserves.

What makes sense for your next trial I I don't know.

You'll.

Comment any further on trial design I know, you're still working that out but.

Thanks.

It sounds like a logical way to center.

Here's here's what I'll tell you teach out its theres still lot of work, we need to do in order to be able to make a commitment to a next trunk.

Fady Ibraham Malik: Difficult to separate that potential effect out absent some measure of progression in a patient population. So it's, in one way, an enrichment strategy to enroll those patients who are faster progressing, but it's also practical. Um, yeah, no, that all makes sense and almost completely precludes my follow-up to that, which is, you know, whether looking at the faster progress, What makes sense for your next trial? I don't know.

We mentioned that we did have a round of questions with FDA type C meeting interaction, but we still would have an end of phase Twob meeting there is still a whole bunch of work, we want to do with our statisticians and with clinical opinion leaders, we not only want to talk to.

Clinical experts and regulatory authorities, but we're doing a very deep dive with payers.

Both in Europe , and the West we want to understand what they perceive to be the more meaningful value drivers before we might commit to another truck. So all this is going to take some time and I think it's the right thing to do.

Robert I. Blum: Comment any further on, You're still working that out, but. Sounds like a logical way to consider it. Here's what I'll tell you, Chad.

To be asking and answering these questions, we'll have more to say as we continue these activities.

Great and then we could just move on quickly to HCM can you maybe briefly educate me on what the important differences are between obstructive and non obstructive at a clinical level that the patients look.

Robert I. Blum: There's still a lot of work we need to do in order to be able to make a commitment to another trial. We mentioned that we did have a round of questions with FDA in a Type C meeting interaction, but we still want to have an end of Phase II meeting. There's still a whole bunch of work we want to do with our statisticians and with clinical opinion leaders. We not only want to talk to clinical experts and regulatory authorities, but we're doing a very deep dive with payers, both in Europe and the U.S. We want to understand what they perceive to be the more meaningful value drivers before we might commit to another trial. All of this is going to take some time, and I think it's the right thing to do to be asking and answering these questions. We'll have more to say as we continue these activities. Great. And then if we could just move on quickly to HCM, can you maybe briefly educate me on..., https://www.youtube.com.au, There are a lot of similarities, but both you guys and my myocardium. Prioritize. Unobstructed view.

Have a lot of similarity FFO, both you guys and myocardial of kind of prioritized.

Constructive I was wondering if there's anything trickier about constructive warm weather clinically or regulatorily or just the heterogeneity or something I.

Any any direction on that would be appreciated. Thanks.

Yes, certainly it so.

The the ATM cases are classified as activity to sub type.

The reason for the classification as at the obstructive patients.

The muscle of the heart so they can symmetrically and it's taken.

To a greater extent right underneath where the blood exit the heart out of the aortic valves and so as the hearts contracting that instruction guests in the way with flood, leaving the heart.

And therefore, it's called obstructive hypertrophic cardiomyopathy.

And in those patients relatively small changes in the way that that.

Fady Ibraham Malik: I was wondering if there's anything trickier about the unobstructed ones, whether it's clinically or regulatoryly or heterogeneity or something. Any direction on that would be appreciated. Yeah, certainly, you know, so the HCM patients are classified into these two subtypes, and the reason for the classification is that in the obstructive patients, the muscle of the heart thickens asymmetrically, and it thickens to a greater extent right underneath where the blood exits the heart out of the aortic valve. And so as the heart's contracting, that obstruction gets in the way of blood leaving the heart In those patients, relatively small changes in the way that that muscle functions can have big impacts on the outflow of blood from the heart because the obstruction; relief of the obstruction can greatly improve forward cardiac output. Non-obstructive patients generally have thickening of the heart all around, and maybe it may not be the same everywhere, maybe a bit asymmetrical, but it isn't right underneath where the outflow relieves the heart.

Muscle function can have big impacts on on the outflow of glut.

From the part because the obstruction.

Lee for the obstructions, Kim and great improve.

Forward cardiac out output.

Then the non instructed pace and generally have.

Beginning of the heart all around and maybe it may not be same everywhere. It maybe a bit HC eight symmetrical, but it isn't.

Right underneath.

The outflow leases at heart.

And those patients their symptoms are.

Derives from how stiff the hard it.

And so.

Different factors are at play you will.

In terms of are leaving them, you really need to probably see improvements in the way the heart Phil.

The way the Hartford models, potentially if may take longer to see it impact.

Of drug therapy in that population, whereas in the obstructive patient.

You can achieve a relatively.

Quick Pharmacodynamic effect is leaving the construction.

And thereby.

Moving their symptoms on the basis of that.

Okay, I guess given that we have an opportunity to them to learn a lot this quarter from them at camp them.

Fady Ibraham Malik: And in those patients, their symptoms are derived from how stiff the heart is and so, [inaudible] on the basis of that. Okay, but I guess given that we have an, learn a lot. Learn a lot.

Fady Ibraham Malik: Page 22 of 22, Yeah, absolutely. I mean, it'll be very interesting to see how the non-instructive patients behave. I'm optimistic that they will find positive effects of the mechanism of action on this patient population and on their symptoms and potentially on their exercise tolerance as well. All right, great.

Two study anything anything you are particularly hoping to learn from that.

Yes, absolutely I mean, if it will be very interesting to see how the non instructed patients behave.

I am optimistic that.

Well, we'll find.

The effects of.

Mechanism of action that.

Patient population.

And on their symptoms and potentially on their exercise tolerance as well.

Alright, great mobile.

Unknown Executive: Well, we'll certainly be paying attention to that and looking forward to you guys starting your own. Thanks for taking my questions. Thank you, Jeff. Your next question comes from the line of Jeff Hung with Morgan Stanley. Good afternoon, Jeff. Hi, this is Hannah on behalf of Jeff Hung.

When you paying attention to that and looking forward you guys starting your own phase two in obstructive. Thanks for taking my questions.

Yes.

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

Good afternoon, Jeff.

Hi, This is hana on for Jeff.

Unknown Executive: We had just a few more questions on CK274. So how long do you expect enrollment to take and when might we see initial data? And then, given that Phase 1 was in healthy volunteers, can you remind us what gives you confidence that we'll see the LVOT gradient improvements in obstructive HCM patients? Yeah, so it's a little early to comment on how long we think the trial will last.

We had just a few more questions on us CK 274, so how long do you expect enrollment to take and worldwide. One might we see initial data and then given that the phase one was in healthy volunteers can you remind us what gives you confidence that we'll see the algeo t. gradient improvements in the obstructive HCM patients.

Yes.

Hello early to comment on how long we think the trial will last.

Fady Ibraham Malik: You know, we expect to see results in 2020 from some set of patients in that trial. We'll have more to say about it as the trial gets underway and begins enrolling patients in our upcoming quarterly call. As to your second question, you know the effect of CK274 in healthy volunteers was to reduce overall cardiac function, and so it was clearly active in that population, and that effect of reducing cardiac contractility is the basis for reducing left ventricular outflow. Yeah, it's not just the phase one data that lends support for that therapeutic hypothesis.

We expect to see results in.

2020 from subset of patients in that trial.

We'll have more to say about in that trial it gets underway and begin enrolling.

In our upcoming quarterly call.

As to your second question.

Effective of CK 274 in healthy volunteers was to reduce overall cardiac function and so it is with clearly active and that population in and that effect of reducing cardiac contractility is the basis for reducing the less than tricolor out.

Track construction, so we fully expect the healthy down volunteer data to be predictive of what we will see.

Patients yeah, it's not just for phase one data that lends support through that therapeutic hypothesis. It's also preclinical data.

Fady Ibraham Malik: It's also preclinical data that are very consistent for pharmacodynamic effects. What I'll also say is, with regard to timing of results... As Fady indicated, that depends on enrollment. It also depends on whether we're going to be dose escalating from 1 to 2 cohorts or 2 to 3 cohorts; that's ultimately going to be determined based on the data we're observing. And then, if I can just ask one more question on the financials. How are you thinking about the cash burn and expenses? Are you still guiding to? I think it was 85 to 90 million in cash burn. That is correct. For 2019, we're still guiding to 85 to 90 next year.

Consistent for Pharmacodynamic effects.

Well I'll also say is with regard to timing of results.

Body indicated that depends on enrollment it also depends on whether we're going to be dose escalating.

From what the two cohorts or two to three cohorts. That's ultimately this will be determined based on the data were observed.

Great and then if I can just ask one more on financials. How are you thinking about the cash Brennan expenses are you still guiding Q I think it was 85 to 90 million in cash burn.

That is correct for 2019 were still guiding to 85 to 90 exit.

Unknown Executive: Okay, great. Thank you. Thank you. [inaudible] for sort of the opportunity for 274 in different types of the condition. So whether it be obstructive or an obstructive or non-obstructive, you know, how do you sort of see that progressing if you could share it? Thanks so much. It all started maybe as a fad east of combat.

Okay, great. Thank you.

Thank you.

Your last question comes from the line of Ted Tenthoff from Piper Jaffray.

Okay.

Hey, guys. How are you seeing comments were taking time.

My question would happen and to put some willing to commit to that.

Or sort of the opportunity for two seven core different type.

Oh, the condition, so whether it be obstruct lower or short term amount obstructive how do you sort of see that progressing if you could share. Thanks.

Yes, I'll start it maybe us paddy to come but.

We've been.

Robert I. Blum: You know, we've been working in this field for quite a long time as pioneers as it pertains to both activating and inhibiting cardiac myosin. We've learned a lot preclinically and clinically that holds true across multiple different patient populations. We certainly understand this biology quite well. As such, we're looking at this development program as pertains to addressing issues of hypercontractility, whether that manifests itself in patients with HCM, obstructive or non-obstructive, but there are also other populations that have hypercontractility, as I'll ask Fady, maybe, to elaborate. Yeah, I think, you know, there they are.

Working in this field for quite a long time as pioneers as it pertains to both activating inhibiting cardiac myosin, we've learned a lot preclinically and clinically that reads across multiple different patient populations and.

We certainly understand this biology quite well.

Such we're looking at this development program as it pertains to.

Addressing issues of hyper contractility, whether that manifests itself in patients with HCM obstructive or nondestructive, but they're also other populations that have hyper contractility.

Last Friday may be to elaborate.

Yes, I think.

There are.

Fady Ibraham Malik: Obviously, the patients with HCM, the obstructive and non-obstructive patients. But there's also a large population of patients with heart failure in preserved objection practice. I think we're learning more about those patients and how to sub-practify them. Certainly, there is going to be a substantial portion, I think, whose basis for their symptoms and their condition is underlying hypercontractility of the heart. Often, you see in these patients very high ejection fractions, hearts that have hypertrophy. They may not have hypertrophy and increases in cardiac function to the degree that the H&M patients do, but they're part of that continuum. They may also provide an eventual opportunity to explore this mechanism. You know, you may have seen an article in the Wall Street Journal yesterday about heart failure and its increasing prevalence and clinical and economic burden. And that's not just systolic dysfunction heart failure. Increasingly, cardiometabolic disease is reading on HF-PF, and there are components and subsets of the HF-PF group that we're especially interested in.

Obviously, the patients with ATM, the obstructive non destructive patient.

It's also a large population of patients with heart failure in preserved ejection fraction and I think we're learning more about.

Those patients and.

How to sub classify them.

Certainly there is going to be a substantial.

Portion I think to the basis for there.

They're kit their symptoms and their condition is underlying hyper contract plays the heart often you see.

In these patients very high ejection fractions hearts that have hypertrophy. It may not have I purchased fee and and.

Increases in cardiac function of the degree that dates the m. patients do but but they're part of that continue often.

They may also provide an eventual opportunity to explore this mechanism it.

You may have seen an article in the Wall Street Journal yesterday about heart failure at this increasing prevalence and clinical and economic burden.

And that's not just historic dysfunction heart failure increasingly.

Cardiometabolic disease is reading on tough tough and there are key components and subsets of the have tough group that we're especially interested in this is a very significant area of ongoing research and.

Robert I. Blum: And this is a very significant area of ongoing research and development at Cytokinetics. So, you know, it's premature to be speculating too much on that until we have more of a basis. Makes a lot of sense. Appreciate the update. Have a good one, guys. Thanks, Jeff.

Development.

Southern Connecticut, so it's premature to be speculating too much on that until we have more of a basis by which we could commit to shareholders as to what we would be expecting to do but please note that it is an area very high interest for us.

Makes sense appreciate the update how's it going guys.

Thanks, Jeff Thanks.

And there are no further questions at this time.

Unknown Executive: And there are no further questions at this time. Thank you, operator, and I want to say thank you and happy Halloween to everybody that joined us on the call. I hope we didn't keep you too long.

Thank you operator, and I want to say, thank you would happy Halloween to everybody that.

I'm joined on the call I Hope, we didn't keep you too long I will say that.

Robert I. Blum: I will say that we shared quite a bit today about how we're thinking about priorities at the company and how we're thinking about extending and preserving capital through our most important value-generating milestones. And I do believe, as we've elaborated, we're aligned with feedback we've received externally from shareholders, but also in keeping with our reputation and history of following the science. As such, we look forward to keeping you updated on our progress as we conclude 2019 and look forward to continuing through 2020. And especially as we recognize there are quite significant value-creating milestones anticipated as we go forward. With that, I'll end the call and thank everybody for their time and your interest in our company. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect. Thanks for watching!

We shared quite a bit today about how we're thinking about priorities at the company and how we're thinking about extending and preserving capital through our most important value generating milestones and I do believe that.

As Weve elaborated we're aligned with feedback we've received externally from shareholders, but also as in keeping with our reputation in history. Following the science.

Such we look forward to keeping you updated on our progress as we could include 2019 appear through 2020, and especially as we recognize there are quite significant value, creating milestones anticipated as we go forward with that we'll end the call and thanks, everybody for their time and your interest in our company.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.