Cytokinetics Inc (CYTK) 2018 Q3 法說會逐字稿

Good afternoon, and welcome, ladies and gentlemen, to the Cytokinetics third quarter 2018 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 request of the company, we will open the call for questions and answers 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.

Good afternoon, everyone, and thank you for joining us today. Robert Blum, our President and Chief Executive Officer, will kick off the call with introductory comments about the current state of our business. Fady Malik, our EVP of Research and Development, will provide updates on our cardiac muscle program focused on the Phase III development of omecamtiv mecarbil. And Brad Morgan, SVP of Research and Nonclinical Development, will discuss progression of AMG 594, the cardiac troponin activator under our collaboration with Amgen, and CK-3773274, or CK-274, our unpartnered cardiac myosin inhibitor. Andy Wolff, our SVP and Chief Medical Officer, can't be with us today, so Fady will then come back and share updates on our skeletal muscle program focused on the development of reldesemtiv and the next-generation fast skeletal muscle troponin activator we are advancing under our collaboration with Astellas. Pete Roddy, our SVP and Chief Accounting Officer, will provide a financial overview for the quarter. And Ching Jaw, our SVP and Chief Financial Officer, will discuss our financial outlook before Robert concludes with additional thoughts on the company and upcoming milestones.

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. Examples of forward-looking statements may include statements relating to our financial guidance and goals, our strategic initiatives, our collaborations with Amgen and Astellas, clinical trials and the potential for eventual regulatory approval of our product candidates. Our actual results may differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our most recent 10-K, 10-Q and 8-Ks. We undertake no obligation to update any forward-looking statements after this call.

And now I will turn the call over to Robert.

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

In recent weeks, we were pleased to announce progress in connection with both the extension and the expansion of our pioneering pipeline of drug candidates. We provided rather in-depth updates at our recent R&D Day, so on today's call, we'll only highlight some of those key advancements and instead elaborate on how we're pointing forward with our 5 investigational medicines in development.

Having recently filed 2 INDs, one for CK-274, our unpartnered cardiac myosin inhibitor; and one for AMG 594, our cardiac troponin activator discovered under our collaboration with Amgen, we're executing well on a purposeful strategy to augment our cardiac muscle programs and reinforce our demonstrated leadership in drug discovery and development relating to modulating the mechanics of cardiac muscle function focused to the potential treatment of cardiovascular diseases. We expect both of these compounds to be in Phase I by year-end.

As you'll hear from Fady in a moment, there is still a very large unmet need for the treatment of heart failure and related diseases of cardiac muscle dysfunction as resonated quite loudly at the Heart Failure Society of America meetings which we attended during the past quarter. GALACTIC-HF, the Phase III cardiovascular outcomes clinical trial of omecamtiv mecarbil, continues to enroll well with nearly 6,000 patients now enrolled in approximately 1,000 centers across 35 countries around the world. This trial ranks amongst the largest heart failure trials ever conducted, and it is encouraging to observe the widespread interest in this first-in-class mechanistic approach to a disease that affects so many at the same time morbidity and mortality remains so high.

As we heard loud and clear when we convene advisory boards of clinicians, payers and patient advocacy groups, there remains a high clinical, economic and societal burden and yet so little biopharmaceutical innovation is directed to the global epidemic of heart failure and related diseases of cardiac dysfunction that only grows more prominent with our aging demographics. At Cytokinetics, we're pleased to be pioneering an entirely new pharmacology of cardiac muscle directed drug candidates that now numbers 3 compounds in development focused to either impaired or excessive cardiac muscle contractility.

We're also pleased to be soon starting METEORIC-HF, the second Phase III clinical trial of omecamtiv mecarbil, which will focus on the potential effect of omecamtiv mecarbil on exercise performance in patients with heart failure and systolic dysfunction.

On the skeletal muscle side of our business, Fady will also elaborate on recent progress in our neuromuscular programs focused to the potential treatment of SMA and ALS, as well as provide perspectives on recent meetings we had with SMA Europe, the umbrella advocacy organization for SMA across Europe, to inform the potential further development of reldesemtiv in patients with SMA. Fady will also discuss progress towards completion of enrollment in FORTITUDE-ALS, the ongoing Phase II trial of reldesemtiv in patients with ALS, which remains on track to complete enrollment soon and to enable presentation of results in the first half of 2019.

As we look toward what lies ahead in the balance of Q4 and to our prospects for 2019, we're optimized, we're energized, and we're proud that our pioneering work in the discovery of novel drug candidates that modulate sarcomere function has now translated into an ever-expanding pipeline of investigational medicines to potentially treat some of the most devastating diseases of muscle dysfunction and weakness.

Now I'll turn the call over to Fady so he can update you firstly on omecamtiv mecarbil.

Thanks, Robert. As Robert mentioned, GALACTIC-HF, the Phase III cardiovascular outcomes clinical trial being conducted by Amgen under our collaboration, continues to progress well. Enrollment has surpassed 70% of its planned 8,000 patients, with over 5,800 patients randomized to date, having a high risk for cardiovascular mortality and heart failure events as intended by the trial design. We are pleased to see robust enrollment across all geographies, including Asia and Latin America where patient recruitment is contributing meaningfully to overall enrollment rates. We expect to complete enrolling patients in GALACTIC-HF during the first half of 2019.

Additionally, we're on track, based on the number of accrued events for the Data Monitoring Committee, or DMC, to conduct a planned interim analysis for futility in the first half of 2019. And the second planned interim analysis, which includes an assessment of efficacy, will occur in 2020. The DMC has been meeting regularly, including again during the recent quarter. The DMC reviews the unblinded data from GALACTIC-HF, and has continued to recommend no changes to the conduct of the ongoing trial.

We've had an opportunity to meet with many of our investigators at the Heart Failure Society of America annual meeting in September, and in that conference, the Chair of the Executive Committee for GALACTIC-HF, Dr. John Teerlink, gave a podium presentation on omecamtiv mecarbil in a session that focused on leading translational science and clinical research. His presentation was very well-received, especially because it highlighted the comprehensive clinical research and associated peer-review presentations and publications that have distinguished the development of omecamtiv mecarbil.

We are pleased to hear that this novel mechanism investigational medicine is top of mind among heart failure specialists. We believe that omecamtiv mecarbil stands alone as the most studied drug candidate developed specifically for the treatment of heart failure, and the heart failure community has engaged strongly around this program.

We also recently presented the design of the second Phase III clinical trial of omecamtiv mecarbil planned to be conducted by Cytokinetics in collaboration with Amgen at our R&D Day. This trial will focus on the potential effect of omecamtiv mecarbil to increase exercise performance in patients with heart failure. METEORIC, which stands for Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure, is a Phase III randomized, placebo-controlled, double-blind, parallel group, multicenter clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing, or CPET, following 20 weeks of treatment.

The trial is designed to enroll approximately 270 patients with heart failure and a reduced injection fraction, randomized 2:1 to omecamtiv mecarbil or placebo, at sites throughout the U.S., Canada and Europe. Primary end point of METEORIC-HF is a change in peak oxygen uptake of CPET from baseline to week 20. The details of this trial design will soon be available on clinicaltrials.gov. We're working together with Amgen to complete startup activities towards the objective of beginning this clinical trial at the end of the year.

With that, I'm going to turn it over to Brad to discuss AMG 594 and CK-274.

Thanks, Fady. Moving to the expansion of our cardiac pipeline, our pioneering expertise in the pharmacology of muscle has recently resulted in 2 new drug candidates now proceeding towards clinical trials in Q4. Amgen recently submitted an IND for AMG 594, a novel, first-in-class, selective, oral, small molecule cardiac troponin activator discovered under our joint research program with Amgen. In preclinical models, AMG 594 binds to an allosteric site on the cardiac troponin complex and sensitizes the cardiac sarcomere to calcium. This mechanism facilitates more actin-myosin cross-bridge formation during each cardiac cycle, thereby resulting in increased myocardial contractility. Like cardiac myosin activation, and unlike traditional ionotropic mechanisms, cardiac troponin activation does not change the calcium transient of cardiac myocytes.

Based on preclinical data, AMG 594 may offer improved efficacy and dose-related convenience relative to omecamtiv mecarbil. We expect Amgen will soon initiate a Phase I study to assess the safety and tolerability of AMG 594 and its potential to increase cardiac function. We are discussing with Amgen the objectives of a potential subsequent Phase II development program that may include evaluation of AMG 594 as a potential treatment for patients with heart failure with reduced ejection fraction, and other types of heart failure, such as right ventricular failure or genetic cardiomyopathies resulting from impaired cardiac contractility.

At our recent R&D Day, we were pleased to also announce that we recently submitted an IND for CK-274; a novel, oral, small molecule cardiac myosin inhibitor for the potential treatment of hypertrophic cardiac myopathy, or HCM. CK-274 was discovered by our scientists, independent of our collaborations, and arose from an extensive chemical optimization program conducted with careful attention to therapeutic index and pharmacokinetic properties. Consequently, we believe CK-274 may translate into a best-in-class approach to the treatment of HCM, a disease characterized by hypercontractility.

In preclinical models, we found that CK-274 reduces myocardial contractility by binding directly to cardiac myosin at a selective allosteric binding site, thus decreasing the number of myosin motors that enter the force-producing state with actin. In contrast to sarcomere activators, like omecamtiv mecarbil or AMG 594, CK-274 reduces the number of active actin-myosin cross-bridges during each cardiac cycle and consequently reduces myocardial contractility. CK-274 may therefore be therapeutically useful in conditions characterized by excessive hypercontractility, such as HCM.

In preclinical models of cardiac function, CK-274 reduced cardiac contractility in a predictable and dose exposure-dependent fashion. In preclinical models of disease, cardiac myosin inhibitors reduced cardiac hypertrophy and cardiac fibrosis, 2 common pathological consequences of HCM. Finally, the preclinical pharmacodynamic parameters of CK-274 were optimized with the objective to maximize potential ease of use in the clinical setting.

We expect to initiate a Phase I study before the end of 2018 to assess the safety, tolerability, pharmacokinetics and effect on cardiac function of CK-274. Subsequently, we are planning a Phase II trial, which will examine this potential to reduce left ventricular outflow tract obstruction in patients with HCM. Left ventricular outflow tract obstruction limits cardiac output and results from excessive hypertrophy and thickening of the cardiac muscle during systole, particularly in the region of intraventricular septum.

Consistent with our industry-leading muscle biology programs, the development program for CK-274 will focus on fully characterizing pharmacokinetic/pharmacodynamic relationships. The program will assess the potential of CK-274 to improve exercise capacity and relieve symptoms in patients with hyperdynamic ventricular contraction and left ventricular outflow tract obstruction due to HCM.

And now I'll turn it back over to Fady to provide updates and perspectives on our skeletal muscle program with a focus on reldesemtiv.

Thanks, Brad. Before I switch gears into our skeletal program, I just want to say it was a very eventful quarter for our cardiac franchise. And the productivity of our research group, both in collaboration with our partners and for our own programs, was extremely gratifying to us. We're pleased to see that the last few years of effort and research culminated in these 2 IND filings submitted last month.

Now moving to our skeletal muscle program in collaboration with Astellas. We've been executing against a broad mid-stage clinical development program to characterize the potential safety, pharmacodynamics, pharmacokinetics and efficacy of reldesemtiv and how this novel mechanism may be applied to patients with neuromuscular and non-neuromuscular diseases and conditions of muscle dysfunction. Last month, we provided an update on the program, and today I'll recap key points with a few additional perspectives.

During the quarter, we presented additional data from CY 5021, a hypothesis-generating Phase II study which showed concentration-dependent increases versus placebo and changes from baseline in Six Minute Walk Distance, a submaximal exercise test of aerobic capacity and endurance, as well as in maximal expiratory pressure, or MEP, a measure of strength of certain respiratory muscles after 8 weeks of treatment with reldesemtiv.

The additional data presented at the Muscle Study Group meeting showed that the increases in Six Minute Walk Distance and MEP observed during the treatment period were sustained for 4 weeks after discontinuation of study drug. Further, post hoc analysis showed that changes from baseline in the Six Minute Walk Distance at 450 milligrams twice daily were all correlated with changes from baseline in the 9 individual domains of the SMA Health Index, or SMA-HI, and the SMA total score to reflect decreasing disease burden as measured by the SMA-HI.

This correlation was nominally statistically significant for 4 of the 9 domains, including fatigue and activity participation, as well as the SMA-HI total score. Of note, decreases in the SMA-HI scores reflect reduced disease burden as measured by that patient-reported outcome measure. Therefore, the negative correlation coefficients indicate that as Six Minute Walk Distance increases, disease burden assessed by the SMA-HI is reduced.

We shared data from CY 5021 at expert adviser meetings in the U.S. and Europe during the recent quarter and received constructive feedback, as well as recommendations to inform potential next steps. We were encouraged by their level of interest and concur that we should pursue a better understanding of the exposure-response relationship, particularly at higher doses in future studies.

Toward that end, Cytokinetics plans to conduct an additional Phase I study of reldesemtiv in healthy volunteers to assess higher doses than were evaluated in the Phase II study of SMA patients and to evaluate exposure related to dose. In addition, we will be engaging FDA in Type C interactions this year regarding the acceptability of Six Minute Walk Distance as an end point for the potential registration program of reldesemtiv in patients with SMA. We're also discussing with Astellas other steps that we may take in 2019.

Recently, Cytokinetics also engaged in meetings in Europe with patient groups, clinical experts and market access representatives regarding the evolving SMA marketplace. Through these discussions, we gained a better understanding of the significant value to patients and their caregivers of a therapy that may improve patient's fatigability and function in their daily lives. In addition, we gained insights to help define clinical development options and appropriate outcome measures for ambulatory and nonambulatory SMA patients as well as the value that this potential therapy may have for payers and related reimbursement considerations.

Turning to FORTITUDE-ALS, our Phase II clinical trial of reldesemtiv in patients with ALS. We're pleased to report that enrollment rates have increased during the quarter, and we're nearing completion of enrollment with more than 400 of the 445 planned patients randomized. We expect to conclude enrollment in this fourth quarter with results from the clinical trial expected in the first half of 2019.

Moving to the non-neuromuscular trials. Together with Astellas, we recently announced results of the Phase II clinical trial of reldesemtiv in patients with COPD and the interim analysis of data from the ongoing Phase Ib study of reldesemtiv in elderly adults with limited mobility or frailty. Unfortunately, the trial in patients with COPD did not meet the primary end point and did not demonstrate a statistically significant treatment difference in any of the secondary end points. Adverse events were similar between groups receiving reldesemtiv and placebo. An interim analysis of the Phase Ib study of reldesemtiv in elderly subjects with frailty was conducted, and the independent Data Monitoring Committee determined that the predefined criteria for futility had been met. As such, Astellas has notified the site investigators to halt further enrollment in the study and proceed the closeout of the study.

It's important to note that the purpose of these studies in non-neuromuscular conditions was to inform future development of next-generation FSTAs and not reldesemtiv. Although the frailty study still needs to be completed and its data fully analyzed, both studies will help elaborate on the translatability of the mechanism of action and guide development towards optimal patient populations.

Finally, under our collaboration with Astellas, we're advancing CK-601, a next-generation FSTA, into IND-enabling studies. This potential drug candidate was designed to have different physiochemical properties than reldesemtiv and may be developed for the treatment of diseases and conditions associated with neuromuscular or a non-neuromuscular etiology and pathogenesis. We're also continuing our joint research program with Astellas providing sponsorship to Cytokinetics' scientific activities through 2019.

And now I'll turn the call over to Pete to provide an update on our financials.

Thank you, Fady. Once I touch on our cash, our revenue and our spending, Ching will review our financial strategies for the balance of 2018 and the outlook for 2019. More details on our actual results are included in the press release itself.

We ended the third quarter with over $210 million in cash, cash equivalents and investments. Our cash includes $10 million from our drawdown of debt following data from the Phase II data for reldesemtiv in spinal muscle atrophy and as specified in our loan agreement. Our revenue in Q3 2018 came primarily from our strategic alliance with Astellas and includes both cash and noncash revenue recognized under ASC 606, the new accounting rules for revenue.

Moving to expenses. We reduced our third quarter 2018 R&D expenses to $21.4 million from $24.9 million in Q3 2017. About 45% of our R&D expenses were attributable to our skeletal muscle contractility programs primarily for development in clinical trials for reldesemtiv, 33% to our cardiac muscle contractility programs and 22% to our other research activities. These changes reflect, as expected, increases we're spending on our recently announced cardiac myosin inhibitor program; the initial spending, including expenses that will be reimbursed by Amgen for METEORIC-HF; and spending for reldesemtiv reimbursed by Astellas that were more than offset by appropriate decreases for tirasemtiv. Our third quarter 2018 G&A expenses fell to $7.2 million from $9.7 million in Q3 2017. Our spending in Q3 2017 included support for pre-commercial work for tirasemtiv.

Ching will take it from here to bridge from our results for Q3 to our financial outlook for the future.

Thanks, Pete. We recently reviewed our strategic plan with our board, providing an operational and financial road map for Cytokinetics over the next 3 years, contemplating different scenarios based on potential clinical trial outcomes during the next year.

As we have previously stated, our financial strategy remains to manage our cash through the readout of results from GALACTIC-HF without relying on dilutive financing. In addition to judicially managing our cash and reducing our costs, we are seeking to raise non-dilutive capital through a potential collaboration relating to our currently unpartnered cardiac myosin inhibitor program, which we expect to advance to Phase I later this year. We also are eligible to receive collaboration milestone payments over the next several years.

While we have not yet provided formal guidance for 2019, we expect our spending in 2019 to be less than that in 2018, even with approximately 30% of the cost to be related to the conduct of Phase I and Phase II studies for CK-274. We're not responsible for expenses related to AMG 594, and the majority of the costs associated with the conduct of METEORIC-HF and FORTITUDE-ALS are covered under our collaborations with Amgen and Astellas, respectively.

Our current cash balance, as well as our expected cash at the end of 2018, should represent over 24 months of forward cash burn, even with Cytokinetics funding one of the two new programs entering clinical trials.

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

Thank you, Ching. So as we highlighted a few weeks ago at our R&D Day, we're turning the page onto a new chapter in Cytokinetics corporate development as we approach the final months of our 20th year of operations; a chapter filled with new investigational medicines entering Phase I studies. At the same time, our later stage potential medicines advance in clinical development toward potentially meaningful results in 2019 and beyond.

Our leading muscle pharmacology pipeline is now comprised of 5 compounds in development. The continued productivity of our research engine is a testament to our pioneering leadership in cytoskeletal and muscle biology, the continuity of our senior management team, our unrivaled experience in clinical research directed to the pharmacology of muscle, and our demonstrated track record to monetize that expertise and multiply it in the form of landmark deals. We look forward to continuing to leverage our learnings across our growing and advancing pipeline, and we remain optimistic about our future.

A final note about our commitment to the patient communities we serve. During the past quarter, we granted the ALS Association Golden West Chapter the Inaugural Cytokinetics Communications Fellowship Grant. The purpose of this grant program is to support increased capacity and community engagement for nonprofit organizations to help fund additional communication resources to educate their community, provide additional support and services, and create connections among patients, caregivers and critical advocacy resources. We look forward to extending this program to other organizations in the years to come.

I mention this because this newer program is but one example of our leadership in the ALS, the SMA and the heart failure communities that have afforded us a meaningful seat at the table to understand the needs of patients and caregivers, to elevate their voice, and to learn how our leading muscle directed drug candidates may ultimately play a meaningful role, alongside other treatments for patients in desperate need.

We take these responsibilities quite seriously, and we listen to the communities we aim to serve. As an example, we recently convened an advocacy summit with organizations in the neuromuscular area, and I'm encouraged that there's a meaningful opportunity for reldesemtiv in SMA and ALS that we hope to address.

Now let me recap our expected milestones for the balance of 2018 and into 2019. For omecamtiv mecarbil, we expect to complete enrollment of patients with chronic heart failure in GALACTIC-HF during the first half of 2019. And we're working toward the objective of initiating METEORIC-HF, the second Phase III trial of omecamtiv mecarbil, which is intended to evaluate its effect on exercise performance in patients with heart failure, that to occur we hope by the end of 2018.

For CK-274, we expect to initiate Phase I studies by the end of 2018. For AMG 594, we expect that Amgen will initiate Phase I studies by the end of 2018. For reldesemtiv, we expect to complete enrollment of patients in FORTITUDE-ALS in this fourth quarter 2018, so that results may be available in the first half of 2019. And for our preclinical research, we expect to advance CK-601 and continued IND-enabling studies, as well as continue research activities under our joint research program with Astellas, directed to the discovery of next-generation skeletal muscle activators. We also expect to continue our other muscle biology focused research, including the expansion of our research activities beyond the contractility of muscle, towards the energetics of muscle.

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

(Operator Instructions) And your first question is from Jeff Hung from Morgan Stanley.

For the additional Phase I that you plan to conduct in higher doses than the Phase II of the SMA, would the plan be that you complete the study before conducting any future pivotal studies in SMA? And what do you see as the timeline for the Phase I study?

So that is correct. I'll turn it over to Fady to elaborate.

Yes, I think our plan is to initiate that Phase I study early next year and complete it to enable the design of a potential study that would be conducted in SMA. So it's a relatively short study to conduct because it's conducted in healthy volunteers at a Phase I unit, and hopefully early in the year next year we'll have those results to guide us to next steps.

Great. And then earlier this week, MyoKardia announced their second HCM and DCM programs. So given that AMG 594 could be used in DCM and CK-274 is being developed for HCM, how do you view the potential market opportunities? Do you view these as big enough for multiple players? Or theoretically, can different agents for HCM and DCM act more complementary to each other, or would they be used more sequentially? Or is there even any reason to think that they could be combined? Just curious how you view these spaces. Thanks.

Yes, I'll start, and maybe Fady, if you want to add afterwards. Certainly the fact that our pioneering leadership with this space has invited other companies to also participate is suggestive of the fact that there's a substantial opportunity. I do believe that there's an opportunity that could be satisfying to multiple companies, recognizing that heart failure is the number one reason why people in the United States are hospitalized, people over age of 65 are hospitalized. You're talking about millions of patients. But with respect to your specific question, we haven't guided to specific indications for AMG 594. And while you mentioned one, I think that's one of several we may consider. And ultimately, we see that there are dozens of potential indications that could relate to various aspects of cardiac dysfunction such that a novel mechanism activator could ultimately play a role in quite a number of different types of indications for what would be a broad development strategy. We and Amgen are still considering how we might approach AMG 594 in concert with the further development of omecamtiv mecarbil, and that's something that we'll shed light on more over time. But I think the bottom line to your question is that with regard to omecamtiv mecarbil, which is most certainly the leading cardiac muscle activator, having been studied in many thousands of patients, we see that there's an opportunity to advance both CK-274 and AMG 594 without potentially cannibalizing the business that we should be building.

And your next question is from Joe Pantginis from H.C. Wainwright.

Robert, I don't know if this is an overnuanced question, but when you look at the details that you gave today for GALACTIC-HF, I think this is the first time you're defining the population a little better by saying that they're in the high-risk group. So just curious if maybe you can provide more color on this population. And when you label this cardiovascular population as high risk, does that lend to the potential for accelerated events and any impact on potential timelines? Thanks.

Yes. So it's not new that we referred to the patients enrolled in GALACTIC as at high risk of morbidities and mortality, and in that way, it's consistent. But I do think your question is still a valid one. Let me break it down a little bit. Heart failure, as you know, representing about 5 to 6 million people in the U.S. alone, breaks out roughly 50/50 into those with systolic dysfunction and those with diastolic dysfunction. And we, with GALACTIC and in this program over many years, over 10 years, have been focused to those patients with heart failure and systolic dysfunction where their cardiac performance has been compromised. But even within that subset, the GALACTIC study is intending to enroll patients who are at high risk of death and other heart failure related events. You may recall, at one time we did a study called ATOMIC; another time a study called COSMIC. ATOMIC represented one end of the spectrum in terms of symptomatic, acutely ill, hospitalized heart failure patients. COSMIC more chronic, asymptomatic outpatients. And GALACTIC really falls in between, as I'll now ask Fady maybe to elaborate and he can go deeper into your question.

Yes, I think the -- we've always pointed out that the study design was meant to enroll a high-risk population. And as we've I think presented our recent R&D Day some characteristics of that population, it's quite consistent with the intent of the study design. The ejection fraction on average is less than 30%. Patients have been hospitalized within the last 4 months. Their NT-proBNPs are over 2,000. And as was intended by the study design, about 25% of them were enrolled from the inpatient setting since the study is enrolling both inpatients and outpatients. All of those characteristics speak to a population that is at high risk. And the event rates that we estimated for the study were based on achieving those characteristics, so I wouldn't necessarily expect the event rates to accrue faster than we expected. I think we're on track with what our initial assumptions were.

No, that's great. Thanks for the added color as we get closer to enrollment of this great study.

And your next question comes from Jason Butler from JMP Securities.

Just thinking back to the R&D Day, a couple of the experts you had there spoke in support of Six Minute Walk Test or Distances as a key end point to focus on moving forward in SMA. When you think about the meetings that you had with stakeholders in Europe, is there similar support for the Six Minute Walk Distance end point? And then also just following on, what other end points did you get from the feedback in Europe in terms of both positive and negative?

Yes. So we have received very consistent feedback both in the U.S. and now in Europe with regard to the meaningfulness of Six Minute Walk Distance as a good proxy measure of fatigability in adults with SMA. As we presented at the R&D Day, it's an assessment for which there's high test/retest reliability or fidelity, and that's been echoed by not only the clinical advisers but the patient advocacy organizations, and that's been a unanimous set of feedback we received. What we've been able to do with these additional ad boards that we've conducted is ask them what other kinds of assessments might correlate or corroborate an effect on Six Minute Walk Distance and, in particular, with respect to things that could be measuring fatigability in upper limb assessments. And that's where we've received some very good feedback about what kinds of things matter to patients, what matters to clinicians and how we might be able to ensure good robustness in those assessments for purposes of conducting a clinical trial. I'd say we're still vetting through some of that feedback. I don't think we yet have enough clarity to be able to point to that, but we are seeking to understand what could be -- if Six Minute Walk Distance may be a primary end point, what could be the confirmatory secondary end points that we might also include in further study.

Great. Helpful. And then in terms of the PK study, can you just talk about -- you obviously learned some -- you got some information out of the SMA trial that spoke to exposure levels. Was there anything that you learned from the frailty or COPD studies that either reinforced or added to your learnings from the exposures in the SMA trial?

I'll ask Fady to comment on that.

Yes, I think the exposures in those trials were also a little lower than we expected. And so I think in general, the change in formulation as we move from healthy volunteer -- the initial healthy volunteers in the Phase II may have resulted in less exposure. So there's a bit of a theme here and what we want to go back is to look at the higher doses that we might then test going forward.

And your next question is from Charles Duncan from Cantor Fitzgerald.

This is Pete on for Charles. Pete Stavropoulos. So my question revolves around the PK data that you presented for the Phase II SMA in June. As everybody -- as you discussed, you had lower exposure levels than anticipated in the healthy volunteers. The question is, do you believe the dosing for the ALS study is sufficient enough? Which exposure levels will you see a signal in the ALS patients?

Yes, so we can elaborate on that. Certainly, we believe that with the doses that we are evaluating in FORTITUDE-ALS that they may point to exposures below where we had initially intended, we still believe that they're consistent with exposures that demonstrated good dose-dependent effects and pharmacodynamic response that were clinically meaningful in prior clinical trials with tirasemtiv, so we still think we're in that same range. We may not be as high as we had anticipated, but we still think we're in the pharmacodynamic range that should show clinical effect. And as we are doing in SMA with this additional Phase I study, we would potentially be able to move even higher with additional doses and exposures where we'd continue in the further development of reldesemtiv in ALS.

And your next question comes from Gil Blum from Needham & Company.

This is about the new program, CK-601. So it seems like you already have a pretty impressive therapeutic window for reldesemtiv. Are you thinking of going into new indications with this next-gen molecule?

Yes, one of the reasons for developing a next-generation molecule was to be able to consider it in other indications, in particular non-neuromuscular indications. So I think the CK-601 brings the possibility of developing this molecule separately from reldesemtiv in distinct groups, either as defined by neuromuscular or non-neuromuscular or even rare disease versus not rare disease type of indications.

And we have no more questions in queue.

Okay. Thank you, operator, and thanks to everybody for your participation in this call today. Clearly, we had a very productive past quarter, and it was showcased at our recent R&D Day. We're really pleased that so many folks were able to come out for that R&D Day and also dial in to the webcast. If you haven't had a chance to do that, it's still available on our website and archived. And I think it does underscore quite nicely the not only expansion of our clinical development pipeline with new drug candidates entering clinical trials, but also the extension as we move in 2018 towards some key data readouts in 2019 and beyond. So both operationally and financially, but as well programmatically, I think things are firing on all cylinders here, and we're really pleased for that. We look forward to providing further updates with the next quarterly call. And with that, operator, we can conclude this call. Thank you very much.

And this does conclude today's conference call. You may now disconnect.