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Good afternoon. Welcome, ladies and gentlemen, to the Cytokinetics' Second 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 a few 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 program for omecamtiv mecarbil as well as preclinical development of our next-generation cardiac muscle activator being developed in collaboration with Amgen and our unpartnered cardiac sarcomere-directed compound.
Andy Wolff, our SVP and Chief Medical Officer, will then share updates on our skeletal muscle program focused on the development of reldesemtiv and provide perspective on the recently reported data from the first Phase II of reldesemtiv and patients with SMA.
Peter 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 as well as our revised 2018 financial guidance, before Robert concludes with additional thoughts on our company outlook 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-K. 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. We had a very productive second quarter of 2018. In particular, we advanced both of our cardiac and skeletal muscle verticals punctuated by the announcement of data from the first Phase II study of reldesemtiv in patients with SMA.
We were pleased to see that treatment with reldesemtiv demonstrated potentially clinically meaningful effects in patients with SMA in six-minute walk distance as well as maximal expiatory pressure. These are important endpoints in SMA as well as other neuromuscular and non-neuromuscular conditions.
And as you may know, six-minute walk distance has been an approvable endpoint for several therapies in both neuromuscular and non-neuromuscular indications. We're continuing to analyze the data from this study and Andy will provide an update as well as address some of the questions we've received from members of the investment community since the Phase II data were announced just a few weeks ago, Andy will also provide an update on the three other mid-stage clinical trials of reldesemtiv that are underway under our collaboration with Astellas.
On the cardiac side of the business, in the second quarter, we continued to prepare in collaboration with Amgen for the second Phase III clinical trial of omecamtiv mecarbil in patients with heart failure. This trial will be conducted by Cytokinetics and we're working toward the objective of initiating this trial by the end of 2018, while Amgen continues to conduct GALACTIC-HF, the Phase III cardiovascular outcomes clinical trial. Fady will elaborate on this program in a moment.
In the second quarter, we also made progress advancing potential drug candidates, firm research relating to both cardiac and skeletal muscle alone and in collaboration with our partners. We look forward to potentially advancing two of these drug candidates into Phase I studies by year end.
In summary, the first half of 2018 has been productive and encouraging for Cytokinetics. We're executing well against our strategy to develop a portfolio of drug candidates that may initially treat diseases of cardiac and skeletal muscle dysfunction and that may also extend to a wide array of diseases and conditions associated with aging and muscle weakness. We're optimistic for what is to come in the second half of the year.
Now, let me turn the call over to Fady, so he can update you on omecamtiv mecarbil as well as our earlier stage potential drug candidates arising from our cardiac research.
Thanks Robert. GALACTIC-HF, the Phase III cardiovascular outcomes clinical trial being conducted by Amgen under our collaboration continues to progress well. Enrollment has now surpassed 50% of the planned 8,000 patients at high risk for cardiovascular mortality and heart failure events.
In collaboration with Amgen, our teams are regularly reviewing patient characteristics and other enrollment data by region as well as accrual of the cardiovascular deaths and heart failure events that comprise the primary composite endpoint.
Additionally, the data monitoring committee has been meeting regularly, including again very recently and suggested no major changes to the conduct of the ongoing trial. We expect to complete enrolling patients with chronic heart failure and GALACTIC-HF during the first half of 2019.
Two planned interim analyses will be conducted; first for futility in 2019, and the second for efficacy in 2020. In Q2, we also continued protocol development, feasibility assessment, regulatory interactions, and other preparations for a second Phase III clinical trial of omecamtiv mecarbil and is planned to be conducted by Cytokinetics in collaboration with Amgen.
As you may recall, this trial will focus on the potential effect omecamtiv mecarbil on exercise performance in patients with heart failure, which could distinguish omecamtiv mecarbil from other medicines used for the treatment of heart failure.
During the quarter, we receive feedback from the FDA on our proposed protocol has recently been finalized. This will be the first trial designed to test whether omecamtiv mecarbil can increase exercise performance versus placebo in this patient population.
We've been asked what makes us believe we would see an improvement in exercise capacity as a result of treatment with omecamtiv mecarbil. From a clinical perspective, given the impact that heart failure has on exercise capacity, one would reasonably expect that therapy that increases cardiac performance and function would increase exercise capacity.
As an example, cardiac synchronization therapy, a device therapy that improves cardiac function and cardiovascular outcomes also improves exercise capacity. Again, we plan to finalize preparations and continue to work toward the objective of beginning this clinical trial by the end of the year.
On the research front, together with Amgen, we continued preclinical development of a next generation cardiac muscle activator and we expect to submit an IND in 2018 and plan to initiate Phase I studies for this potential drug candidate by the year end or early 2019.
This compound arose from joint research between Cytokinetics and Amgen. It's distinct from omecamtiv mecarbil and we're excited for its prospects as it moves towards clinical trials. We should be able to share more details about this potential drug candidate later this year at a planned R&D Day.
Finally, we also continued IND-enabling studies of our unpartnered cardiac sarcomere-directed compound. In preparation to advance the Phase I this year, we also engaged with FDA to solicit feedback to inform our development plans. This potential drug candidate arose out of independent research at Cytokinetics and affords us yet another promising development program that we plan to speak about at our planned R&D Day.
Now, I'll turn the call over to Andy for updates and perspectives on our skeletal muscle program with a focus on reldesemtiv.
Thanks Fady. As you know during the quarter, we reported data from the first Phase II study of reldesemtiv in adolescent and adult patients with SMA. We believe that this hypothesis generating its primary objective to determine potential pharmacodynamic effect of reldesemtiv after multiple oral doses in patients with SMA as well as secondary objectives to evaluate the safety, tolerability, and pharmacokinetics of reldesemtiv.
As you also know, we're developing reldesemtiv in collaboration with Astellas as a potential treatment for people with SMA and other debilitating diseases and conditions associated with skeletal muscle weakness and/or fatigue.
The study showed dose in concentration-dependent increases and changes from baseline in six-minute walk distance, a sub maximal exercise test of aerobic capacity and endurance, and maximal expiratory pressure or MEP, a measure of strength of certain respiratory muscles after eight weeks of treatment with reldesemtiv.
Other assessments in the study including the Hammersmith functional motor score extended, revised upper limb module, timed up and go, and forced vital capacity did not demonstrate meaningful differences between reldesemtiv versus placebo.
Since reporting the data from the study, we've had the opportunity to discuss them with our investigators and key opinion leaders as well as analysts and investors. I'd like to provide additional context and perspective on interpreting the clinical meaningfulness of the data and review potential next steps in the development program for reldesemtiv. I will then provide updates on the other ongoing mid-stage clinical trials of reldesemtiv in patients with ALS, COPD, and frailty.
I'd first like to address a question relating to the Hammersmith scale which is an endpoint we assessed in this study and has been used in other studies. The Hammersmith scale is the endpoint for which nusinersen or SPINRAZA was approved. It is a key measure to assess developmental milestones in infants and children. It is an appropriate endpoint that has been demonstrated to be useful in assessing the therapeutic effects of SMN-directed therapies.
However, because the Hammersmith scale is directed primarily to evaluating early developmental milestones in infants and small children, it is rarely used clinically in older patients. It is a test of maneuverability more than a test of fatigability and therefore, it is not viewed by many expert SMA clinicians as a useful assessment in the adolescent and adult population of SMA patients living with muscle weakness.
We included this assessment in our study because we wanted to test any functional and respiratory measures that could be relevant to this population. That said, as we saw in the study and as we continue to learn in clinical practice, it is not a commonly used assessment in the older patient population.
For another measure, six-minute walk distance, we saw about a 25-meter increase with the high dose of reldesemtiv with statistically significant dose dependence. Similar magnitudes of effect have been observed following administration of enzyme replacement therapies as well as with treatment for pulmonary hypertension leading to approvals of novel therapies for diseases of significant unmet medical need. We're very encouraged by the observed effects of reldesemtiv on six-minute walk distance in this study.
Furthermore, data from our study support the evaluation of higher doses with reldesemtiv in potential future clinical trials in SMA for three reasons; first, because no efficacy plateau was demonstrated; second, because no dose limiting safety or tolerability issues were observed; and third, because the exposures we achieved at the higher dose in the study were only about half what we expected based on a prior study of reldesemtiv in healthy subjects. In that study, those higher exposures were also well-tolerated and associated with increased pharmacodynamic effect relative to the lower exposures.
To adolescents and adults in our study had a baseline six-minute walk distance of between 250 and 300 meters and they are generally living functional lives. For them a 25-meter or 10% increase in six-minute walk distance may enable them to perform activities of daily living with less fatigue. Things like walking more readily through an airport, raking leaves, or simply feeling more confident in leg strength to step on or off a curb. These could be important improvements for these patients and experts have advised that six-minute walk distance is the most viable assessment for an ambulatory SMA population.
It's important to remember that while the advent of gene-directed therapies will no doubt transform the course of SMA disease progression, patients treated with these therapies still have residual muscle dysfunction, weakness, and early fatigability. Our expectation is that as these babies with SMA survive into later childhood, adolescence, and adulthood, there may be as many as 5,000 to 10,000 ambulatory SMA patients just in the United States alone living longer with their disease, but still with muscle dysfunction and weakness. Therefore, a skeletal muscle activator like reldesemtiv may prove to be an effective complement to SMN-directed therapies.
In terms of next steps, we're still discussing the data with our partner Astellas and have not yet had the opportunity to review these data with regulatory authorities. We will continue to seek regulatory and expert guidance together with Astellas to chart a course for a potential Phase III program on a timeline hopefully to be agreed later this year.
Moving, now to the other mid-stage trials of reldesemtiv; FORTITUDE-ALS, our Phase II clinical trial of reldesemtiv in patients with ALS continues to recruit with more than half our target enrollment completed.
Last quarter, we indicated we were adding sites in Australia and Europe to increase enrollment and some of these sites are now open and screening patients. Enrollment has been slower than we experienced in our recent Phase III study of tirasemtiv in patients with ALS -- VITALITY-ALS. We believe this may be related to the availability and uptake of edaravone in the U.S. as evidenced by enrollment rates approaching historical averages in Canada where edaravone is not yet available.
We've worked hard to increase the enrollment rate in the U.S. over the last two quarters. However, it has remained steady despite our efforts. Therefore, we now anticipate we will complete enrollment in the fourth quarter of this year and expect to report results from this trial in the first half of 2019.
Moving to the non-neuromuscular trials, Astellas completed enrollment in the Phase II clinical trial of reldesemtiv in patients with COPD and we expect to report data in this third quarter.
In addition, Astellas will conduct an interim analysis of data from the ongoing Phase Ib study of reldesemtiv in elderly adults with limited mobility or frailty also in this third quarter of 2018.
And now, I will turn the call over to Pete to provide an update on our financials.
Thank you, Andy. After I provide updates on our cash, our revenue, and the impact of the new accounting rules on revenue recognition for our strategic alliances with Amgen and Astellas and then spending on R&D and G&A, Ching will review our guidance for 2018 and related financial strategies. More details are included in the press release.
We ended the second quarter with $232 million in cash, cash equivalents, and investments. Regarding revenue from our strategic alliance with Amgen, in 2016, we opted to fully co-invest $40 million in Phase III development program of omecamtiv mecarbil in exchange for a total incremental royalty from Amgen of up to 4% on increasing worldwide sales of omecamtiv mecarbil outside Japan.
Payments we made to fund the option in 2016 and 2017 reduced research and development revenues for those years. These payments reduced our revenue in 2017, but no longer. We recognized a so-called contract liability as of January 1st along with a corresponding adjustment to our retained earnings.
As of June 30th, we had just one more payment of $6.3 million and in July, we made that final payment and now have paid Amgen all $40 million of our co-investment commitments.
Once we initiate the second Phase III clinical trial of omecamtiv mecarbil, which Cytokinetics will conduct, we'll see R&D revenue from Amgen for reimbursement of our related expenses. Our revenue in Q2 2018 came from our strategic alliance with Astellas and includes both cash and non-cash revenue recognized under ASC 606, those new accounting rules.
Moving to expenses, we reduced our second quarter 2018 R&D expenses to $22 million from $26 million in Q4 2017. About 59% of our R&D expenses were attributable to our skeletal muscle contractility programs, which include both expenses associated with development and clinical trials for reldesemtiv, 23% to our cardiac muscle contractility programs, and 18% to our other research activities.
These changes reflect as expected increases for reldesemtiv that are reimbursed by Astellas and appropriate decreases for tirasemtiv. We're starting to see the effects of spending on our cardiac sarcomere-directed program in these percentages too.
Our second quarter 2018, G&A expenses fell to $8 million from $10 million in Q4 2017 as expenses for commercial readiness for tirasemtiv were completed earlier this year. This drug continues to highlight how our commercial planning colleagues went to great lengths to whenever possible make planning commitments contingent on the potential positive results of VITALITY-ALS. Again, we've reduced those activities and the related expenses in 2018.
I'll stop there and Ching will share an update on our financial strategies.
Thanks Pete. As our press release indicates, we have updated our financial guidance for 2018. We are reducing both our 2018 spending and revenue guidance by $5 million. This revised guidance does not affect our projected net cash utilization for the year.
The main driver for the reduced spending is the delay in enrollment of FORTITUDE-ALS trial with a corresponding reduction in cash revenues as the cost associated with that trial are being reimbursed by our partner Astellas. Again, we do not anticipate any change to our net cash utilization for 2018.
Once again, our new financial guidance for 2018 is as follows; the company anticipates cash revenue for 2018 to be in the range of $12 million to $18 million; operating expenses will be in the range of $100 million to $110 million; and net cash utilization will be approximately $100 million.
With the current cash of $232 million at the end of the second quarter, this represents over 24 months of forecast runway given our 2018 guidance. We are in the process of developing a strategic plan which will provide an operational and financial roadmap for Cytokinetics over the next three years. As the plan contemplates different scenarios based on potential clinical outcomes over the next 12 months, our principal financial strategy remains to manage our cash through the readout of results from GALACTIC-HF without that relying on dilutive financing.
In addition to judiciously managing our spending and looking for ways to reduce costs, we are seeking to raise non-dilutive capital through a potential collaboration relating to our currently on partner cardiac sarcomere-directed program which we expect to advance to Phase I later this year.
We also are eligible to receive collaboration milestone payments over this time. We have been and will continue to take a strategic risk-mitigated approach to our financials and we are confident that we will continue to maintain a strong cash position while we advance our pipeline.
With that summary, I'll now turn the call back over to Robert.
Thank you, Ching. So, as you heard, we have made significant progress through the first half of 2018 across our growing pipeline of muscle biology directed drug candidates. And as we advanced through our 20th year of operations, our innovative research engine remains productive.
During the quarter, we continued collaboration activities under our joint research program with Astellas directed to the discovery of next generation skeletal muscle activators, we expect to submit an IND in 2018 for a next generation cardiac muscle activator under our collaboration with Amgen and plan to initiate Phase I studies for this potential drug candidate by year end or early 2019. As Fady mentioned, we look forward to telling you more about this compound at our planned R&D Day later this year.
We also conducted regulatory interactions and IND-enabling studies for our unpartnered cardiac sarcomere-directed compound and will also have more to say about this program at the R&D Day. We expect to begin clinical trials with that potential drug candidate also this year.
We're proud of our leadership in muscle biology and I'm gratified for the commitment, creativity, and camaraderie demonstrated by our scientists with our collaboration partners especially.
We also extended that commitment across our patient advocacy partnerships this quarter, renewing and extending partnerships with both the ALS Association, the ALS Association Golden West Chapter as well as with Cure SMA.
Our activities increasingly focused on education, awareness, fundraising, and care services for ALS and SMA at a time when we're seeing exciting progress and promise in our research and in innovation.
Now, let me recap our expected milestones for 2018. For omecamtiv mecarbil, we expect to complete enrollment of patients with chronic heart failure into GALACTIC-HF during the first half of 2019 and we're working toward the objective of initiating the second Phase III trial of omecamtiv mecarbil which is intended to evaluate its effect on exercise performance in patients with heart failure that by the end of 2018.
For reldesemtiv, we expect results from a Phase II clinical trial of reldesemtiv in patients with COPD in this third quarter 2018. We expect Astellas to conduct an interim analysis of data arising from a Phase Ib clinical trial of reldesemtiv in adults with limited mobility or frailty also in Q3 2018. And we expect to complete enrollment of patients in FORTITUDE-ALS in Q4 2018 so that results may be available in the first half of 2019.
For our preclinical research, we expect to submit an IND in 2018 for next generation cardiac muscle activator under the collaboration with Amgen and plan to initiate Phase I studies for this potential drug candidate by year end or early 2019. We expect to advance an unpartnered cardiac sarcomere-directed compound through IND-enabling studies in 2018 to enable initiation of Phase I by the end of 2018. And we expect to continue research activities under our joint research program with Astellas directed to the discovery of next generation skeletal muscle activators.
Operator, with that, we can now open the call up to questions please.
[Operator Instructions]
Your first question comes from the line of Joe Pantginis with H.C. Wainwright.
Good afternoon Joe.
Hey guys, good afternoon. Thanks taking the question. I think maybe this question might be for Andy, but thank you for offering the additional perspective on the SMA data and I guess especially the impact on the daily lives of how it might benefit these patients; you said walking through an airport or stepping off a curb. So, I guess as you look forward to the drug potentials potential, how do you think these observations might carry over to other populations like ALS and the other populations that reldesemtiv is in right now?
Well, I think it's very encouraging for all the ongoing clinical trials. We've definitely seen evidence of a clear pharmacodynamic effect that in a range of magnitude that has been associated with approvals with other treatments where six-minute walk has been used as an endpoint and there are several.
And as you know there's a long list of neuromuscular and non-neuromuscular conditions and diseases that are associated with muscle wasting and weakness. So, I think the key is to focus and not get too distracted by the panoply of other places we could go and just tick through them one at a time.
I'll elaborate a little bit on that. As your question points out, there are those things you measure in a clinical trial and those things you learn also through anecdote. And we have not only seen effects on an endpoint that we believe albeit subject to further discussion with regulatory authorities could support potential registration if confirmed in a larger longer study.
But also we're learning things from talking to investigators now that they've seen the data and have the randomization codes and also from their patients communicating through to them. That suggests that not only was reldesemtiv well-tolerated and that was one of the key questions coming into this study certainly coming out of the experience with tirasemtiv, we wanted to know whether reldesemtiv would be well-tolerated in a study like the one we did in SMA and we believe we've asked and answered that question.
But also we're seeing effects and things that speak really to activities of daily living and how patients with SMA currently impaired by their muscle dysfunction are able to do more and do it for longer. And in that regard, we think this augurs extremely well for what could be the therapeutic potential were we to proceed forward in a registration program.
So, we still need to get our arms around how best to design the proper Phase III registration study and do that together with our partners at Astellas. We're convening expert panels with advisors to learn not only from key opinion leaders who conduct clinical research in this community, but also from advocacy representatives who have their finger on the pulse of patients as to what really matters. And we're going to take that advice in terms of how best to proceed into our thinking as we contemplate a potential path forward and we hope to have a lot more to share about that in the coming months.
No, that's very helpful. Thank you. And if I could just ask a quick logistical question. Looks like we're really getting towards the end of -- or seeing a light at the end of the tunnel with regard to GALACTIC, this very large study. Can you remind us have you disclosed or will you disclose now with regard to the two planned interims for both futility and efficacy? Are you providing any of the statistics around that?
I don't think we'll be providing any specifics around those, but we certainly summarize what the outcome of those analyses were.
Got it. Okay.
We still need to sort through this together with Amgen, but we have guided to the fact that based on the accrual of events, we believe that we will have enough events to enable a futility analysis that would occur in 2019 and subsequent to that, we would expect that we might have accrued enough events such that an analysis that could provide for early stopping were we to achieve overwhelming efficacy would occur subsequent to that in 2020. But were the study to go to full term; that would expect to wrap-up in 2021. So, that's the best guidance that we can provide at this time. And hopefully as we get closer to those interims, we'll be in a better position to speak about what we learn.
Fair enough. Thanks a lot guys.
Thank you.
Your next question comes from the line of Matthew Harrison with Morgan Stanley.
Hi Matthew.
Hey this is this Ishmael for Matthew. I just have two questions on ALS and SMA. On the FORTITUDE, why is your enrollment taking a little longer than expected? And given the results so plasma exposure and SMA, have you gone back to look at your dosing strategy in ALS? Most importantly, can you confirm you feel confident you'll hit the required plasma levels in ALS? And secondly on SMA? While later this year do you think you'll be able to be in a position to further comment on the next studies? And more importantly if you think there could be pivotal studies? Thank you.
Good question. So, just to summarize, you've got a question relating to enrollment. With regard to FORTITUDE-ALS, I'll ask Andy to address that. With respect to plasma exposures in the ALS study, maybe I'll ask Fady to speak to that. And then I'll take the third question relating to timing on decisions.
Well, I think we did address that enrollment in FORTITUDE-ALS. We have every reason to believe it's ability of edaravone which really wasn't competing for patients when we were doing VITALITY-ALS. Patients are allowed to be on edaravone to come into the study and the randomization is stratified according to whether patients are receiving it or not. But we do want them to have had at least the first two cycle, so they understand what the burden of edaravone treatment is and whether or not they really have the capacity to also participate in another clinical trial and also so that adverse events that may be associated with edaravone treatment are less likely to be confounded with adverse events that then occur in a clinical trial.
But that adds usually around six weeks from the time the patient is first offered the opportunity to participate in the study and then we'll often say that they would prefer to go on edaravone first and they do. And in many cases, their vital capacity is falling below our inclusion criteria. They are no longer eligible for the study by the time they've had their first two cycles of edaravone. That has happened several times.
And then not infrequently, I mean edaravone is intensive treatment regimen. Every other week, five days a week after the first cycle and that's more than people -- they don't -- just then that that's what they think they can handle.
So, it definitely has impacted enrollment and as I mentioned during the call, you can sort of infer that from the facet in Canada where there is no edaravone. Our enrollment is about where it was with VITALITY-ALS in terms of our enrollment rate. So, hopefully, these other countries where there is not edaravone, we will see better enrollment there.
Maybe just to elaborate a bit on that before I turn it back to Fady. Based on the enrollment rate that we're seeing now, we do believe that were this to continue, this study will conclude enrollment in the fourth quarter. And even as a further insurance, we're adding more sites.
So, I think that while we do have a modest delaying in the enrollment of FORTITUDE-ALS, we think we've got our arms around that and should be able to position to bring this study home in terms of enrollment in the fourth quarter and therefore see data in the first half of the year.
Now, you asked a question about exposures based on what we learned in the SMA study and how that may play to our therapeutic hypothesis in the FORTITUDE study. So, I'll turn that over to Fady.
Yes, I think the exposures certainly we achieved in SMA were adequate to see a clinical effect of the drug in that population and the pharmacodynamic effect at those exposures equals or exceeds that of tirasemtiv that if you compare them based on their pharmacodynamics as we studied in healthy volunteers.
So, we think that the dosing in the ALS patients is adequate to see a pharmacodynamic or an effect on the primary endpoint of slowing the decline in vital capacity. And then an open question depending on its tolerability and so forth will be whether we might, like in SMA, think of a strategy of setting a higher dose as we advance into the next Phase of development.
So, I think basically we'll continue with the FORTITUDE study as is being planned and then used those results to help guide us in terms of the next -- design of the next study.
But to underscore we do believe we're in the pharmacodynamic range with these exposures that should enable us to see effects at least as we saw in the BENEFIT-ALS study which was demonstrating effects on slow vital capacity that supported movement into Phase III.
We may be even higher with these exposures with regard to those effects and we do believe the FORTITUDE-ALS study is designed properly such that we should see confirmation of that kind of effect.
I want to answer your other question which is when might we have a decision regarding next steps pertaining to reldesemtiv in SMA. And to the best of my abilities, I'll give you clarity as to where we are. We're in discussions with Astellas about what those next steps could look like and ultimately we're going to want to seek regulatory feedback in connection with that as obviously takes a few months.
My hope is that we'll have gathered enough information between our involvements with key opinion leaders and in discussions with Astellas during the third quarter such that we should be able to provide some better information on our Q3 earnings call or certainly before now the end of the year.
With that said, however, there's work that has to occur and until that works gets done, I can't be any more definitive than that.
Okay, great. Thank you.
Thank you.
Your next question comes from the line of Jason Butler with JMP Securities.
Hey Jason.
Hi thanks for taking the questions. Just -- now that you had the opportunity to speak to KOLs about SMA data, can you just give us some more color into the feedback you're getting from them in terms of things like endpoints selection to use their six-minute walk test versus not using the Hammersmith, dose dependency, and things like that?
Yes, I mentioned this on a call we had immediately following the release of the data, but I'll say it again for those that weren't on that call. When we had first shared these data with investigators, the evening before they were presented more publicly at the Cure SMA Meeting. The first question I posed to the investigators was do these data hold together in your mind for the fact that we're seeing an effect on six-minute walk distance, but not the Hammersmith. And I was met with a bunch of skeptical eyes as to why I even might ask that question in light of the fact that we did see effect on six-minute walk distance and probably should never have assumed an effect on Hammersmith in this population.
And what I was told by that group and it was a unanimous view of that group is that effects on six-minute walk distance in their mind are in fact speaking to an assessment that is the highest fidelity, most reliable test, retest in that population and therefore, evidence to what would be most meaningful clinically to that population of adults living with this muscle weakness and residual dysfunction.
So, I think there is at least amongst those investigators a clear consensus that six-minute walk distance should be a registerable endpoint and that's what we should advocate to regulatory authorities.
That said, we still want to probe deeper with regard to both investigators and also others who weren't participants in the study. And we've got a series of those kinds of interactions scheduled over these next couple of weeks in order to get their feedback. But I do think that for those people who were participating in the study, they were extremely encouraged by these data and were immediately going to so what does the next study look like.
Great. And then just one additional question on the -- in the patients -- for the six-minute walk test, you had some patients those have responded very well and showed much larger improvements than the average of 25 meters. Have you had a chance to take a look for any identifying characteristics of those patients who did respond better to the drug?
I would have to say that the number of patients was relatively limited and it makes drawing those kinds of conclusions I think fairly, fairly dangerous. So, I mean we saw an improvement. It is really robust. It was very clearly related to plasma concentration which I think helps you believe that it's real. The higher the exposure they had, the longer they went in general. It really wasn't driven by a couple of outliers. I mean any assessment, we're always going to have some people that respond more robustly than others. That's just the nature of clinical research. But I think if you examine the data, you look at the waterfall plots and so forth and so on, it's a fairly robust effect that was observed. Particularly, it's a higher dose than the ambulatory patients.
Okay, great. Thanks for taking the questions.
Thanks Jason.
Your next question comes from the line of Chad Messer with Needham & Co.
Hi Chad.
Great. Thanks. Hi good evening and thanks for taking my question. Just wondering for FORTITUDE, given that you're allowing edaravone, but it's causing -- wreaking a little bit of havoc with your enrollment. If you see any read-through to a market should you guys get approval, how do you see edaravone being there kind of affecting your use? It sounds like there may be issues for example with getting both drugs onboard in some patients. Just wondering if you had any thoughts?
I don't really think. So, I think there's a big difference between being prescribed an oral medication that you can go home and take twice-a-day without having to go in for clinic visits on a weekly and every two-week basis at the beginning of a clinical trial and go through that. Let's face it, the hassle of being in a clinical study. My experience of the ALS patients is they want everything they can possibly get. And I believe if reldesemtiv is approved, they will use it over a background of edaravone as we're studying it right now because there won't be much of a barrier to them doing that. Clinical trial is different from you know taking the drug in clinical practice.
The other thing I'll mention is that the Phase II study FORTITUDE-ALS is a 445-patient study. It's a large study. It's a larger than many Phase III studies in patients with ALS. And while it is taking us a little bit longer to enroll this study, it is still enrolling well and we're adding more centers and it will conclude we expect later this year. So, I don't want to imply that there are insurmountable challenges here. We think we've got our arms around them and it is taking us a little bit longer, but it should happen.
All right, great. Thanks. And then just wondering if you would be willing to discuss a little bit on some of your earlier stage programs. You've got and unpartnered sarcomere-directed cardiac program. Maybe just at a basic biology level, how does that differ from your cardiac muscle activator approach? I mean are there sort of a segregation like a gross segregation of types of indications that the new drugs would be appropriate for?
Yes, I think in terms of where we would be heading with those two programs, where we are heading with omecamtiv mecarbil and where we would be heading with the new program, there clearly are different indications and different patient populations. I can't really speak precisely to the mechanism of action we plan to do that at R&D Day in October. But it is something that has come out of our laboratories here, worked on for a number of years now, and is progressing well through IND-enabling studies and we plan to file an IND and move into clinical development this year.
To that point, if you think about the company at its present form with one program in Phase III, another advancing into Phase II and we expect at least two new compounds moving into Phase I if not three over the next year.
The development pipeline at Cytokinetics is more broad and robust than any other point in our history. And I think that speaks to our leadership in this space and the innovation and these are first-in-class molecules for which, yes, we have to do some pioneering work and that sometimes takes a bit longer. But the upside for patients and obviously also for other stakeholders is quite high.
All right, great. Thanks.
Thank you.
Your next question comes from the line of Ted Tenthoff with Piper Jaffray.
Hi Ted. Ted, you with us?
Operator, we might should go to the next one.
You hear me okay or--.
Well, now Ted, now we can hear you. Thank you.
Sorry, I think my headset -- speaker might [Indiscernible]. So, anyway, thanks for the update. A lot of questions answered. I want to shift gears just a little bit to expectations from the COPD read-out from the Astellas study, just to kind of get ballpark, what should we be thinking? What should we be hoping to see from that study? Thanks.
Yes, probably worthwhile for us to speak to its designed and what might be expected coming out the other side. I'll turn to you, Andy, to do that.
So, the study enrolls patients into a two-peered crossover design that patients get a week of treatment of 500 milligrams twice daily. And then there's a watch out for two weeks -- two weeks of treatment I should have said, watch out in two weeks and then they get placebo or because it's randomized and double-blind and may get it in the other order placebo first and then reldesemtiv.
The primary endpoint is a constant work rate exercise task which is individualized to each patient so that when they get into the double-blind portion of the study, they can predictably do this leg extension exercise against a constant workload for about four to eight minutes. And the investigators have sort of demonstrated that that's optimal then for demonstrating treatment effects on top of that. If they go too long as they're being screened in, they can't go all four minutes, then they decrease the work rate and try them again until they get them at baseline into that four to eight minute endurance range. That's the primary endpoint.
Okay. Thank you. All right, that's helpful. Thank you very much.
Thank you, Ted.
And your last question comes from the line of Vernon Bernardino with Seaport Global.
Good afternoon Vernon.
Good afternoon everyone and thanks for taking my question. Hope all of you guys are doing well. Just one question. As you know one of my favorite subjects and the favorite subject of mine at Cytokinetics is omecamtiv. You've commented on it before, but just wondering if you could remind us the rationale for exercise performance as far as the second Phase III study you want to pursue the decision process and studies that perhaps you could point to in which exercise performance in heart failure patients had--.
Yes, I can take that. So, I think first it's useful to understand what we're studying and measuring GALACTIC and we're looking at mortality -- cardiovascular mortality and heart failure events and we're also measuring patients symptoms using the Kansas City Cardiomyopathy Questionnaire as a secondary endpoint in GALACTIC. However, exercise capacity tolerance is an important feature of heart failure, it's one of the things that heart failure patients complain of the most they often present with their first complaint is that they have reduced exercise capacity that then leads to a work-up and a diagnosis of heart failure.
And so if you think about developing a compelling rationale for the use of omecamtiv mecarbil, ideally, you'd like to have evidence that supports it -- beneficially affects all of those things. And something like exercise capacity is very difficult to measure quantitatively in a study, the size of GALACTIC and you don't need that many patients to quantitate the effect of that. And so that in part is the compelling rationale for designing a separate study to look at exercise capacity of patients treated with omecamtiv mecarbil.
Now, the reason that they develop exercise intolerance is because they have reduced cardiac function and there's not as much blood and oxygen carrying blood that's being delivered to the muscles and muscles develop early fatigue and then undergo actually chronic changes that reduce their efficiency.
So, with the treatment of patients, as chronic heart failure improves, you do see improvements in exercise tolerance. In the case of ACE inhibitors for instance, in the case of synchronization therapy, maybe the one place where it hasn't been demonstrated is an effective therapy or with beta blockers. But beta blockers have direct effects -- negative effects on skeletal muscle function and so while they are good for the heart, they may not be so good for exercise capacity.
So, I think there's a strong rationale for us to study omecamtiv mecarbil, to look at its effects for on exercise capacity and we did see a positive effect on that particular endpoint. I think it's something that is of great value to patients.
Terrific. Thanks for that. And on to a second subject if I may. Regarding reldesemtiv, do you have any early results as far as drug-drug interactions at edaravone?
Yes, we don't expect there to be any drug-drug interactions with edaravone and reldesemtiv based on their in-vitro and in-vivo drug metabolism.
And actually just to add on reldesemtiv was selected to, not deem a catalyzed by any of the cytochrome P450 enzymes to a large extent. So, we have expected relatively few drug-drug interactions.
That's actually great to know. Thank you very much. Appreciate that.
Thank you, Vernon.
And there are no further questions at this time.
So, I want to thank all the participants in our teleconference today for your continued support and interest in Cytokinetics. The second quarter was a very productive and positive quarter for the company and for our advancement of muscle-directed drug candidates.
And as you also heard so too was it productive for our research moving compounds through to our IND-enabling studies that we expect should represent expansion of our pipeline later this year.
I think Cytokinetics is on very solid footing as we approach now, this second half of the year, with strong financials. You heard about having over two years of cash. And as we think about our financial strategy, we think we're in a good stead and good position to be able to execute well on these plans.
We look forward to keeping you abreast of our progress. And with that operator, I think we can conclude the call. Thank you.
Ladies and gentlemen, thank you for participating in today's Cytokinetics' second quarter 2018 conference call. You may now disconnect.