Good afternoon, welcome, ladies and gentlemen, to the Cytokinetics Q1 2018 conference call. At this time, I would like to inform you that this call is being recorded and that all participants are in 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, 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 sarcomere activator and our cardiac sarcomere-directed compound. Andy Wolff, our SVP and Chief Medical Officer, will share updates on our skeletal muscle program focused on the development of reldesemtiv.
Pete Roddy, our SVP and Chief Accounting Officer, will provide a financial overview for the quarter, Ching Jaw, our SVP and Chief Financial Officer, will recap our 2018 financial guidance as well as strategies to extend our cash runway before Robert concludes with additional perspectives 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 for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. 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 might differ materially from those projected in these forward-looking statements.
Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our most recent 10-K and 8-Ks. We undertake no obligation to update any forward-looking statements after this call. Now, I will turn the call over to Robert.
Thanks, Diane. Thanks again to everyone for joining us on the call today. In the first quarter of 2018, we made key progress advancing our muscle biology-directed drug candidates now in mid- and late-stage clinical trials across a spectrum of diseases and conditions of impaired muscle function. We continued protocol development and other readiness activities in collaboration with Amgen for the second phase III clinical trial of omecamtiv mecarbil in patients with heart failure. We are finalizing preparations to ensure readiness to begin this trial on a timeframe to be agreed soon. As a reminder, this trial will be conducted by Cytokinetics, mostly at Amgen's expense, under our collaboration, while Amgen continues to conduct GALACTIC-HF, the phase III cardiovascular outcomes clinical trial.
That trial continues to enroll with patients randomized to date having a risk profile consistent with the trial design. Fady will elaborate on that program in a moment. As recently announced, during the quarter, we also completed enrollment of cohort 2 in our phase II clinical trial of reldesemtiv in patients with SMA under our collaboration with Astellas. Now we look forward to reporting data later in this quarter at the Cure SMA conference. Additionally, we continue to enroll patients in FORTITUDE-ALS, and Astellas continue to enroll clinical trials of reldesemtiv in patients with COPD and also in elderly subjects with limited mobility. Andy will provide updates on that program shortly. In the first quarter, we continued to advance potential drug candidates arising from our research pertaining to both cardiac and skeletal muscle, alone and in collaboration with our partners.
We will have more to say about the specific mechanisms of these compounds and their potential patient populations that they may serve at an R&D day we are planning for the second half of this year. I continue to be optimistic about Cytokinetics opportunities this year. The results we expect to see from the phase II clinical trials program of reldesemtiv will shed light on what we believe may be the potential to impact a spectrum of diseases and conditions of impaired muscle function, from rare neuromuscular diseases to diseases associated with aging, those characterized by muscle weakness that affect a growing population of aging baby boomers. With these data in hand, we and our partner, Astellas, can hopefully begin building the path forward towards those phase III programs and advancing key objectives of Cytokinetics Vision 2020.
Let me turn the call over to Fady so he can first update you on omecamtiv mecarbil.
Thanks, Robert. GALACTIC-HF, the phase III cardiovascular outcomes clinical trial being conducted by Amgen under our collaboration, is proceeding well, with regulatory approvals now complete in 35 countries participating in this trial and all countries, and sites in those countries currently enrolling patients. As Robert mentioned, we're pleased to note that the trial is on track and enrollment is proceeding towards 50% completion, with patients randomized to date having a risk profile consistent with the trial design. In collaboration with Amgen, our teams are regularly reviewing patient characteristics and 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 for GALACTIC-HF has been meeting regularly and reviewing data arising from the trial. There have been no major changes to the trial following these reviews.
We expect to complete enrolling patients with chronic heart failure in GALACTIC-HF in approximately one year. We also continue protocol development, feasibility assessments, regulatory interactions, and other readiness activities for a second phase III clinical trial of omecamtiv mecarbil that is planned to be conducted by Cytokinetics in collaboration with Amgen. As a reminder, this trial will focus on the potential effect of 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 convened an advisory board meeting to review the study design and received positive and constructive feedback. We also conducted proprietary market research to better understand physician perceptions of increased exercise capacity. We found that more than 80% of key opinion leaders and nearly 70% of cardiologists view this as highly beneficial and a clinically meaningful endpoint.
67% of internists, who increasingly are seeing and treating these patients, viewed increased exercise capacity as a potential added benefit of omecamtiv mecarbil, addressing a significant unmet need to improve patient quality of life. Our goal is to finalize preparations to ensure readiness to begin this trial in a timeframe to be agreed upon soon. Together with Amgen, we're working on a development plan for a next-generation cardiac muscle activator that we have advanced from our research collaboration. Now I will turn the call over to Andy for updates and perspectives on our skeletal muscle program with a focus on reldesemtiv.
Thanks, Fady. Our clinical operations teams, both here and at Astellas, were quite productive in the first quarter, conducting a broad phase II clinical trials program for reldesemtiv in neuromuscular and non-neuromuscular diseases characterized by impaired muscle function. I'll first provide an update on progress against the four clinical trials underway under our collaboration with Astellas, and then touch on our plans to transition patients currently receiving tirasemtiv in VIGOR-ALS, the open-label extension trial for patients who completed VITALITY-ALS to a managed access program. As Robert mentioned and as recently announced, data from our phase II clinical trial of reldesemtiv in patients with SMA will be presented by Dr. John Day, Professor of Neurology and Pediatrics at Stanford Medical Center, and the principal investigator of the study at the 2018 annual Cure SMA Conference on June 16th in Dallas.
The study has enrolled 70 patients, 39 in Cohort 1 and 31 in Cohort 2. As a reminder, enrollment in this study was stopped short of the intended goal of 72 patients after a blinded analysis of variability for the change from baseline of several of the efficacy measures demonstrated that the trial appears to have sufficient statistical power to detect differences versus placebo in the efficacy endpoints. Given the evolving therapeutic landscape in SMA, moving forward expeditiously to understand if there is a potential effect of reldesemtiv on the function of patients with SMA is critical. It is important to remember that this is a phase II exploratory hypothesis-generating trial with no single primary endpoint. The results will inform what may be a path forward for reldesemtiv in this patient population, and we look forward to sharing the data with the SMA community.
FORTITUDE-ALS, our phase II clinical trial of reldesemtiv in patients with ALS, continues to enroll with more than 150 patients randomized as of April 19th. We are adding sites in Australia and Europe with the expectation that they will contribute to overall enrollment. Over the past several months, senior members of our team have visited nearly every site participating in FORTITUDE-ALS to engage with our investigators, who continue to be optimistic about the potential of reldesemtiv in their ALS patients. Our goal is to complete enrollment this summer, and we remain on track to report data in the second half of this year. Moving to the non-neuromuscular trials, Astellas has nearly completed enrollment in the phase II clinical trial of reldesemtiv in patients with COPD.
More than 20 patients have now been enrolled in the phase I-B study of reldesemtiv in elderly adults with limited mobility, toward a goal to enroll 60 patients. We expect results from the COPD trial in the second half of 2018 and expect Astellas to conduct an interim analysis of data from the phase I-B study in elderly adults in Q4 2018. Skeletal muscle activation remains an exciting, viable, and potentially versatile mechanism to explore across a spectrum of rare neuromuscular diseases, as well as in impaired muscle function associated with aging that impacts a growing population of aging baby boomers. We look forward to results from these trials later this year and to advancing a potential phase III development program in collaboration with Astellas. We are pleased to continue pursuing this novel mechanism with a shared vision.
Finally, I'd like to update you on the status of VIGOR-ALS, the open-label extension clinical trial of tirasemtiv for patients who completed VITALITY-ALS. During the quarter, we convened an advisory board of ethicists, patient advocates, trial investigators, and experts in pre-approval access to assess whether and how best to continue providing tirasemtiv to those people living with ALS currently in VIGOR-ALS. Informed by this advisory board, we decided to close VIGOR-ALS and transition to a managed access program to provide continued access to tirasemtiv for patients still receiving treatment. The managed access program will include only patients still receiving tirasemtiv in VIGOR-ALS and not any other patients with ALS. We are grateful to the advisors who helped inform a strategy that we believe is in the best interests of patients in VIGOR-ALS who want to remain on tirasemtiv.
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 a little on the impact of the new accounting rules on revenue recognition for our strategic alliances with Amgen and Astellas, and spending on R&D and G&A, Ching will review our guidance for 2018 and related financial strategies. More details on the financial results are included in the press release itself. We ended the first quarter with $255.5 million in cash equivalents, and short-term and long-term investments. Regarding revenue from our strategic alliance with Amgen, as you'll recall, we exercised our option to fully co-invest $40 million in the 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 that option in 2016 and 2017 reduced research and development revenues for those years. Under the new accounting guidance, these payments no longer reduce our revenue. We recognized a so-called contract liability as of January 1st, along with a corresponding adjustment to our retained earnings. As of March 31st, we have two more payments of $6.3 million in Q2 and Q3, and then we'll have paid all $40 million of our co-investment commitment. Once we initiate the second phase III clinical trial with omecamtiv mecarbil, which Cytokinetics will conduct, we'll see R&D revenue from Amgen for reimbursement of the related expenses. All of our revenue in the first quarter 2018 came from our strategic alliance with Astellas. First, we recognized R&D services of $3.6 million and license revenues of $1.7 million from the ongoing development activities in ALS and SMA.
Our first quarter 2018 R&D expenses were reduced to $22 million from $26 million in the fourth quarter of 2017. About 78% 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 and tirasemtiv, 9% to our cardiac muscle contractility programs, and 13% to our other research activities. These percentages approximate what we've seen in prior quarters with as-expected increases for reldesemtiv that are reimbursed by Astellas and appropriate decreases in spending for tirasemtiv. Our first quarter 2018 G&A expenses fell to $9 million from $10 million in Q4 2017 as expenses that we incurred in 2017 for commercial readiness for tirasemtiv were reduced. As mentioned in our last call, our commercial planning colleagues went to great lengths to, where possible, make planning commitments contingent upon potential positive results of VITALITY-ALS.
I'll stop there. Ching will share an update on our financial strategies.
Thanks, Pete. I would like to reiterate our financial guidance for 2018, remind you of our strategy to extend our cash runway through GALACTIC-HF, what we believe to be the most valued catalyst for the company. The company anticipates cash revenue for 2018 will be in the range of $17 million-$23 million. Operating expenses will be in the range of $105 million-$115 million. Net cash utilization will be approximately $100 million. This guidance is unchanged from the one we gave in February. Q1 spending is in line with our internal expectations. With the current cash of $255.5 million, this represents over 24 months of cash runway given our 2018 guidance. We have stated, our goal is to manage our cash through the GALACTIC-HF results without relying on dilutive financing.
In addition to judiciously manage our spending, we will look for opportunities to raise non-dilutive capital through potential collaboration deals for our unpartnered 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 are proud to have raised an equivalent amount of capital from collaborative partners and capital markets throughout our company's history. Always, we will take a strategic and risk-mitigated approach to our financials. We are confident that we will continue to maintain a strong cash position while we advance our pipeline. That summary, I will now turn the call back over to Robert.
Thank you, Ching. As you've heard, we made good progress in the first quarter of 2018, advancing our pipeline of muscle biology-directed drug candidates. With five potential therapies moving through various stages of development, Cytokinetics continues to demonstrate leadership in areas of science and biology. We are powering innovation in diseases like SMA and ALS, also have opportunity to bring meaningful new approaches to the treatment of heart failure, COPD, and frailty. In Q1, we were thrilled to welcome Dr. Rob Califf to our board of directors. I've known Rob for many years. I'm quite gratified and excited to have him join our board. His expertise in cardiology and global clinical research will no doubt strengthen our overall ability to execute against our Vision 2020.
His advice will be especially valuable regarding omecamtiv mecarbil in our phase III clinical trials program in collaboration with Amgen, as well as our preclinical compounds directed towards other severe cardiac diseases. As always, we celebrate and acknowledge the brave people for whom we do all of this. This quarter, we joined the Global Rare Disease Day initiative, an international campaign led by the European Organization for Rare Diseases and the National Organization for Rare Disorders, and shine a light on the innovative research powering therapeutic advances for people living with rare diseases. Let me recap our expected milestones for 2018. For omecamtiv mecarbil, we expect to complete enrollment of patients with chronic heart failure in GALACTIC-HF in approximately one year.
We expect to finalize preparations for the second phase III trial of omecamtiv mecarbil in 2018, which is intended to evaluate its effect on exercise performance in patients with heart failure. For reldesemtiv, we expect results from a phase II clinical study of reldesemtiv in patients with SMA in Q2 2018. We expect results from a phase II clinical trial of reldesemtiv in patients with ALS in Q4 of 2018. We expect results from a phase II clinical trial of reldesemtiv in patients with COPD in the second half of this year. We expect Astellas to conduct an interim analysis of data arising from a phase I-B clinical trial of reldesemtiv in adults with limited mobility by the end of the year. For preclinical research, we expect to advance one development compound under our collaborations with Amgen and Astellas to phase I in 2018.
We also expect to advance an unpartnered cardiac sarcomere-directed compound through IND-enabling studies in 2018 to enable initiation of phase I, also in 2018. 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.
At this time, ladies and gentlemen, if you would like to ask a question, press star then the number 1 on your telephone keypad. Again, that is star, then the number 1. Our first question is from the line of Matthew Harrison with Morgan Stanley.
Hello, Matthew.
Hey, this is Ishmail on for Matthew. Thank you for taking our question. Can you just walk us through how you'll be comparing the SMA data you'll generate to the data from SPINRAZA? Are there any specific endpoints or markers that you think are more relevant than others? Secondly, we understand enrollment is on track for ALS and data set for this year. However, are there any scenarios where the readout could be pushed to 1Q 2019? Also, any commentary regarding tolerability on a blinded basis or patients on the higher dose will be highly appreciated. Thank you.
Sure. Lots of good questions. Let me try to start, then I may turn it over to my colleagues. With regard to reldesemtiv and SMA, clearly this is a different mechanism of action than is nusinersen. As we've combed the literature, we think that the preclinical data with regard to nusinersen speak more to what's functional protein expression and less to functional measures that we'll be evaluating in our program. It's difficult to make a comparative statement in any like models. In this phase II study, as you know, we're looking at patients receiving both a low dose and a higher dose versus placebo, and within each of those groups, cohorts are divided ambulatory and non-ambulatory, and within each 2 to 1 drug versus placebo.
With regard to the assessments we're making, they really are functional assessments, as I'll ask my colleagues to elaborate here in a moment. In that way, I don't think you can make a comparative statement with regard to nusinersen. The patients in our study, to be clear, are not receiving nusinersen. Our study began before nusinersen was approved. Maybe I'll ask Andy and Fady to speak to what are those functional assessments and what we might expect from the study.
Well, there are numerous functional assessments. The Hammersmith scale is probably the most commonly used in clinical trials with patients with SMA, and that's one that we're using. In addition, the Revised Upper Limb Module
Assessing upper limb function is probably one of the more standard measures of pulmonary function, including maximal expiratory pressure, inspiratory pressure, and vital capacity. I think those are the ones that are probably most easily recognizable.
Yeah. Also, we're looking at respiratory function as well. I think one of the key differentiators between the data that have emerged with SPINRAZA is primarily in SMA type 1. The use has been in patients, young children, in the early years of their condition. In this trial, we've been studying patients 12 years and older that generally have stable disease. We're looking for functional improvement rather than trying to ameliorate the decline in their function as the treatment with SPINRAZA does in the earlier patient groups.
Clearly, the commercial availability of nusinersen is a watershed moment for the treatment of SMA, and it's abundantly clear that that approach, as well as other gene-directed approach like that of the gene therapy, offer great promise. We truly do see that this oral drug candidate may afford a complement for those patients living longer with impaired muscle function and weakness. That's truly the therapeutic hypothesis that we'll be looking to understand with these data from this hypothesis-generating study. Your next question related to reldesemtiv in ALS, I think you asked the question, what's the possibility that this may get pushed out? I think, based on having attended an investigators meeting yesterday at the AAN, I can say that there's a good deal of enthusiasm around this study.
There aren't a lot of other competing studies right now for ALS. I think with enrollment now proceeding well in over 50 centers across North America and soon also in other countries, we think we're on track to see data by the end of the year. We're still enrolling the study. Therefore, the possibility does exist that we would see that it gets pushed into 2019. That's not our expectation right now based on where we stand.
Your last question related to tolerability. While we remain blinded, we are, as you know, looking at blinded data. I think we are encouraged by the fact that the tolerability of reldesemtiv continues to hold for what we believe to be a better-tolerated compound relative to tirasemtiv, as should be expected given that it was designed specifically to engineer away some of the liabilities of tirasemtiv we know for it crossing the blood-brain barrier. So far so good based on what we can tell from blinded data. We'll look forward to seeing those unblinded data later this year. I think that covered off on your questions. Operator, we can move on to the next one.
Thank you for the context. Very helpful.
Sure.
Our next question is from the line of Chad Messer with Needham & Company.
Hi, Chad.
Great.
Hi.
Good afternoon. Thanks for taking my question. I was wondering if we could maybe discuss a little bit more the objectives of the omecamtiv exercise tolerance phase III that you want to run and how you're going to use that to differentiate versus other heart failure treatments. Is it the case that other heart failure treatments don't help exercise tolerance or just that they haven't measured it? If there's any sort of examples of what kind of endpoints would be possible to measure in a heart failure population for exercise tolerance, any kind of examples of what might even be possible, that would be very helpful.
Sure. I can speak in some generalities and later this year we'll speak more specifically about what the study will be designed to do. Your first question really is whether current therapies have demonstrated or have they even been studied in terms of their effects on exercise tolerance, and indeed they have. Beta blockers, for instance, have been studied and data published on several different papers that don't improve exercise tolerance in heart failure patients. Beta blockers have a kind of a negative effect on skeletal muscle function directly. Obviously, over time, they have a not very positive effect on cardiac function, and so the overall effect is relatively neutral. The ACE inhibitors have also been examined in this way a long time ago.
In fact, I think one of the ACE inhibitors is the only heart failure drug that has a labeled claim for improvement of exercise tolerance. The MRAs haven't really been looked at in a rigorous fashion and other therapies, probably the most key one is our device therapies such as cardiac resynchronization therapy. Their exercise improvement was the basis of approval of the first device, the first cardiac resynchronization device in heart failure. I'd say that the effect on exercise is mixed across different heart failure therapies.
There are different ways of measuring exercise tolerance that have been employed. Six-minute walk time is one mechanism for measuring exercise tolerance. It has its challenges. Cardiopulmonary exercise testing is a quantitative way of looking at exercise tolerance. It has positives and negatives as well. There are also newer ways of looking at activity, AKA Ella and an Apple Watch or some sort of device that measures steps or how often people are active and moving around as a way to look at activity over several days in a row rather than just a specific instance of testing someone. So you'll see, I think, as we articulate the details of the protocol, we'll have solid ways of assessing exercise, quantitative ways of assessing exercise performance.
We'll employ some of these newer measures, and we'll also be looking at patient symptoms and heart failure as they're related to their improvement in exercise performance. Is that?
Great. Yeah, that was very helpful, and I appreciate it. You actually prompted me to check my own Apple Watch and see how my heart was doing. I appreciate that.
Sure.
Glad we could be of service, Chad.
Our next question is from the line of Jason Butler with JMP Securities.
Hi, Jason.
Hi, Robert. Thanks for taking the questions. Just two on the SMA study. Could you, just as clarification point to start with, is it fair to assume we should not expect to see a top-line press release before the conference in the middle of June?
Yeah. It's a good question. Based on the fact that this is a hypothesis-generating study, not a hypothesis-testing study, our current view, absent having seen the data, is that it may not rise to the level of materiality prompting the need to disclose the top-line data. Having a look at all of these different endpoints and not knowing, obviously, the totality of those data, it's difficult to understand how we might summarize it strictly by top-line announcement. That said, until we see the data, it's hard to know for sure. Based on where we think we are relative to last patient, last visit, database lock, and data analyses, it's going to be tough coming up right against the Cure SMA meeting. Currently, we're not anticipating that there would be a top-line release in the days to weeks leading into that meeting.
That could change if we feel prompted based on the data themselves as we now prepare to see it.
Okay. That's helpful. Then can you just walk us through the dose selection, what drove dose selection for the first two cohorts, whether you think that there's an opportunity to go to higher doses? When you look at the blinded tolerability, do those data support the potential to go to higher doses? Thanks.
Well, the doses were selected based on a phase I study you might remember where we stimulated the fibular nerve of healthy volunteers and found concentrations that were clearly associated with increases in skeletal muscle force production in those volunteers. The drug does appear to be well-tolerated if you look at the blinded data, I wouldn't rule out the possibility that we may choose to go higher, that will be based not only on tolerability but what we see in terms of efficacy when we unblind the study.
Yeah. At some point, we get to limits on what we can practically deliver in the way of drug. We do have what we think is a considerably more well-tolerated fast skeletal troponin activator, that seems to be borne out by these data, albeit still blinded. We do think that we're within the pharmacodynamic range of what was evaluated in phase I healthy volunteers, therefore, we do believe that we're getting proper exposures in order to be able to see a signal of activity here across these different endpoints.
Great. Thanks for taking the questions.
Thank you.
Our next question is from the line of Charles Duncan with Piper Jaffray.
Hi, Charles.
Hey, guys. Good afternoon. Thanks for taking the questions. Had a couple, actually, on OMG and then reldesemtiv. Just quickly kind of going back to an early set of questions regarding that new phase III that you guys will be conducting. I'm really intrigued with that in terms of if you can provide any more color on potential time frames. Would you anticipate being able to be in the clinic with that study this year? Is it possible that that data could or that study could actually read out before the GALACTIC-HF study?
Hey, Charles. Yeah, good questions. With regard to timing, as we mentioned, it really is something that still needs to be agreed, and there are a couple things that are factoring into that timeline to agreement. One is just understanding from some ongoing regulatory interactions that we've got a final protocol, and we understand From the standpoint of feasibility of the study, what's going to be required in order to make it happen. Then we have to just sort through a couple of practical issues with Amgen in order to ensure that we're well coordinated and integrated with respect to drug supply, systems, safety reporting, and all of those kinds of things that are getting ironed out. I do think that there's a possibility that this could start later this year, and therefore we're readying for that possibility.
There still needs to be some of these things to get finalized in order for that to occur. In terms of the timeframe, the study's going to be substantially smaller than the GALACTIC-HF study, but we have conducted feasibility assessments and working together with CROs, we understand sort of what to expect in terms of enrollment rates, number of centers, et cetera. The goal is to, while starting this study later than GALACTIC-HF, ensure that it's finishing before or at least concurrent with GALACTIC-HF so that we have data from both studies in the same general timeframe. That's going to enable us to be in a position where both studies could hopefully form the basis of regulatory submissions. That's the intention.
Okay. That's very helpful. When you consider the patient population, I know that you're still finalizing this, but could you characterize at all the types of patients that you would anticipate being able to enroll in that study?
Yeah, these are going to be patients that will be similar to those that we're studying in GALACTIC-HF with a couple important exceptions. One is we obviously don't want patients that have been hospitalized in the recent past to when they are randomized, because hospitalization changes your exercise tolerance. We're looking for a patient population where they have a more stable baseline. They'll have reduced ejection fraction like patients in GALACTIC-HF, and they'll also need to demonstrate reduced exercise tolerance prior to being enrolled.
Okay. I appreciate that, Fady. Moving on to reldesemtiv. Yeah, lots going on in SMA. Was at AAN, sorry, I missed you, Robert. Clearly very exciting times for that area, it did seem like there's a complete lack of work with, I'll call it later-stage patients or older patients. I guess I'm wondering when you think about the evolving treatment paradigm there, and you mentioned that your study started before nusinersen was actually approved, how do you think about the opportunity? I know this is really a study meant to generate a hypothesis, but right now, could you see yourselves moving forward in SMA given the feedback that you've gotten with KOLs?
The answer to that question is yes. We and Astellas are looking at these data as hopefully being therefore informing the path to phase III and regulatory submissions that would lend support for movement to phase III based on these data. Our expectation is that with nusinersen as well as gene therapy and other SMN-directed therapies, there's going to be an increasingly large population of patients living longer with SMA, but with residual weakness. This mechanism should, hopefully, based on the therapeutic hypothesis, address those limitations, if not afford them improvements and increases in function over time. It should be quite complementary, both with regard to mode of administration, but also mechanism of action.
We're quite optimistic, I know Astellas shares that same alignment with us that this could be quite promising for a new approach to the treatment of these patients, expecting that this population grows over time as well.
Last question, I appreciate you taking all the questions, is on reldesemtiv potential in ALS. Our diligence has suggested that frankly, investigators were really quite disappointed, I guess I'm trying to gauge whether or not that's because of the paucity of really interesting innovation within ALS or if it's really driven by mechanism. You said that you met with people, you felt good about the enrollment and interest in the trial. Can you have any further learnings from Vitality, and can you give us any insights on why there's continued interest in reldesemtiv within the ALS community?
Yeah. I'll start. Then ask Andy as well to join in. When you said folks were disappointed, I'm assuming you meant with regard to the results from VITALITY-ALS.
Yeah.
Surely we were disappointed as well. A couple things to note about that trial, now that we've had some time and distance from that trial, while it may read more optimistically for reldesemtiv. We've been poring over a lot of additional analyses, some pre-specified and others post-hoc analyses with respect to that trial, there are a couple things that stand out. One is, clearly the tolerability issues with tirasemtiv confounded the interpretation of those results. When looked at on an intent-to-treat basis, we had only a modest treatment effect observed with tirasemtiv versus placebo, that was clearly disappointing and not sufficient for submission to regulatory authorities, at least encouraging enough that there was some activity there that bore further investigation.
When we look at the as-treated population, recognizing about a third of the patients were not able to continue their treatment and dropped out based on mostly mild tolerability issues, still sufficiently a nuisance that they dropped out. When you look at the as-treated population, we saw a borderline statistically significant effect that was durable over time. That suggests to us that there is a biologic activity for this mechanism of action. As we've talked to investigators, between me and Fady and Andy and others here at the company, we visited over 50 different clinical centers participating in FORTITUDE-ALS in this first quarter. As we had conversation after conversation, it was extremely encouraging that mechanistically, the sites see benefit and merit to the approach we're taking with reldesemtiv, recognizing that it should be more well-tolerated and also potentially more potent.
As such, I think there's enthusiasm because this is a compound for which mechanistically there's over 1,000 patients that have been studied in ALS, and we've seen consistent effects that bore out for this approach. That's uncommon in ALS, in as much as generally speaking, in clinical trials, we've known very little about the mechanism and how it may translate to a therapeutic effect, given how little we know about the etiology of this disease. Given all of that, I'd say relative to other clinical trials, there's more support, more interest, more enthusiasm for this trial than is the case otherwise, and we're hopefully going to be in a position to enroll adequate numbers of patients. This will be a roughly 450-patient study. That by itself is larger than most phase III studies in neuromuscular diseases.
This phase II trial really should inform what we hope will be support for movement into phase III. The other thing to mention is in our VITALITY-ALS trial, we had a slower than expected decline in those patients who received standard of care in placebo. That's something that we're still trying to get our arms around. Some data were presented today at AAN from another sponsor bearing out that the placebo event rate in studies with ALS is different in 2018 than perhaps it was in 2015 and 2016. The good news is we believe we have, even as that may be the case in the FORTITUDE study, adequate statistical power to bear out the expectations and the therapeutic hypothesis. It's a dynamic space that we are staying very close to.
As such, I think the FORTITUDE-ALS study is amongst the clinical researchers, the most important study that should read out this year.
That's helpful, Robert. One last question regarding that event rate. Do you think that that is the kind of typical thing that you see with more intensive therapy and perhaps even better awareness often attributed to being involved in a clinical trial? Do you think there's some organic shift in terms of how patients are reacting to current standard of care in ALS?
I don't know what it is, I don't think it's just due to being in a clinical trial because these patients are progressing at a rate that is different from other patients in clinical trials that are fairly recent and that use very similar entry criteria that produce very similar baseline characteristics. Despite the similar baseline characteristics, our patients went on to progress meaningfully more slowly than patients in recent but earlier trials. There does appear to be something different in the population. It may be just that ALS care in general has become better. It's difficult for us to actually put our finger on any one thing that would support that view.
Okay. We'll look forward to that data towards the end of the year and appreciate the added info and color. Thanks, guys.
Thank you, Charles.
Next question is from the line of Vernon Bernardino with Seaport Global. Please go ahead.
Hi, Vernon.
Hi, everyone. Thanks for taking my question. Good afternoon. Regarding the FORTITUDE-ALS study, it's good that some of these patients who want to remain are going to be able to continue receiving tirasemtiv. How long have the longest patients now been on tirasemtiv, and what are the long-term expectations, if there are any, as far as these patients that may provide you insight into tirasemtiv as well as reldesemtiv?
I think the answer to the first part of the question, how long have they been on, some have been on as long as two and a half years. Just to remind you, VITALITY-ALS included about a little over a year of
Exposure, we certainly started VITALITY-ALS. It took us about a year to enroll that trial. Without having a calendar in front of me, I'd say we have about two and a half years' worth of continuous exposure in some patients. We're not expecting necessarily to get any data out of them per se, as we transition them to a managed access program. Obviously, as we conclude VIGOR, we will look to see if there are any interesting findings in the open label extension. I think the main thing that we get out of it is that the mechanism of action appears to be very safe, well-tolerated for a long time in this patient population, and we know that now having conducted VIGOR and VITALITY.
There are approximately 90 to 100 of these patients that are still receiving tirasemtiv in VIGOR who appear interested in converting over to a managed access program. To be clear, we have indicated that we've suspended the development of tirasemtiv. This is not with the goal of resurrecting the development of tirasemtiv as much as it's to do the right thing by these patients who believe that tirasemtiv is serving them well. In as much as they've committed to our clinical research, we want to reciprocate by making tirasemtiv available to them for so long as they want to stay on it. I do think this affords us insights into the long-term tolerability for this mechanism, but that was less of concern to us.
We believe that for those patients who did tolerate tirasemtiv in VITALITY-ALS, as I mentioned before, they appear to have benefited from it and want to stay on it. I think that is most important because from our standpoint, that reads positively on what we might expect from reldesemtiv in FORTITUDE-ALS.
That's a great segue because part of my thought is mechanistically, reldesemtiv is different, you also have some follow-on compounds. I was just wondering if it also informs you as far as structures that may be similar to tirasemtiv that have improved tolerability, or it's just really a hard stop here.
Yeah, I think.
As far as that structural history
We've continued to develop additional compounds with the same mechanism of action, bind in the same place, but they don't have any structural relationship necessarily to tirasemtiv.
We understand the SAR around this pretty well with different lead series having advanced, but with the goal with reldesemtiv and others to ensure that they don't cross the blood-brain barrier. Why we had these tolerability issues with tirasemtiv is not a mystery. We believe we do have an understanding as to what mechanistically is contributing to the off-target effect, and we believe we've successfully engineered that away with reldesemtiv and also the follow-on compounds as your question suggests.
Yes. Terrific. The only other question I have is regarding omecamtiv. As you know, I often ask you about ENTRESTO and Novartis' plans for that. At this point, it's just one more phase III study that you have planned for omecamtiv?
That's correct. We and Amgen have agreed on these two studies, GALACTIC-HF and this other one. That's not to say that in the future, there might not be other studies that we might also agree on, but these are the ones that we're pointing to today.
Terrific. That's all I have. Thanks for taking my questions. I'm looking forward to Cure SMA.
Thank you.
That there are no other questions in the queue. I'll turn it back over to management for any closing remarks.
Thank you, operator. Thank you to everybody who participated in this call today. Q1 was obviously a very important quarter for us. We continue to be enthusiastic about our prospects for this year and afterwards. With that, we will conclude the call. We appreciate your continued support and interest in our company. Operator, with that, let's close the call, please.
Ladies and gentlemen, this does conclude today's conference call. Thank you for your participation. You may now disconnect.