Good afternoon, and welcome, ladies and gentlemen, to the Cytokinetics First Quarter 2019 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 question 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. Then Fady Malik, our EVP of Research and Development, will provide updates on our cardiac muscle programs, including the Phase III development of omecamtiv mecarbil, our cardiac myosin activator and the Phase I development of AMG 594, our cardiac troponin activator, both under our collaboration with Amgen as well as the development of CK-two seventy four, our wholly owned cardiac myosin inhibitor. Andy Wolf, our SVP and Chief Medical Officer, will then share updates on our skeletal muscle program focused on the recently announced results from FORTITUDE ALS, the Phase II clinical trial of reldesemtiv in patients with ALS under our collaboration with Astellas. Pete Roddy, our SVP and Chief Accounting Officer, will then provide a financial overview for the quarter and Qing Zha, our SVP and Chief Financial Officer, will discuss corporate development strategies before Robert concludes with additional thoughts on the company's outlook and expected 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. 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. 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 have a lot to cover on our call today, and I want to start by saying how pleased I am with the progress we made across our pipeline of muscle directed investigational medicines during the Q1 and now again into the Q2 of 2019. Our pipeline of 5 drug candidates across both our cardiovascular and neuromuscular verticals is advancing, and it's extremely gratifying to see our teams working urgently and collaboratively towards our mission to improve the health span of people with devastating diseases of impaired muscle function as well as conditions of muscle weakness. There is no more devastating disease than ALS, as you've heard me say over the course of our decade long skeletal muscle activator clinical development activities. That's why the results that were presented earlier this week at AAN and further elaborated in our recent conference call are so important to the ALS community and also to Cytokinetics.
As we announced, while the pre specified analyses for the primary and secondary endpoints, those being slow vital capacity, ALSFRS R and slope of the muscle strength mega score, while those were not conventionally statistically significant with a P value less than 0.05, overall, patients on reldesemtiv declined less than patients on placebo for all three endpoints on all dose levels of reldesemtiv. Importantly, we have now observed that skeletal muscle activation slows the decline of SVC in patients with ALS in 3 large international trials. Moreover, for the first time, FORTITUDE ALS demonstrated a clinically meaningful slowing of the decline of the ALS FRS by 25% when all active groups combined were compared to placebo. This is an especially gratifying finding given that ALSFRS is a generally accepted endpoint by regulatory authorities for registration and one that we find encouraging as we chart a potential path forward for reldesemtiv in this patient population. As you know, we do Phase II clinical trials in order to understand the effects of a potential new treatment across doses, time points, endpoints and subgroups.
We do that in order to be able to properly design a Phase 3 clinical trial that could have the robustness with a statistical significance of p less than 0.05 then in order to support potential registration and marketing authorization. I would assert that we most definitely accomplished the objectives that we established for FORTITUDE ALS and we believe the results lend support for progression of reldesemtiv into further clinical trials. And this sentiment was communicated to us by many of our key opinion leaders and site investigators. Andy will elaborate on that in a moment. Now moving to our cardiovascular programs.
During the quarter, we passed through the first planned interim analysis of GALACTIC HF, which was designed to assess for the potential of futility. While we are confident in that outcome, it's still nice to have it behind us and we believe given the thousands of patients now in this clinical trial, some of whom have been on therapy for over 2 years, it marks an important milestone for the progress of omecamtiv mecarbil. We also continued site activation and enrollment in METEORIC HF, the 2nd Phase 3 clinical trial of omecamtiv mecarbil, and we remain on track with timelines for that trial. And finally, we continued the Phase 1 study of CK-two seventy four, our wholly owned cardiac myosin inhibitor, which we're developing for the potential treatment of hypertrophic cardiomyopathies. We look forward to results from that ongoing Phase 1 study in the Q3, but we also are continuing start up activities for our Phase 2 program with CK-two seventy four that should be underway in the second half of the year.
To be clear, our engine for innovation and development in muscle biology and its related pharmacology continue to be productive for Cytokinetics in the first quarter, and we're optimistic about our future. Now with that, I'll turn the call over to Fady to elaborate on our cardiovascular programs.
Thanks, Robert. As mentioned, GALACTIC HF, the Phase 3 cardiovascular outcomes clinical trial being conducted by Amgen under our collaboration continued during the quarter following the first planned interim analysis. This analysis conducted by the data monitoring committee included consideration of pre specified criteria for futility. And upon review of the data, the DMC recommended the trial continue without changes to its conduct. The futility analysis was triggered once a pre specified number of cardiovascular deaths stipulated by the trial's protocol had occurred in GALACTIC HF.
As a reminder, the 2nd planned interim analysis in GALACTIC HF, which includes an assessment of potential efficacy, is projected to occur in the first half of twenty twenty. We're in the midst of surpassing historical precedents in terms of the number of patients and patient years on treatment for therapies intended to improve cardiac function. As we approach the close of screening in GALACTIC HF in the Q2 of 2019, we believe passing through this first planned interim analysis further derisks this Phase III clinical trials program. Also during the quarter, we opened METEORIC HF to enrollment. The 2nd Phase 3 trial is designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity is determined by cardiopulmonary exercise testing following 20 weeks of treatment.
It's being conducted by Cytokinetics under collaboration with Amgen. Our goal for the year is to activate the majority of our participating sites distributed across the U. S, Canada and Europe. As previously stated, we expect results to be available around the same time that GALACTIC HF is anticipated to read out in 2021. At the American College of Cardiology meeting in March, Doctor.
John Tierlink, Chair of the COSMIC HF and GALACTIC HF Executive Committees, presented results from COSMIC HF, our Phase 2 clinical trials on omecamtiv mecarbil, comparing subgroups in atrial fibrillation and normal sinus rhythm. The analysis showed that measures of cardiac function, including systolic injection time and stroke volume, as well as ventricular volumes, heart rate and NT proBNP did not differ statistically according to the presence or absence of atrial fibrillation at baseline in both subgroups. This is important given that atrial fibrillation is a common comorbidity in people with heart failure. In fact, its prevalence increases with increasing heart failure severity and affects up to 40% of those with New York Heart Association class for disease. By design, approximately 25% of the patients enrolled in GALACTIC HF have atrial fibrillation.
So we're pleased to see that the treatment effects and safety of omecamtiv mecarbil in this subgroup did not differ substantially from patients who did not have atrial fibrillation. Also during the quarter, we announced the initiation of a Phase 1 study of AMG 594 that is being conducted by Amgen in collaboration with Cytokinetics. The study includes single and multiple ascending dose cohorts to assess the safety and tolerability of AMG 594 and its potential to increase cardiac function. As you may recall, AMG 594 is a novel, selective, oral, small molecule cardiac troponin activator discovered under our joint research program with Amgen. Together with Amgen, we're evaluating various approaches to its development program and look forward to expanding on this later in the year.
Moving to our cardiac myosin inhibitor program, we continued the conduct of CY-six thousand and eleven, the Phase 1 first in human study of the cardiac myosin inhibitor CK-three seventy seven-three thousand two hundred and seventy four or as I'll call it from now on CK-two seventy four. The study in healthy participants is nearing completion of the single and multiple ascending dose portions. As you know, we are developing this investigational medicine for the potential treatment of hypertrophic cardiomyopathy and expect to advance this and other compounds in a broad development program. As we continue preclinical work in parallel with the Phase 1 study of CK-two seventy four, we see a profile emerging that may provide distinct advantages beyond PK alone, in part perhaps stemming from its distinct binding site. We believe further its pharmacokinetics may provide important treatment benefits by potentially optimizing the time to reach target doses and providing symptom relief.
During the quarter, we continued to engage with leading physicians in the field of hypertrophic cardiomyopathy, most recently at the ACC meeting. The feedback remains positive for potential 1st nidescent class therapy for patients with hypertrophic cardiomyopathy, and we're pleased with the strong interest of this community in our clinical trial program. We remain energized about the productivity and promise of our expanded cardiovascular pipeline, particularly given the increasing global burden of heart failure. It's truly that it is under a burden that is truly underappreciated. Recently, for example, I heard a statistic that might help put it into perspective.
A woman today has a 1 in 4 chance of dying from heart disease, but she has only a 1 in 40 chance of dying from breast cancer. In other words, the risk of a woman dying from heart disease is 10 times greater than her risk of dying from breast cancer. Clearly, there's a huge need not only to raise awareness of heart disease and heart failure in particular, but also to deliver novel therapies to treat the underlying mechanistic dysfunction of the heart. Cytokinetics has pioneered the pharmacology of muscle directed drug candidates, and our cardiovascular pipeline of clinical programs is now comprised of 3 promising compounds. And now I'll turn the call over to Andy to elaborate further on the results of FORTITUDE ALS.
Thanks, Fady. As Robert mentioned, we recently announced results from FORTITUDE ALS, the Phase 2 clinical trial of reldesemtiv in patients with ALS. Many of you may have participated in the event we held earlier this week, so I won't repeat all the results from the trial now. Instead, I'll provide additional perspectives based on our experience at AAN and discussions of the data from FORTITUDE ALS with clinicians, key opinion leaders and the advocacy community. We were extremely pleased to hear from leading clinicians who have been conducting clinical research in ALS for upwards of 30 years that these results despite not beating statistical significance in the primary and secondary efficacy analyses are among the most compelling and encouraging from Phase 2 clinical trials conducted in the past 25 years.
During our investigator meeting, in which Doctor. Schechner presented the results for the first time, we had the opportunity to speak to our investigators regarding their interest in continuing to pursue clinical trials for this mechanism. Everyone to whom we spoke supported pressing forward, None of our investigators at the meeting suggested otherwise. As we discussed on our call on Monday, the effects of reldesemtiv seen in FORTITUDE ALS on ALSFRS R, a relative reduction of 25% in its drop compared to placebo are consistent with a clinically meaningful effect. Recall that Mitsubishi Tanabe conducted a trial of 139 narrowly defined patients with demonstrated disease progression and found a 33% change in the rate of progression in ALSFRS R after 24 weeks of treatment with edarabone.
The magnitude of the effect at 12 weeks was about 8% and recall FORTITUDE ALS is a 12 week trial. Several of our investigators were especially encouraged by our results in FORTITUDE ALS, given the breadth of our entry criteria relative to those for the successful edaravone registration trial. After 12 weeks of treatment in FORTITUDE ALS, the average ALSFRS R total score on reldesemtiv was 0.9 points higher than on placebo. We can put this into perspective in at least 2 ways. First, a one point reduction in the 48 point scale of the ALSFRS R total score could be the difference between a patient speaking normally or having detectable speech disturbances or walking normally versus having early ambulation difficulties.
These are meaningful changes in terms of the patient's ability to remain independent and continue activities of daily living. 2nd, as we elaborated in our press release Sunday, a published survey of U. S. ALS clinicians indicated that a large majority of them viewed a reduction of 20% to 25% in the rate of decline in the ALS FRS R as we observed in FORTITUDE ALS, to be clinically meaningful. Finally, given that the curves depicting patients on reldesemtiv and those on placebo separated discernibly after only 2 weeks and continued to diverge in favor of reldesemtiv versus placebo with continued treatment, it's conceivable that we might even see greater differences versus placebo after 24 weeks of treatment in a longer trial.
Additionally, we believe the fact that no one subgroup appeared to be driving the results of this trial is especially encouraging. Stated another way, placebo did not appear to outperform reldesemtiv for any subgroup across both primary and secondary efficacy analyses at 12 weeks post randomization. The effects of reldesemtiv were consistent across all patient subgroups we examined for all doses and endpoints. I'd also like to address the dose dependent increase in the estimated glomerular filtration rate or eGFR, which we calculated from Clystatin C and observed in FORTITUDE ALS. While the data are still very fresh, we have had an opportunity to review the findings with nephrologists as well as with ALS clinicians.
Importantly, they found it reassuring that the decline in renal function seems to resolve when reldesemtiv is stopped and that your analyses were generally free of casts, red cells and white cells,
which are markers
of renal tubular injury or inflammation. We will continue to evaluate this laboratory signal as we design future clinical trials and ensure appropriate monitoring. However, the investigators with whom we have spoken generally currently believe that these changes are easily monitored and manageable, especially in the context of a clinical trial. We are still conducting additional analyses of the data and we'll be meeting with our colleagues at Astellas over the coming months to discuss potential further development. Finally, under our collaboration with Astellas, we also continued preclinical development of our fast skeletal muscle troponin activator CK-six zero one and our joint research program focused on pursuing other next generation skeletal muscle activators.
Now I will turn the call over to Pete to update you on our financials.
Thank you, Andy. I'll first provide an update on cash, revenue and spending and then Ching will review our corporate development strategies. As usual, more details on our actual results are included in the press release itself. We ended the Q1 with $177,000,000 in cash and investments. Our cash includes $5,000,000 generated from our ATM facility.
Our revenue in Q1 2019 came from our strategic alliances with Astellas and Amgen. For Astellas, we continue to recognize revenue for reimbursement of our research and development for both FORTITUDE ALS and our joint research program. For Amgen, we have revenue related to reimbursement of our development expenses for METEORIC HF and our revenues include both cash and non cash revenue recognized under ASC 606. Our Q1 2019 R and D expenses increased to $23,500,000 from 22 $100,000 in the Q1 of 2018, primarily because of increased activity for METEORIC HF and CK-two seventy four, offset in part by lower spending in our neuromuscular vertical. Almost half of our R and D expenses were attributable to our cardiovascular programs, as expected given activity for METEORIC HF and the cardiac myosin inhibitor program.
About 30% of our expenses were allocable to our skeletal muscle programs with the remainder going to early research activities. Our Q1 2018 G and A expenses were almost flat at $9,400,000 up slightly from $9,300,000 in Q1 2018. Before I hand the call over to Qing to provide an update on corporate strategies, I'd like to note that earlier in the Q1, we announced via Form 8 ks that I will be retiring at the end of May. It's been my honor and privilege to work on behalf of the patients we serve and for you, our stockholders. I want to thank Robert, Ching and the rest of the team at Cytokinetics for the opportunity to help bring our vision to fruition.
Thanks, Pete. Before I address our corporate development strategy, I want to take a moment to thank Pete for his commitment and service to Cytokinetics over the past 2 years. Pete has contributed greatly to our accounting and overall finance operations and his dedication and hard work will be missed. Stepping into replace Pete will be Robert Wong, an accomplished financial leader with 30 years of finance and management experience. Robert joins us following a 23 year career at Genentech, where he was most recently the Interim Chief Accounting Officer and responsible for accounting and financial reporting across the company as well as leading roles for integration of Intermune, Canox and Ceragon.
Robert also led the financial integration of Genentech following the Roche acquisition into its global network. Prior to Genentech, Robert spent 7 years at Ernst and Young. We are pleased to welcome him to Cytokinetics. Moving to our corporate development strategy. As we have previously stated, our strategy remains to manage our cash prudently through the expected readout of results from GALACTIC HF in 2021.
During the quarter, we executed on multiple strategies to meet that objective, including continuing to engage in potential collaboration discussions relating to our cardiac myosin inhibitor program as one avenue to raise additional capital. Finally, with the result from Fortitude ALS now in hand, we will evaluate our strategic planning scenarios to determine appropriate prioritization of investment in that program alongside our wholly owned cardiac myosin inhibitor program, which we expect to advance into Phase 2 later this year. In addition to potential access to additional capital from new partnering initiatives, I will remind you that we are eligible for over 500,000,000 dollars in pre commercialization milestone payments under our existing collaborations as well as additional reimbursement of sponsored research and development activities. In closing, we believe that we have prepared well for the positive momentum we are experiencing in our advancing clinical programs with a strong balance sheet and access to additional capital. And with that, I will now turn the call back over to Robert.
Thank you, Qing. So as you've heard, it's been a very productive quarter and we remain energized by the outlook for the company. In particular, as the ALS community recently kicked off ALS Awareness Month in May, we're honored to have delivered such encouraging results earlier this week. In spite of FORTITUDE ALS not having met conventional standards for statistical significance. On our Q4 earnings call held back in February, we discussed our planning against a range of potential outcomes for FORTITUDE ALS and for other programs.
Now, with the results of FORTITUDE ALS in hand, we believe they support progression of reldesemtiv into further clinical trials toward potential registration, and we look forward to working with our partner Astellas to determine potential next steps. That will take some time as we expect to conduct further analyses, engage with HTAs as well as regulatory authorities, all of which needs to occur before considering a timeline as well as a design and a budget for potential next trial. And to be clear, we don't expect the next trial could begin in 2019, but we will be proceeding with urgency nonetheless, and we look forward to providing updates. In the meantime, our focus for the company, as outlined in our R and D Day last fall, remains on advancing our exciting and industry leading cardiovascular pipeline with priorities focused to omecamtiv mecarbil and CK-two seventy four for the balance of 2019. We have a unique opportunity in this space to leverage our pioneering science in the discovery and development of drug candidates to modulate cardiac muscle contractility and to potentially bring novel therapies to millions of patients suffering from heart failure in its multiple forms and hypertrophic cardiomyopathies.
Now, let me recap our expected milestones for 2019. We expect to close screening of patients in GALACTIC HF in the Q2 of 2019 and we expect to conduct METEORIC HF in patients with heart failure throughout 2019. We expect data from the Phase 1 study of CK-two seventy four in healthy subjects in the Q3 of 2019. And for AMG 594, we expect that Amgen will continue conducting the Phase 1 study throughout 2019. For reldesemtiv, we'll continue to evaluate the results from FORTITUDE ALS and be discussing and planning next steps in the development program with our partner Astellas.
And for preclinical research, we expect to continue our research activities under our joint research program with Astellas directed to the discovery of next generation skeletal muscle activators throughout 2019 as well we also expect to continue our other muscle biology focused research, including the ongoing expansion of our research activities beyond the contractility of muscle towards the energetics of muscle. And operator, with that, we can now open up the call to questions.
Your first question today comes from the line of Jason Butler with JPM Securities. Your line is open. Please go ahead.
Hello, Jason. 2
on CK-two seventy four. Could you maybe elaborate a little on the advantages that you think the drug might have with respect to the binding site? And then secondly, I know I may be jumping forward a little bit here, but when you think about the first Phase II trial for 2/74, what would be the goals you would be looking to achieve? And how would you even with this first trial potentially look to demonstrate initial differentiation clinically or with the development program?
Thanks. Sure. I'll start off and then I'll ask Fadi to elaborate. Firstly, with respect to the binding sites, so these differences are still being clarified in ongoing research. So I don't want to make too much of it absent having the clinical evidence to support what may be those differences.
But we do believe that CK-two seventy four may have a privileged binding site that could give rise to distinctive advantages visavis the clinical profile. That's still to be borne out in ongoing activities. But I also would suggest that that's not the principal differentiation between CK-two seventy four and mavacamten or other compounds that may be developed in this space. And we have, as we've already mentioned in our R and D Day, elaborated on some of those and Fady will speak to those here in a minute. And then lastly, I'll also ask Fady to speak to what may be differentiated approaches that you will see in our Phase 2 program, some of which we've spoken to, others of which will be elaborated more in time.
Yes. So I think just in terms of biology of the molecule, a different binding sites provides an opportunity for differential pharmacology. And we, I think, work very hard in the preclinical development to maximize the therapeutic index of CK-two seventy four even amongst its most closely related analogs and providing a shallower exposure response relationship potentially makes titration of this class of medicines easier in patients down the road. The other is, as we talked about, ensuring its pharmacokinetics would be useful for rapid symptom release. And what do we mean by that?
Primarily just that as new drug these patients are symptomatic obviously, which is why they seek medical attention. And as you initiate new therapy, how long does it take you to get to a target dose that potentially release symptoms. And so we believe 274 will allow for titration of dose in a relatively
facile fashion.
The clinical program will be designed to elucidate some of these things, both in terms of turnaround, how quickly can patients go from one dose to the next dose in terms of looking for reversibility of effect and other things like that. And there are other aspects of the clinical program probably we'll elaborate on as we come more proximal to those particular studies.
Yes. Just to point out, we expect to be in Phase II enrolling patients later this year. And when we do that, we'll speak to the design of the Phase II program. Suffice it to say that for having been in this space for a very long time, developing cardiac myosin activators and now a cardiac myosin inhibitor, we think that we can import a lot of learnings that would afford us advantages now in a next generation approach. With all emphasize that we believe that mavacamten looks to be very promising in its ongoing clinical trial program.
That's not to take anything away from that development program, but we do think that there's an opportunity with a compound that has differential pharmacology associated with different physiochemical properties that, that could afford certain advantages that we will explore.
Great. Very helpful. Thanks for taking the question.
Thank you.
Your next question comes from the line of Ted Tenthoff with Piper Jaffray. Your line is open.
Hi, Ted. Hi, Ted. Hey, how are you guys? And congratulations on the data earlier this week, incredibly difficult disease and I was really pleased to see the stock respond positively to the beta. I had a real quick question on this and I appreciate that there's a lot of people you have to talk to.
But with respect to dosing here and this kind of relates back to what we saw with reldesemtiv in SMA. Is there the potential to go above the top dose that you explored and maybe see if even you can get more from the dose benefit?
It's a good question. And as Fady can point out, we're still in the midst of those analyses. I'll turn it over to him to respond.
Hey, Fadi.
Yes. I mean the pharmacodynamic effects certainly extend or they increase potentially with higher dose, in the healthy volunteer studies we've done. But in FORTITUDE where we studied 3 doses 150, 30450, it didn't seem to be much of an advantage of chronic therapy at between 300 say and 450. And so it's I think fair to ask whether there is a significant benefit to going higher than 450 at least with reldesemtiv. You see because the FCS obviously be balanced by tolerability and with the higher doses, we began to see some renal dysfunction that we obviously want to minimize in a study going forward.
So I think in SMA, we bracketed those doses. We did 150 and 450 to 300. In all of these patient populations, kidney function is essentially normal at baseline. And so modest decrements aren't probably don't create significant problems for these patients. But I think in the balance of benefit and risk, we would probably aim for around the middle dose of 300.
But more work will continue for us to think about that, how to maximize exposure and also maximize safety.
Okay.
It comes with the territory yes, thank you, Chad. It comes with the territory that for us forging a new path with a first muscle directed therapy being evaluated specifically for ALS and SMA that we're going to learn things along the way. And we're learning and reporting externally at the same time, and there's still a lot more data analysis that needs to happen. The data that we shared publicly at AAN, we've only had for a couple of weeks and there's a significant number of additional analyses that are planned as well as other things that we want to discuss with Astellas. So it's going to take us a while to get our arms around these data in order to understand what it might mean for next trials.
And then, we would want to discuss that with regulatory authorities. So bear with us as we go through that process, but recognize still that we believe that there is a dose dependent effect and then we want to make sure we can maximize the pharmacologic effect, while at the same time maintaining good balance with what we know to be a safety and tolerability profile.
Your next question comes from the line of Gil Blum with Needham and Company.
Hi, Gil.
Hello, everyone. It's Gil on for Chad. A bit of a modeling question. You guys gave guidance at the end of last year and it seems like spend is a bit high for this quarter. Are you guys reiterating guidance?
I just want to
make sure.
I'll turn it over to Ching to respond to that.
So no, we're not reiterating guidance. So the guidance remains the same. Our net cash burn for the year will be between $85,000,000 90,000,000 dollars There is spending seasonality based on the progression of clinical trials, as you know, for biotech companies. So the fact that the Q1 spending might be a little bit higher than you expected is nothing of concern. Just to clarify, we are reiterating guidance.
We're not revising guidance. We're keeping guidance as it was in the Q4 earnings call. I
got that. And my other question is about the one unit difference in the ALSFRS. So as you've mentioned that this is not exactly a linear response, but is this one unit more important for someone later in their disease progression or earlier in the disease progression? Maybe a bit of color on that?
I think I would argue that it's important to patients throughout their disease progression. When therefore they sure don't want to be a 3. Once they become
a 3, they'd like to stay there as long as
they can before they become a zoo. So we've talked a lot about this both with patients and their physicians. People want to preserve their functionality for as long as they can at whatever point in the disease they are.
And maybe a few additional comments. The ALSFRS R is an excellent tool for understanding the decline of function in ALS patients across a population suffering from the disease. Some people are faster, some people are slower. And it's pretty linear, about 1 point a month in that population. But it doesn't decline uniformly across all subgroups.
So what Andy was mentioning of 1 point in 12 weeks, earlier in the disease onset, that decline may be more prevalent in fine and large motor function subgroups like we saw in FORTITUDE ALS later in the disease progression, maybe more pronounced in the respiratory subgroup. What was especially reassuring to us in looking at the results of FORTITUDE ALS is that where the placebo group was declining the most, that's where the greatest treatment differential was favoring reldesemtiv versus placebo. So it would be expected, therefore, that as the placebo group may decline more and more in the other subgroups over time, There too, should we be seeing effects that favor reldesemtiv versus placebo.
All right. Thank you very much for the clarification. That helps a lot.
Thank you.
Your next question comes from the line of Jeff Hung with Morgan Stanley. Your line is open.
Thanks for taking the questions. In the last few months, you mentioned that there was a scenario where you might deprioritize the skeletal muscle franchise and focus on the cardiac muscle franchise. So just to confirm, it sounds like that scenario is now off the table?
Yes, it's a very good question. And it's not one I think I can answer yet fully and completely, these results being so new. But I don't think we have data from FORTITUDE ALS that causes us concern regarding the potential path forward. I do think we have results from FORTITUDE ALS that bear elaboration and further clinical trials. But how we do that ultimately depends on what we and Astellas may agree to do.
And that's something that will take some time and not something that will impact our spending in 2019. I think it could impact our spending in 2020, but even that may be negligible because as we may move forward with reldesemtiv in further clinical trials, we're eligible for milestone payments that may partially offset the expenditure of a net out of pocket that we would be expected. So it's fully our expectation right now based on what we know that we could move forward with reldesemtiv and it would have relatively low impact, if any, to our net spending. So I think when we said on our February earnings call that we'd have to consider that possibility of focusing to our cardiac vertical and perhaps deemphasizing our neuromuscular one, I don't foresee that occurring right now, but it's still imperative that we'd be prudent in terms of how we manage our capital and where we invest. And certainly in 2019 and potentially throughout 2020, the majority of the incremental net out of pocket spending would likely be around our cardiac muscle programs.
Great. And then now that the 42 data read out, how are you and Astellas thinking about the SMA program? And what are the next steps? Any updates on the Phase 1 in healthy volunteers for higher doses? And is that still expected this quarter?
Yes. I think with again, with these data in ALS, the data we have in SMA, the question is how will the neuromuscular program come together, and in particular, what doses will we use going forward? The 300 milligram dose, we used in ALS seems to be the best balance of efficacy and tolerability. We didn't use that dose in the SMA study, but it as we said, there wasn't a big difference in dose response in the ALS study. So going forward, if we did plan to go forward in SMA, probably that dose would sort of be the right balance in that patient population as well.
But I think overall, we are informed by the Phase 2 clinical data and the Phase 1 clinical data that we're accumulating will also help determine whether we need to push dose at all.
And to answer that also in the context of your first question, how we think about SMA is in part informed by how we're thinking about ALS and both against the backdrop of our priority towards our cardiovascular medicines vertical. And therefore, we have to reevaluate some of these things. What's noteworthy is that there's a tremendous urgency in the areas of ALS and in the area of SMA, as you know, there are investigational medicines and others coming forward to approval that look to be altering the landscape of that disease. So one could argue that we still have a bit to learn from how adolescents and adults with SMA may be doing on gene directed treatments like SPINRAZA, like the gene therapy or like other oral therapies and that it may be incumbent upon us to understand that unmet need before we might design a pivotal registration study regarding reldesemtiv in SMA. And in that way, a watch and wait or a deferral in SMA could make a lot of sense and prioritize ALS over SMA.
I'm not saying that's our decision, but I am saying that's one potential scenario that we need to put on the table to understand exactly what we're aiming for in SMA as that area is very rapidly evolving. And with that said, while those treatment modalities look extremely promising, they are unquestionably leaving a deficit of muscle weakness and at the same time, there are safety and tolerability issues there too. So if we're trying to demonstrate superiority over standard of care, we have to make sure that we're clear on what background therapy is delivering. So, these are all things that we take into consideration in performing the calculus over what will be our strategy in the neuromuscular space.
Great. Thanks. And one last one, if I may. For 274, it's currently wholly owned. So you guys have talked about this
a little bit today, but maybe can you remind us
how you're thinking about this program if you think that you would
partner out certain geographies? Thanks.
Yes. Another good question. So, geographies?
Thanks.
Yes, another good question. So with regard to CK-two seventy four, we do believe that it is partnerable. We've had very active discussions for a long time regarding the partnering of it. And in fact, we have deferred on certain partnering activities until such time as we knew what we were dealing with regard to reldesemtiv and understanding what might be our appetite for increased investment spend in the area of ALS and SMA. Now with those data from FORTITUDE ALS in hand, we convene discussions with our Board about whether we should bring one of those partnering deals home or otherwise might we consider restructuring the way we think about our access to capital.
I would say that you should assume that we are still intending to partner in the cardiac sarcomere inhibitor area, and that will be something that we can speak to more over time.
Thank you.
Thank you.
And we have no further questions at this time. I'll turn the call back to the presenters for closing remarks.
Thank you, operator. Firstly, I'd like to make a couple of comments about the upcoming retirement of Pete Roddy. I'd like to thank Pete for all the work that he's done for cytokinetics, but also recognize that he and I have worked together for nearly 30 years. And both as a friend and colleague, he's amongst the best at what he does, and he will be missed here at Cytokinetics, but I also am very grateful that we'll have his continued service as a consultant to us. I'd also like to thank everybody on the call today for your interest, for your understanding about the FORTITUDE ALS results and how they fit into the context of our corporate development strategy, recognizing that things are not always as they may first appear.
And clearly, in the area of pioneering pharmacology, we have an opportunity to forge a new path, and we think we're doing that with our muscle directed investigational medicines, not only in ALS, but also in other areas. So thank you to everybody on the call today for your continued support and your interest in Cytokinetics. And operator, with that, we can now conclude the call. Thank you.
Thank you to everyone who joined us today. This does conclude today's conference. You may now disconnect.