Cytokinetics Inc

NASDAQ:CYTK

Earnings Call Transcript 2019-Q1

[Operator]

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 a 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.

[Diane Weiser]

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 program, including the Phase 3 development of omecamtiv mecarbil, our cardiac myosin activator and the Phase 1 development of AMG 594, a cardiac troponin activator both under our collaboration with Amgen as well as the development of CK-274, our wholly-owned cardiac myosin inhibitor.

Andy Wolff, 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 2 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 Ching Jaw, 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 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. We undertake no obligation to update any forward-looking statements after this call.

And now, I will turn the call over to Robert.

[Robert Blum, President and Chief Executive Officer]

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 first quarter, and now again into the second quarter of 2019.

Our pipeline of five drug candidates across both our cardiovascular and neuromuscular verticals is advancing and 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 analysis 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 p value less than 0.05.

Overall, patients on reldesemtiv declined less than patients on placebo for all three and points on all those levels of reldesemtiv. Importantly, we have now observed that skeletal muscle activation slows the decline of SVC in patients with ALS in three large international trials.

Moreover, for the first time, FORTITUDE-ALS demonstrated a clinically, meaningful slowing of the decline of the ALSFRS 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 2 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 the statistical significance of p less than 0.05 than in order to support potential registration and marketing authorization.

I would assert that we most definitely accomplish 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 inside 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 two years; it marks an important milestone for the progress of omecamtiv mecarbil.

We also continued site activation and enrollment in METEORIC-HF, the second phase 3 clinical trial of omecamtiv mecarbil, and we remain on track with timelines for that trial. And finally, we continue the Phase 1 study of CK-274, 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 third quarter. But we also are continuing startup activities for our Phase 2 program with CK-274 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 continued 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.

[Fady Malik]

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 trial continue without changes to its conduct.

The futility analysis was triggered once a pre-specified number of cardiovascular deaths stipulated by the trials protocol had occurred in GALACTIC-HF. As a reminder, the second planned interim analysis in GALACTIC-HF which includes an assessment of potential efficacy is projected to occur in the first half of 2020.

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 second quarter of 2019, we believe passing through this first planned interim analysis further de-risks this Phase 3 clinical trials program.

Also during the quarter, we opened METEORIC-HF to enrollment. The second phase 3 trial is designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo, and exercise capacity as 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, Dr. John Teerlink, Chair of the COSMIC-HF and GALACTIC-HF Executive Committee 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 ejection 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, it's 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 continue to conduct a CY 6011. It’s a Phase 1 first in-human study of the Cardiac myosin inhibitor CK-3773274 or as I'll call it from now on CK-274. The study in helping 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-274, we see a profile emerging that may provide distinct advantages beyond PK alone and 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 first death-in-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. Truly, it is under a burden that is truly under appreciated.

Recently for example, I heard a statistic that might help put it into perspective. A woman today has a one in four chance of dying from heart disease, but she has only a one in 40 chance of dying from breast cancer.

In other words, the risk of a woman dying from heart disease is ten times greater than the 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 three promising compounds.

And now, I'll turn the call over to Andy to elaborate further on the results of FORTITUDE-ALS.

[Andy Wolff, Senior Vice President and Chief Medical Officer]

Thanks, Fady. As Robert mentioned, we recently announced results from FORTITUDE-ALS to Phase 2 clinical trials and reldesemtiv in patients with ALS. Many of you may have participated in the events 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 AAM 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 analysis, are among the most compelling and encouraging from Phase 2 clinical trials conducted in the past 25 years.

During our investigator meeting, in which Dr. Shefner [ph] 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 edaravone.

The magnitude of the effect at 12 weeks was about 8% and recall FORTITUDE-ALS of 12-week trial. Several of our investigators were especially encouraged by our results in FORTITUDE-ALS given that 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 two 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.

Second, as we elaborated in our press release Sunday, a published survey of U.S. ALS clinicians indicated that a large majority of them due to reduction of 20% to 25% in the rate of decline in the ALSFRS-R as we observed in FORTITUDE-ALS to be clinically meaningful.

Finally given that the curves depicting patients enrolled reldesemtiv in both on placebo separated discernably after only two 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 and a longer trial.

Additionally, we believe the fact that no one subgroup appeared to be driving the results of this trial, which is especially encouraging. Stated another way, placebo did not appear to outperform reldesemtiv for any subgroup across both primary and secondary efficacy analysis at 4 weeks post randomization.

The effects of reldesemtiv were consistent across all patients’ subgroups we examined, for all those as an end point. I'd also like to address the dose dependent increase in the estimated glomerular filtration rate or eGFR, which we calculated from cystatin 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 ALS clinicians. Importantly, they found it reassuring that the decline in renal function seems to resolve when reldesemtiv is stopped and that urinalysis 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 analysis 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-601 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.

[Pete Roddy]

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 our actual results are included in the press release itself.

We ended the first quarter with $177 million in cash and investments. Our cash includes $5 million generated from our ATM facility. Our revenue in Q1, 2019 came from our strategic alliances with the 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 first quarter 2019 R&D expenses increased to $23.5 million from $22.1 million in the first quarter of 2018, primarily because of increased activity for METEORIC-HF and CK-274 offset in part by lower spending in our neuromuscular vertical.

Almost half of our R&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 first quarter 2018 G&A expenses were almost flat at $9.4 million up slightly from $9.3 million in Q1, 2018. Before I hand the call over to Ching to provide an update on corporate strategies, I'd like to note that earlier in the first quarter we announced via Form 8-K 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.

[Ching Jaw]

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 two years. He has contributed greatly to our accounting and overall finance operations and his dedication and hard work will be missed.

Stepping in to 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, Tanox and Seragon.

Robert also led the financial integration of Genentech, following the Roche acquisition into its global network. Prior to Genentech, Robert spent seven years at Ernst & 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 our multiple strategies to meet that objective, including continuing to engage in potential collaboration discussions relating to our cardiac milestone inhibitor program, as one avenue to raise additional capital.

Finally, with the result from FORTITUDE-ALS already in hand, we will evaluate our strategic planning scenarios to determine appropriate prioritization of investment in that program, alongside our wholly owned cardiac milestone 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 million 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.

[Robert Blum, President and Chief Executive Officer]

Thank you, Ching. 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. When our Q4 earnings call fell 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 analysis engaged with HDAs 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&D day last fall remains on advancing our exciting and industry leading cardiovascular pipeline, with priorities focused on omecamtiv mecarbil and CK-274 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 second quarter 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-274 in healthy subjects in the third quarter 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.

[Operator]

[Operator Instructions] Your first question today comes from the line of Jason Butler with JPM Securities. Your line is open. Please go ahead.

[Robert Blum, President and Chief Executive Officer]

Hello, Jason.

[Jason Butler, JPM Securities]

Two on CK-274 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 2 trial for 274, what would be the goal as 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.

[Robert Blum, President and Chief Executive Officer]

Sure. I'll start off, and then I'll ask Fady to elaborate. Firstly, with respect to the binding site, 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-274 may have a privileged binding site that could give rise to distinctive advantages vis-à-vis 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-274 omecamtiv or other compounds that may be developed in this space. And we have as we've already mentioned in our R&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.

[Fady Malik]

Yes, so I think just in terms of the biology of the molecule, a different binding site provides an opportunity for differential pharmacology. And we, I think work very hard in the preclinical development to maximize the therapeutic index of CK-274 even amongst the – its most closely related analogs and in 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 relief. And what do we mean by that? You know primarily just that as new drug or these patients are symptomatic obviously, which is why they seek medical attention and is initiating therapy, you know how long does it take you to get to a target dose that potentially relieves symptoms.

And so, and 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 and how quickly can patients go from one dose to the next dose in terms of looking for reversibility of effects, and other things like that. And there are other aspects of the clinical program probably will elaborate on as we come more proximal to those particular studies.

[Robert Blum, President and Chief Executive Officer]

Yes, just to point out. We expect to be in Phase 2 enrolling patients later this year, and when we do that, we'll speak to the design of the Phase 2 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 learning’s that would afford us advantages now in a next generation approach.

With all that said, let me emphasize that we believe that omecamtiv 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 physio chemical properties that that could afford certain advantages that we will explore.

[Jason Butler, JPM Securities]

Great. Very helpful. Thanks for taking the question.

[Robert Blum, President and Chief Executive Officer]

Thank you.

[Operator]

[Operator Instructions] Your next question comes from the line of Ted Tenthoff with Piper Jaffray. Your line is open.

[Robert Blum, President and Chief Executive Officer]

Hi, Ted.

[Ted Tenthoff, Piper Jaffray]

Thank you very much. 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 data. 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 that dose benefit? Thank you.

[Robert Blum, President and Chief Executive Officer]

It’s a good question and as Fady can point out, we're still in the midst of those analysis. I’ll turn it over to him to respond. Hey, Fady.

[Fady Malik]

Yes. I mean the – 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 three doses; 150, 300, and 450 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, we see because the FCS obviously be balanced by tolerability and with the higher doses we began to see some renal dysfunction that we obviously would want to minimize in a study going forward.

So, I think on in SMA, we bracketed those doses; we did 150 and 450 onto 300 in all of these patient populations. Kidney function is essentially normal at baseline, and so modest decrement 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, more work will continue for us to think about that how to maximize exposure and also maximize safety.

[Robert Blum, President and Chief Executive Officer]

It comes with the territory -- yes, thank you, Fady. 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 analysis 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.

[Ted Tenthoff, Piper Jaffray]

Okay. It makes a lot of sense. Thank you.

[Robert Blum, President and Chief Executive Officer]

Thank you.

[Operator]

Your next question comes from the line of Gil Blum with Needham and Company. Your line is open.

[Robert Blum, President and Chief Executive Officer]

Hi, Gil.

[Gil Blum, Needham and Company]

Hello, everyone. It's Gil on for Chad. A bit of modeling question. You guys gave guidance at the end of last year and that seems like spends a bit high for this quarter. Are you guys reiterating guidance? I just want to make sure.

[Robert Blum, President and Chief Executive Officer]

I'll turn it over to Ching to respond to that.

[Ching Jaw]

So no, we’re not reiterating guidance. So the guidance remain the same. Our net cash burn for the year will be between $85 million and $90 million. There is spending seasonality based on the progression of clinical trials for a biotech company, so the fact that the Q1 spending might be a little bit higher than you expect, there is nothing of concern.

[Robert Blum, President and Chief Executive Officer]

Just to clarify, we are reiterating guidance. We’re not revising guidance. We’re keeping guidance as it was in the Q4 earnings call.

[Gil Blum, Needham and Company]

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 if 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?

[Fady Malik]

I think, I would argue that it’s important to patients throughout their disease progression and therefore they sure don't want to be a three. Once they become a three, they’d like to stay there as long as they can before they become a two. 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 of the disease they are.

[Robert Blum, President and Chief Executive Officer]

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 one point a month in that population, but it doesn’t decline uniformly across all subgroups, so what Andy was mentioning at one 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.

[Gil Blum, Needham and Company]

All right. Thank you very much for the clarification. That helps a lot.

[Robert Blum, President and Chief Executive Officer]

Thank you.

[Operator]

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

[Robert Blum, President and Chief Executive Officer]

Good afternoon, Jeff.

[Jeff Hung, Morgan Stanley]

Thanks for taking the questions. In the last few months, you mentioned that there was a scenario where you might deprioritized 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?

[RobertBlum]

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 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.

[Jeff Hung, Morgan Stanley]

Great, thanks. And now that the FORTITUDE 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?

[Robert Blum, President and Chief Executive Officer]

Yes. I think with -- again with the data in ALS, data we have in SMA the question is to how will the neuromuscular program come together and in particular what doses will we use going forward. The 300 milligram dose we use 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’re 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.

[Fady Malik]

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 toward our cardiovascular medicines vertical.

And therefore, we have to reevaluate some of these things. What’s noteworthy is that there is 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 estimate 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 are 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.

[Jeff Hung, Morgan Stanley]

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 are thinking about this program if you think that you would partner out certain geographies. Thanks.

[Robert Blum, President and Chief Executive Officer]

Yes. Another good question. So with regard to CK-274, 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 through 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.

[Jeff Hung, Morgan Stanley]

Thank you.

[Robert Blum, President and Chief Executive Officer]

Thank you.

[Operator]

And we have no further questions at this time. I'll turn the call back to the presenters for closing remarks.

[Robert Blum, President and Chief Executive Officer]

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 among 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 the 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.

[Operator]

Thank you to everyone who joined us today. This does conclude today’s conference. You may now disconnect.