Good afternoon. I'm Serge Belanger , one of the healthcare analysts at Needham. Want to welcome everybody to Needham's 25th Annual Healthcare Conference. For our next fireside chat session here this afternoon, we have Cytokinetics, like an emerging specialty cardiology disease company. Started commercializing their first product earlier this year, and I think still has some important clinical development catalysts coming up as well. From the company, we have Fady I. Malik, Executive VP of R&D, as well as Andrew Callos, who's the Chief Commercial Officer of the company. I'll hand it over to you gentlemen for a quick overview of the company, and then we'll jump to Q&A.
Sure. Thank you, Serge. As probably many listening know, Cytokinetics is a company that's been around for quite some time now, having really pioneered the modulation of muscle contractility as the therapeutic mechanism, both in heart failure with omecamtiv mecarbil and now in hypertrophic cardiomyopathy with aficamten, or now known as MYQORZO, our first approved product, which received FDA approval at the end of 2025, approval in China as well at the end of 2025, and then the European Commission decision soon to follow there in February of this year. It's been an exciting beginning of 2026 for us as we've launched MYQORZO in the United States, and we're preparing to do so in Europe as well.
Our partner, Sanofi in China, is also moving forward with the launch there, and we're very excited to see MYQORZO get out to patients, as I'm sure you'll hear about more later on in this talk. With that, I'll just turn it back to you, Serge, and we could go straight to Q&A.
All right. Maybe we'll start with the commercial launch of MYQORZO. Product was approved in late December, launched in 1Q. Andrew, maybe just highlight for us the differentiation. I think there was a lot of focus on approval and the differentiation of the label and the REMS versus the product that's already in the market. What are some of the key differences that are worth highlighting?
Sure. The research we've done market research-wise really led to our positioning and our overall campaign. The differentiation really starts with efficacy in terms of the potential ability to make patients improve symptoms fairly rapidly with the ability to titrate as early two weeks and every two weeks, but with a window of flexibility that titration could occur within two weeks or all the way up to eight weeks. A six-week window. Rapid onset of effect, flexibility in titration, and in our clinical trial, we saw no symptoms of heart failure or heart failure hospitalization associated with EF lowering, which also is a point of differentiation that we certainly highlight in our campaign. The campaign generally, we typically start with efficacy. We talk about those safety elements that are important for physicians to understand and know.
The drug-to-drug interaction, the lack of drug-to-drug interaction, monitoring that is needed for REMS, and the dosing, these are the elements in terms of reasons to believe, if you will, but it really does start with the efficacy component, given the speed of onset.
Got it. Like we mentioned earlier, launch got underway in January. Maybe just highlight how many reps are out there, and what has been the initial focus of that launch?
Sure. We have over 125 commercial field sales colleagues in the U.S. that are focused on both market access as well as driving demand. There's really the phases of launch. There's two phases of launch we're really looking at. The first phase that we're in now is those we call velocity accounts. There's about 750 prescribers who were 80% of the CMI market today. Those velocity accounts is where we're focused with the goal of achieving greater than 50% NBRX share, new to brand prescriptions, i.e., new patients. All the new patients who get added this year, that more than half of them would be on MYQORZO. That's phase I of launch, and that's where we are today. Phase II is the increased breadth. MAPLE certainly will help accelerate that, as will guidelines, assuming that MAPLE will help inform guidelines.
Phase II will be to increase breadth of prescribing. We're calling on around 11,000 cardiologists, the vast majority who have never written a CMI, probably around 8,000 or so, maybe 7,500 who have never written a CMI. Again, 700 of those 11,000 we call on are writing 80% of the market. Phase I is depth, do well in where the vast majority of patients are being treated with the CMI. Phase II then is expand prescribing. We already are seeing some expanded prescribing in our first quarter, which we'll highlight in our earnings call.
Got it. On the reimbursement process here, obviously, new product, you're starting off at zero. How do you expect it to ramp up? I guess in the initial phase, is it mostly medical exceptions or quick start programs that provide access to patients?
Sure. The vast majority of the CMI market today is in Medicare, over 60%. In Medicare, we're nearly at comparable access to CAMZYOS. Most of Medicare is not officially covered, if you will. It goes through medical exception. We're getting reimbursed very successfully through Medicare today. Medicare, we're expecting parity this quarter. We're getting close to that position already. Commercial is about 30% of the overall, a mix of prescriptions. Commercial will ramp more slowly. Commercial, we do have some level of coverage by plans. It's a plan-by-plan decision. Most of the larger plans have what they call new-to-market blocks in place while they're reviewing the clinical details of MYQORZO to add to formulary.
We do expect that by the fourth quarter of this year that we'll have comparable commercial access to CAMZYOS, and we're on target and track to do that based on what we've achieved so far. For those who are commercially insured who don't have access, we do have a bridge program where a patient can receive up to 12 months of free drug while these plans go through that review process, or an individual goes through a medical exception or a prior approval. The Medicare side, we can reimburse up to two months free while they're going through the review process as well. We do have support programs in place while coverage is coming online. To date, the commercial side, there's been a little bit of friction point in terms of slowing launch down, but not meaningfully.
Okay. Going back to Medicare, you mentioned most of it's getting through medical exception.
Correct, through medical exception.
You mentioned parity. Is that parity to CAMZYOS or parity to other products?
Parity to CAMZYOS.
Okay. Got it. Okay. I believe in your last launch update for Q4, which was late February.
Yep.
I don't remember the exact date, but remind us again, how many docs had been trained on the REMS? I don't know if you gave any patient start details at that point, but if there's any warehouse patients that were awaiting approval and availability of the product.
Sure. At that earnings call, that was the fourth quarter earnings call, we were, I think, three weeks or so into our product approval or available, I should say. Approval did occur at the end of December, the second half of December. Product was available the second half of January, as was the REMS program. At that earnings call, we talked, I think it was a little over 700 REMS-certified HCPs, if I recall correctly. That number has obviously grown significantly, and we'll give those metrics at our earnings call, what those numbers look like in terms of prescribers. Same with patients. What I can say is that we track, as you'd expect, many metrics associated with launch and trajectory of launch. We're looking at patients, time to paid dispense. We're looking at things like coverage, the number of hospital pharmacies that can order.
We're tracking from a metric point of view, but at each metric we look at, we're either at or above what our internal expectations were for the first quarter. Obviously, we'll share many of those metrics in our earnings call.
Okay.
Oh, I'm sorry. Warehousing patients you asked.
Yeah.
I can't point to a metric. It's hard to track exactly what that number is. There were many physicians who told us that they did warehouse some patients, and we do have probably on the end of the spectrum of those who have many patients that were warehoused, that have more than maybe would be typical for a launch for a subset of physicians. It's really hard to give you a number in terms of number of warehouse patients. We know it occurred. I know there's 10+ physicians who stated they had warehouse patients, but I don't know to what effect that is.
Okay. Should we still look at the launch of CAMZYOS as potential proxy for how things could unfold for MYQORZO, or kind of a baseline on which you can potentially improve upon?
Sure. I think the MYQORZO launch, we did point to CAMZYOS as same market, not that different in timing, kind of same environment from a payer point of view. Obviously, a second to market to a large pharma with lots of resources that was ambitious. Our point of view would be despite second to market, despite sharing or competing for patients, and growing the market overall, the expectation that we have is that MYQORZO will be, from a launch trajectory, at or better than where BMS launched in their first year. We're maintaining that point of view.
Okay. I think you've already filed the MAPLE data to update the label.
That's correct.
That was done over this recently, I imagine?
Yeah.
Just curious how you expect that could change the overall kind of treatment paradigm. I'm asking, I guess, are CMIs still kind of second-line after beta blockers and the other options that are currently used for OHCM?
Sure, maybe I'll start backwards. I'm not expecting beta blockers not still to be first-line. I think really what MAPLE will do from a payer point of view is likely make less restrictive utilization management criteria, less restrictive prior auth criteria.
Okay.
Some payers have two steps, both beta blocker and calcium channel blocker. Having less getting patients on a CMI faster from a reimbursement point of view is really what MAPLE will do in the near term. Beta blockers do work for some. I know they don't change gradient as the MAPLE saw, which obviously is a key indicator of efficacy, but beta blockers do help some patients feel better. They're easy to get reimbursed. They're cheap. They're still going to play a role, likely. The expectation, I think, our base case is in 2027 guidelines would be updated, as well as by the end of this year, fourth quarter this year, our label would be updated. It's not a new indication. It's the same patient population. It's just further describing the utilization, relative to standard of care.
Beta-blockers are first-line therapy in the treatment guidelines, and I'm not expecting that to be changing overall. I think what MAPLE does in terms of commercially, and this really gets back to those two phases of launch where I talked about in the 750 Velocity accounts, or prescribers, where our focus is achieving greater than 50% new-to-brand share, which then over time would be leading the market. Phase two is expanding to general cardiology.
Yeah.
Where MAPLE really does add to, and we did our market research several times, and we got a pretty consistent answer, is that when a general cardiologist understands that what they're using, i.e., beta-blocker, doesn't impact gradient or efficacy or many biomarkers, and they're not impacting the underlying disease, they feel a call to action to utilize a therapy specific for the disease. If guidelines are updated to include CMIs faster to use or even alongside beta-blockers as a first-line therapy, that'll certainly fuel that as well, as general cardiology is definitely influenced from a guideline and want to follow best practice from a medical point of view and where the evidence is. We certainly see MAPLE as a major accelerator for the breadth of prescribing increase, which our expectation would probably start next year on a larger scale.
Clearly, you're going to get a label change for MYQORZO, but do you expect the MAPLE data to also impact the CMI class in general, including CAMZYOS? Will the changes simply just apply to MYQORZO, I guess is the question.
Yeah. From a guideline point of view, maybe Fady has a point of view on this. All I can say is that I'm sure it'll help the category. It informs patients. From a clinical trial point of view, MAPLE really is the only thing that informs that. From a promotional point of view, Cytokinetics obviously will be promoting the MAPLE data.
Yeah
Given where the evidence got generated from, which certainly provides a level of advantage. From a guideline point of view, I'm certain that guidelines will reference this trial, et cetera. How they're named, that's really hard to say. I don't know, Fady, if you have a point of view on that.
Historically, the U.S. guidelines have been very driven by published data, and they don't extrapolate beyond published data. Sometimes the European guidelines may be a bit more flexible in that regard, I suppose. I think, as Andrew says, we're the only group that has the data that can really speak to it. It's an important contribution to the field to understand how their standard of care performs and how aficamten performs relative to that. We hope it elevates cardiac myosin inhibitors in general from the bottom of the guidelines to higher up. Right now, they are kind of the last line of therapy, and I can tell you the data for calcium channel blockers and disopyramide are not a whole lot better than that for beta blockers. We hope that they'll be considered on par with first-line therapy.
Yeah. Andrew, you mentioned you were getting ready to launch in Europe. Maybe just highlight the market opportunity here versus what it is in the U.S., and remind us of any inroads that CAMZYOS has been able to achieve in the European market for CMIs.
Sure. We entered the U.S. market with broad awareness of the CMI category, as well as MYQORZO. Europe is the same. When you enter a specialty market where it's a subset of physicians or KOLs at major academic centers, many of these centers were in clinical trials, and the awareness is also high. We are launching in Germany in the second quarter, so the quarter we're in. Our expectation is that we'll launch in probably one or two other markets by the end of the year and all major markets across Europe, Western Europe, in 2027. That's our expectation. The market opportunity from a patient population point of view is similar to the U.S. There's a little over 100,000 obstructive HCM patients across the European markets where we'll commercialize that are both symptomatic and eligible for treatment of a CMI.
Obviously, the difference in Europe is where you get central approval, plus the U.K., plus Swissmedic. Those approvals allow you regulatory approval, but it doesn't allow for reimbursement. Reimbursement is done on a country-by-country basis, which is why we go with Germany first. Germany allows you to launch with free pricing while you're negotiating. The other markets, you have to get access, and reimburse at the government level as the government is the payer before you can launch, and hence, that's why the launch is kind of spread out in Europe overall. Given the population is the same, the only difference really is price point. The price point in Europe is generally around 15%-20% of the U.S. That's what we're expecting.
Overall, Europe at peak, when you're in peak in U.S. and peak in Europe will be about 15% of the overall market for us, meaningful. I know many companies do not, especially for their first launch in Europe. They really focus on the U.S. I think the difference in this market is it's because it is a specialty cardiology market where, one, you need a small footprint. You don't need a lot of sales representatives. We only have headquarters-based personnel in the EU4 and U.K. We hire reps and medical colleagues when reimbursement occurs on a country-by-country basis. We're doing it in a very efficient way from an OpEx point of view, and confident that no one could bring MYQORZO to market better than we can.
I think the combination of what's really required from an investment point of view, understanding the market, understanding and knowing many of the KOLs, and doing it in a cost-efficient way, even leveraging resources in the U.S. to do so, is what gave us the confidence that we can be successful in Europe.
Yeah. Well, we'll be looking forward to the Q1 update on the MYQORZO launch, that's for sure. Let's move on to ACACIA-HCM and NHCM. Fady, you have a big data readout coming up. I think it's this quarter. I don't know if you've given more granularity on that timing besides Q2. Maybe we can start there. Just Q2 still?
That's a simple one. Yeah, I know we haven't updated our guidance.
Yeah
Beyond Q2.
All right. It could be tomorrow.
I'll say it won't be tomorrow. How about that?
All right. Thank you. Maybe to start off with, just highlight the differences between OHCM and NHCM, and then we can talk about the ACACIA study design and the endpoints.
Right. Well, with OHCM, you have a clear biomarker of disease severity, which is the gradient, and it's a means of selecting patients that may receive sizable or less sizable treatment effects. NHCM, by definition, there is no gradient, and so you rely on other things to help you assess patient severity, things like biomarkers of NT-proBNP, patient symptoms, reduced KCCQ scores. The most important thing, obviously, is making sure that you have NHCM patients in the study, and NHCM is often a kind of a visual diagnosis. It certainly is a genetic disease in many, but you don't always have the genetics available at the time patients are eligible for trials. The visual appearance on echocardiography is really what drives diagnosis, and in fact, the guidelines don't actually require a genetic diagnosis.
It's a diagnosis of visualization and thickness of the heart. In our trial, we have, obviously, entry criteria that help us select patients, but we also have trained HCM expert who can visually assess each of the echoes of the patients coming into the trial, and help to qualify them properly.
I guess based on what you saw in the REDWOOD-HCM data, is that what gives you confidence for ACACIA?
Yeah
Warnings from the ODYSSEY-HCM trial? Is it a combination of both?
I think it's all the above. If you look at our development program in NHCM, it built on what we obviously established with the obstructive patients, range of tolerable doses, how do we approach dosing and avoid treatment interruptions or episodes of heart failure. In NHCM, there's no gradient to tell you when to stop dosing. The strategy is different. It's sort of a maximum effective dose as opposed to a-- I'm sorry, maximum tolerated dose as opposed to a minimal effective dose. And so we piloted that strategy in phase two and it was quite successful. No treatment interruptions. The patients improved their symptoms and functional class, and biomarkers responded in the right way, and the echocardiographic parameters of cardiac relaxation improved as well.
Those patients went on then for an open-label extension, where now they've been studied for more than two years, and we continue to see very positive responses to aficamten, and in most cases, the patients have achieved an NYHA Class I. When you design a phase III trial, one of the most important things is how do you dose the drug? What's the right dose or the dosing scheme? I think we had that quite well described in the phase II. It gives us confidence that the treatment algorithm we're using in phase III is going to be effective at getting patients to the right exposure and not lead to an excessive intolerance or treatment interruptions and other things. The conduct of the trial, I think, also gives us confidence. As I said, we have a very experienced team.
They've been together through the conduct of all our HCM trials from REDWOOD-HCM to where we are today. Finally, I would just say that the ODYSSEY-HCM data were quite encouraging. They didn't meet statistical significance on either of their endpoints, but both endpoints were trending in the right direction with effects on both peak VO2 and the KCCQ that we think will translate ultimately in ACACIA.
I'll ask the question we get from investors, and we'll continue getting until the data reads out. I guess, what's the bar for success on the dual primary endpoints and what is needed for approval?
Well, the last question is an easy one. Nobody knows the answer, right? There's no drug that's ever been approved in non-obstructive HCM, and so there's no real standard set. I think what matters is that you have a drug that's clinically meaningful and impactful. If I believe the data we have from our phase II data, we certainly have a medicine that is meaningful and impactful in those patients. The simplest thing would be for both endpoints to be statistically significant. We powered the trial in such a way that I think if they're statistically significant, then the effect size is meaningful. We didn't overpower it to come up with non-meaningful treatment effects. The statistically significant number should yield us a clinically meaningful effect.
Obviously, all of this is new ground to be plowed with regulators as we share the data with them and begin to discuss the effectiveness of aficamten in this patient population.
In terms of clinically meaningful, is that a five-point delta on KCCQ? What does it look like?
We powered the study. It's a 90% power at a five-point change in KCCQ relative to placebo. We also have good, if you will, the minimal detectable difference that we think would be statistically significant is closer to three and a half-four. The same thing goes for peak VO2, where we powered it for change in 1.0, but a statistically significant difference could probably be as low as 0.6-0.7. I think anything in that range, the higher the number is, the more obvious. As I said, there are no established standards in NHCM, and that's what the data will inform.
Okay. You mentioned obviously the most straightforward path here is stat sig on both endpoints. What happens in the alternative where only one is stat sig, and it just becomes an FDA decision, or you still have confidence that it could support approval?
It's always the totality of the evidence, and so it wouldn't look good, for instance, if they went in the opposite direction. That would not be a great scenario. On the other hand, if one's a near miss and the other one's positive, that's good. The other secondary endpoints are important as well. The NYHA class, we have another measure of exercise performance. There are other indicators there of effects and biomarkers that we think are important. So I think the overall picture ultimately will inform the discussion. I think also just to think about this as it's not a first approval for aficamten.
The drug's already out into the real world. And so when you think about a patient population with NHCM that really have no effective treatments, none of the medicines like beta- blockers, calcium channel blockers, and so forth, have ever been shown to be effective in NHCM. There's no surgical alternative here like in OHCM. You'd hope that there'd be also regulatory flexibility exercised in that particular scenario.
One of the other questions we get is the level of detail that we should expect in the initial readout. Are we going to be able to see? Yeah, that's basically it. How much are we going to be able to see? How much will you keep for disclosure at a medical meeting?
Well, that's still really a matter of negotiation, right? We know what our obligations are. We want to obviously meet them, but we also want to try and preserve a presentation of the trial at the ESC, which would be what we would target. We go through a process with the meeting organizers at the ESC, and we'll see where we land.
Okay. Full details will be at ESC in late August?
Well, we haven't been accepted there, nor have we even submitted anything, but I presume this is going to be an important study for them and would eventually make its way to the program.
Got it. Okay. Before we move on to pipeline, we did have one question come in regarding, maybe for Andrew, how do you think about launching a drug outside the U.S. given the uncertainty around MFN?
Yes, sir. MFN, the GUARD Model in MFN is really where the impact would be. Obviously, this is still a fluid situation and it's something we're tracking very closely. We're not changing our plans currently in terms of launching, even if MFN GUARD were to hit, one, at five years. Two, it would likely not be effective to 2028 because that would take that long for us to likely hit the threshold where it kicks in. If it kicks in, then we only may have three years of impact, or maybe four, at 20% of our Medicare population, which is a single-digit gross-to-net impact. If it launched the way that it's at least proposed in the latest we've seen around it.
It's something we're monitoring, something that we feel we can manage if it occurs, but nothing that we're going to change our current plans, our strategy, or have access to our MYQORZO for patients in Europe. We'll adjust if we need to, if it gets more onerous than the initial proposal. Many of the experts we talk to feel like, if it is implemented, it'll likely still be adjusted, maybe even with an orphan carve-out or other mechanisms maybe to lessen the impact. We'll continue to monitor it.
Okay. Another question for Fady regarding the ACACIA study. Remind us of the alpha levels that you need to meet for the co-primary endpoints and the alpha recycling between those endpoints.
The endpoints are split evenly for the primary analysis, 0.025 on KCCQ and 0.025 on peak VO2. There is some accommodation for recycling alpha that allows for slightly more power and higher alpha to be pulled back until one of the endpoints should it fail. I think I don't need to go into the details really of that here.
Okay. Let's move on to the pipeline. Well, I guess omecamtiv phase III COMET-HF trial is ongoing. Goal for this year is just recruitment. Is that kind of where we are, or are we at a point where we can start talking about timelines for readout?
I think we'll have a better sense of that later this year. I think we're well into the study. All the sites are open for the most part in the U.S., Canada, Europe. We're planning to open China shortly. We see good interest in enrolling this population. We get a lot of positive feedback on the medical need for a medicine that can be used in a severe heart failure population where a standard of care can be tricky to implement because of either effects on blood pressure or kidney function or other things. I think later this year we'll be far enough into enrollment where we can probably project where we think it'll land. From there, down the road, we'll give some estimate of where we think the trial will land from an event.
It's an event-driven trial, so even when you finish enrollment, you're sitting and waiting, counting events until you complete study.
Okay. The earlier stage program in HFpEF, ulacamten, maybe highlight the differences of the mechanism of action here, how it differs from aficamten .
Yeah. Ulacamten, we call it a cardiac myosin inhibitor because it decreases the contractile function of the sarcomere. The binding site for ulacamten is different and unique from that of either aficamten or the mavacamten binding site. It binds on near the regulatory light chain of myosin. It provides sort of a unique biological mechanism to explore in patients. We are enrolling a patient trial now in HFpEF. One of the goals is to understand dosing, and the other goal is to really think about the patient population, where this would be applicable and the breadth of it. That study is called AMBER-HFpEF, and we're in the midst of doing that as a relatively modest dose-finding study right now.
When do you expect results from AMBER-HFpEF, or initial results?
We're enrolling the first cohort. We haven't really said when results would necessarily be available. Hopefully, we'd have some preliminary results by the end of the year. When we decide to report those hasn't really been f irmed up.
All right. We only have a couple minutes left. Maybe just give us an overview of financials and your cash balance runway.
Sure. My disclosure is that you're talking to the R&D guy who's now giving financial guidance. But, so I'll refer you to our quarterly press release at our Q4 for details. But we have over a billion dollars in cash and cash equivalents, very well-capitalized. We have other access to capital as well, either through loans that we can access from our Royalty Pharma deal, or other ways of accessing capital. The company's well-positioned to execute on its goals, which are to launch in Europe this year, to continue to expand the launch of aficamten in the U.S., and then to further its pipeline with COMET-HF being probably the most proximal value creator in the pipeline.
A t the same time, we're interested in growing and continuing to expand the pipeline behind that. I t's an exciting time for Cytokinetics. Lots of balls in the air, good execution along all lines. We look forward to what I think will be a very eventful and satisfying 2026.
All right. I think with that said, we'll have to wrap it up. We're up on time. I want to thank you both for spending time with us this afternoon and giving us an overview of Cytokinetics, and obviously we'll keep an eye out for that ACACIA readout coming soon.
Great. Thank you, Serge.
Thanks for having us, Serge.
That's right.
Yep. Take care.