Okay. Anyways, well, since we started a little bit late, which is totally on me. I'm Emily Field covering U.S. Biopharma here at Barclays. That's how I decided, okay, 'cause I was like, we got the whole squad. CEO Robert I. Blum, and
EVP of R&D, Fady I. Malik. Sung Lee, CFO.
Okay, great. Well, okay, 20 minutes. Let's go. Obviously everyone's just really focused on.
MYQORZO.
MYQORZO launch. I think, you know, people are trying to get some sort of early metrics on what you're going to disclose versus not disclose. You know, now that, what, maybe three weeks in, four weeks in, what can you tell us about the launch thus far?
To underscore, we only launched in late January, so we're really only a month in. The early signs are encouraging. As we said on our earnings call, we're looking at a couple of key metrics. We'll get disciplined in repeating the same KPIs with our Q1 earnings call and afterwards. Ahead of that, what should we be focused on? Ahead of that, we're focused on the following. What's the awareness of MYQORZO? As we went out and did some market research, there's over 90% awareness of MYQORZO among the high-volume prescribers for CAMZYOS, the other cardiac myosin inhibitor. Over 90% of the targeted cardiologists that we've been focused on are already aware of our studies, our product, and have been waiting.
We were encouraged by the fact that many of them had already been warehousing patients awaiting the approval. It was very soon after product was in channel that we already had over 700 cardiologists go through our REMS program, and within days, already dispensing MYQORZO to patients who were prescribed it. That's a very good sign. We saw prescriptions coming not just from the currently 700 cardiologists accounting for over 80% of the CAMZYOS scripts, but we saw prescriptions coming from cardiologists who had never written a prescription. That's encouraging. Then I guess the other early indicator of interest is that we're already getting requests from our medical information hotline for how does one go about switching patients.
Oh, okay.
That's interesting. I wouldn't make more of that than that it's interesting, not yet compelling. We're certainly not going to move the needle for the overall picture of adoption based on switches. But it suggests to me that prescribers who are targets are already aware of differences and can be expected to switch patients who might not be performing at the most optimal levels on the existing cardiac myosin inhibitor, CAMZYOS. Maybe they're on the 2.5 mg or 5 mg dose strength of CAMZYOS. They're still burdened with symptoms, and maybe that cardiologist may be looking to switch that patient.
Yeah, because at least the switch opportunity I don't think is something that you've emphasized as a near-term opportunity.
We won't.
But ...
We won't. It's not.
But-
Gonna drive this business.
I mean, what sort of feedback are you getting from prescribers? Because obviously there is a difference in the REMS, which is, you know, we can just look at full stop. What sort of feedback are you getting in terms of the switch opportunity from initial prescribers?
Again, I don't want to make more of it than what I did-
Yeah.
...which is to say that people understand the differences. I do believe that MYQORZO offers a different experience for physicians from the standpoint of speed of onset of action.
Mm-hmm.
Ability to get to target dose and steady state exposures more rapidly. That's enabling a physician experience, a patient experience that we've been focused on for all the time we've been developing aficamten and MYQORZO.
Mm-hmm.
Our promotion strategy is kind of pillared across safety and efficacy as translates into differentiated label and REMS, but also how do we make this a physician and office experience that's unique to this opportunity and a patient experience and getting patients all the way through to reimbursement as promptly and easily as possible. Because this is all we do and this is what we built our commercial organization around, we think we can build something that's more tailored, custom to this opportunity and bespoke to the market opportunity.
Okay. Yeah. Maybe kind of continuing with the launch story before getting into pipeline, maybe from a financial perspective, how are you thinking about investment in both the commercial organization in the U.S. and also in Europe, which I know takes a lot of time. I just moved back, so I know that takes a lot of time. Yeah, in terms of just sort of the pushes and pulls from a cash balance perspective versus now being a revenue-generating company.
Maybe I'll start, and then I'll turn it over to Sung. We're ambitious. When we think about mission and purpose, we think about bringing this science and medicine to patients globally. As such, we're now launched in the United States.
Mm-hmm.
We're approved in Europe, and we're gonna be launching in Q2 in Germany. Our partner, Sanofi, is approved and launching in China. Soon, afterwards, we expect our partner Bayer to be getting approval and launching in Japan. If you think about our Vision 2030, it speaks to global access to this medicine for the benefit of patients globally, and we're committing to do that at least ourselves in North America and Europe. To that point, how we go about it, we have to be good students of what other companies in front of us have done and what they've learned. We're investing in Europe on a gated basis, stage to reimbursement, as we learn more from Germany, France, Italy, U.K., and Spain. Maybe with that, I'll ask Sung to elaborate.
Yes. Emily, I would say well ahead of the launch in the U.S., we did some things on the finance side to really shore up our balance sheet in order to be able to launch in the U.S., but also in Europe, as Robert said. Going back to May of 2024, we expanded our strategic partnership with Royalty Pharma, which has provided some critical funds in terms of the commercial launch. September of last year, we had a very successful convertible notes offering. We really started this year with a solid balance sheet. We have our capital allocation priorities, and it shouldn't be a surprise, the launch in the U.S. and Europe. Also, as Robert said, investing in our pipeline to advance our ongoing development programs.
We have a very productive research organization and expect us to do some things, additionally in our pipeline in the future.
Okay. Fantastic. Well, yeah, maybe then to pivot about, you know, catalysts that investors are watching very closely, the ACACIA-HCM readout. Perhaps it would be helpful to talk about the setup into this and, you know, obviously the ODYSSEY trial was unsuccessful, and how your trial is perhaps, you know, maybe just from like a structural perspective, tailored a little bit differently. Then we can, I guess, pivot into what are the most important points to look for when we do get that headline.
Yeah. Fady should speak to this in more detail, and I'll just start by saying this ACACIA-HCM study represents an opportunity for aficamten, now called MYQORZO, to be potentially showing evidence of clinical safety and efficacy in a population of non-obstructive HCM, a population that, based on claims data, is roughly equivalent in size to the obstructive HCM population. The difference being that, there are no approved treatments in nHCM and for which, you don't have a gradient, a pressure gradient, to necessarily manage to. It's a market for which there's high overlap in terms of high volume prescribers, but for which the market dynamics are slightly different.
We've designed a study, the same team that we've had in place for over five years that has designed and conducted SEQUOIA-HCM, MAPLE-HCM, FOREST-HCM, CEDAR-HCM, and now ACACIA-HCM, is in place and lending oversight to the conduct of this trial. Under Fady's supervision, we're quite hopeful for what it may read out in results in Q2. With that, maybe I'll ask Fady to speak to it in more detail.
Sure. We went about the process of examining the effect of aficamten in non-obstructive HCM very deliberately. One of the challenges is how do you dose the drug in nHCM? In oHCM, you tend to dose to the minimum effective dose because as soon as the gradient comes below a certain threshold, you stop dose escalation. There is no gradient in nHCM. The strategy is one more of maximum tolerated dose. In that context, you need to understand what doses are well-tolerated, you know, what's the right way to titrate dose, what are the right thresholds.
In phase II, we piloted that very deliberately testing doses of 5 mg, 10 mg, and 15 mg, escalating dose for ejection fraction of 60% or greater, holding dose steady if you're between 50% and 60%, and decreasing dose, not interrupting dose for a EF of 40%-50%. That strategy worked very well. We didn't see any treatment interruptions. We had a couple asymptomatic EFs below 50%, which responded immediately to down titration. Going from, you know, 40 patient experience to now a 500 patient experience, we're pretty confident in the dosing paradigm that it shouldn't lead to treatment interruptions, and it shouldn't lead to, you know, kind of being stuck on low doses. You know, when you looked at the ODYSSEY data, that was one of the issues that they had in ODYSSEY.
They had about a 20% treatment interruption rate, and there was some evidence that, you know, a sizable portion of the population were probably treated with the lowest doses of 1 mg, 2.5 mg, or 5 mg, as supposed to being able to escalate to higher doses. Dosing, very important. I think we got it right. We'll know when we unblind the data. You know, secondly is conduct of the trial. You know, as Robert said, we've done six trials, you forgot REDWOOD-HCM, in this area, with the same team of experienced physicians that have expertise in HCM, myself included, and then a clinical operations team, core labs that have worked with us through this entire period.
We've optimized over that time how do you train sites in terms of the endpoints, KCCQ, pVO2, echoes, acquiring echoes. How do you qualify patients for the study? You have entry criteria, but NHCM is kind of a visual diagnosis. If you really want to know what you're getting in the trial, you have to look at the echoes, and we have a team that does that. I think in terms of setup and the way the trial is conducted, we feel very confident that, you know, there are no methodological issues that should lead to results that are ambiguous. What we saw in terms of phase two data were encouraging. You know, we saw patients whose biomarkers improved, their echoes relaxation parameters improved, and their KCCQs and NYHA class improved.
We've seen that now, you know, for over two years in our open-label extension. We like the setup going into-
Yeah.
...the trial.
Just to confirm investor expectations, because you will hopefully want to present the full data side at a medical meeting, the press release that will come out in Q2 will be mostly qualitative.
I think in general, that's what I would expect.
Yeah.
We'll try and see what we can get into it, but it's a negotiation between us and, you know, the people that hold the cards in terms of the medical meeting. It is important that we get these data out in front of a large medical audience. You know, there's a tremendous amount of press around these large medical meetings besides the people that are in the audience, which number in the thousands. The investor community is important. Obviously, the cardiology community, getting the message to them is also, in the long term, very important to us.
In terms of, like, from a commercial perspective, like a halo effect if ACACIA-HCM were to be successful, like, do you see that as having an impact on current MYQORZO sales?
Yeah. I think it's legitimate to assume there's some form of halo effect that if we hit on ACACIA-HCM, that'll bleed over to OHCM.
Mm-hmm.
Just simply because it's reinforcing of the clinical safety and efficacy in an adjacent population. Again, I wouldn't put a lot of stock in that until such time as.
Okay.
Hopefully it's reflected in FDA-approved label, and we can promote to it, and the guidelines will be updated to reflect the use of MYQORZO in that population. But I do know there's high level interest in ACACIA-HCM, and it might translate into some wider adoption, maybe even for the full category, in oHCM.
Okay, great. Well, maybe like taking a step back. I used to cover Novartis, but obviously, and there was a lot written in the media, and I don't want to rewrite history. Maybe now that you're in your first commercial launch, the huge catalyst coming up, maybe it would be helpful to just maybe take a step back and think about, like, from a strategic perspective, how you see Cytokinetics, and also going it alone in Europe, which I thought was a very interesting decision just because a lot of your competitors that are launching cardio drugs choose a partner in Europe. Maybe it would be a good talking point, just talking about like overall strategic vision and then pipeline beyond MYQORZO.
Yeah. Why did we go to Europe? We committed to Europe in part because we can, and I would argue most biopharma companies shouldn't, because they don't have the redundancy in the pipeline or the business prospects where they can do that in a way that returns on investment, the way we believe we do. MYQORZO, even as would be priced at $0.15-$0.20 on the dollar relative to U.S. pricing, can be a profitable opportunity in Europe if we do it smartly, and that's an oHCM by itself. Add in nHCM, and it's even more so. Would we have gone to Europe if we hadn't built this company the following way?
Fady and I started this company 27+ years ago, and we've always intended to be a commercial enterprise, always rooted in one area of science and biology that we pioneer and lead and better than anyone else, and for which we have a portfolio of programs all directed to the same molecular target, all directed to the same concentrated customer segment, where we have the ability to build a specialty cardiology franchise, the likes of which, frankly, don't otherwise exist in peer group companies. We're enabled to go forward and build a very valuable company for science, medicine, and patients and also shareholders, and do that as an independent, autonomous company. Because frankly, it's a bit of a mature birth to commercialization as we go forward with MYQORZO in oHCM and hopefully soon afterwards in nHCM.
Right behind it, we have omecamtiv mecarbil being developed in a confirmatory phase III study in advanced heart failure, a very high unmet need, and ulacamten, another cardiac myosin inhibitor, in a subset of patients with advanced HFpEF. This is, if you will, a somewhat uncommon situation of a franchise.
Pipeline moving forward from clinical research through regulatory sciences and into the marketplace. We think that can become a very impactful company both for patients and shareholders.
Yeah. That's a problem. Maybe just to touch on the pipeline assets behind aficamten, and when we might see additional clinical data on that.
Sure. You know, the most advanced program is the omecamtiv mecarbil program. It's a drug that's a cardiac myosin activator. It's being studied in severely reduced ejection fraction heart failure. These are patients, the number in the hundreds of thousands in just the United States. They've kind of exhausted most medical therapies and are still hospitalized, have a very high risk of mortality. We are executing COMET now, about 2,000 patient trial. It's enrolling this year. It'll enroll through the early part of 2027, event-driven with a clinical composite outcome of heart failure events and CV death and a couple other components. That trial, talk about setup.
You know, that trial was set up by a positive 8,000-patient trial in heart failure that met its endpoint, had an 8% reduction in heart failure events and CV death. While it didn't lead to a drug approval, you know, it gave us very strong evidence for where the treatment effect was concentrated, and ultimately, we designed COMET in that population. I think, you know, when you look at pipeline, we have ACACIA-HCM, and ACACIA-HCM potentially leading to label expansion for aficamten. Following that, we have omecamtiv mecarbil and again, what you might consider kind of a specialty cardiology population. Behind that, we have ulacamten, which is a different cardiac myosin inhibitor, that we're examining in heart failure with preserved ejection fraction-
Mm-hmm.
...which we think is an adjacent population to some of the nHCM type of patients. That's in phase II, kind of a dose-finding phase II study now called AMBER-HFpEF.
Okay. Well, great. I think we're just about at time. Robert, if you wanna give any last words, just 'cause it's such an exciting year for the company.
Yeah, I'll just end by.
Before we conclude.
Maybe the same way we started. You know, this is a team that's been in place together for a long time. We've committed to an area of biology we know better than anyone else, and it's yielding great clinical evidence to support therapeutic hypothesis across different specialty cardiology indications. As that translates to a business, we've now turned the page onto commercialization. We should be measured by how quickly we can grow the top line and do that in a responsible way to our fiduciary obligations, both with regard to the P&L and also shareholder value. I think we're on our way. This year will be one where not only should we be assessed by how well we commercialize MYQORZO in the U.S. and Europe, but how do we grow that opportunity? Hopefully, ACACIA-HCM shines a light on a new opportunity for nHCM.
Great. Well, thank you so much for coming, and thanks, everybody. We'll keep going on with the conference. Thank you.