Cytokinetics, Incorporated ($CYTK)

Anyway, since we started a little bit, it's totally on me. I'm Emily Field covering U.S. biopharma here at Barclays, and we are -- that's why I got the whole squad. So CEO, Robert Blum and...

EVP of R&D, Fady Malik, Sung Lee, CFO.

Okay. Great. Well, okay. So 20 minutes, let's go. So obviously, everyone is just really focused on MYQORZO launch. And I think if you are trying to get some sort of early metrics on what you're going to disclose versus not disclosed. So now that, what, maybe 3 weeks in, 4 weeks in, what can you tell us about the launch thus far?

So to underscore, we only launched in late January, so we're really only a month in, but the early signs are encouraging. And as we said on our earnings call, we're looking at a couple of key metrics. We'll get discipline to repeating the same KPIs with our Q1 earnings call and afterwards. But ahead of that, what should we be focused to? Ahead of that, we're focused on the following: what's the awareness of MYQORZO. So as we went out and did some market research, there's over 90% awareness of MYQORZO amongst the high-volume prescribers for Camzyos, the other cardiac myosin inhibitor. So over 90% of the targeted cardiologists that we've been focused to 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. And it was very soon after a 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. So 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. So that's encouraging. And 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, so 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. So maybe they're on the 2 to 5 -- 2.5 or 5-milligram dose strength of Camzyos. They're still burdened with symptoms and maybe that cardiologist may be looking to switch that patient.

Yes. Because at least the switch opportunity, I don't think is something that you've emphasized as a near-term opportunity.

Then we won't. We won't. It's not going to drive the business.

Well, I mean, what terms of feedback are you getting from prescribers? Because obviously, there is a difference in the REMS, which is we can just look at full stop. But what sort of feedback are you getting in terms of the switch opportunity from initial prescribers?

So again, I don't want to make more of it than what I did, which is to say that people understand the differences. But I do believe that MYQORZO offers a different experience for physicians from the standpoint of speed of onset of actions, ability to get to target dose and steady state exposures more rapidly. That's enabling of a physician experience, a patient experience that we've been focused to for all the time we've been developing aficamten MYQORZO. 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 in getting patients all the way through to reimbursement as promptly and easily as possible. And 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, accustomed to this opportunity and bespoke to the market opportunity.

Okay. Yes. And then maybe kind of continuing with the launch story before getting into pipeline. 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 -- I just moved back. So that takes a lot of time. But yes, in terms of just sort of the pushes and pulls from a cash balance perspective versus now being a revenue-generated company?

Maybe I'll start, and then I'll turn it over to Sung. So 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. We're approved in Europe, and we're going to be launching in Q2 in Germany. And our partner, Sanofi, is approved and launching in China soon afterwards, we expect our partner, Bayer, to be getting approval and launching in Japan. So 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. And we're investing in Europe on a gated basis, stage to reimbursement as we learn more from Germany, France, Italy, U.K. and Spain. So maybe with that, I'll ask Sung to elaborate.

Yes. So 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. So 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. And then September of last year, we had a very successful convertible notes offering. So 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. But also, as Robert said, investing in our pipeline to advance our ongoing development programs, but also we have a very productive research organization and expect us to do some things additionally in our pipeline in the future.

Okay. Fantastic. Well, yes, maybe then to pivot about catalysts that investors are watching very closely the ACACIA readout. Perhaps it would be helpful to talk about the setup into this and obviously, the ODYSSEY trial was unsuccessful and how your trial is perhaps maybe just from like a structural perspective, tailored a little bit differently. And then we can, I guess, pivot into what are the most important points to look for when we do get that headline.

Yes. So Fady should speak to this in more detail, and I'll just start by saying, this ACACIA study represents an opportunity for aficamten now called MYQORZO to be potentially showing evidence of clinical safety and efficacy in a population of nonobstructive HCM, a population that based on claims data is roughly equivalent in size to the obstructive HCM population. But the difference being that there are no approved treatments in nHCM and for which you don't have a gradient to pressure gradient to necessarily manage to. So 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 5 years that has designed and conducted SEQUOIA, MAPLE, FOREST, CEDAR, and now ACACIA, is in place and lending oversight to the conduct of this trial. And under Fady supervision, we're quite hopeful for what it may read out in results in Q2. And with that, maybe I'll ask Fady to speak to it in more detail.

Sure. So we went about the process of examining the effect of aficamten in nonobstructive HCM very deliberately. One of the challenges is how do you dose the drug in nHCM. And oHCM, tend to dose to a minimum effective dose because you -- as soon as a gradient comes below a certain threshold, you stop dose escalation. There is no gradient in nHCM that strategy is one more of maximum tolerated dose. And so in that context, you need to understand what doses are well tolerated, what's the right way to titrate dose, what are the right thresholds. And so in Phase II, we piloted that very deliberately testing doses of 5, 10 and 15 milligrams, escalating dose for ejection fraction of 60 or greater. Holding dose steady if you're between 50 and 60 and decreasing dose, not interrupting those for ES of 40 to 50. And that strategy worked very well. We didn't see any treatment interruptions. We had a couple asymptomatic ES below 50, which responded immediately to down titration. And so going from 40 patient experience to now a 500 patient experience, we're pretty confident in the dosing paradigm that shouldn't lead to treatment interruptions and it shouldn't lead to kind of being stuck on low doses. 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 a sizable portion of the population will probably treated with the lowest doses of 1, 2.5 or 5 milligrams and as opposed to being able to escalate to higher doses. So dosing, very important, I think we got it right. We'll know when we unblind the data. Secondly is conduct of the trial. As Robert said, we've done 6 trials, you forgot REDWOOD 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, echos, acquiring echos, how do you qualify patients for the study, you have entry criteria, but nHCM is kind of a visual diagnosis. And so if you really want to know what you're getting in the trial, you have to look at the echos and we have a team that does that. So I think from terms of setup and the way the trial is conducted, we feel very confident that there are no methodological issues that should lead to results that are ambiguous. What we saw in terms of Phase II data were encouraging. We saw patients whose biomarkers improve, their echos relaxation parameters improved and their KCCQ and NYHA class improved, and we've seen that now for over 2 years in our open-label extension. So we like the setup going into the trial...

And 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. We'll try to see what we can get into it, but it's a negotiation between us and 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. 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. And so the investment community is important. Obviously, the cardiology community, getting the message to them is also in long term, very important to us.

And then in terms of -- like from a commercial perspective, look, a halo effect if ACACIA were to be successful, like do you see that as having an impact on current MYQORZO sales?

Yes. I think it's legitimate to assume there's some form of halo effect that if we hit on ACACIA that will bleed over to oHCM is 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 that 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, 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. So I used to cover Novartis but obviously -- and there was a lot written in the media, and I'm not -- don't want to rewrite history. But -- so maybe now that you're in your first commercial launch, a huge catalysts coming up. Maybe it would be helpful to just maybe you could step back and think about like from a strategic perspective, how you see Cytokinetics and also going in alone in Europe, which I thought was a very interesting decision just because a lot of your competitors that are launching cardio drugs you choose a partner in Europe. So maybe it would be a good talking point just talking about like overall strategic vision and then pipeline beyond MYQORZO?

Yes. So 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. So MYQORZO, even as would be priced at $0.15 to $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. But would we have gone to Europe if we hadn't built this company the following way? Fady and I started this company 27-plus 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. So 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. So 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, and we think that can become a very impactful company both for patients and shareholders.

Yes. That's super helpful. Maybe just to touch on the pipeline assets behind aficamten and when we might see additional clinical data on that?

Sure. The most advanced program is the omecamtiv mecarbil program. It's drug that's a cardiac myosin activator is being studied in severely reduced ejection fraction, heart failure. So 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, having a very high risk of mortality. So we are executing COMET now, about a 2,000-patient trial. It's enrolling this year. It will enroll through the early part of 2027, event-driven with clinical composite outcome of heart failure events and CV death and a couple of other components. That trial, talk about setup, 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. And while it didn't lead to a drug approval, it gave us very strong evidence for where the treatment effect was concentrated and ultimately, we designed COMET in that population. So I think -- when you look at pipeline, we have ACACIA, ACACIA 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 another cardiac, a different cardiac myosin inhibitor that we're examining in heart failure with preserved ejection fraction, which we think is an adjacent population to some of the nHCM type of patients. And that's in Phase II kind of a dose-finding Phase II study now called AMBER-HF.

Okay. Well, great. I think we're just about at time. So, Robert, if you want to give any last words just because it's such an exciting year for the company, just to conclude.

Yes. I'll just conclude maybe the same way we started. 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 on to 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, and 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 U.S. and Europe. But how do we grow that opportunity. And hopefully, ACACIA shines a light on a new opportunity for nHCM.

Great. Thank you so much for coming, and thanks, everybody. Well, keep going with the conference. Thank you.