Great. Thank you everyone for joining. I am Max Skor, a Biotech Analyst with Morgan Stanley. Before we get started, for important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. I am very happy to welcome the Cytokinetics team, Robert Blum, CEO, Sung Lee, CFO, Andrew Callos, Chief Commercial Officer, Fady Malik, Research and Development. Welcome, team. Thank you very much for joining us today.
Thank you.
Maybe just to start off, Robert, we are in the early stages of the MYQORZO launch. Could you just walk us through key learnings at this point and what we should really focus on going forward into year-end?
MYQORZO aficamten was engineered with certain properties in mind and was developed very much to elaborate on those properties. I think those are playing well to what we hope ultimately proves competitive advantage in the marketplace. Ease of use, flexibility, convenience, these are things that we think matter, especially for a second to entry in a category of cardiovascular medicine. I do believe that, as we have projected, we are on track for some pretty ambitious goals. Goals like preferential share of new scripts by the end of the year. Goals like parity market access. That is all translating into very solid launch velocity and momentum. Andrew can elaborate, but we reported our full second quarter, and in that quarter, as you should expect, we saw a majority of new scripts coming from velocity accounts, those roughly 700 accounts that represent over 80% of the historical CMI business.
But what was also encouraging, and this is imperative to growing the category, is that there were at least half of prescription, I'm sorry, half of prescribers coming from either historically, physicians who had not prescribed a CMI or had not done so in a while. And that speaks to their comfort with MYQORZO, especially given a differentiated REMS risk mitigation, and also where we believe the data, strong data publications support its use. We're really optimistic and encouraged coming out of Q2. Q3 continues to look promising, and we're looking forward to sharing results at our next earnings call.
Great. Thank you. MYQORZO's new-to-brand share exceeded 40% in June, and you're targeting more than 50% CMI new patient preference share by year-end. What are the biggest drivers required to close the gap, and what could allow the share gains to occur more quickly?
Some of that relates to market access, where those barriers are being chipped away, and we expect parity by the end of the year. But maybe I'll ask Andrew to elaborate on how we get to that goal.
Sure. From a new-to-brand share of 50%, as you mentioned, end of the second quarter, we were above 40% and still trending in that direction, over 50%. When we look at what it's going to take to get there, our strategy has always been to the higher we decile physicians every 10%, and the higher the decile means the most productive physicians we have the highest share, and it goes down from there. So it continues to get the centers of excellence on board and expand the market. As we expand the market below decile 10 and 9, they're the highest, spend more time with our field force, spend more time with those customers. And generally those, as you go down, those deciles are less familiar with the details of the data and the differentiation, so there's an education component as well.
But what we've learned, no surprise, is that differentiation matters, the REMS matters, the experience and the process of getting a patient on therapy and going through the REMS matters, and market access matters. So it's reinforcing those elements, as well as you go down. But we remain confident in that goal of greater than 50%, because when we focus resources, we're seeing the share difference.
Great. And I think, Robert, you touched on this in the opening remarks, but more than half of MYQORZO prescribers have been low-volume CMI prescribers or physicians writing their first CMI prescription. What are you seeing in terms of conversion from initial trialing to repeat prescribing and greater prescribing depth?
So on average, those new to CMI prescribing or those that had not written a script for CAMZYOS in quite some time, on average, they are three prescriptions already. So it's not like it's one-off. We're seeing repeat prescribing. And this is a category where we're also very pleased to see a couple other things coming forward. One is very strong adherence and compliance on the part of patients. Patients, when they get a CMI prescription, and especially for MYQORZO, are staying on it, and I think that's essential to the kind of growth trajectory we're highlighting. The other thing that's really nice to see is that as physicians are prescribing, the time from prescribing to dispensing, the time from dispensing to revenue reimbursement is short.
At one time upon launch, I think analysts in general were assuming it might take at least 60 days to see that conversion from dispensing to reimbursement, where that on average is closer to three weeks today. So we're really pleased to see that. I think that speaks volumes to the kind of demand, the quality of the demand that we're seeing with MYQORZO.
Can we just touch on the sales force and any feedback you are getting from physicians on the early launch? Is the differentiated REMS resonating? Are there any roadblocks right now that you are working on to try and fix and expedite the launch?
I will ask Andrew to comment, but with any launch, there is going to be some friction points. What I am especially proud of is how our team is responding to those and knocking them down in order to accelerate the launch. Andrew, do you want to speak to that?
Sure. I think what we are hearing from our field force is what I mentioned before, is that the understanding the differentiation is important. We cannot assume, especially as you go outside of the centers of excellence, that cardiologists understand the data and the differences in the data, as well as the process, the REMS process, to get a patient enrolled and on therapy. I think there are critical components. The other key area is when you look at general cardiology, and we did not have as much focus on general cardiology, those who have not prescribed. I think we are very pleased to see that 40% of our prescribers were the core, what we call velocity accounts, 80% of the market. Then 30% had written very little CMI, and 30% were naive to CMI. That 30% were naive to CMI is where the majority of the market growth occurred.
It validated what our expectation was that we do well in the velocity accounts, the 40% of the physicians. To expand the market at the same time, we need to do well in expanding the market to really have the category and the brand get into the growth phase that we expect. Really pleased to see that. When you get into that 30% of the market, again, it is differentiation, process, REMS, and access. That is really the thing that we are focused on. When physicians do understand that, we are seeing a preference share.
Prior to FDA approval and launch, we were projecting that if approved, we should expect a differentiated risk mitigation profile, a differentiated REMS. The FDA did approve MYQORZO, and the REMS is different, and I think it's proof positive as to how that difference is being appreciated by customers that we're seeing category growth in the market, and especially in the community, where community cardiologists who might not previously have been comfortable writing a prescription, perhaps because they thought a REMS was an insurmountable hurdle, now they feel comfortable with MYQORZO. That's even as admittedly, we launched with a REMS that was more manual, less automated.
People don't necessarily all understand that with a REMS, there is a process back and forth with FDA, and as we have evolved the REMS to make it more system-wide and integrated across different personnel within the cardiology office, we've been lowering barriers to wider adoption amongst more cardiologists, more comfortable prescribing MYQORZO. As we get to potentially over 50% preferential share of new scripts, I think it speaks to, again, those REMS, that treatment experience, patient experience being more and more embraced by more cardiologists.
Can you touch on potentially patients switching from CAMZYOS to MYQORZO? What feedback, what's driving that at this point? Are physicians comfortable doing that, and how do you expect that to evolve over time?
Yeah. It's roughly 5%-7% of the sales we've reported to this point. It's not core to our strategy to be encouraging of that switching, but it is organically occurring. Maybe I could ask Fady to comment on what might be prompting that, and there is an investigator-sponsored or initiated study that is evaluating how best to do that.
Yeah. There are several reasons for potential switching from one to the other. Perhaps difficulty in up titrating with residual symptoms or gradients, drops in EF that require treatment interruption, DDIs that are bothersome to the patient because of a particular medicine they would prefer to be on. All of these things contribute to physicians deciding to switch from one to the other. And how to do that, we never studied that formally, but there is an ongoing investigator-initiated study to look at a particular means of doing that relatively efficiently, primarily by discontinuing CAMZYOS for a couple of weeks and then starting
MYQORZO at week two and titrating as per normal. So we'll see how that looks, probably early next year sometime.
Okay, that's helpful. So what are the remaining opportunities to reduce the time from prescription to paid therapy, and how much could improved access contribute to the launch trajectory?
Andrew, do you want to take that?
Sure. I don't know if there's a lot more we're going to do to change the time to therapy. We're right around three weeks in terms of paid therapy, which is where we're going to see it in steady state. We may improve that by a few days over time as payers and their policies are clearer to physicians. In terms of access, clearly anywhere where we still have kind of new to market blocks, where we have to go through a medical exception process, that certainly does slow down or speed bump, if you will, patients getting on therapy. There are instances where patients can't get on therapy. We do provide free drug. Sometimes those patients get put on a competitive product because of that market access situation. Nothing outside of the normal, ordinary course for a launch.
But I think we're quite pleased with where we stand in terms of time to paid therapy and the percentage of patients of over 80% who are on paid therapy.
Okay, you're also launching in Europe. Could you speak to the opportunity there and when we or how should we think about the contribution to the overall revenue picture?
Yeah, we believe very strongly that we have an obligation to patients, especially in countries that participated actively in our clinical research. We did commit to a go to Europe strategy, and we have now launched in Germany. Soon we'll be launching in other countries, U.K. by the end of the year, Italy, France, Spain, and others next year. Knowingly, pricing in those countries is not on par with that in the United States. But at the same time, we believe we can build a profitable business with MYQORZO in oHCM by itself and add to that nHCM, and that can even get more attractive. Maybe I'll ask Sung to comment on where ultimately Europe may line up relative to the U.S. in terms of the total financials picture.
Sure. Happy to do that. If we look at the total worldwide opportunity for MYQORZO, Europe in the end could represent approximately 15%-20% of that pie, which would be very significant for us considering this is in a blockbuster category and potentially in a second indication in nHCM. It is a very valuable opportunity for us.
Okay, that is helpful. Before moving on to ACACIA-HCM and the non-obstructive opportunity, you have several, let us say, layers of development going forward. We have approval in obstructive right now. We have the MAPLE-HCM sNDA and PDUFA date coming up, and then potential submission of the non-obstructive label expansion towards the end of the year. Could you talk a bit about how you are investing in these opportunities, the sales force going forward, and just positioning as more data you just presented at ESC, but how physicians are responding to this approach?
Yeah. I think one of the hallmarks of Cytokinetics, both past and future, is our science. We came to market with MYQORZO and oHCM with many dozens of manuscripts published in peer-reviewed journals to be enabling of our commercialization. Science to medical to commercial, we have been enabled in oHCM, first with SEQUOIA-HCM, then MAPLE-HCM, and as you point out, an sNDA pending FDA review and EMA. Next up is nHCM, and we recently presented the results and published them of the study called ACACIA-HCM. This speaks to strategy. It is not accidental, it is very much on purpose that Cytokinetics, as a pioneer, should be leading in extending this category from oHCM to nHCM, and ultimately as we build our business from HCM to heart failure.
While it might have taken us a while as a company to go from R&D to commercialization, we do think we have competitive advantage for our leadership in this space. You asked about nHCM. This is a very important opportunity for Cytokinetics in as much as if approved, MYQORZO would be the only medicine approved across the broad spectrum of HCM-o and n, and it is the same customer segment that is prescribing for nHCM as is targeted for oHCM. We think we have a cohesive strategy between R&D and medical and commercialization to build on. One should expect that this should continue, that as we demonstrate our leadership in oHCM and category growth, that should extend to shareholder returns in nHCM.
Great. Based on the ACACIA-HCM trial, which met both primary endpoints showing improvement in symptoms, exercise capacity. Following the ESC presentation, what findings do you believe are most important for physicians assessing the clinical relevance of the results and identifying appropriate patients for treatment?
Yeah. Before I turn it over to Fady to answer, I will just say that we are especially pleased with the results from ACACIA. Those data underscore a consistency across endpoints, time points, prespecified subgroups, and I believe very comprehensively and robustly make a compelling case for the approval of aficamten in nHCM. Maybe to specify and elaborate, I will ask Fady to comment.
Yeah. So the presentation and the publication in The New England Journal of the data, I think underscored their relevance to treating nHCM. As Robert said, when you looked at the endpoints across all the subgroups that we examined, there was a consistency of effect. I know people want to somehow identify a population that would be more responsive. I would not say any of the subgroup analyses suggested that. Obviously, I think more symptomatic patients will likely be the patients that end up trying MYQORZO first in that indication, if approved. But the benefits were seen widely, and there was an analysis that was also published in Circulation that showed the majority of patients responded in different domains, whether it was improvement in peak VO2 or NYHA class or what we call a patient global assessment of severity.
These metrics together, you saw multi-domain responses in patients with not only symptomatic and functional improvements, but improvements in biomarkers and also cardiac structure. So there is a consistency but also a breadth of effect that you see when you look at the data. I think as we continue to elaborate the data in more detail, people will appreciate the number of people, for instance, that transition from Class III to Class II, the number of Class I patients that appear, and will appreciate the effects beyond, say, what the numbers were in the primary endpoints.
Maybe if we can just touch on or compare and contrast the obstructive opportunity to the non-obstructive opportunity. Is the patient experience different? Are these patients generally taken care of in different facilities or by different centers of excellence, et cetera? Any comment on that?
Well, I think in general, the patients end up being treated when they get referred in the same places by the same physicians. They're seeing both nHCM and oHCM patients. I think where the opportunity lies is that the nHCM patients are more difficult to identify, so I think there's an opportunity in the broader cardiology community to raise awareness, to look for the particular phenotype that we're talking about, and either to treat them there or ultimately refer them. In oHCM, there's a murmur. When people do a general cardiac exam, and they put a stethoscope on someone's chest, often they hear a murmur that leads to an evaluation and a diagnosis. In nHCM, because there's no obstruction, there's no murmur, and patients come to attention in more subtle ways because of complaints of shortness of breath or difficulty exercising, and eventually they get a workup.
It's more underrecognized compared to oHCM.
At the same time-
Can I add real quick?
Go ahead.
We look at claims data when we build our field force, and we build our field force for o and n. It is the same physicians, and we know that from claims data. The slight difference may be in that it is about 60% of oHCM patients who are New York HA Class II, III, so it is about 120,000. Where the nHCM, it is about half, which is maybe about 100,000. The total prevalence is 50/50, but prevalence in terms of those that are symptomatic is slightly less for n. That split is probably two-thirds/ one-third within n, Class II versus Class III.
Nobody should take away from that the disease burden with nHCM is any less. These are patients that suffer in much the same way, and absent any approved therapy, it is a high unmet need.
Okay. What advantages do you think you have having potentially both obstructive and non-obstructive on the label? What are you hearing from physicians? What kind of groundwork do you have to put out or start to lay out to prepare the launch or potential launch?
Now that we have the data presented and published, we can incorporate it into target product profiles and scenarios and do proper quantitative market research. It's already knowable. It stands to reason that if one product is approved for both oHCM and nHCM, and we know that a REMS program can be a challenge, that physicians are likely going to be adopting one cardiac myosin inhibitor for the benefit of the broader spectrum of their patients. With that said, we still need to do certain legwork, and maybe I'll ask Andrew to speak to the kinds of activities that are already underway.
Yeah. I mean, on a large scale, the infrastructure's in place. The people are in place. The brand positioning doesn't really change in terms of the core position. The things we're doing are investing in disease state awareness, understanding the patient, understanding the journey of the patient, how long it takes to get the therapy, what's going to activate them. So there's a lot of market research and understanding, both from the physician point of view as well as the patient point of view. Starting to, as well, interact with payers. So they're the activities, but the core brand, the infrastructure, the people, there's really not much add there at all. The field force is calling on the right physicians already.
The payers already know the category, and the physicians, at least anecdotally we've talked to, doing ad boards, et cetera, they're pretty excited about the opportunity to have a therapy to provide to patients. This is, I think, the fifth or sixth shot on goal for this category and the first time a trial's been successful. So the physicians we're talking to are very pleased and intend on using, if approved, MYQORZO for nHCM.
I should maybe ask Fady to comment, but we haven't yet spoken about the importance of guidelines, and cardiologists tend to be very closely monitoring and adherent to guidelines when they publish. SEQUOIA-HCM, MAPLE-HCM, ACACIA-HCM, they may all factor into the way guidelines evolve. Maybe, Fady, you could speak to that.
Yeah. The current guidelines were published before those data all came to light. In fact, they came out just before, I think, SEQUOIA-HCM, or just right after SEQUOIA-HCM was read out and presented. So between the last guidelines and now, the data from SEQUOIA-HCM, the data from MAPLE-HCM, which is the head-to-head trial of metoprolol versus aficamten as monotherapy, and then ACACIA-HCM, have all read out, have all published. Guidelines generally look to published data in order to incorporate their use in their deliberations of how to write those guidelines. Both the U.S. and European guidelines, I think, will see updates in 2027, and I expect to be substantially improved, if you will, with respect to the positioning of CMIs in the treatment paradigm.
Right now, if you read the guidelines, cardiac myosin inhibitors are positioned basically as a treatment of last resort, which makes no sense, especially given what we've shown with MAPLE-HCM and the lack of effectiveness of metoprolol in that setting, and the highly effective use of aficamten in that setting. I think we're going to see a change in the way they're positioned, and ultimately, I think that will also help drive the category.
Okay. Maybe before moving on to the broader pipeline, could we talk just about the launch curve? What should we expect going into year-end 2027? Any acceleration, I guess, in the fourth quarter?
I will ask maybe Andrew and Sung to speak to this, but keep in mind we are very much in growth phase. We expect that to continue. Andrew, do you want to start?
Sure. I would not expect any major hockey stick inflection point. I think we are going to see continuous growth. We will see the market continuing to grow. A lot of it will depend on getting expansion of prescribing as well. NHCM, if approved, certainly will be a catalyst in the HCM category to expand, and I would expect there would be a halo effect from a speed to launch. My expectation is nHCM will go slightly faster, if not the same as oHCM. But again, I think this is a category where physicians need to understand the REMS. It is a whole office treatment, so it is not just the physician prescribing and the patient goes.
The nurses, the office staff, the echo techs, there is a kind of whole team that is involved in patient care, and that certainly is probably an element of why we will see the growth that we expect.
I think once you get into past 2027, and there is a lot of clear understanding and process flows built into practices, as well as expanding prescribers, that is when we can maybe start to see even broader uptake at a faster growth rate.
Yeah. I think Andrew said it well. I will just remind everyone, historically, cardiovascular launches tend to be linear in the early years. Of course, we would like to be better than that, but it remains to be seen, and we are focused on execution.
Great. What should we be focused on beyond aficamten? How should we be thinking about the bar for omecamtiv mecarbil? Anything else in your pipeline that we should keep an eye on and start doing work on?
This is the elegance of our corporate development strategy that's been in place for many years. As a pioneer and a leader in sarcomere biology and how that's applied to specialty cardiology, we have a three-legged stool strategy that starts with HCM and extends to HFpEF and HFrEF. We have, in a confirmatory phase III study, omecamtiv mecarbil being developed for advanced and severe heart failure. Omecamtiv mecarbil has already been the subject of a positive Phase III study in a broader population of heart failure with reduced ejection fraction, and now is in a confirmatory study. Maybe I'll ask Fady to comment on why we're optimistic about that confirmatory study.
Yeah. That's COMET-HF, and in COMET-HF, we had the benefit of a large trial prior to it, GALACTIC-HF, that looked at the effectiveness of omecamtiv mecarbil. That was a positive trial. It met its primary endpoint, statistically significant, but where the effectiveness was concentrated in a population of patients that had lower ejection fractions, what we call severely reduced cardiac function. In COMET-HF, as we designed it, we focused more on that patient population via the entry criteria, EF less than 30%, higher biomarkers, which are indicators of heart failure severity, NT-proBNP of 1,000 pg/mL versus 400 pg/mL, hospitalization within the last year. That defines a patient population with a very high event rate. You see event rates of 30%- 40% per year in populations like that. When you compare that to atherosclerosis, where you're talking about 2% or 3% per year.
The burden of heart failure hasn't gone away, and we think with the data that we've generated supportive of the design of COMET-HF, we're very confident in its outcome, and we think omecamtiv will turn out to be a very important medicine for those patients.
Aficamten is a cardiac myosin inhibitor. Omecamtiv is a cardiac myosin activator. We know a lot about this biology, and that is informing the strategy. In GALACTIC-HF, we had, while a positive study, admittedly a more modest effect, a hazard ratio of 0.92, p less than 0.05, but only about an 8% relative risk reduction, albeit in important clinical cardiovascular outcomes. We have seen in recent weeks how difficult it is to see a positive effect in cardiovascular clinical outcomes with a number of other programs failing to do that. Omecamtiv succeeded in that way in GALACTIC-HF, but where admittedly the effect was more modest, and now this confirmatory study, COMET-HF, will go after those sicker patients who, within COMET-HF, we saw a doubling of the overall effect size. There are reasons to be optimistic and encouraged that COMET-HF could read out positively.
Great. With a few minutes left, just to ask maybe a broader question. How is the rise of China origin innovation changing your competitive positioning and your R&D or BD playbook?
It is a very good question, and it is something that we are actively in tune with. We have, from a corporate development standpoint, and a goal with regard to our Vision 2030, to be augmenting of our pipeline, and that speaks to both advancement of organic, but also the in-licensing of inorganic programs. For those inorganic programs, we are looking at a number of opportunities that are incubating in China. I would not say our strategy is exclusive to China, but we are very China-centric in thinking about where we might be able to find places where we could identify adjacencies to the things that we ourselves do well. I believe that the world order has shifted. The balance geographically has shifted to the point where any business development team should be looking in China much the way we are.
Great. I think that is it. We are up on time. Thank you very much, Cytokinetics team.
Thank you.
Thank you.