Wanna welcome everybody to the Leerink Global Healthcare Conference. I'm Roanna Ruiz, one of the senior biotech analysts here at Leerink, and it's my pleasure to welcome the team from Cytokinetics today. We've got Robert Blum, CEO; Fady Malik, EVP of Research and Development; and Ching W. Jaw, CFO. Thanks so much for joining us.
Thank you.
Thank you.
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I know everybody knows Cytokinetics pretty well, but I'll start with a big-picture question to set the stage before we dive into details. Could you recap how things have been going for Cytokinetics, what milestones you've achieved recently, and what you're most looking forward to going forward?
For those who may not be as familiar, ours has been a commitment to one area of biology, turning it into new pharmacology and advancing it over more than 25 years. We are now turning the page onto commercialization with recent FDA approval of aficamten, indicated for adult patients with obstructive hypertrophic cardiomyopathy. It's approved in the U.S., Europe, and China. We're transitioning to a forward-integrated global commercial company, still rooted in the original science.
Fady Malik, as our first employee and scientist, and I together have devoted over 25 years to this science. This first approval, MYQORZO in oHCM, may soon be followed by NHCM, nonobstructive hypertrophic cardiomyopathy. We also have two late-stage programs for advanced heart failure—one with reduced ejection fraction, the other preserved ejection fraction.
We're a throwback in our focus on one area of biology, scaling it into a business with multi-billion-dollar global potential. We're growing R&D and commercial activities in the U.S. and Europe, and things are going well.
Sounds great. Let's dig into the upcoming ACACIA-HCM in nHCM. Investors have questions about the risk-reward profile. Could you explain your thinking on this readout, what gives you conviction for aficamten, and how you plan to move forward assuming positive results?
nHCM represents about 50% of the HCM market opportunity. We now have approval for oHCM, and we’re hopeful ACACIA-HCM, with readout in Q2, can support MYQORZO in nHCM. We are optimistic based on phase 2 work and the design and conduct of phase 3. I’ll ask Fady to speak about the trial design and our optimism .
ACACIA was designed using phase 2 experience to understand dosing in nHCM. Unlike oHCM, which has both a gradient and ejection fraction for dosing, nHCM only has ejection fraction, which also sets our safety bar. Phase 2 piloted dosing successfully: about 85% of patients reached the two highest doses, 15 or 20 mg.
We had very few treatment interruptions—only 2 out of 40+ patients required a dose decrease, no treatment interruptions. That was a successful pilot of our dosing strategy, which we then implemented in ACACIA. Phase 2 data showed the biological rationale was valid, with biomarkers like NT-proBNP decreasing. Echocardiographic indicators of cardiac relaxation improved. In ODYSSEY-HCM, the trial of Camzyos, similar trends were seen, though that trial had about a 20% rate of treatment interruptions, whereas we expect around 3–5%.
In terms of trial conduct, we have extensive experience with HCM trials and many in-house experts to ensure the right patients enter the study. Over the last couple of years, blinded data have evolved within our assumptions for powering endpoints. All of this supports confidence in phase 2 data and the trial’s conduct.
Sounds good. I want to double-click a bit. How are you thinking about a possible win for ACACIA if, say, one endpoint is statistically significant but another just trends positively or narrowly misses? Can you frame how you think about these different scenarios for investors?
nHCM has no effective medical or surgical treatments. In oHCM, surgical options exist, but nHCM has none. Treatment effects are likely smaller in nHCM because there is no obstruction, but even smaller effects are meaningful.
We’ve seen meaningful results in open-label extensions, with the majority of patients becoming essentially Class I and asymptomatic after extended treatment. Combining a trial positive on both endpoints, the open-label experience, and the lack of effective treatments makes a compelling case. Challenges increase if only one endpoint is met, but there are few alternatives. Regulators may still support the therapy.
I agree.
I think to underscore Fady’s point, the study is positive if we hit on either endpoint.
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It’s certainly better if both endpoints are met, but hitting either is a win. As long as the other endpoint isn’t moving negatively, a positive trend is a big plus. It depends on how endpoints move together. Does a larger effect on one endpoint correspond to a larger effect on the other? How does it correlate with non-co-primary endpoints like NYHA improvement? Observing REDWOOD-HCM cohort 4 and open-label extension data gives us reason to be optimistic for phase 3.
Fady, you mentioned effects might be smaller in non-obstructive versus obstructive HCM. Are you referring to peak VO2, KCCQ, or both when considering primary endpoints?
Primarily peak VO2. In SEQUOIA-HCM, we powered for a 1.5 change. Without a gradient, impact is likely smaller, so we powered this trial for 1.0, with 90% power. At a 0.025 threshold, we can detect a change of around 0.6, less than in oHCM. Without the gradient, the drugs are still effective.
This doesn’t mean smaller changes aren’t meaningful. Analyses of minimally important differences in peak VO2 suggest even 0.5 changes correlate with symptomatic improvement. We believe these changes are clinically meaningful.
Got it. If ACACIA is positive, how do you envision the non-obstructive HCM data being disclosed and eventually getting into the label for aficamten or MYQORZO? How could that drive greater prescribing and awareness?
We've done market research suggesting that if ACACIA is positive—and we’ll know that in Q2—we should see a halo effect even for oHCM in the second half of this year, even without promotion. The cardiology community would likely be impressed with the breadth of MYQORZO’s application in HCM. We’d also refine the target product profile with actual data. There should be some halo effect in the latter half of the year.
Of course, FDA approval is required to promote these findings. Guidelines would likely reflect updates around 2027. If MYQORZO becomes the only cardiac myosin inhibitor indicated for both O and nHCM, that’s a significant milestone.
Sticking with the label expansion theme, you had positive MAPLE-HCM data recently. How do you see that enhancing the label, shifting cardiologists from beta blockers, and encouraging use of aficamten or MYQORZO? How will that evolve over time?
MAPLE-HCM could be a game changer in medical therapy for HCM. It’s less about labeling and more about guidelines. The trial showed aficamten’s effectiveness and highlighted beta blockers’ limitations. Guidelines currently position cardiac myosin inhibitors at the bottom: try everything else first. In reality, the most effective therapy is placed last. If that fails, surgery may be considered.
It doesn’t make sense because most other therapies are minimally effective. MAPLE-HCM demonstrates aficamten as the most effective therapy. We are sharing these data through medical affairs and guideline committees, who have shown strong interest. If access and pricing weren’t issues, discussions would be straightforward since the highest-quality data come from our trials.
Switching to commercial questions, you’re launching MYQORZO in oHCM. How is that going so far? What’s the value proposition and cardiologists’ reaction?
The launch is going well. FDA approval came in late December. About 125 U.S.-based Cardiovascular Account Specialists promoted in their territories through January. Drug supply and REMS weren’t fully operational until the third week of January. Once enabled, physicians could prescribe, and first dispensing happened within days. Some cardiologists had patients waiting for approval.
By our mid-February earnings call, over 700 HCPs were REMS-certified in just a few weeks. One week included a launch meeting with sales colleagues out of territory. There was significant pent-up demand. In an ATU study, MYQORZO awareness exceeded 90%, which is extremely high in this cardiology community familiar with us. Our lead clinical researchers also come from these KOL ranks.
Having presented and published these data over several years contributed to strong MYQORZO interest. It’s only been a few weeks, so there isn’t much more to report yet.
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We’ll have updates on the Q1 call in Q2. For now, we’re very pleased with the launch progress.
Early days, but looking forward, which patients will likely get MYQORZO first? Do you expect treatment-naive patients or some switching? How will these trends evolve?
BMS has sold Camzyos for over 3 years, reporting $1B worldwide in 2025, mostly in the U.S. They’ve reached 15–20% of eligible patients. Many undiagnosed patients exist, so there’s ample space for MYQORZO. About 700 cardiologists account for 80% of Camzyos prescriptions.
Most early MYQORZO patients are treatment-naive. Switches are expected but aren’t core to strategy or the label. Some patients on low-dose Camzyos who remain symptomatic will naturally switch.
Most patients receiving MYQORZO will be naive to Camzyos.
How does category expansion and other tailwinds layer into the MYQORZO launch? What do you expect for the ramp this year and in future years?
We’re focusing on 700 high-volume U.S. cardiologists, already engaged over 90%. Another 2,000 have prescribed Camzyos at least once, and 7,000–8,000 have seen many oHCM patients but haven’t prescribed Camzyos. It’s important to reach and engage all these groups about MYQORZO.
We want to see those cardiologists as well, but with less reach and frequency. We’re approaching this market in a segmented way, and it’s working. Feedback has been encouraging. Some dispensing is already happening outside the first and second layers. With this label and REMS, we aim to address market opportunity for category growth. Often, second-to-market cardiology drugs with strong safety and tolerability profiles become best-in-class. That’s not lost on us.
Got it. A couple of pipeline questions: omecamtiv mecarbil and ulacamten—what are the most underappreciated aspects of these programs, and what should investors watch?
Omecamtiv mecarbil has extensive phase 2 and phase 3 data, including a successful phase 3 trial. The ongoing trial, COMET-HF, targets a concentrated population with more severe heart failure. It’s enrolling well, with results expected in about 2 years. Endpoints include heart failure hospitalization and cardiovascular death.
This could transform heart failure care with a drug that doesn’t lower blood pressure and improves outcomes for difficult-to-treat patients. HFpEF in ulacamten is early stage, with lower event rates and a heterogeneous population. Phase 2 focuses on patients similar to the non-obstructive HCM population as a model for HFpEF.
We’re also interested in ulacamten because it has a different myosin binding site than aficamten, which may offer distinct pharmacology, potentially relevant even to oHCM.
One question from investors on ulacamten: if everything goes well and the program moves into phase 3, any early thoughts on trial design or endpoints?
Phase 3 guidance for heart failure would rely on function and outcomes. We might design a hybrid program incorporating features of both approaches. It would be a small program, but a sizable outcomes trial in HFpEF. With ACACIA-HCM data, our conviction to invest in such a program could grow over time.
Super interesting. A bigger-picture question: Cytokinetics has many moving pieces. How are you prioritizing capital allocation across R&D, commercial, and other initiatives?
We started the year with $1.2 billion in cash and investments, a solid position. Priorities include funding the ongoing U.S. launch of MYQORZO and building commercial capabilities in Europe, where we have approval and are preparing to launch in Germany in Q2. We’re also advancing our pipeline, which remains a key capital allocation focus.
Got it. For Europe, initial plans for Germany: how are you approaching aficamten launch and detailing cardiologists?
Launch is planned for Q2. Germany requires fewer reps than the U.S., and pricing is lower—15–20% of the U.S. dollar. BMS has already generated tens of millions in Germany and over $100M ex-US in 2025. Our goal is to build a profitable European business with concentrated investment in sales and marketing, starting with Germany.
We’ll scale resources country by country, based on reimbursement. Our medical affairs team in Germany is established, and sales reps will be online soon. We’re taking a similar approach in France, Italy, Spain, and the UK, starting small until reimbursement is secured.
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We’re taking a gated, disciplined approach to Europe. Others may have expanded too quickly, but we’re pacing methodically.
Last question: what’s still underappreciated in Cytokinetics’ story, and what might surprise investors?
BMS paid $13B for MyoKardia, expecting $3–4B peak sales for Camzyos globally. They are on track. MYQORZO’s FDA and European approvals, clinical safety, and patient experience could make it best-in-class. That’s just oHCM; nHCM could at least double the opportunity. Significant upside exists if we execute well.
Pipeline arbitrage is notable, particularly heart failure. Current market cap doesn’t reflect pipeline value, and analyst expectations for oHCM are below BMS Camzyos commitments. We have an opportunity to build substantial shareholder value and are already moving in that direction.
Great. That wraps our time. Thank you all for joining—really great discussion.
Thank you.
Thank you.