Good morning, and welcome, ladies and gentlemen, to Cytokinetics conference call. At this time, I'd like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call for questions and answers after the presentation. We will allow for one question per participant. I will now turn the call over to Diane Weiser, Senior Vice President of Corporate Communication and Investor Relations. Please go ahead.
Good morning. Thanks for joining us on the call today to discuss the regulatory update related to omecamtiv mecarbil. On the call with me today are Robert Blum, President and Chief Executive Officer, who will make opening remarks, and Fady Malik, EVP of Research and Development, Andrew Callos, EVP and Chief Commercial Officer, and Ching Jaw, SVP and Chief Financial Officer, who will participate in our Q&A. Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings. We undertake no obligation to update any forward-looking statements after this call.
Now, I will turn the call over to Robert.
Thank you, Diane. Thanks to everyone for joining us this morning. Yesterday, we issued a press release announcing that Cytokinetics received a complete response letter from the FDA regarding the new drug application for omecamtiv mecarbil, our investigational selective small molecule cardiac myosin activator, which we've been developing for the treatment of heart failure with reduced ejection fraction, or HFrEF. FDA communicated that GALACTIC-HF is not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death in adults with chronic heart failure with HFrEF in lieu of evidence from at least 2 adequate and well-controlled clinical investigations. FDA stated that results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF with benefits that outweigh the risks.
As we stated in our press release, we expect to request a meeting with FDA in order to understand FDA's views regarding the CRL and what may be required to support potential approval of omecamtiv mecarbil. However, please know that we have no plans to conduct an additional clinical trial of omecamtiv mecarbil, and our focus remains on the development program for aficamten, our next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, the Phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy, or HCM. We are obviously extremely disappointed with this outcome relating to omecamtiv mecarbil, especially considering the high unmet need for innovative treatments for patients suffering from worsening heart failure.
As Fady and others at our company can attest, we are truly humbled by the overwhelming support we've received from representatives of the heart failure community since the advisory committee meeting back in December and has continued in these last 24 hours. With that said, however, this is a scenario we prepared for. As you know, we have taken a prudent approach to commercial investment spending. While we built out some of the requisite corporate functions that are required to support launch readiness, we did not hire any of the sales representatives that would otherwise necessitate a potential restructuring. As such, those commercial colleagues we do have on board will be asked to refocus their work streams in support of pipeline programs.
On a parallel path to learning more from FDA about what may be required to achieve approval of omecamtiv mecarbil in the United States, we will continue to press forward with plans to seek regulatory approvals in other countries as part of our corporate and business development strategies. We believe omecamtiv mecarbil may still play an important role in the treatment of heart failure, particularly amongst the hardest to treat and sickest patients who have fewer options left to manage their worsening disease. To be clear, ours is a broad pipeline of novel muscle biology-directed drug candidates, and we are well-positioned to advance the clinical development program of aficamten, our next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, the Phase 3 clinical trial. We do expect results later this year.
In addition, 2 more phase 3 trials are planned to begin this year, one more in obstructive HCM during the first half of the year and one more in non-obstructive HCM in the second half of this year. You're gonna be hearing more about these plans later today on our Q4 2022 earnings call. Additionally, the commercial infrastructure we've prudently built over the past year paves the way for the future potential approval and launch readiness of aficamten. As a reminder, the specialty cardiovascular franchise commercial team that has been focused to omecamtiv will now turn attentions to aficamten and its go-to-market planning. Just to be clear and to reiterate, we have no plans to conduct an additional clinical trial of omecamtiv mecarbil. Later today on our earnings call, we will provide financial guidance for the year.
What I will say now is that in 2023, 2/3 of our R&D spending will be allocated to aficamten. As we continue in our 25th year of operations, Cytokinetics is no stranger to challenges, and we've never been defined by them. Instead, we've defined ourselves by how we respond to adversity. I'm proud of our history of strategic planning, and that informs how we prepare for and rise above challenges like the CRL for omecamtiv mecarbil, and that's exactly what we will do today and going forward. As we said before, we've steadfastly built a deep and broad pipeline of potential muscle-directed therapies so that the company does not have to pivot on any one program.
We remain optimistic about our future, and I wanna thank our dedicated team of employees who are so committed to our mission of bringing forward potential new medicines for patients with diseases of impaired muscle function. Moreover, I wanna thank the patients and the investigators who dedicated so diligently to the clinical trials program of omecamtiv over the many years. Operator, with that, we can now open up the call to questions.
As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please limit yourself to one question. Please stand by while we compile the Q&A roster. Our first question is from Justin Kim with Oppenheimer. Your line is open.
Good morning, Justin.
Hi, good morning. Good morning, Robert. I'm sorry to hear about the news. While it may be a little premature to discuss this, is there anything the team thinks is important to communicate with the FDA that hasn't been discussed, which might change the path forward for omecamtiv mecarbil? Just how should we think about maybe the chances for the
Thank you. One moment for our next question. Our next question is from Madhu Kumar with Goldman Sachs. Your line is open.
Good morning.
Hey, guys. Thanks for taking good morning, boys. I think these are your questions. I guess kind of following on Justin's question. In your discussions with other regulatory bodies outside of the FDA, have you gotten a sense that they view the data from GALACTIC-HF differently in terms of the substantial evidence of efficacy to support the idea of pursuing this in other geographies outside of the US?
I think it's too early to know that for sure, but what I can say is our strategy in regulatory jurisdictions outside the United States is different from the strategy we pursued initially with FDA and is more focused to the narrower patient population in GALACTIC-HF that responded better. I don't think we can necessarily compare one to the other because the strategies are different, and we'll hopefully be in a position to produce a different outcome.
Okay, great. Thanks very much. We'll see you later today.
Thank you.
Thank you. One moment for our next question. Our next question is from Ashwani Verma with UBS. Your line is open.
Hi there. Thanks for taking my question. This is Fatima on behalf of Ash Verma from UBS. I just wanted to ask a question on a different topic about non-obstructive HCM. We're curious what we can learn from the ACC presentation about aficamten's potential use in the setting for a non-obstructive. We know that this is an open label REDWOOD-HCM study cohort, it seems like you clearly saw a signal that gave you confidence to start a phase 3. Also any clarity you can provide on the potential duration of therapy in non-obstructive, that would be really helpful for what you're going with in phase 3.
Sure. We'll answer that question, albeit a bit briefly because we'll be in a position to elaborate more, this afternoon, but I'll ask Fady to take your question, please.
Yeah, I mean, I think just, with regards to your question, you know, with a non-obstructive HCM, the clinical trial that we've designed and prepared to execute, we aren't necessarily going to speak to the details of that yet. We have said, you know, fairly clearly that we expect the duration of treatment to be longer than certainly than REDWOOD-HCM, but also, longer than SEQUOIA-HCM, just given the nature of the disease. We'll give you some more details on that this afternoon.
She also asked about what would be the nature of the presentation, what might be included this weekend. I will say that we're going to be providing information at the poster presentation, which is on Sunday, and we'll be following that with a call Monday morning. Fady, maybe you can highlight in general what types of information would be included in that poster.
Sure. Yeah, the poster is gonna include some of the information that we have gleaned from and reported similarly in our obstructive HCM cohort. Biomarkers, symptoms, dosing, safety. I would look for those parameters in our poster this weekend.
Thank you for the question.
Okay, great. Thank you so much. Thank you.
Thank you. One moment for our next question. Our next question is from Salim Syed with Mizuho. Your line is open.
Morning, Salim.
Great. Good morning, Robert. My sympathies to the team. I know you guys worked really hard on this application and development program. I guess one question from me on the conversations with the FDA. I know you're going more towards a sound like a broader strategy in the U.S. and sounds like a narrower strategy or narrower like population subset ex-U.S. I take it those discussions also happened with the FDA, perhaps getting a label here for a subset population. I'm just sort of curious, how do we bridge that gap here? Is that something they just didn't want to really consider?
Yeah.
If you could just help us bridge it. Thank you.
Yeah. I think it's a good question. I saw your note last night referring to whether there would be potential for a resubmission based on the narrower label. We did have those discussions with FDA. The complete response letter makes it seem pretty clear that FDA was not approving of omecamtiv mecarbil based on GALACTIC-HF, even as we indicated a willingness to support an approval that would be for the narrower population. I think the FDA is unequivocally indicating that they expect to see another study before they might consider approval of omecamtiv mecarbil.
Got it. Thank you so much.
Thank you.
Thank you. One moment for our next question. Our next question is from Joe Pantginis with H.C. Wainwright. Your line is open.
Morning, Joe.
Hey, guys. Good morning. thanks for taking the question. Robert, two-pronged regulatory question. further, to the U.S. approach, was there anything in, specific in the CRL yet ahead of your meeting with regard to any suggestions, regarding an additional study or the type of study? could that potentially be used by a potential U.S.-based company that might take the drug on? secondly, the second part of the regulatory question is, can you summarize any ex-U.S. regulatory feedback that you've had to date? Thank you.
Sure. Regarding the first part of your question, yeah, there were some comments about what that next study might need to be inclusive of in order to be able to support approval. The way the drug is dosed and how it's titrated in order to be able to support both the safety and the efficacy and overall be persuasive with regard to benefit risk, those were not things that we were surprised to see in the letter, and I think those are things consistent with the dialogue we had with FDA. Yes to your question, these are informative, were we to be partnering in the United States to anybody that would be funding and operationalizing that study were that to be supportive of a potential approval in the United States.
Regarding the second part of your question, in Europe, again, I think it's too early. Much like we said we wouldn't do in the U.S., I don't wanna do this as it relates to Europe either in terms of play-by-play, when we are still early in that dialogue. You know, if there's something material that we need to be disclosing to shareholders as it relates to omecamtiv mecarbil ex-U.S., we'll certainly do that. Right now, those conversations are still in the early innings, so to speak, and I wouldn't think that there's anything that's yet telling or we could say is predictive of how they go in some of these ex-U.S. geographies.
Appreciate the comments. Thank you.
Thank you.
Thank you. One moment for our next question. Our next question is from Charles Duncan with Cantor Fitzgerald. Your line is open.
Hey, Charles.
Hi, Rob. Hi, it's Pete Zobropoulos on for Charles. How you doing, Robert and team?
Good, Pete. Thanks.
How does the OMI non-approval set your sales marketing infrastructure up for success going forward with afi in terms of redirecting efforts? Or would it be better to have OMI approved? In addition, you know, is there any cost savings with this news, when will they be realized?
Sure. I'll start, I'll turn it over to Andrew and then also over to Ching, for your question, but I'll start with just the following. You know, this is a company that for many years, over 20 years, has been focused to research and then research and development. As we have brought on board commercial colleagues over the last couple of years, they've been building an IQ here at the company that's been very helpful, constructive to enabling go-to-market strategies. Certainly, we were commercial ready for omecamtiv mecarbil were to be approved, even as we stopped short of hiring salespeople until such time as we knew the PDUFA action, and now we won't do that. That IQ remains and will also be amortized around how we think about go-to-market for aficamten and reldesemtiv and other pipeline products.
We have now expertise in-house. We have systems and processes and people who have a commercial mindset that's informing of how we do R&D as well, and that's a plus. I'll ask Andrew to comment on how this may now be redeployed for aficamten in particular, and then I'll ask Ching to comment on spending. Andrew?
Sure, Robert. Robert covered most of it, but we're within the window of when we would start building for a launch of aficamten. The systems, the processes, the people across all functions in commercial are in place. Largely, you know, over 90% of our commercial colleagues are focused on a portfolio of products. If you're in pricing or analytics or distribution or sales, the design and idea was always to be focused on multiple products. It's really now just a pivot. We were going to expand our organization by around 200 people, of which about 25% of those would have been home office-based people to focus on both omecamtiv and aficamten. Omecamtiv is not approved, we're not gonna do that. We'll stay kind of at the size we're at.
We won't be expanding, and we'll be shifting to focus on aficamten, and as the year progresses, likely reldesemtiv as well. Ching, for the second part.
Thanks. In terms of spending this afternoon during the earnings call, we'll be giving guidance on this year's spending. It's safe to say that the CRL does decrease what would have been expected to spend for a commercial launch in 2023. We actually planned for this possible scenario by gating majority of the potential commercial spend on FDA approval. As Andrew said, now that we don't have an approval, we won't be hiring the sales representatives, and we won't be spending the marketing dollars that we would have needed to spend had we received approval. Stay tuned. More to come this afternoon.
All right. Thank you. Thank you for taking our questions.
Thank you.
Thank you. One moment for our next question. Our next question is from Lauren Timmins with Piper Sandler. Your line is open.
Good morning.
Hi, team. Good morning. This is Lauren on for Yasmeen Rahimi. Just a quick question. I think you guys answered a lot of the questions already. For the study, could you just provide a little bit more color? Are there potential for smaller like bridging studies that you could be done for approval? Have they made it clear that they want a larger outcome study? Thanks.
That's one of the things we wanna better understand in meeting with the FDA. I don't believe a bridging study, given the way that's classically defined, would be sufficient to provide the persuasive evidence as could be confirmatory of what we saw in GALACTIC-HF. Our operating assumption, the base case, is that it would need to be a study that would be an outcomes trial, not necessarily as large as GALACTIC-HF, but certainly as would be measuring outcomes that could be evaluated pairwise with what we saw in GALACTIC-HF.
Great. Thank you.
Thank you. One moment for our next question. Our next question is from Tessa Romero with J.P. Morgan. Your line is open.
Morning.
Hi, guys. Good morning. This is Taylor on for Tess. I was just wondering, so what read-throughs, if any, are there from the CRL to the rest of the pipeline? In particular, I was wondering if you could talk a little bit about CK-136, which is also trying or aims to increase cardiac sarcomere contractility, albeit by targeting troponin instead of myosin. As a follow-up, have you talked about which indications are in focus for CK-136, and what are you willing to disclose about it at this time? Thank you.
Sure. Good questions. I don't foresee that there's any read-through from the CRL for omecamtiv mecarbil as relates to others of our pipeline programs. It was very specific to the body of evidence generated in the clinical trials program of omecamtiv mecarbil. With that said, to your question, we are developing other cardiac myosin inhibitors as well as a cardiac troponin activator, including CK-136. CK-136 is being positioned for a potential treatment of augmenting cardiac performance like does omecamtiv mecarbil, but it's early in its clinical development, and it's in Phase 1 right now. We'll be able to elaborate more on our plans for 136 once we see data from Phase 1 in terms of safety, tolerability, et cetera. Fady has historically commented on where we might go with it, and I'll ask him to repeat some of those comments.
Yeah. I mean, I think with regards to CK-136, its novel mechanism of action, different from omecamtiv mecarbil, you know, we've elected to think about pursuing it in types of heart failure that aren't defined really as the general population of HFrEFs. More specialty, smaller indications not well served by current clinical trials or data. These might include things related to right ventricular heart failure or congenital diseases that lead to heart failure or other conditions that, you know, you don't think of as the broad population of heart failure with reduced ejection fraction.
Okay. Great. Thank you so much for taking the question.
Thank you.
Thank you. One moment for our next question. Our next question is from Srikripa Devarakonda with Truist Securities. Your line is open.
Hey, guys. Thank you so much for taking my question, and my sympathies to the team. I know you guys worked really hard, and this isn't the outcome that the company or the patients were hoping for. Apologies if I missed any color on the data that's upcoming for non-obstructive HCM. Presumably, we'll hear a lot of detail post your presentation at ACC. Just wondering what the next steps are for the Phase 3 trial, given that you expect to initiate it in second half of 2023. Also, from an unmet need and a KOL interest perspective, how different do you see this as being versus obstructive HCM around the same time period?
Sure. I'll answer the first part and ask Fady to speak to the second part. As it relates to our planning to start a Phase 3 study in NHCM for aficamten, we are in those preparations now, including as we engage with regulatory authorities around a protocol that would be finalized to support the start of the study in the second half of the year. We are already well into those activities, and we'll speak specifically to our plans, including some high level description of what a study could look like later today. As it relates to feedback from opinion leaders, maybe Fady can speak to the differences in how they think about a cardiac myosin inhibitor in NHCM versus OHCM.
Well, I think, you know, everyone recognizes that in NHCM, our treatment options are far more limited. None of the current medical therapies have really any impact on the disease. They're not surgical options for the disease. They're quite excited about the potential for a targeted therapy in this condition that may modify patient symptoms and ultimately change the course of their disease. You know, in thinking about how you approach it, I think, as we've talked about before, you can't expect there to be as rapid a resolution of symptoms and maybe maximal treatment effect as you might with OHCM, given the fact that there's no gradient to get rid of.
You may rely more on remodeling of the heart and slower changes that occur over time. Symptom improvement and functional improvements, very important to them in this patient population. It's really what drives their reason they come see, you know, doctors and would obviously be the focus of a Phase 3 clinical trial.
Great. Thank you. Just 1 question on omecamtiv. You know, KOLs we've spoken to have indicated that they would like to have this as an option for especially the very severe patients. You know, unless there's a way for possible approval in the United States, is there even a potential path for like a compendia listing so that it's accessible to patients?
That's a good question, I agree with you that heart failure specialists, those who treat these patients, including those who write guidelines for the management of these patients, have already voted with their own voices as to how they feel about omecamtiv mecarbil, editorials and articles written in support of its use. The fact of the matter is the drug is not approvable based on GALACTIC-HF, as was made clear by FDA. There's no thought about any other way in which we might be able to make it available in the United States, outside of what would be a potential next trial, which for which we have no plan to do. We'll continue to pursue its availability outside the United States at this time.
Okay. Thank you so much.
Thank you.
Thank you. One moment for our next question. Our next question is from Jason Zemansky with Bank of America. Your line is open.
Good morning.
Good morning, everyone, and thank you so much for taking our questions. Let me also offer my apologies on the news. Maybe to circle back on kind of your earlier comments on no plans for an additional trial. I'm curious as to what's going into that decision. You know, fundamentally, if FDA says that while maybe another outcome study is necessary, it can be smaller and more targeted within a smaller patient population, maybe necessitating less investment, would that potentially influence your decision as far as maybe having another clinical study? Thank you.
I'll tell you what goes into that decision is that is we recognize that as we can only control that which we can control, we should be focused on aficamten. We have in aficamten an opportunity with a pivotal Phase 3 trial readout later this year and two other studies that we need to get started. We recognize where we, as fiduciaries and shareholder interests, need to be redirecting, and that's what we should do. You're right. It's possible that FDA would be accepting of another study that would be a smaller, more focused study. Right now, our plans are focused on aficamten and the rest of our pipeline and what it's gonna take to get those to the next level.
Thanks for the color.
Thank you. One moment for our next question. Our next question is from Jason Butler with JMP Securities. Your line is open.
Hi. Thank you.
Morning, Jason.
Morning, Robert. I guess my question is just in terms of the restructuring the commercial organization, is there now more that you can do to be ready for aficamten than if you were launching omecamtiv? Or is it simply that you won't be adding more resources and therefore you would've been able to do all this stuff for afi anyway? I guess the kind of the same question for ALS commercial prep, is there more that you can now do there ahead of Phase 3 results? Thanks.
Yeah. Firstly, I just wanna ensure clarity around your question. We are not restructuring as relates to this news, but rather instead, redirecting and refocusing folks to activities in support of aficamten and reldesemtiv, things that we would be needing to do in this calendar year anyway, but now for which we have the resources in place to refocus to those activities without having to add resources or spending associated with those resources that would have been the case were we to be marketing omecamtiv, going to market with omecamtiv this year. We won't be doing that, and our spending will be reflective of none of those additional adds. I'll ask Andrew to comment, but, you know, we're within that window, especially knowing that there is another company in the market with a cardiac myosin inhibitor.
There are things we need to be doing in 2023 that we will now be able to make a priority for aficamten. Andrew?
Thanks for the question. Now that we have all functions on board, there's a lot more we can be doing. We'll be doing additional HEOR and value studies, engaging with a broader base of KOLs, trying to establish more awareness and disease state education with broader cardiology as compared to those HCM centers of excellence, will not only be able to engage kind of top payers but regional payers as well. The payers understand Cytokinetics, kind of our corporate goals and pipeline, and that we will have a product likely if approved for HCM in 2025. These are the kinds of things we will be able to do. Instead of recruiting and bringing people on board and building systems, we'll be operationalizing those systems as well.
It does give us quite a head start as compared to if this were our first launch and we hadn't prepared for omecamtiv.
You can imagine, for instance, in our medical affairs teams, where those people will now be redirecting their energies in support of concluding SEQUOIA-HCM and getting two other studies up and running this year and ensuring that those are enrolling at a good pace. Many thanks to Andrew and other colleagues in the company who in anticipation of this potential outcome, a CRL for omecamtiv mecarbil, already have been presenting internally and with our board those plans that would enable us to pivot were we to get a CRL. Now that we know we have a CRL, we will be pivoting and executing on those plans that are very well considered.
Okay. Thank you, Robert.
Thank you.
I'm showing no further questions at this time. I would now like to turn the conference back to Robert Blum, President CEO, for closing remarks.
Thank you, operator, thanks to everybody who joined us on this call today. Make no mistake about it, getting a CRL for omecamtiv mecarbil is a big disappointment. We obviously have been committed and devoted to the advancement of a cardiac myosin activator for quite some time, over 30 clinical trials and over 15 years in development. We have to own it. Thanks to prudent planning and investment spending and contingencies, we will weather this storm much like we have addressed other setbacks in the past. It's how we respond to adversity that defines us, and we'll be stronger for it. Our resolve increases and our resilience is our hallmark, and that's been true for Cytokinetics for many years, and now we'll be focused on aficamten. Aficamten has major milestones coming up this year, including this coming weekend.
We'll be looking forward to focusing to aficamten and spending in investment activities that are redirected to where aficamten can make its mark for our science and for the benefit of patients. With that, we'll bring this call to a close. We invite you to join us this afternoon for our Q42022 earnings call, at which time we'll elaborate on those things that are milestones and guidance for this coming year. Thanks very much.
This concludes today's conference call. Thank you for participating. You may now disconnect.