Welcome everyone to the 41st annual JP Morgan Healthcare Conference. My name is Tessa Romero. I'm one of the senior biotech analyst here at JP Morgan. I'm joined by Taylor Hanley and Adhiraj Chauhan from the team. Our next presenting company is Cytokinetics. Speaking on behalf of the company, we have CEO Robert Blum. Before I turn it over to Robert, I just wanted to highlight that there is a Q&A for those listening on the webcast. If you get your question in there, I'm happy to kind of squeeze it in there on your behalf. With that, Robert, over to you.
Thank you. Thank you to JP Morgan for inviting Cytokinetics to be presenting an update here at the 2023 conference. I'm very pleased to be speaking on behalf of Cytokinetics. This is a very important year. I'll be making some forward-looking statements. I'll draw reference to the SEC filings for caveats on those statements. We don't undertake obligation to update with regard to those statements. I'll be speaking and providing an update on a company that is committed with high conviction to this mission, a mission to bring forward new medicines to improve health span of patients with devastating cardiovascular and neuromuscular diseases rooted in impaired muscle function. Our focus is on muscle biology. This is a structure, the sarcomere, which is the fundamental unit of the mechanics and contractility of muscle.
Ours is the first company to industrialize this structure for high-volume drug discovery. Over many years, we've advanced now compounds discovered and optimized, characterized, and now developed by scientists and clinicians at Cytokinetics, anchored in this structure. This is a structure that gives muscle force and power, and we've identified activators and inhibitors of this structure. Lead amongst those are our cardiovascular drug candidates that'll be elaborated on the next slide. You can see we have quite a number of compounds that target different isoforms of myosin, which is the mechanical chemical enzyme largely responsible for driving the activity of this structure. If you look at our pipeline, you see the pipeline of a company that's committed to original drug discovery and innovation divided into two verticals.
Those drug candidates that either activate or inhibit proteins involved in the mechanics and contractility of cardiac muscle or skeletal muscle. Lead amongst these are our cardiovascular drug candidates, including aficamten, an inhibitor of cardiac myosin, now in a phase III study, a pivotal phase III study for the potential treatment of hypertrophic cardiomyopathy. You'll be hearing a lot more about that here in a moment. Also, omecamtiv mecarbil, pending FDA approval as a potential new treatment for heart failure, and still other compounds on this slide. You'll see that this is a slide of a company that's mature through its research and development, and we aim to be the leading company with emphasis to specialty cardiology in the biopharmaceutical sector. We'll be speaking about how we can build a franchise strategy in terms of how to get there.
In terms of 2023, what are the key priorities? They're listed here. First and foremost is continuing execution of SEQUOIA-HCM. That's the pivotal study for aficamten for the potential treatment of obstructive hypertrophic cardiomyopathy. At the same time, advancing a broad development program for aficamten in obstructive and non-obstructive HCM. We'll be hearing later about how we intend to commit investment capital in large part disproportionate to everything else in favor of aficamten. We also are engaging with FDA ahead of a February 28 PDUFA date for the potential treatment of omecamtiv mecarbil. I'll have some things to provide updates on that in a moment.
We also have another phase III drug candidate in reldesemtiv, and we wanna continue execution of the pivotal study, COURAGE-ALS, through its completion of enrollment in this calendar year, while at the same time advancing an early-stage development pipeline for drug candidates that are also rooted in contractility, as well as expanding that pipeline with new compounds coming out of research into development. Let's start with cardiac muscle, and in particular, what's our franchise strategy? How does that read on aficamten in particular? We intend to build synergies associated with aficamten and potentially omecamtiv mecarbil around a commercial franchise. What does that mean?
It means focusing to the commercial readiness around where a sales organization of roughly 150-200 people potentially could provide sufficient reach and frequency in order to become a leading company specialized in this sector. That means also building out the commercial support functions, market access, analytics, learning and development, pricing, forecasting, and other things as to be enabling of a go-to-market strategy. Already, we've deployed medical affairs and medical scientists in the field who are assisting with the conduct of clinical trials, as well as disease state education and awareness. There are corporate support functions that are important associated with IT, finance, et cetera, in order to make that happen. Who are we targeting?
We're targeting those roughly 1,000 hospitals and fewer than 10,000 cardiologists who are the high volume prescribers for specialty cardiology medicines that are rooted in diseases of muscle function. With omecamtiv being potentially the first to market, aficamten being the one to quickly follow behind, we're building an infrastructure that we think can be supportive of an emerging specialty cardiology franchise with high economies and synergies, as you can see depicted here. To this point, we've hired roughly one-third of the people that we would expect to be required in order to make that happen. We've got a cardiovascular franchise team of roughly 75 people, about 10 of whom are solely dedicated to omecamtiv. That means that the other 65 are engaging in activities that would benefit the company for what is both aficamten and omecamtiv.
You can see on the right-hand slide, those activities that are underway have been already pre-NDA filing and those that would be gated upon NDA approval. Still roughly 2/3 of the field-based personnel would be gated upon potential approval. What does that mean for aficamten? We're looking at a market that is large but growing, where the majority of the candidate patients are still largely undiagnosed. Roughly 280,000 diagnosed HCM patients in the United States, about 190,000 of whom are symptomatic. You can see here that number's expected to grow and the largest proportion still undiagnosed. aficamten as a next-in-class inhibitor of cardiac myosin, we're aspiring to a target profile that would be enabling of category expansion to those patients currently undiagnosed. Rapid onset of action, precise dosing, simplicity of use, rapid reversibility.
These are things that we think build on phase II data we've already seen and should hopefully be therefore confirmed in the ongoing phase III study. Those phase II data came from REDWOOD-HCM cohorts I and II. This is the trial schema. It was a study of roughly 10 weeks of dosing. Cohort I, lower dose. Cohort II, higher dose. As you can see here, results just recently, a couple of weeks ago, published in the Journal of the American College of Cardiology. As you can see here, dose-dependent rapid reductions in resting gradient, left ventricular outflow tract gradient, and Valsalva. These are impressive data that were already presented and published, and we believe augur well for what we should see in phase III.
Also when looked at across responder definitions, responder meaning patients who, after treatment, have gradients resting less than 30 millimeters of mercury and Valsalva less than 50. You can see dose-dependent increases in those responder definitions across cohorts I and II. Importantly, without treatment-related SAEs, strong reversibility, and also accompanied by statistically significant reductions in NT-proBNP and improvements in NYHA class as depicted on this slide. These data are already well socialized, and we think set expectations for what we should be seeing in the pivotal study, as I'll speak in a moment.
We are also conducting a cohort IV in patients with non-obstructive HCM. At this meeting, we're pleased to present that we completed enrollment in cohort IV in the fourth quarter of last year. You can expect results from this open-label cohort in this first half of this year. These data are encouraging. We've already seen them as open-label. They already set the table for us to be planning for an end of phase II meeting and the start of a phase III study later this year. We've also been presenting open-label extension from REDWOOD-HCM in a study we now call FOREST-HCM. You can see here as already presented out to six months, consistent and sustained reductions in resting gradients, as well as improvements in NYHA Class and changes from baseline in KCCQ.
This again speaks favorably to what we should expect in a phase III study. You'll see more data from that open-label extension this year. It wouldn't be right to present those data without fair balance. You can see here the safety data underscore good safety and tolerability, and both with regard to REDWOOD-HCM and FOREST-HCM, you're seeing a favorable profile in terms of treatment interruptions, discontinuations, SAEs, and the stopping criteria of LVEF below 40. We're incredibly encouraged by these data, speak to what we hope now to see in SEQUOIA-HCM. SEQUOIA-HCM is the ongoing phase III study. The plan is to enroll at over 100 and plus 100 sites in U.S., Europe, and Asia. This study is enrolling well with our Q4 earnings call in February.
We'll give an update on enrollment. We're also guiding to results in the second half of this year from this pivotal study that should set the stage for approval, hopefully next year. This study is looking at endpoints out to 24 weeks, hence why the six month data from the OLE speak favorably to what we hope to be seeing in SEQUOIA-HCM. We also are seeing in the open label extension data that give us confidence that physicians feel comfortable withdrawing frontline beta blocker therapy and still are seeing good gradient reductions, improvements in NYHA Class without also reductions in LVEF. That informs then the design and conduct of a trial that will be underway soon as well.
Another phase III study will be starting soon in obstructive HCM. Think of this study, if you will, as a potential phase IV like study that we're also just starting early. It's not pivotal to the registration strategy, but we do believe it'll be supportive of use post-approval. You see here a broad development program for aficamten across obstructive and non-obstructive HCM. This is our highest priority commitment in 2023, and you can see all those studies and timelines factored there. Our goal is to do this such that we are filing an NDA next year for potential approval next year. Aficamten is targeting patients with a high unmet need.
We believe that the healthcare professionals, based on market research, see that the rapid onset of activity, the improvement in symptoms, reduction in thickness of walls, septal wall thickening, would suggest this could be a next-in-class profile contributing to a meaningful expansion in the category. You see the characteristics of the ideal HCM patient for aficamten. These are patients who are symptomatic and uncontrolled and also newly diagnosed, to my point about category expansion. Our brand strategy that informs market access, detailed here. We're gonna be competitive in the HCM market by expanding the customer segment that will be comfortable using inhibitors of cardiac myosin to maintain patients on therapy and to also penetrate into the undiagnosed sector of that marketplace. Here you can see some high-level comments about our market access strategy. It is now underway.
Our go-to-market strategy is already being implemented in 2023 to support a potential approval in 2024. I don't want to simply talk about aficamten without also providing an update on omecamtiv, even though it's not our highest priority for 2023. You may know that omecamtiv was the subject of an advisory committee meeting in December. The advisory committee vote did not go our way. They voted eight to three against the overall benefit risk for omecamtiv in the overall treatment population. We are continuing engagement with FDA. We have interactions throughout this and next month ahead of a PDUFA date of February 28, and we'll have more to say about this with our upcoming earnings call. We continue to prepare for the potential commercial launch as may follow that PDUFA date.
We do believe that there is still a very high unmet need in patients with Heart Failure with reduced Ejection Fraction, especially in patients who are intolerant to guideline-directed medical therapy. As you can see on this slide, only about 23% of patients with HFrEF are on the three pillars of therapy. Many patients don't get to optimal doses. Because of comorbidities, many patients can't be on all three GDMT treatments, and therefore, they drop off therapy. We believe these are the type of patients who might best benefit from omecamtiv mecarbil, as would be not foundational, but add-on therapy for heart failure. You can see it's a large market. It's still an epidemic in this country, but for which we're not focused to all such patients.
We're focused to those same patients where there'd be high overlap with where we expect to be with aficamten. Roughly 2 million patients who have ejection fractions less than 30%, recent hospitalization, and are, because of limitations in GDMT, they still have opportunity to benefit from an add-on therapy like omecamtiv mecarbil. These are the results from the pivotal phase III study. This was a study that was over 8,000 patients. It's the second-largest heart failure study ever conducted. The study was positive, P less than 0.05. In fact, P equals 0.025. Admittedly, a modest reduction, 8% relative risk reduction in the overall population. If you look at those patients who are more severely ill, more advanced heart failure, you see a larger treatment effect that's clearly evident in the patients with ejection fractions below 30%.
Also, when you look at class three and four patients or recently hospitalized patients, there's a meaningful treatment benefit in these pre-specified subgroups. It's okay to look at pre-specified subgroups when the overall population saw a clinically benefit and a statistically significant one. We're looking at these pre-specified subgroups as could inform potential strategy. When you look at patients who are intolerant to GDMT, you see an even larger 38% relative risk reduction. Patients who are seeing mortality trends also in favor of omecamtiv, even when treated with GDMT. Here again, favorable tolerability and safety underscoring that the benefit risk, perhaps in this subset of the overall population, is still favorable. I'll now switch gears and quickly talk about our other program in phase III.
This is a program for reldesemtiv, a skeletal muscle troponin activator being developed for the potential treatment of ALS. ALS is getting a lot of attention these days. Cytokinetics hosted a fundraiser for a nonprofit last night, hundreds of people were in attendance recognizing the high unmet need in ALS for education, awareness, and new medicines. We conducted a large phase II study of over 400 patients, what we saw across three doses in phase II was a consistent effect across all doses in reducing slow vital capacity relative to placebo or standard of care. A nominally statistically significant finding in a smaller phase II study intended to be hypothesis generating. When combining those doses to get more statistical power, you see an over 25% relative risk reduction in slow vital capacity.
You also see that the ALSFRS, the pivotal endpoint for registration in ALS trials, also saw a meaningful reduction, clinically relevant, favoring reldesemtiv when added to standard of care. That effect was even more pronounced in patients who were more rapidly progressing. We began to look at these in a post-hoc way, admittedly, in order to inform a phase III study design for COURAGE-ALS to look at those patients less than 24 months since diagnosis and who have more compromised ALS functional scale status. COURAGE-ALS has already enrolled over 300 patients. It should be completing enrollment after we conduct an interim analysis in the first half of this year, and our goal is to see results from this study next year. I'll now end with just a couple of slides on our corporate profile.
Here's our balance sheet as of the end of Q3. You can see at that time, approximately $900 million in cash and cash equivalents. We ended the year with over $800 million on our balance sheet. We'll be updating our financials and financial guidance with our Q4 earnings call in February. Here's what I'd like to leave you with. We intend to be committing, as far as investment spending, a majority of our R&D dollars towards aficamten. As you can see here, approximately 60% of planned R&D spending this year still representing over two years of cash from the beginning of this year, and that's going to aficamten this year. In terms of milestones, you see them broken out here. On the first row, you're seeing things that are earlier in the year. On the second row, things that are later in the year.
We intend to make aficamten our highest corporate priority, as you can see here, but also setting the table for the franchise strategy that is, we believe the hallmark of our future successes with omecamtiv, and also setting the table for what could be the second vertical going to market, and that's reldesemtiv. A busy year, lots of news flow, lots of catalysts and milestones, and we look forward to keeping you abreast of our progress through the year. With that, I'll end the presentation. Thanks very much, and we'll turn it now to questions.
Great. Yep. Now we're gonna flip over into our 20-minute Q&A session. Robert's joined by Fady Malik, EVP of Research and Development at Cytokinetics. Welcome both. Please just kinda wave your hand at me if you have any questions 'cause we're having some technical difficulties with the Q&A queue. Just wave your hand if you have any questions. I'll get us started here. Starting with aficamten, how is your enrollment progressing in SEQUOIA-HCM? It sounds like you're on track to share data in the second half of this year. Maybe help us frame what level of detail we could see in the top-line data release later this year.
I think we accomplished what we set out to accomplish in 2022, which enables us to be confident about completing enrollment here in first half 2023 to be enabling of at least top-line results in the second half. Fady oversaw the execution of a SWAT team that went out and visited nearly all of the enrolling sites all around the world in Q3 and Q4 to be ensuring that we're enrolling well. I'm not gonna comment today on where we are specifically in terms of enrollment, but we will provide an update with our Q4 earnings call, and maybe I'll ask Fady to comment on what we might could expect from results later this year.
Yeah. I think, you know, by the end of this year, we'd hope to be able to report top-line results. I would say that, you know, we'll definitely give some sense of, obviously if the trial was positive, to what extent we're happy with the data. We may not include a lot of details because we'd obviously like to keep the trial eligible for a late-breaking presentation at an upcoming medical conference. I think, as we have in the past, we've provided sufficient detail for people to understand, you know, what the results will be like when they're fully-
Okay.
-presented.
Okay. Why was peak VO2 chosen as the primary endpoint of SEQUOIA versus gradient or another endpoint? kinda what is the bar you think you need to hit there? I believe that the trial is powered for a 1.5 difference between your two arms. just help us understand that a little bit. Then have you previously collected any peak VO2 data with AFI?
Well, peak VO2 was selected because it's an objective measure of exercise performance, and that's one of the things that these patients suffer from is reduced exercise performance. They have trouble walking up stairs or even walking up streets that have slopes in them or inclines in them. Peak VO2 and the exercise test that accompanies the measurement of that is the most objective measurement of exercise performance. Things like left ventricular outflow tract gradient or other biomarkers don't necessarily rise to the level of being a functional or symptomatic improvement. In terms of a approvable endpoint, generally, you have to show an improvement in function or symptoms. That's the rationale for using an exercise endpoint as the primary endpoint. The second part of your question is-
Bar to hit.
The bar to hit, right. We powered to study at a, at 1.5. You know, in general, in the heart failure field, an improvement of 1.0 is felt to be clinically meaningful. We chose a somewhat higher bar. We actually have very good power to see 1.5, you know, in excess of 90%. It was the improvement, roughly, that was seen with mavacamten in EXPLORER-HCM study. It was 1.4. We powered the study to be able to see that or better.
Kinda what is the feedback from docs? Is it 1.5 is sufficient? That seems to be the feedback we get, that that's, like, the clinically meaningful kind of-
Yeah. I mean, as I said earlier, the literature supports even a 1.0 as being clinically meaningful.
Okay. Yeah. Okay.
As importantly as peak VO2, you know, with measurements of symptoms as we're doing in terms of KCCQ, the Kansas City Cardiomyopathy Questionnaire, and NYHA Class, you know, are also important measures of patient, symptomatic improvement.
Yep. Yeah, which kinda gets me to my next question. Sort of what are the key secondary symptom improvements we should be focusing on here? What does your market research suggest are the most important measures for physicians? Sort of, you know, give us a sense for what sort of placebo-adjusted bar you might like to hit on either NYHA Class or KCCQ improvement to kind of say, "Okay, this program is differentiated.
Well, you named the, you know, the probably the most important secondary endpoints of NYHA Class and KCCQ. These are generally very well correlated, you know, with physicians' impressions of how patients are doing as well as patient impressions of how they're doing and are important to assessing the impact of the drug on patient well-being. You know, we would like to see for NYHA Class, obviously, that the majority of patients achieve a one or more Class improvement. The NYHA Class are four classes, and fourth class is essentially symptoms at rest. We don't enroll too many of those patients 'cause they probably need more urgent resolution of their symptoms. We mostly enroll Class 2s and 3s because Class one is asymptomatic. You know, we'd like to see the 2s go to one.
That's a pretty high hurdle because to have no symptoms is a tough one. Going from three to two is a bit easier, which is, you know, moderate to severe to mild to moderate. You know, one or more class improvement, I think, in the majority of patients is what we'd like to see. With KCCQ, I think it's, you know, a scale that's not as frequently used to assess patients, but has very good validation in the literature in terms of its correlation with patient quality of life. Generally, a five point or more improvement is what's considered meaningful there. As we presented in some of our open-label data, you know, we were seeing improvements far in excess of that.
We think that this, you know, these therapies, these class therapies have a real impact on patient wellbeing.
I might just add that when you do the market research here, physicians favor function and then symptoms. Patients, symptoms, then function.
Mm-hmm.
It's a dynamic where, you know, there's some patients who are gonna be themselves pushing to be on a new therapy, and you're gonna need to demonstrate that the drug is doing more than just simply increasing exercise capacity. They're gonna wanna know that they feel better, that their wellbeing is improved. Physicians are also very much focused to ease of use, reversibility, and properties around therapeutic window and rapid onset of action. These are the kinds of things that do score high in our market research, underscoring a potential favorable adoption associated with a next-in-class profile.
Yep. How important is kind of the faster time to titration to your efficacy profile, do you think?
Well, you know, I think it matters the most to the patient, frankly. I mean, it doesn't. Our endpoint's measured at 24 weeks. The faster onset is not really captured in that 24-week endpoint. If you're a patient and you have a highly symptomatic disease, what would you rather have? Would you rather pursue a therapy that maybe in two to four weeks may alleviate symptoms or longer than that? I think it's important from the point of patient ease, symptom relief, getting benefits and seeing something for, you know, all the effort that they're investing in getting on these therapies.
Okay. That's helpful. I think I'd be a little bit remiss not to ask a question here on safety, because we know that's incredibly important. As we think about safety of Affi, we know that left ventricular ejection fraction is sort of the key endpoint to monitor there. As you think about the trial, sort of what rate of drops kind of transiently below that kind of 50% line do you think could be acceptable in SEQUOIA? Maybe it makes sense to just recap what you've seen so far with the, with the candidate in your studies.
We've seen really very few. I think Robert showed a slide with three drops in LVEF below 50%. Two of them were during a dose-finding range. In a dose-finding study where we were sort of honing how we dose the drug. It's important also to recognize that they were completely asymptomatic. They continued to be symptomatically improved. I think the key is that in both cases, in each of the cases where we've seen them, you could just reduce the dose of the drug, and their ejection fraction would return above that 50% limit. We haven't had any treatment interruptions for low ejection fraction, which is also disruptive. You know, that EF less than 40 is really, I think, where the safety zone lies.
In that way, I think the dosing has been predictable and so far the profile looks pretty good.
What's also important around safety is what happens as you get farther away from the physician's office, what's happening in the open label extension, and when patients are taking other concomitant meds, are there any drug-drug interactions that might alter the pharmacokinetics? It's nice to see that in the open label extension out to six months and through this calendar year, you'll see data, even longer that underscore that this drug appears to be able to be used safely regardless of what other things are going on in that patient's life.
Okay. Just get in there if there's no audience questions. How are the site read focused echoes that I believe that you're using for your titration visits at, I believe, week two, week four, week eight, or I'm sorry, week two, week four, week six, week eight, different from a full echo in terms of kind of the time that's required of them and sort of the physician burden?
Right. We introduced those focused echoes primarily to reduce patient and physician burden because there are only two things you need to know at those visits. You know, what's the gradient, and what's the ejection fraction. Those focused echoes really are intended to measure those two things. That, you know, that should take about 15 minutes. A full echo where you measure all kinds of blood flows and various different parameters in terms of cardiac function and valve leakiness and so forth, it can take upwards of 45 minutes to an hour. We certainly have those at certain time points, so we can get a fuller picture of how cardiac function has changed, but it's not necessary to draw it to inform dosing.
Simpler, easier, and hopefully that's what will be implemented down the road.
Okay.
Thank you very much for the presentation. One of the questions I have is around how you see efficacy translating from the obstructive patient population to the non-obstructive patient population. A related question is in terms of would you envisage the need for dose titration and perhaps how you would do that in the absence of an LVOT gradient in the non-obstructive population?
We haven't, you know, obviously we haven't yet presented any data from the non-obstructive, so it's a little hard to answer your question. The, you know, there are measures in common, such as NYHA Class and KCCQ, that we would expect to be positively impacted by the drug, as well as biomarkers like NT-proBNP or troponin. We think there are some parallels in terms of the two conditions, despite the lack of a gradient, that would inform, you know, whether patients are actually doing better. Those are informative to us, you know, thinking about how to design and execute a phase III.
As to dosing, I think that's a good question because, you know, how do you dose this drug, and the fact that with the obstructives, you have something that's abnormal, a gradient, and you wanna get rid of it. You can dose till it's gone and then stop. In this case, there isn't such a marker, what we've been doing is dosing essentially up to the highest dose tolerated in the absence of a significant drop in ejection fraction. You know, I think the study is one reason why we enrolled 40 patients. We wanted a pretty good sense of how that strategy would work before we embarked on a, you know, much larger phase III study. That seems to be going okay.
The thing that you didn't ask, but I'll answer anyway, is that the duration of treatment here also matters. As we move from OHCM to NHCM, I think it's reasonable to expect that it may take longer to see a benefit of a myosin inhibitor producing the kinds of endpoints that would ultimately satisfy regulatory authorities.
One more, if I could, on aficamten, and then maybe we'll wrap it up in the next couple minutes here. You know, when we talk to docs about the program, I think there seems to be a little bit of debate about what could a potential REMS program be for aficamten. I think there are a lot of different views out there. Just curious, what is your view on kind of a REMS and kind of, you know, would you have one for affi? Would you not have one? Or is it really gonna be dependent upon what data we see in SEQUOIA?
It's easy to address that because it all will be data dependent.
Yeah.
on what we see in SEQUOIA-HCM. There are different forms of REMS. There are ETASU REMS and informational REMS. There are different forms of ETASU REMS. I do believe that it's reasonable to believe that if the data from aficamten demonstrate in phase III what we're seeing in phase II, especially in the open-label extension, we shouldn't need to be expecting or assuming the most restrictive kinds of REMS, where it requires physician and pharmacist and patient certifications and frequent echoes and all the things that might come with a more extensive REMS. Again, it's data dependent, as we'll hopefully be able to show with results later this year.
Unfortunately, we're not gonna have too much time here to talk about omecamtiv and the rest of the pipeline, which you touched on, Robert. You know, with your cash runway position, you know, what are the anticipated milestones for the company within that runway? How does this change if omecamtiv is approved or if it's not approved, you know, in the next couple of months to weeks here, weeks to months here?
We did those things in 2022 to be prepared for scenarios we're confronting in 2023. We executed on corporate development deals, and Ching, our CFO, is in the audience. He did a masterful job of getting deals done that afford us access to additional capital if omecamtiv is approved, so that our net burn wouldn't necessarily change that much. Our gross burn, yes. Our net burn, not so much, because we have access to a line of credit to support the commercial launch of omecamtiv with terms that are well below market rate right now, especially in this inflationary environment. We like where we sit. If omecamtiv is approved, yeah, our gross spending goes up, but our net spending really not so much.
We're in a good position, I think, to build that franchise that I mentioned before, without that coming at the expense of what shareholders are most concerned about, which is the investment capital available to deploy for aficamten. We start this year with well over two years of cash, given our burn rate of 2022, as could be projected for 2023. We'll update on what will be our net operating burn with our upcoming earnings call in February.
Great. I think that's probably a good place to leave it. Thank you so much, Robert and Fady, and thanks for all of our listeners for joining.