Fulcrum Therapeutics, Inc. (FULC) Earnings Call Transcript & Summary

All right. Welcome to the team from Fulcrum Therapeutics. Thanks so much for joining us.

Thank you for having us.

I appreciate the time today. So maybe we'll just get started. I think it's always helpful to get a bit of an overview. So let's start with overview of the company and what you view as the key value drivers over the next, let's call it, 12 to 24 months.

Sure, absolutely. And thanks so much for having us at the conference. So Fulcrum Therapeutics is a biotech company focused in identifying rare diseases where we can use oral therapy to modify gene expression, where there continues to be a high unmet need. We're focusing 2 key areas, which I'm sure we'll probably get into a little bit. FSHD, a bit of a mouthful, but we'll talk a little bit about what FSHD is in just a little bit as well as sickle cell. And then over the next sort of 12 to 18 months, the fourth quarter of this year is a big quarter for us, where we will be reading out our pivotal data from our Phase III study we call the REACH study for the treatment of FSHD.

Perfect. Let's start with that then and we do anticipate the Phase III data later this year. Before we really dig in, let's just start at a high level. What exactly is FSHD. I also prefer not to go with the full word because it is a mouthful. How big is the market? And what do we know about the biology behind FSHD?

Yes. So FSHD stands for facioscapulohumeral muscular dystrophy. So this is the second most common form of muscular dystrophy affects mainly the muscles in the shoulder girdle as well as the face, but it can also affect muscles in the lower extremities as well. From a prevalence standpoint, I mentioned it was the second most common form of muscular dystrophy about 30,000 patients in the U.S., about 750,000 patients outside of the U.S. And currently, these patients have no treatment options, which is why we're so excited about the fourth quarter data readout this year in our pivotal study we call REACH.

Perfect. And maybe you could explain the mechanistic rationale for losmapimod in this niche population.

Yes, absolutely. So losmapimod is the drug that will be reading out the Phase III data in Q4 of this year. And essentially, what losmapimod does is it essentially reduces this aberrant expression of this gene we know as DUX4. And essentially, what DUX4 -- DUX4 essentially sort of turns on during embryogenesis but then it's shut off. And I think for patients with FSHD, they have this aberrant expression of the DUX4 gene and what losmapimod has been able to show in vitro studies in a very dose-dependent way is that we can decrease levels of DUX4 and essentially, by doing that, we can preserve these patients' muscle function, which we were able to demonstrate in some of the clinical findings in our Phase II study, which just recently appeared in the Lancet Neurology publication.

Okay. Yes, you referenced the Phase II study. It did technically miss on the primary input, which was modulation of DUX4 expression but it did hit, as you mentioned on the secondary endpoints around clinical function. So how should we understand that result relative to the decision then to move forward with the program?

Sure. Absolutely. So I think what we found in our Phase II study, you mentioned we did not hit the primary endpoint, which was a reduction in DUX4 gene expression. And what we know about DUX4 is it is a highly variable gene. And so let me provide a little bit more sort of quantification of what I mean by highly variable. DUX4 is only expressed in, call it, 1 out of 2,000 to 3,000 myonuclei in the muscle cell. So you have very much of a sort of needle in a haystack issue that you're dealing with here because it's only expressed in a relatively small number of myonuclei in the muscle cells at any given period of time. But what we did show in our Phase II study on a number of these secondary end points, many of which were functional. We did show an improvement in reachable workspace, and we'll -- that's a new and novel endpoint. We'll talk a little bit about probably get into what are the -- what is reachable workspace. We also show an improvement in shoulder abductor dynamometry, so essentially sort of people were able to sort of use their shoulders much more than they otherwise could have if they were on placebo during that 48 weeks. We also saw a number of patient reported outcomes, which were also positive as well as a really interesting endpoint around muscle fat infiltration. And essentially, that's sort of the last step in the pathogenesis of this disease in that once the muscle fiber gets replaced with fat, it's very difficult to do anything. And what we showed in that Phase II study and we can get into some of the specifics is that we were able to sort of prevent that muscle infiltration over that 48 week period of time to a much greater extent than the patient that were on placebo during that 48-week study.

Yes. Maybe let's double-click on some of those endpoint tickets, which of them, in particular, the concordance across these end points that give you the most confidence as you move into Phase III?

Yes. It's really this functional endpoint called reachable workspace, and maybe let me turn it over to Iain to talk a little bit about what reachable work is, and what we were able to show in our Phase II study around this new novel endpoint, which happens to be the primary endpoint for the REACH study that we are reading out in the fourth quarter of this year.

Yes. So the reachable workspace is an objective manner to measure the extent to which a patient can move their upper extremity in space. So it captures the full movement of, if you can imagine, a hemisphere in front of you, the full extent to which that that's REACH. And so it incorporates activities around the shoulder joint predominantly, but it's not 1 specific movement or 1 specific muscle, it's capturing that in its entirety. And it's measured not by somebody looking and calculating or doing some kind of observation. It's captured by a camera, standardized camera at a set distance away from the patient who then goes through a stereotypical set of movements. That is supervised. The movements are supervised, the data are captured by the camera and then deconvoluted to generate this hemisphere, the surface area that they can reach. And that is correlated with the functional abilities around the shoulder joint. And what we showed in the Phase II study is that patients who are on placebo during that 48-week period showed a measurable decline in the reachable workspace whereas those that were on losmapimod that same period showed a stabilization or maybe even a slight improvement in that.

Okay. Muscle fat infiltration is another interesting endpoint that you showed. So I guess, could you contextualize for us if any other drugs or anything else has been able to demonstrate that benefit on muscle fat infiltration? And what kind of confidence that gives you.

You want to take that?

Yes. So muscle fat infiltration is the final common end pathway of a number of muscular dystrophies, but I don't believe that any drugs have been approved using that particular endpoint, but there's a lot of interest in it because it is that end pathway of muscle disease and is a particular characteristic of FSHD. If you look at the scans of these patients, you see over time how that muscle is converted to fat as a result of the aberrant expression of DUX4. And again, what we were able to show in the Phase II study, where we look at muscles based on how much fat they have at baseline. So we don't focus in on the really end-stage muscles that are more than 50% fact replaced and we don't focus in on the very mildest muscles that have less than 10%, but we look in that middle zone where they're showing some signs of fat infiltration already but not so far progressed at their end stage and it's in that group of muscles that we were able to show, again, similar to the reachable workspace that the placebos are showing here an increase in muscle fat infiltration over that period, whereas the folks that got losmapimod are essentially stable over that time period.

Maybe spending a bit more time on these endpoints. What do you see in terms of correlation between probably in particular reachable workspace and then other measures of quality of life or functional benefit.

Yes. So some of that work was done prior to Fulcrum studies by Bionic, the company that's developed the reachable workspace instrument. And they've previously shown and reported a very nice correlation between reachable workspace and the Neuro-QoL upper extremity patient-reported outcome that -- at the higher end of the reachable workspace, which is associated with better function. They have better function as evidenced by the Neuro-QoL upper extremity instrument. That instrument is now also 1 of our secondary endpoints in Phase III. And they've also been able to show a correlation with activities of daily living to the extent that patients with a reachable workspace score greater than 0.7 had minimal impact on their activities of daily living, whereas as the score decreases, there's a greater impact on the activities of daily living that's been observed.

Very helpful. All of this was recently published in the Lancet Neurology article. Maybe what key tidbits do you think we should take away from kind of the full publication of the data.

Yes. There was a very nice commentary that accompanied that. And I think they highlighted a couple of things about the study. One, this was the first interventional -- 1 of the largest interventional studies in FSHD period, but the first to really show a benefit on outcomes. And the outcomes in this case were structural on the MRI, functional like the reachable workspace and dynamometry and also on patient-reported outcomes. And so it's really the first time that, that's been demonstrated in the FSHD patient population with a therapeutic. And I think that that's really the thing that gives people excitement and encouragement.

Okay. Great. Maybe with that, in mind, walk us through the Phase III trial design, including some of the key parameters and assumptions that inform patient selection, trial size, the duration of the study and then the endpoints.

Okay. Excellent. So just to compare and contrast the Phase II and the Phase III, Phase II was 80 patients, 40 in each group, 1:1 randomization losmapimod, placebo, followed by an open-label extension. That overall design is preserved in Phase III 1:1 randomization, 48-week treatment period, open-label extension. In Phase II, it was focused in on FSHD type 1 patients. which is about 95% of all FSHD. The Phase III includes a small number of type 2 patients clinically and functionally are indistinguishable. It's just the genetic underpinning by which they cause the increased DUX4 expression is different. But there are some type 2 patients in the Phase III study. The powering of the Phase III was based on the effect size observed in that Phase II study. And with the observed effect size on the reachable workspace as well as the standard deviation of the reachable workspace change from baseline in that study. We ended up starting the Phase III at about 93% powered with 230 patients to be enrolled. At the end of the day, there was such demand for the study at the clinical sites that we ended up over enrolling the study unintentionally, of course. And so instead of 230, we had 260 patients. And of that 260 that 242 type 1s, 18 type 2s. So it's a small percent of type 2s, which is what you'd expect from the epidemiology but we moved from an expected type 1 population of 210 to an axle of 230 that pushed the power from 93% to 96% in that study. Reachable workspace is the primary endpoint and the key secondary endpoints are mostly derived from the Phase II study, and they include the patient global impression of change. which was positive in the Phase II study, the MRI fat infiltration in the intermediate muscles that we discussed, which was positive in the Phase II study and the shoulder abducted dynamometry, which again was positive in the Phase II study. And then the fourth is the Neuro-QoL upper extremity, not in the Phase II, but previous data, as we mentioned earlier, showing a correlation. So that's at a high level of what that study looks like.

Okay. You mentioned that there was maybe like a minor difference in patient inclusion criteria. But how did you define the patient population that would be enrolled in the Phase III study? What are some of the key parameters there?

Yes. Yes. So there are a couple of things that were done and it's really mostly to constrain the patient population to the FSHD patients that are most likely to show progression over the course of the trial. In Phase II and in Phase III, the same clinical severity score, which is reaching clinical severity score was applied. That's applied exactly the same in Phase II as it is in Phase III. It excludes patients who are in wheelchairs who are not ambulatory at the severe end of the disease. And at the mild end of the disease, those patients who clinically minimally impacted. So that focuses the population. In addition, in Phase III, which was not in Phase II, we have a screening reachable workspace exam that occurs prior to the baseline exam. And that is similarly used to exclude the patients on the high end of the reachable workspace, which as we know from previous work is associated with minimal impact on activities of daily living, and that's a 0.7 score. And then on the low end, the 0.2 of those patients who are so severely impacted they're unlikely to show benefit. So we have an additional constraint that was not present in Phase II, which tightens it up somewhat and we'll be releasing this week at the FSHD society meeting in Denver. The baseline characteristics of both studies, we will be able to see the similarity between the studies in a numerical sense.

Okay. Great. And you mentioned the powering is 93% or was planned and now is 96%. But I guess, in terms of what is required to be shown in order to achieve statistical significance. What is the difference in reachable workspace you're looking for?

Yes. So again, based on the Phase II data, the magnitude of that change on the reachable workspace scale was 0.05 on a baseline score of 0.53 to 0.54. And so that's the treatment effect, the difference between the placebo and the active arm.

So about 10%.

Yes. So about a 10% change. that's the statistically significant because of the over powering, that magnitude of change could be about half of what that is. So half of that 0.05 to 0.025 and still reach statistical significance.

And in terms of standard deviation because I do get this question from -- what did you see in like kind of what's embedded in the trial assumptions?

Yes. So the exact standard deviation in the change from baseline of reachable workspace from Phase II was applied to the power calculation for Phase III. So the expectation is the magnitude of change from Phase II, the standard deviation from Phase II, and we assume the 10% dropout rate in both of the studies as part of the assumptions.

Okay. And then as you think about like how variable reachable workspace has proven to be across studies of that endpoint, what sort of expected of patients in this.

Yes. So we looked at -- there are a number of ways that this has been looked at in terms of test-retest that's been published, showing a very high correlation between the test-retest evaluations. We also looked at the placebo group within the Phase II study. So patients who weren't expecting to get a therapeutic benefit. And in those patients showed a very high correlation of reachable workspace from exam to exam. And it's not done just at baseline and then at 48 weeks, which I think sometimes folks assume there are a number of intermediate measurements that are taken. So it's baseline week 4, 12, 24, 36 and 48. And we use all of those data combined in a model in order to get the change from baseline over that 48-week period.

Okay. That's super helpful. Given the reachable workspace is somewhat -- I mean it's used, but it's somewhat of a novel endpoint, particularly from a regulatory perspective. I guess, what is the view from regulators on this as a registrational trial endpoint?

Yes. So from the get-go, this was proposed by Fulcrum as the primary endpoint for [indiscernible] the Phase III study, and that's remained the case. We've not received any alternative endpoints or suggestions for alternative primary endpoints from the agency. Clearly, a recognition that it's a novel endpoint. There are no drugs that have been approved using the reachable workspace before. There are no drugs ever been proven to be successful...

Have proved in FSHD anyway...

Before either, and we know from our discussions with FDA that they're hearing more about it as an endpoint because other sponsors are coming to them with this. So to some extent, they've expressed appreciation for the work that we're doing, a lot of the way to establish reachable workspace as an important clinically meaningful endpoint. And I think what we're doing in collaboration with them and the discussions have been with both the review division as well as the COA division on this is really establishing what are the particular questions that they expect us to be able to answer at the time of our NDA submission, and we have agreements on that and we're focused on executing on that plan.

Okay. What other secondary endpoints do you think regulators are going to care the most about is to look at the totality of data?

Yes. And I think the totality of data is an important aspect of this, and that's certainly been articulated. As I mentioned before, they're divided into a few buckets. The MRI is an important one because that is a whole body MRI. It's not focused specifically on the shoulder girdle like the primary endpoint, and it gives us a systemic look at what's going on with the pathology of the disease. So I think that's going to be an important one. That's one of our key secondary endpoints. The PROs like the patient global impression of change are important because that gives you insight into how the patients are feeling. And then the -- and it's the [indiscernible] as well as the Neuro-QOL upper extremity that are secondary end points. And then the last one is the shoulder abducted dynamometry, which is really a strength measurement of the abducters, which is probably the motion that these patients have the most difficulty with is getting their arms up above their -- up above their shoulders up above their head. So I think those are the key 4 secondary endpoints, obviously, along with the safety of the drug, and that's 1 of the benefits that we have that is not common in these rare diseases because the drugs being studied in other indications, very large patient safety database that looks favorable and certainly a profile in FSHD patients that looks very similar to that in other indications. So that I think the safety is a very important part of the totality of evidence along with those secondaries that I mentioned.

Yes. That's great. So pending positive Phase III results, maybe talk to us -- you didn't miss in a bit of time already on the market opportunity, but talk to us about the commercial opportunity as you see it within FSHD, particularly around like patient identification and finding these patients.

Sure, sure, absolutely. As I mentioned at the outset, about 30,000 patients in the U.S. and maybe just for sake of simplicity, let's start there, which is where a big focus of our pre market prelaunch activity is. So we know that most of these patients are currently treated by 1 of a number of neuromuscular specialists that reside at these muscular dystrophy clinics around the country. In terms of what percent are diagnosed, I'll say let's look at a genetic test clinical confirmation. And what we know right now from work that we've done is that genetic testing is used in about 20% to 30% of these patients. And that shouldn't come as a surprise because if there are no treatment options for these patients, why would you spend the time, the effort and the money to do the genetic test to confirm that the patient has FSHD. So obviously, we would expect that when a drug does become available, we would expect the use of genetic testing in patients with FSHD should grow considerably. We also anticipate that many of the payers will require a confirmed genetic testing before actually approving the drug.

Okay. So in terms of standard of care right now, I guess, what is the standard of care? And where are these patients mostly being treated?

Yes. So a lot of them are being treated, as I mentioned, at -- by the neuromuscular specialists at these -- the MDA or the Muscular Dystrophy Association clinics around the around the country. In terms of how they're being treated, as I mentioned at the outset, which is why I think we're so excited about this opportunity is these patients have nothing. There are no drugs for the treatment of FSHD. And there's no drugs that are used off label for the treatment of these patients. Steroids don't work. They will take -- there is pain associated with the disease. And so many times, patients will take over-the-counter medications nonsteroidals for the treatment of that disease. Many of them are seen by a physiatrist so assisted devices for walking, 20% of these patients ultimately become wheelchair bound. But I think that's one of the things that we find so exciting is to be able to be on the cutting edge of delivering the first ever approved product for these 30,000 patients in the U.S. that suffer from this terrible disease.

Okay. So then in terms of like the portion of these patients, that would be good candidates for losmapimod, like how do you think about placing out the patient population? Or is there any?

Yes. So we've done some research based on the data. But our plan is to embark upon a pretty extensive research study once we get the results in the fourth quarter of this year in the REACH study to essentially be able to show that patient -- sorry, show that product profile to the physicians and ask them what percent of their patients they would treat. There has been some anecdotal work done by other research analysts that cover us in addition to yourself, Corinne. And I think what we've heard and maybe to sort of reframe the question, I think when the question has been posed to physicians, what patients would you put on this drug? I think many times they say...

What patients would I not put on this drug.

Exactly. Like what patients would I not put on this drug. And what we hear across the board is that probably for those patients that are too far gone because, as Iain mentioned, the data that we have right now in our Phase II study shows that essentially we can stop the progression of the disease over a 48-week and an additional 48 weeks, so a total of 96 weeks, we essentially can stabilize their disease. But if a patient is too far gone and by too far gone, I mean, the muscle fibers have been infiltrated with fat. They're real chair bound, there's really not much you can do for those patients. That's probably the small segment of the market, the physicians say, these are the patients that I may not put on the drug. But if you think about maybe even a patient that may be a healthy patient that's early in their disease, the idea of being able to put a patient on a drug that has the potential to stabilize their disease for many, many years to come. I think that's an area where physicians find it particularly an exciting opportunity for these patients.

Yes. That makes sense. So then as you think about like the size of the sales force and infrastructure that will need to be in place to support a launch like this, I guess, talk to us about how you're thinking.

Sure. So one of the things I say internally is that if we're going to err on the side of underfunding versus overfunding the launch, specifically in the U.S., we're always going to err on the side of over funding. And so our cash runway, which I'm sure we'll talk about a little bit later, has very sort of aggressive numbers in for the commercial launch in the U.S. In terms of the size of the sales force, we've done a little bit of that sizing, but I would say probably the best place to direct people to would be maybe the most recent launch in another neuromuscular disease FA or Friedreich's ataxia. And when Reata launched that drug, that drug has actually done very, very well with very healthy pricing. And I think they launched with somewhere between 40 or 50 sales representatives specifically in the U.S. And with that, you can pretty adequately cover the neuromuscular specialists that are seeing these patients at these muscular dystrophy centers.

You recently announced a partnership with Sanofi for the ex U.S. launch. Talk to us about why you thought the deal was important to do, particularly now and what it offers you in terms of the economics?

Sure. Yes. So maybe just very specifically about the economics then we can talk strategically. So yes, just a couple of weeks ago, we announced a partnership with Sanofi, where they will take all ex U.S. rights. We have U.S. rights. There was an $80 million upfront payment there, a number of clinical, regulatory and sales milestones that, over the lifetime of the drug, add up to about $975 million. There's also cost sharing on any of the development work that needs to be done on a go-forward basis from the date that deal was signed and we estimate that, that total cost for the losmapimod study, for all future studies is about $50 million. So Sanofi would be on the hook for that, we would be on the other hook for that. And then from a royalty standpoint, we've got royalties that's starting to sort of mid sort of the low double digits and get up to the sort of the mid-20s as revenue scale. I think strategically, I mean, we selected Sanofi because we believe unequivocally that they're the best part. They've got a very, very strong $3 billion neuromuscular global franchise with some of their drugs to treat Fabry's disease and Pompe's disease. So very good clinical, regulatory and commercial infrastructure. And I think strategically, one of the things that we like most about Sanofi is they can -- they essentially can -- they can get this drug to patients in ex U.S. markets much quicker than we could ever do on our own. So if you think about the planning that we were doing to launch in Europe prior to the initiation of the deal, we had that on about a sort of 12- to 18-month lag compared to our assumptions around the U.S. launch, which we're anticipating in 2026. And Sanofi has been able to essentially sort of accelerate that such that the European launch appears to be on track similar to around the same time as the U.S. launch.

Okay. Last question on losmapimod, and then we'll spend a couple of minutes maybe on Pociredir. The intellectual property, remind us what you have.

So composition of matter has expired, but we do have very strong method of use patents as well as future patents that [indiscernible] pending that we believe would further strengthen the patent state for losmapimod. And those method of use patents extend out until 2038 with [Audio Gap] standpoint to extend those patents beyond '23.

[indiscernible] I know we don't have a ton of time left, so we'll just do a [Audio Gap].

Do you want to maybe start. Here we are. It's called the PIONEER study. That study was placed on clinical hold last year. We got off clinical hold in August of last year. We are actively activating sites. We've got a number of sites that are activated. And on a go-forward basis, our plan is to enroll 10 patients in a 12-milligram cohort, and those patients will be dosed over a 3-month [indiscernible]. And then we're going to be escalating to a 20-milligram cohort, also 10 patients, study duration is also sort of 3 months. And what we saw in patients prior to the initiation of the hold is that we were showing very, very, very impressive levels of fetal hemoglobin after only 6 weeks of dosing in the 12-milligram cohort. So we had patients that were coming into that study in the sort of 10%, 15% baseline fetal hemoglobin. And after only 6 weeks of dosing with the 12 milligram, we were getting some of those patients up to about 25%. And we'll probably talk a little bit about sort of what's your sort of threshold like what are you getting to? And what are you hoping that you'll be able to see in terms of increases in [ fetal hemoglobin ]? And what does that do just to the symptoms of the patients who have this disease.

Yes. To that point, I think you've talked about an update this year. What could be included in that update? And what would you look to show to give us some confidence [indiscernible] working.

Sure, sure. Yes. So as I mentioned, I think that what the cell and gene therapies, the more recently improved cell and gene therapies have been able to demonstrate is that if you can get patients to fetal hemoglobin levels north of high 20s, there's a very, very strong inverse correlation between increases in fetal hemoglobin and drop in vaso-occlusive crises or these pain crises of these sickle cell patients experience. And what the literature has demonstrated very clearly is that getting patients north of the high 20s, essentially, their disease becomes asymptomatic. And the cell and gene therapies have been able to demonstrate that. So right now, our plan is, as I said, to enroll 10 patients in the 12 milligram, 10 patients in the 20. We haven't provided a lot of guidance in terms of when we would expect to see that. But what we have said is once we get a critical mass of patients in that 12 milligram, so we can see what that enrollment trajectory looks like, and we can see patients are coming from specifically which sites. I think at that point, once we have a critical [Audio Gap] they are more specifics in terms of when we'll have the results of the 12-milligram and when we'll have the results of the 20 milligram. They are being done sequentially. So we would share the data set on the full 10 patients in the 12-milligram 3 months of duration, followed at some point in the future after we share the results of the 12-milligram and 20-milligram cohort.

Okay. And then as you think about the question post clinical hold was which patient population would be able to [Audio Gap] but that's not the end game for you, I don't believe. So maybe talk to us about what you need to show to kind of get back to a broader patient group.

Sure. So just real quick, and then I'll turn it over to Iain. So right now, if you look at our more a more narrowly defined inclusion exclusion criteria. We believe in the U.S. about 7.5% to 10% of the 100,000 patients with sickle cell meet that inclusion/exclusion criteria. And I think you're 100% right that, that's not our sort of -- that's not the commercial market opportunity for us. I think it's really getting the data and then having a subsequent conversation with the agency. And Iain has up been a large part of those conversations much more than I have.

Yes. And I think one of the important things that we learned as part of those conversations because we did discuss with the agency, the restrictions on the gene therapy inclusion criteria at that time knowing, of course, that gene therapy with its myeloablative conditioning regimens and so on is of itself likely associated with risks, including malignancy. And so we asked FDA how they view that and their response to us well. We view this as a risk benefit calculus, and we know that the benefit of gene therapy ultimately is essentially a cure of the disease. And so they're balancing out the risk and the benefit. And I think for Pociredir at an early stage of development, we have some really encouraging efficacy data, but we don't have a big body of evidence on that yet. And so our approach is very much focused on filling out that efficacy side of the equation to speak to the benefit of the therapy that will then help to balance the risk and the benefit and also the patient population in the light of that. So it's going back with some of the efficacy data that we're generating now in PIONEER that will be important for that.

Okay. Maybe the last question for me. cash runway? Where are you? And how do you think about sources of capital?

Sure. Absolutely. So I think with the recently announced deal with Sanofi with that $80 million upfront and some near-term milestone payments. That puts us into 2027 from a cash runway standpoint. And that assumes success on both the losmapimod program as well as Pociredir. I think the other key assumption is that assumes very, very well-funded launch in the U.S.

Okay. Great. I think that takes us about the time. It's a great way to wrap up. Very much appreciate it. Thanks, the team from Fulcrum Therapeutics for joining us, and thanks to everyone joining us here for the Goldman Sachs Global Healthcare Conference.

That's great. Thanks so much, Corinne.

Thanks.