NASDAQ:FULC Fulcrum Therapeutics Q3 2023 Earnings Report $5.66 -0.08 (-1.31%) As of 09:58 AM Eastern This is a fair market value price provided by Polygon.io. Learn more. Earnings HistoryForecast Fulcrum Therapeutics EPS ResultsActual EPS-$0.39Consensus EPS -$0.44Beat/MissBeat by +$0.05One Year Ago EPSN/AFulcrum Therapeutics Revenue ResultsActual Revenue$0.76 millionExpected Revenue$1.81 millionBeat/MissMissed by -$1.05 millionYoY Revenue GrowthN/AFulcrum Therapeutics Announcement DetailsQuarterQ3 2023Date11/7/2023TimeN/AConference Call DateTuesday, November 7, 2023Conference Call Time8:00AM ETUpcoming EarningsFulcrum Therapeutics' Q2 2025 earnings is scheduled for Monday, May 12, 2025Conference Call ResourcesConference Call AudioConference Call TranscriptPress Release (8-K)Quarterly Report (10-Q)Earnings HistoryCompany ProfilePowered by Fulcrum Therapeutics Q3 2023 Earnings Call TranscriptProvided by QuartrNovember 7, 2023 ShareLink copied to clipboard.There are 8 speakers on the call. Operator00:00:00Good morning, and welcome to Fulcrone Therapeutics Third Quarter 2023 Financial Results and Business Update Conference Call. Currently, all participants are in a listen only mode. This call is being webcast live on the Investors section of ForChrome's website at www.fullchrometx.com and is being recorded. Please be reminded that remarks made during this call may contain forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about the company's future expectations and plans, clinical development timelines and financial projections. Operator00:00:45While these forward looking statements represent Fulcrum's views as of today's, this should not be relied upon as representing the company's views in the future. Full Prime may update these statements in the future, but is not taking on any obligation to do so. Please refer to Fulcrum's most recent filings with the Securities and Exchange Commission for a discussion on certain risks and uncertainties associated with the company's business. Leading the call today will be Alex Appear, CEO and President of Fulcrum. Joining Alex on the call are Alan Musso, Chief Financial Officer and Doctor. Operator00:01:22Ian Frazer, Interim Chief Medical Officer. After providing updates on our key programs, there will be a brief Q and A in which Alex, Alan and Ian will be available to answer your questions. With that, it's my pleasure to turn the call over to Alex. Sir, you may begin. Speaker 100:01:40That's great. Thanks, Dewanda, and thanks to all of you for joining us today. We are pleased with the progress that we've made in the Q3 of 2023 advancing our 2 clinical assets, losmapimod and poseradir. In addition, we remain well capitalized with a cash position of $257,000,000 as of September 30 and have extended our cash runway into 2026 through a strategic review and budget process only on our essential priorities. So what I'd like to do this morning is to provide an update on our 2 key programs, losmabumon, pervasioscapulohumeral muscular After which, I'll turn it over to Alan for some financial highlights. Speaker 100:02:33So let's start with our most advanced program, losmethimod. Just as a quick reminder, losmafimod is a selective p38 alpha beta MAP kinase inhibitor It's currently in Phase 3 development for the treatment of FSHD for which there are currently no approved treatment options. FSHD is a form of muscular dystrophy with an estimated patient population of 30,000 in the U. S. Alone. Speaker 100:03:01The disease is characterized by a slow and progressive loss of muscle function over many years, resulting in significant impairment of upper Like reaching for a cup of coffee in the kitchen cabinet, brushing your teeth, feeding oneself and even practicing good hygiene. These critical factors and our insights on the genetic underpinnings of FSHD drove us to identify and develop a safe and effective treatment option with the potential to slow disease progression for these patients. In September of this year, we completed enrollment in REACH, our global Phase 3 trial for losmafimod, which we initiated in June of 2022. We believe that the rapid pace of enrollment of the 260 patients into the trial is a real testament to the high unmet need of this rare disease. We are on track to report top line in the Q4 of 2024, which will bring us one step closer to delivering the first ever FDA approved therapy for FSHD. Speaker 100:04:09Now let me just give a quick reminder to everybody about REACH. REACH is a 48 week trial intended to be registration enabling both in the U. S. And in ex U. S. Speaker 100:04:19Geographies. The primary endpoint for the study is the change from baseline in the relative surface area or RSA score, which is a quantitative assessment of Reachable Workspace or RWS. This is a measure of Upper extremity range of motion and function that specifically evaluates shoulder and arm mobility using 3 d motion sensor technology. Preserving this upper extremity function is critical for patients to maintain their independence and their ability to perform some of these activities of daily living that I spoke about earlier. As part of this study, we'll also be looking at other key secondary endpoints like muscle fat infiltration or MFI, which is an important marker of disease pathology measured by whole body MRI as well as reported quality of life measures and healthcare utilization questionnaires that will help inform our thinking on our payer strategy as we begin preparing for commercial launch here in the U. Speaker 100:05:21S. We are pleased to have reached, there is no pun intended there, this critical milestone and we look forward to sharing with everyone top line results in the Q4 of next year. So let me now move on to posiridir, our oral fetal hemoglobin inducer or HBF for short for the potential treatment of patients with sickle cell disease. In August 2023, the FDA lifted the clinical hold On our investigational new drug application for prociridare for the potential treatment of sickle cell disease, Our interactions with the FDA were productive and collaborative throughout the hold and we're pleased to have aligned on a revised inclusion exclusion criteria that targets a more severe patient population for this Phase 1b study. I think it's also important to note that there were no changes in the protocol defined dose escalation scheme or the 3 month treatment duration. Speaker 100:06:21We are working hard to resume Enrollment in the Phase 1b study at the 12 milligram dose followed by the 20 milligram dose of posiridir, each of these dose cohorts are scheduled to enroll 10 patients. We are reactivating current sites as well as identifying new sites in the U. S. And ex U. S. Speaker 100:06:39That are excited to participate. Now as many of you know, activating new sites takes time given the contracting and IRB approval process. I think once we have a few months of enrollment under our belt, we'll be in a far better position to estimate when we would expect to have results Of the 12 milligram and the 20 milligram to share with everyone. I just want to take a minute and talk about why we're so excited about prociradir given the fact that this is only in a Phase 1b study. So data that we obtained prior to the clinical Specifically, after only 42 days of treatment, we observed up to a 10 percentage point increase In fetal hemoglobin from baseline or total fetal hemoglobin of approximately 25%. Speaker 100:07:39We believe that as an oral HBF inducer, we believe that Posider has the potential to provide a differentiated therapeutic option for patients living with sickle cell disease. Addressing the significant unmet need in sickle cell remains a Key priority for us and we look forward to providing further updates in our progress. So with that clinical update, I'll now turn it over to Alan, our Chief Financial Officer, Sir, who will provide an update on our financials. Alan has been a great addition to the team since joining in August and he will be invaluable as we move into the next phase of growth and continue to advance our mission of delivering these transformative therapies. So, Alan, over to you. Speaker 200:08:22Thank you, Alex. Let me start with our cash position. We ended September 30, 2023 with cash, cash equivalents and marketable securities of $257,100,000 And during the Q3, our net cash burn was 21,100,000 We continue to operate from a strong financial position and based on our recent operating results and current projections, We now expect our cash runway to extend into 2026, an update from our prior guidance of mid-twenty 25. In the Q3 of 2023, our collaboration revenue was $800,000 That compares to $1,200,000 for the Q3 of 2022. Our research and development expenses were $18,200,000 for the Q3 of $23,000,000 compared to $15,400,000 for the Q3 of 2022. Speaker 200:09:17The increase of $2,800,000 was primarily due to increased costs associated with the advancement of our Phase 3 REACH trial, including the completion of enrollment during September of 2023. Our general and administrative expenses were $10,000,000 for the Q3 of 2023 as compared to $9,700,000 for the Q3 of 2022. The increase of $300,000 was primarily due to increased facilities, professional services and software costs. Our net loss was $24,000,000 for the Q3 of 2023 and that compares to $23,700,000 for the Q3 of 2022. And with that, let me turn Speaker 100:10:00it back over to Alex. Great. Thanks, Alan, and again, great to have you on Speaker 300:10:03the team. So, Tawanda, let's go ahead and Speaker 100:10:05open it up for questions. Operator00:10:36Our first question comes from the line of Corrine Jenkins with Goldman Sachs. Your line is open. Speaker 200:10:42Good morning. This is Craig on for Corrine. So I had one specifically related to vosirudir. And I guess with that Phase 1b study, What do you guys hope to see in order to consider moving forward the program? And based on that, what do you think you need to show from a risk benefit point of view In order to get the FDA to maybe reconsider the current patient population you're evaluating the agent and so maybe a broader one? Speaker 200:11:10Thank you. Speaker 100:11:11Yes, it's great. Thanks for the question, Craig. And let me turn that over to Ian Frazer, our Chief Medical Officer. Ian has really been instrumental in Driving those conversations with the FDA, so I think he's probably best equipped to answer that question. Speaker 300:11:24Yes. Thanks, Alex, and thanks for the question. As Alex mentioned earlier, at the 12 milligram dose that we've studied to date, which was only a partial cohort, essentially only 3 patients And the longest duration of 42 days, so just 6 weeks halfway in to the treatment period, we were seeing rises of around 10 percentage Points in the fetal hemoglobin. Obviously, it depends where your baseline HBF starts out as to where you end up. And there was at least one patient there started out at about 15 relatively high and reached 25, which we believe and I think Backed by the literature that once you enter the high 20% range of total HBF That you significantly impact the symptoms of sickle cell disease. Speaker 300:12:16So that's the range that I think will be Most convincing to reach and I think what we're trying to demonstrate with this is with the 12 milligram dose as we extend the duration of dosing Up to the full 3 months, how much higher do we get the fetal hemoglobin to rise and across the entire cohort at Different baseline field hemoglobins, how high do each of those individuals reach. So that's our intent. That's The target towards which we are shooting, and as we've articulated previously based on our earlier healthy volunteer data, We believe that there is even further incremental efficacy to be gained as we go up from 12 milligrams to the next dose around 20 milligrams, And we fully expect that, that will outperform even the 12 milligram dose. So that's the directionality that we expect. That's the region of total HBF that we think will be significantly transformative. Speaker 300:13:21And that's what the Data we'll be looking for as we start to dose in this cohort. Speaker 100:13:26Yes. And then Craig, this Speaker 400:13:27is Alex. Let me just sort of Speaker 100:13:28answer specifically your question about What do you feel like we need to show to the FDA to expand the patient population beyond where we are today? I think obviously the FDA looks at everything from a risk benefit perspective. And right now, we've shown some benefit, I'll be in a very small number of patients. So if we're able to achieve what Ian spoke about, we'll take that information Back to the FDA and have what we believe is a very sort of thoughtful discussion armed with much more data to show how this drug can benefit And from there, we believe that over the long run, we will be able to expand that patient population. I think what's important to remember is that There's been a lot of talk recently over the past couple of weeks with the Vertex CRISPR cell and gene therapy Compound as well as bluebirds. Speaker 100:14:21And I think that if you look at the levels of fetal hemoglobin that they're able to get up to in the sort of 30s, We do believe that with based on what we've been able to show prior to the hold, we believe that with 3 months of dosing with 12 milligram and potentially 3 months of dosing with a 20 milligram, we may be able to get up to similar levels. And I think that's Very, very exciting for the sickle cell community and for the patients specifically. Speaker 200:14:52Got it. Thank you very much. Operator00:14:55Thank you. Please stand by for our next question. Our next question comes from the line of Dae Gon with Stifel, your line is open. Hi. Speaker 500:15:12This is Benavir on for Dagon. Thanks for taking our question. Just a couple on placerider. How challenging has it been to re sign some of the prior trial sites to participate in the trial at this point? Can you share some color on that? Speaker 500:15:25And What are some of the questions that they're having about the clinical hold and how they can feel more comfortable about drug safety? And then a follow-up To that is, we know that you're not exactly sure about when you're going to have data on Poserador, but is it more likely to be mid year or year end or somewhere in between, If not at a conference, maybe just a presentation through the company. Thank you. Speaker 100:15:47Yes, that's great. Thanks, Batya. And let me start and then, Ian, please feel free to jump in So just as a quick reminder, we had 7 sites in the Phase 1b study Prior to the initiation of the hold and it's just as a reminder that was an all comer study. So our plan specific and they were all U. S. Speaker 100:16:08Our plan specifically in the U. S. Is to double the number of sites specifically in the U. S. As well as to look outside of the U. Speaker 100:16:19S. As well. And we feel that we need to go to a greater number of sites simply because we have a more Narrowly defined inclusion, exclusion criteria. So it will be a more difficult trial to enroll than we have in the past. I think what we've been hearing from physicians and I'd like Anne to comment on this as well, but I think what we've been hearing from physicians is The benefits that this drug as an oral HBF inducer can provide to patients, right? Speaker 100:16:48We've been able to show up until now that With 6 weeks of dosing at a 12 milligram dose, we can get patients to total fetal hemoglobin levels of 25. And I think that's really exciting for the sites and the physicians that are going to participate in this study and I think it's also very exciting For the patients as well. I think in terms of when we think we'll be able to show that, I think right now Our focus has really been on engaging with the centers. Once we have those centers stood up, we've got a couple of IRBs that have already approved it. We have one site that is ready to start receiving drug, and we're also doing a lot with the community, sickle cell community in around those sites to really sort of Educate the community about this very, very interesting study that the center is now participating in. Speaker 100:17:41So that's really been our focus. I think at this point, Ben and Ziron, I think if I was to give you sort of any indication, the only thing I would know with great certainty is that, And that indication or that guidance would be incorrect. So I think give us a couple of months, let us get a couple of Months of patient enrollment under our belt, as I've said in the past. And I think at that point, we'll be in a much better position to provide more specific guidance that I feel I feel more comfortable out. So anything else you think around the centers, Ian? Speaker 300:18:13Yes. Thanks Alex. I can provide a little bit of color around the types of sites themselves. And as Alex alluded to earlier, study was an all comer study. And so we were at a number of sites That started out essentially as pediatric sites and because of the way that sickle cell disease care is administered, A lot of the pediatric sites hold on to their older patients as they go into adulthood because they don't have great partners to transfer those patients to. Speaker 300:18:45And so we had a number of those sites within the study originally. Those are obviously Somewhat younger patients overall, less treatment experienced and less severe impact of disease just given the duration that they've experienced. And what we're finding as we go out is that a number of those sites feel that they don't have quite the level of severity or Previous treatment experience that we might need for the protocol. And so those are sites that are not continuing, but some of them Clearly still do have those patients. So that's been one experience and then we've also broadened our net And now looking at a number of sites that treat exclusively adults that obviously do have many of these more severely impacted patients. Speaker 300:19:35And so we are bringing them into the fold as well. So we're casting a wide net. We've noticed those subtleties of the patient populations at the different sites And we're meeting with lots of investigators. Speaker 500:19:49Excellent. Thank you so much. Speaker 100:19:51Thank you. Operator00:19:53Thank you. Please stand by for our next question. Our next question comes from the line of Joseph Schwartz with SVB Leerink. Your line is open. Speaker 600:20:11Hi, it's Joe Schwartz from Leerink Partners. I was wondering if you could talk some more about how the new Inclusion criteria negotiated with the FDA could influence the profile of disease severity, which will be reflected in the future cohorts for the Phase 1b for paciradir. And do you think that paciradir will still be able to generate an I guess I'm wondering if you think the patients in future cohorts will have as much of an opportunity to reach the 20% range you referenced earlier, If they're starting out at lower baseline levels compared to those who were treated previously? Speaker 100:20:57Great question, Joe. I think to answer that, let me turn that one over to Ian. Yes, absolutely. Speaker 300:21:02And it's one that we've given a lot of thought to and I think it will be interesting to see The data as it rolls out, I think I'd make a couple of comments about it. One is in the 16 patients that we've treated Thus far in the 1b study, it's a pretty high rate of baseline fetal hemoglobins. And while we don't have full 3 months data in all of them, The initial trajectory of increase in HBF is pretty consistent across all of those. So it didn't seem as though it was higher, A steeper rate at the higher baseline HBFs and the lower ones appear to be responding just as well. So that's the first point. Speaker 300:21:45The second point is, I think the mechanism of action being distinct from that Of HU has some advantages in this respect. Obviously, we'll need to demonstrate that as we move into the more severely impacted patients, But it's not operating through a stress erythropoiesis type response, which HU is. There's some discussion about whether that mechanism Might be susceptible to depletion of stem cells or fatigue in the marrow or whatever description you want to append to it. So I think that the differentiated mechanism of action acting through alterations in gene transcription are likely to be Successful in that more severely impacted patient population, but we'll get the patients in and we'll I have to demonstrate that in the clinic and that's our expectation. Speaker 600:22:37Interesting. Thank you. And then could you just walk us Through the calculus you employed to develop the estimate that your inclusion criteria for PERSERADIR covers 7,500,000 to 10,000 Sickle cell patients in the United States. And I'm just wondering how confident you are in that estimate as you engage with the sites now? And What do you expect the screen failure rate for patients to be going forward? Speaker 100:23:02Yes, maybe As it relates to the screen failure rate, I'll ask Ian to answer that. But yes, let me give a bit of color, Joe, in terms of how we got to that number. I think what's important to remember in looking at the inclusion, exclusion criteria, these are people that have either Tried or failed on some of these advanced therapies or for whatever reason don't have access to the advanced therapies Voxelador and I was mad because of the simple fact that they don't have proper insurance or their co pays are too high. So let me give you some high level numbers. We know that from 2019, when both VOXX and CRIS launched through 2022, both of those Products each generated about 10,000 prescriptions. Speaker 100:23:55We know that About 25% of those prescriptions never converted to a patient start and our assumption there is that Those patients simply didn't have proper insurance cover or didn't have access to the drug due to payer related issues. What we also know is that during the 1st year, you saw about a 30% discontinuation rate, with VOXX, we don't actually have specific numbers for crizanlizumab Discontinuation rates in the 1st year, but you could always you could assume that it's probably similar to VOXX, maybe a little bit higher because it does require Sort of infusions at an infusion center. So sort of doing all of that math gets you to around sort of 75,000 to 10000 patients. Where that number may be overestimated is the fact that not all of those patients meet the patient severity criteria, But where that number may be an underestimate is the fact that it doesn't include any prescriptions In 2023, we only have prescriptions through 2022. So sort of taking all of those numbers into consideration, That's how we sort of arrived at the 75,000 to 10000 patients in the U. Speaker 100:25:17S. That meet that Inclusion, exclusion criteria, which represents about 7.5% to 10% of the total 100,000 patient population. Did you want to address your second question? Speaker 300:25:30Yes. So this is Ian. We haven't projected a screen fail rate At this point, I can tell you that for the initial phase of the study, where we recruited 16 patients, That screen fail rate was a little over 50%. So it was a relatively high screen fail rate at that point And we're sort of carrying that forward at the moment even though patient population is likely to be more severe. We have more experience with the sites and with the education of the sites around the protocol and so expect to be able to help with patient selection in that fashion. Speaker 100:26:11That's very helpful. Thanks for all the insight. Yes. Thanks, Joe. Operator00:26:16Please stand by for our next question. Our next Question comes from the line of Edward Denhofer with Piper Sandler. Your line is open. Speaker 400:26:30Great. Thank you. Good morning, everyone. Speaker 100:26:32Good morning, Ned. Hi, Ted. Speaker 400:26:35So no one ever asks a question on poor little lasmapimod. So I guess I'll be the one to ask it. With all of the with the data coming in the back half of next year, what are some of the Commercial prep that you're doing. And as you kind of project out here, what's the calculus between Keeping it and launching it yourself, partnering it, maybe partnering it overseas, kind of where just update us on sort of where your head is on that. Thanks. Speaker 100:27:05Yes, absolutely. Thanks so much for the question, Ted. And I appreciate you asking a question on lasmapamat. Thank you. So yes, just as a quick reminder, we would have we plan to have top line results in the Q4. Speaker 100:27:18We would then file the NDA sometime in early 2025 for an approval sometime in 2026. We've been very clear that we believe that we can launch this drug quite successfully In the U. S. With a fairly sort of modest commercial infrastructure, while at the same time looking for partners ex U. S. Speaker 100:27:41And we will begin the process of sort of standing up that commercial organization, the end of this year, beginning of next year, starting with our first Kind of key hire, which would be that Chief Commercial Officer. And I think one of the reasons that we're so excited about Our ability to be able to do this ourselves is a fairly sort of concentrated market, it's a fairly small number of neuromuscular specialists that treat these patients with FSHD. They're very, very well organized from a patient advocacy standpoint We have an excellent relationship with the FSHD Society. And the fact that there are Currently no treatment options and the drug that's probably the closest behind us is probably 2 to 3 years Roche's product that's a myostatin inhibitor. It's 2 to 3 years behind us. Speaker 100:28:35We believe that we really do have an opportunity to be successful with this launch in the U. S, doing it ourselves And then the ability to help a tremendous number of patients in the U. S. As well as working collaboratively with a partner ex U. S. Speaker 100:28:49To help patients around the world. Speaker 400:28:53That's super helpful. And I do think it will garner more attention as we get into New Year. So thanks for the update. Speaker 700:28:58Yes. Thanks, Operator00:29:00Ted. Please stand by for our next question. Our next question comes from the line of Matthew Bigler with Oppenheimer and Company. Your line is open. Speaker 700:29:16Hey, guys. Thanks for the question. I will also jump on the FSHD bandwagon here. I wanted to ask maybe about some different scenarios for REACH3 and specifically if you saw a path forward, If the study doesn't hit or maybe narrowly misses the reachable workspace endpoint, like do you think the biomarker endpoint might be Efficient. I guess taking a page out of Sarepta's playbook and what we've seen now over the last couple of weeks, what kind of what are your thoughts there? Speaker 700:29:49Thanks. Speaker 100:29:50Yes, great question, Matt. Thanks for that. So let me turn that one over to Ian. Speaker 300:29:54Yes, thanks, Matt. So just to be clear, in terms of Biomarkers in reach, we are not evaluating the DUX4 transcriptome, which was evaluated in the Phase 2 study, is that's not really a feasible clinical trial measure to make. What we do have, however, are a number of secondary endpoints that are different than the reachable workspace endpoint. And those include the MRI endpoints, which I guess could be considered a biomarker, which evaluates the accumulation of fat In muscle tissue that still has what looks like normal contractile muscle interspersed With fat and so that we also showed in the Phase 2 study as for the reachable workspace That you've got a stabilization of that fat accumulation relative to the placebos who showed an increase. So we think that that's clearly An important secondary endpoint, we also have an evaluation of dynamometry, so conventional muscle strength testing, which we're evaluating. Speaker 300:31:03We have some patient reported outcomes that reflect on both Patient global impression of change, but also some specific questions related to FSHD itself. And so there are a number of those secondaries that I think will be important to consider irrespective of what happens to the primary endpoint. But if as you articulate the primary misses narrowly, I think having all of those secondaries trending In a favorable direction towards loss macromod over placebo will be extraordinarily helpful And persuasive in that context. Speaker 700:31:46Yes. I agree with that. Thanks for the question. Speaker 100:31:48Yes. And Matthew, this is Alex. The only other thing I would add to what Ian said is going back to something I said earlier regarding prociridir and how the FDA looks at everything from a risk benefit Perspective, I think what's also important to note is that when we file our NDA with the FDA, we will have over 3,600 patients in our Patient Safety Database. And this has been shown to be a very, very safe drug. And so I think that that is a really important So the piece of information that the FDA will look at as it considers the safety and efficacy data in totality and decides whether to approve this drug or not for patients For which they have none. Speaker 700:32:30Yes, makes sense. Thanks. Yes, thanks Matt. Operator00:32:34Please stand by for our next question. We have a follow-up from the line of Dae Gon with Stifel. Your line is open. Speaker 500:32:48Hi. Just one more question from us. For SSHD, can you remind us of the powering for Reach and the assumptions that went into it for the Reachable Workspace? Given that it's a mobility test, how should we think about it in the context again of the recent EMBARK trial failure? And what read through for the powering assumptions for Reach? Speaker 100:33:08Yes, great question. Let me turn that over let me turn that one over to Ian. Speaker 300:33:11Yes. So REACH was powered based on the observed data from from REDOX 4 from the Phase 2 study. And you may recall that was an 80 patient study, 40 in each arm. And essentially what we took was the change from baseline to the treatment effect glasumab Minus placebo on the reachable workspace and also assessed the variability in the measurements in that particular cohort and then applied it to the power calculations for the REACH study. The REACH study was originally powered On a total enrollment of 230 patients with an expectation that 210 of them would be FSHD Type 1 and 20 of them would be Type 2, and that's a reflection of the relative epidemiology of Type 1 versus Type 2. Speaker 300:34:06Type 1 is Overwhelmingly the most prevalent, 95% or so of that. The REDUX-four study enrolled only Type 1s. And so even though we are enrolling some Type 2s in the REACH study, we powered the study on only the Type 1. So the study was powered on an expectation of 210 Type 1 patients in the REACH study And that gave us a power of 93% or 94% using the magnitude of change and the standard deviation from REDUX-four. As it turns out, when we cut off screening for the REACH study based on what we thought the Screen fail rate was going to be in order to reach those 230 patients. Speaker 300:34:55The screen fail rate dropped down and we ended up enrolling a number of more patients. And so at the end of the day, the total enrollment was 260 instead of 230. And of that 260, there were 18 FSHD Type IIs, so we now have 242 FSHD I. So 242 versus the original powering around 210. So that bumps the power up into over 95% using the same assumptions from REDOX 4. Speaker 300:35:27So that was an inadvertent over enrollment that wasn't our intention, but was a reflection of the enthusiasm at the sites and the Fact that the sites had gotten better at screening the patients until the screen failure rate dropped down. And so that's where we stand based on our Actual enrollment now in reach. Speaker 500:35:50Well, thank you. Operator00:35:55Thank you. Ladies and gentlemen, this concludes the question and answer portion of the call. I would now like to turn the call back over to Fulcrum's CEO, Alex for closing remarks. Speaker 100:36:06Thanks, Towanda. So just to quickly wrap up, we remain as we always have deeply committed to treating the root cause of genetically defined rare diseases and bringing these transformative therapies to patients. Before we conclude today's call, as I always like to do, I'd Just like to extend my sincere appreciation and gratitude to my fellow Fulcrum teammates, to the physicians we work with to advance our clinical trials, And finally, and most importantly, to the patients who participate in our clinical trials as well as their families. Without them, We would not be able to achieve our goals as a company. Thanks again everyone who joined the meeting who joined the call this morning. Speaker 100:36:47Please stay safe and healthy. Operator00:36:50Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.Read morePowered by Conference Call Audio Live Call not available Earnings Conference CallFulcrum Therapeutics Q3 202300:00 / 00:00Speed:1x1.25x1.5x2x Earnings DocumentsPress Release(8-K)Quarterly report(10-Q) Fulcrum Therapeutics Earnings HeadlinesEarnings call transcript: Fulcrum Therapeutics Q1 2025 reveals improved net lossMay 3 at 10:56 AM | uk.investing.comFulcrum Therapeutics, Inc. (FULC) Q1 2025 Earnings Call TranscriptMay 2, 2025 | seekingalpha.comShocking AI play that’s beats Nvidia by a country mileYou’ve seen the headlines about Nvidia. Now Tim Sykes is sounding the alarm — because what CEO Jensen Huang is about to announce could change the AI market once again. 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Email Address About Fulcrum TherapeuticsFulcrum Therapeutics (NASDAQ:FULC), a clinical-stage biopharmaceutical company, focuses on developing products for improving the lives of patients with genetically defined diseases in the areas of high unmet medical need in the United States. Its product candidates are losmapimod, a small molecule for the treatment of facioscapulohumeral muscular dystrophy is under phase III clinical trial; and pociredir, a fetal hemoglobin inducer for the treatment of sickle cell disease and beta-thalassemia is under phase I clinical trial. The company is also discovering drug targets for the treatments of rare neuromuscular, muscular, central nervous system, and hematologic disorders, as well as cardiomyopathies and pulmonary diseases. Fulcrum Therapeutics, Inc. has collaboration and license agreement with Acceleron Pharma Inc. to identify biological targets to modulate specific pathways associated with a targeted indication within the pulmonary disease space; and MyoKardia, Inc. to discover and develop therapies for the treatment of genetic cardiomyopathies. Fulcrum Therapeutics, Inc. was Incorporated in 2015 and is headquartered in Cambridge, Massachusetts.View Fulcrum Therapeutics ProfileRead more More Earnings Resources from MarketBeat Earnings Tools Today's Earnings Tomorrow's Earnings Next Week's Earnings Upcoming Earnings Calls Earnings Newsletter Earnings Call Transcripts Earnings Beats & Misses Corporate Guidance Earnings Screener Earnings By Country U.S. Earnings Reports Canadian Earnings Reports U.K. Earnings Reports Latest Articles Is Reddit Stock a Buy, Sell, or Hold After Earnings Release?Warning or Opportunity After Super Micro Computer's EarningsAmazon Earnings: 2 Reasons to Love It, 1 Reason to Be CautiousRocket Lab Braces for Q1 Earnings Amid Soaring ExpectationsMeta Takes A Bow With Q1 Earnings - Watch For Tariff Impact in Q2Palantir Earnings: 1 Bullish Signal and 1 Area of ConcernVisa Q2 Earnings Top Forecasts, Adds $30B Buyback Plan Upcoming Earnings Fortinet (5/7/2025)ARM (5/7/2025)AppLovin (5/7/2025)MercadoLibre (5/7/2025)Lloyds Banking Group (5/7/2025)Manulife Financial (5/7/2025)Novo Nordisk A/S (5/7/2025)Uber Technologies (5/7/2025)Johnson Controls International (5/7/2025)Walt Disney (5/7/2025) Get 30 Days of MarketBeat All Access for Free Sign up for MarketBeat All Access to gain access to MarketBeat's full suite of research tools. 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There are 8 speakers on the call. Operator00:00:00Good morning, and welcome to Fulcrone Therapeutics Third Quarter 2023 Financial Results and Business Update Conference Call. Currently, all participants are in a listen only mode. This call is being webcast live on the Investors section of ForChrome's website at www.fullchrometx.com and is being recorded. Please be reminded that remarks made during this call may contain forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about the company's future expectations and plans, clinical development timelines and financial projections. Operator00:00:45While these forward looking statements represent Fulcrum's views as of today's, this should not be relied upon as representing the company's views in the future. Full Prime may update these statements in the future, but is not taking on any obligation to do so. Please refer to Fulcrum's most recent filings with the Securities and Exchange Commission for a discussion on certain risks and uncertainties associated with the company's business. Leading the call today will be Alex Appear, CEO and President of Fulcrum. Joining Alex on the call are Alan Musso, Chief Financial Officer and Doctor. Operator00:01:22Ian Frazer, Interim Chief Medical Officer. After providing updates on our key programs, there will be a brief Q and A in which Alex, Alan and Ian will be available to answer your questions. With that, it's my pleasure to turn the call over to Alex. Sir, you may begin. Speaker 100:01:40That's great. Thanks, Dewanda, and thanks to all of you for joining us today. We are pleased with the progress that we've made in the Q3 of 2023 advancing our 2 clinical assets, losmapimod and poseradir. In addition, we remain well capitalized with a cash position of $257,000,000 as of September 30 and have extended our cash runway into 2026 through a strategic review and budget process only on our essential priorities. So what I'd like to do this morning is to provide an update on our 2 key programs, losmabumon, pervasioscapulohumeral muscular After which, I'll turn it over to Alan for some financial highlights. Speaker 100:02:33So let's start with our most advanced program, losmethimod. Just as a quick reminder, losmafimod is a selective p38 alpha beta MAP kinase inhibitor It's currently in Phase 3 development for the treatment of FSHD for which there are currently no approved treatment options. FSHD is a form of muscular dystrophy with an estimated patient population of 30,000 in the U. S. Alone. Speaker 100:03:01The disease is characterized by a slow and progressive loss of muscle function over many years, resulting in significant impairment of upper Like reaching for a cup of coffee in the kitchen cabinet, brushing your teeth, feeding oneself and even practicing good hygiene. These critical factors and our insights on the genetic underpinnings of FSHD drove us to identify and develop a safe and effective treatment option with the potential to slow disease progression for these patients. In September of this year, we completed enrollment in REACH, our global Phase 3 trial for losmafimod, which we initiated in June of 2022. We believe that the rapid pace of enrollment of the 260 patients into the trial is a real testament to the high unmet need of this rare disease. We are on track to report top line in the Q4 of 2024, which will bring us one step closer to delivering the first ever FDA approved therapy for FSHD. Speaker 100:04:09Now let me just give a quick reminder to everybody about REACH. REACH is a 48 week trial intended to be registration enabling both in the U. S. And in ex U. S. Speaker 100:04:19Geographies. The primary endpoint for the study is the change from baseline in the relative surface area or RSA score, which is a quantitative assessment of Reachable Workspace or RWS. This is a measure of Upper extremity range of motion and function that specifically evaluates shoulder and arm mobility using 3 d motion sensor technology. Preserving this upper extremity function is critical for patients to maintain their independence and their ability to perform some of these activities of daily living that I spoke about earlier. As part of this study, we'll also be looking at other key secondary endpoints like muscle fat infiltration or MFI, which is an important marker of disease pathology measured by whole body MRI as well as reported quality of life measures and healthcare utilization questionnaires that will help inform our thinking on our payer strategy as we begin preparing for commercial launch here in the U. Speaker 100:05:21S. We are pleased to have reached, there is no pun intended there, this critical milestone and we look forward to sharing with everyone top line results in the Q4 of next year. So let me now move on to posiridir, our oral fetal hemoglobin inducer or HBF for short for the potential treatment of patients with sickle cell disease. In August 2023, the FDA lifted the clinical hold On our investigational new drug application for prociridare for the potential treatment of sickle cell disease, Our interactions with the FDA were productive and collaborative throughout the hold and we're pleased to have aligned on a revised inclusion exclusion criteria that targets a more severe patient population for this Phase 1b study. I think it's also important to note that there were no changes in the protocol defined dose escalation scheme or the 3 month treatment duration. Speaker 100:06:21We are working hard to resume Enrollment in the Phase 1b study at the 12 milligram dose followed by the 20 milligram dose of posiridir, each of these dose cohorts are scheduled to enroll 10 patients. We are reactivating current sites as well as identifying new sites in the U. S. And ex U. S. Speaker 100:06:39That are excited to participate. Now as many of you know, activating new sites takes time given the contracting and IRB approval process. I think once we have a few months of enrollment under our belt, we'll be in a far better position to estimate when we would expect to have results Of the 12 milligram and the 20 milligram to share with everyone. I just want to take a minute and talk about why we're so excited about prociradir given the fact that this is only in a Phase 1b study. So data that we obtained prior to the clinical Specifically, after only 42 days of treatment, we observed up to a 10 percentage point increase In fetal hemoglobin from baseline or total fetal hemoglobin of approximately 25%. Speaker 100:07:39We believe that as an oral HBF inducer, we believe that Posider has the potential to provide a differentiated therapeutic option for patients living with sickle cell disease. Addressing the significant unmet need in sickle cell remains a Key priority for us and we look forward to providing further updates in our progress. So with that clinical update, I'll now turn it over to Alan, our Chief Financial Officer, Sir, who will provide an update on our financials. Alan has been a great addition to the team since joining in August and he will be invaluable as we move into the next phase of growth and continue to advance our mission of delivering these transformative therapies. So, Alan, over to you. Speaker 200:08:22Thank you, Alex. Let me start with our cash position. We ended September 30, 2023 with cash, cash equivalents and marketable securities of $257,100,000 And during the Q3, our net cash burn was 21,100,000 We continue to operate from a strong financial position and based on our recent operating results and current projections, We now expect our cash runway to extend into 2026, an update from our prior guidance of mid-twenty 25. In the Q3 of 2023, our collaboration revenue was $800,000 That compares to $1,200,000 for the Q3 of 2022. Our research and development expenses were $18,200,000 for the Q3 of $23,000,000 compared to $15,400,000 for the Q3 of 2022. Speaker 200:09:17The increase of $2,800,000 was primarily due to increased costs associated with the advancement of our Phase 3 REACH trial, including the completion of enrollment during September of 2023. Our general and administrative expenses were $10,000,000 for the Q3 of 2023 as compared to $9,700,000 for the Q3 of 2022. The increase of $300,000 was primarily due to increased facilities, professional services and software costs. Our net loss was $24,000,000 for the Q3 of 2023 and that compares to $23,700,000 for the Q3 of 2022. And with that, let me turn Speaker 100:10:00it back over to Alex. Great. Thanks, Alan, and again, great to have you on Speaker 300:10:03the team. So, Tawanda, let's go ahead and Speaker 100:10:05open it up for questions. Operator00:10:36Our first question comes from the line of Corrine Jenkins with Goldman Sachs. Your line is open. Speaker 200:10:42Good morning. This is Craig on for Corrine. So I had one specifically related to vosirudir. And I guess with that Phase 1b study, What do you guys hope to see in order to consider moving forward the program? And based on that, what do you think you need to show from a risk benefit point of view In order to get the FDA to maybe reconsider the current patient population you're evaluating the agent and so maybe a broader one? Speaker 200:11:10Thank you. Speaker 100:11:11Yes, it's great. Thanks for the question, Craig. And let me turn that over to Ian Frazer, our Chief Medical Officer. Ian has really been instrumental in Driving those conversations with the FDA, so I think he's probably best equipped to answer that question. Speaker 300:11:24Yes. Thanks, Alex, and thanks for the question. As Alex mentioned earlier, at the 12 milligram dose that we've studied to date, which was only a partial cohort, essentially only 3 patients And the longest duration of 42 days, so just 6 weeks halfway in to the treatment period, we were seeing rises of around 10 percentage Points in the fetal hemoglobin. Obviously, it depends where your baseline HBF starts out as to where you end up. And there was at least one patient there started out at about 15 relatively high and reached 25, which we believe and I think Backed by the literature that once you enter the high 20% range of total HBF That you significantly impact the symptoms of sickle cell disease. Speaker 300:12:16So that's the range that I think will be Most convincing to reach and I think what we're trying to demonstrate with this is with the 12 milligram dose as we extend the duration of dosing Up to the full 3 months, how much higher do we get the fetal hemoglobin to rise and across the entire cohort at Different baseline field hemoglobins, how high do each of those individuals reach. So that's our intent. That's The target towards which we are shooting, and as we've articulated previously based on our earlier healthy volunteer data, We believe that there is even further incremental efficacy to be gained as we go up from 12 milligrams to the next dose around 20 milligrams, And we fully expect that, that will outperform even the 12 milligram dose. So that's the directionality that we expect. That's the region of total HBF that we think will be significantly transformative. Speaker 300:13:21And that's what the Data we'll be looking for as we start to dose in this cohort. Speaker 100:13:26Yes. And then Craig, this Speaker 400:13:27is Alex. Let me just sort of Speaker 100:13:28answer specifically your question about What do you feel like we need to show to the FDA to expand the patient population beyond where we are today? I think obviously the FDA looks at everything from a risk benefit perspective. And right now, we've shown some benefit, I'll be in a very small number of patients. So if we're able to achieve what Ian spoke about, we'll take that information Back to the FDA and have what we believe is a very sort of thoughtful discussion armed with much more data to show how this drug can benefit And from there, we believe that over the long run, we will be able to expand that patient population. I think what's important to remember is that There's been a lot of talk recently over the past couple of weeks with the Vertex CRISPR cell and gene therapy Compound as well as bluebirds. Speaker 100:14:21And I think that if you look at the levels of fetal hemoglobin that they're able to get up to in the sort of 30s, We do believe that with based on what we've been able to show prior to the hold, we believe that with 3 months of dosing with 12 milligram and potentially 3 months of dosing with a 20 milligram, we may be able to get up to similar levels. And I think that's Very, very exciting for the sickle cell community and for the patients specifically. Speaker 200:14:52Got it. Thank you very much. Operator00:14:55Thank you. Please stand by for our next question. Our next question comes from the line of Dae Gon with Stifel, your line is open. Hi. Speaker 500:15:12This is Benavir on for Dagon. Thanks for taking our question. Just a couple on placerider. How challenging has it been to re sign some of the prior trial sites to participate in the trial at this point? Can you share some color on that? Speaker 500:15:25And What are some of the questions that they're having about the clinical hold and how they can feel more comfortable about drug safety? And then a follow-up To that is, we know that you're not exactly sure about when you're going to have data on Poserador, but is it more likely to be mid year or year end or somewhere in between, If not at a conference, maybe just a presentation through the company. Thank you. Speaker 100:15:47Yes, that's great. Thanks, Batya. And let me start and then, Ian, please feel free to jump in So just as a quick reminder, we had 7 sites in the Phase 1b study Prior to the initiation of the hold and it's just as a reminder that was an all comer study. So our plan specific and they were all U. S. Speaker 100:16:08Our plan specifically in the U. S. Is to double the number of sites specifically in the U. S. As well as to look outside of the U. Speaker 100:16:19S. As well. And we feel that we need to go to a greater number of sites simply because we have a more Narrowly defined inclusion, exclusion criteria. So it will be a more difficult trial to enroll than we have in the past. I think what we've been hearing from physicians and I'd like Anne to comment on this as well, but I think what we've been hearing from physicians is The benefits that this drug as an oral HBF inducer can provide to patients, right? Speaker 100:16:48We've been able to show up until now that With 6 weeks of dosing at a 12 milligram dose, we can get patients to total fetal hemoglobin levels of 25. And I think that's really exciting for the sites and the physicians that are going to participate in this study and I think it's also very exciting For the patients as well. I think in terms of when we think we'll be able to show that, I think right now Our focus has really been on engaging with the centers. Once we have those centers stood up, we've got a couple of IRBs that have already approved it. We have one site that is ready to start receiving drug, and we're also doing a lot with the community, sickle cell community in around those sites to really sort of Educate the community about this very, very interesting study that the center is now participating in. Speaker 100:17:41So that's really been our focus. I think at this point, Ben and Ziron, I think if I was to give you sort of any indication, the only thing I would know with great certainty is that, And that indication or that guidance would be incorrect. So I think give us a couple of months, let us get a couple of Months of patient enrollment under our belt, as I've said in the past. And I think at that point, we'll be in a much better position to provide more specific guidance that I feel I feel more comfortable out. So anything else you think around the centers, Ian? Speaker 300:18:13Yes. Thanks Alex. I can provide a little bit of color around the types of sites themselves. And as Alex alluded to earlier, study was an all comer study. And so we were at a number of sites That started out essentially as pediatric sites and because of the way that sickle cell disease care is administered, A lot of the pediatric sites hold on to their older patients as they go into adulthood because they don't have great partners to transfer those patients to. Speaker 300:18:45And so we had a number of those sites within the study originally. Those are obviously Somewhat younger patients overall, less treatment experienced and less severe impact of disease just given the duration that they've experienced. And what we're finding as we go out is that a number of those sites feel that they don't have quite the level of severity or Previous treatment experience that we might need for the protocol. And so those are sites that are not continuing, but some of them Clearly still do have those patients. So that's been one experience and then we've also broadened our net And now looking at a number of sites that treat exclusively adults that obviously do have many of these more severely impacted patients. Speaker 300:19:35And so we are bringing them into the fold as well. So we're casting a wide net. We've noticed those subtleties of the patient populations at the different sites And we're meeting with lots of investigators. Speaker 500:19:49Excellent. Thank you so much. Speaker 100:19:51Thank you. Operator00:19:53Thank you. Please stand by for our next question. Our next question comes from the line of Joseph Schwartz with SVB Leerink. Your line is open. Speaker 600:20:11Hi, it's Joe Schwartz from Leerink Partners. I was wondering if you could talk some more about how the new Inclusion criteria negotiated with the FDA could influence the profile of disease severity, which will be reflected in the future cohorts for the Phase 1b for paciradir. And do you think that paciradir will still be able to generate an I guess I'm wondering if you think the patients in future cohorts will have as much of an opportunity to reach the 20% range you referenced earlier, If they're starting out at lower baseline levels compared to those who were treated previously? Speaker 100:20:57Great question, Joe. I think to answer that, let me turn that one over to Ian. Yes, absolutely. Speaker 300:21:02And it's one that we've given a lot of thought to and I think it will be interesting to see The data as it rolls out, I think I'd make a couple of comments about it. One is in the 16 patients that we've treated Thus far in the 1b study, it's a pretty high rate of baseline fetal hemoglobins. And while we don't have full 3 months data in all of them, The initial trajectory of increase in HBF is pretty consistent across all of those. So it didn't seem as though it was higher, A steeper rate at the higher baseline HBFs and the lower ones appear to be responding just as well. So that's the first point. Speaker 300:21:45The second point is, I think the mechanism of action being distinct from that Of HU has some advantages in this respect. Obviously, we'll need to demonstrate that as we move into the more severely impacted patients, But it's not operating through a stress erythropoiesis type response, which HU is. There's some discussion about whether that mechanism Might be susceptible to depletion of stem cells or fatigue in the marrow or whatever description you want to append to it. So I think that the differentiated mechanism of action acting through alterations in gene transcription are likely to be Successful in that more severely impacted patient population, but we'll get the patients in and we'll I have to demonstrate that in the clinic and that's our expectation. Speaker 600:22:37Interesting. Thank you. And then could you just walk us Through the calculus you employed to develop the estimate that your inclusion criteria for PERSERADIR covers 7,500,000 to 10,000 Sickle cell patients in the United States. And I'm just wondering how confident you are in that estimate as you engage with the sites now? And What do you expect the screen failure rate for patients to be going forward? Speaker 100:23:02Yes, maybe As it relates to the screen failure rate, I'll ask Ian to answer that. But yes, let me give a bit of color, Joe, in terms of how we got to that number. I think what's important to remember in looking at the inclusion, exclusion criteria, these are people that have either Tried or failed on some of these advanced therapies or for whatever reason don't have access to the advanced therapies Voxelador and I was mad because of the simple fact that they don't have proper insurance or their co pays are too high. So let me give you some high level numbers. We know that from 2019, when both VOXX and CRIS launched through 2022, both of those Products each generated about 10,000 prescriptions. Speaker 100:23:55We know that About 25% of those prescriptions never converted to a patient start and our assumption there is that Those patients simply didn't have proper insurance cover or didn't have access to the drug due to payer related issues. What we also know is that during the 1st year, you saw about a 30% discontinuation rate, with VOXX, we don't actually have specific numbers for crizanlizumab Discontinuation rates in the 1st year, but you could always you could assume that it's probably similar to VOXX, maybe a little bit higher because it does require Sort of infusions at an infusion center. So sort of doing all of that math gets you to around sort of 75,000 to 10000 patients. Where that number may be overestimated is the fact that not all of those patients meet the patient severity criteria, But where that number may be an underestimate is the fact that it doesn't include any prescriptions In 2023, we only have prescriptions through 2022. So sort of taking all of those numbers into consideration, That's how we sort of arrived at the 75,000 to 10000 patients in the U. Speaker 100:25:17S. That meet that Inclusion, exclusion criteria, which represents about 7.5% to 10% of the total 100,000 patient population. Did you want to address your second question? Speaker 300:25:30Yes. So this is Ian. We haven't projected a screen fail rate At this point, I can tell you that for the initial phase of the study, where we recruited 16 patients, That screen fail rate was a little over 50%. So it was a relatively high screen fail rate at that point And we're sort of carrying that forward at the moment even though patient population is likely to be more severe. We have more experience with the sites and with the education of the sites around the protocol and so expect to be able to help with patient selection in that fashion. Speaker 100:26:11That's very helpful. Thanks for all the insight. Yes. Thanks, Joe. Operator00:26:16Please stand by for our next question. Our next Question comes from the line of Edward Denhofer with Piper Sandler. Your line is open. Speaker 400:26:30Great. Thank you. Good morning, everyone. Speaker 100:26:32Good morning, Ned. Hi, Ted. Speaker 400:26:35So no one ever asks a question on poor little lasmapimod. So I guess I'll be the one to ask it. With all of the with the data coming in the back half of next year, what are some of the Commercial prep that you're doing. And as you kind of project out here, what's the calculus between Keeping it and launching it yourself, partnering it, maybe partnering it overseas, kind of where just update us on sort of where your head is on that. Thanks. Speaker 100:27:05Yes, absolutely. Thanks so much for the question, Ted. And I appreciate you asking a question on lasmapamat. Thank you. So yes, just as a quick reminder, we would have we plan to have top line results in the Q4. Speaker 100:27:18We would then file the NDA sometime in early 2025 for an approval sometime in 2026. We've been very clear that we believe that we can launch this drug quite successfully In the U. S. With a fairly sort of modest commercial infrastructure, while at the same time looking for partners ex U. S. Speaker 100:27:41And we will begin the process of sort of standing up that commercial organization, the end of this year, beginning of next year, starting with our first Kind of key hire, which would be that Chief Commercial Officer. And I think one of the reasons that we're so excited about Our ability to be able to do this ourselves is a fairly sort of concentrated market, it's a fairly small number of neuromuscular specialists that treat these patients with FSHD. They're very, very well organized from a patient advocacy standpoint We have an excellent relationship with the FSHD Society. And the fact that there are Currently no treatment options and the drug that's probably the closest behind us is probably 2 to 3 years Roche's product that's a myostatin inhibitor. It's 2 to 3 years behind us. Speaker 100:28:35We believe that we really do have an opportunity to be successful with this launch in the U. S, doing it ourselves And then the ability to help a tremendous number of patients in the U. S. As well as working collaboratively with a partner ex U. S. Speaker 100:28:49To help patients around the world. Speaker 400:28:53That's super helpful. And I do think it will garner more attention as we get into New Year. So thanks for the update. Speaker 700:28:58Yes. Thanks, Operator00:29:00Ted. Please stand by for our next question. Our next question comes from the line of Matthew Bigler with Oppenheimer and Company. Your line is open. Speaker 700:29:16Hey, guys. Thanks for the question. I will also jump on the FSHD bandwagon here. I wanted to ask maybe about some different scenarios for REACH3 and specifically if you saw a path forward, If the study doesn't hit or maybe narrowly misses the reachable workspace endpoint, like do you think the biomarker endpoint might be Efficient. I guess taking a page out of Sarepta's playbook and what we've seen now over the last couple of weeks, what kind of what are your thoughts there? Speaker 700:29:49Thanks. Speaker 100:29:50Yes, great question, Matt. Thanks for that. So let me turn that one over to Ian. Speaker 300:29:54Yes, thanks, Matt. So just to be clear, in terms of Biomarkers in reach, we are not evaluating the DUX4 transcriptome, which was evaluated in the Phase 2 study, is that's not really a feasible clinical trial measure to make. What we do have, however, are a number of secondary endpoints that are different than the reachable workspace endpoint. And those include the MRI endpoints, which I guess could be considered a biomarker, which evaluates the accumulation of fat In muscle tissue that still has what looks like normal contractile muscle interspersed With fat and so that we also showed in the Phase 2 study as for the reachable workspace That you've got a stabilization of that fat accumulation relative to the placebos who showed an increase. So we think that that's clearly An important secondary endpoint, we also have an evaluation of dynamometry, so conventional muscle strength testing, which we're evaluating. Speaker 300:31:03We have some patient reported outcomes that reflect on both Patient global impression of change, but also some specific questions related to FSHD itself. And so there are a number of those secondaries that I think will be important to consider irrespective of what happens to the primary endpoint. But if as you articulate the primary misses narrowly, I think having all of those secondaries trending In a favorable direction towards loss macromod over placebo will be extraordinarily helpful And persuasive in that context. Speaker 700:31:46Yes. I agree with that. Thanks for the question. Speaker 100:31:48Yes. And Matthew, this is Alex. The only other thing I would add to what Ian said is going back to something I said earlier regarding prociridir and how the FDA looks at everything from a risk benefit Perspective, I think what's also important to note is that when we file our NDA with the FDA, we will have over 3,600 patients in our Patient Safety Database. And this has been shown to be a very, very safe drug. And so I think that that is a really important So the piece of information that the FDA will look at as it considers the safety and efficacy data in totality and decides whether to approve this drug or not for patients For which they have none. Speaker 700:32:30Yes, makes sense. Thanks. Yes, thanks Matt. Operator00:32:34Please stand by for our next question. We have a follow-up from the line of Dae Gon with Stifel. Your line is open. Speaker 500:32:48Hi. Just one more question from us. For SSHD, can you remind us of the powering for Reach and the assumptions that went into it for the Reachable Workspace? Given that it's a mobility test, how should we think about it in the context again of the recent EMBARK trial failure? And what read through for the powering assumptions for Reach? Speaker 100:33:08Yes, great question. Let me turn that over let me turn that one over to Ian. Speaker 300:33:11Yes. So REACH was powered based on the observed data from from REDOX 4 from the Phase 2 study. And you may recall that was an 80 patient study, 40 in each arm. And essentially what we took was the change from baseline to the treatment effect glasumab Minus placebo on the reachable workspace and also assessed the variability in the measurements in that particular cohort and then applied it to the power calculations for the REACH study. The REACH study was originally powered On a total enrollment of 230 patients with an expectation that 210 of them would be FSHD Type 1 and 20 of them would be Type 2, and that's a reflection of the relative epidemiology of Type 1 versus Type 2. Speaker 300:34:06Type 1 is Overwhelmingly the most prevalent, 95% or so of that. The REDUX-four study enrolled only Type 1s. And so even though we are enrolling some Type 2s in the REACH study, we powered the study on only the Type 1. So the study was powered on an expectation of 210 Type 1 patients in the REACH study And that gave us a power of 93% or 94% using the magnitude of change and the standard deviation from REDUX-four. As it turns out, when we cut off screening for the REACH study based on what we thought the Screen fail rate was going to be in order to reach those 230 patients. Speaker 300:34:55The screen fail rate dropped down and we ended up enrolling a number of more patients. And so at the end of the day, the total enrollment was 260 instead of 230. And of that 260, there were 18 FSHD Type IIs, so we now have 242 FSHD I. So 242 versus the original powering around 210. So that bumps the power up into over 95% using the same assumptions from REDOX 4. Speaker 300:35:27So that was an inadvertent over enrollment that wasn't our intention, but was a reflection of the enthusiasm at the sites and the Fact that the sites had gotten better at screening the patients until the screen failure rate dropped down. And so that's where we stand based on our Actual enrollment now in reach. Speaker 500:35:50Well, thank you. Operator00:35:55Thank you. Ladies and gentlemen, this concludes the question and answer portion of the call. I would now like to turn the call back over to Fulcrum's CEO, Alex for closing remarks. Speaker 100:36:06Thanks, Towanda. So just to quickly wrap up, we remain as we always have deeply committed to treating the root cause of genetically defined rare diseases and bringing these transformative therapies to patients. Before we conclude today's call, as I always like to do, I'd Just like to extend my sincere appreciation and gratitude to my fellow Fulcrum teammates, to the physicians we work with to advance our clinical trials, And finally, and most importantly, to the patients who participate in our clinical trials as well as their families. Without them, We would not be able to achieve our goals as a company. Thanks again everyone who joined the meeting who joined the call this morning. Speaker 100:36:47Please stay safe and healthy. Operator00:36:50Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.Read morePowered by