Fulcrum Therapeutics Q1 2024 Earnings Call Transcript

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Provided by Quartr
May 13, 2024

There are 10 speakers on the call.

Operator

Good morning, and welcome to Fulcrum Therapeutics First Quarter 2024 Financial Results and Business Update Conference Call. Currently, all participants are in a listen only mode. This call is being webcast live and can be accessed on the Investors section of Fulcrum's website at www.fulcrumtx.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.

Operator

While these forward looking statements represent Forecom's views as of today, this should not be relied upon as representing the company's views in the future. Fulcrone may update these statements in the future, but it's not taking on an obligation to do so. Please refer to Fulcrum's most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with the company's business. Leading the call today will be Alex Sapir, CEO and President of Fulcrum. Joining Alex on the call are Alan Musso, Chief Financial Officer Doctor.

Operator

Ian Frazier, Senior Vice President of Early Development and Paul Bruno, Senior Vice President of Business and Corporate Development. After providing updates on our key programs, there will be a brief Q and A in which Alex, Alan, Ian and Paul will be available to answer your questions. With that, it's my pleasure to turn the call over to Alex.

Speaker 1

That's great. Thanks, Shannon, and thanks to all of you for joining us on the call this morning. Beyond another solid quarter of progress across our 2 clinical stage assets, losmapimod and placeridere, we are super excited to announce our collaboration and license agreement with Sanofi for the development and commercialization of blosimapimod. So what I'd like to start off by doing this morning is just provide an overview of the structure and strategic importance of this collaboration with Sanofi. In brief, Sanofi will obtain exclusive commercialization rights for lasmapimod outside of the U.

Speaker 1

S. And that will allow Fulcrum to focus our efforts on planning for a strong U. S. Commercial launch in 2026. This collaboration allows both parties to do what we each do best.

Speaker 1

It combines Fulcrum's expertise in FSHD with Sanofi's exceptional regulatory development and commercial capabilities across approximately 100 countries outside the U. S. Importantly, having a partner like Sanofi will allow us to reach patients in ex U. S. Markets quicker than we could do on our own and mitigates the commercial execution risk that is typically inherent for any biotech company undertaking the commercial launch of its first product on its own.

Speaker 1

We believe we have selected the best losmapimod and we look forward to delivering on our shared commitment to addressing the unmet need of patients with FSHD. We're also very pleased with the deal terms, which allows us to retain substantial ex U. S. Value in both the near term and over the product lifecycle. In short, we will receive $80,000,000 upfront, which enables us to fund the launch of losmapimod in the U.

Speaker 1

S. With non dilutive capital. We're also eligible to receive up to an additional 975,000,000 specific regulatory and sales milestones along with the tiered royalties starting in the low teens of annual net sales of losmapimod outside of the U. S. The companies will also share equally in the global development costs for losmapimod going forward.

Speaker 1

Now before providing an update on our 2 clinical assets, posiridir and losmapimod, I would also like to take the opportunity to welcome our newly appointed Chief Medical Officer, Doctor. Patrick Korn, an accomplished industry veteran who has This is an ideal time for path appointment and with the complementary This is an ideal time for path appointment and with the complementary expertise of Doctor. Ian Frazer, we are well positioned as we advance toward near term inflection points. Pat does send his apologies as he's unable to attend today's meeting on account of a family emergency. So let's go a bit deeper and start with our most advanced program, losmafimod, which as most of you know, is an oral small molecule selective p38 alpha beta MAP kinase inhibitor that inhibits SUX4 expression and thus prevents downstream muscle death in patients with FSHD.

Speaker 1

As a quick reminder, FSHD is a rare form of muscular dystrophy with an estimated U. S. Prevalent patient population of 30,000. FSHD is characterized by a slow but relentless loss of muscle function year after year, resulting in significant impairment of upper extremity muscle function and mobility. And while there is a degree of heterogeneity in the onset and disease progression of FSHD, many patients are unable to perform daily life activities that you and I take for granted and thus are unable to live independently.

Speaker 1

Ultimately, 20% of FSHD patients become wheelchair bound. There are currently no approved treatment options for these patients, which underscores the significant unmet need for this debilitating disease. Our Phase 2 study, the REDOX 4 trial, was recently published last month in Lancet Neurology and demonstrated improvements in functional outcomes as measured by reachable workspace, structural outcomes as measured by muscle fat infiltration and patient reported outcomes for patients treated with lasmapimod all as compared to placebo. Building on the encouraging clinical benefit and favorable tolerability observed in our Phase 2 trial, we completed enrollment in our global Phase 3 trial for losmapimod in September of last year with a total of 2 60 patients. And as of the end of April of this year, 146 of the 260 patients had completed the 48 week treatment period and 144 of these patients elected to continue into the open label extension of the study in a fully blinded fashion.

Speaker 1

This very high percentage of patients opting to move into the open label phase is similar to what was observed in our Phase 2 clinical trial and indicative of the high unmet clinical need for patients with FSHD. We are on track to report top line in the Q4 of this year, which will bring us one step closer to delivering the first ever FDA approved therapy for patients with FSHD. Now as a quick reminder, our Phase III trial, the REACH trial, it is a well powered 48 week trial intended to be registration enabling both in the U. S. And in ex U.

Speaker 1

S. Geographies. The primary endpoint for reach is the change for baseline in the relative surface area or RSA, which is a quantitative assessment of reachable workspace. RSA is a measure of upper extremity range of motion and muscle functions that specifically evaluate shoulder and arm mobility using 3 d motion sensor technology and has been shown to correlate with abilities to perform certain activities of daily living. In our Phase II study, losmabumab demonstrated a 10% net change in the RSA score relative to placebo at 48 weeks.

Speaker 1

Based on our collaborative interactions with FDA and in particular with the clinical outcomes assessment group or COA at FDA, we are currently assessing the extent to which a specific change in the RSA score is meaningful to patients. Additionally, key secondary endpoints include muscle fat infiltration or MFI, which is an important marker of disease pathology measured by whole body MRI, shoulder dynamometry, as well as self reported quality of life measures and healthcare utilization questionnaires that will help inform our thinking on our payer strategy as we begin for our commercial launch here in the U. S. Taken together, we continue to take important steps forward to position Fulcrum for commercial readiness. Now turning to prociradir, our oral HBF inducer for the potential treatment of patients with sickle cell disease or FCD for short.

Speaker 1

The elevation of fetal hemoglobin or HBF is a validated therapeutic rationale for FCD, a lifelong inherited blood disorder that severely impairs quality of life for approximately 100,000 people in the U. S. And approximately 4,400,000 people worldwide. This makes sickle cell disease one of the most prevalent non malignant hematologic diseases. Now historically, the standard of treatment for FCD has involved blood transfusions, pain medications and hydroxyurea, but all of these treatments only focus on symptom relief.

Speaker 1

And while exciting scientific progress has enabled the advancement and more recently the approval of gene editing therapeutic approaches, we believe there remains a high unmet need for a safe and accessible therapeutic option that are broadly protective of FCD symptomatology. As a 1st in class oral small molecule HBF inducer, we believe procuredir has the potential to address this unmet need. So in August of 2023, the FDA lifted the clinical hold on the Phase 1b study we call the PIONEER study. It's important to note there were no changes in the protocol defined dose escalation scheme or the 3 month treatment duration. We continue to work expeditiously to reinitiate the PIONEER study and we have activated several new sites and are building key relationships with leading physicians in the FCD community.

Speaker 1

Cohort 3 of the Phase 1b trial will evaluate Posiridir at the 12 milligram once daily dose with a dosing duration of 3 months, followed by cohort 4 at the 20 milligram once daily dose also for 3 months. Both cohorts are expected to enroll approximately 10 patients. We look forward to building on the encouraging clinical data obtained prior to the clinical hold, which demonstrated that prociridir increased total HBF of a magnitude that could translate into a meaningful improvement in disease severity. More specifically, after only 42 days of treatment, we observed up to a 10 percentage point increase in HBF from baseline or total HBF of approximately 25%. We believe that pocerigare as an oral HBF inducer has the potential to provide a differentiated therapeutic option for patients living with sickle cell disease.

Speaker 1

Addressing the unmet significant unmet need in sickle cell in the sickle cell community remains a key priority for us and we are excited to build on this momentum in the years ahead. And so with that update on the business, let me now turn it over to our Chief Financial Officer, Alan Musso, to run through our financials. Alan, over to you. Thanks, Alex.

Speaker 2

I'll now go over our financial results for the Q1 ended March 31, 2024. As of March 31, 2024, cash, cash equivalents and marketable securities were $213,300,000 as compared to $236,200,000 as of December 31, 2023. The decrease in our cash position of $22,900,000 is due to net cash used in operating activities. As of March 31, 2024, on a pro form a basis, $80,000,000 milestone due under the collaboration and license agreement with Sanofi, our cash, cash equivalents and marketable securities were $293,300,000

Speaker 1

We had no collaboration revenue

Speaker 2

in the Q1 of 2024 compared to $300,000 for the Q1 of 2023. The decrease was attributable to the completion of our research services during the Q4 of 2023 under our MyoKardia collaboration agreement. Research and development expenses were $19,800,000 for the Q1 of 2024 as compared to $16,700,000 in the Q1 of 2023. The increase of $3,100,000 was primarily due to increased costs related to the advancement of the REACH clinical trial. General and administrative expenses were $10,100,000 for the Q1 of 2024 as compared to $11,500,000 for the Q1 of 2023.

Speaker 2

The decrease of $1,400,000 was primarily due to decreased employee compensation costs. And our net loss was $26,900,000 for the Q1 of 2024 as compared to $24,800,000 for the Q1 of 2023. Finally, based on our current operating plans, we now expect that our cash, cash equivalents and marketable securities, together with the $80,000,000 upfront payment to be received from Sanofi, will be sufficient to fund its operating requirements into 2027. With that, let me turn it back over to you, Alex.

Speaker 1

That's great. Thanks so much, Alan. So before opening up for questions, Shannon, I just wanted to remind everybody of the key events for this quarter. We selected the ideal partner incentive fee to commercialize losmaphimod outside the U. S.

Speaker 1

We extended our cash runway into 2027, we enriched our leadership team and we activated several new sites for our Phase 1b 1b PIONEER trial with VoceraVeer. We remain on track to report top line data for the Phase 3 REACH trial in the Q4 of 2024 and continue to prepare for the potential NDA filing and commercial launch of losmaphimod in the U. S. We look forward to building on this momentum in the months years ahead. And with that, Shannon, let's go ahead and open it up for questions.

Operator

Thank you. Our first question comes from the line of Edward Tenthoff with Piper Sandler. Your line is now open.

Speaker 3

Great. Thank you very much and congratulations on the partnership and all the progress of the corner.

Speaker 1

Thanks, Ted.

Speaker 3

So, quick question. When it comes to, actually manufacturing drug and things like that for the partnership, can you walk us through how that works? And then just anything else we should think about in terms of final things that need to happen ahead of the Phase III data, obviously, final patient visits and all of that stuff. But just anything else that you guys are focused on as we drive towards the data in the Q4 for lasmapimod? Thank you.

Speaker 1

Yes, it's great, Ted. Thanks so much. And joining us on the call is Paul Bruno and Paul is our Head of Corporate Strategy and Business Development, really the individual at Fulcrum who really led the deal efforts with Sanofi. So maybe, Paul, I'll turn that over to you to address the manufacturing question and then one of the more general questions Ted had.

Speaker 4

Yes. Thanks, Ted. So right now, the plan is for us to continue supplying for both clinical and commercial globally. There is the opportunity and flexibility for Sanofi to take over manufacturing and supply in the future.

Speaker 3

Great. Thank you. And then just in terms of final work towards the Phase 3 readout, anything we need to be focused on? Thanks.

Speaker 1

Yes. Nothing off hand, but maybe I'll turn it over to Ian.

Speaker 5

This is Ian, Ted. No, that's all pretty much on track and unaffected by this. We are proceeding with that. We know who the last patients in the study are, where they are, and obviously, we are working with those sites to make sure there are no delays there. But that continues unaffected at this point.

Speaker 3

Well, tough to imagine a better partner. Congratulations, guys.

Speaker 1

Yes. Thanks so much, Ted.

Operator

Thank you. Our next question comes from the line of Gregory Renzo with RBC Capital Markets. Your line is now open.

Speaker 6

Hey, good morning, Alex and team. Congrats on the progress in the deal and thanks for taking the question.

Speaker 1

Thanks, Craig.

Speaker 6

And maybe just a couple from us. Just first question, when we look across the competitive landscape for FSHD development, especially when it comes to trial design and endpoints. Maybe beyond DUX expression, we do know that Avedity plans to report data on the changes to gene expression downstream to DUX4. So I'm just curious what can you tell us about lasmapimod's ability to impact that expression downstream of DUX4? And maybe how can we think about that and Los Bapmab being positioned competitively in light of this?

Speaker 6

And then I have

Speaker 5

a follow-up.

Speaker 1

Yes, great question, Greg. And let me start and then I'll turn it over to Ian for some more detail. And yes, Avedi has talked a lot about the fact that AOC 10 20 directly inhibits DUX 4. I think that the clinical impact of that still remains to be seen. They have talked a lot about being able to measure genes downstream to DUX4 because of the challenges that we've spoken about and they've spoken about, about the stochastic nature of DUX4 and how difficult it is to measure.

Speaker 1

Now we do know that lasmapimod works upstream from DUX4, but we also know that lasmapimod can reduce DUX4 gene expression in preclinical models. And we also know that losmapimod has been able to reduce gene expression that are downstream to DUX4 in preclinical models as well. And maybe, I guess, Ian, just to elaborate on that a little bit, maybe I'll turn it over to you to maybe talk a bit more detail about some of the genes that we have been able to reduce downstream to DUX4.

Speaker 5

Yes, absolutely. Yes, all the work that was done to identify lasmapimod as a potentially useful agent in FSHD was done in vitro in cells derived from patients with FSHD. The myoblast from those patients differentiated in vitro into myotubes. In that process, DUX4 typically is upregulated. We've been able to show across a range of cells derived from different patients, both FSHD1 and FSHD2 that there very clearly is a significant reduction in DUX4 itself, which you can measure in vitro somewhat more readily than you can in vivo.

Speaker 5

And that along with those concentration dependent reductions in DUX4 across those myo tube cultures, you see a concomitant decrease in the number of the downstream genes that we know are impacted by DUX4 that are regulated by DUX4 and show a concentration dependent decrease in all of those as well as decreases in markers of apoptosis in the muscles and ultimately decreases in muscle cell death. So that mechanism is fully fleshed out in cultures. And as Alex alluded to, the challenge in the clinic is demonstrating that in the biopsies from these patients. And I think one of the challenges in addition to the stochastic nature of DUX4 expression is the variability in the tissue content of the biopsies. In the clinic, these are not normal muscles, so there's a bunch of fat, fibrous tissue, inflammatory tissue, extracellular matrix components and so on that lead to the variability in documenting that.

Speaker 5

But the overall pathway in vitro in those myotube cultures is very clear, concentration dependent reduction in DUX4 and similarly reduction in the downstream gene impacted by DUX4.

Speaker 6

That's great. Really appreciate that. And then just on the deal this morning, we certainly heard your mention of the benefit of Sanofi reaching multiple countries and Europe building out to focus stateside and on the U. S. Just wanted to ask just to receive a little more color on maybe some of those additional inputs that you and the team had in consideration of these deal terms reflecting the full value of lismapimod.

Speaker 6

But can you just talk through some of the deal terms and what inputs that you use to feel comfortable with the value calculus here?

Speaker 1

Yes. Thanks, Greg. And I'll start and then Paul, if I missed anything, please jump in. I think 1st and foremost, we've been very clear that it has always been our goal to try to find us to us to get losmapimod to patients around the world faster than we could do on our own simply because of the scale of the commercial infrastructure that Sanofi has. And then with the upfront payment and the cost sharing, we obviously can take that capital, that non dilutive capital and really apply our effort and more importantly, our focus on ensuring that we can have the best possible launch here in the U.

Speaker 1

S, which obviously we have been we've been obviously gearing up for. I think one of the reasons you'll see that the deal terms were quite competitive and significantly above comps for products that have yet to flip over the Phase 3 card is, I think, simply because of the competitive nature of this. There was a number of parties that were interested, not surprising. FSHD is a large market in the U. S, about 30,000 patients, some estimate about 1,000,000 patients outside of the U.

Speaker 1

S. And there are currently no treatment options. And Fulcrum has what we believe to be probably about a 3 year head start before the next closest competitor comes into play. So I think for all of those reasons, we could not be happier with the partner that we've selected. It allows us to get the drug faster to patients that we could do on our own outside of the U.

Speaker 1

S, but it also allows us as a small biotech company to focus on what still continues to this day to be the most profitable and lucrative market in the world, that being the U. S. Market.

Speaker 6

Fantastic. Thank you.

Speaker 1

Thanks, Greg.

Operator

Thank you. Our next question comes from the line of Corinne Johnson with Goldman Sachs. Your line is now open.

Speaker 7

Thanks and good morning. You mentioned in the answer to the last question that you plan to use this upfront capital in supporting the launch. I guess, what are your top priority action items that you think will be necessary to set up with strong launch out the gate? And then I'd be curious if you could talk to what you view as Sanofi potentially bringing to the table as a potential partner or as a partner now for ex U. S.

Speaker 7

Commercialization beyond just kind of the financial terms? Thanks.

Speaker 1

Sure, sure. No, absolutely. Thanks, Corinne, for asking the question. Yes, I think one of our key priorities on the commercial side is to bring on board a very, very strong Chief Commercial Officer that has experience of launching rare diseases in the pharmacy benefit portion of the payer space. And we're having a number of conversations with a number of very, very talented Chief Commercial Officers that meet that criteria.

Speaker 1

So that's obviously going to be our first important hire. And then we'll be doing a couple of additional hires this year, particularly around market access and we more than likely will end up recruiting somebody who is exclusively focused on ensuring that genetic testing does not become an impediment to access at launch. So I think those are some of our key priorities right now for the U. S. I think what Sanofi brings and we talked a little bit about this during our prepared remarks.

Speaker 1

I think beyond the financials, I mean, they have a very, very strong neuromuscular franchise with their programs such as Fabrizyme and Cerezyme, Myozyme. I mean that's a $3,000,000,000 portfolio globally. So they've got a very, very strong commercial footprint. But beyond that, they obviously have very strong regulatory as well as clinical expertise in the neuromuscular space as well. So having that expertise as we're negotiating with the various regulatory agencies around the world as well as with the various pricing and reimbursement agencies in various countries around the world.

Speaker 1

I think that, that experience that Sanofi brings to the table will be invaluable.

Operator

Great. Thank you.

Speaker 1

Thank you, Corinne.

Operator

Thank you. Our next question comes from the line of Joseph Schwartz with Leerink Partners. Your line is now open.

Speaker 8

Great. Congratulations on the deal. I have a question on, losmabmod and also one on Pacira Deer. So first on one with losmabmod, I was just wondering if you can tell us how your work to establish the clinical meaningfulness of certain changes in RWS is going. Can you outline the process of performing that analysis and where you are in that process and when we might see some data on that front?

Speaker 1

Yes, that's great. Thanks so much, Joe. And thanks for your kind words earlier. Yes, I think to answer the question, we're doing a lot of work on clinical meaningfulness. I've been working very closely with the co division of the FDA.

Speaker 1

But maybe just get into some of the specifics, let me turn it over to Ian.

Speaker 5

Yes. Thanks, Alex. Thanks, Joe. So there are 3 main steps as part of the work that's ongoing and that we've aligned with the agency. The first is a survey that has now been completed and that is asking patients with FSHD what is most important to them in terms of activities of daily living.

Speaker 5

That was a 100 patient survey unrelated to treatment with plasmathemont. Again, that is completed. The 2 other components are ongoing at the moment. The first is a cross sectional study, again, in patients with FSHD, but not being treated with lasmapimab and performing reachable workspace assessments on those patients and then matching up the ability of those patients to do the important activities of daily living, which were identified in the initial step. And so that's my questionnaire in those patients.

Speaker 5

So mapping which will work space there to the questionnaire of their ability to perform those activities and that assessment recruiting those patients into that is active and ongoing at the moment and that's going to be a total of about 50 patients. And then the last component, the 3rd component of this is as part of the REACH study. So patients who've been treated could either osmathimod or placebo undergoing structured exit interviews from the study to get insight from them on what difficulties they had with activities of daily living as part of their participation in the study. That work is ongoing and will only complete once the REACH study itself is complete and we have all the data. So we expect all of these strands of data to be pulled together and available in around the same timeframe as we expect the top line data from the REACH study and that those will be around the same time.

Speaker 8

Okay. Thanks. That's very helpful. And then can you update us on-site activation in the ongoing study for vosiradir? And at what point do you think you could share some data from this study, either in terms of calendar timing or how you're thinking in terms of numbers of patients you're aiming for before giving us the first look?

Speaker 8

That would be very helpful.

Speaker 1

Yes, absolutely. Thanks, Jill. I'm happy to take that one. Yes, so we will be sharing information when we have completed the 10 patients in the 12 milligram cohort and all 10 of those patients have completed the 3 month study duration. And we intend to share that with everybody in advance of Cohort 4, which is the 20 milligram cohort.

Speaker 1

Again, our expectation there is that we would share the 20 milligram cohort data once those 10 patients have completed the full 3 months of dosing. We have been pleased with the site activation efforts to date. I would say that there is a strong interest from many sickle cell centers about the promise of having a once daily oral medication that has the potential to raise levels of HBF to that seen with the cell and gene therapies. We haven't yet provided any specific guidance on when we would be able to share that information because what we want to make sure that we do, Joe, is I mean, 1st and foremost, we want to make sure that we don't give a number that we don't feel comfortable with in terms of particular quarter. So what we said to folks is that we want to have a critical mass of patients in that 12 milligram cohort before we come back to everyone and let them know what in what quarter we'll have the 12 and in a subsequent quarter the 20 milligram.

Speaker 1

And I think just having that critical mass of patients, it allows us to know a couple of things, right. It allows us to sort of see what that enrollment trajectory looks like, but it also allows us to see which sites have been the strong enrollers and to be able to go back to those PIs at those sites and really them point blank how many more patients that they have. So until we have that critical mass of patients or once we have that critical mass of patients and we can more accurately predict what that enrollment trajectory looks like, that'll be the point in time in which we'll come back to everybody with more specificity around which quarter we would share the 12 milligram followed by the quarter in which we would share the 20 milligram.

Speaker 8

Very helpful. Thanks and congrats again. Yes. Thanks,

Operator

Joe. Thank you. Our next question comes from the line of Dae Gon with Stifel. Your line is now open.

Speaker 9

Hey, good morning guys. Thanks for taking our questions and congrats on the deal and progress as well. I'll start with the losmapamide question. In your prepared remarks, Alex, you talked about, about 146 of your patients being complete as of April 24, 144 electing to go into open label. So curious in terms of the Sanofi deal, I guess when did this deal kind of get underway and to what extent were they kind of given the access to the data room?

Speaker 9

I know it's blinded, but kind of curious how much access they have there? And I've got a follow-up.

Speaker 1

Sure. Absolutely, Dae Gon. And maybe to and thanks for your kind words as well. Maybe to answer that question, I'll turn it over to Paul, who's really been the person that's been leading the charge on the we've been in conversations obviously for some period of time with

Speaker 5

the folks

Speaker 1

at Sanofi. But Paul, do you want to maybe just talk a little bit about kind of when these conversations got quite serious? Yes. I mean, the conversation

Speaker 4

has been taking place for over the past year. Again, it's been a competitive process with a number of parties. They have had broad access to all the confidential information related to the program. I will explicitly note that they have not seen any blinded reach data, neither have we. But other than that they've had broad access to the program materials.

Speaker 9

Okay, great. Thanks for the details, Paul. Maybe the next question is when you think about the Sanofi infrastructure, especially ex U. S. Access to ex U.

Speaker 9

S. Regulators, I guess, can you just remind us where things stand in terms of the Phase 3 reach design? How comfortable is the EMA as well as ex US regulators about that particular endpoint as it pertains to FSHD approvability? Thanks so much guys.

Speaker 1

Yes, absolutely, Dae Gon. Thanks for the question. Maybe let me turn that

Speaker 5

one over to Ian. Yes. Thanks, Dae Gon. So we have engaged with the European regulators. There was some initial engagement prior to the study, which was done on a country by country basis rather than central process with the EMA.

Speaker 5

But more recently, we have engaged with the EMA somewhat late in the process while the trial was underway. I think they recognize the endpoints that we've established. They also recognize that our interactions with them were after the trial that are already being initiated and so opportunities to impact that were limited. But I think there's an understanding of our primary endpoint and the way that we've structured the secondary endpoints. And I think overall agreement that that seems to be a reasonable design from their point of view.

Speaker 9

Great. Thanks so much and congrats again guys.

Speaker 1

That's great. Thanks, Egon.

Operator

Thank you. Our next question comes from the line of Matthew Beegler with Oppenheimer. Your line is now open.

Speaker 6

Hey, good morning guys. I'll extend our congrats as well. I just wanted to maybe tag along to that last question about the partnering process here. And specifically, if you can comment on how receptive the partners were to the RWS endpoint. Is this something that they've seen before?

Speaker 6

Or did it kind of require a lot of handholding, with Paul and team throughout the due diligence process? Thanks.

Speaker 1

Yes, great question, Matt. Maybe to answer that, I'll probably best person to answer that would be Paul.

Speaker 4

Yes. Thanks, Matt. No, we have been broadly educating folks on RWS. I don't think to a greater degree than you would for any other novel endpoint. I think it was also one of the major reasons that we were excited about Sanofi as a potential partner between their deep neuromuscular expertise, but also their expertise with novel endpoints.

Speaker 4

I think this really was an ideal match for Fulferm, particularly for this rare disease drug development program.

Speaker 8

Thanks.

Speaker 5

Great. Thanks, Matt.

Operator

Thank you. And I'm currently showing no further questions at this time. I'd like to hand the call back over to Alex for any closing remarks.

Speaker 1

That's great. Thanks so much, Shannon, and thanks to all of you for joining again. Maybe just in closing, we as always remain deeply committed to treating the root cause of genetically defined rare diseases and bringing transformative therapies to patients. And before we conclude today's call, as I always like to do, I would like to extend my sincere appreciation and gratitude to my fellow Fulcrum teammates, to the physicians we work with to advance our clinical studies, and finally and most importantly to the patients and their families. Thanks everybody who joined this morning and please stay safe and healthy.

Speaker 1

Thanks.

Operator

This concludes today's conference call. Thank you for your participation. You may now disconnect.

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Key Takeaways

  • Fulcrum signed an exclusive ex-U.S. licensing and commercialization agreement for losmapimod with Sanofi, securing $80 million upfront, up to $975 million in milestones, tiered royalties starting in the low teens, and equal cost‐sharing of global development.
  • The Phase 3 REACH trial for losmapimod in FSHD has fully enrolled 260 patients, with ~146 completers by April and top-line results expected in Q4 2024; ~99 % of completers entered the open‐label extension, reflecting strong patient demand.
  • Phase 2 data from the REDOX 4 study published in Lancet Neurology showed functional, structural, and patient-reported benefits for losmapimod versus placebo, supporting its potential as the first FDA-approved FSHD therapy.
  • Fulcrum’s HBF inducer prociradir resumed Phase 1b (PIONEER) after FDA lifted its hold, with cohorts at 12 mg and 20 mg once daily planned to assess up to a 10 percentage-point increase in fetal hemoglobin.
  • As of March 31 2024, Fulcrum held $213.3 million in cash (pro forma $293.3 million post-Sanofi payment), incurred a net loss of $26.9 million in Q1, and expects funding into 2027 to support operations.
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Fulcrum Therapeutics Q1 2024
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