Q1 2025 Fulcrum Therapeutics Inc Earnings Call
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I'll come to coffee chocolate experts quarter, 2025 financial results and business update conference call.
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Clinical development timelines and financial projections.
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Alex Sapir: Leading the call today will be Alex Sapir, CEO and president of BOL Com.
Alan Musso: Joining Alex on the call are Alan Musso, Chief Financial Officer.
Alan Musso: To providing updates on our company's key programs there'll be a brief Q&A in which the bulk management team will be available for questions.
Alex Sapir: With that it is my pleasure to turn the call over to Alex.
Alex Sapir: Thank you Olivia and good morning, everyone and thanks for joining us today, so before jumping into the updates for the quarter I just wanted to take a moment to welcome Dae Gon ha. The newest member of the Fulcrum management team as our senior Vice President head of strategy and business development.
Alex Sapir: Now there is no stranger to fulcrum, nor to the sickle cell space for the past five years Dagon was an equity research analyst at the banking firm Stifel covering broke ground.
Alex Sapir: <unk>, whose first day with the company is today will be focused on overall corporate strategy and business development here at fulcrum as we continue our efforts in sickle cell disease and other benign hematological conditions.
Alex Sapir: So now, let's turn to the updates for the quarter. The past several months have been an exciting period for fulcrum as we've continued to make good progress with our lead program <unk>, which is currently enrolling in a phase one b trial, a trial that we call pioneer for the treatment of sickle cell disease and inherited blood disorder.
Alex Sapir: <unk> approximately 100000 people in the U S and approximately $4 4 million people worldwide I am pleased to announce that we've completed enrollment in the 12 milligram cohort cohort three with a total of 16 patients enrolled and plan to share results of this cohort in early Q.
Alex Sapir: Three of.
Alex Sapir: These data will include key baseline.
Alex Sapir: <unk> characteristics adverse events magnitude of hbf induction and changes in other important hematological parameters measured throughout the study.
Alex Sapir: Let me spend a bit of time, providing some details on the 16 patients. The majority of these patients have come from sites in the U S with the remainder coming from a single site in South Africa.
Alex Sapir: Their median fetal hemoglobin level at the start of this study was seven 7% with a mean value of seven 6%.
Alex Sapir: To date no patients have discontinued from the study and we continue to see greater than 90% adherence to the once a day oral drug regimen.
Alex Sapir: Furthermore, we are pleased to report that the data monitoring committee for the pioneer study after reviewing interim data from the 12 milligram cohort recommended that we continue the study as planned with the initiation of the 20 milligram cohort cohort four which is now underway and currently screening.
Alex Sapir: <unk> patients.
Alex Sapir: We remain on track with our plans to report data from cohort for the 20 milligram cohort by the end of 2025 now.
Alex Sapir: We continue to believe that inducing fetal hemoglobin is the optimal strategy for treating sickle cell disease evidence for this approach continues to grow as highlighted by not only the recently approved gene therapies, but recent data analysis, showing that even modest increases in fetal hemoglobin correlate.
Alex Sapir: To reduced disease severity.
Alex Sapir: Specifically, our recent data analysis that was presented at Ash last December shows that for every 1% increase in hbf, there was a 4% to 8% reduction in basal occlusive crises or voc's. These voc's occur when sickle red blood cells prevent oxygenated blood from getting to the <unk>.
Alex Sapir: <unk>, resulting in debilitating pain, often requiring hospitalization or visits to the emergency room. Additionally.
Alex Sapir: Additionally, fetal hemoglobin levels in the mid 20% range have shown a near abolition of these vlccs that I spoke about based on <unk> mechanism of action and the data that we have previously disclosed we believe that <unk> has the potential to provide a differentiated therapeutic option for people living.
Alex Sapir: With sickle cell disease, and we look forward to providing important clinical data this year to further validate our potentially transformative approach with <unk>.
Alex Sapir: At the upcoming European Hematology Association meeting or <unk> for short, which is being held in June in Milan, We have two abstracts that have been accepted for poster presentation.
Alex Sapir: <unk> include preclinical target engagement and reverse ability of gene expression data with <unk> as well as clinical data from our previously completed phase one healthy volunteer study.
Alex Sapir: Now beyond <unk>, we continue to advance our earlier stage development program for the potential treatment of inherited aplastic anemia, as such as Diamond Blackfin anemia, or DBA Schwartzman Diamond syndrome, and Franconia anemia, we plan to submit an IND for DVA in the fourth quarter.
Alex Sapir: Of this year.
Alex Sapir: And with that overview I will now turn it over to our Chief Financial Officer, Alan Musso to run through the financials over to you Alan.
Alan Musso: Thanks, Alex.
Alan Musso: Now go over our results for the quarter ended March 31 2025.
Alan Musso: Our research and development expenses were $13 4 million for the first quarter of 2025 compared to $19 8 million for the first quarter of 2024.
Alan Musso: A decrease of $6 4 million was due to the discontinuation of our <unk> program.
Alan Musso: And the global development cost sharing reimbursement under the Sanofi collaboration.
Alan Musso: Partially offset by increased costs related to the advancement of the phase <unk> pioneer trial this year there.
Alan Musso: The general and administrative expenses were $7 million for the first quarter of 2025 compared to $10 1 million for the first quarter of 2024 three.
Alan Musso: $3 1 million decrease is primarily due to decreased employee compensation costs as a result of the reduction in workforce implemented in the third quarter of 2024.
Alan Musso: Net loss was $17 7 million for the first part of 2025 compared to a net loss of $26 9 million for the first quarter of 2024.
Alan Musso: And turning to the balance sheet. We ended the first quarter of 2025 with cash cash equivalents and marketable securities of $226 6 million.
Alan Musso: $241 million as of December 31, 2024.
Alan Musso: The $14 4 million decrease is primarily due to cash used to fund the operating activities.
Alan Musso: And finally, turning to cash guidance based on our current operating plans. We continue to expect that our existing cash cash equivalents in marketable securities will be sufficient under operating requirements into at least 2027 and with that I'll turn the call over to back to you al that's great. Thanks, Alan So to conclude <unk> is off to a solid.
Alan Musso: In 2025, and we're very much looking forward to delivering two important data releases this year with the pioneer trial, so with that overview of the business and the financials that Alan went over Livia, Let's go ahead and open it up for questions.
Speaker Change: Ladies and gentlemen, as a reminder to ask a question you will need to press star one on your telephone and wait for your name to be announced to withdraw your question simply press Star One again, please standby, while we compile Kenny roster.
Speaker Change: Our first question coming from the line of Joe Schwartz with Leerink Partners. Your line is now open.
Great. Thanks, so much congrats on all the progress.
Speaker Change: Hi to dig on look forward to working together again.
Speaker Change: I was wondering if you could talk some more about the quantum of data you expect to report from the 12 milligram cohort of pioneer midyear what range of follow up duration do you anticipate we'll see for the 16 patients have been enrolled and when we get any data on markers of hemolysis. In addition to.
Speaker Change: Hemoglobin data for these patients.
Speaker Change: Yes, Great question, Joe Thanks for asking it to answer that I will turn that.
Speaker Change: Answer over to <unk>.
Speaker Change: And Fraser, our head of development, who is actually versus in the room, but it wasn't it wasn't introduced it at the outset of the call and you want to take that yeah. Thanks. Thanks, Alex maybe for the first the second part of your question Joe markers of Hemolysis, Yes, we'll be providing hematological parameters the blood counts.
Speaker Change: Rubens and so on.
Speaker Change: As indicators of hemolysis.
Speaker Change: With respect to the first part of your question, we will have all the data for all 16 patients on the treatment.
Speaker Change: Phase of the study so that's the three month treatment duration, and then a subset of patients with a four week follow up.
Speaker Change: After that.
Speaker Change: It probably will not be all <unk> 16 for the full four weeks based on the data cuts that we will have a subset of those patients.
Speaker Change: Great. Thanks, that's super helpful and then.
Speaker Change: I guess does the observed dosing provide you with.
Speaker Change: <unk>.
Speaker Change: Specific data on the number of doses that patients are receiving real time and do you happen to have any of that data.
Speaker Change: Andy.
Speaker Change: You could share with us.
Speaker Change: Yeah.
Speaker Change: Yes, Joe is this sort of related to the to the 90% adherence number that we referenced in our opening remarks.
Speaker Change: Yes, yes.
Speaker Change: I guess.
Speaker Change: And is there any more color that you can provide on the timing of the doses are they all within the prescribed time frame.
Speaker Change: <unk>.
Speaker Change: I guess, how many doses have occurred.
Speaker Change: To date, yes.
Speaker Change: Yes.
Speaker Change: It's a great question, Joe I appreciate you asking it so let me let me give us maybe a little bit of background. So just for everybody. That's on the call. It is an oral once daily dosing and the way that we're able to capture.
Speaker Change: Parents rates is not through the more traditional kind of pill counts at the end of the month, where the patient comes in and gets their their next bottle.
Speaker Change: It's really using this.
Speaker Change: Hi tool that we've mentioned and that is listed in our Investor presentation, AI cure and this is something where the actual patient has to sort of registered themselves on this.
Speaker Change: Hi tool show that they've actually put the drug in their mouth have swallowed. It. They then have to open their mouth to show that the that the drug is gone and then and then we get reports I wouldn't necessarily say on a on a real time basis, but we get them in a very sort of timely manner as do the as do the sites as well and so that's really.
Speaker Change: Where that where that 90%.
Speaker Change: Where that 90% number is coming from not not really from the more traditional.
Speaker Change: Days that people measure adherence to drag around <unk>.
Speaker Change: Around pill counts.
Speaker Change: Anything else you'd want to add to that.
Speaker Change: Other than that the patient selects the time of day that they wanted to take their medication and the App will remind them at that time. So everything is built around that.
Speaker Change: Update that they're taking it.
Speaker Change: And that gets captured as well, yes. So we certainly can capture that Joe.
Speaker Change: You mean that they are using the tool, which we which we know they are in greater than 90% of cases. So we can actually determine are they actually taking it exactly at eight o'clock every day for the full 84 days or not I don't have that I don't have that data handy.
Speaker Change: I'm not we haven't really discussed whether that's something that we'll be presenting when we shared the data in an early Q3 does that does that answer your question yes.
Speaker Change: Yes, Thats excellent we're looking forward to your updates this year. Okay. Thanks for the insights yes. Thanks, so much Jeff for the questions.
Thank you.
Next question coming from the line of Matthew <unk> with Oppenheimer. Your line is now open.
Speaker Change: Oh, great Hammer on.
Speaker Change: Offer my congrats as well.
Speaker Change: Thanks for the updated color here the baseline hbf is a bit higher I think at 7% than we anticipated and then like the severity of disease for these patients at entry. So number one do you think you've gotten a representative sample of the broader demographic youre going to be trying to treat here.
Speaker Change: When we do get the data and number two do you think <unk> should work equally well or perhaps even better in patients with higher baseline hbf.
Speaker Change: Yeah, Great Great question, Joe sorry, great questions, Matt Thanks for asking them, Yes, let me, maybe just comment a little bit on your first sort of comment that it was a little bit sort of higher than many people had expected I think that what we were hearing in our normal course of conversations with investors is that because this was a more.
Speaker Change: Severe patient population I think some were worried that.
Speaker Change: You were seeing.
Speaker Change: Our baseline fetal hemoglobin and the very sort of low single digits and if they are in the very low single digits. It is going to be very difficult to get them to a number that people can get excited about so I think when we saw what the baselines were at seven.
Speaker Change: 777% for the median and mean value of $7 six we thought.
Speaker Change: It was important to sort of share that with.
Speaker Change: With folks because again I think many people were thinking that or these baseline fetal hemoglobin levels could be extremely low given the severity of the patients that we're enrolling and then maybe an answer to your other two questions. Let me turn that one over to Ian.
Ian: Yes, I would think Matt.
Speaker Change: In that.
Speaker Change: General population with larger numbers those that have the more severe phenotype will tend to have lower baseline.
Speaker Change: Hemoglobin.
Speaker Change: Have a smaller sample size here.
Speaker Change: At the moment and spends a range of those baselines I don't think there's anything unexpected.
Speaker Change: On debt.
Speaker Change: As Alex said, we thought it was helpful to provide that additional bit of color.
Speaker Change: Leading into the data readouts.
Speaker Change: With respect to your other question about responsiveness I think at the moment, we don't have any reason to believe that your baseline level of <unk>.
Speaker Change: Hbf in and of itself determines your response to <unk> and we've certainly seen from the initial 16 patients enrolled at some at the low end had a pretty robust induction of hbf.
Speaker Change: In response to drug I think what is fair to say is that if youre starting very low.
Speaker Change: Where you eventually Max out.
Speaker Change: At steady state on therapy.
Speaker Change: Maybe.
At a lower absolute fetal hemoglobin than if you were starting at a higher level, but I think we need the fuller data set to be able to comment further on that.
Speaker Change: Okay Awesome that makes a lot of sense, if I could just maybe squeeze one quick one and then on the guide going from I guess mid year to early <unk> is that just kind of nuts and bolts of the execution of the clinical trial or are you actually want to get more follow up on potential disease modification endpoints such like that.
Speaker Change: You very much.
Speaker Change: Yes, Matt I think it was really just more of the execution of the trial, we thought that obviously, having more patients versus less patients would be better. The fact that we've enrolled 16 and as Ian said, we'll have the we'll have the full treatment data for all of those 16 patients at the at the end of Q3, So I'm sorry, it's.
Speaker Change: The beginning of Q3, so that was really I think the reason that debt.
Speaker Change: That we tightened that guidance, but still that guidance has always been in the sort of mid mid year range.
Speaker Change: Okay.
Speaker Change: Thank you.
Speaker Change: And our next question coming from the line of tempo.
Speaker Change: MS. <unk> your line is now open.
Speaker Change: Great. Thank you.
Speaker Change: Thank you very much for taking my call and I apologize I'm bouncing between calls today, but I just wanted to get a sense.
Speaker Change: Four.
Speaker Change: I apologize if this was.
Speaker Change: But what is what's a win for you guys on the 12 week data.
Speaker Change: Obviously, we saw somewhere around 10%, there's going to be some differences in terms of our patients who are enrolled maybe for <unk>.
Speaker Change: <unk>.
Speaker Change: Equivalent will be different but what are you guys really focused on from that data.
Speaker Change: To know that.
Speaker Change: <unk>.
Speaker Change: Working.
Speaker Change: Yes in the ballpark of about two point.
Speaker Change: Yes. Thanks for the question Ted I'll start and then I'll turn it over to Ian for any additional color as we've said in the past and as we said in our opening remarks, I think that any increase in fetal hemoglobin is beneficial to the patients and even something as small as a 1% increase can lead.
Speaker Change: To a 4% anywhere from 4% to 8% reduction in <unk>. We also know that based on.
Speaker Change: Drugs that have been approved for the treatment of sickle cell.
Speaker Change: Yossi reduction somewhere in the sort of 25% to 50% range is considered clinically meaningful for the patients and that has been the basis of approval. So where are you sort of net out in that 4% to 8% range you could easily have single digit absolute single digit increases.
Speaker Change: As in fetal fetal hemoglobin.
Speaker Change: Compared to where the patients were at baseline and that can be clinically meaningful.
Speaker Change: For the patients.
Speaker Change: Once you get to that 25% range, that's really where it becomes transformative for patients.
Ian: Maybe let me stop there and see what would what additional color Ian Ian wants to add.
Ian: I think Ted you alluded to what we had seen seen before and we're looking to see with as we brought in the numbers of patients in the cohorts that we reaffirm that magnitude of induction and as Alex said.
Ian: The.
Ian: Mid single digit percent increases in fetal hemoglobin are expected to be clinically meaningful.
Ian: Great.
Ian: Looking forward.
Speaker Change: Thanks, Dave and thanks cause it really makes a lot of time.
Ted: Thanks Ted.
Ken: Thanks, Ken.
Speaker Change: Our next question coming from the line of Kristen <unk> with Cantor Fitzgerald. Your line is now open.
Speaker Change: Hi, good morning, everybody very encouraging to see you ended up with 16 patients in this cohort and that enrollment overall seems to be going a lot faster than a lot of us expected.
Speaker Change: Much of this in your opinion could just be attributed to the loss of Fox, Brian and different dynamics or how much of it is attributed to getting more sites on board.
Speaker Change: Yes, yes.
Alex Sapir: Yes, Kristen it's Alex Thanks for thanks for the question I think it is.
Speaker Change: It's a combination.
Speaker Change: Both and when you say getting sites on board I think what we what we have now is we've got the right sites onboard and what I mean by right sites is these are sites that we know and to treat older patients that maybe have more severe disease I E either for boc over at <unk>.
Speaker Change: <unk> month period of time or <unk>.
Speaker Change: A six month period of time, so these patients do tend to be.
Speaker Change: More severe so I think that part.
Part of that is driven by the fact that we've got the right sites onboard I think part of it is also driven by the fact that.
Speaker Change: <unk> is no longer available and obviously the patients that were on Voc cellar door, obviously, we're very interested and actively managing their disease. So once they had to go up I think that many of those patients were going back to their physicians and saying what else is what else is available and then I would say the third factor.
Speaker Change: Or is just kind of overall excitement and momentum.
Speaker Change: Round fetal hemoglobin induction as really what we believe is there.
As the path forward to really potential LTC transformative treatment options for these patients and with us being very much sort of at the forefront and leading that charge.
Speaker Change: <unk> get excited about the drug they start.
Speaker Change: Get excited about the trial they start the patient.
Speaker Change: They hear positive sentiments from their patients and that just sort of feeds even greater success.
Speaker Change: Greater greater enrollment into the.
Speaker Change: Into the study.
Speaker Change: And anything you want to add there.
Speaker Change: Additional bit of color would be I think we've articulated previously how getting some of these sites that are best matched to this patient population.
Speaker Change: It takes a long time to get those sites up and running and there is that lag phase and I think what we're seeing is.
Speaker Change: That lag face being overcome those sites being activated but.
Speaker Change: The right sites being able to recruit patients and Thats really.
Speaker Change: But with the recruitment in the study.
Speaker Change: Okay. Thanks, and I know you talked about that you don't currently have reason to believe that baseline levels will determine your responses, but has there been any work or research John to understand why certain patient populations may present, a more severe.
Speaker Change: Why these patients don't respond to other therapies that are part of your inclusion exclusion criteria and I think ultimately what I'm trying to go with my question.
Speaker Change: If you're able to show response in a population that's already deemed to be.
Speaker Change: Severe and tougher to treat with any intervention how does that help us understand how the data can translate potentially to a more traditional all comers population.
Speaker Change: And you want to take that.
Speaker Change: That's a great question and I think that lots of components there Kristen on the one hand.
Speaker Change: Sure.
Speaker Change: The relationship between the underlying genetics and the <unk>.
Speaker Change: Severity manifestations of the disease.
Speaker Change: And <unk> is obviously, a big contributor to that but there are other components related to that as well and then secondly is the aspect of responsiveness to therapy is being able to provide benefit to those patients and I think thats going to be different for different therapies different therapies will have different reasons for.
Speaker Change: Responsiveness on non responsiveness I think as we move through our clinical program.
Speaker Change: Those are things that we're going to be looking for are there key issues that we can tease out determining responsiveness or not.
Speaker Change: And translating to benefit so I think thats, an important piece of it.
Speaker Change: With respect to the translate ability to the less severe patient population, we do have.
Speaker Change: Data from the initial 16 patients in this study.
Speaker Change: Who were less clinically severe at the outset and while we don't have really clinical data because it because it's a short study we do have their hbf responses in those.
Speaker Change: As I think everyone knows have been very encouraging.
Speaker Change: So we certainly expect to see that responsiveness, there and even at the high end of.
Speaker Change: Baseline fetal hemoglobin.
Speaker Change: Small increments, even on top of relatively high baselines are clearly associated with benefit as well. So we would expect to see that translate to.
Speaker Change: Yes.
Alex Sapir: Thanks, Alex.
Alex Sapir: Yeah. Thanks, Kristen next question operator.
Speaker Change: Thank you and as a reminder to ask a question. Please press star one.
Speaker Change: Our next question coming from the line of Gregory <unk> with RBC capital markets. Your line is now open.
Speaker Change: Good morning, Alex and team, it's a niche on for Gregg. Thanks for the updates this quarter and for taking our questions. Just a couple from US first given the shifts at the FTA. How are you thinking about the impact to <unk> broader development such as on endpoint selection hbf as a surrogate marker, which I know you've talked about before and even the overall development timeline for <unk>.
Speaker Change: Your take on the current setup with regulators and then just quickly.
Speaker Change: In your deck, you know novel Hbf Inducers in your discovery pipeline could you share how you're thinking about differentiating from other mechanism in the landscape such as was the greater <unk>, one inhibitors et cetera to bring that novelty. Thanks, so much.
Speaker Change: Yes.
Speaker Change: Good question Denise I appreciate you asking them maybe to answer those let me let me turn this over to Ian.
Speaker Change: Yes.
Speaker Change: And I think what we'll be doing as we've articulated previously is that at the end of the 20 milligram cohort.
Speaker Change: At the end of the Phase <unk> study will be interacting with the FDA and the.
Speaker Change: Phase one interaction and I think that'll be our opportunity to get a gauge on that thinking as we discuss plans for the next study there so.
Speaker Change: Thats, an upcoming interaction, which is planned and which we expect will occur at the end of the at the end of the 20 milligram cohort.
Speaker Change: With respect to the other hbf and uses I think.
Speaker Change: Looking more broadly.
Speaker Change: Agnostic lead compounds that are able to induce hbf I think it's early days in the clinic for some of the other end uses that have just entered the clinic in the last year or so including as you mentioned was the greatest in the with <unk> the greater from from BMS GSK.
Speaker Change: <unk> one inhibitor.
Speaker Change: We don't have any clinical data from those as yet, but we'll be monitoring those closely and looking for alternative ways of inducing HBO.
Anish: Great. Thanks, so much thanks Anish.
Speaker Change: Thank you.
Speaker Change: And I'm showing no further questions in the Q&A queue at this time.
Speaker Change: This concludes today's conference call. Thank you all for your participation and you may now disconnect.
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