Q3 2024 Fulcrum Therapeutics Inc Earnings Call
Any increase in fetal hemoglobin is beneficial for patients with sickle cell disease, and most importantly, when sickle cell patients achieved fetal hemoglobin levels in the mid to high twenties. Their disease presentation may become asymptomatic, we believe that as a novel inducer of fetal hemoglobin <unk>.
Has the potential to provide a differentiated therapeutic option for people living with sickle cell disease. We look forward to building on the encouraging clinical data generated prior to the whole, which demonstrated that <unk> increased total fetal hemoglobin of a magnitude that could translate into meaningful improvements in disease.
<unk>.
Beyond <unk>. We are also focused on advancing our early stage development programs in inherited a plastic anemias, such as diamond Black fanned anemia, or DBA, Schwartzman Diamond syndrome, or STS and Ben Kony anemia under our licensing agreement with camp four we anticipate.
Additional information regarding a development candidate and plans for IND, enabling studies in the near future.
I also wanted to provide some updates on the management and board of Directors front. This morning, we announced that Rachel King has joined our board of directors, having served as the CEO at Bayou executive in residence at NEA as well as CEO of several early stage biotech companies Rachel's experience is well aligned with fulcrum need.
Given where we are in our evolution. She currently serves on the board of Novavax and Glycomed ex Rachel will be replacing Jim Collins, who who will be transitioning to an advisory role on our science and Technology Committee I am personally excited to have Rachel joining us and also pleased that we will continue to benefit from Jim.
<unk> deep scientific acumen and sound judgment.
Now on the management front, Dr. Thomas Winkler joined US in September as our Vice President of Hematology preclinical hematology hematology clinical development and has assumed responsibility for our hematology program, but also for the pioneer study.
Thomas has a distinguished career within the within the Hematology branch of the NIH before transitioning to industry, where he focused on developing numerous hematology assets at both <unk> and Astrazeneca are.
Additionally, Pat Horn, our Chief Medical Officer has decided to retire at the end of this year.
Pat joined <unk> earlier, this year and was instrumental in leading clinical development for the reach study hiring key talent like Thomas and building out the medical team as we prepared for the launch of <unk>.
I'd like to personally thank Pat who is here with us in the room today. Thank you Pat as.
As well as express my appreciation to Thomas for bringing his strong hematology background <unk> at such a critical time.
And with that I will now turn it over to our Chief Financial Officer, Alan Musso to run through the numbers Alan over to you.
Alan Musso: Thanks, Alex.
Alan Musso: I will now review our financial results, starting with our cash position.
As of September 32024, cash cash equivalents in marketable securities were $257 2 million <unk>.
Compared to $236 2 million as of December 31, 2023.
Alan Musso: The increase in our cash position is due to the $80 million upfront payment that we received from Santa fee in the second quarter.
Alan Musso: We offset by cash used to fund our operating activities and 2024.
Alan Musso: We had no collaboration revenue in the third quarter of 2024 compared to <unk> 8 million for the third quarter of 2023.
Alan Musso: The decrease of 800000 was due to the completion of our research services under our collaboration agreement with myocardial during the fourth quarter of 2023.
Alan Musso: Our research and development expenses were $14 6 million for the third quarter of 2024 compared to $18 2 million for the third quarter of 2023.
Alan Musso: The decrease of $3 6 million was primarily due to the global development cost sharing reimbursements under our collaboration with Sanofi for less mathematic.
Alan Musso: Partially offset by increased costs related to the advancement of our phase <unk> pioneer trial.
Alan Musso: General and administrative expenses were $8 4 million for the third quarter of 2024 compared to $10 million for the third quarter of 2023.
Alan Musso: A decrease of $1 6 million was primarily due to decreased employee compensation costs as a result of our reduction in workforce implemented in the third quarter of 2024.
Alan Musso: The net loss of $21 7 million for the third quarter of 2024 compared to a net loss of $24 million for the third quarter of 2023.
Alan Musso: Finally, turning to our cash guidance, we expect to end 2024, with approximately $240 million of cash cash equivalents and marketable securities.
And we expect that in 2025, our cash burn will be approximately $55 million to $65 million.
Alan Musso: Based on current operating plans, we expect that our existing cash cash equivalents and marketable securities will be sufficient to fund our operating requirements into at least 2027.
Speaker Change: And with that let me turn the call back over to you. Okay. Great. Thanks, So much Alan and I think with that overview of the business and the financials. Michelle why don't we go ahead and open it up for questions.
Speaker Change: Thank you to ask a question. Please press star one on your telephone and wait for your name to be announced.
Speaker Change: To withdraw your question. Please press star one one again and our first question will come from Matthew Biegler with Oppenheimer. Your line is now open.
Matthew Biegler: Hey, guys. Thanks for the update this morning, maybe just a high level question, Alex on the platform tackling how youre thinking that seen in the pipeline with.
Matthew Biegler: New wholly owned asset how do you think about the difference between keeping a wholly owned versus partnering something out and.
Maybe.
Matthew Biegler: Nextgen asset are there certain disease therapeutic areas that you want to focus and that means that the focus the hematology going forward or are you kind of open to exploring new avenues.
Speaker Change: Yes, that's great Matt. Thanks, so much for the thanks, so much for the question. Yes. So we do have a very rich preclinical pipeline I would say that the most advanced preclinical program that we have as I mentioned during the prepared remarks is our program that we have for inherited aplastic anemia.
Speaker Change: Which do include DBA.
Speaker Change: Swagman Diamond syndrome, or STS Franconia anemia <unk> syndrome.
Speaker Change: We do expect to announce more updates in the near future around the selection of a development candidate and IND, enabling studies. So that is by far our most advanced program.
Speaker Change: And as you know.
Speaker Change: Came from the deal that we signed with <unk> in September of last year, we do have the global rights for those I think for the time being we are going to continue to progress those ourselves and then obviously there is always an option for potential.
Speaker Change: Potential licensing.
Speaker Change: Or potentially markets outside of the U S. Similar to what we did with the.
Speaker Change: With the Sanofi deal with <unk>, but right now our focus is really on progressing some very very interesting work that we've got going on in our discovery efforts. Most notable is the work we're doing.
Speaker Change: In some of these inherited aplastic anemia that I mentioned, Ian anything you would add to that.
Ian: No I think.
Ian: Or is it pretty comprehensively okay.
Ian: Thanks, guys I appreciate it.
Speaker Change: Yes, Thanks, Matt.
Speaker Change: And our next question will come from <unk>.
Speaker Change: Uh-huh with Stifel. Your line is open.
Speaker Change: Great. Good morning, guys. Thanks for taking our questions and congrats on the progress.
I guess two questions on <unk> specifically.
Speaker Change: Going back to your 10-Q filing it seems like on the risk section you have been having this information of the language around request for information to defy the potential risk at any further studies that may be conducted in healthy volunteers.
Speaker Change: You are announcing your intention to do another healthy volunteer studies. So curious what exactly was the feedback from the FDA post ox brighter withdraw that led you to having this trial run sort of concurrent with the pioneer study and then second I guess.
Speaker Change: Terms of the African conduct.
Speaker Change: Just curious what have been sort of the latest FDA feedback on whether or not that meets our standards for the FDA review. Thanks, So much.
Speaker Change: Sure Yeah. Thanks, Dae gon, so much for the question and I'll, probably I'll add a little bit of color on the first question on that over to Ian and then as it relates to the second question around African content I'll punt that over to a.
Speaker Change: I'll punt that over to Pat Yes, So I think just to remind everybody on the call.
Speaker Change: When we get off clinical hold there was no additional clinical or preclinical data that the FDA required prior to going into patients. There was some additional work that the FDA did require of us in order to.
Speaker Change: Progress with healthy volunteers and based on the discussions that we've had with the agency. We are as I mentioned in the prepared remarks, we are moving forward with the work that we need to do in healthy volunteers to really inform the overall clinical development plan and the eventual package that will be that will become the NDA, but I think more specifically, let me, let me turn that over.
Speaker Change: Ian maybe to get into a little bit more detail yeah. Thanks, Alex.
Speaker Change: So.
Speaker Change: It is important to recognize that these healthy volunteers studies, where are studies that have been planned all along they are part of the routine.
Speaker Change: <unk> of our compound.
Speaker Change: Studies that look at.
Speaker Change: Evaluations of new formulations as they get introduced into the clinic some of the drug drug interaction studies.
Speaker Change: And studies to more find me delineate metabolism and excretion overcome so those are our standard drug development studies that were always part of the program.
Speaker Change: Alex mentioned there was this differentiation at the time of the clinical hold between the.
Speaker Change: Patient studies and resuming patient studies was entirely around redefining that patient population and bouncing risk benefit and then on the healthy volunteer side, who are segregated out because of course, there's no benefit to.
Speaker Change: Two individuals participating in healthy volunteer studies.
Speaker Change: And so we've.
Speaker Change: Perform those and are now progressing with the studies as part of the overall development plan.
Speaker Change: Really coincidental around the timing of the ox Friday withdrawn Theres no no link between resumption of those studies and the occupied what's wrong.
Speaker Change: Yes, and then and then they've gone as it relates to your second question before turning it over to Pat I think maybe just real quickly.
Speaker Change: For some of the patients that we have enrolled to date they are coming from.
Speaker Change: African countries and I will say that we've actually been pretty pleased with some of the compliance that we've seen to date in terms of the regulatory his take on patients coming from from sites in Africa, maybe I'll turn that one over to Pat to provide a little bit more detail.
Speaker Change: Yes.
Speaker Change: FDA has a long history of accepting data from extra time.
Speaker Change: Most of the large phase III studies now our global sites and in diseases, such as sickle cell anemia, where the population is really concentrated in different geographies.
Speaker Change: There's a long history I think the majority of study in sickle cell that have led to approval and that are currently ongoing in phase two and phase III have included.
Speaker Change: In sub Saharan Africa, especially.
Speaker Change: The FDA is really only concerned about the quality data and that they are followed GCB and as part of our.
Speaker Change: Progress in <unk>.
Speaker Change: Im going activity study, we review each of these sites before we select sites that have experience most of them have experienced in previous sickle cell study and most of the sites. We're looking at have been audited by regulatory agencies. Some even by the FDA. So we feel confident in the sites we've selected and.
Speaker Change: Their ability to produce acceptable data for the phase one study and even for future registration studies.
Speaker Change: Great Yeah, thanks for taking our questions.
Speaker Change: Alright.
Speaker Change: No worries. Thanks Aegon. Thanks, so much operator next question.
Speaker Change: And our next question will come from Edward <unk> with Piper Sandler Your line is open.
Speaker Change: Great. Good morning, everyone and thanks for taking my question.
Speaker Change: Following up on <unk> question.
Speaker Change: I wanted to get a little sense in terms of.
Speaker Change: Can you provide any better guidance.
Speaker Change: How the data.
From Pioneer May rollout next year will you report it altogether.
Speaker Change: Would you split the 12 and 20, Meg and kind of reported out as it's available.
Speaker Change: Quickly do you envision being able to transition from that.
Speaker Change: Into a registrational study thank you.
Speaker Change: Yeah, that's great. Thanks, so much for asking the question al.
Speaker Change: I'll address the first part of your question excuse me and then I'll turn it over to Pat to address the second part of your question. Yes. So as we've said in the past we do intend to share the 12 milligram cohort, which is being run sequential to the 20 milligram. So those those two datasets will come out at <unk>.
Speaker Change: <unk> points in time in 2025, and so we do intend to share those independent of one another.
Speaker Change: We are pleased with the progress that we are seeing right now with with enrolment. We absolutely have the right sites that are now in place and we're continuing to add new sites.
Speaker Change: And as we've always said once we build that critical mass of patients will come back to everybody with more specificity specifically when in 2025, we will have data to.
Speaker Change: Sure. So I think right now.
Speaker Change: Is a bit premature to give any more specific guidance, but as I said in some of my prepared remarks.
Speaker Change: We do intend to provide more detailed guidance on our plan to share data early in the new year.
Speaker Change: Early 2025, so I think more specifically about your question in terms of what's the next study. After this maybe I'll I'll turn that one over to Pat.
Speaker Change: Great.
Speaker Change: Thomas Winkler since he's been here has been working with our head of regulatory and our regulatory group to really define the clinical development program for <unk>. Following this phase IV.
Speaker Change: And there are multiple possibilities since we have orphan drug designation, we are entitled to in the Phase One study with the FDA, which we plan to make use of it. So we will take the data from the pioneer study take a proposed clinical development plan to the FDA and then get their agreement and that may be.
Speaker Change: That may be the ability to move quickly to a phase II phase III study, which may be registrational or it may be.
Speaker Change: Separate phase II, followed by a phase III study, but that will depend on the data from pioneer and the feedback from the FDA.
Speaker Change: Yes, and then Ted maybe the only other thing that I would add is the.
The abundance of evidence to show that increases in fetal hemoglobin improves not only symptomatology in terms of reduction in <unk>, but also overall survival and as we've said and shared with you. Many times once you get patients over that sort of mid to high <unk> their disease does become asymptomatic. So I think there is.
There is certainly internal discussion going as well as to when is the right time to discuss.
Speaker Change: Fetal hemoglobin potentially as a.
Speaker Change: As a surrogate endpoint that we may use in and one of our further development one of our further studies for the pioneer development program. So that's that work is still ongoing but I think I think that is an important point to make just because how strongly the relationship is based on the data that is out there to show that.
Speaker Change: <unk> and fetal hemoglobin have.
Speaker Change: Very very noticeable impact on survival as well as reduction in <unk>.
Speaker Change: Great. Thank you so much for the color and look forward. This thing is a couple of weeks here.
Speaker Change: Yeah, that's great. Thanks, so much Tad operator next question and our next question comes from Chris <unk> with Cantor Fitzgerald. Your line is open.
Speaker Change: Hi, everyone. This is Rick Miller on for Christian Thanks for taking our question just a quick follow up on the healthy volunteer studies, you've talked about initiating how are you thinking about dosing in these trials and how does this relate to kind of the previous phase one trial dosing strategies, you looked at and in terms.
Speaker Change: Main outcomes here with Steve most of them looking at safety or are there any kind of PK PD measures you're interested in getting a look at thank you.
Speaker Change: Yes, it's great question, Rick and I think to answer that and let me, let me kick that one over to Ian.
Yes, Thanks, Rick.
Ian: Studies are predominantly looking at peak.
Speaker Change: PK profiles in this case.
Speaker Change: Both from the perspective of the AD media absorption.
Speaker Change: Dubuque the metabolism of the drug.
Standard radio labeled study that gets done in development. So thats one of the studies.
Speaker Change: Teed up measuring the drug in the blood and the excretion in the yard and the stool for example, and then the other studies are primarily focused on.
Speaker Change: Measuring the PK, so new formulations as they come into development.
Speaker Change: <unk> will be given to healthy volunteers and typically single dose PK studies, where you measure the performance of.
Speaker Change: Of the new formulation and comparing the old formulation for the drug drug interaction studies is giving posted earlier in the presence of other agents that are commonly used in order to evaluate any impact on the plasma pharmacokinetics of the drug. So those are the studies that are in line as part of the over.
Speaker Change: <unk> development program, and what we will be doing.
Speaker Change: We obviously look at safety and Tolerability is a key endpoint in all of those studies.
Speaker Change: But.
Speaker Change: The important driver of the results then that goes back to inform the clinical program and the patients is around the PK.
Speaker Change: Thank you.
Speaker Change: Yes, Thanks, Rick Operator next question and our next question comes from Gregory <unk> with RBC capital. Your line is open.
Speaker Change: Great. Thanks, Good morning, Alex.
Speaker Change: Good morning, Greg updates, thank you and thanks for taking the questions just a couple from from Us Alex.
Speaker Change: Just as you as you reflect on the map of Mod experience. How are you using that that journey to inform the value proposition the risk assessment of future programs, not just with <unk>, but but also of course with the early discovery programs and then maybe secondly, if.
Speaker Change: If you could just comment a bit about how you expect to balance the in.
Speaker Change: The early discovery programs internally and.
Speaker Change: And with camp that that Youre that youre looking at versus a thought of looking externally for assets and then maybe I'll sneak a third one if I may for Alan.
Speaker Change: Maybe related to all of this as you've talked a bit about our resources and spend for 2025, how does that allocation pan out how should we be thinking about what's what's implied in some of the.
The runway there thanks, so much guys.
Yes, thanks, so much Greg great great Great set of questions. Yes, I think if we if we do a comparison and contrast of Lowe's map of Mod versus <unk> I think they are very different I think.
Speaker Change: Some of the challenges that we knew going into the phase III study.
With <unk> is it was a new novel endpoint and it was very it was very effort dependent I think what we see with <unk> and what we know about <unk> in terms of the patients that we're enrolling in the study prior to the initiation of the hold in very impressive increases that we saw in <unk>.
Speaker Change: A lemur globally as well as the abundance of literature out there to show that increases in fetal hemoglobin have a direct impact on patients.
Speaker Change: Crises as well as their overall survival I think they I see them as dairy I see them as very sort of different development programs as we move forward.
Speaker Change: And I think as I mentioned earlier after after one of paths last comments, we are having internal discussions given how strong. The evidence is we've been working very closely with some.
Speaker Change: Ex FDA consultants to really understand it does it makes sense or when is the right time to approach the agency and their surrogate endpoint group within the agency around the potential to use.
Speaker Change: Fetal hemoglobin as a surrogate endpoint obviously the agency does have a history of proving up.
Other products in sickle cell disease, using surrogate endpoints is as we know I think as you think about sort of early discovery versus externally.
Speaker Change: As Alan mentioned, we've got a very robust balance sheet into at least 2027 and that is assuming success with all of our programs. So that's advancing the <unk> program. Once we completed this phase <unk> study into phase II and phase III. So we certainly <unk>.
Speaker Change: Have the <unk>.
Speaker Change: Financial ability to go out and look at external assets.
Speaker Change: But I think we've got a lot of really exciting things going on in early discovery. If we were to look externally at potentially opportunities to bring in house, given how robust our balance sheet is we will continue to be very judicious and highly selective the company has had a.
History of of doing deals, but those deals I think have been an excellent terms and we've been very sort of smart judicious as to in terms of what we decided to bring in so if we were to do something.
Speaker Change: It would be at the level of sort of intelligence and just sort of deep diligence that we've historically done with other licensing opportunities of assets that we brought in and then maybe Alan to answer. His third question, Yes, Alex I think you addressed some of it.
Alan Musso: Greg as we guided we expect next year next year spend to be $55 million to $65 million and that anticipate.
Speaker Change: <unk>.
Speaker Change: Funding of <unk> and maximizing the opportunity there.
Speaker Change: Funding, our preclinical programs and seeing those advanced forward. So we feel like we are fortunate to be in really good shape with our cash position at this time.
Speaker Change: Great. Thank you guys.
Speaker Change: Yes, Thanks, Greg.
Speaker Change: And our next question comes from Joseph Schwartz with Leerink. Your line is open.
Hi, Andrew Park dialing in for Jonathan Thanks for taking our question.
Speaker Change: So this time I E. You presented a map of sites, you're Onboarding and I believe they were 11 in the U S and two ex U S.
Speaker Change: Curious what your latest thoughts are on these sites and then separately I believe that you plan to activate up to 20 sites. That's what you said on a previous call with more sites to activate what you've mentioned on today's call. So I was curious if you've identified the remaining seven sites and where you are on the onboarding process for that thank you.
Yes, it's a great question and I'll start and then I'll turn it over to Pat to provide a little bit more detail. So yes. You are correct. We have 12 sites activated I would say that some of the more recently activated sites. Both here in the U S as well as the ex U S are absolutely the right sites that we that are in place now.
Speaker Change: And again I'm pleased with some of the early insights we're seeing in terms of patient enrollment our goal is still to.
Speaker Change: Ramp up and enrolled 20 sites by the end of this year, we were at a.
Speaker Change: Both Pat and I were at a investigator meeting.
Speaker Change: In Dallas, just this past Friday, we had 15 sites represented many of the existing sites, but also several new sites that will be activated in the coming months, but maybe Pat do you want to sort of give a little bit more specificity in terms of when we would expect to have those additional sites onboard it yet so we are actively.
Speaker Change: Working on activation and we have.
Speaker Change: To your question, we have identified the sites that we believe will be successful in recruiting pioneer.
Speaker Change: The majority of those remain in the U S. But there are some in Africa.
Speaker Change: And we are working to activate all of those we have activated.
Speaker Change: I don't know the exact number but many more since the <unk> meeting and we continue we have in the next couple of months, we have to activation and site initiation visits planned for.
Speaker Change: Pretty much the remaining sites.
We continue to.
Speaker Change: And like I said, we think these sites will be sufficient to enroll pioneer.
Speaker Change: She continues to engage new sites and new investigators.
Speaker Change: Partly for future studies.
Speaker Change: Because there has been an increased interest in <unk> and hemoglobin F. Inducers. So we continue to engage with new sites and there is a possibility that some of them. If theyre activation could be quick enough could also joined and help with pioneer.
But it's predominantly more for future studies.
Speaker Change: Great. Thank you.
Speaker Change: Yes, thanks, so much for the question.
As a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced.
Speaker Change: And our next question comes from Corinne Johnson with Goldman Sachs. Your line is open.
Good morning, everyone.
Speaker Change: You mentioned that that disparity there.
Speaker Change: Program.
Speaker Change: And then I guess does that apply to a broader scope of patients and it's currently allowed within the trial or would that be specific to this higher risk scrip, you're currently focused on.
Speaker Change: Yes, so maybe I'll start and then I'll turn it over to Alan for more specifics in terms of the funding and what we've allocated yes. So as we've said.
Speaker Change: In the past.
Alan Musso: We believe that once we're able to show the benefits that that based on the data that we had prior to the initiation of hold with these additional 20 patients we will be able to have a future conversation with the agency as Pat mentioned at the end of the Phase one program to really look to expand the patient.
Alan Musso: Population beyond the more severe patient population that we are out there.
Alan Musso: That we're currently targeting because I think obviously for the for the agency Theyre thinking about everything from a from a risk benefit and as we've talked about in some of our preclinical work. There was this carcinogenicity risk that was seen that was really the impetus for the reason for the hold but there were also some of the <unk>.
Alan Musso: <unk> impressive levels of fetal hemoglobin that we saw in the first 15 patients. So our goal is to get these additional 20 patients with its more severe patient population enrolled have them complete their entire three months of dosing take a look at that data and then approach the agency about expanding the patient population beyond where we are today and then al.
And in terms of the specifics around the funding of what that looks like and what the study looks like and so.
Alan Musso: We are sort of budgeting and forecast process encompasses taking the development plans and.
Alan Musso: And for Us to where we expect the program will go not only next year, but beyond that and then allocating the capital towards that so that's the guidance that we gave which is sort of complete.
Alan Musso: In anticipation for this year youre going forward.
Thank you.
Speaker Change: Thanks, Karen.
I show no further questions at this time.
Speaker Change: This does conclude today's conference call. Thank you so much for participating you may now disconnect.
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