Q4 2024 Fulcrum Therapeutics Inc Earnings Call
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Speaker Change: Leading the call today will be Alex Sapir, CEO and president of Broadcom.
Speaker Change: Joining Alexandre car, Alan Musso, Chief Financial Officer, and Dr. Ian Frazier Senior Vice President of a fairly early development.
Speaker Change: To providing updates on our company's key programs there'll be a brief Q&A in which Alex calling in and we'll give that but to answer your questions with that it's my pleasure to turn the call over to Alex.
Speaker Change: Great. Thanks, so much Marvin and good morning, everyone and thank you for joining us today.
Speaker Change: The latter part of 2024 and early 2025 has been an exciting period for fulcrum with notable progress for our lead program for Sera Dear currently in development for the treatment of sickle cell disease with the team we have in place a year end cash position of 241 million and <unk>.
Speaker Change: Lastly, two data readouts over the next 12 months 2025 is poised to be an important year for fulcrum and more critically for patients with sickle cell disease and other benign hematological conditions.
Speaker Change: So let me get into some of the details and I'll begin by giving you an update on <unk>, our oral hbf inducer for the treatment of sickle cell disease.
Speaker Change: Now as many of you know sickle cell disease is a lifelong inherited blood disorder that severely impact quality of life for approximately 100000 people in the U S and $4 4 million people worldwide.
Speaker Change: Historically, the standard treatment for sickle cell disease has involved blood transfusions pain medications and hydroxyurea, focusing primarily on symptom relief.
Speaker Change: Despite the approval of gene editing therapies and their ability to increase fetal hemoglobin levels to transformation to transformational levels for patients. There remains a significant unmet need for safe and accessible oral therapeutic options that are broadly protective of sickle cell symptomatology.
Speaker Change: This unmet need is further underscored by the recent global withdraw a box right.
Speaker Change: And is the first in class oral small molecule Hbf inducer, we believe post Sera Deere has the potential to address this high unmet need.
In our phase one b trial of <unk>, which we call. The pioneer trial, we have made good progress enrolling patients in activating sites and I am pleased to report that we recently enrolled our 10 patients in the 12 milligram cohort with the potential to enroll additional patients currently in screening.
Speaker Change: Prior to the next cohort the 20 milligram cohort being open for enrollment.
Speaker Change: Just on the progress that we've made with enrollment we remain committed to share data from the 12 milligram cohort in mid 2025, and the 20 milligram cohort by year at now.
Speaker Change: Now just as a quick reminder, patients enrolling cohort three are receiving 12 milligrams of <unk> once daily while patients in cohort four will receive 20 milligrams once daily.
Speaker Change: Each cohort has a dosing duration of three months followed by a one month follow up visit by the patient.
Speaker Change: We believe that inducing fetal hemoglobin is the optimal strategy for treating sickle cell disease evidence for the benefits of fetal hemoglobin continues to grow as highlighted by the recent data presented at Ash last December showing that even modest increases in hbf correlate to reduce disease severity.
Speaker Change: Specifically, each 1% increase in hbf was shown to provide a 4% to 8% reduction in painful and at times debilitating basal occlusive crises or <unk>.
Speaker Change: Anymore once hbf levels reach into their mid twenties patients experienced a near abolition of vlccs.
Speaker Change: 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 patients living with sickle cell.
Speaker Change: Beyond <unk>, we continue to make progress in other rare benign hematological conditions. In particular, we are currently conducting IND, enabling studies for an oral compound. We believe has the potential to treat inherited aplastic anemia, as such as diamond blacks and anemia.
Speaker Change: Or DBA for short Schwartzman Diamond syndrome in Franconia anemia, and we plan to submit an IND for diamond Black fan in EMEA in the fourth quarter of this year.
Speaker Change: With that let me now turn it over to our Chief Financial Officer, Alan Musso to run through the financials Alan over to you.
Alan: Thanks, Alex.
Speaker Change: I'll now go over our results for the fourth quarter and for the full year ended December 31, 2024, beginning with results for the quarter.
Speaker Change: We had no collaboration revenues in the fourth quarter of 2024 compared to 900000 for the fourth quarter of 2023.
Speaker Change: The decrease was due to the completion of our research services under our myocardial collaboration agreement during the fourth quarter of 2023.
Speaker Change: Our research and development expenses were $11 7 million for the fourth quarter of 2024 compared to $19 million for the fourth quarter of 2023.
Speaker Change: The decrease of $7 3 million was primarily due to decreased costs associated with the discontinuation of our road map and mud program and global development cost sharing reimbursements under the collaboration with Abbvie.
Speaker Change: Actually offset by increased costs related to the advancement of the phase one b pioneer trial.
Speaker Change: General and administrative expenses were $7 7 million for the fourth quarter of 2024 compared to $9 9 million for the fourth quarter of 2023.
Speaker Change: The decrease of $2 2 million was primarily due to decreased employee compensation costs, resulting from the workforce reduction implemented in the third quarter of 2024.
Speaker Change: Our net loss was $16 6 million for the fourth quarter of 2024 compared to a net loss of $24 8 million for the fourth quarter of 2023.
Speaker Change: I will now review the results for the full year ended December 31 2024.
Speaker Change: Collaboration revenue was $80 million for the year ended December 31, 2024, compared to $2 8 million for the same periods in 2023.
Speaker Change: The increase of $77 2 million was primarily due to recognition of the 80 million upfront license payment received from Sanofi during 2024.
Speaker Change: The research and development expenses were $63 4 million for the year ended December 31, 2024, compared to $71 8 million for the same period in 2023.
The decrease of $8 4 million was primarily due to global development cost sharing reimbursements under our collaboration with Sanofi.
Speaker Change: Offset by increased costs related to the advancement of the phase one b pioneer trial.
Speaker Change: General and administrative expenses were $36 4 million for the year ended December 31, 2024, compared to $41 7 million for the same period in 2023.
Speaker Change: A decrease of $5 3 million was primarily due to decreased employee compensation costs. As a result of the workforce reduction implemented in the third quarter of 2024.
Speaker Change: Our restructuring expenses were $2 1 million for the year ended December 31, 2024 compared to no restructuring expenses during the same period of 2023.
Speaker Change: The increase was due to the workforce reduction implemented in the third quarter of 2024, primarily related to severance costs.
Speaker Change: And our net loss was $9 7 million for the year ended December 31, 2024, as compared to $97 3 million for the same period in 2023.
Speaker Change: And now turning to the balance sheet. We ended 2024 with cash cash equivalents in marketable securities of $241 million.
Speaker Change: Compared to $236 2 million as of December 31, 2023.
Speaker Change: The increase in our cash position was due to the $80 million upfront payment. We received from Sanofi in the second quarter of 2024, partially offset by the cash used to fund our operating activities in 2024.
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 to fund our operating requirements into at least 2027.
Speaker Change: And with that let me turn the call back over to Alex that's great. Thanks, So much Alan and so with that overview of the business and the financial debt. Alan just went through Marvin lets lets go ahead and open it up for questions.
Speaker Change: Thank you at this time, we will take the question and answer session. As a reminder to ask a question you'll need to press star one one on your telephone and wait for your name to be announced to try. Your question. Please press star one again please.
Speaker Change: Please stand by while we compile the Q&A roster.
Christian <unk>: And our first question comes from the line of Christian <unk> of Cantor Fitzgerald. Your line is now open.
Speaker Change: Hi, This is Rick Miller on for Christian Thanks for taking our questions. We've just got two for you today can you give us any color on when you would look to meet with the FDA as it relates to the 12 milligram and 20 milligram cohort Readouts and also what do you think the bar is on fetal hemoglobin and Boc reduction now that there have been changes in the sickle cell space.
Yes.
Speaker Change: Yes, I think to answer that question Rick Thanks for asking it's a good question I think to answer that let me I'll turn it over to Ian and then if Ive got any additional.
Speaker Change: Additional comments to make I can add those after after Ian Ian over to you.
Ian Ian: Yeah, Thanks, Alex and thanks, Rick for the question. So what we've said in the past is that we aim to complete the 12 milligram and 20 milligram cohorts before going back to the FDA to review the next steps in the program.
Speaker Change: We've also said that depending on the data emerging.
Speaker Change: The study it could potentially go back to the agency earlier with.
Speaker Change: With the data from the 12 milligram cohort itself so.
Speaker Change: All dependent on on the data emerging from that cohort and we will review it and make that decision at the time.
Speaker Change: To your second question.
Speaker Change: <unk>, which relates to the extent of fetal hemoglobin induction I think there've been a number of movements in the space that have really reinforced the importance of fetal hemoglobin in the overall treatment of sickle cell disease, both from the gene therapy side.
Speaker Change: Were increases in fetal hemoglobin that extended up into the low 40% range have shown to be.
Speaker Change: Clearly.
Speaker Change: Transformational for those patients in terms of reductions of acute symptoms.
Speaker Change: The overall data epidemiologic pharmacologic and genetics suggest that there is clearly benefit to.
Speaker Change: To be gained from increases of fetal hemoglobin that are even lower than that.
Speaker Change: We know as Alex mentioned in his remarks at the beginning of that.
Speaker Change: Of this meeting.
Speaker Change: Were published by Novo.
Speaker Change: At Ash just this last December which was a review of previously conducted studies in the sickle cell space indicated that a one percentage point increase in fetal hemoglobin.
Speaker Change: Was associated with a 4% to 8% reduction in acute voc's. So so even at that relatively low increase in fetal hemoglobin. There is benefit to be had if we look at what's been approved based on Boc's L. Glutamine was approved by FDA with a 25%.
Speaker Change: Reduction in Boc, so that at least was was one benchmark for what was considered to be clinically meaningful in that space. So I think that's the one piece of it and the other piece is some work that we've done ourselves emphasis.
Corporate tax in analysis of real World data from picnic health, indicating that as you increase fetal hemoglobin from very low levels up to around the mid 20% range you get an incremental reduction in the likelihood that youll experience of boc during the year.
Speaker Change: That mid 20% range the curve flattens out in the.
Probability of having.
Speaker Change: And the following year is close to zero and so putting those two together small increases can be clinically meaningful and beneficial once you get to the mid 20% range transformational for the patients and then Rick. This is Alex the only other thing I would add related to your first question in terms of engagement with.
Speaker Change: With the agency and we stated this in the past as well as a separate works.
Speaker Change: Separate work stream, we do plan to engage with the agency on the use of fetal hemoglobin as a surrogate endpoint potentially for our next study that we would conduct with thought with posterior so those discussions are ongoing but I think as Ian said any increase in fetal hemoglobin.
Speaker Change: <unk>.
Speaker Change: Market reduction of iOS and then once you get to that mid 25%. That's when you see a near abolition of Ibs C. So I think there's a tremendous amount of data on the use of hbf and its impact on.
Clinical manifestations of the disease and so we will be engaging with the agency on the possibility of using hbf as a surrogate endpoint for the next study that we plan to conduct what puts you are there.
Speaker Change: That's great. Thank you for the color, yes, thanks, so much.
Speaker Change: Okay.
Speaker Change: Thank you Juan for next question.
Speaker Change: Our next question comes from the line of Joe Schwartz with Leerink Partners. Your line is now open.
Joe Schwartz: Great. Thanks, very much I was wondering if you can give us any insight into the types of patients who have been enrolling in pioneer to date, given the detailed rubric required to identify those who are eligible to enroll and involves a number of criteria I'm. Just wondering if any particular patterns are presenting themselves.
Speaker Change: Especially now that the withdrawal of <unk>.
Speaker Change: Mike might be influencing things and then I have a follow up thanks, yes. Thanks, Joe. It's a good question I. Appreciate you asking I'll start and then I'll turn it over to Ian for any additional color there that I missed.
Speaker Change: The 10 patients we have enrolled to date come from both South Africa and the U S. As you articulated in your question. These patients do tend to be on the more severe side. So it would not be unexpected to see their their baseline fetal hemoglobin lower than what we show.
Speaker Change: In the first 15 patients that were enrolled in this study, but we have yet to.
Speaker Change: Share details at any of the details around baseline fetal hemoglobin and I think as we previously have said our plan is to release.
The full dataset once that does become available and again, we do remain on track to.
Speaker Change: To share that data and the 12 milligram cohort by by mid year any anything else you would add to that Ian.
Speaker Change: We've spoken about the specific inclusion exclusion criteria for the new part of the study emerging from the clinical hold and the patients are conforming to those new inclusion exclusion criteria. So I don't think theres anything surprising different or any unusual patterns that are emerging.
Speaker Change: From that today, that's pretty much in line with what we expected based on on those inclusion exclusion criteria.
Speaker Change: We do obviously.
Speaker Change: Have benefit.
Speaker Change: Patients now not being able to access <unk> ox brighter.
Speaker Change: Those patients have to wash out of that therapy, and so that process is sort of just coming to fruition now not everybody stopped immediately on the day it was withdrawn.
Speaker Change: But those patients are obviously lacking in other options and they do have the option of enrolling in our study maybe maybe Joe the only other thing I would add is the high level of.
Speaker Change: Adherence to study study drug that we are seeing so we're using a pretty innovative AI tool from this company called AI cure it really sort of monitors the patient taking the drug on a on a daily basis and we're seeing.
Speaker Change: Adherence rates across these 10 patients that have enrolled we don't have a lot of data on the 10 patients. They were only recently enrolled but we're seeing adherence to study drug rates.
Speaker Change: North of 90%. So that's also been that's also been really pleasing to see.
Speaker Change: Okay, great. Thanks that was going to be my second.
Speaker Change: Question. So I appreciate that color, but maybe I can just ask.
Whether there's a particular hurdle that the <unk> needs <unk> clear before we can advance to the 20 milligram cohort can you talk about.
Speaker Change: How that process of evaluation will go with the D SMB.
Speaker Change: Yes, sure I'll sort of provide a couple of the fact that I will turn it over to Ian to get into more specifics in terms of exactly what that DMC. The data monitoring committee is looking for so just to remind everybody wants the eighth patient has completed their 30 days of dosing that is when we.
Speaker Change: We can call the DMC together to review the to review the data and I'll have Ian just touch on that in just a minute so that that meeting with the DMC is in the process of being scheduled as you can imagine these are busy thought leaders. So in addition to.
Speaker Change: Making sure that that a patient has completed a 30 days of dosing Thats also just logistically, making sure that the <unk>.
Speaker Change: Schedules of all of these busy people are aligning but that the scheduling of that DMC meeting to review that data is.
Speaker Change: In the process of being scheduled do you want to maybe talk a little bit about what the DMC is actually looking for sure happy to do that and maybe just to add that.
Speaker Change: There always was right from the beginning of the study which is our first in patient dose escalation there always was.
A pause between sequential cohorts with a review of the data.
Speaker Change: In order to allow the subsequent cohort to proceed and that review is always primarily focused on safety and tolerability.
Speaker Change: A DMC now will convene to review.
Speaker Change: The 12 milligram cohort.
Speaker Change: With respect to advancing to the 20 milligram cohort and their focus is again, primarily around safety and tolerability of the acute safety and tolerability of the compound.
Speaker Change: It will have access to and we will review the hbf data and any other associated immunological data with that with the primary.
Speaker Change: Motivate or the primary decision around progression to 20 milligrams will be based on the safety and Tolerability observed.
Joe Schwartz: Thanks for all the color Thanks, Joe.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Our next question comes from the line of Matthew Taylor of <unk>.
Speaker Change: Your line is now open.
Matthew Taylor: Hey, good morning, guys. Thanks for the update.
Speaker Change: Maybe just a little bit more granularity on the type of data that we're going to be getting first mid year and then yearend does that do you think it will be mature enough to have a readout on any early vse events mid year, I mean, I'd imagine, you're probably seeing a pretty high baseline rate at PNC, given kind of the secured new patient population youre enrolling.
Speaker Change: So maybe just like any details around kind of what we should expect in terms of the types of data would be super helpful. Thanks, Yeah, Great. Great question that I appreciate you asking it and I'll start and then maybe turn it over to Ian for any additional color. So I think if you look at the data that we shared in the first 15 patients where we showed.
Speaker Change: Hbf levels at baseline and then at the at the end of the study I think we will certainly be sharing that will also be sharing other biomarkers, such as reticulocyte counts red cell red cells distribution with.
Speaker Change: I believe that <unk> is something that we are.
Obviously, something that we are tracking but I think given the fact that this is only a three month.
Speaker Change: Only a three month study where the patients are on drug for a period of three months.
It would be sort of unlikely to see a reduction in voc's during that relatively short period of time, but maybe let me kick it over to Ian to see what additional color. He can add yeah, we will certainly provide that data.
Speaker Change: Study, obviously is not focused on that as an efficacy readout for the reasons that Alex just mentioned, but we are collecting the data and what I think we will have.
Speaker Change: At a higher level than we did have with the previous cohorts is what the frequency of doses of these patients coming into the study was.
Speaker Change: Originally when the study was an all comers study there was no requirement for severity and so those.
Speaker Change: <unk> frequencies were not captured in the database in the same way as they are being now because of the inclusion exclusion criteria. So we will have a little more granularity around the baseline <unk> of these patients and then we'll report out the doses that occur on.
Speaker Change: <unk> study as well, but purely in a descriptive sense given the number of patients.
Speaker Change: Short duration of the study and so on yes, and then maybe Matt just the other thing to add which I failed to which is probably important given the fact that this is a phase one safety study is obviously, we'll be sharing all of the all of the important safety data as well that generates from these out of these 20 or some odd patients that we'll have across these two co.
Speaker Change: Courts.
Speaker Change: Awesome looking forward to it thanks, yeah. Thanks, so much Matt.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Our next question comes from the line of caffeine Hallmark of Banc of America Securities. Your line is now open.
Speaker Change: Hi, This is jeremy either on conferencing. Thanks for taking our question and maybe a quick question on the FSA scheme. It out Thats expected in March just wondering what the key takeaways you guys are thinking will be from the presentation and if theres any potential interest in exploring fsh deal with another follow on program just given your past experiences.
Speaker Change: Yes, Jeremy it's a really good question and I. Appreciate you asking I'll start and then I'll turn it over to Ian to provide additional color. So as we said when we shared the data to the top line late last year. We are committed to make sure that we presented at the MBA Conference, which is now scheduled for.
Speaker Change: In March the 19th I believe and then we will obviously be publishing at some time sometime around mid year.
Speaker Change: I think what's interesting about this data set is.
Speaker Change: The drug performed as we would have expected and it performed very consistently with what we saw in the in.
Speaker Change: In the Phase III study. The challenge was is that during that 52 weeks. The placebos performed better than we had expected.
Speaker Change: Placebo adjusted basis, there was there was no change.
Speaker Change: Obviously, the prevailing hypothesis is.
Speaker Change: Could it be during that year that the mind overtook the disease recognizing that while this is a relentlessly.
Speaker Change: Asleep progressing disease, it is slow to progress and so.
Speaker Change: The prevailing hypothesis is could you do a longer term study.
Speaker Change: Two years for example, where the mine does not have the ability to continue to overtake the disease during that two year period, but the disease overtakes. The by then and I think.
Speaker Change: We feel that that is not the most appropriate way to deploy our capital right. Now. So we do not have any plans to continue with <unk>, but it is quite possible that one of the other players in the lost Matt I'm sorry in the Fsh field may have an interest in looking at that.
Speaker Change: Later, when it finally gets presented and published in and possibly sort of taking it.
Speaker Change: In conducting that longer term study, but for us as a company we feel the most appropriate way to deploy our precious and scarce capital is really focus on the exciting things that we have going on.
Speaker Change: In benign hematology in particular sickle cell and then some of these other inherited aplastic anemia that I spoke about.
Speaker Change: Ian.
Ian Ian: You want to add.
Ian Ian: Just to be specific the MDA oral presentation, which Alex alluded to is focused on the primary endpoint key secondary endpoints and the <unk>.
Ian Ian: So that those will be the highlights from that presentation and then we're also preparing a more detailed manuscript that will include those endpoints, but also a broader array of the secondary endpoints as well. So that's the manuscript that we intend to publish later on we also have additional work going.
Ian Ian: To ensure that the work that we did around the reachable workspace the validation of that.
Ian Ian: So on that too.
Ian Ian: Will be made public.
Ian Ian: Great. Thanks for that color and then maybe a quick question for Alan just just curious on how we should be thinking about operating expenses in 2025 relative to 2024 should we expect to see some additional restructuring fees in 2025 or is that largely been completed yes.
Alan Musso: Good question the restructuring activities are completed but we do now have a smaller organization and we've guided that we anticipate our cash burn in 2025 to be between.
I am sorry, 55 and $65 million.
Alan Musso: Pointed that's about $60 million so.
Alan Musso: But what we're thinking.
Alan Musso: Great. Thanks, Yeah, Thanks, Jeremy for the question.
Alan Musso: Thank you one moment for our next question.
Edward: Our next question comes from the line of Edward <unk> of Piper Sandler. Your line is now open.
Speaker Change: Great. Thank you very much Anna congressional progress two quick questions Firstly.
Edward: When we close too.
Edward: <unk> and <unk>.
Speaker Change: Roland has the requirement of <unk> plus another advanced therapy.
Edward: The removal of Oxford.
Edward: Complicated enrollment at all or are there still enough patients who were on Oxford.
Edward: That enrollment criteria and then secondly, when it comes to sort of the safety.
Edward: The F&B is going to be there or are there any special things, we should be aware of.
Edward: On the standard.
Ian Ian: Is required. Thank you yeah, two really good questions and I. Appreciate you asking them I think to add to those mouth to turn those over to Ian.
Ian Ian: Yes, absolutely.
Ian Ian: Ted Thanks for the question the the issue around the HQ and the advanced therapies.
Ian Ian: Is actually probably simpler now for this study than prior to the withdrawal of box brighter and it's simply because of the language of the protocol specified prior experience with H U and at least one of the three at the time available therapies, which were right Chris.
Speaker Change: <unk> was a madman enel glutamine, we know that both <unk> and <unk>.
Speaker Change: <unk> not had very wide uptake in the patient population Nox Friday was being used fairly widely.
Speaker Change: The.
Speaker Change: Withdrawal a box Friday, it's essentially fulfill that criteria as being not available because that was one of them.
Speaker Change: Potential.
Speaker Change: Reasons for that.
Being on that particular therapy, so to some extent.
Speaker Change: The withdrawal.
Speaker Change: Made it somewhat easier.
Speaker Change: The patient recruitment perspective.
Speaker Change: With respect to the second question around the <unk> no.
Speaker Change: Specific safety signal that they're that they're targeting.
Speaker Change: You May recall, we had conducted previously our first in human study in healthy volunteers.
Approximately 100 healthy volunteers in that study and there were no dose limiting toxicities or safety signals acute safety signals of concern in that study and then the initial cohorts of the pioneer study that two 6%.
Speaker Change: Few patients that were enrolled at the 12 milligram dose again, there were no consistent concerning safety signals or dose limiting toxicity.
Speaker Change: They're going to be passed to broaden broaden out looking at all of the safety labs.
Speaker Change: Sure.
The stations and so on but there is no specific issues that they will be looking at.
Speaker Change: Maybe just to add a little bit more color on the on the first question around concomitant Meds I think as Ian said, although our glutamine and crystallize the mab or not broadly used in the U S and outside of the U S or estimate and are they are probably a couple of thousand patients that.
Speaker Change: In the U S that are on <unk> and <unk> and then the original protocol Ah patients could not be on either one of those therapies and in our trial, but now based on our recent protocol Amendment, which we have.
Speaker Change: <unk> approval on from the from the agency.
Speaker Change: Patients can be on concomitant <unk> mab and Meanwhile, while being in the study so.
Speaker Change: I think that's also an important point to make in addition to the ox bright point that that.
Brian: Yes, Hi, Brian Yeah, that's Super helpful. And then just one quick one if I may when it comes to sort of pizza profile.
Speaker Change: For use of the drug again.
Speaker Change: It's very early do you anticipate visit would be used after HQ failure causes some of the limitation of not being able to be on both <unk> and <unk>.
Speaker Change: Plus here or there or where do you really see per theater fitting into the treatment landscape again.
Speaker Change: Accepting that but it's still pretty early and we don't.
Speaker Change: Really the data, yet, but where do you view the premier.
Speaker Change: Yes. It is.
Ted: An excellent question Ted again.
Ted: Really appreciate you asking it I think.
Ted: Yes.
Speaker Change: Two points I'll make and then I'll turn it over to Ian you are correct.
Speaker Change: As an early study and at this point the agency is that out of the out of an abundance of caution let's exclude hydroxyurea.
Speaker Change: This current study I think as we gather more data.
Speaker Change: And and have.
Speaker Change: Ongoing discussions with the agency at the end of this year. Once we have the 12 and 20 milligram in hand, obviously, one of the things that we'll be asking for.
Speaker Change: From the agency as to possibly relax some of that inclusion exclusion criteria because many patients are on hydroxyurea and from a commercial standpoint that would be that would be quite challenging if our pivotal study for this drug at some point in the future excluded the use of Hydroxyurea. So that's obviously something.
Speaker Change: That we would reengage with the agency on very similar too.
Speaker Change: The ox Friday label that did allow the use of hydroxyurea in terms of where the drug will be used.
Speaker Change: I'll just go back to what I said earlier based on the data that we've generated to date and based on what we know about fetal hemoglobin.
Speaker Change: With any increase in fetal hemoglobin being beneficial to the patients even a 1% increase in fetal hemoglobin, but once you can get patients to 25. These patients really do become.
Speaker Change: Asymptomatic and the presentation of their disease.
Speaker Change: As evidenced by the.
Speaker Change: Near abolition of Boc.
Speaker Change: We would expect this drug to be sort of broadly used.
Speaker Change: Cross many patients based on again, what we're seeing and what we believe we will see.
Speaker Change: Mid year and by the end of the year with the 12 and the 20 milligram, whether it actually becomes first line in place of HQ I. Just don't think we have enough information at this point of the profile of the drug to really sort of provide any accuracy in terms of where we think ultimately it will be positioned but it really truly.
Speaker Change: Does have the potential as we believe to transform how patients are treated if we can get to the levels of hbf that we believe we can get to with not only the 12 to.
Speaker Change: The 20 milligram cohort.
Great. Thank you very much for all that color.
Speaker Change: David coming up in the middle of this year, Yeah. That's great. Thanks, so much to add.
Speaker Change: Thank you Amit for next questions again, as a reminder to ask a question you will need to press star one on your telephone.
Speaker Change: Our next question comes from the line of Gregory <unk> of RBC capital markets. Your line is now open.
Speaker Change: Hi, 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.
Speaker Change: First how receptive has the FDA to data either historic or currently showing an association between Hbf induction and VLC reduction what are the hang ups here and second as you think about pipeline where else outside of Hematological diseases might you be able to leverage your platform what's of interest on the BD front. Thanks, so much.
Alan Musso: Yes, Great question, maybe I will turn the first question over to Ian and then I'm happy to talk a little bit about a little bit give you a little bit of color into that the second question that you asked.
Speaker Change: Yes.
Speaker Change: First one on initiatives around hbf and the agencies view and that's something as Alex mentioned earlier is something that we are directly going to be addressing with the agency. So this is independent of our interactions with them around the clinical data from the pioneer study, but more generally around the data.
Speaker Change: That exist that support the use of hbf as a surrogate endpoint and so that interaction is going to take place this year.
Speaker Change: We are actively pursuing that we will get some specific feedback from them. As you are aware I'm sure. There hasnt been drugs previously approved for sickle cell.
Speaker Change: The basis of Hbf induction alone, but we believe that there are abundant data now.
Speaker Change: There are both genetic epidemiologic pharmacologic and gene therapy that speak to the importance of hbf induction in sickle cell disease and would support its use as a surrogate endpoint. So so thats why we are specifically going to be asking.
Speaker Change: The agency about that yeah and then.
Speaker Change: Our niche from a from a BD standpoint, we're always evaluating opportunities and again I think you were right to point out that our sweet spot is really benign hematological diseases, where there is an unmet need that remains quite high.
What we feel is that the good news is that we don't necessarily have to transact, but we obviously do have a robust balance sheet that we could transact if we found.
Speaker Change: Really interesting asset in a rare benign hematological disease, where the unmet need was high but we certainly don't need to I think given the high level of interest with sickle cell, but also some of the other inherited aplastic anemia that we're studying for which we'll have our first.
Speaker Change: And submitted by the end of the year I think the only other one that I will highlight and this is some data that Pfizer recently pointed.
Speaker Change: Rented at <unk> and that's the use of.
Speaker Change: <unk> inhibitors in prostate cancer.
Speaker Change: <unk>.
Speaker Change: PRC two inhibitor, it's actually a <unk> inhibitor not an E.
Speaker Change: EBITA like <unk>, but they have a product called member metastatic reasonably.
Speaker Change: The reason I'm, bringing this up we've had a lot of investors sort of ask about that they showed in 80 patients.
Speaker Change: Mark.
Speaker Change: Reduced risk of disease progression.
Speaker Change: And that by about 50% and so there is some believe that targeting the <unk> subunit of the PRC too complex may have some potential advantages over targeting the DHT sub unit, which never metastatic with with Pfizer. So we're conducting some preclinical.
Speaker Change: Experiment now using some xenograft models to evaluate several compounds in our in our library.
Speaker Change: I am going into oncology is not something we're intending to do but I think given the high level of interest in the use of <unk> inhibitors in prostate cancer with Pfizer's product in Orange product. It's something that we are looking looking at from a preclinical standpoint again, given some of the potential advantages there.
Speaker Change: E inhibitor may have over member metastatic or X product, which are which are <unk> inhibitors.
Speaker Change: Great. Thanks, so much for the color really appreciate it yes. Thanks Anish.
Speaker Change: Thank you I'm showing no further questions at this time. Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.