Q1 2022 Fulcrum Therapeutics Inc Earnings Call
Yeah.
Operator: Good morning, and welcome to Fulcrum Therapeutics' first quarter 2022 conference. Currently, all participants are in a listen-only mode.
Good morning, and welcome to Fulcrum Therapeutics first quarter 2022 conference call.
Currently.
All participants are in a listen only mode.
Operator: There will be a question and answer session at the end. I would now like to turn the call over to Naomi Aoki, Senior Vice President of Corporate Communications and Investor Relations at Fulcrum. Please proceed.
There will be a question and answer session at the end of this call.
I would now like to turn the call over to Naomi Aoki scene.
Senior Vice President of corporate Communications and Investor Relations at Fulcrum.
Please proceed.
Naomi Aoki: Thank you. Good morning, and welcome to the Fulcrum Therapeutics conference call. Please be reminded that remarks made during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about our future expectations and plans, clinical development timelines, and financial projections. While these forward-looking statements represent our views as of today, they should not be relied upon as representing our views in the future.
Thank you good morning, and welcome to Vulcan Therapeutics Conference call. Please be reminded that remarks made during this call may contain forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.
May include statements about our future expectations and plans clinical development timelines and financial projections. While these forward looking statements represent our views as of today, they should not be relied upon as representing our views in the future.
Naomi Aoki: We may update these statements in the future, but we are not taking on an obligation to do so. Please refer to our most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with our visits. With me on today's call are Brian Stewart, President and Chief Executive Officer, Judy Gunn, our President of R&D, and Esther Rajavelu, our CFO. Chris Moravido, Chief Medical Officer, and Paul Bruno, our Executive Director of Corporate Development, will also be available for Q&A. Let me run quickly through this morning's agenda.
We may update these statements in the future, but we are not taking on an obligation introduced out please refer to our most recent visit.
Journeys and exchange Commission for a discussion of certain risks and uncertainties associated with our business.
With me on today's call are Bryan Stuart President and Chief Executive Officer, Judy done, our president of R&D, and Aster, Washington, Our CFO , Chris <unk>, our Chief Medical Officer.
And Paul <unk>, our executive staff.
Corporate development will also be available for Q&A, let.
Let me run quickly through this morning's agenda.
Naomi Aoki: Brian will begin the call with a corporate overview, key updates, and review of upcoming milestones. Judy will review our FTX 6058 program, and Esther will cover our financials.
Ryan will begin the call with a corporate update and review upcoming milestones. Judy will work you are MTX 60, 15 program <unk> will cover our financial and then Brian well open the call for Q&A with that it's my pleasure to turn the call over to Brian .
Naomi Aoki: And then Brian will open the call for Q&A. With that, it's my pleasure to turn the call over to Brian. Thank you, Naomi. Good morning, everyone, and thank you for joining us. At Fulcrum, our mission is to treat the root cause of rare genetic diseases, and we are advancing two important clinical stage assets that support that mission. The first is our phase three FSHD program, which is positioned to be a first to market therapy for an untreated patient population.
Thank you Naomi good morning, everyone and thank you for joining us today.
Fulcrum, our mission is to treat the root cause of rare genetic diseases and we are advancing two important clinical stage assets that support that mission.
The first is our phase III Fsh D program that is positioned to be a first to market therapy for an untreated patient population.
Naomi Aoki: The second is our program for sickle cell disease and other hemoglobinopathies, a once daily HBF inducer that has the potential to be the first oral therapy that can broadly improve outcomes for these diseases. We have made significant progress across these programs in the first quarter.
The second is our program for sickle cell disease, and other haemoglobinopathy, a once daily Hbf inducer with the potential to be the first oral therapy that can broadly improve outcomes for these diseases.
We have made significant progress across these programs in the first quarter.
Brian Stewart: I'll start with an update on FTX 6058, our oral HBF inducer for sickle cell disease and other hemoglobin disorders. 6058 shows great promise in addressing critical unmet needs in these patient populations. The current treatment landscape consists of therapies that only target select symptoms of sickle cell disease.
I will start with an update on <unk> hundred 58, our oral hbf inducer for sickle cell disease and other hemoglobin office.
658 shows great promise in addressing critical unmet needs in these patient populations.
The current treatment landscape consists of therapies that only target select symptoms of sickle cell disease H.
Brian Stewart: HPF is the only mechanism that has been shown to broadly improve clinical outcomes including anemia, VOC events, pain, fatigue, and acute chest pain. As the only agent in development with the potential to induce HBF, we believe that 6058 is uniquely positioned in the current and emerging landscape. In January, we announced that we had dosed our first patient in our Phase 1b trial at a starting dose of 6mg. We plan to share initial data from the ongoing 6mg dosing cohort, including measures of HBF induction, at the European Hematology Association Congress taking place from June 9th through 12th. We also plan to open the next dosing cohort in the Phase 1b trial this quarter, and we'll have more details to share on that cohort along with the data at EHA. Notably,
<unk> is the only mechanism that has been shown to broadly improve clinical outcomes, including anemia.
VLC events pain, fatigue, and acute chest syndrome as the only agent in development with the potential to induce hbf. We believe at $6 58 is uniquely positioned in the current and emerging landscape.
In January we.
We announced that we dosed our first patient in our phase <unk> trial at a starting dose of six milligrams. We plan to share initial data from the ongoing six milligram dosing cohort, including measures of Hbf induction at.
At the European Hematology Association Congress, taking place from June nine through 12.
We also plan to open the next dosing cohort in the phase one B trial this quarter and we'll have more details to share on that cohort along with the data at <unk>.
Notably.
Brian Stewart: This update will be the first look at HBF protein induction in people living with sickle cell disease receiving 6058. Based on data from other HBF mechanisms and the process of erythropoiesis, we would anticipate seeing signs of protein induction after one month of treatment, with potentially maximal protein induction at three to five. As a reminder, our Phase 1B trial is an early proof-of-concept study that is designed to provide evidence over a range of doses that 60-58 increases HBF.
This update will be the first look at hbf protein induction in people living with sickle cell disease, receiving $6 58.
Based on data from other hbf mechanisms and the process of Erythropoiesis, we would anticipate seeing signs of protein induction. After one month of treatment with potentially maximal protein induction at three to five months.
As a reminder, our phase one b trial is an early proof of concept study that is designed to provide evidence over a range of doses at $60 58 increases hbf.
Brian Stewart: For these initial data, we would consider evidence of HBF induction as a proof of concept for this program. Typically, people with sickle cell disease have HBF levels of 5 to 10%. However, a subset of people with sickle cell trait have additional mutations that result in elevated levels of HPF, a condition known as hereditary persistence of fetal hemoglobin.
For this initial data we would consider evidence of hbf induction is a proof of concept for this program.
Typically people with sickle cell disease have hbf levels of 5% to 10%.
However, a subset of people with sickle cell trait.
Additional mutations that result in elevated levels of hbf.
<unk> known as hereditary persistence of fetal hemoglobin. These.
Brian Stewart: These individuals have little to no symptoms of sickle cell. These clinical and genetic data clearly demonstrate that increases in HBF improve outcomes. Based on this well-understood data, KOLs consistently state that an absolute 5 to 10% increase in HBF baseline levels, beyond baseline levels, would be transformative for patients and would be used as standard of care. Our robust preclinical data and our phase one data and healthy volunteers give us reason to believe that we can achieve these absolute five to 10% increases that will be life changing for people with sickle cell. We also believe that 6058 could be a transformative therapy for other hemoglobinopathies, including beta thalassemia.
These individuals have little to no symptoms of sickle cell disease.
These clinical and genetic data clearly demonstrated the increases in hbf improve outcomes.
Based on this well understood data.
<unk> consistently state than an absolute 5% to 10% increase in hbf baseline level beyond baseline levels would be transformative for patients and would be used as standard of care.
Our robust preclinical data in our phase one data in healthy volunteers give us reason to believe that we can achieve these absolute 5% to 10% increases that will be life changing for people with sickle cell disease.
We also believe that $6 58 could be a transformative therapy for other haemoglobinopathy, including beta thalassemia and.
Brian Stewart: And we are committed to developing 6058 in these patient populations as well. This morning, we updated the anticipated timing of the initiation of the trial in non-sickle cell hemoglobinopathies to the second half of the year. This shift in timing allows us to focus on expeditiously advancing our development plans in sickle cell disease while remaining well positioned to successfully execute a trial in another hemoglobin. Moving on to Los Mappamon, our phase 3 candidate for FSHD, which is the second most common form of muscular dystrophy.
And we are committed to developing $6 58 in these patient populations as well.
This morning, we updated the anticipated timing.
Of the initiation of the trial in non single cell haemoglobinopathy through the second half of the year.
This shift in timing allows us to focus on expeditiously advancing our development plans in sickle cell disease, while remaining well positioned to successfully execute a trial and other hemoglobin audit fees.
Moving on to <unk>, our phase III candidate for Fsh D, which is the second most common form of muscular dystrophy we.
Brian Stewart: We remain on track to begin dosing patients in our Phase 3 REACH trial this quarter. As the first ever phase three trial in FSHD approaches a landmark study that brings us one step closer to delivering a potentially life-changing therapy to people with this severe and debilitating disease, Willis-Mathemata is positioned to be the first-to-market therapy for FSHD.
We remain on track to begin dosing patients in our phase III reach trial this quarter.
As the first ever phase III trial, and Fsh D reaches a landmark study that brings us one step closer to delivering a potentially life changing therapy to people with this severe and debilitating disease.
Gross map a modest addition to be the first to market therapy for Fsh D and based on the data to date, we believe it has the potential to slow or stop disease progression and in some cases, even improve function.
Brian Stewart: And based on the data to date, we believe it has the potential to slow or stop disease progression and, in some cases, even improve lung function. REACH will evaluate los mapimod compared to placebo in adults with FSHD over a 48-week treatment period with REACHable Workspace, or RWS, as the primary endpoint. The trial design reflects key learnings from the READUPS-IV Phase 2b trial. Most notably, that we can show a measurable clinical benefit in 48 weeks and that RWS is a quantitative measure of function that is sensitive to disease progression during that time. Based on these insights and the data from Redux 4 demonstrating clinical benefits, we align with regulators on key aspects of the design of REACH. In March, we presented data supporting RWS as a quantitative and relevant measure of function at the Muscular Dystrophy Association Clinical and Scientific Conference
Reach will evaluate <unk> compared to placebo in adults with Fsh D. Over a 48 week treatment period with reachable workspace for our W. S. As the primary endpoint.
The trial design reflects key learnings from the Readouts for phase two B trial.
Most notably that we can show a measurable clinical benefit and 48 weeks and that our Ws is a quantitative measure of function that is sensitive to disease progression in that timeframe.
Based on these insights and the data from redux for demonstrating clinical benefit we aligned with regulators on key aspects of the design of reach.
In March we presented data supporting our WNS as a quantitative and relevant measure of function at the muscular Dystrophy Association clinical and scientific conference.
Brian Stewart: That same month, we hosted an event with leading KOLs to discuss the unmet need in FSHD, key measures of disease progression, and the design of the REACH trial with a focus on RWF. Together with the FSHD Society, we also hosted a webinar on REACH for the patient community. Additionally, in April, at the American Academy of Neurology annual meeting, we presented clinical data supporting the potential of los mapemad as well as the design of REACH.
That same month, we hosted an event with leading kols to discuss the unmet need and Fsh D key measures of disease progression and the design of the reach trial with a focus on our W. S.
Together with the Fsh D Society, we also hosted a webinar on reach for the patient community.
Additionally in April .
American Academy of Neurology annual meeting, we presented clinical data supporting the potential of <unk> as well as the design of reach.
Sure.
Brian Stewart: We are proud of the progress that we have made with Los Mapos, and this mark an important milestone for Fulcrum and for the FSHD community. There are currently no approved drugs for FSHD and nothing else in the clinic. People with FSHD lose strength, function, independence, and mobility as the disease advances.
We are proud of the progress that we've made with Lowe's mathematics reach marks an important milestone for fulcrum and for the Fsh D community.
There are currently no approved drugs for Fsh D and nothing else in the clinic.
People with Sshd lose strength function independence, and mobility as the disease advances.
Brian Stewart: There is an urgent need for a drug that can slow or stop disease progression. The data we reported last year from Redux 4 demonstrate Los MapaMod's potential to do exactly that, showing delayed progression and improvement in measures of function. Both SMAP and MOPD are also supported by extensive safety and tolerability data. In addition to our progress with initiating REACH, we've also made significant gains in preparing for the potential of commercial law. Beyond Building the Internal Infrastructure Needed for Success
There is an urgent need for a drug that can slow or stop disease progression the.
The data we reported last year from Readouts for demonstrate <unk> potential to do exactly that.
Showing delayed progression and improvement in measures of function.
<unk> is also supported by an extensive safety and Tolerability database.
In addition to our progress with initiating reached we've also made significant gains in preparing for the potential commercial launch.
Beyond building internal infrastructure needed for success we.
Brian Stewart: We have progressed the commercial formulation of Los Mapos. Additionally, we continue to engage with patients, care partners, and care providers to ensure Los Mapamon has the maximal potential to meet the community's expectations. 6058 and Los MapaMod, as well as our ongoing collaborations, are testaments to the power of FulcrumSeq, our product engine and the innovation backbone of our company. FulcrumSeq has allowed us to rapidly identify novel, high-quality targets that modulate the root cause of rare genetic diseases. And it continues to power our pipeline.
We have progressed the commercial formulation of <unk> backlog.
Additionally, we continue to engage with patients care partners and care providers to ensure <unk> has the maximum potential to meet the community's expectations.
$6 58, and <unk> as well as our ongoing collaborations are a testament to the power of fulcrum fee, our product engine and the innovation backbone of our company.
Fulcrum seek has allowed us to rapidly identify novel high quality targets that modulate the root cause of rare genetic diseases and it continues to power our pipeline.
Brian Stewart: We remain on track to nominate our next development candidate by the end of this year and submit what will be Fulcrum's fourth IND by the end of the first quarter of 2023. As we advance two potentially life-changing therapies through clinical development while expanding our pipeline, we are well-positioned to establish Fulcrum as a leading rare disease company supported by a strong financial foundation and a cash runway into 2024. With that, I'll turn it over to you.
We remain on track to nominate our next development candidate by the end of this year and submit will be fulcrum fourth IND by the end of the first quarter of 2023.
As we advance to potentially life changing therapies through clinical development, while expanding our pipeline, we are well positioned to establish <unk> as a leading rare disease company supported with a strong financial foundation and a cash runway into 2024.
With that I'll turn it over to Judy.
Judy Gunn: Thank you, Brian. As we look ahead to our data disclosure at IHA, I'd like to review our 6058 program for sickle cell disease and other hemoglobin oxidases. Sickle cell disease is a genetic disorder of the red blood cells caused by a mutation in the HBD gene.
Thank you Brian .
We look ahead to our data disclosure at <unk> I'd like to review, our EBIT a program for sickle cell disease and other hemoglobin on each.
Sickle cell disease is a genetic disorder of the red blood cells caused by a mutation in the HBV gene.
Judy Gunn: It is the most common type of inherited hemoglobinopathy and affects an estimated 100,000 people in the United States and millions more worldwide. People with sickle cell disease experience anemia, vaso-occlusive crises, or VOCs, and other serious morbidities such as stroke and acute chest syndrome. In addition to having a devastating impact on people's quality of life, these complications significantly increase the risk of dying from sickle cell disease. HBF induction is the only mechanism that has been shown to broadly improve outcomes for key symptoms of sickle cell disease.
It is the most common type of inherited Haemoglobinopathy and affects an estimated 100000 people in the United States and millions more worldwide.
People with sickle cell disease experienced media.
These are occlusive crises or voc's and other serious morbidities, such as stroke and acute chest syndrome.
In addition to having a devastating impact on People's quality of life. These complications significantly increased the risk of dying.
Okay.
Yeah.
Hbf induction is the only mechanism that has been shown to broadly improve outcomes for key symptom of sickle cell disease.
Judy Gunn: To build on Brian's remarks about the transformative potential of HBF induction, Consistent with the persistence of fetal hemoglobin data, numerous published analyses demonstrated that higher HCF levels lead to better clinical outcomes. A systematic review of the literature shows that increases in HCF of 3-7% are associated with fewer VOC events, strokes, hospital admissions and transfusions, fewer incidences of acute chest syndrome, and decreased risk of mortality. These data support the view that we consistently hear from KOLs that increases of five to 10% fetal hemoglobin over baseline would be transformative for people with sickle cell disease as the only oral HBF inducer in the clinic. We believe that 6058 has a tremendous opportunity to address the unmet medical need for better treatment options for people with sickle cell disease. We discovered 6058 using our Fulcrum-Seq product engine.
To build on Brian's remarks that the trends formative potential of hbf induction.
Consistent with the persistence of fetal hemoglobin data.
<unk> published analyses demonstrated that higher hbf levels lead to better clinical outcomes.
It's just a matter of review of the literature shows the increases in <unk> of 3% to 7% are associated with fewer boc events strokes hospital admissions and transfusions fewer incidents of acute chest syndrome and decreased risk of mortality.
These data support the view that we consistently hear from Kols.
The increases of 5% to 10% fetal hemoglobin over baseline would be transformative for people with sickle cell disease.
As the only oral hbf induced during the clinic.
We believe that $6 58 has a tremendous opportunity to address the unmet medical need for better treatment options for people with sickle cell disease.
We discovered 60 58, using our <unk> <unk> product engine.
Judy Gunn: Preclinically, across multiple in vivo and in vitro assays, 6058 generated a consistent two to threefold induction in HVG mRNA that translated into the same fold induction in HVF protein. Last year, we transitioned to the clinic and announced positive phase one healthy volunteer data that demonstrated robust increases in HBG mRNA at multiple doses. 6058 was also generally well tolerated.
Preclinical across multiple <unk> in in vitro assays 60, 58 generated a consistent two to three fold induction in <unk> mrna that translated into the same old induction in hbf proteins.
Last year, we transitioned to the clinic and announced positive phase one healthy volunteer data that demonstrated robust increases in <unk> mrna at multiple doses.
58 was also generally well tolerated.
Judy Gunn: We are now dosing people with sickle cell disease long enough to observe increases in HBF protein. As a reminder, this Phase 1b study is designed to have up to three dosing cohorts to allow us to explore a range of doses and identify the optimal dose to take into a registration-enabling trial. We are currently dosing patients in the first dosing cohort at a six MIG once daily dose. The data we are presenting at EHA in June will be initial data from a small number of subjects enrolled in this cohort and will include measures of HBF protein.
We are now dosing people with sickle cell disease long enough you observed increases in hbf protein.
As a reminder, this phase <unk> study is designed to have up to three dosing cohorts to allow us to explore a range of doses and identify the optimal dose to take into a registration enabling trial.
We are currently dosing patients in the first dosing cohort.
<unk> once daily dose.
The data we are presenting at <unk> in June will be initial data from a small number of subjects enrolled in this cohort and will include measures of hbf protein.
Judy Gunn: For these initial data, we are looking to see evidence of HDF protein induction, which would provide proof of concept for this program. We expect to open our next dosing cohort in the Phase 1b trial this quarter, and we'll share additional details on that cohort along with the data update at EHOP. We're pleased with the progress we've made in advancing both 6058 and Los Maclemod, both potentially life-changing therapies for populations with significant unmet medical needs. And with that, I'll turn it over to Esther.
For these initial data we are looking to see evidence of H C. F protein induction, which would provide proof of concept for this program.
We expect to open our next dosing cohort in the phase one B trial this quarter and will share additional details on that cohort along with the data update at Ehealth.
We're pleased with the progress we've made in advancing both 60 58 analysts map a lot both potentially.
Life changing therapy for populations with significant unmet medical needs.
And with that I will turn it over to Esther.
Thanks Judy.
Esther Rajavelu: Thank you. Today, I will share with you an update on our financial performance. We are operating from a position of financial strength, ending the first quarter with $195.1 million in cash, cash equivalents, and marketable security.
Okay, and then share with you an update on our financials.
We are operating from a position of financial strength, ending the first quarter with $195 1 million in cash cash equivalence and marketable securities.
Esther Rajavelu: Based on our current plans and projections, we expect this will support our operations into 2024. In the first quarter of 2022, we recognized collaboration revenue of $2.6 million compared to $4.8 million during the first quarter of 2021. This decline is primarily tied to reduced research services we provided to our collaboration partners this quarter. First quarter 2022 research and development expenses were $17.8 million compared to $16.3 million for the first quarter of 2021.
Based on our current projections.
Projections, we expect this will support our operations into 2024.
Sure.
2022.
A nice collaboration that means a few points.
Thanks Sterling.
Okay.
<unk> 8 million during the first quarter of 2021.
This decline is primarily tied to the industry.
Two our collaboration partners this quarter.
First quarter of 2022 research and development expenses by $17 8 million compared to $16 3 million for the first part of 2021.
Esther Rajavelu: And G&A expenses were $10.8 million this quarter, compared to $5.5 million for the first quarter of 2021. These increases were primarily due to the advancement of our clinical programs, as well as increases in employee-related expenses to support our growth. Our net loss for the first quarter of 2022 was $28.9 million, compared to a net loss of $17 million for the first quarter of 2021.
And G&A expenses by $10 8 million this quarter compared to $5 five level.
2021.
These increases are primarily due to the advancement of our clinical programs as well as increases in employee related expenses to support our first.
Our net loss for the first quarter of 2022 with.
$28 9 million compared to a net loss of $17 million.
2020 months.
Brian Stewart: With that, I'll turn it back to Brian. Thanks, Esther. As you've heard today, the first quarter of 2022 has been a productive one for Fulcrum, and we have even more to look forward to as we continue advancing our promising programs in FSHD, sickle cell disease, and other hemoglobinopathies, as well as to leverage FulcrumSeq to build out our pipeline. We look forward to sharing additional key updates later this quarter. Operator, you may now open the line for me. Thank you. At this time, if you would like to ask a question, please press star 1 on your telephone keypad. Again, that is star number one on your telephone.
With that I'll turn it back to Brian .
Thanks, Aster as you've heard today, the first quarter of 2022 has been a productive one for fulcrum and we have even more to look forward to as we continue to advancing our promising programs in fsh D sickle cell disease, and other haemoglobinopathy as well as to leverage fulcrum seek to build out our pipeline, we look forward to sharing additional.
Key updates later this quarter.
Operator, you May now open the line for questions.
Thank you at this time, if you would like to ask a question. Please press star one on your telephone keypad.
Again that is star one on your telephone keypad.
Operator: Your first question comes from the line of Judah Frommer from Credit, Fairliones. Hi, thanks for taking the question and good morning. There's a couple for us.
Your first question comes from the line of Judah Frommer from Credit Suisse. Your line is open.
Judah Frommer: Is there any way you can give us some kind of enrollment update for the first cohort of 6058 Phase 1B and an idea of potentially how many patients we can get data on at EHA that have been dosed out to 12 weeks? And then, on the second cohort, can you remind us of key considerations you'll have in terms of deciding whether you'll dose higher or lower in that cohort and what the read-throughs might be from that? Thanks for the questions, Judah. So why don't I turn it over to Chris, and we can speak to both of them.
Hi, Thanks for taking my question and good morning, just a couple for US is there any way you can give us some kind of enrollment update for the first cohort of a 6058 phase one b and an idea of potentially how many patients.
We can get data on that.
That have been dosed out to 12 weeks.
And then on the second cohort can you remind us the key considerations, you'll have in terms of deciding whether youll dose higher or lower in that cohort and what the read throughs might be from that.
Yes.
Okay.
Sure. Thanks for the questions Judah So why don't I turn it over to Chris and we can speak to both of those one the first question Roland and the second question just on the additional.
Brian Stewart: One, the first question on enrollment, and the second question just on the additional dosing cohorts and how we're thinking about that as we move forward here with 1B. Hi Jada, thanks for the quick questions. So, as you know, we are currently in the Phase 1B trial dosing the first cohort at six milligrams. And just to give you a reminder, the six milligram dose was selected based on the data that we developed in the Phase 1 trial in Healthy Volunteers that showed after just two weeks of dosing, we saw a two and a half fold increase in HP gamma mRNA, which on our hands empirically translates into what has the potential to be robust increases in patients if patients are dosed long enough.
Dosing cohorts and how we're thinking about that as we move forward here with the one base.
Hi, Judy.
Thanks for the quick questions. So as you know.
No. We are currently in the phase one b trial dosing the first cohort at six milligrams and just to give you.
The six milligram dose was selected based on the data that we developed in the phase one trial in healthy volunteers.
As showed after just two weeks of dosing we saw two five fold increase in each began mrna which on our hands and currently translates into what has the potential to be robust increases in patients. The patients are dosed long enough. So the phase <unk> data that we're excited to share data on.
Brian Stewart: So the Phase 1B data that we're excited to share data on at EHA in just a few weeks will be an update on initial patients from that cohort that have been treated in accordance with protocol. And as you remember, the protocol allows for the primary analysis of one month, which gives us flexibility in determining using data, dosing decisions. I'll answer your next question in a second, and then out to three months, which should give us a sense about what the ultimate potential of this drug is. And before I answer the second question, The purpose of this study is to provide early proof of concept.
Coming up.
In just a few weeks will be an update.
Initial patients from that cohort that have been treated in accordance with the protocol as you remember the protocol allows for the primary analysis of one months, which gives us flexibility in determining.
Using data dosing decisions I'll answer your next question in a second.
And then after three months, which should give us a sense about what the ultimate potential of this drug is and before I answer the second question.
The purpose of this study is early proof of concept is to give us a sense that we are translating HD camera mrna into protein, which ultimately has tremendous potential therapeutic benefit as Judy and Brian both.
Chris Moravido: It's to give us a sense that we are translating HP gamma mRNA into protein, which ultimately has tremendous potential therapeutic benefit, as Judy and Brian both went through. It's also to provide us information about dose, and it should give us information about a range of doses and their effects on HPF in people with sickle cell disease. So, when we think about the next dose cohort and what that dose should be, number one, we want to make a data-driven decision.
Went through it's also to provide us information about dose and it should give us information about a range of doses and their effects on hbf and people with.
Sickle cell disease. So when we think about the next dose cohort and what's their dose is number one we want to make a data driven decision. So we will be looking at not only the healthy volunteer data by incoming data from the <unk> B study.
Chris Moravido: So, we will be looking at not only the healthy volunteer data but incoming data from the 1B study to inform our modeling and simulation. We will be looking at events of any kind, we will be looking at how well patients are all feeling about the drug, and we will make a decision based on what the dose can be. And to remind you, we have the ability to go up or down with the next cohort. And the dose range for the next cohort, as stated, is between 2 and 20 milligrams. Great, thank you. Fulcrum Fulcrum, and your next question comes from the line "Dae Gon Ha" from Stiefel.
To inform our modeling and simulation.
I'll be looking at.
Yes, if any will be looking at how well patients are all feeling about the drug and it makes a decision based on those can be and to remind you. We have the ability to go up or down with the next cohort and the dose range for the next cohort as stated is between two and 20 milligrams.
Great. Thank you.
And your next question comes from the line of Dae Gon Ha from Stifel. Your line is open.
Dae Gon Ha: Your line is open. Hey, good morning, guys. Thanks for taking our questions. Maybe I'll just piggyback off of the 6058 question as well. So when we think about the data upcoming, I guess, in their prepared remarks, you talked about the five to 10% absolute improvement from baseline being transformative, but you also talked about two to three fold induction seen pre-clinically. So can you maybe help us sort of set expectations going into IHA? Is it five to 10%?
Hey, good morning, guys. Thanks for taking our questions maybe I'll just piggyback off of $6 50, a question as well.
So when we think about the data upcoming I guess in their prepared remarks, you talked about the 5% to 10% absolute improvement from baseline being transformative, but you also talked about two to three fold induction seen pre clinically. So can you maybe help us sort of set expectations going into <unk>.
Is it 5% to 10% or is it two to three fold induction recognizing baseline levels could be somewhat variable and then just to follow up on that kind of curious on your third dose cohort.
You have the optionality for that you've been talking about cohorts, one and two for now so what would it take for you to consider I guess opting into cohort number three thank you very much.
Dae Gon Ha: Or is it two to three times the induction, recognizing that baseline levels could be somewhat variable. And then just to follow up on that, kind of curious about your third dose cohort. I know you have the optionality for that you've been talking about cohorts one and two for now. So what would it take for you to consider, I guess, opting into cohort number three? Thank you very much.
Yes. Thanks for the question John maybe I will take the first one and then as it relates to dosing I'll turn it back over to Chris for a veto so.
Brian Stewart: Maybe I will take the first one, and then, as it relates to dosing, I'll turn it back over to Chris Morabito. So I think first and foremost, as we've said, and as you heard Judy say here earlier today, based on the strong data that exists from people with hereditary persistence of fetal hemoglobin and the consistent feedback that we get from KOLs, we think that 5 to 10 percent absolute increases in HBF would lead to transformative therapy and one that would be utilized as standard of care.
First and foremost.
Most is as we've said and as you.
Judy say here earlier today.
Based on the strong data that exists from people with hereditary persistence of fetal hemoglobin and the consistent feedback that we get from Kols that we think that 5% to 10%.
Absolute increases in Hbf would lead to a transformative therapy and one that would be utilized a standard of care. So that is our goal for the program.
Brian Stewart: So that is our goal for the program. I think as we get towards this initial data, as Chris said, obviously, first and foremost, we hope to be able to see HBF protein increases. And as a reminder, when we shared our phase one healthy volunteer data last year, we were both because we were dosing healthy people and we were only dosing for 14 days. That wasn't a sufficient amount of time to be able to show that.
I think as we get towards this initial data as Chris said, obviously first and foremost we hope to be able to see hbf protein increases and as a reminder, when we shared our phase one healthy volunteer data last year, we were both because we were dosing healthy and we were only dosing for 14 days that wasn't it.
Sufficient amount of time to be able to show that so first and foremost we want to see that we are increasing hbf and secondly, it's important that we see a path towards getting to that 5% to 10% absolute increase so our therapeutic goal hasnt changed I think one of the things that we've always talked about that we were very encouraged by.
Brian Stewart: So first and foremost, we want to see that we are increasing HBF. And secondly, it's important that we see a path towards getting to that 5 to 10% absolute increase. So our therapeutic goal hasn't changed.
Brian Stewart: I think one of the things that we've always talked about that we were very encouraged by is that as we looked preclinically across different assays, we consistently saw a two to threefold induction in both mRNA and protein. I think we find that very encouraging as we get towards having data in patients. However, as we transition into patients, we've also said that one of the reasons we've always shared fold increases is because the assays had different starting levels. We know from other clinical trials, as well as literature, that patients, people living with sickle cell disease, typically have five to 10% baseline levels.
Is as we look to pre clinically across different assays, we consistently saw a two to three fold induction in both mrna and protein I think we find that very encouraging as we get towards having data in patients.
As we transition into patients. We've also said that one of the reasons. We've always shared fold increases is because the assays had different starting levels. We know from other clinical trials as well as literature that patients people living with sickle cell disease, typically have 5% to 10% baseline levels. So moving.
Forward, we'll be focusing on what are the absolute increases in protein and I think that's very much what clinicians and kols want to see and how they want to see the data.
Brian Stewart: So moving forward, we'll be focusing on what are the absolute increases in protein. And I think that's very much what clinicians and KOLs want to see and how they want to see the data. With that, let me turn it over to Chris, and we can talk about dosing. Yeah. Hi Dagon.
Chris Moravido: As Brian mentioned, we're looking for data that support the path forward towards establishing what the therapeutic benefit of this drug is, and ultimately, that will be defined in the phase two trial that we initiate, which we intend to be a pivotal trial. In order for us to get to that pivotal trial as fast as possible, we're doing this 1B over multiple cohorts. And to answer questions specifically about the CERT cohort, we'll make a data-driven decision. If we have enough data after just two cohorts to inform the dose selection for Phase 2, that's it. If we need more data, we'll open up that CERT cohort.
With that let me turn it over to Chris and we can talk about dosing.
As Brian mentioned, we're looking for data that support the path forward towards establishing what the therapeutic benefit of this drug is and ultimately that will be defined in the phase II trial that we initiate which we intend to be a pivotal trial in order for us to get to that pivotal trial as fast as possible. We're doing this one be over multiple quarters.
And to answer your question, specifically about the third cohort, we will make a data driven decision. If we have enough data. After just two cohorts to inform the dose selection for the phase III. That's it if we need more data.
The third cohort.
Chris Moravido: If I can just maybe follow up on the preclinical data. Just looking back at CTX001, there was a translational gap, right, going from preclinical 2 to 3-fold induction into what they're seeing in the clinic today, which is pretty phenomenal. Maybe a question for Paul: is there a translational gap that we should also expect with EED inhibition, or is that not so much the case given the guide RNA versus EED inhibition mechanistic difference?
If if I kind of just maybe a follow up on the preclinical data.
Just looking back a CTX double a one there was a translational gap right going from preclinical two to three fold induction into what they're seeing in the clinic today, which is pretty phenomenal.
Maybe a question for Paul is there a translational gap that we should also expect with the E. D inhibition or is that not so much the case given the guide RNA versus <unk> inhibition mechanistic difference. Thanks again bye.
Paul Bruno: Thanks again. Yeah, thanks, Dagan. So, based on all the preclinical data that we generated today, what I would say is that for all of the HVF mechanisms that we've profiled, the way that they're translated to the clinic is either the same level of induction or greater. So, you know, there's always the potential, we could potentially see greater induction as we translate this to the clinic, but we'll need to see what that looks like based on the emerging clinical data.
Yes, I think so.
Based on all the preclinical data that we've generated to date, what I would say is for all of the hbf mechanisms that we've profiled.
The way that has translated to the clinic because either the same level of induction or greater so theres always the potential we could potentially see greater induction of.
Translate into the clinic.
But we will need to see what that looks like based on the emerging clinical data and as Brian alluded to earlier, while we are focused on the two to three fold ins.
Paul Bruno: And, you know, as Brian alluded to earlier, while we're focused on the two to three-fold induction and the possibility for us to translate to greater levels in the clinic, what we're hearing from the KOLs, what we're seeing from emerging gene therapy data and from our FLR data suggests that a five to 10% increase over baseline levels would be transformative. Thanks again, guys. Thank you very much. Your next question comes from the line by Ted Tenthoff from Piper Sandler. Irlande, great.
Induction and the possibility for it to translate to greater levels in the clinic and what we're hearing from the Kols, what we're seeing from emerging gene therapy data in from our SLR data suggest that a 5% to 10% increase over baseline levels would be transformative.
Yeah.
Great. Thanks again guys.
Thanks, Dave.
Your next question comes from the line of Ted <unk> from Piper Sandler.
Your line is open.
Ted Tenthoff: Thank you very much, Emma. Thanks for the very clear... Guidance and Expectations on 6058. Just to switch it up a little bit, I'll ask... What are your expectations for enrollment? How quickly do you think that study could enroll? Thanks. Okay.
Great. Thank you very much thanks for the very clear.
Gaza and snacks like pixel.
So part of it.
Switch it up a little bit.
Or what are your expectations for enrollment quickly do you think.
That study could overall thanks.
Okay.
Okay.
Unknown Executive: You know, in terms of when we think about REACH, what we know is the data that we have already collected from our vast experience with the REDOX-4 trial, as well as how we are hearing from patients and people who treat FSHD in terms of their enthusiasm for REACH. So we are confident that we have a great runway to a reasonable time for enrollment. And in fact, as you know, we're not doing an interim analysis on this program, primarily because we think that the enrollment speed will be such that we don't want to slow down the program.
You know I insurance, when we think about reach what we know is the data that we have already collected from our vast experience with the <unk> trial as well as how we are hearing from patients and people, who treat fsh D. In terms of their enthusiasm port reach.
So we are confident that we have a great runway to a reasonable time for enrollment and in fact as you know we're not doing an interim analysis in this program, primarily because we think that the enrollment speed will be such that we don't want to slow down the program and so we think our timeline will be.
Unknown Executive: And so we think our timeline will be very reasonable and perhaps better than the timeline or the rate of enrollment that we had in the initial Redux 4 trial, primarily because of the enthusiasm that the patients and clinicians have based on the Redux 4 data. Yep, excellent. Thanks. And obviously, there are huge unmet medical needs. Thanks so much. Your next question comes from the line of Joseph Schwartz from SVV.
Very reasonable and perhaps better than the timeline or the rate of enrollment that we had on the initial readouts for trial, primarily because of the enthusiasm that the patients and clinicians have based on the readouts for data.
Yes, Craig.
Obviously this is a medical need thanks, so much.
Your next question comes from the line of Joseph Schwartz from <unk>.
Your line is open.
Joseph Schwartz: Your line is open. Great, thanks so much. I was wondering if you could frame out for us how much data we should expect for 6058 and Iha in June in terms of the number of patients and the duration of therapy and how will you be reporting and interpreting data for different patients treated for different durations? Have you thought about the kinds of analyses that you'll be presenting and how confident are you that you'll be able to interpret them clearly, just given the numbers, the different numbers, and perhaps the low numbers of patients at different durations?
Great. Thanks, so much I was wondering if you could.
Frame out for us how much data, we should expect for $60 58.
In June in terms of like the number of patients and the duration of therapy.
Would you be reporting in interpreting data for.
Different patients treated for different durations have usama.
The times of analyses.
That you'll be presenting and how.
How confident are you that you'll be able to interpret some.
Clearly just given the numbers the different numbers and perhaps low numbers of patients at different durations.
Joseph Schwartz: Thanks for the question, Joe. Let me turn it over to Chris, and we can speak broadly about that, about expectations for EHOP, and think about this initial data set. Yeah, Joe. This is Chris.
Alright, Thanks for the question, Joe Let me turn it over to Chris and we can speak broadly about that about expectations for Ehealth thinking about this initial data set.
Yes.
Joe.
Yeah.
Chris Moravido: So, you know, as mentioned before, we are showing initial data from the 6 milligram cohort, and the treatment duration is up to three months for this cohort, so we expect to be able to provide a meaningful suggestion of the clinical benefit of 1658 in terms of its ability to increase HPF. We haven't been guided specifically as to what we'll show at EHR, and we look forward to being able to share these data at EHR. But we do intend to show what we think is a meaningful increase in HPF, informed by other clinical parameters and laboratory values that also suggest the potential for therapeutic benefit in these patients. Okay, great. Thanks.
So as mentioned before we are showing initial data from the six milligram cohort.
And the treatment duration is up to three months for this cohort, which we expect to be able to provide a meaningful suggestion of the clinical benefit of <unk> 58 in terms of its ability to increase hbf, we haven't guided specifically as to what we'll show at <unk> and we look forward to being able to share those data at Ada.
But we do intend to show what we think is a meaningful increase on hbf informed by other clinical parameters.
Laboratory values that also suggests the potential for therapeutic benefit in these patients.
Joseph Schwartz: And then, as far as the REACH trial execution goes, can you give us a sense of, you know, to what extent do you think actual enrollment of patients may be a rate-limiting factor for the pace of REACH versus setting up sites, given you've got some specialized procedures being performed in order to evaluate patients? Can you give us a sense of, you know, what you think the heaviest lifting will be for executing REACH in terms of, like, site activation versus, you know, patient enrollment?
Okay, great. Thanks, and then as far as the reach trial.
Execution goes.
Can you give us a sense of.
To what extent do you think.
Actual enrollment of patients maybe a.
Limiting factor for the pace of reach versus setting up sites, given you've got some special ones.
Procedures being.
Performed in order to evaluate patients can can you give us a sense of.
What do you think where do you think the heaviest lifting will be for executing reach in terms of like site activation versus patient enrollment.
Thank you.
Joseph Schwartz: Thank you. Yeah, thanks for the question, Joe. So in terms of reach, I think one of the things that Judy alluded to is that we were very encouraged based on what we saw last time in our Redux 4 Phase 2B trial. And just a reminder, that was 80 subjects. It was one of the largest trials ever done in FFHD.
Yes. Thanks for the question Joe So in terms of reach I think one of the things that Judy alluded to is that we were very encouraged based on what we saw last time in our redux for phase two B trial, and just a reminder, that was 80 subjects.
It was one of the largest trial ever done an fsh D and I think in the rare disease space. There is always a question of.
Brian Stewart: And I think in the rare disease space, there's always a question of how quickly enrollment can take place. And as Judy mentioned, there is such unmet need for FSHD; it's the second most prevalent form of muscular dystrophy. Not only is there nothing else approved, but there's not anything else even in the clinic.
How quickly can enrollment take place and as Judy mentioned, there is such an unmet need and Fsh D. It's the second most prevalent form of muscular dystrophy, not only is there nothing else approved but there's not anything else even in the clinic and as a result of that and I think the enthusiasm for the program. The <unk> four trial was able to.
Brian Stewart: And as a result of that, and I think the enthusiasm for the program, the Redux 4 trial was able to enroll very quickly with 80 subjects. So as we transition now to phase three, and we think about both finding additional subjects for the trial, as well as, like you said, site activation, we're really able to leverage the success from Redux 4 for both. So we're able to go back and utilize some of the same sites from Redux 4 plus add additional sites. And unfortunately, for people living with FSHD, the dynamics haven't changed since we ran Redux 4. There are no other therapeutic alternatives. In fact, there are no other programs in the clinic.
To enroll very quickly with 80 subjects. So as we transition now to the phase III and we think about that both finding additional subject for the trial as well as like you said site activation, we're really able to leverage the success from Readouts for for both so we're able to go back and utilize some.
The same sites from Redux, four plus add additional sites and unfortunately for people living with Fsh D. The dynamics haven't changed since we ran redux for there are no other therapeutic dose.
Therapeutic alternatives there are no other programs in the clinic. So we think as a result of both of those will have a very clear path towards enrollment and as that progresses, we intend to provide an update on both.
Brian Stewart: So we think as a result of both of those, we'll have a very clear path towards enrollment, and as that progresses, we intend to provide an update on both when enrollment should complete and when data should be available. Great, thanks for the call. Your next question comes from the line of Matt Biegler from Oppenheimer. Your line is, Hey guys, thanks for the questions. Two quick ones for me.
When enrollment should complete and when data should be available.
Great. Thanks for the color.
Your next question comes from the line of Matt <unk> from Oppenheimer. Your line is open.
Matt Biegler: We obviously talked a lot about HPF and precedents for protein expression just in the development of sickle cell drugs, but something that I don't think doesn't get talked about as much but probably should be are benchmarks for F-positive cells. Are there any precedents that you can point to for the degree of pancellularity that you'd like to achieve for 60-58 that could have meaningful downstream impacts on things like POC? And second, just a quick one in terms of, can you tell us the actual data cutoff that will be included in the EHOP presentation?
Hey, guys. Thanks for the questions two quick ones for me.
We obviously talked a lot about hbf and precedents for protein expression just in the development of sickle cell drugs, but.
Something that I don't think it doesn't get talked about as much but probably should our benchmarks for <unk> positive cells are there any precedents that you can point to for the degree of Pan cellular therapy that.
That you'd like to achieve for 60 58 that that could have a meaningful downstream impacts on things like POC and.
And second just a quick one in terms of.
Can you tell us the actual data cutoff that will be included in the presentation. Thanks.
Matt Biegler: Thanks. Yeah, so why don't I turn it over to Paul and we can talk about pancellularity, including what we observed preclinically, which I think we find very encouraging, and then we can turn it back over to Chris for IHOP. Thanks, Brian. Yeah, in terms of F cells, you know, the measurement itself is somewhat subjective.
So why don't I turn it over to Paul and we can talk about pan cellular already including what we observed pre clinically, which I think we find very encouraging and then turn it back over to Chris for you.
Yes.
Thanks, Brian .
Yes in terms of the measurement itself is.
Somewhat subjective so it's a little hard to compare across different studies, one thing I will notice that the greater the pain cellular already the greater the translation of potential clinical benefit as Brian alluded to pre clinically we see very high levels of vessels near.
Paul Bruno: It's a little hard to compare across different studies, but one thing I will note is that the greater the pancellularity, the greater the translation to potential clinical benefits. As Brian alluded to, preclinically, we see very high levels of F cells, near, and near 100% pancellularity in our preclinical assays.
100% Ancillula hurting our preclinical assays, our hope is to see how that translates in the clinic as well and we are collecting endpoints to inform on that.
Chris Moravido: Our hope is to see how that translates in the clinic as well, and we are collecting endpoints to inform on that. Yeah, Matt, your second question about data cutoffs, you know, as mentioned, we're going to provide initial data, and the six milligram cohort; we haven't guided specifically as to what we're going to show. But we intend to show data that should provide proof of concept, really proof of concept for 6058 in people with sickle cell dysplasia. Okay, great. We'll see you in Vienna.
Yes, Matt Your second question about data cutoff as mentioned, we are going to provide an initial data on the six milligram cohort, we haven't guided specifically as to what we're going to show, but we intend to show data that should provide proof of concept early proof of concept for 658.
People with sickle cell disease.
Okay, Great, we'll say it again.
Thanks.
Operator: Thanks. Again, if you would like to ask a question, please press star 1 on your telephone keypad. Again, that is star one on your telephone.
Again, if you would like to ask a question. Please press star one on your telephone keypad.
Again that is star one on your telephone keypad.
Matthew Harrison: Your next question comes from the line of Matthew Harrison from Morgan Stanley. Your line is open. Hi, thanks for taking our question. This is Wenjiang online for Matthew.
Your next question comes from the line of Matthew Harrison from Morgan Stanley . Your line is open.
Wenjiang: So our question is, given that you already expect your study to start the pivotal study for 6058 in early 2023. So we're wondering what gives you the confidence given that you are still seeking the best dose, like the second cohort, you haven't decided on the dose, and you even plan for core three with maybe potential data-driven analysis. So how have you come up with the early 2023 timeline? Yeah, absolutely. And you're right.
Hi, Thanks for taking our question. This is what got online format deal. So our question is.
Given that you already expect study start the pivotal study for 658 in early 2023. So we're wondering what gives you the confidence given that.
You are still sticking for the past dose.
A second cohort do you haven't decided like all of us at <unk>.
For Q3, with maybe a potential data driven.
So how have you come up with the train three timeline.
Wenjiang: Our goal, and I think as we've stated all along, that if we're able to see robust HBF increases, our goal is to transition into a registrational trial as early as possible in 2023. We do believe that that is consistent with what we're hearing from the KOLs, that this would be a drug, because of the benefits of HBF, that would be broadly utilized and has the potential to be standard of care. Let me turn it over to Chris.
Yeah, absolutely and you're right our goal.
Think as we've stated all along that if we're able to see robust hbf increases.
Our goal is to transition into a registrational trial as early as possible in 2023, we do believe that that is consistent with what we're hearing from the kols that this would be a drug because of the benefits of hbf that would be broadly utilized and has the potential to be standard of care.
Chris Moravido: We can talk about how we're thinking about the Phase 1b trial, looking at the different doses really in order to support that and to support transitioning into a registrational trial with as few doses as is feasible. So we're doing everything possible now to prepare for the start of the study in 2023, and we assume that, based on the strength of the preclinical and early clinical data from healthy volunteers, we should be able to demonstrate early proof of concept.
Let me turn it over to Chris We can talk about how we're thinking about the phase one b trial.
At the different doses really in order to support that and to support transitioning into a registrational trial.
With as few doses as its feasible.
Great.
So we're doing everything possible now to prepare for the start of the study in 2023, and we're assuming just based on the strength of the preclinical and early clinical data from healthy volunteers that we should be able to demonstrate early proof of concept and then the work becomes choosing the dose. So we will spend the time between now.
Chris Moravido: And then the work becomes choosing a dose. So we'll spend the time between now and the first patient in that phase two trial collecting data to determine that dose. We're making drugs, we're starting to talk to sites, we're getting involved with patients and patient care partners to be ready to start this trial as soon as possible so that the infrastructure is built, and all we need to do, ultimately, is that dose selection. Okay, cool. Thanks.
And the first patient in our phase two trial collecting data to determine the dose for making drug we're starting to talk to sites, we're getting involved with patients and patient care partners to be ready to start this trial as soon as possible. So the infrastructure is built and then all we need to do ultimately is that dose selection.
Okay cool thanks.
Operator: Thank you. This concludes the Q&A session for today. I would like to turn the call over to Brian Stewart for closing remarks. Thank you so much. Thanks, everybody, for joining us today. And we appreciate the continued support of Fulcrum. Have a great day. Notice The Voice.
Thank you. This concludes the Q&A session for today I would like to turn the call over to Bryan Stuart for closing remarks.
Thank you so much thanks to everybody for joining us today and we appreciate the continued support of fulcrum have a great day.
This concludes today's call Goodbye you may now disconnect.
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