Q3 2020 Fulcrum Therapeutics Inc Earnings Call
Good morning, and welcome to Fulcrum Therapeutics third quarter 2020 conference call. Currently all participants are in a listen only mode. There will be a question answer session. At the end of this call I would now like to turn the call over to Christine <unk> director of Investor Relations and corporate communications that Fulcrum. Please proceed.
Operator: Good morning, and welcome to Fulcrum Therapeutics' third quarter 2020 conference call. Currently, all participants are in a listen-only mode.
Operator: There will be a question and answer session at the end of this call. I would now like to turn the call over to Chrissy Warrick, Director of Investor Relations and Corporate Communications at Fulcrum. Please continue.
Yes, good morning, and thank you for joining US earlier. This morning, we issued a press release outlining our recent progress and financial results for the third quarter and 2020.
Chris Calabrese: Thank you, Sonia. Good morning, and thank you for joining us. Earlier this morning, we issued a press release outlining our recent progress and financial results for the third quarter of 2020. If you don't have a copy of the release, you can find it in the investor relations section of our website at fulcrumtx.com. 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.
A copy of the release you can find it in the Investor Relations section of our website Opentext.
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 95.
You can include statements about our future expectations 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. We may update these statements in the future we are not taking on obligation to do so.
Robert J. Gould: 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 business. With me on today's call are Robert Gould, President and Chief Executive Officer, Owen Wallace, Chief Scientific Officer, and Brian Stewart, Chief Operating Officer. Now, let me quickly run through this morning's agenda. Robert will begin the call with an overview of our recent progress, Owen will provide an update on our sickle cell program and product engine, and Brian will cover our front end. With that, it's my pleasure to turn the call over to Robert. Robert.
Please refer to our most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with our business.
With me on today's call are Robert Gould, President and Chief Executive Officer, I wouldn't Wallis Chief Scientific Officer, and brain Stewart Chief operating officer.
Quickly run through this morning's agenda.
Robert will begin the call with an overview of our recent progress and we will provide an update on our sickle cell program and product engine and Brian will cover our financials.
With that it's my pleasure to turn the call over to Robert Robert.
Robert J. Gould: Thanks, Christy, and good morning, everyone. Thank you for joining us today. This quarter, we've seen tremendous progress throughout the company as we strive to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. In research and development, we made important progress with our program evaluating losmaphimod, a selective P38 MAP kinase inhibitor, in fascioscapulohumeral muscular dystrophy, or FSHD. We're now in clinical development with FCX 6058 and screening healthy volunteers in our phase one sickle cell trial. We initiated LOSSFIT, our Phase 3 trial with LossMakamod for the treatment of COVID-19. Our discovery product engine continues to grow.
Thanks, Christine and good morning, everyone. Thank you for joining us today.
This quarter, we've seen tremendous progress throughout the company as we strive to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need and.
Research and development, we made important progress with our program evaluating lost Massimo on a selective T 38 map kinase inhibitor in Fassio scapula, humoral muscular dystrophy for FSC industry.
We're now in clinical development is FCX, 60, 58, and screening healthy volunteers in our phase one sickle cell trial.
We initiated last fit our phase three trial just mapping on for the treatment of COVID-19.
Our discovery product engine continues to grow in July we executed a collaboration with Myokardia to identify therapeutics that address the genetic drivers of cardio my offices.
Robert J. Gould: In July, we executed a collaboration with Myocardia to identify therapeutics that address the genetic drivers of cardiomyopathy. Our progress in FSHD and sickle cell disease has been highlighted in multiple posters accepted at various scientific meetings, and we made key appointments to our management team. Before turning the call over to Alan to discuss the progress in our program to elevate fetal hemoglobin for the potential treatment of sickle cell disease and beta thalassemia, I'd like to review our program with osmophomide for the treatment of FSHD. FSHD is a rare progressive and disabling disease characterized by severe muscular degeneration that occurs as skeletal muscle is replaced by fat. Unlike other diseases that can be characterized by the lack of a gene, FSHD is characterized by the aberrant expression of the gene Dux4, the root cause of the disease. Overexpression of Stux4 results in apoptosis, muscle death, and deterioration.
Are progressing after surgery in sickle cell disease has been highlighted multiple posters accepted at various scientific meetings and we made key appointments to our management team.
Before turning the call over to owing to discuss the progress in our program to elevate fetal hemoglobin for the potential treatment of sickle cell disease, and beta thalassemia I'd like to review our program. The trust mapping on for the treatment of Fs HD.
Fsh to use a rare progressive and disabling disease characterized by severe muscular degeneration that occurs a skeletal muscle is replaced by fat.
Like other diseases that can be characterized by the lack of a gi adverse HD is characterized by the ever an expression of the gene ducs for the root cause of the disease.
Thanks for express and results in a buck josias muscle dassen deterioration.
Robert J. Gould: This is the second most common muscular dystrophy with no current treatment option. LASMAPMOD has previously demonstrated safety and tolerability in approximately 3,500 subjects across multiple indications and is the only potential treatment in clinical development. This quarter, we presented multiple posters at the International Congress of the World Muscle Society. These posters highlighted our integrated approach to evaluating FSHD patients. We have also made tremendous progress with our clinical strategy, utilizing molecular biomarkers, imaging, functional readouts, and patient-reported outcomes. These studies have enabled the design of clinical trials to evaluate the potential benefits of LossMapMod in FSHD patients. The encouraging data reported from our interim analysis suggest Laspatimon may be reducing DUX4-driven gene expression and that mussels with the highest DUX4-driven gene expression in pre-treatment biopsies show large reductions following treatments with loxamethamide compared to placebo.
This is the second most common muscular dystrophy with no current treatment options.
Yes, Matt Marsh has previously demonstrated safety and Tolerability in approximately 3500 subjects across multiple indications and is the only potential treatment in clinical development.
This quarter, we presented multiple posters at the international Congress of the World Muscle Society. These.
These posters highlighted our integrated approach to evaluating Fs HD patients.
We have also made tremendous progress with our clinical strategy utilizing molecular biomarkers imaging functional redoubts and patient reported outcomes. These studies have enabled the design of clinical trials to evaluate potential benefits of lost maximize NFS HD patients.
Encouraging data reported from our interim analysis suggest plus five on maybe reducing duxford Durbin gene expression and the muscles with the highest dose for driven gene expression and treat pretreatment biopsies show large reductions following treatments last maps more compared to placebo.
We remain on track to announce full data in the second quarter Twentytwenty one.
Robert J. Gould: We remain on track to announce full data in the second quarter of 2021. Data will include the primary endpoint, reduction from baseline of ducts, forgery, and gene expression in all patients. Additionally, we'll report a pre-specified sensitivity analysis assessing biopsies with the highest pretreatment level of DUX4-driven gene expression and key secondary and exploratory endpoints. We believe we will be able to provide the most comprehensive assessment of any therapeutic in FSHD with the totality of data in the second quarter next year, and we will not report top line results separately. We also look forward to the continued analysis of the ongoing single center open label study, which includes change from baseline in skeletal muscle, MRI biomarker, and several clinical outcome assessments in subjects who have been treated for up to a year.
Data will include the primary endpoint reduction from baseline of drugs for grid gene expression in all patients. Additionally, we reported pre specified sensitivity analysis assessing biopsies with the highest pre treatment level of drugs for driven gene expression and key secondary and exploratory endpoints.
We believe we'll be able to provide the most comprehensive assessment of any therapeutic NFS HD with the totality of data in the second quarter next year, and we will not report topline results separately.
We also look forward to the continued analysis of the ongoing single Center Open label study, which includes change from baseline in skeletal muscle and MRI biomarker and several clinical outcome assessments in subjects, who have been treated up to a year.
[noise] rough Dx 60, 58, we recently presented comparative pharmacology data and additional preclinical data supporting the future development sickle cell disease and beta thalassemia.
Robert J. Gould: For FTX 6058, we recently presented comparative pharmacology data and additional preclinical data supporting the future development of FTX 6058 in sickle cell disease and beta thalassemia. FTX 6058 is a highly potent small molecule inhibitor of EED designed to induce the expression of fetal hemoglobin to treat the root cause of sickle cell disease. Owen will discuss this potentially promising and differentiated therapeutic option for patients in more detail, and will share more on December the 15th when we host a Key Opinion Leader Symposium with sickle cell experts. Now, to our COVID program.
FCX 60, 58 say highly potent small molecule inhibitor of E designed to induce expression of fetal hemoglobin to treat the root cause of sickle cell disease on.
Oh, and we'll discuss this potentially promising and differentiated therapeutic option for patients in more detail and we'll share more on December the 15th when we host to key opinion leaders symposium with sickle cell experts.
Turning now to our Cobot program as a reminder, last fed is an international multicenter phase three trial with less mcmoran for hospitalized subjects with COVID-19.
Robert J. Gould: As a reminder, LOSFID is an international, multi-center, phase three trial with LossMathMod for hospitalized subjects with COVID-19. The trial is designed to assess the safety and efficacy of a 15 milligram, twice per day, oral dose of Lost Math Mod compared to placebo for 14 days, on top of standard of care in approximately 400 subjects who are at risk of progression to critical illness based on older age and The primary endpoint is the proportion of patients who progress to death or respiratory failure by day 28. While we saw some delays in opening trial sites in August and September, we continue to make progress in patient enrollment and anticipate providing an update on the LossFit trial in the first quarter of 2021. As part of our progress, we've also expanded our management. I'm pleased to announce today that Kurt Oldmans will join Fulcrum at the end of the month as our General Counsel.
The trial is designed to assess the safety and efficacy of the 15 milligram twice per day World. Those have lost Matt mine compared to placebo for 14 days on top of standard of care and approximately 400 subjects were at risk of progression to critical illness based on older age and elevated systemic and some.
Nation.
The primary endpoint is the proportion of patients who progressed to Jeff respiratory failure by day 28.
Well, we saw some delays in opening trial sites in August and September we continue to make progress in patient enrollment and anticipate providing an update on the loss for trial in the first quarter of 2021.
As part of our progress we've also expanded our management team.
I'm pleased to announce today that Curt omens, who joined full clearance at the end of the month as our general Counsel Kurt brings a wealth of experience from his prior roles at Davita Ray Novo Nordisk, new dry like covering a variety of leave awards, including regulatory and intellectual property.
Robert J. Gould: Kurt brings a wealth of experience from his prior roles at DeVita, Array, Novo Nordisk, and Eli Lilly, covering a variety of legal roles, including regulatory and intellectual property. We've also appointed Dr. Alan Zekiewicz to serve as a clinical advisor following the departure of Diego Kadavid, as announced in our release. Alan has served on our board since 2016 and has made important contributions to advancing our pipeline of clinical programs. Previously, he was founder and CEO of Abide Therapeutics, and prior to Abide, he spent a number of years at Merck, where he served as the senior vice president of clinical research. We'll be launching a search for a chief medical officer, but in the meantime, I look forward to benefiting from Alan's expertise as part of our executive team. I'm also pleased to announce that Kim Hazen has been promoted to Senior Vice President, Human Resources. Kim has been an invaluable member of the leadership team since she joined Fulcrum in 2017.
We've also appointed Dr. around Zika, which to serve as a clinical advisor following the departure of Diego cut to beat as announced in our release Alan.
Alan has served on our board since 2016 and has made important contributions to advancing our pipeline of clinical programs freebie.
Previously Alamos founder and CEO of abide therapeutics and prior to abide he's been a number of years at Merck, where he served as senior Vice President clinical research will.
We will be launching a search for a chief medical officer, but in the meantime look forward to benefitting from Allen's expertise as part of our executive team I.
Im also pleased to announce that Kim Hasan has been promoted to senior Vice President human resources.
Kim has been an invaluable member of the leadership team since you joined Fulcrum and Twentyseven chain.
Lastly, I'd like to thank everyone at Fulcrum, who continues to be phenomenal through these challenging times, we've made a tremendous amount of progress all while keeping our patient communities at the forefront of what we do.
Robert J. Gould: Lastly, I'd like to thank everyone at Fulcrum who continues to be phenomenal through these challenging times. We've made a tremendous amount of progress, all while keeping our patient communities at the forefront of what we do. With that, I'll turn it over to Owen.
With that I'll turn it over to Alan.
Owen Wallace: Thank you, Robert. To begin, I just want to add to some of the key points related to our FSHD program that Robert mentioned. We're encouraged by the data indicating that losmaphomide may be reducing Dux4-driven gene expression and that muscles with the highest Dux4-driven gene expression in pretreatment biopsies showed large reductions following treatment with losmaphomide compared to placebo. The full data set, which we expect to announce in the second quarter of 2021, will bring us many new insights on the potential of LASMAP mod to treat FSHD. We are grateful to our outstanding team of investigators and to all the patients who continue to support this important clinical program. Now, moving to FDX 6058, our candidate for sickle cell disease and beta-thalassemia.
Thank you Robert to begin I, just want to add to some of the key points related to our EPS HD program that Robert mentioned, we're encouraged by the data, indicating that lost map a month, maybe reducing deaths sport given gene expression and that muscles with the highest exports have been gene expression in pretreatment biopsies.
Joe just large reductions following treatment with lots of mathematics compared to placebo.
The full dataset, we expect to announce in the second quarter of Twentytwenty, one well bring us many new insights on the potential of less not from us to treat fsh fee.
Grateful to our outstanding team of investigators until all the patients who continue to support this important clinical programs.
Now moving to Ft, Xsixty pit gates are candidates for sickle cell disease and beta thalassemia we.
Owen Wallace: We recently presented preclinical data, including comparative pharmacology, during the Sickle Cell Disease Research and Educational Symposium and National Sickle Cell Disease Scientific Meeting in September, where we also disclosed EED as our drug target. Sickle cell disease is a genetic disorder caused by a mutation in the adult form of hemoglobin. The result of the mutation is less efficient oxygen transport and the formation of red cells that are sick. Sickle cell patients typically suffer from serious complications, such as anemia, pain, and vaso-occlusive crises.
We recently presented preclinical data, including comparative pharmacology, joining the sickle cell disease research and educational symposium, a national sickle cell disease scientific meeting in September we also disclosed E.D. as our drug targets.
Sickle cell disease is a genetic disorder caused by a mutation in the adult form of hemoglobin the.
The results of the mutation is less efficient oxygen transports and the formation of red cells that are sickle cell.
Sickle cell patients typically suffer from serious complications such as anemia pain and basal occlusive crisis.
Sickle cell disease affects an estimated 100000 patients in the United States and millions worldwide.
Owen Wallace: Sickle cell disease affects an estimated 100,000 patients in the United States and millions worldwide. Increasing fetal hemoglobin can have a transformative impact on patients with sickle cell disease, including reducing both recurring events and mortality and increasing the likelihood of asymptomatic presentation. We believe an oral small molecule capable of raising fetal hemoglobin has broad applicability across sickle cell patients and has the potential to be a very impactful therapy. We have shown that FTX6058 selectively up-regulates fetal hemoglobin in both human cellular models and mouse models of sickle cell disease. The treatment of human CD34 positive cells from healthy and sickle cell disease donors with FTX6058 resulted in fetal hemoglobin levels up to approximately 30% of total hemoglobin with minimal undesirable effects on cell health.
Increasing fetal hemoglobin can have a transformative impact for patients with sickle cell disease, including reducing both hiring events and mortality and increasing the likelihood of asymptomatic presentation.
We believe an oral small molecule capable of raising fetal hemoglobin has broad applicability across sickle cell patients and has the potential to be a very impactful therapy.
We have shown that Stx 60, 58 selectively up regulates fetal hemoglobin in both human cellular models and mouse models of sickle cell disease.
The treatment of human CD 34 positive sales from healthy and sickle cell disease donors with FCX 60, 58 resulted in fetal hemoglobin levels up to approximately 30% of total hemoglobin with minimal undesirable effects on self help.
Owen Wallace: We believe that this is a superior preclinical profile relative to standard of care, hydroxyurea, and other mechanisms that have been reported to induce fecal hemoglobin, and that the impressive pharmacological profile of FTX6058 supports its potential as a disease-modifying therapeutic that could have a broad impact on safety. Based on the data we've seen to date, we believe FTX6050ase could be a Our program has generated significant enthusiasm in the sickle cell community with our unique mechanism of action, and we look forward to sharing more about our program at our upcoming KOL event on December 15, as well as hearing from Dr. Maureen Echebe and Dr. Gerd Globel. With our IND now open, we're excited to begin dosing in our Phase 1 trial in healthy adult volunteers this quarter. This phase one trial will evaluate 60-58 safety, tolerability, pharmacokinetics, and target engagement in both the single ascending dose study and a multiple ascending dose study.
We believe that this is a superior preclinical profile relative to standard of care Hydroxyurea and other mechanisms that have been reported to induce fetal hemoglobin.
And that the impressive pharmacological profile Fdx 60, 58 supports its potential as a disease modifying therapeutic that could have a broad impact on symptoms.
Based on the data Weve seen to date, we believe Fdx 60, 58 could be a transformative therapy for sickle cell disease.
A program has generated significant enthusiasm and the sickle cell community with our unique mechanism of action and we look forward to sharing more on our program at our upcoming KL event on December 15, as well as hearing from Dr., Morris Chemie and Dr. Gert curb global.
With our eye. Indeed now open we're excited to begin dosing in our phase one trial in healthy adult volunteers. This water is.
Phase one trial will evaluate 60, 58 safety Tolerability pharmacokinetics and target engagement in both.
Single ascending dose study and a multiple ascending dose study.
Owen Wallace: We expect to report data from this Phase 1 trial in mid-2021 and advance 6058 into sickle cell patients as quickly as possible. Additionally, our non-provisional composition of matter patent application has been published, and we will have three posters at the American Society of Hematology meeting next month as well. Moving on to our research, we are very pleased with the progress of our preclinical portfolio. Our discovery platform has resulted in the clinical programs we have discussed today, in addition to enabling the collaborations with Acceleron and Myocardia. Fulcrum Sikh has grown significantly this year.
We expect to report data from this phase one trials in mid Twentytwenty, one and advance 60 58 into sickle cell patients as quickly as possible.
Additionally, our non provisional composition of matter patent applications published and we will have three posters at the American Society of Hematology meeting next month as well.
Moving to our research efforts we.
We are very pleased with the progress of our preclinical portfolio. Our discovery platform has resulted in the clinical programs. We have discussed today. In addition to enabling the collaboration with Acceleron Myokardia.
Welcome seek has grown significantly this year.
Owen Wallace: FulcrumSeq is our proprietary connectivity map database that integrates the identification of druggable targets and signaling pathways in human cell models that recapitulate genetically defined disease. This database consists of high-dimensional RNA-seq and high-content imaging data to characterize the biological effects of our proprietary chemical probes and functional genomics libraries in complex cell models in both healthy and diseased patients. The unique insights that we've gained from this approach have resulted in several new discovery programs that have emerged from our Fulcrum Seek and Target Identification platform, which are currently being prioritized and, With that, I'll turn the call over to Brian for an update on our financials for the quarter.
Come seek as our proprietary connectivity map database that instigate integrates the identification of Druggable targets and signaling pathways human cell models at recapitulate genetically defined diseases.
This database consists of high dimensional or in a seat and high content imaging imaging data to characterize the biological effects of our proprietary chemical pro and functional genomics libraries in complex cell models in both healthy and disease patients.
Unique insights that we've gained from this approach has resulted in several new discovery programs that have emerged from our fulcrum seek and target identification platform, which are currently being prioritized.
With that I'll turn the call over to Brian for an update on our financials for the quarter Brian. Thank.
Brian Stewart: Thanks, Owen. We entered the third quarter of 2020 with $127 million in cash, cash equivalents, and marketable securities. Based on our updated operating plan and projections, we believe this will support our operations into the second quarter of 2022, allowing us to advance LOS MAPIMOD and FSHD in COVID-19, advance FTX 6058 in hemoglobinopathies, such as sickle cell disease, and invest in our discovery stage. Research and development expenses for the quarter ended September 30th, 2020 were $15.6 million compared to $13.5 million in the third quarter The increase of $2.1 million was primarily due to increased costs to support our ongoing planned clinical trials, as well as increased personnel-related costs to support the growth of Fulcrum's research and development organization. General and administrative expenses were $5.3 million for the third quarter of 2020 as compared to $3.5 million for the third quarter of 2019. The increase of $1.8 million was primarily due to increased costs associated with operating as a public company, as well as increased personnel-related costs to support the growth of our organization.
Thanks, So when we entered the third quarter 2020, with a $127 million in cash cash equivalents and marketable securities.
Based on our updated operating plan and projections. We believe this will support our operations into the second quarter of 2022.
Allowing us to advance was map of modern efforts HD encoding 19.
Yes, 60, 58, hemoglobinopathies, such as sickle cell disease and invest in our discovery stage efforts reach.
Research and development expenses for the quarter ended September Thirtyth, 2020, or $15.6 million compared to $13.5 million in the third quarter of 2019, the increase of $2.1 million was primarily due to increased costs to support our ongoing planned clinical trials as well as increased personnel related costs.
To support the growth of Bookworms research and development organization.
General and administrative expenses were $5.3 million for the third quarter 2020, as compared to $3.5 million for the third quarter of 2019.
The increase of $1.8 million was primarily due to increased costs associated with operating as a public company as well as increased personnel related cost to support the growth of our organization our.
Our net loss was $19 million for the third quarter of 2020 as compared to a net loss of $60.5 million for the third quarter of 2019.
Brian Stewart: Our net loss was $19 million for the third quarter of 2020 as compared to a net loss of $16.5 million for the third quarter of 2019. However, overall, we continue to expect several upcoming catalysts. We expect to report full data from Redux 4 and FSHD, including muscle biopsy, exploratory, and clinical outcome assessments in the second quarter of 2021. We plan to begin dosing in our phase one healthy volunteer trial with FTX 6058 for sickle cell disease this quarter and report data in mid-2021. We'll provide an update on our lowest bid trial in the first quarter of 2021, and we'll continue to advance our discovery programs from our product engine while making progress with our partners at Acceleron and Myocardia. We're very excited about the work ahead as we continue to execute on our plans and look forward to keeping you updated on our progress in the months ahead.
Overall, we continue to expect several upcoming catalysts, we expect to report full data from redux for NFS, HD, including muscle biopsy exploratory and clinical outcome assessments in the second quarter of 2021.
Plans to begin dosing in our phase one healthy volunteer trial with FCX 60, 58 for sickle cell disease. This quarter and report data in mid 2021.
We'll provide an update on our lowest bid trial in the first quarter of 2021 and will continue to advance our discovery programs from our product engine, while making progress with our partners at Acceleron and Myokardia.
We're very excited about the work ahead as we continue to execute on our plans and look forward to keeping you updated on our progress in the months ahead.
Operator, you May now open up the line for questions.
Thank you and our mine or to ask the question you will need to press star one on your telephone to withdraw your question press the pound key.
First question comes from Ted Tenthoff of Piper Stanley. Your line is now open.
Great. Thanks for the update if you hear from you all.
Really exciting for progress going on both clinical and preclinical.
Operator: Operator, you may now open up the line for questions. Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Our first question comes from Ted Tenthoff of Piper Sandler.
I'm wondering because it sits just with respect to the refinement.
Hi, Andy.
Merck had three dogs.
What what kind of uptick should we be expecting from the cobot study and.
Is there any particular reason that we work at top line data from reductions in the first quarter and just kept the full readout personally I think that's that's what's the important part anyway. Thanks.
Edward Andrew Tenthoff: Your line is now open. Great. Thanks for the update. Good to hear from you all and really looking forward to the progress going on both clinical and preclinical. I wanted to get a sense just with respect to the refinement of timing, both on MOSFET and Redux.
Thanks, Ted let me take just the second question on reduction Fsh the first.
We believe we will be able to provide the most comprehensive assessment of loss mathematics.
Robert J. Gould: What kind of updates should we be expecting from the COVID study? And is there any particular reason that we won't get top-line data from Redux in the first quarter and just get the full readout? Personally, I think that's the important part anyway.
The totality of the data.
That includes not only the dub four driven gene expression, but also an MRI whole body MRI and <unk> as a key secondary endpoint in a number of exploratory endpoints that are looking at muscle function measurements patient reported outcomes, we thought providing that that that complete package.
Robert J. Gould: So thank you, Thanks, Ted. Let me take the second question on redox and FSHD first. We believe we'll be able to provide the most comprehensive assessment of lost methamide with the totality of the data, which includes not only the duct core driven gene expression but also MRI, whole-body MRI, and as a key secondary endpoint and a number of exploratory endpoints that are looking at muscle function, measurements, patient-reported outcomes, and we thought providing that complete package of data was the best way to assess the potential benefit I think that was the last time I did it.
To date it was the best way to assess the potential benefit of loss map modified the fs HD patients rather than fragmenting it out.
That's fair enough to go ahead. Thank you.
Yeah. Thanks Ted.
Turns of the loss the update as we mentioned site openings were slower than expected in August and September and so we'll give an update on the on the status of the trial in the first.
Okay, well, thanks, Robert Thanks for the update and congrats on the good progress.
Thank you and our next question comes from Joseph Schwartz of SCB Leerink. Your line is now open.
Robert J. Gould: Thank you. Yeah, thanks, Ted. In terms of the loss fit update, as we mentioned, site openings were slower than expected in August and September.
Great. Thanks, very much I had a couple of questions on 60 58, given the recent disclosures I was wondering if you could walk us through the different means of quantification of H. behalf.
Robert J. Gould: And so we'll give an update on the status of the trial first. Excellent. Well, thanks for the update and congratulations on all the good progress. Thank you. And our next question comes from Joseph Schwartz of SCV Larynx. Your line is now open.
Elevation that you.
That you ran in your preclinical experiments and.
Describe for us what the.
Those measures.
Measures like H. plc mass spec and flow cytometry or are telling you.
Joseph Patrick Schwartz: Great, thanks very much. I had a couple questions on 6058, given the recent disclosures. I was wondering if you could walk us through the different means of quantification of HBF elevation that you ran in your preclinical experiments. Describe for us what each of those measures like HPLC, mass spec, and flow cytometry are telling you when you conclude that you could potentially have potentially superior attributes relative to other agents. Hi Joe, this is Owen.
When you conclude that you could have potentially superior attributes relative to other agents.
Hi, Joe This is Ellen and yeah, we're very excited about the preclinical asset portfolio and and says simple program and the data that Weve generated I think is very consistent it preclinically with lots and they are ready.
Straight persistence of fetal hemoglobin phenotype is in sickle individuals. So these are people who have a sickle cell mutation, but also have another mutation that causes them to continue to expand fetal hemoglobin and at many of these are asymptomatic, particularly if they occur.
Owen Wallace: Yeah, we're very excited about the preclinical portfolio and sickle program. And the data that we've generated, I think, is very consistent preclinically with what the hereditary persistence of the fetal hemoglobin phenotype is in sickle individuals. So these are people who have a sickle cell mutation but also have another mutation that causes them to continue to express fetal hemoglobin. And many of these are asymptomatic, particularly if they achieve around 30% of fetal hemoglobin levels. In our preclinical models, particularly in CD34 positive cells, we have looked at a variety of measures of fetal hemoglobin induction. One key attribute is the pancellularity of fetal hemoglobin induction, and this is measured by the number of F-cells or the percent of F-cells, which are fetal hemoglobin-expressing cells.
Around 30% of fetal hemoglobin levels.
And our preclinical models, particularly in the CD 34 positive sales, we have looked at a variety of measures of people hemoglobin induction.
One key attributes is the pet and cellular therapy of people hemoglobin induction and this is measured by the number of F. sales or the percent of event sales, which are fetal hemoglobin expressing cells and we've used a flow cytometry to get an estimation of the percentage of SL.
Owen Wallace: And we've used flow cytometry to get an estimation of the percentage of F-cells with 60-58 treatment, and we're seeing upwards of 80-90% of the cells expressing fetal hemoglobin, so we think that's a very attractive profile. The other key measures that we have made are with regard to total fetal hemoglobin levels and induction. And we've looked at that in two different ways. One is using HPLC, which is really the gold standard for the measurement of fetal hemoglobin. And a complementary technique is mass spectrometry.
Sales with 60, 58 treatment and were seeing at upwards of of add 80% to 90% of the cells expressing fetal hemoglobin. So we think thats a very attractive profile.
The other key measures that we have made are with regard to total fetal hemoglobin levels, an induction and we've looked at that in two different ways. One is using H.P.L.C.M., which is really the gold standard for the measurement of people hemoglobin.
And the complementary technique is mass spectrometry.
Owen Wallace: And again, using those two techniques, which are very consistent in their data, we're seeing upwards of 20 to 30 percent induction of fetal hemoglobin across multiple different human derived cells, both sickle cell donor and healthy donor as well. So we think it's a very attractive preclinical profile. Great, thanks. That's helpful context.
And again using those two techniques, which are very consistent in their data at we're seeing an upward of 20% to 30% induction of fetal hemoglobin across multiple different human derived cells, both sickle cell donor and healthy donors wells.
So we think it's a very attractive preclinical profile.
Great. Thanks, that's helpful context, and then on your phase one LD volunteer study or will that be long enough to see.
Owen Wallace: And then on your Phase 1 Healthy Volunteers study, will that be long enough to see fetal hemoglobin improvements, or should we be focused more on F cells? Do you have enough preclinical tox coverage to make that long enough that it could show some interesting signals? The Phase I is really designed for safety, tolerability, PK, and target engagement. We don't anticipate dosing for longer than two weeks in healthy volunteers. So we think there's a very low likelihood, just given the kinetics of red blood cell formation in healthy individuals, that we'll see an elevation of HBF or even a significant increase in F-cells in healthy individuals. Our general strategy is to progress through the Phase I trial in healthy volunteers as rapidly as possible and then move into sickle cell disease patients because we believe that will offer the best opportunity to see an increase, both in F-cells and Yeah, that makes sense.
The globe and improvements or should we be focused more on F. So.
Do you have enough pre.
Preclinical tox coverage to two.
To make that long enough that it could show some interesting signals.
And the phase one and it's really designed for safety Tolerability and PK target engagement, and we don't anticipate dosing longer than two weeks in healthy volunteers and so we think there is a a very low likelihood just given the kinetics.
Red blood cell formation in healthy individuals that we'll see a an elevation of hps or even a significant increase in f. sales in Healthys. Our general strategy is to progress through the phase one trial in healthy volunteers as rapidly as possible and then.
Move into and sickle cell disease patients as we believe that will offer the best opportunity to see an increase both in ESS sales and fetal hemoglobin and given the increased dynamics of fat blood cell.
Production in formation in sickle patients relative to help these.
Yeah that makes sense. Okay. Thank you for taking my question.
Owen Wallace: Okay. Thank you for taking my question. Thank you. And again, ladies and gentlemen, if you would like to ask a question at this time, please press star and then one on your touchtone telephone. And our next question comes from Matthew Harrison of Morgan Stanley. Your line is now open. Good morning, everyone. This is Kostas Son on behalf of Matthew.
Thank you and again, ladies and gentlemen, if he would like to ask a question at this time. Please press Star then one on your Touchstone telephone.
And our next question comes from Matthew Harrison of Morgan Stanley. Your line is now open.
Good morning, guys do on DC cost us on for Mark I have a quick question on 60 58.
Kostas Son: I have a quick question on 6058. Can you please talk a little bit about the development plans after phase one? In particular, are you planning to also evaluate this compound in beta thalassemia or just sickle cell disease? And are you also planning to evaluate it in combination with hydroxyurea, like other trials do, or as monotherapy only? Thank you. We, to touch on your last question first, Kosta, we have profiled the molecule in combination with hydroxyurea preclinically, and we believe that the profile is certainly additive potential with standard of care and hydroxyurea.
The police talk a little bit about the development plans after the phase one impact.
In particular.
How do you plan to also evaluate these compound could be done, let's see me out just sequencing disease and how do you also planning to evaluate the thing that combination with hydroxyurea like I'll, just tie else do or as a monotherapy only thank you.
We to touch on your last question first that customer and we have.
Profiles the molecule in combination with Hydroxyurea pre clinically and we believe that the profile is certainly an additive potentially with standard of care in Hydroxyurea. We also believe that a up regulator fetal hemoglobin could be used in combination with.
Owen Wallace: We also believe that an up-regulator of fetal hemoglobin could be used in combination with some of the other approaches that are being pursued clinically for sickle cell disease. So absolutely, that's on our radar screen. With regard to the development plan post phase one, we're still working through all of those details, and we're definitely considering moving into beta thalassemia as well. We believe, as I just previously mentioned, that the opportunity to see an up-regulation of fetal hemoglobin can be most effectively measured in sickle cell disease patients.
And some of the other approaches that are being pursued clinically for sickle cell disease. So absolutely that's on our radar screen.
With regard to the development plan post phase, one where it's still at working through all of those details.
Were definitely I'm, considering moving into beta thalassemia as well, we believe as I. Just previously mentioned that the opportunity to see an up regulation of fetal hemoglobin can be most effectively and measured likely in sickle cell disease patients and.
Owen Wallace: And then once we've got that initial data, certainly there's an opportunity to move into beta thalassemia patients as well. Thank you. And ladies and gentlemen, this does conclude our question and answer session. I would now like to turn the call back over to Robert Gould for any further remarks. I just want to thank you all for joining us today and for your support of Fulcrum. I also want to thank all the patients and investigators that have been participating with us as we move our clinical programs forward. The team here at Fulcrum hopes you all stay healthy and safe. Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.
Then once we got that initial data as certainly there's an opportunity to move into beta thalassemia patients as well.
Thank you.
Thank you.
And ladies and gentlemen, this does conclude our question and answer session I would now like to turn the call back over to Rebecca for any further remarks.
I just want to thank you all for joining us today and for your support a fulcrum I also want to thank all the patients and investigators that have been participating with us as we move our clinical programs forward.
The team here at Fulcrum Hope you all stay healthy and safe. Thank you.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
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