Q1 2021 Fulcrum Therapeutics Inc Earnings Call
[music].
Good morning, and welcome to Fulcrum Therapeutics first quarter 2021 conference call. Currently all participants are in a listen only mode. There will be a question and answer session at the end of this call.
Operator: Good morning, and welcome to Fulcrum Therapeutics' first quarter 2021 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 Christy Warwick, Director of Investor Relations and Corporate Communications at Fulcrum.
I'd now like to turn the call over to Kristy Warwick director of Investor Relations and corporate communications at Fulcrum. Please proceed.
Thank you operator, good morning, and welcome to the Fulcrum Therapeutics Conference call.
Christy Warwick: Thank you, operator. Good morning, and welcome to the Fulcrum Therapeutics Conference Call to discuss our first quarter 2021 financial results and recent corporate highlights. Earlier today, we issued a press release. For those of you who don't have a copy, you can access it in the Investor Relations section of our website at fulcrumcx.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.
As our first quarter 2021 financial results and recent corporate highlights.
Earlier today, we issued a press release for those of you who don't have a copy you can access it in the Investor Relations section on our website.
<unk>, TX dot 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.
These may include statements about our future expectations and plans clinical development timelines and financial projections.
Christy Warwick: 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. We may update these statements in the future, but we are not taking on an obligation to do so.
While these forward looking statements represent our views as of today, they should not be relied upon as representing our views on the future.
We may update these statements in the future, but we are not taking on an obligation to do so.
Christy Warwick: Please refer to our most recent filing 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 Brian Stewart, President and CEO; Chris Moxson, Chief Scientific Officer; Peter Thompson, Vice President of Finance and Accounting; and Judith Dunn, President, Research and Development. Let me quickly run through this morning's agenda. Brian will begin the call with a corporate overview. Chris will provide a more detailed review of our program in sickle cell disease in our product engine, and Peter will cover our front end. With that, it's my pleasure to turn the call over to Brian. Thank you, Christy.
Please refer to our most recent filings with Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with our business.
With me on today's call on Bryan Stuart President and CEO, Chris <unk>, Chief Scientific Officer, Peter Thomson, Vice President Finance on the Kelly and Judith President Research and development.
Let me quickly run through this morning's agenda, Brian will begin the call with a corporate overview.
This will provide a more detailed review of our program in sickle cell disease are a product engine and Peter will cover on friendships.
With that it's my pleasure to turn the call over to Bryan Bryan.
Thank you Christy good morning, everyone and thank you for joining US today, it's been an exciting and fast moving quarter for forward. We continue to make important progress across our clinical development programs discovery collaborations and product engine and expect to have meaningful updates from multiple key initiatives in the near term.
Brian Stewart: Good morning, everyone, and thank you for joining us today. It's been an exciting and fast-moving quarter for Fulcrum. We continue to make important progress across our clinical development programs, discovery collaborations, and product engine, and expect to have meaningful updates from multiple key initiatives in the near term. I'd like to first start with our product engine, Fulcrum Seek, which is a powerful and differentiated approach that serves as the innovation backbone for our company.
I'd like to first start with our product engine fulcrum fee, which is a powerful and differentiated approach that serves as the innovation backbone for our company.
Fulcrum seek has allowed us to rapidly identify novel high quality targets that modulate the root cause of genetically defined rare diseases.
Our lead programs in both fast Scapulohumeral muscular dystrophy or Fsh D.
And select Haemoglobinopathy or identified by earlier version of Fulcrum seek and remain on track.
Enabling drug discovery at an unprecedented scale in disease relevant settings, fulcrum fee creates an unparalleled opportunity to efficiently grow our pipeline of therapeutics and develop root cause treatments for genetically defined rare diseases with this in mind. Our goal is to bring forward to <unk> over the next 24 months.
Brian Stewart: FulcrumSeq has allowed us to rapidly identify novel, high-quality targets that modulate the root cause of genetically defined rare diseases. Our lead programs in both fascio-scapulohumeral muscular dystrophy, or FSHD, and select hemoglobinopathies were identified by our earlier version of Fulcrum-Seq and remain on track. By enabling drug discovery at an unprecedented scale in disease relevant settings, Fulcrum C creates an unparalleled opportunity to efficiently grow our pipeline of therapeutics and develop root cause treatments for genetically defined rare diseases. With this in mind, our goal is to bring forward two INDs over the next 24 months. The full LOS-MAP-A-MOD data from Redux IV and FSHD will be presented next month at the FSHD International Research Conference.
The fullest map them on data from redox foreign Fsh D will be presented next month at the FSA The International Research Congress on.
I'll have more to share on that in a few minutes, but these data will provide new insights that will inform the clinical path forward and Fsh D. Following data availability will meet with the FDA to discuss the path to registration and with Ft 6058 will have data from the phase one trial in healthy adult volunteers midyear and we anticipate initiating.
Dosing in people living with sickle cell disease by the end of the year. Additionally.
Additionally, we have further enhanced our leadership team with the appointment of Dr. Judith done.
As our president of research and development and today, we announced the appointment of Dr. Chris <unk>, Our Chief Medical Officer, both Judy and Chris have extensive experience in drug discovery and clinical development.
Judy has held multiple roles in global research and development, including leadership roles at Roche and Pfizer and Chris also has extensive leadership experience at biotech companies, including most recently as Chief Medical Officer at <unk>.
Brian Stewart: I'll have more to share on that in a few minutes, but these data will provide new insights that will inform the clinical path forward for FSHD. Following data availability, we will meet with the FDA to discuss the path to registration. And with FTX 6058, we'll have data from the Phase I trial in healthy adult volunteers by mid-year, and we anticipate initiating dosing in people living with sickle cell disease by the end of the year.
<unk>, Chris held leadership roles at Takeda, San <unk> and Merck, we are thrilled to have both of them as part of our team.
Now, let's turn to Loews map them out for Fsh D. As a reminder, fsh D is a rare progressive and disabling disease characterized by severe muscular degeneration that occurs as skeletal muscle is replaced by fat.
We estimate there are approximately 16% to 38000 patients in the U S and similar incidents worldwide, leading to an estimated global patient population of 300 to 780000 patients.
There are currently no approved therapeutics for Fsh day, and fulcrum is advancing the only known industry sponsored clinical trial evaluating a potential treatment.
Brian Stewart: Additionally, we have further enhanced our leadership team with the appointment of Dr. Judith Dunn as our President of Research and Development, and today we announced the appointment of Dr. Chris Morabito as our Chief Medical Officer. Both Judy and Chris have extensive experience in drug discovery and clinical development. Judy has held multiple roles in global research and development, including leadership roles at Roche and Pfizer, and Chris also has extensive leadership experience at biotech companies, including most recently as chief medical officer at Cardurian. Prior to Cardurian, Chris held leadership roles at Takeda, Sanofi, and Merck. We are thrilled to have both of them as part of our team.
Our development program and fsh be builds on the established safety of low <unk> demonstrated an approximately 3600 subjects. We have made tremendous progress with our integrated Sshd clinical development strategy evaluating molecular biomarkers as well as structural and functional measures and.
Patient reported outcomes.
This strategy includes natural history studies to better understand disease progression.
Preparatory studies to establish a biomarker and clinical endpoints as well as studies that have demonstrated muscle penetration and target engagement for those mathematics.
Recently.
At the virtual muscular Dystrophy Association conference in March we presented new data related to the use of imaging biomarkers and clinical outcome assessments for Fsh D. <unk>.
Presentations included development of a whole body muscle skeletal MRI protocol day.
To show this can capture heterogeneity and provide important information about disease severity.
Meaningful composite MRI measurements demonstrated correlation with relevant Fsh day functional endpoints.
Brian Stewart: Now, let's turn to Los Mathemat for FSHD. As a reminder, FSHD is a rare, progressive, and disabling disease characterized by severe muscular degeneration that occurs as skeletal muscle is replaced by fat. We estimate there are approximately 16,000 to 38,000 patients in the U.S. and similar incidents worldwide, leading to an estimated global patient population of 300,000 to 780,000 patients. There are currently no approved therapeutics for FSHD, and Fulcrum is advancing the only known industry-sponsored clinical trial evaluating a potential treatment.
Specifically these data were the first to demonstrate strong correlations of muscle fat infiltration and muscle fat fraction with timed up and go sshd timed up and go and reachable workspace, which measure impact on function.
This work has helped to inform the design of Fulcrum is current.
Ongoing studies of <unk> in patients with Fsh D, which include a single site phase II open label study as well as read ups for <unk>.
As a reminder, <unk> is an international phase II B double blind placebo controlled trial almost map of margin approximately 80 subjects with genetically confirmed <unk> HD.
We are on track to report results from this trial next month.
We and others in the field have demonstrated the ducks for expression occurs on a spectrum and we believe that all people with Fsh D will have muscles that exhibit high <unk> driven gene expression.
Biomarker data reported from Redux force interim analysis indicated that muscles with the highest docs four driven gene expression and pretreatment biopsies showed larger reductions following treatment with both map of margin compared to placebo.
Brian Stewart: Our development program in FSHB builds on the established safety of los mapimod demonstrated in approximately 3600 subjects. We have made tremendous progress with our integrated FSHB clinical development strategy, evaluating molecular biomarkers, as well as structural and functional measures and patient-reported outcomes. This strategy includes natural history studies to better understand disease progression.
We look forward to the Readouts for data readout, which will include the entirety of the biomarker data as well as outcomes from structural functional and patient reported measures will be encouraged if we continue to observe evidence of trends similar to the interim analysis in high expressing muscle biopsies from most map them on treated patients.
<unk> will be encouraged if we observe trends of benefit and secondary endpoints like muscle skeletal MRI clinical outcome assessments, where patient reported outcomes.
We believe <unk> has the potential to establish a new treatment paradigm for people living with Sshd and reflects our continued commitment to research the targets genetically defined rare diseases with high unmet need I would like to now turn the call over to Chris. Thanks.
Thanks, Brian.
Brian Stewart: Preparatory studies to establish a biomarker and clinical endpoints, as well as studies that have demonstrated muscle penetration and target engagement for LISMAP. Recently, at the virtual Muscular Dystrophy Association conference in March, we presented new data related to the use of imaging biomarkers and clinical outcome assessments for FSHD. Presentations included the development of a whole body muscle skeletal MRI protocol.
Neat research focus of silicone positions us to pursue targeted indications, where we believe we can develop safe and effective therapies to rebalance gene expression.
By working to understand and then target the root causes of disease, we have the best chance to optimize the potential efficacy of treatments and more broadly transform the way these diseases are being treated.
Research approach has enabled us to rapidly progress clinical programs intended to treat serious diseases beyond sshd, including select hemoglobin <unk>, such as sickle cell disease and beta thalassemia.
Sickle cell disease is the most common type of inherited Haemoglobinopathy and affects an estimated 100000 people in the United States and millions more worldwide.
Brian Stewart: Data show this can capture heterogeneity and provide important information about disease severity. Meaningful composite MRI measurements demonstrated correlation with relevant FSHD functionalities. Specifically, these data were the first to demonstrate strong correlations of muscle fat infiltration and muscle fat fraction with timed up-and-go, FSHD timed up-and-go, and reachable workspace, which measure impact on, This work has helped to inform the design of Fulcrum's current, ongoing studies of lozomabimide in patients with FSHD, which include a single-site Phase II open-label study, as well as a redox.
Genetic disorder caused by mutation in the adults from of hemoglobin <unk>.
Our results for the mutation is less sufficient oxygen transport and the formation of sickle red cells.
Living with sickle cell disease, typically suffer from serious complications, which can lead to anemia pain and basal occlusive crises of our POC as well as shorten lifespan.
Increasing fetal hemoglobin can have a transformative impact for patients, including reduced recurring pain crisis events reduced mortality and increased likelihood of asymptomatic presentation.
We believe this significant unmet need remains with existing sickle cell disease treatments.
Most therapies focus on the symptoms either on reducing pain episodes or ameliorating anemia.
More elaborate attempts seem to functional cures, namely Humana hematopoietic stem cell transplants and cell therapies, often utilize harsh conditioning regiments, which have inherent safety risks that may limit when and how they will be utilized.
Brian Stewart: As a reminder, Redux IV is an international, Phase IIb, double-blind, placebo-controlled trial of lismaphimodin in approximately 80 subjects with genetically confirmed FSHD. We are on track to report results from this trial next month. We and others in the field have demonstrated that DUX4 expression occurs on a spectrum, and we believe that all people with FSHD will have muscles that exhibit high DUX4-driven gene expression. Biomarker data reported from REDUX4's interim analysis indicated that muscles with the highest DUX4-driven gene expression in pretreatment biopsies showed larger reductions following treatment with losemethamide compared to placebo.
We believe Theres, a great opportunity with after you ex $6 58.
<unk> oral once daily therapy intended to treat the root cause of the disease, and therefore potentially address both anemia and boc.
People living with sickle cell disease, and beta thalassemia represent a diverse global population in great need of an effective therapy that can be accessed and administered with EPS. We.
We believe that an oral small molecule that can meaningfully increased levels of fetal hemoglobin will not only provide the therapeutic benefit and convenience of oral administration, but also the distribution at scale that this global population needs.
Thus, we believe <unk> 658 has the potential to be an impactful therapy.
Recently at the American Chemical Society meeting, we presented the medicinal chemistry strategy, perhaps you're at 658, including some initial PK data from the single ascending dose.
A portion of our phase one trial in healthy volunteers.
658, selectively upregulation of fetal hemoglobin in a pan cellular matter in both human cellular models and mouse models of sickle cell disease.
The treatment of human CD 34 positive cells from healthy and sickle cell disease donors with F $206 58.
<unk> and fetal hemoglobin levels of up to approximately 30% of total hemoglobin hemoglobin with no observed effects on cell health.
Brian Stewart: We look forward to the Redux 4 data readout, which will include the entirety of the biomarker data, as well as outcomes from structural, functional, and patient-reported measures. We will be encouraged if we continue to observe evidence of trends similar to the interim analysis and high-expressing muscle biopsies from most MAPMOD-treated patients. Additionally, we would be encouraged if we observe trends of benefit in secondary endpoints like muscle skeletal MRI, clinical outcome assessments, or patient-reported outcomes.
We believe this is a superior preclinical profile relative to the standard of care Hydroxyurea as well as other mechanisms that have been reported to induce fetal hemoglobin.
I'm also pleased to report that our composition of matter patent has been issued giving us patent protection until 2040.
We continue to enroll in our phase one sad portion and recently began enrolling in the multiple ascending dose or mad portion of the trial.
This phase one study in healthy volunteers is evaluating safety tolerability pharmacokinetics and target engagement of <unk> 58.
Based on our PK PD modeling, we anticipate that the pharmacological doses will be in the six milligram 20 milligram range, which is where we anticipate maximum levels of target engagement.
Recent reports suggest that red blood cell pathways from healthy volunteers is approximately 30 days, which may limit the opportunity to observe effects on fetal hemoglobin and a 14 day Mad study.
Brian Stewart: We believe Los Matamon has the potential to establish a new treatment paradigm for people living with FSHD and reflects our continued commitment to research that targets genetically defined rare diseases with high unmet needs. I would like to now turn the call over to Brian.
However, we will be measuring fetal hemoglobin mrna levels and the number of particular sites containing field fetal hemoglobin and the mad cohorts to monitor potential early signs of efficacy.
We expect to report data from the Sad and Mad cohorts mid 2021, which is where we will also outline our future clinical plans and.
And we anticipate dosing the first cohort of people living with sickle cell disease by the end of this year.
Chris Calabrese: Our unique research focus at Fulcrum positions us to pursue targeted indications where we believe we can develop safe and effective therapies to rebalance gene expression. By working to understand and then target the root cause of the disease, we have the best chance to optimize the potential efficacy of treatments and, more broadly, transform the way these diseases are being treated. This research approach has enabled us to rapidly progress clinical programs intended to treat serious diseases beyond FSHD, including select hemoglobinopathies, such as sickle cell disease and beta thalassemia.
We intend to continue our dialogue with the FDA and other health authorities as the program progresses.
Data warrants, we plan to seek orphan drug fast track and breakthrough therapy designations.
The opportunity to bring a new oral therapy for people living with sickle cell disease is a very exciting prospect for us with the potential to be a significant advance in treatment in the years ahead.
Moving to our research efforts, we are very excited about the productivity of the of our proprietary target discovery platform <unk>.
We have several discovery programs that span our core focus areas of muscular hematologic and CNS disorders.
Our unique approach is designed to identify starting points on a more technically enabled from a drug discovery perspective, as evidenced by the rapid progression from target I'd to IMD for Fsh D and sickle cell programs.
So the target is currently being assessed and we continue to explore both internal medicinal chemistry campaigns as well as opportunities to in license advanced chemical matter.
Chris Calabrese: Sickle cell disease is the most common type of inherited hemoglobinopathy and affects an estimated 100,000 people in the United States and millions more worldwide. It's 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 sickle red cells. People living with sickle cell disease typically suffer from serious complications, which can lead to anemia, pain, and vaso-occlusive crises or VOCs, as well as a shortened lifespan.
Our goal is to bring forward to <unk> over the next 24 months.
Fulcrum fee because advanced significantly on many fronts multiple advances in next generation sequencing and cell biology have allowed us to model complex human biology, and generate data at unprecedented scale.
Convergence with the knowledge of the root cause of genetically defined rare disease creates the ability for folks to discover and develop potential treatments for rare diseases with a level of productivity that was historically not possible.
Whether through the use of patient derived cells or view of the application of single cell genomics to patient biopsies that revealed that this regulated sell states from biological drivers of a given disease, the resulting high fidelity assays offer a remarkable level of clinical relevance can translate ability.
From this sophisticated product engine, we use machine learning algorithms to analyze the large amounts of functional morphological and transcriptional data they are generated with great precision and at great scale.
Chris Calabrese: Increasing fetal hemoglobin can have a transformative impact for patients, including reduced recurring pain crisis events, reduced mortality, and increased likelihood of asymptomatic presentation. We believe significant unmet need remains with existing sickle cell disease treatment. Most therapies focus on the symptoms, either reducing pain episodes or ameliorating anemia.
The result is highly de risked targets that are extensively enabled for further characterization.
We believe fulcrum seat is an important evolution in our product engine to identify targets informed by clinical biology, and thus more predictive of desired therapeutic outcomes.
Moreover, fulcrum sika supported the development of the clinical programs discussed today and has enabled our ongoing collaborations with accelerant and myocardial which continued to proceed well.
In summary, we believe we are well positioned to deliver a constant stream of therapeutic innovation from our labs and with our partners with that I'll now turn the call over to Peter.
Thanks, Chris.
Ended the first quarter with $143 $9 million in cash cash equivalents and marketable securities based on our current plans and projections. We continue to expect this will support our operations into the fourth quarter of 2022 caliber.
Chris Calabrese: More elaborate attempts aimed at functional cures, namely hematopoietic stem cell transplants and cell therapies often utilize harsh conditioning regimens, which have inherent safety risks that may limit when and how they will be utilized. We believe there's a great opportunity with FDX 6058, a projected oral once-daily therapy intended to treat the root cause of the disease and therefore potentially address both anemia and VOCs. People living with sickle cell disease and beta thalassemia represent a diverse global population in great need of an effective therapy that can be accessed and administered with ease.
Collaboration revenue for the first quarter of 2021 was $4 8 million compared.
Compared to zero point $8 million of collaboration revenue recognized during the first quarter of 2020.
Research and development expenses for the first quarter of 2021 were $16 3 million compared.
Compared to $14 5 million.
In the first quarter of 2020.
General and administrative expenses for the first quarter of 2021 were $5 5 million.
As compared to $5 1 million for the first quarter of 2020.
And our net loss was $17 million for the first quarter of 2021 compared to a net loss of $18 5 million for the first quarter of 2020.
With that I'll turn it back to Bryan Bryan.
Thanks, Peter we have a lot of work ahead as we continue to execute on our plans. We'll report complete low smack of my data from <unk> four at the Sshd IRC will have data from the phase one trial with SPX $60 58 in healthy volunteers midyear and anticipate initiating a trial in people with sickle cell disease by the end of the year.
Chris Calabrese: We believe that an oral small molecule that can meaningfully increase levels of fetal hemoglobin will not only provide the therapeutic benefit and convenience of oral administration but also the distribution at scale that this global population needs. Thus, we believe FTX6058 has the potential to be an impactful therapy. Recently, at the American Chemical Society meeting, we presented the medicinal chemistry strategy for FTF 6058, including some initial PK data from the single ascending dose, or SAD, portion of our Phase I trial on healthy volunteers. FTX6058 selectively upregulates fetal hemoglobin in a pancellular manner in both human cellular models and mouse models of sickle cell disease.
And we plan to bring forward <unk> from our product engine over the next 24 months.
In closing, we expect many significant advancements and clinical updates across our pipeline and I look forward to keeping you updated on our progress on the months ahead.
Operator, you May now open the line for questions.
As a reminder.
To ask a question you will need to press star one on your telephone to withdraw your question press the pound or hash key.
Your first question comes from Joseph Schwartz with SBB Leerink.
Hi, Good morning. This is Kelly on for Joe Schwartz.
Could you talk a bit about the FX HD patients enrolled and Readouts for where are they in their disease progression and is there anything you can share with us regarding baseline characteristics.
And maybe how many of those muscle biopsies would be considered high expressing.
Yes.
Yes. Thank you for the question I would say in terms of baseline characteristics, we will certainly be able to share more when we have the full dataset at the IRC.
Chris Calabrese: The treatment of human CD34 positive cells from healthy and sickle cell disease donors with FGX6058 resulted in fetal hemoglobin levels of up to approximately 30% of total hemoglobin with no observed effects on cell health. We believe this is a superior preclinical profile relative to the standard of care hydroxyurea, as well as other mechanisms that have been reported to induce fetal hemoglobin. I'm also pleased to report that our Composition of Matter Patent has been issued, giving us patent protection until 2040.
But at a high level from an inclusion criteria perspective from.
We tried to keep a relatively broad inclusion criteria. So there is a clinical severity score that ranges from one to five.
And we tried to <unk>.
Select patients that were between two and four so these are patients that are symptomatic.
And showing signs of the disease in their muscles are affected by the disease.
But they're not patients that are <unk>.
Completely wheelchair bound so we tried to be very well balanced in our inclusion criteria, but also have a broad range of patients that are actively being affected by the disease.
Makes sense, thanks, and maybe one more given this phenomenon at that high effect for expressing muscles are able to show the best reduction on.
Chris Calabrese: We continue to enroll in our Phase I SAD portion and recently began enrolling in the Multiple Ascending Dose, or MAD, portion of the trial. This Phase 1 study in healthy volunteers is evaluating safety, tolerability, pharmacokinetics, and target engagement of FTX6058. Based on our PK-PD modeling, we anticipate that the pharmacological doses will be in the 6 mg to 20 mg range, which is where we anticipate maximum levels of target engagement. Recent reports suggest that red blood cell half-life in healthy volunteers is approximately 30 days, which may limit the opportunity to observe effects on fetal hemoglobin in a 14-day MAD study.
What are your expectations for the primary endpoint in Chile really be focusing more on the pre specified sensitivity analysis.
Yes, I think we were certainly encouraged by the interim analysis with the results that we saw in the large reductions that we saw in the lowest map of my arm relative to placebo at the same time just as a reminder, the interim analysis only focused on.
On the primary endpoint for a subset of the patients. So it was only the first 29 patients and it was only the primary endpoint the benefit that we have in the full dataset is that we'll be able to see the biomarker data across all of the patients. Both on those mathematic placebo will be able to see the pre specified sensitivity analysis.
And Additionally, we will be able to observe all of the structural functional endpoints as well as patient reported outcomes. So as we go into this data as we mentioned we will certainly be encouraged if the interim analysis is recapitulated and we observe large reductions in the highest expressing muscle biopsies.
Ali will obviously be very encouraged if we identify trends of benefit across any of the secondary exploratory where patient reported outcomes and just as a reminder, any trends of benefit would truly be unprecedented as there are no therapeutic alternatives available for these patients today.
Chris Calabrese: However, we will be measuring fetal hemoglobin mRNA levels and the number of reticulocytes containing fetal hemoglobin in the MADD cohorts to monitor potential early signs of efficacy. We expect to report data from the SAD and MAD cohorts in mid-2021, which will also outline our future clinical plans, and we anticipate dosing the first cohort of people living with sickle cell disease by the end of this year
Great looking forward to again.
Thank you.
Your next question comes from Ted <unk> with Piper Sandler.
Great. Thank you from a fair amount of congrats on a on the progress.
Well net rebar carbonate.
On the positive data.
What does that look like and what could we expect growth potential stocks. Thank you.
Yes, Hi, Ted good morning.
I think we would emphasize we would certainly be very encouraged by.
Chris Calabrese: We intend to continue our dialogue with the FDA and other health authorities as the program progresses. As the data warrants, we plan to seek Orphan Drug, Fast Track, and Breakthrough Therapy designations. The opportunity to bring a new oral therapy to people living with sickle cell disease is a very exciting prospect, with the potential to be a significant advance in treatment in the years ahead.
Recapitulate, the interim analysis and seeing a reduction in the highest expressing muscle biopsies or observing these trends of efficacy in any of the secondary exploratory endpoints or patient reported outcomes.
So that's certainly what we'll be focused on his day to gets analyzed and on the other side of that we will certainly plan on engaging with the FDA as we've talked about in the past.
Unfortunate that there are no therapeutic available for these patients today there is no other industry sponsored programs in the clinic.
Chris Calabrese: Moving to our research efforts, we are very excited about the productivity of our proprietary target discovery platform, Fulcrum-C. We have several discovery programs that span our core focus areas of muscular, hematologic, and CNS disorders. Our unique approach is designed to identify starting points that are more technically enabled from a drug discovery perspective, as evidenced by the rapid progression from target ID to IND for our FSHD and sickle cell programs. For the targets currently being assessed, we continue to explore both internal medicinal chemistry campaigns as well as opportunities to enlicense advanced chemical matter. Our goal is to bring forward two INDs over the next 24 months. Fulcrum Seek has advanced significantly on many fronts.
And we will look forward to engaging with the agency I would also add we were very encouraged last year that the FDA held a patient focused drug development day.
For FX HD and they were able to engage directly with people living with Fsh D as well as advocacy as well as family members to truly understand the impact of the disease.
On on the patients who are affected by it.
So we found that very encouraging and we will look forward to interacting with the agency on the other side of data.
Great. Thank you very much from procuring from Treasury corporate Gardner.
Thanks debt.
Your next question comes from Matthew Harrison with Morgan Stanley.
Hi, Good morning, just cost us on from Moscow, two questions from US one on sickle cell disease. The other on Fsh Steve on.
Sickle cell disease from what we understand the prediction about the clinical doses.
Chris Calabrese: Multiple advances in next-generation sequencing and cell biology have allowed us to model complex human biology and generate data at unprecedented scales. The convergence with the knowledge of the root cause of genetically defined rare diseases creates the ability for Fulcrum to discover and develop potential treatments for rare diseases at a level of productivity that was historically not possible. Whether through the use of patient-derived cells or via the application of single-cell genomics to patient biopsies that reveal the dysregulated cell states and biological drivers of a given disease, the resulting high-fidelity assays offer a remarkable level of clinical relevance and translatability. From this sophisticated product engine, we use machine learning algorithms to analyze the large amounts of functional, morphological, and transcriptional data that are generated with great precision and at great scale.
Mostly driven by the preclinical AUC findings and based on your data that you recently presented the AUC and clearly cause about one five times higher non-GAAP.
So we are on that it gives vs has any impact.
Back on your expectations around <unk> or maximum target engagement doses for phase II.
So why don't I turn it over to Chris to speak to our dosing projections, yes. Thank you very much for the question.
So youre right we did see.
Greater exposure higher than expected exposure at the lower doses.
And that May mean in fact that we do see higher levels of target engagement at lower doses in the.
Healthy volunteer subjects than we initially modeled.
Either way, we will be encouraged if we see <unk>.
Terrific and levels of target engagement, either at lower doses or the doses that we initially models.
And again the intent of the study is to not only understand safety and Tolerability and target engagement, but also to look for signs of potential efficacy, but really the goal is to.
Chris Calabrese: The result is highly de-risked targets that are extensively enabled for further characterization. We believe Fulcrum-Seq is an important evolution in our product engine to identify targets informed by clinical biology and thus more predictive of desired therapeutic outcomes. Moreover, FulcrumSeq has supported the development of the clinical programs discussed today and has enabled our ongoing collaborations with Acceleron and Myocardia, which continue to proceed well. In summary, we believe we are well positioned to deliver a constant stream of therapeutic innovation from our laboratories and with our partners. With that, I'll now turn the call over to Peter. Thanks, Chris. We ended the first quarter with $143.9 million in cash, cash equivalents, and marketable securities.
Select the doses that we would intend to move into patients living with sickle cell disease.
Thank you very much and just one follow up have you kept you already selected the doses in phase III or not you haven't finalized that.
We have not finalized that and we are still very much in the midst of the healthy volunteer study.
Great. Thank you and one quick on Fsh fee are you planning to topline any data ahead of the Comcast or you would be presenting everything at the Congress. Thank you.
Yes, Hi, Cosmos I think are our plan right now is to present full data at the Fsh DIR C and that will be in in late June and we're excited to do that.
Okay. Thank you and we look forward to it.
Again, ladies and gentlemen, if you have a question at this time. Please press star and then the number one.
Your next question comes from <unk> Ahmad with Bank of America.
Peter Thompson: Based on our current plans and projections, we continue to expect this will support our operations into the fourth quarter of 2022. Collaboration revenue for the first quarter of 2021 was $4.8 million, compared to $0.8 million of collaboration revenue recognized during the first quarter of 2020. Research and development expenses for the first quarter of 2021 were $16.3 million, compared to $14.5 million in the first quarter of 2020. General and administrative expenses for the first quarter of 2021 were $5.5 million, as compared to $5.1 million for the first quarter of 2020.
Good morning, guys. Thanks, so much for taking my questions.
One question on sickle cell as you look forward to the development of this particular program.
How should we be thinking about what we should consider to be clinically meaningful data as it relates to efficacy.
There are there companies using obviously different mechanisms of action to treat patients.
But you would certainly have.
A dosing method of advantage and so how do you weigh that versus.
Efficacy expectation based on any kind of feedback that you've received from physicians. So far and then secondly, as we look to the rest of your pipeline. What is your longer term goal of how many programs you'd like to have in the clinic at any given time.
What might be some areas of focus for the company into cash.
From wise that you could potentially share. Thank you.
Yes. Thank you for the questions and I'll turn it over to Chris to speak to the first question on fetal hemoglobin induction.
Peter Thompson: And our net loss was $17 million for the first quarter of 2021 compared to a net loss of $18.5 million for the first quarter of 2020. With that, I'll turn it back to Brian.
One of the things, we're obviously very excited about with the approach.
Is that by inducing fetal hemoglobin, we have the ability obviously address both presentations of sickle cell disease, both anemia, driven disease, and boc driven disease, and we view that as being a very meaningful advantage and the other element. We can speak to is because of the data that is available from her.
Brian Stewart: Thanks, Peter. We have a lot of work ahead as we continue to execute on our plan. We'll report complete Los Mathemod data from Redux 4 at the FSHD IRC.
Patients that have hereditary persistence of fetal hemoglobin theres, a tremendous amount of literature and data that really supports the benefit of inducing fetal hemoglobin and the effect that that can have on symptoms of the disease, but I'll turn it over to Chris Yes. Thank you Brian.
Brian Stewart: We'll have data from the Phase 1 trial with FTX 6058 and Healthy Volunteers by mid-year, and we anticipate initiating a trial in people with sickle cell disease by the end of the year. And we plan to bring forward two INDs from our product engine over the next 24 months. In closing, we expect many significant advancements and clinical updates across our pipeline, and I look forward to keeping you updated on our progress in the months ahead.
Maybe ill.
We're still in the midst of designing our clinical trials.
<unk> living with sickle cell disease.
But to build upon what Bryan talked about again, we believe that up to 60 58 has the opportunity to be a best in class.
Therapy.
Oral once daily administration.
The therapeutic benefits of elevating fetal hemoglobin as Brian spoke to on really the distribution at scale that this global patient population needs.
Certainly we'll be looking for elevation of fetal hemoglobin.
But we also understand that.
The levels of fetal hemoglobin induction that we.
Observed pre clinically have the potential to provide benefit to patients all along the spectrum.
Brian Stewart: Operator, you may now open the line for questions. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound or hash key. Your first question comes from Joseph Schwartz on SVB Lyrinc.
That is you can elevate fetal hemoglobin to levels that would significantly reduce the risk of shortened lifespan that these patients unfortunately experience or elevate fetal hemoglobin significantly to reduce the risk of recurring events and we certainly have seen evidence pre clinically that we have the ability to elevate fetal hemoglobin levels to.
Are those that are associated with asymptomatic presentation. So we remain extremely excited about the molecule on its potential in the clinic.
Operator: Hi, good morning. This is Kelly Gurskis on behalf of Joe Schwartz. Could you tell us a bit about the FSHD patients you enrolled in Redux? Where are they in their disease progression? And is there anything you can share with us regarding baseline characteristics, such as maybe how many of those muscle biopsies would be considered high-expressing? Thanks. Yeah, thank you for the question. I would say, in terms of baseline characteristics, we'll certainly be able to share more when we have the full data set at the IRC. But at a high level, from an inclusion criteria perspective, we tried to keep a relatively broad inclusion criteria.
And then regarding your second question in terms of the productivity of the product engine.
As we stated.
We intend and our goal is to have two new <unk> over the course of the next 24 months and I think most importantly, as we think about fulcrum seek we're extremely enthusiastic about the advances that we've made so as we look at our two clinical programs to date those have come from our earlier version of the product engine were extreme.
We are excited about those but I'll turn it over to Chris and we can just speak to some of the advances in scale.
Our discovery efforts, which we believe should really facilitate not only these next two ind's, but a very rich clinical development pipeline in the years ahead.
Welcome to the advances we have made with fulcrum seek truly are astounding.
This allows us not only to double down on the areas, where we've had success already in muscle in hematology.
Brian Stewart: So there's a clinical severity score that ranges from one to five, and we tried to select patients that were between two and four. So these are patients that are symptomatic and showing signs of the disease, and their muscles are affected by the disease, but they're not patients that are completely wheelchair-bound.
And build upon the deep R&D expertise that we now have.
That allows us to frankly consider other franchise areas other therapeutic areas.
With the scale of fulcrum seek we can potentially screen on entire franchise in one shot.
So this allows us to readily consider new therapeutic area opportunities in house.
Well as through new partnerships in a much more integrated fashion so.
Brian Stewart: So we tried to be very well balanced in our inclusion criteria but also have a broad range of patients that are actively being affected by the disease. That makes sense, thanks. And maybe one more, given this phenomenon that the high effect for expressing muscles is able to show the best reduction, what are your expectations for the primary endpoint? And should we really be focusing more on the pre-specified sensitivity analysis? Yeah, I think we were certainly encouraged by the interim analysis with the results that we saw and the large reductions that we saw in the los mapumad arm relative to placebo.
Again, we remain very very excited about the opportunity that fulcrum presents for the future.
Okay. Thank you.
I'm showing no further questions at this time I would now like to turn the call back to Bryan Stuart.
Thank you. Thank you all for joining us today and for your support of Fulcrum have a great day.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
Goodbye.
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Pardon.
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Brian Stewart: At the same time, just as a reminder, the interim analysis only focused on the primary endpoint for a subset of patients. So it was only the first 29 patients, and it was only the primary endpoint. The benefit that we have in the full data set is that we'll be able to see the biomarker data across all of the patients, both on lesmaphimod and placebo; we'll be able to see the pre-specified sensitivity analysis.
On.
[music].
Brian Stewart: And additionally, we'll be able to observe all of the structural and functional endpoints, as well as patient-reported outcomes. So as we go into this data, as we mentioned, we'll certainly be encouraged if the interim analysis is recapitulated, and we observe large reductions in the highest expressing muscle biopsies. Additionally, we'll obviously be very encouraged if we identify trends of benefit across any of the secondary exploratory or patient-reported outcomes. And just as a reminder, any trends of benefit would truly be unprecedented as there are no therapeutic alternatives available for these patients today. Great; I'm looking forward to June. Thank you. Your next question comes from Ted Tenthoff with Piper Sandler.
Operator: Thank you so much. And congratulations on all the progress. So just thinking about Redux for a minute, assuming positive data, you know, what does that look like?
Operator: And what could we expect as the next potential steps? Thank you. Yeah, hi, Ted.
Brian Stewart: Good morning. I think we would certainly be very encouraged by either recapitulating the interim analysis and seeing a reduction in the highest-expressing muscle biopsies or observing these trends of efficacy in any of the secondary exploratory endpoints or patient-reported outcomes. So, that's certainly what we'll be focused on as data gets analyzed. And on the other side of that, we certainly plan on engaging with the FDA. As we've talked about in the past, it's unfortunate that there are no therapeutics available for these patients today. And there are no other industry-sponsored programs in the clinic.
Brian Stewart: And we'll look forward to engaging with the agency. I would also add that we were very encouraged last year that the FDA held a patient-focused drug development day for FSHD. And they were able to engage directly with people living with FSHD, as well as advocates, as well as family members, to truly understand the impact of the disease on the patients who are affected by it.
Brian Stewart: So we found that very encouraging, and we'll look forward to interacting with the agency on the other side of data. Great, thank you very much and for the patience really pulling for you guys. Thanks, guys. Your next question comes from Matthew Harrison with Morgan Stanley. Hi, good morning. This is Kostas on for Matthew.
Operator: Two questions from us. One on sickle cell disease and the other on FSHD. On sickle cell disease, from what we understand, the projections about the clinical doses were mostly driven by the preclinical AUC findings. And based on your data that you recently presented, the AUC in the clinic was about 1.5 times higher than your projection. So we are wondering if this has an impact on your expectations around efficacious or maximum target engagement doses for Phase 2.
Operator: So why don't I turn it over to Chris to speak to our dosing projections. Yeah, thank you very much for the question. So you're right, we did see greater exposure, higher than expected exposure at the lower doses.
Chris Calabrese: And that may mean, in fact, that we do see higher levels of target engagement at lower doses in healthy volunteer subjects than we initially modeled. Either way, we will be encouraged if we see significant levels of target engagement, either at lower doses or at the doses that we initially modeled. And again, the intent of the study is to not only understand safety and tolerability and target engagement but also to look for signs of potential efficacy.
Chris Calabrese: But really, the goal is to select the next doses that we would intend to move into patients living with sickle cell disease. Thank you very much. And just one follow-up question: have you already selected the doses in phase two, or not? You haven't finalized it yet?
Chris Calabrese: We have not finalized that, and we are still very much in the midst of the Healthy Volunteer study. Great, thank you. And one quick question on FSHD.
Operator: Are you planning to topline any data ahead of the Congress, or will you be presenting everything at the Congress? Thank you. Hi Costas, I think our plan right now is to present full data at the FSHB IRC, and that will be in late June, and we're excited to do that. Thank you, and we look forward to it. Again, ladies and gentlemen, if you have a question at this time, please press star and then the number one. Your next question comes from Tazin Ahmed with Bank of America.
[music].
Operator: Good morning, guys. Thanks so much for taking my questions. One question on Sickle Cell: as you look forward to the development of this particular program, how should we be thinking about what we should consider to be clinically meaningful data as it relates to efficacy? And then, secondly, as we look to the rest of your pipeline, what is your longer-term goal for how many programs you'd like to have in the clinic at any given time? What might be some areas of focus for the company indication-wise that you could potentially share? Thank you.
Brian Stewart: Yeah, thank you for the questions. And I'll turn it over to Chris to speak to the first question on fetal hemoglobin induction. I think one of the things we're obviously very excited about with the approach is that by inducing fetal hemoglobin, we have the ability to address both presentations of sickle cell disease, both anemia-driven disease and VOC-driven disease. And we view that as being a very meaningful advantage. And the other element we can speak to is, because of the data that is available from those patients that have hereditary persistence of fetal hemoglobin, there's a tremendous amount of literature and data that really support the benefit of inducing fetal hemoglobin and the effect that that can have on symptoms of the disease. But I'll turn it over to Chris.
Chris Calabrese: Yeah, thank you, Brian. We're still in the midst of designing our clinical trials for patients living with sickle cell disease. But to build upon what Brian talked about, again, we believe that FTX 6058 has the opportunity to be a best-in-class therapy, oral once-daily administration, the therapeutic benefits of elevating fetal hemoglobin, as Brian spoke about, and really the distribution and scale that this global patient population needs. Certainly, we'll be looking for elevation of hemoglobin, but we also understand that the levels of fetal hemoglobin induction that we have observed preclinically have the potential to provide benefit to patients all along the spectrum.
Chris Calabrese: That is, you can elevate fetal hemoglobin to levels that would significantly reduce the risk of shortened lifespan that these patients unfortunately experience, or you can raise fetal hemoglobin significantly to reduce the risk of recurring events. And we certainly have seen evidence preclinically that we have the ability to raise fetal hemoglobin levels for those that are associated with asymptomatic presentation. So we remain extremely excited about the molecule and its potential in the clinic
[music].
Brian Stewart: And then regarding your second question, in terms of the productivity of the product engine, I think, as we stated, we intend and our goal is to have two new INDs over the course of the next 24 months, and I think, most importantly, as we think about Fulcrum-Seq, we're extremely enthusiastic about the advances that we've made. So, as we look at our two clinical programs to date, those have come from our earlier version of the product engine.
Brian Stewart: We're extremely excited about those, but I'll turn it over to Chris, and we can just speak to some of the advances in scale in our discovery efforts, which we believe should really facilitate not only these next two INDs but a very rich clinical development pipeline in the years ahead.
Chris Calabrese: Fulcrum-Seq, the advances we have made with Fulcrum-Seq truly are astounding. This allows us not only to double down on the areas where we've had success already in muscle and hematology but also to build upon the deep R&D expertise that we now have but allows us to frankly consider other franchise areas, other therapeutic areas, and with the scale of Fulcrum-Seq, we can potentially screen an entire franchise in So, this allows us to readily consider new therapeutic area opportunities in-house, as well as through new partnerships, in a much more integrated fashion.
Chris Calabrese: So, again, we remain very, very excited about the opportunity that Fulcrum-Seq presents for the future. Okay, thank you. I'm showing no further questions at this time. I would now like to turn the call back to Brian Stewart. Thank you. Thank you all for joining us today and for your support of Fulcrum. Have a great day. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Goodbye.
Operator: Iain Fraser, Joseph Schwartz, Edward Tenthoff, Matthew Biegler, Robert Gould, Chris Calabrese, Iain Fraser, Alan Musso, Fulcrum Iain Fraser, Joseph Schwartz, Edward Tenthoff, Matthew Biegler, Robert Gould, Chris Calabrese, Iain Fraser, Alan Musso, Fulcrum [inaudible] Iain Fraser, Joseph Schwartz, Robert Gould, Chris Calabrese, Iain Fraser, Alan Musso, Robert Gould, Chris Calabrese, Iain Fraser, Robert Gould, Joseph Schwartz, Robert Gould, Joseph Schwartz, Iain Fraser, Robert Gould, Joseph Schwartz, Iain Fraser, Robert Gould, Iain Fraser, Joseph Schwartz, Edward Tenthoff, Matthew Biegler, Robert Gould, Chris Calabrese, Iain Fraser, Alexander Sapir, Alan Musso, Fulcrum, Iain Fraser, Joseph Schwartz, Robert Gould, Chris Calabrese, Iain Fraser, Alexander Sapir, Iain Fraser, Joseph Schwartz, Edward Tenthoff, Matthew Biegler, Robert Gould, Chris Calabrese, Iain Fraser, Alan Musso, Fulcrum, Chris Calabrese, Joseph Schwartz, Edward Tenthoff, Robert Gould, Chris Calabrese, Iain Fraser, Calabrese, Unknown Executive, Corinne Jenkins, Dae Ha, Joori Park, Iain Fraser, Robert Gould, Chris Calabrese, Unknown Executive, Corinne Jenkins, Dae Ha, Joori Park, Iain Fraser, Robert Gould, Chris [inaudible]