Q2 2020 Fulcrum Therapeutics Inc Earnings Call
A question and answer session.
Operator: I'd now like to turn the call over to Crispy Warwick, Director of Investor Relations and Corporate Communications at Fulcrum. Please proceed. Thank you, Anthony.
Oh, I don't like to turn the call over to Christy work director of Investor Relations and corporate Communications Fulcrum. Please proceed.
Thank you Anthony good morning, Thank you for joining US earlier today, we issued to press releases when outlining the results of our interim analysis, there was not muddied up a safety and another out linear recent corporate program and financial results for this every quarter 2020.
Unknown Executive: Good morning, and thank you for joining us. Earlier today, we issued two press releases, one outlining the results of our interim analysis for Lowe's, Maffimod, and FSHD, and another outlining our recent corporate progress and financial results for the second quarter of 2020. You can find both of these in the investor relations section of our website at fulcrumts.com.
You can find both of these any investor relations section of our website.
Yeah.
Please be reminded that remarks made during this call may contain forward looking statement, it's in the meaning of a private Securities Litigation Reform Act of 1985.
Unknown Executive: 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.
These may include statements about our future expectations plans clinical development timelines and financial projection.
Well. These forward looking statements represent our views as of today it should not be relied upon as representing RBC future remain upbeat. These statements in the future, but we're not taking on an obligation.
Unknown Executive: 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; Diego Cadavid, Senior Vice President of Clinical Development; Owen Wallace, Chief Scientific Officer; and Brian Stewart, Chief Operating Officer. Let me quickly run through this morning's agenda.
Please refer to our most recent filings with the Securities Exchange Commission for discussion of certain risks and uncertainties associated with it.
With me on today's call, a Robert Gould, President and Chief Executive Officer.
Yeah, it'll probably be senior Vice President clinical development, only Wallis Chief Scientific officer embraced <unk> Chief operating officer.
Let me quickly run through that brings agenda.
Robert J. Gould: Robert will begin the call with an overview of our recent progress. Diego will discuss the interim results of the Redux 4 trial in more detail, as well as our COVID program. Owen will provide updates on our Sickle Cell program with FulcrumSeq, and Brian will cover our financials. With that, it's my pleasure to turn the call over to Robert.
Robert will begin the call with an overview of our research program do you go interim results with a read outs for trials in more detail as older hoping for a brief.
We will provide updates on our sickle cell program was spoken see unbridled cover finance.
With that it's my pleasure to turn the call over to Robert Robert.
Robert J. Gould: Thank you, Christy. Good morning, everyone. And thank you for joining us today. I first want to thank our team who have been phenomenal through the past several months, as you'll see from all the progress we have to report on our call today. I'd like to begin with an overview of the interim analysis from our REDOX-4 trial in fascio-scapulohumeral muscular dystrophy, or FSHD. Today, we announced interim results from the first 29 subjects from our Phase 2b Redux 4 trial in FSHD. This interim analysis looked at the primary endpoint of DUX4-driven gene expression and did not look at any functional or exploratory endpoints. Los Macomod was generally well tolerated, with no drug-related serious adverse events reported.
Thank you Christine good morning, everyone. Thank you for joining us today I first want to thank our team has been phenomenal through the past several months, but you'll see from all of the progress we have to report on our call today.
I'd like to begin with an overview the interim analysis from a reduction for trial that she was scapula humeral muscular dystrophy or Fsh D.
Today, we announced the interim results from the first 29 subjects from our phase to be read outs for trial Annapolis HD.
This interim analysis looked at the primary endpoint of dogs for Durbin gene expression and did not look at any function more exploratory and.
Well, it's not Mod was generally well tolerated no drug related serious adverse events reported. This is the first day than ever generated from a placebo controlled clinical trial to evaluate the impact of a therapy on the root cause that affects each day.
Robert J. Gould: This is the first data ever generated from a placebo-controlled clinical trial to evaluate the impact of a therapy on the root cause of FSHD. While there was not a separation of the 16-week cutoff from placebo in analyses of the overall population, we were very encouraged to see that those muscle biopsies with the highest pre-treatment Duxford-driven gene expression in a pre-specified sensitivity analysis showed higher ductility. On the COVID front, we were very pleased to be able to announce a new program last quarter to develop a therapeutic to treat hospitalized patients with COVID-19 and very quickly got the green light from the FDA to initiate Phase 3 clinical trials. Top-line results from this pivotal study are projected to read out in the first quarter of 2021. We also continue to make progress with FTX6058, an oral small molecule therapeutic designed to induce the expression of fetal hemoglobin in select hemoglobin options.
Well there was lots of separation to 16, we've cut off from placebo in analyses of the overall population. We were very encouraged to see that those muscle biopsies with the highest pretreatment duxford driven gene expression.
We specified sensitivity analysis showed a large reduction.
On the Cobot front, we were very pleased to be able to announce a new program last quarter to develop a therapeutic to treat hospitalized patients with cobot 19, and very quickly got the green light from the FDA to initiate phase three clinical trial.
Topline results from this pivotal study are projected to read out in first quarter 20 to 21.
We also continued make progress would have T X 60, 58, an oral small molecule therapeutic design to induce expression fetal hemoglobin in select hemoglobinopathies.
Robert J. Gould: We plan to begin clinical development before the end of the year and look forward to being able to expand our pipeline efforts to address the unmet needs of sickle cell patients. On the research stage front, we continue to make progress building out FulcrumSeq, our proprietary database designed to identify small-module drug candidates, continuing research activities under our collaboration with Acceleron, and adding a new research collaboration with Myocardia focused on genetic drivers of cardiomyopathy. Finally, we completed a $68.5 million private placement, extending our cash runway into the first quarter of 2022.
We plan to begin clinical development before the end of the year and look forward to being able to expand our pipeline aperture to address the unmet needs of sickle cell patients.
On the research stage front, we continued to make progress building out fulcrum seek our proprietary database designed to identify small molecule drug candidates continuing research activities under our collaboration with Acceleron and adding a new research collaboration with myocardial.
Custom genetic drivers cardio my offices.
Finally, we completed the 68.5 million dollar private placement extending our cash runway into the first quarter of Twentytwenty true.
Robert J. Gould: It's been an inspiring few months at Fulcrum, and with so many anticipated key milestones in the months ahead, we're all really looking forward to being able to report on our progress along the way. So let's get into the Redux IV intro now. I'll provide some background before turning it over to Diego to discuss the data. 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've heard from so many patients and families, including many who participated in the Patient-Focused Drug Development Day hosted at the FDA, just how debilitating this disease can be. 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.
It's been uninspiring few months in fulcrum with so many anticipated key milestones in the months ahead, we're all really looking forward to being able to reported in our progress along the way so let's dig into the redux for interim analysis I'll provide some background before turning it over to Diego to discuss the data.
As a reminder, fs HD is a rare progressive and disabling disease characterized by severe muscular degeneration that occurs skeletal muscle is replaced by facts.
We've heard from so many patients and families, including many who participated in the patient focused drug development day posted at the FDA just how debilitating this disease can be.
Unlike other diseases that can be characterized by the lack of a gene fs HD is characterized by the after an expression of the gene ducs for the root cause a bit disease.
Robert J. Gould: DUX4 expression results in apoptosis, muscle death, and deterioration. We at Fulcrum discovered that LossMathMod, a selective P38 MAP kinase inhibitor, reduced DUX4-driven gene expression in pre-clinical studies. We estimate there are approximately 16,000 to 38,000 patients in the U.S. and similar incidents worldwide, leading to projections of 300,000 to 780,000 patients globally. There are currently no approved drugs for FSHD, and we're advancing the only known industry-sponsored clinical trial evaluating a potential treatment. Our own evidence, as well as independent evidence, suggests we do not have to turn DUX4 off completely to provide benefit. There is a spectrum of DUX4 expression and FSHD presentation that suggests that even an incremental reduction may be beneficial to patients. Thus, we believe, as do independent researchers, that any reduction in DUX4-driven gene expression has the potential to benefit patients.
For expression results in a pop doses muscle death from deterioration, we had fulcrum discovered that lost matrimony selective P 38 map kinase inhibitor reduce ducs for driven gene expression in preclinical studies.
We estimate there are approximately 16 to 38000 patients, who U.S. and similar incidents worldwide, leading to projections of 300 to 780000 patients globally.
There are currently no approved drugs for efforts HD, we're advancing the only known industry sponsored clinical trial evaluating a potential tree.
Our own evidence as well as independent evidence suggests we do not have to turn ducs were off completely to provide benefit there's a spectrum of dogs for expression NFS HD presentation that suggested even an incremental reduction may be beneficial to patients. Thus, we believe as two independent researchers that any reduction in Duxford Durbin gene.
Expression has the potential for benefit to patients.
As far as expressed to Caustically and the muscles of fsh treat patients an expression levels can vary widely from both independent researchers as well as our own for perjury studies, we know that efforts HD patients continue to express stocks for overtime is that disease progresses throughout the body.
What this means that said, where we cannot define people with fsh. She is high and low expressing patients expression levels varied by region of muscle within each patient.
We're encouraged with the data reported today that showed a promising reduction in the ducks for driven genes in the muscles expressing the highest stocks for given jeans at baseline.
Robert J. Gould: DUX4 is expressed stochastically in the muscles of FSHD patients, and expression levels can vary widely. From both independent researchers, as well as our own preliminary studies, we know that FSHD patients continue to express DUX4 over time as the disease progresses throughout the body. What this means is that while we cannot define people with FSHD as high and low-expressing patients, expression levels vary by region of muscle within each patient.
I'd like to thank the efforts HD patients and those participating this trial for their commitment through the cobot 19, you're not for them.
Now I'll turn it over to Diego to go through the interim analysis in more detail Diego.
Thank you Robert.
Please looks 40, so our international phase to be double blind placebo controlled trial blows my Piedmont in 80 subjects, we genetically confirmed Memphis H D.
The primary endpoint over the trial is the change from baseline Indoximod, leaving gene expression in affected skillet than most.
Robert J. Gould: We're encouraged by the data reported today that showed a promising reduction in the DUX4-driven genes in the muscles expressing the highest DUX4-driven genes at baseline. I'd like to thank the FSHD patients and those participating in this trial for their commitment during the COVID-19 epidemic. I'd now turn it over to Diego to go through the interim analysis in more detail.
In the wake up call. These 19, we extended the we look for China from 24 to 48 weeks with an open label extension to follow.
Subjects received a muscle biopsy at baseline.
Either 16, or let's say six weeks.
Do you to list of caustic nature of doctors want expression on why Rancho but also an expression between muscles. We've seen any individual patient we utilized in my guided biopsy to identify those small somebody else most likely to exposed looks for.
Diego Cadavid: Thank you, Robert. Redux 4 is our international phase 2b double-blind placebo-controlled trial of los mapimod in 80 subjects with genetically confirmed FSHD. The primary endpoint of the trial is the change from baseline in doxoid-driven gene expression in affected skeletal muscle. In the wake of COVID-19, we extended the Redux 4 trial from 24 to 48 weeks, with an open-label extension to follow. Subjects receive a muscle biopsy at baseline and either 16 or 36 weeks. Due to the stochastic nature of dog sore expression and wide range of dog sore expression between muscles within an individual patient, we utilized MRI-guided biopsy to identify those muscle areas most likely to express dog sores.
American accurately identify affected muscles.
He cannot determine the level of cultural agreement gene expression, we've seen an individual patients muscle.
To address this Charlie sheen identifying muscle biopsies, we tie base I know swords, even gene expression in order to quantify a reduction we pre specified a sensitivity analyses of the defendant ranges self expression.
We saw something to him analyses highlighted.
A greater than a south sinful defunding.
Between pretreatment muscle biopsies, we hire them the older adults towards even gene expression.
This confirms what we say preclinical research what all this is safety subjects do like some lines you split clinically had high base and also do in gene expression and we upset every though shiny none of them.
Diego Cadavid: MRI can accurately identify affected muscle, but it cannot determine the level of doxoid-driven gene expression within an individual patient's muscle. To address this challenge in identifying muscle biopsies with high baseline doses for driven gene expression in order to quantify a reduction, we pre-specified a sensitivity analysis of the different ranges of expression. Results from the interim analysis highlighted a greater than a thousandfold difference between pre-treatment muscle biopsies with higher and lower doxoid-driven gene expression. This confirms what we say in preclinical research where all the FSHD subjects derive cell lines used preclinically at high baseline doses for driven gene expression, and we observe a reduction in all of them.
That's how we sold the 1004 to be financing don't sort of even gene expression absurd between biopsies.
We believe that observing a reduction may require cup trade muscle biopsies, we hired a baseline expression.
As shown on slide 13.
Muscle biopsies with higher base I provide greater dynamic range to up says a reduction compared to most from biopsies with nowhere baseline.
Using their pre specified since he pvt analysis based on earnings from our wide open label study.
They tell him analyses have avoided the treatment effect on docs for three when gene expression.
So biopsies, we the highest space I think station they hire ranges were comparable to live ranges in the cell line. She is speaking again.
[noise] interim analysis of the first 29 randomized subjects assess changes seem basing docs was even gene expression in subjects, who had the 16 week biopsy.
Diego Cadavid: As a result of the 1,000-fold difference in doxoid-driven gene expression observed between biopsies, we believe that observing a reduction may require capturing muscle biopsies with higher baseline expression. Ashonim Slai 13, Muscle biopsies with higher baseline expression provide greater dynamic range to observe a reduction compared to muscle biopsies with lower baseline expression. Using a pre-specified sensitivity analysis based on learnings from our open-label study, the interim analysis evaluated the treatment effect on Dox4-driven gene expression in muscle biopsies with the highest baseline expression. The higher ranges were comparable to the ranges in the cell lines used preclinically.
The study remains blinded.
And we have not looked at individual subject data at the start.
Do you seem ternium analyses wants so some not powered for the statistical significance.
I'm pretty especially for high sensitivity generally she's was intuitive to evaluate treatment effects on muscle biopsies, we that range. So based on those floods even gene expression.
Human Slide 15, you can see from the demographic seen maintaining my analysis that subjects were well balanced these doing this might be more than placebo.
In this might be more treated subjects.
I mean, maybe on drug concentration was greater than a hands in a more lean muscle.
I'm not drug related essays way reported.
On slide 16.
Yeah, no showing they look to data on our lean at scale.
I would choose how PCR data is traditionally the slate.
You can see that to date applause.
Diego Cadavid: The interim analysis of the first 29 randomized subjects assesses changes in baseline dogs for driven gene expression in subjects who had their 16-week biopsy. The study remains blinded, and we have not looked at individual subject data at this time. This interim analysis was also not of powerful statistical significance.
Only muscle biopsies on the left.
And ice expressing biopsy some that right.
[noise] here, we see the results when I look tend to scale.
Given the greater than a thousand sort of different in seemed Doxil agreement gene expression between biopsies we.
We saw no separation from let's see when that totally randomize population assessed as seen on the list.
Underlying results shown absurdly low slightly more treatment in the high six Tracy muscle biopsies.
Diego Cadavid: A pre-specified sensitivity analysis was included to evaluate treatment effects on muscle biopsies with a range of baseline doses for driven gene expression. Here on slide 15, you can see from the demographics in the interim analysis that subjects were well balanced between Luzma Pimota and placebo. In-Laws Mapping-Mode-Treated-Subjects, mean median drug concentration was greater than 100 nanomolar in muscle, and non-drug related essays were reported. On slide 16, we are now showing the Log2 data on a linear scale, which is how PCR data is traditionally displayed. Here you can see the two data plots, with all muscle biopsies on the left and highest-expressing biopsies on the right. Here we see the results on a log 10 scale.
38 fold reduction in expression in the low smart be more three then on.
Those who sat Fi 0.4 fold reduction in placebo.
The highest expressing muscle biopsies represent the top acquired time, all biopsies assessed for baseline docs ones, even gene expression.
Due to covert 19, we amended we look forward from 24 to 48 weeks.
Which gave us the opportunity to enter the 60 week interim analyses on the initial 29 randomized subjects.
We are encouraged by these results suggest those might be more maybe with using those funds even gene expression the root cause so puts us ht.
Why we did not see a separation from placebo when that total population.
The 16 week cut off date I'd high six but she muscle biopsies is consistent we they nishal data from the open label study.
Diego Cadavid: Given the greater-than-a-thousand-fold difference in doxo-driven gene expression between biopsy, we saw no separation from placebo in the total randomized population assessed as seen on the left, and a large reduction observed with LossMap Remote Treatment in the highest expressing muscle biopsy, a 38-fold reduction in expression in the loss mapping mode treated arm, versus a 5.4 fall reduction in placebo. The highest-expressing muscle biopsies represent the top quartile of biopsies assessed for baseline doxoid-driven gene expression. Due to COVID-19, we amended Redux 4 from 24 to 48 weeks, which gave us the opportunity to introduce a 16-week interim analysis on the initial 29 randomized subjects. We are encouraged by these results that suggest loss-mapping mode may be reducing toxoid-driven gene expression, the root cause of FSHD.
We believe that though let's just say she patients have mostly hi, those funds even gene expression and then those might be more has the potential tool set up NFI tool if its HCT patients.
Do you think 30 monopoly she's had shown as seen on certainly shows data on that change from baseline in effect didn't want to select 16 weeks of treatment.
About a third of the total 80 patients enrolled in the results for trial.
We are working now to advance say without import them next step seem these program.
We continue to collect additional data from the wheels for trial.
We look forward to seeing topline results in Q1, 2021, and the full results by Q2 2021.
These will include not only that full data set on there is also driving gene expression.
I'd also like whole body about I evaluation.
Change from baseline in skeletal muscle volume.
Starting fixation I'm sad replacement.
Diego Cadavid: While we did not see a separation from placebo in the total population at the 16-week cutoff, the data in the highest-expressing muscle biopsies are consistent with the initial data from the open-label study. We believe that all FSHD patients have muscles with high toxoid-driven gene expression and that Losma Pimot has the potential to offer a benefit to all FSHD patients. This interim analysis has shown us important initial data on the change from baseline in affected muscles at 16 weeks of treatment in about a third of the total 80 patients enrolled in the Redux 4 trial. We are working now to advance several important next steps in this program. We will continue to collect additional data from the RIDOSOL trial, and we look forward to seeing top-line results in Q1 2021 and the full results by Q2 2021. This will include not only the full data set on the doxo-driven gene expression but also the whole body MRI evaluation. Change from baseline in skeletonal Muscle Volume, Fat Infiltration, and Fat Replacement, and several clinical outcome assessments, including clinician-reported, patient-reported, and assessments of muscle function and strength.
And similar clinical outcome assessments, including clean Michel reported patient reported an assessment of muscle function and the strength.
We also look forward to the continued analyses of the single sent that open label study, which also includes some analysis of change from baseline in the skeletal muscle memory biomarker and seven that clinical outcome assessments over the longer term treatment.
To help us better than this time, the potential benefit of most might be modine Memphis HD.
We will start to X. I mean changes from baseline by Q PCR in muscle biopsies in Twentyfold, all that a gene transcripts that may show important process of muscle health, including muscle regeneration sad that we'll see shown information on them so that.
Now, let me briefly walk through our Colby program, which we are also very excited about.
We also are developing those might be more esa treatment for called lead 19 patients.
We believe that they need additional pizza 38, you said compelling approach to address multiple components of the disease and that lows might be more and has competitive advantages, including a unique mechanism of action or administration.
Potential for using combination therapy.
Extensive safety has told me that levy.
We believe the rapid initiation of these people without charge reflects the strength of the data supporting this research and the pricing need for effective set up these definitely gives them more really de associated with called 19.
Diego Cadavid: We also look forward to the continued analysis of the single-centered open-label study, which also includes an analysis of change from baseline in skeletal muscle MRI biomarkers and several clinical outcome assessments over longer-term treatment to help us better understand the potential benefit of the loss mapping model in FSHD. We will start to examine changes from baseline by QPCR in muscle biopsies of 24 other gene transcripts that measure important processes of muscle health, including muscle regeneration, fat deposition, inflammation, and cell death. Now, let me briefly walk through our COVID program, which we are also very excited about. We also are developing los mapimoras, a treatment for COVID-19 patients. We believe that inhibition of P38 is a compelling approach to address multiple components of the disease.
The last week, they see Todd we'd be conducted on approximately 21 site CB United States, Mexico in South America.
And we Mtc paid dosing this those patient in the coming days.
These values designed to us as the safety and efficacy.
Some 15 milligrams twice the they owed on those some of those might be more compared to placebo for 14 days on top of standard of care in approximately 400 patients hospitalized weve always 19.
I'm not to recycle probation two critical illness based on older age on elevated systemic inflammation.
The primary endpoint is that proportional patients who progressed to death or respiratory failure by day 28.
Topline data is expected to we reported in the first quarter 2021.
Diego Cadavid: And that Los Mapi Mode has competitive advantages, including a unique mechanism of action, oral administration, potential for use in combination therapy, and extensive safety and tolerability. We believe the rapid initiation of this pivotal trial reflects the strength of the data supporting this research and the pressing need for effective therapies that reduce the morbidity associated with COVID-19. The Lozbitt Phase III trial will be conducted at approximately 21 sites in the United States, Mexico, and South America, and we anticipate enrollment of the first patient in the coming days. This trial is designed to assess the safety and efficacy of a 15 milligrams twice per day oral dose of los mapimod compared to placebo for 14 days on top of standard of care in approximately 400 patients hospitalized with COVID-19 and at risk of progression to critical illness based on older age and elevated systemic inflammation. The primary endpoint is the proportion of patients who progress to death or respiratory failure by day 28. Top-line data is expected to be reported in the first quarter of 2021. I'll now turn the call over to Owen.
I'll now turn the call lower tooling.
Thanks, Diego our Hemoglobinopathies program has continued to advance towards clinical development and we plan to initiate a phase one trial in sickle cell disease by the end of the year.
Our approach is focused on the upregulation of fetal hemoglobin, which could be beneficial for both sickle cell disease and beta thalassemia.
Clinical candidate FCX, 60, 58, and been profile broadly in preclinical in vitro and Nvvault models sickle cell disease, and we've seen robust elevation of hps concentrations that we believe will be readily achieved in humans based on the pharmacokinetic profile of the compound.
We've had an abstract accepted for oral presentation at the 14th annual sickle cell disease research and educational Symposium next month, we filed our non provisional patent application.
We also continued to make progress on our research and early clinical portfolio.
We have advance our work on fulcrum seat I proprietary connectivity map database and integrates the identification of double targets and signaling pathways in human cell models that we can pigeon late genetically defined diseases.
Owen Wallace: Thanks, Diego. Our hemoglobinopathy program has continued to advance towards clinical development, and we plan to initiate our phase one trial in sickle cell disease by the end of the year. Our approach has focused on the upregulation of fetal hemoglobin, which could be beneficial for both sickle cell disease and beta thalassemia.
This platform meld cellular modeling hi, contact Txi content technologies, pharmacogenomics and machine learning.
We generate high dimensional data using barneys seek and high content damaging to create a database of profiles from my proprietary chemical probe library and functional genomics and complex sell models.
Owen Wallace: Our clinical candidate, FTX6058, has been profiled broadly in preclinical, in vitro, and in vivo models of sickle cell disease, and we've seen robust elevation of HPF at concentrations that we believe will be readily achieved in humans based on the pharmacokinetic profile of the compound. We've had an abstract acceptance for oral presentation at the 14th Annual Sickle Cell Disease Research and Educational Symposium next month, and we filed We also continue to make progress on our research and early clinical portfolio. We have advanced our work on FulcrumSeq, our proprietary connectivity map database that integrates the identification of druggable targets and signaling pathways in human cell models that recapitulate genetically defined disease patterns. This platform melds cellular modeling, high-content technologies, pharmacogenomics, and machine learning. We generate high-dimensional data using RNA-seq and high-content imaging to create a database of profiles from our proprietary chemical probe library and functional genomics in complex cell models.
Using a scalable cloud based data architecture, and AI and machine learning tools to classify chemical probes and targets, we select those that modulating gene expression to treat and down will cause of genetically defined diseases.
Collaboration with Acceleron continues to advance.
We recently announced a research and discovery collaboration with Myokardia.
Under the agreement Myokardia will have access to full conns unique proprietary target discovery engine to identify therapies and controlled the expression of genes that are known to be the underlying drivers of genetic cardio my off of these.
Group will be eligible to receive research reimbursement development and commercial milestone payments of approximately $300 million for the first product and up to $150 million for additional products as well as tiered royalties.
These collaborations highlight the broad applicability about product engine to discover and develop new treatments and genetically defined rare diseases with high unmet need.
With that I'll now turn the call over to Brian for an update on our financial results for the quarter, Brian. Thanks, Ellen we entered the second quarter of 2020 with $131.7 million in cash cash equivalent in marketable securities not including the $12.5 billion, we receive from Myokardia since the close of the core.
Owen Wallace: Using a scalable cloud-based data architecture and AI and machine learning tools to classify the chemical probes and targets, we select those that modulate gene expression to treat the known root cause of genetically defined diseases. Our collaboration with Acceleron continues to advance, and we recently announced a research and discovery collaboration with Myocardia. Under the agreement, Myocardia will have access to Fulcrum's unique proprietary target discovery engine to identify therapies that control the expression of genes that are known to be the underlying drivers of genetic cardiomyopathy. Fulcrum will be eligible to receive research reimbursement, development, and commercial milestone payments of approximately 300 million dollars for the first product and up to 150 million dollars for additional products, as well as tiered royalties.
Based on our current operating plan and projections. We believe this will support our operations into the first quarter 2022, allowing us to advance wasn't Appleton HD reach topline data in the low speed trial and bring FCX 60, 58 into the clinic, while continuing to invest in our discovery state effort.
Research and development expenses for the quarter ended June Thirtyth, 2020 were $12.8 million compared to $10.9 million in the second quarter 2019.
Increase of $1.9 million was primarily due to increased personnel related costs to support growth of footprint research and development organization as well decreased costs related to the advanced and it was mathematic for the treatment of Fs HD.
Brian Stewart: These collaborations highlight the broad applicability of our product engine to discover and develop new treatments for genetically defined rare diseases with high unmet needs. And with that, I'll now turn the call over to Brian for an update on our financial results for the quarter. Brian?
General and administrative expenses were $5.1 million for the second quarter 2020, as compared to $2.6 million for the second quarter 2018, the increase of $2.5 million is primarily due to increased cost associated with operating as a public company as well increased personnel related costs to support the growth of our organization are now.
Brian Stewart: Thanks, Owen. We have entered the second quarter. 2020 with $131.7 million in cash, cash equivalents, and marketable securities, not including the $12.5 million we received from Myocardia since the close of. Based on our current operating plan and projections, we believe this will support our operations into the first quarter of 2022, allowing us to advance close MAP-MOD and FSHD, reach top-line data in the lowest bid trial, and bring FTX 6058 into the clinic while continuing The increase of $1.9 million was primarily due to increased personnel-related costs to support the growth of Fulcrum's research and development organization, as well as increased costs related to the advancement of Mappamon for the treatment of FFHD. General and administrative expenses were $5.1 million for the second quarter of 2020, as compared to $2.6 million for the second quarter of 2019.
Loss of $50.7 million for the second quarter 2020, as compared to a net loss of $13.2 million per second quarter 2008.
Overall, we continue to expect several upcoming catalysts, we expect to report topline data from our phase three most of the trial and Koby 19 in the first quarter 2021.
We expect to report topline data from read outs for in the first quarter 2021, with full data, including exploratory and clinical outcome assessment and the second quarter 2021.
We also plan to initiate a phase one trial.
Yes, 60, 58 in sickle cell disease, and disclose the biochemical target by the end of year and we'll continue to advance our discovery.
Programs from a product and while making progress with our partners at both Acceleron and Myokardia. We're very excited about the work ahead as we continue to execute on our plan and look forward to keeping you updated as our progress continues in the months ahead.
Operator, you May now open the line for questions.
[noise]. That's a reminder, that's a question when you to press forward one I wonder if all the phone to withdraw your question press the pound Keith.
Your first question comes from a line of Joseph Schwartz from past few Leerink Airlines now open.
Thanks, so much and congrats on all the progress.
Was wondering if you could talk a little bit about what the effects on drug and placebo for the patients and the other courthouse look like and what do you see driving the overall affected that patients and the highest ducs for core tile.
And then as a follow up are you implementing any in just adjustments are enhancements to redux for now to learn from this finding.
And can you can you make any adjustments.
Brian Stewart: The increase of $2.5 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. Our net loss was $15.7 million for the second quarter of 2020, as compared to a net loss of $13.2 million for the second quarter of 2019. Overall, we continue to expect several upcoming catalysts. We expect to report top-line data from our Phase 3 low-spin trial in COVID-19 in the first quarter of 2021. We expect to report top-line data from Redux 4 in the first quarter of 2021, with full data, including exploratory and clinical outcome assessments, in the second quarter of 2021. We also plan to initiate the Phase I trial with FTX6058 in sickle cell disease and disclose the biochemical target by the end of the year. We will continue to advance our discovery.
Given you've already obtained pretreatment biopsies from all of the patients.
Thanks, Joe This is Robert.
As as we showed in the overall analysis of the total population there was no separation from placebo.
We were encouraged by the highest cortiles showing to 38 full production and cost Batman treat patients, but the overall effect not separate from placebo I think your second question was.
Are we going to make adjustments to the redux for trop now we're excited about the results we've seen to date, we're continuing to.
Look forward to collecting the MRI data in the clinical outcome.
Assessment, we will be we will be generating additional data on the muscle health gene.
Including markers of muscle grows inflammation a pop toast.
Yes, and and those additional analyses, we think give us insight into that continued progression of UBS.
It's effective drug on the disease. We also have 36 week biopsies that have not yet been assay.
Or assessed.
As we mentioned Weve just these 29 patients only represent about a third of the patients that are in the overall 80 patient trial. So we'll be collecting the rest of the data as we proceed.
Thank you.
And our next question Paul for long enough Deacon Hall from BT RG. Your line is now open.
Brian Stewart: Programs from our product engine while making progress with our partners at both Acceleron and Myocardium. We're very excited about the work ahead as we continue to execute on our plan and look forward to keeping you updated as our progress continues in 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 1 on your telephone. To withdraw your question, press the pound key. Your first question comes from a line by Joseph Schwartz from SV Lierink. Your line is now open.
Great. Thanks, very much for taking my questions and good morning to all of you So Robert or maybe even Derek Diego wanted to dig into the data you presented a little bit.
To the extent possible I was wondering if he can talk about the methodology of or I guess, what gene or genes are behind this delta C.T. as you add aside from the Q PCR I mean, we've seen some several candidate genes from the literature as well as from your previous publications or presentations at.
And for example is this one gene like Mbd three L. Two or as these CAD four or is it a composite summation score that a that that's being presented and I guess just related to that is they're very ability. If you want to look at individual genes like do you actually see differential effects.
Robert J. Gould: Thanks so much, and congrats on all the progress. I was wondering if you could talk a little bit about what the effects of the drug and placebo for the patients in the other quartiles look like, and what you see driving the overall effect. Is it patients in the highest DUX4 quartile? And then, as a follow-up, are you implementing any adjustments or enhancements to REDUX4 now to learn from this finding, and can you make any adjustments? Given that you've already obtained pre-treatment biopsies from all of the patients. Thanks, Joe. This is Robert.
I've lost map amod, depending on what GGR look at and I've got a follow up thank you.
Yeah, I don't think too for the question. This is diego. So these primary endpoint USIS upon the sale of.
And docs or a regulated jeans, it's very similar to that one we reported on a in 2020.
Robert J. Gould: As we showed in the overall analysis of the total population, there was no separation from placebo. We were encouraged by the highest quartiles, showing a 38-fold reduction in BOSMAP mod treatment patients, but the overall effect did not separate from placebo. I think your second question was:
Ladies and was that result, so far really a careful selection process that began with whats known in the lead to chiller and then advancing its what we have said being said align Sunday muscle biopsies.
Robert J. Gould: Are we going to make adjustments to the Redux 4 trial? Now, we're excited about the results we've seen to date. We're continuing to...
So we ended up with small panel of genes each one hadid sown validate it Q Pcr assay.
In addition, eating tilts three housekeeping genes that are optimized for human skeletal muscle and that is how we do the ice they'll TFC d.
Unknown Executive: I look forward to collecting the MRI data and the clinical outcome assessment. We will be generating additional data on the multiple health genes. Including markers of muscle growth, inflammation, apoptosis, and those additional analyses we think give us insight into the continued progression of... Dispective Drug on the disease. We also have 36 week biopsies that have not yet been assayed or assessed. As we mentioned, the 29 patients only represent about a third of the patients that are in the overall 80 patient trial, so we'll be collecting the rest of the data as we proceed. And your next question, from the line of Dae Geun Ha from BTIG. Your line is now open. Great, thanks very much for taking our questions, and good morning to all of you.
We Don how boxes to the individual gene says five of these seem paid him analyses is just on the only look using that they called panel, but as part of next steps those opportunities when cone.
Great. Thank you Diego and then on the data again, just wondering this highest a core tile.
What's the time it I guess on a relative basis. So I guess, if we look forward to say all of end of 880 patient data. Once you collect them given that I guess progression of gene expression seems to be fairly stagnant over time.
What is the cut off going to be or is that going to be a moving target as you collect the remaining 61, where a 51 patient data.
Diego Cadavid: So Robert, or maybe even Diego, I wanted to dig into the data you presented a little bit. To the extent possible, I was wondering if you could talk about the methodology of, or I guess what gene or genes are behind this Delta C-T as you assayed from the qPCR. I mean, we've seen several candidate genes from the literature as well as from your previous publications or presentations at AAN, for example. Is this one gene, like MBD3L2 or Z-scan4, or is it a composite summation score that's being presented? And I guess just related to that, is there variability? If you were to look at individual genes, like do you actually see differential effects of lismap and mod depending on what gene you look at? And I've got a follow-up. Thank you. Yeah, no, thank you for the question. This is Diego.
Yeah. So you are correct. These quite a ton was defined on all baseline.
So just from that 29 subjects as we accumulate more data remember this is really the first clinical trial ever doing these we will learn more about what a.
Could be up obtain shaped cut off for idec sold we believe that every patient on they lean muscle at least at some point has very high dose for an EPS encouraging that we have seen that results showing those biopsies.
These Steve sensitivity analyses was pre specified because as we have seen you know what pretty patent, though these studies and so many biopsy something they open label study that these distributional Stokes 40 sub says we use or am I guided buyouts.
Diego Cadavid: So this primary endpoint uses a panel of dogs for regulated genes. It's very similar to the one we reported at AAN 2020. This was the result of a really careful selection process that began with what's known in the literature and then advanced it through what we observed in cell lines and muscle biopsies. So we ended up with a small panel of genes. Each one has its own validated qPCR assay. In addition, it includes three housekeeping genes that are optimized for human skeletal muscle. And that is how we derive the Delta CT. We don't have access to the individual genes as part of this interim analysis. It's just an early look using the whole panel.
Okay and then last question for me is do you have any hypothesis around widen less map amod would be able to induce.
Hi expression of Ducs for driven James.
Yes, I think there was some correction data, it's now dive eating juices expression. What these infinium analysis is showing India, India biopsies, we think ice expression you said results show relative to placebo and we have some idea of what they make any small perhaps you could be.
But there's really no EXINI proof.
Okay. Thanks for taking my questions.
And your next question, California, 15, Amod from Bank of America underlying snow.
Diego Cadavid: But as part of the next steps, those opportunities will come. Great. Thank you, Diego. And then on the data again, just wondering if this highest quartile was determined, I guess, on a relative basis. So, I guess if we look forward to, say, all of N of 80 patient data once you collect them, given that, I guess, progression of gene expression seems to be fairly stagnant over time, what is the cutoff going to be, or is that going to be a moving target as you collect the remaining 51 patient data? Yeah, so you are correct.
Hi, Good morning, guys. Thanks, so much for taking my question.
Can you maybe tell us in a real world setting what proportion of the what you define as high expressing piece and make up the overall fsh, Steve population you have anything for that.
Thanks disease.
We don't actually think there's high and low expressing patients.
All of the Fsh G patients are expressing.
Muscle are expressed in flux foreign causing the FX HD.
MRI, what we are doing is optimizing our biopsy sample to the higher expressing muscles with within that patients.
Diego Cadavid: This quarter was defined on all baseline biopsies from the 29 subjects. As we accumulate more data, remember, this is really the first clinical trial ever to do this. We will learn more about what could be a potential cutoff for hydroxyl. We believe that every patient and every muscle, at least at some point, has a very high dose of hydroxyl. And it's encouraging that we have seen a reduction in those biopsies. This sensitivity analysis was pre-specified because, as we have seen in our preparatory studies and in some early biopsies obtaining the open-label study, that this distribution of DOX4 is observed when you do MRI-guided biopsy. Okay, and the last question for me is, do you have any hypothesis around why Lasmappamod would be able to induce the expression of DUX4-Driven Genes?
There are higher than Richie score the more expression of Ducksworth driven gene expression. There is an more affected the patient sorry, the Richie score.
The clinical severity score and choose to score these patients.
And that's an important concept, it's not that the there are high mode specifications, but rather there are high and low expressing biopsies as we do these needle biopsies.
Okay, so taking that into account.
You know for the rest of the two thirds of the patients for what we await a biopsy result, if we get a similar trends on expression. That's observed here. The biopsies do you think Sta would accept assessments of the stocks for expression just from the.
Diego Cadavid: Yeah, I think there's a correction there. It's not that it induces expression. What this interim analysis is showing in the biopsies with the highest expression is a reduction relative to placebo, and we have some idea of what the mechanism of action could be. But there's really no definite proof.
Perhaps the is that did have at the high expression, meaning do you think that this this in any way changes the potential of trying to apply let's say if the faulty this that looks similar to that and you have this pre specified analysis do you think it changes your view on fts receptivity to being able to apply.
Diego Cadavid: Okay, thanks for taking our questions. And your next question, call from the line is Kazeem Ahmad from Bank of America. Your line is now open.
Unknown Executive: Hi, good morning, guys. Thanks so much for taking my questions. Can you maybe tell us, in a real-world setting, what proportion of these, what you define as high-expressing patients, make up the overall FSHD population, if you have any sense for that? Thanks, Susie. We don't actually think there's high and low expressing patience.
The status that rather than needing to do a phase three.
Yeah, we think that all the pay fs HD patients or have the potential to benefit.
From the treatment with loss map mine because of the significant unmet need and because of that common root cause of the b dubs for driving disease. As we proceed through the rest of the fall and complete the study we're going to be looking at the totality of the data that we have to continue the conversations with the FDA that we have just to remind.
Unknown Executive: We all have the FSHG patients are expressing; the muscle is expressing ducts for and causing the FSHD. By MRI, what we are doing is optimizing our biopsy sample to the higher expressing muscles within the patient. The higher the Ritchie score, the more expression of DUX4-driven gene expression there is, and the more effective the patients are. The Ritchie score is a clinical severity score that's used to score these patients. And that's an important concept.
You with Duxford driven gene expression is the primary endpoint, we have important other assessments, including.
MRI look looking at muscle volume fat infiltration as well as a number of clinical assessments of route reachable workspace timed up and go and very rich clinical trial looking at at the potential benefit of loss fat model across the entire patient population across the entire presentation of the disease.
Okay and maybe the last question I know you haven't publicly stated Youre your powering assumption for the study but.
Unknown Executive: It's not that there are high and low-expressing patients, but rather, there are high and low-expressing biopsies as we do these needle biopsies. Okay, so taking that into account, you know, for the rest of the two-thirds of the patients for which we await the biopsy results, if we get a similar trend in expression that's observed through the biopsies, do you think FDA would accept assessments of the Sux4 expression just from the biopsies that did have the high expression, meaning, do you think that this in any way changes the potential of trying to apply this, let' We think that all FSHD patients have the potential to benefit from treatment with LossMapMod because of the significant unmet need and because of the common root cause of Duxford driving the disease.
Is there any thought about potentially increasing the number of patients in that study are you comfortable with what you have.
Okay.
Yeah, I know, we believe our regionally we had a powerful 66 subjects. We increased the sample to go to 18 randomized one to one that we don't have a plan to increase enrollment. We believe these numbers of patients ease Sofia sand and also in addition, we enrolled 14 patients.
Let's say paid study they open label study at a single side, we chatted all ongoing on draw on day, we provide at least on data.
We also have they open label extension of results for so all that patients some plus he will eventually we draw along into low sloppy mode and that gives us an additional opportunity to explore what treatment effects those might be multi screen.
Okay. Thank you.
And your next question thoughtful line of Penn.
That's helpful from Piper Sandler Your line is now open.
Great. Thank you very much money never thanks for taking my question.
Diego Cadavid: As we proceed through the rest of the fall and complete the study, we're going to be looking at the totality of the data that we have to continue the conversations with the FDA that we have begun. Just to remind you, Duxford-driven gene expressions, the primary endpoint; we have important other assessments, including MRI looking at muscle volume and fat infiltrate, as well as a number of clinical assessments around reachable workspace, timed up and go, and a very rich clinical trial looking at the potential benefit of LossMapMod across the entire patient population and across the entire presentation of the disease. Okay, and maybe the last question, I know you haven't publicly stated your powering assumption for the study, but is there any thought about potentially increasing the number of patients in this study, or are you comfortable with what you have?
Congrats on the preliminary findings definitely encouraging them I'm looking for more data I'm wondering just kind of thinking about this with respect to.
Tissue penetration them and by the distribution again appreciating that associates, the us more muscle focus, whereas Cobra. It is probably more and more tissue poke focus but have you picoway is from what you saw in this first [laughter] group of patients to the ongoing.
Phase three study just in terms of obviously target engagement, but also.
Distribution, thanks very much.
Yes, Thanks Ted.
As part of this interim analysis, we did measured less Batman muscle concentrations.
In the.
Patients that received last night from on and that was greater than 100, nanomolar concentration than Weve seen previously so very very great consistency with our prior results.
Diego Cadavid: Yeah, no; we believe originally we had a plan for 66 subjects. We increased the sample to go to 80, randomized one to one, and we don't have a plan to increase the enrollment. We believe this number of patients is sufficient. And also, in addition, we enrolled 14 patients in a separate study, an open-label study at a single site, which are all ongoing on the drug, and they will provide additional data. We also have the open label extension of Redux 4.
We had reported.
Additionally, in the preclinical studies, we show we showed good.
Bio distribution of loss Batman.
In in the preclinical species. So we don't think there there is a read through.
In terms of the mechanisms.
She has K had previously done a whole body auto radiography assessment again showing good.
Diego Cadavid: So all the patients on placebo eventually will roll on into LOS MAPI mode, and that gives us an additional opportunity to explore what treatment effects LOS MAPI mode is having. Okay, thank you. And your next question, call from the line is Ted Tenthoff from Piper Sandler. Your line is now open.
Exposure throughout all the all the tissues of the body.
As as we had shown previously in our earlier studies, we were seeing a good target inhibition good reduction.
In in targeting gauge Min Hsp 27 phosphorylation I in our phase one studies and so we think that that the.
Unknown Executive: Great, thank you very much, everyone, and thanks for taking my question. Congratulations on the preliminary findings. Definitely encouraging, and I'm looking forward to more data. I'm wondering, just kind of thinking about this with respect to Tissue Penetration and Biodistribution.
MOSFET trial, the trial last Batman and commitment patients.
As a good good chance of having great exposure based and all the data we generated to date.
Great. Thank you very very much looking toward more data.
And again, if you like you asked a question first started in the number one on your telephone keypad.
Our next question comfortable line of Joseph Schwartz from SVB Leerink. Your line is now open.
Unknown Executive: Again, appreciating that FSHD is more muscle focused, whereas COVID is probably more lung tissue focused. But any takeaways from what you saw in this first group of patients to the ongoing phase three study, just in terms of obviously target engagement, but also distribution? Thanks so very much.
Hi, again, thanks for taking my follow up.
I wanted to follow up on something that was raised earlier regarding the increases in ducs for gene expression that were detected cross so many placebo as well as drug treated patients and and get your thoughts and.
What do you make of this you think this is actually happening or is it best attributed to assay variability, particularly at low levels of Duxford gene expression.
Unknown Executive: Yeah, thanks, Ted. As part of this interim analysis, we did measure los matemad muscle concentrations in the patients that received Los Maquemon, and that was greater than the 100 nanomolar concentration that we'd seen previously. So, very, very great consistency with our prior results that we had reported. Additionally, in preclinical studies, we showed good biodistribution of Los Maquemon in preclinical species.
And what does the concordance between the amount of Ducs for gene expression as quantified by and MRI and muscle fat infiltration and stir positivity.
Relative to biopsies.
And is there any way to determine how much ducs for gene expression.
Might be.
Inpatients muscles with less invasive means.
Unknown Executive: So we don't think there is a read-through. In terms of the mechanisms, GSK had previously done a whole body autoradiography assessment, again showing good exposure throughout all the tissues of the body. As we had shown previously in our earlier studies, we were seeing good target inhibition, a good reduction in target engagement, HSP27 phosphorylation, in our phase one studies. And so we think that the MOSFET trial, the trial of Los Matamon and COVID patients has a good, good chance of having great exposure based on all the data we've generated today. Great
Having seen this data.
The be interesting get your your thoughts now that that we have additional information.
Hi, Joe This is Alan.
Take the first part and then maybe let Diego comments as well.
We don't think there is a meaningful increase and certainly there is no separation between loss map of mods and placebo and I think it gets to this point around the dynamic range between high expressing biopsies and low expressing biopsies, we see more than a thousand.
Unknown Executive: Thank you very, very much. I'm looking forward to more data. And again, if you would like to ask a question, press star then number one on your telephone keypad. Our next question comes from the line of Joseph Schwartz from SVB Lyrinc. Your line is now open.
Bose added change.
In expression and I think when you're in that very low range. There's just natural variability and a likelihood that you might see a nominal increase but I don't think it's a meaningful increase I think were much more encouraged by the data with high expression, because we think we got.
Unknown Executive: Hi, again, thanks for taking my follow-up. I wanted to follow up on something that was raised earlier regarding the increases in DUX4 gene expression that were detected across so many placebo as well as drug-treated patients and get your thoughts. What do you make of this?
Sufficient dynamic range at that point to actually measure. This 38 fold reduction that we observed which is a lot greater than than placebo.
And then I'll address the am I right, because that's a really important question on them.
Unknown Executive: Do you think this is actually happening, or is it best attributed to assay variability, particularly at low levels of Dux4 gene expression? And what is the concordance between the amount of Dux4 gene expression as quantified by MRI and muscle fat infiltration and STIR positivity relative to biopsies? And is there any way to determine how much Duxford gene expression there is?
So there's really no other way to mesh adults for activity on adults holds even gene expression, except molecularly taking piece you out. Some also so so we as meet its on our ability to sample.
If you want us sampled multiple times.
We chose to little neither biopsies, we check that surely small pieces, so because of bad limitation from the design of the study. We incorporated these caused body quantitative came out I. Unlike needle biopsies, we have a large color that's almost every.
Owen Wallace: might be in patients' muscles with less invasive means. Having seen this data, it would be interesting to get your thoughts now that we have additional information.
Owen Wallace: I'll take the first part and then maybe let Diego comment as well. We don't think there is a meaningful increase. Certainly, there's no separation between loss mafomad and placebo. And I think it gets to this point around the dynamic range between high-expressing biopsies and low-expressing biopsies. We see more than a thousandfold change in expression.
Affected muscle.
And we really add encouraged the fact that we extended the placebo controlled to 48 weeks, it's now giving us a much longer wrong way to look at these process does fall is clearly link to limit I Echo TVT loss of muscle.
Increase of fat.
And as they Marsalisly placed by the fact that east loss of function and these have really be I called that connecting the results that's very clear from the research.
Owen Wallace: And I think when you're in that very low range, there's just natural variability and a likelihood that you might see a nominal increase, but I don't think it's a meaningful increase. I think we're much more encouraged by the data with high expression because we think we've got a sufficient dynamic range at that point to actually measure this 38-fold reduction that we observed, which is a lot greater than on placebo. And then I'll address the MRI, because that's a really important question. So there's really no other way to measure dogs for activity or dogs for driven gene expression except molecularly, taking tissue out of a muscle. So we are limited in our ability to sample.
Thank you.
And your next question costs for one if Matthew Harrison from <unk> Morgan Stanley. Your line is now open.
Hey, Thanks, Good morning, Thanks for taking my question.
I guess, maybe two for me first one can you just talk a little bit more specifically about why if you think you have.
The right amount of drug levels in the muscle are you not seeing.
Ducs for reduction broadly across all patients that are used are you, suggesting that there's a group of patients that just don't have enough docs for expression for you to lower it and I guess, it's not clear to me maybe you could just touch on that a little bit and I've a follow up.
Yes. This is at Olin again, Matt at Yeah, We think that when were in these lower levels there are.
No relatively few transcript that are actually being amplified by the Q PCR and there is variability from my biopsy to biopsy.
Diego Cadavid: And if you want to sample multiple times, we chose to do needle biopsies, which are actually small pieces. So because of that limitation from the design of the study, we incorporated this whole body quantitative MRI. And like needle biopsies, we have a large coverage of almost every affected muscle. And we really are encouraged by the fact that we extended the placebo control to 48 weeks.
So we think that it's just very difficult to detect a robust reduction when you're already down at a very low level. So that's why we've sat really focused on these high expressing EM initial muscle biopsies, because we can see.
Diego Cadavid: It's now giving us a much longer runway to look at this process. DOGS4 is clearly linked to MRI activity, loss of muscle, and increase in fat. And as the muscle is replaced by fat, there is loss of function and disability. I call that connecting the dots.
I robust dynamic range there.
And.
We actually identified this initially from our analysis on the open label study, where we demonstrated at the same phenomenon that winds that patients that an initial high level at baseline there was an ability to look for a reduction, whereas it was much more and very.
Diego Cadavid: That's very clear from the literature. And your next question, across the line is Matthew Harrison from Morgan Stanley. Your line is now open. Hey, thanks. Good morning. Thanks for taking the question. I guess maybe two for me.
Stability in the low expressing and muscle biopsies.
Okay, and then and then maybe could you just comment on your view then in need in these patients are there other.
Unknown Executive: First one, can you just talk a little bit more specifically about why, if you think you have the right amount of drug levels in the muscle, are you not seeing ducts for reduction broadly across all patients? Are you suggesting that there's a group of patients that just don't have enough ducts for expression for you to lower it? I guess it's not clear to me. Maybe you could just touch on that a little bit, and then I have a follow-up. Again, this is Owen again, Matt.
Gene expressions or other biomarkers that you could look at that to see or get some conviction whether or not.
Modulating diseases with patients that have low levels that it's going to actually impact motor function or other asked me to other clinically measurable aspects of the disease.
Yes, and this is that when again, so again just to reiterate we think that all patients.
Owen Wallace: Yeah, we think that when we're at these lower levels, there are, you know, relatively few transcripts that are actually being amplified by qPCR. And there's variability from biopsy to biopsy. So, we think that it's just very difficult to detect a robust reduction when you're already down at a very low level, so that's why we've really focused on these high-expressing initial muscle biopsies, because we can see a robust dynamic range there. [inaudible] We actually identified this initially from our analysis of the open label study, where we demonstrated the same phenomenon that with patients at an initial high level at baseline, there was an ability to look for a reduction, whereas there was much more variability in the low-expressing muscle biopsies.
Both high and low expressing muscles.
As their disease progressive.
And we think that and in addition to at reducing Ducs for which is dependent on and again. The biopsying. There's also an ability. If you ask two to look at more general markers of muscle health. So as a part of our Q PCR panel we.
Actually looked across multiple other jeans, and they have not yet being analyzed but and we think that those genes will actually offer potentially a great at chance to look at and things like my Agenuss is in inflammation and ended the Genesis is.
Owen Wallace: Okay, and then maybe could you just comment on your view then in these patients? Are there other gene expressions or other biomarkers that you could look at to see or get some conviction whether or not, treating the disease with patients that have low levels is going to actually impact motor function or other clinically measurable aspects of the disease? Yes, this is Owen again.
Thats right. So we have 24 additional mouth muscle health transcript that that can be evaluated that I think will give us that debt at picture that you're asking about.
Okay. Thanks very much.
And there are no further questions at this time I'll turn the call over to Robert Gould.
So I want to thank you all for joining us today and for your support a fulcrum you hope you in your families. All stay healthy in say since we continue to explore the exciting opportunities. We have ahead of us at fulcrum. Thank you.
Owen Wallace: So again, just to reiterate, we think that, you know, all patients have both high and low expressing muscles as their disease progresses. And we think that, in addition to reducing duct spore, which is dependent on, you know, the biopsy, there's also an ability, as you asked, to look at more general markers of muscle health. So as a part of our qPCR panel, we actually looked across multiple other genes, and they have not yet been analyzed. But we think that those genes will actually offer a potentially great chance to look at things like myogenesis, inflammation, adipogenesis, etc.
Ladies and gentlemen, this concludes todays conference call. Thank you for participating you may now disconnect.
[noise] Goodbye.
[music].
Owen Wallace: So we have 24 additional muscle health transcripts that can be evaluated that I think will give us that picture that you're asking about. Okay, thanks very much. And there are no further questions at this time. I'll turn the call over to Robert Gould. So I want to thank you all for joining us today and for your support of Fulcrum. We hope you and your families all stay healthy and safe as we continue to explore the exciting opportunities we have ahead of us at Fulcrum. Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Goodbye.
Robert J. Gould: Iain Fraser, Robert Gould, Chris Calabrese, Dae Ha, Joori Park, Iain Fraser, Alexander Sapir, Alan Musso, Fulcrum Iain Fraser, Robert Gould, Chris Calabrese, Iain Fraser, Alexander Sapir, Alan Musso, Fulcrum