Q1 2020 Earnings Call
[music].
Good morning, and welcome to welcome Therapeutics first quarter 2020 conference call.
Currently all participants are listen only mode.
I will be a question answer session at the end of this call Avenue at the turn called a richer Tracy Ward.
Director of Investor Relations and corporate communications.
Please proceed.
Excuse me Dream.
And welcome to the children Therapeutics conference call to discuss our first quarter 2020 financial results and recent corporate highlights.
Earlier today, we issued a press release outlining our recent program.
For those of you don't have a copy you can access it in the Investor Relations section of our website <unk> 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 of 1995.
These may include statements about our future expectations and planned clinical development timeline and financial projection.
Well. These forward looking statements represent our views as of today, you should not be relied upon as representing our views in the future.
I see these statements in the future, but we're not taking on an obligation to do so.
Please refer to our most recent filings with the Securities and Exchange Commission for discussion of certain risks and uncertainties associated with our business.
With me on today's call, a Robert Gould, President and Chief Executive Officer.
Go kind of be senior Vice president of critical development.
I wouldn't Wallis Chief Scientific officer, and bring Stewart Chief operating officer.
Let me quickly run through this morning's agenda.
Robert will begin the call with an overview of our recent progress.
Yeah, Bill will discuss our 60 program.
We will discuss their sickle cell program in research efforts and Brian will cover our financials before opening the call for Tonight.
With that it's my pleasure to turn the called oversee Robert Robert.
Thank you Christine good morning, everyone and thank you for joining us today.
I first want to thank the healthcare workers investigators and caregivers for their courage and passion as they continue to sports. So many during the challenges of cobot 19.
Our Hearts go watch every one of its been impacted.
To all of our friends colleagues in the patient communities. We serve we hope you are keeping safe and healthy.
Focus mission and purpose remain unchanged as we work to discover and develop therapeutics to treat genetically defined diseases by addressing the root cause.
I'm proud of how our employees have risen that evolving challenges of the cold at 19 and damage.
I'd like to begin by highlighting some of our recent updates and accomplishments.
Today, we announced an amendment to read outs for our phase Twob trial with last month in patients with Fassio scapula, humeral muscular dystrophy or Fsh D.
Diego will go over the amendment more detail.
These changes will extend the patient treatment from the original trial design and we believe will provide a more robust data set all addressing the challenges presented by cobot 19.
Early in the quarter, we received orphan drug designation from U.S. food and drug administration for less my margin NFS HD.
I'm pleased to report that we have also received orphan designation from the European Commission for last night from Mark for the treatment of FSC cheap.
Like in the U.S. orphan designation is granted by the European Commission to drugs that are intended for the treatment prevention or diagnosis of life threatening are chronically debilitating rare diseases.
We're extremely pleased to have received this designation further supporting the advancement last month's FSC cheap program.
We recently presented dose dependent target engagement data skeletal muscle come or phase, one trial, which last night Amman during a virtual clinical trials session muscular Dystrophy Association meeting.
We continue to make progress with Stx 60, 58, an oral small molecule therapeutic designed to induce expression of fetal hemoglobin in select Hemoglobinopathies, you'll hear about her sickle cell program promote one later in the call.
We also continued to make progress on our early research stage activities, including building on fulcrum see our proprietary product engine designed to identify drug targets programs and clinical development candidates in a broad range of genetically defined diseases, and we initiated research activity under our collaboration with.
Acceleron.
I'd now like to during the call over to Diego for an update on the Fsh Deprogram Diego.
Thanks Robert.
A reminder, it's a C.G. so progressive disease characterized by you see view muscular degeneration.
Cause us scale it doesn't most somebody's replaced by subs.
We estimate that approximately 16 to say the 8000 patients in the U.S.
See me know into this one way.
<unk> current keen no approved drugs for instance, H D.
Only on advancing the only known industry sponsored clinical trial evaluating a potential treatment.
Unlike other diseases that can be characterized by their lack of a gene.
It's it's HD is characterized by day barron's expression nobody gene docs for the root cause severe disease.
We absolutely come discovered that deals might be monks selected P.T.D.A. <unk> kinase inhibitor raise used expression of dose floating preclinical studies. We therefore believe deals might be more represents a flotation no instead of beauty collection for it to say she patients.
I would only have meetings as well it seemed dependent everything's suggests that we do not have to turn don't sort of computing to provide benefit.
That is have spectrum of don't sort expression on FX HD presentation that suggest that even any kind of maintain resumption may be beneficial to patients.
Those we believe I still independent researchers that any reduction in those two or three been gene expression has the potential benefit to patients.
He looks 40, so many international another phase to be.
I will blind placebo controlled trial abuse lumpy molding patience, we genetically confirmed fsh d.
We completed enrollment of 80 patients at the end of February which exceeded the 66, we had a reaching that you plan.
The primary endpoint over the trial used the change from baseline in those four dreaming gene expression in affected skeletal muscle.
We also competed and won many know why phase two single site open label trial, which has been impacted by colleagues 19 now we are considering next steps.
40, cronies dedicated to maintaining their highest standouts in patient education safety.
In the planning and execution of our clinical research programs. The safety Autoweb Genie cuts out do you see funds under healthcare providers as well as they say they feel today that we call lags remains paramount.
The wakeup call, we think Dean I know middle tier one clinical trial sites, most phones triad related activities.
We quickly implemented plans to limit the potential disruptions well what is just say she program.
No aging and these I know that results for into that a pretreatment biopsies.
Followed by a second biopsy had weak 16 of the 24 week treatment periods.
Following the 24 week trial patients had the opportunity to roll into an open label extension.
I have two they probably 19 pandemic sweaters folks 80 patients completed 24 weeks of treatment, including their week 16 biopsy on all enrolled in the open label extension.
The call we'd 19 pandemic continue our team in collaboration we don't want investigate those extended that results for child from 24 to 48 weeks.
These allows the approximately 67 subjects currently continuing into try out to receive all biopsy as either a week 16 or under the amended protocol and we've said he seeks an after completing the 48 week dream MPT and rolling into the open label extension.
To summarize and reserves for trial has been extended Flynn from 24 to 48 weeks with an open label extension to funnel.
Patients we receive on muscle biopsy out either 16 or 36 weeks. These extension we applied to the approximately 67 patients still enrolling the trial 112 have already completed on having rolling in two they open label extension.
As part of them all the integration to live trial. We will also conduct an interim analyses approximately 25 subjects, who have completed those 16 week by ops.
We anticipate shedding data from these infinium analyses of subjects Doxil Dreaming gene expression on signature in this third quarter and over this year.
We expect to report top line data on the primary endpoint in the first quarter of 2021.
Extensions from 24 to 48 weeks or someone else allows for a long good assessment in a placebo control design of the skeletal muscle amount I secondary endpoint under various exploratory clinical endpoints such as reach I will work space.
This HD times up on gold muscle function measures patient reported outcomes.
From both independent researchers as well that's somewhat over it but at least studies. We know there's also gene signature is stable over the timing this population.
We believe that they're longer we were able to treat patients the greater good potential Ben if people most must be most may have on the root cause somebody sees.
We strongly believe these changes to that result sort of study I think that based incentives on their patient community I'm for a wide their best opportunities what Bob do you think most on development Airport as we launch was raised the challenges presented by call we'd 19.
These changes have these signs when they wouldn't patients on investigators to continue participation in reserves for and will allow us to collect essential data to support continued dialogue with regulators.
I'll now turn the call over to our win a win.
Thanks Diego.
Fulcrum, we pursue targeted indications what we believe we can develop safe and effective small molecules therapies to rebalance gene expression.
And our work across various indications we consistently aim to address the root causes of disease to increase the potential efficacy of these treatments and more broadly transform the way these diseases are being treated.
In spite of the challenges posed by Cobot 19, we've continued to make progress on our research and early clinical portfolio as an essential business. We continue lab operations, albeit on a more limited spaces.
As the results we continue to advance the collaboration with Acceleron as well as our internal portfolio.
We have also advanced our work on fulcrum seek a proprietary product engine design to identify drug targets programs and clinical development candidates in a broad range of genetically defined diseases.
By combining high throughput ornate sequencing cellular imaging data on large scale machine learning, we're monitoring more than 10000 molecular and cellular features generated by the small molecule probe and CRISPR perturbed budget libraries.
Understanding there. Thanks on gene expression is fundamental to our therapeutic strategy to modulate the genetic root cause of disease.
Welcome seek is not only the core of our target identification strategy. It also provides us with a unique understanding of how cellular function is altered in human disease.
I'd like to thank our employees, who have continued to work diligently to the cobot 19 crisis to advance our research programs, especially those who are coming into the lab working under social distancing and enhanced health and safety guidelines.
[noise] Likewise, our Hemoglobinopathies program has continued to advance towards the IMD de filing our approach has focused on the upregulation of fetal hemoglobin, which could be beneficial for both sickle cell disease and beta thalassemia.
By increasing levels of H.B.S. to compensate for the mutated hemoglobin in sickle cell patients. We believe that we can develop and deliver a potent effective and selective therapy for patients.
This therapeutic strategy is supported by human genetics, and pharmacology data were increasing levels of H.B.S. have been shown to be associated with improved prognosis and outcomes, suggesting that H.B.S., maybe a surrogate endpoint in future clinical trials.
We're very pleased with our recent progress our clinical candidates FCX 60, 58 has been profile broadly in preclinical in vitro and in vivo models of sickle cell disease, and we've seen robust elevation and eight of H.B. AF and drug concentrations that we believe will be readily achieved in humans based on pharma.
Kinetic profiling of the come back.
We've had an abstract accepted to the for oral presentation at the 14th annual sickle cell disease research and educational symposium scheduled for September of this year.
We have also filed our non provisional patent application and we've completed our I and the enabling studies and toxicology work with Stx and 60 58, we plan to submit the I envy in sickle cell disease in the second half of Twentytwenty and initiate a phase one trial by the end of the year.
With that I'll now turn the call over to Brian for an update on our financial results for the quarter Brian.
Thanks, selling in these unprecedented times fulcrum is committed to making a difference for patients with EPS HD in select hemoglobinopathies, such a sickle cell disease.
We are proceeding with a great sense of urgency to bring these potentially transformative therapies to patients. We ended the first quarter 2020 was $81.2 million in cash cash equivalents in marketable securities based in our current operating plan and projections. We believe this will support our operations into the third quarter 2021, allowing us to advance.
Lets mathematics office HD.
He bring Stx 60, 58 into the clinic, while continuing to invest in our discovery stage efforts.
Research and development expenses for the quarter ended March 30, Onest 2020 were $14.5 million compared to $34.6 million into first quarter 2019.
Included in that $34.6 million was $25.6 million.
Im onetime cost associated with the issuance of series B convertible preferred stock under the company's license agreement with GSK for the rights to lets not them up.
Excluding these one time costs the increase of $5.5 million was primarily due to increased costs related to the advancement of both map amount for the treatment of FX HD as will decrease personnel related costs to support the growth a full crumbs research and development organization.
General and administrative expenses for the first quarter or 2020 were $5.1 million as compared to $2.6 million for the first quarter 2019. This increase was primarily due to increased personnel related costs to support the growth of our organization as well as increased cost associated with operating as a public company.
Overall, we remain on determine our mission and continue to expect several upcoming catalysts.
We'll report the interim analysis from Redux for the third quarter of this year will initiate the phase one trial with Stx 60, 58 in sickle cell disease and disclose the biochemical drug target by the end of year and we'll continue to advance our discovery programs from our product engine, while making progress with our partners and accelerate.
We're excited about the work ahead and we continue as we continued executing our plans and we look forward to keeping you updated our progress in the months ahead.
Operator, you May now open the line for questions.
[noise] [noise] [noise] [noise], operator, we're now ready for questions.
[noise].
Operator.
Ladies and gentlemen to ask the question at this time you need to fresh start didn't wine Touchstone telephone if your question that's an accurate.
Need to remove he suffered a hugely expensive yeah.
Sam that'll be compared to Q1 last thing.
And our first question comes from Matthew Harrison with Morgan Stanley You May proceed.
He is that cost us on toward Masekela. Thank you for taking down question on just a couple of questions from my side or the first one these where the you guys expect to lose any positive given that you will only have 25 subjects in the.
Yes. The team did he might not be ceased do you think goodwill heavy enough power to see a signal there or do you expect the data only get to be detection to show you an improvement or not.
Yes. Thank you for that question do you see I will kind of in.
The sample size scale fady subject fees, we really be Sep has appropriate power to answer that question at the end over the prior Ptwenty five subjects. We believe we gave us any shallow part you need to know cut that Diana and help us pretty bad then on make some energy insights.
Two phase three planning.
Okay. Thank you and a follow up question on when do you need to recruit additional subjects or do you believe you'll have a all decide to acute need at this point.
We have completed recruitment we believe we have on this subject Sweeney.
Okay, and then finally.
I was wondering where that in the second part when you expect all the subjects to happen biopsy.
Steve not 56 weeks given that that might be secondly, wait for the pandemic. <unk> addition, I lab and second wave will fall in fixed parents.
How set then you out of you can have all the subject complete the second biopsy 76 weeks and whether that is any actions you're taking to mitigate piece at east coast or losing some patients that again. Thank you.
Yes, we when we aim amended the protocol, we carefully can see there exactly what you're referring to so we'd be able to some windows time when those around the 36 week.
On sites, a hot 60 bps were less patients. So right now we anticipate that we get did that either that week 16 or not we say these seeks regardless.
Okay. Thank you very much.
And our next question comes on sports.
Thank you May proceed.
Good question would be can you talk about how you arrived at a doubling in duration for the Redux protocol with respect to the clinical endpoints.
Well patience and redux for still be evaluated at 24 weeks and how many patients are hitting this time point in the second half of this year when it seems like social distancing like relax and then when would most patients be hitting the 48 week time coin.
Have you know have you done analysis there to consider that you know this isn't your best interest to.
Given how one however, this pandemic.
Might evolve with respect to much different waves based on where you were enrolling these patients.
Yes, they results for triad completed enrollment in about six months between August of last year on February of this year does for their patients are moving across all they'd be seats are way up here, though six months.
A but we decided to extend this study.
I know you should note 24 weeks, because we believe and based on what is happening on what we expect to happen we colleagues 19.
These we gave flexibility for their patients to collect data.
Gross a much longer period, where we expect the clinics to we are hoping if anything told me thinking.
So overall, we believe that even if some 24.
24 week be seats out amazed patients would come back later on as you know I should say, Steve said slowly progressive disease, we are not counting acuity Vince so as long as we are collecting data over time, we believe we'll be able to answer the efficacy questions.
Especially many sites had a C opioid pain, perhaps of the pandemic he's not affecting every site.
Mhm and are you able to bring patients in and just stride Paula irons, a little bit warmer and in this period, we seem to be entering.
As we speak now could you bring patients and for an evaluation can you talk about.
Was it just at 24 and 48 weeks that.
The clinical assessments are being performed or you have any ability to.
Speaking on some additional outsized without making pro additional protocol. It doesn't sound like you know require you to take a elfa hits.
Yes. This amendment bill flexibility so all that we see somebody reaching that protocol over 24 weeks out all payments I set out Oh pain patients had called mean.
On the amendment provides additional opportunities said, we'd say C suite 48, we'd extended windows. So we really aim.
Even opportunities to capture as much that out regardless of what happens with colleagues 19, we very fortunate that not only the sites by the patients had very committed.
And that's reflecting the hype.
Subject retention, we have on the tire.
Mhm, that's very helpful. Thank you and then.
Have you been able to garner and insights to date from the open label trial. It sounds like you suggested its been impacted from covert 19, and I heard your evaluating the next steps there so.
Why is definitely impacted more it sounds then redux for can you provide any any color on that front.
Yes. They open label studies have single site. So you don't have these opportunity, we having really looks for when we have many sites under 41 region.
Toppings to be where these side easy is heavily affected of closing actually be larger.
Thats side, you've seen the Netherlands.
We have always costs here that I learned entirely they'd be guiding although so obviously, we have had valuable learnings from that try and which has always been the goal clean form one we don't really for selling that says we believe these style has been helpful.
That's that's helpful. Thanks for the color.
As our next question copper Tazeen Ahmad with Bank of America.
You May proceed.
[laughter].
I just wanted to clarify your your powering assumptions. So you previously thought that the study would be powered to show a 50% reduction I've talked for a week 16 or just based on the changes that you're talking about how does that affect the potential path.
Two accelerated approval.
Have you spoken without the I thought the killer item.
I just I mean this is Robert just a distance.
Like correction on we I don't believe that we did powered the study for 50% reduction and the ducks for that was not one of the original assumption, but I'll, let diego to speak to that the powering assumptions made.
Yeah, we that's always correct we have never.
These skills, what they have some shown in south Florida power.
These amendments.
Not impacting the power. They sample size is the same either only add some flexibility because they own treatment muscle biopsy can be at week six team always say seeks oh, we don't really expect I loss of subjects space. Some of these amendment therefore not.
Unknown Executive: BF-WATCH TV 2021
He has changed how well they powering assumptions.
Okay, and how are you taking into account you're effectively increasing the length of the study to a year or what do you see on compliance rates for the study so far and does this increase do you have any buffer if you will for potential drop outs on the study with the extent the time as observation.
Unknown Executive: Good morning, and welcome to Fulcrum Therapeutics' first quarter 2020 conference call. Currently, all participants are in a listen-only mode.
Unknown Executive: 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 Ward, Director of Investor Relations and Corporate Communications at Fulcrum. Please proceed. Thank you, Dimitri.
Yeah. Thanks Dizzying this is Robert again.
Christy Ward: And welcome to the Fulcrum Therapeutics conference call to discuss our first quarter 2020 financial results and recent corporate highlights. Earlier today, we issued a press release outlining our recent progress. For those of you who don't have a copy, you can access it in the investor relations section of our website, fulcrumtx.com.
One of the things that we've really been struck with is the cooperation of to patients and their willingness to take.
Take lost snap moderate as.
Just to remind you as you know, it's an oral drug taken place.
Really seven in half milligram tablet, so two tablets and morning, two tablets in the evening and we just had.
Christy Ward: 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. We may update these statements in the future, but we are not taking on an obligation to do so.
Not only a high retention rate and the patients, but we believe.
Hi compliance.
As well the original and so the original.
Trial was enrolling 66 patients and because of the response, we had from a patient community. The opportunity. We had we actually increased that to 80 patients. So even if things were to change for the patients. We do believe that we're still.
Going to be able to have you original 66 patients, but but at this point in time, we believe we're going to be able to retain most most of the patients that are currently in the study if not all of them are currently and study.
Christy Ward: 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. Robert will begin the call with an overview of our recent progress. Diego will discuss our FSHG, Owen will discuss our Sickle Cell Program and research efforts, and Brian will cover our financials before opening the call for Q&A. With that, it's my pleasure to turn the call over to Robert.
Okay and my last question is about quickie on a biopsy at 16 link or 13 cents. How did you come up with with 30 effects and how do you feel confident animal and pet gritty Oh. He closed the readings that full time period, because it's a big gap between the two.
Yes, this year ago.
So we have.
I don't know why don't preparatory study to look at the start really de everybody I'll be able to adults for gene signature and Im not sure that he study.
Robert J. Gould: Thank you, Christy. Good morning, everyone, and thank you for joining us today. I first want to thank the healthcare workers, investigators, and caregivers for their courage and compassion as they continue to support so many during the challenges of COVID-19. Our hearts go out to everyone who's been impacted. To all of our friends, colleagues, and the patient communities we serve, we hope you are staying safe and healthy. Fulcrum's mission and purpose remain unchanged as we work to discover and develop therapeutics to treat genetically defined diseases by addressing their root cause. I'm proud of how our employees have risen to the evolving challenges of the COVID-19 pandemic.
Yes on that was still one of seeks eight weeks apart.
They are kind of they make a group moves that west on hold out when they show had donnatal way that yet apart and they were ready genericized shares all that data with us. So we know from these two studies that these stuff sort of seeing that should have the population the I really steady stable. So these days.
Ted value between eight weeks or not yet apart.
She Kelly gives us good day and argument that as long as you were collecting repeated biopsies, we've seen that instead of as we don't expect any impact on grade everybody I'd be deal or do you also signature.
Robert J. Gould: I'd like to begin by highlighting some of our recent updates and accomplishments. Today, we announced an amendment to Redux IV, our Phase IIb trial with los mafiamad, in patients with fascioscapulohumeral muscular dystrophy, or FSHD. Diego will go over the amendment in more detail.
Robert J. Gould: These changes will extend patient treatment from the original trial design and we believe will provide a more robust data set while addressing the challenges presented by COVID-19. Early in the quarter, we received orphan drug designation from the U.S. Food and Drug Administration for Lusmaphomide in FSHD. I'm pleased to report that we have also received orphan designation from the European Commission for Lusmaphomide for the treatment of FSHD. Like in the U.S., orphan designation is granted by the European Commission to drugs that are intended for the treatment, prevention, or diagnosis of life-threatening or chronically debilitating rare diseases.
So let's say these seeks we came in terms of building flexi, we did for the patients on sites who had not.
Obtained this 16 week biopsy.
They tighten their meet malls.
Assuming that over time, there wouldn't be as easily be sensitise, we'd be able to reopen them bring their patients aim to obtain these biopsies each city six weeks, but we have about window. So sites some patients can be flexible and we believe that.
He is the best chance to collecting they efficacy endpoint.
Without losing power and keeping the acquired.
[noise] energy.
Robert J. Gould: We are extremely pleased to have received this designation, further supporting the advancement of Los Mapimans FSHD program. We recently presented dose-dependent target engagement data in skeletal muscle from our phase one trial with Lasman Kamad during a virtual clinical trial session at the Muscular Dystrophy Association meeting. We continue to make progress with FDX 6058, an oral small molecule therapeutic designed to induce expression of fetal hemoglobin in select hemoglobinopathies. You'll hear about our sickle cell program from Owen later in the call. We also continue to make progress on our early research stage activities, including building out FulcrumSeq, our proprietary product engine designed to identify drug targets, programs, and clinical development candidates in a broad range of genetically defined diseases. And we initiated research activities under our collaboration with Acceleron. I'd now like to turn the call over to Diego for an update on the FSHD program. Diego.
Ladies and gentlemen, if you have any questions or comments at this time.
Please press Star then one.
And our next question comes from Ted Tenthoff Hyper Sandler you May proceed.
Well, thank you for the up there I'm wondering what.
[laughter] or Dessel card and didn't mean to.
You are correct. Its personal start again would this be her proved up network scarred at some point next year and you know how you know it's still early <unk>, Chris Krueger cookbook, what would you be in this room for Uh Huh.
Yeah, It's had a so I think first of all the interim analysis to 16 week data, we're doing that in order to gain insight into what our phase three trial design might look like so we can begin that planning earlier as you know we had originally.
Diego Cadavid: Thanks Robert. As a reminder, FSHD is a progressive 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. There are currently no approved drugs for FSHD. And we are advancing the only known industry-sponsored clinical trial evaluating a potential treatment. And, like other diseases that can be characterized by the lack of a gene, FSHD is characterized by the aberrant expression of the gene DOX4, the root cause of the disease.
Projected the topline data in the third quarter to begin that planning from Matt that planning process. We think can be really informed by the 16 weeks interim.
Analysis data.
That we're doing a and again remind you any any kind of conditional approval would require confirmatory trial anyway, and that was <unk> point of having the the topline data available. So we can begin that planning process.
Oh, Yeah, David do you want to add a little more detail on line.
No I I'm seeing if anything as we said having a longer duration of treatment against just see will not only make this study betting that morning pharmacies.
Diego Cadavid: We at Fulcrum discovered that losmapimod, a selective P38 MAP kinase inhibitor, reduced the expression of DOX4 in preclinical studies. We therefore believe Los Mapimos represents a potential novel therapeutic option for FSHC patients. [inaudible] as well as independent evidence suggests that we do not have to turn DOCS4 off completely to provide benefits. There is a spectrum of drugs for expression and FSHT presentation that suggests that even an incremental reduction may be beneficial to patients. We believe, as independent researchers, that any reduction in dose-for-driven gene expression has the potential for benefit to patients. Redux IV is our international Phase IIb double-blind placebo-controlled trial of glosmopimod in patients with genetically confirmed FSHD.
Yeah.
Looking forward to the interim update thank him or her card.
Okay.
Ladies and gentlemen, this now concludes actually any portion of today's conference I would now like to trying to call a richer practical for any closing remarks.
Want to thank you all for joining us today and for your interest in Florida Fulcrum.
Please note that we are all hoping you and your families remain healthy unsafe and thanks again for your time today.
Ladies and gentlemen, thank you for attending today's conference. This doesn't put the program you may all disconnect everyone have a great. Okay.
Good bye.
Diego Cadavid: We completed enrollment of 80 patients at the end of February, which exceeded the 66 we had originally planned. The primary endpoint of the trial is the change from baseline in dose for driven gene expression in affected skeletal muscles. We also completed enrollment in our phase two single-site open label trial, which has been impacted by COVID-19, and we are considering next steps. Fulcrum is dedicated to maintaining the highest standards of patient and clinician safety in the planning and execution of our clinical research programs.
Diego Cadavid: The safety of our clinical trial participants and their health care providers, as well as the integrity of the data we collect, remains paramount. In the wake of COVID-19, a number of our clinical trial sites postponed trial-related activities, and we quickly implemented plans to limit the potential disruption to our FSHD program.
Diego Cadavid: The original design of the Redux 4 included a pre-treatment biopsy, followed by a second biopsy at week 16 of the 24-week treatment period. Following the 24-week trial, patients had the opportunity to roll into an open-label extension. Prior to the COVID-19 pandemic, 12 of the 80 patients completed their 24 weeks of treatment, including their week 16 biopsy, and all enrolled in the Open Label Extension. As the COVID-19 pandemic continued, our team, in collaboration with our investigators, extended the Redux 4 trial from 24 to 48 weeks. This allows the approximately 67 subjects currently continuing in the trial to receive a biopsy at either week 16 or under the amended protocol at week 36 and, after completing the 48-week treatment period, to roll into the open-label extension. To summarize, the Redux IV trial has been extended from 24 to 48 weeks, with an open-label extension to follow. Patients will receive a muscle biopsy at either 16 or 36 weeks.
Diego Cadavid: This extension will apply to the approximately 67 patients still enrolling in the trial, while 12 have already completed and have enrolled into the open-label extension. As part of the modification to the trial, we will also conduct an interim analysis of approximately 25 subjects who have completed their 16-week biopsy. We anticipate sharing data from this interim analysis of subjects' Dox4-driven gene expression signatures in the third quarter of this year, and we expect to report top-line data on the primary endpoint in the first quarter of 2021. The extension from 24 to 48 weeks also allows for a longer assessment in a placebo-controlled design of the skeletal muscle MRI secondary endpoint and the various exploratory clinical endpoints, such as reachable workspace, FSHD We know the Dobson gene signature is stable over time in this population.
Diego Cadavid: And we believe that the longer we're able to treat patients, the greater the potential benefit those mapping modes may have on the root cause of the disease. We strongly believe these changes to the Redux4 study are in the best interest of the patient community and provide the best opportunity to advance this important development effort as we work to address the challenges presented by COVID-19. All of these changes are designed to enable patients and investigators to continue participation in Redux4 and will allow us to collect essential data to support continued dialogue with regulators. I'll now turn the call over to Owen. Owen?
Owen Wallace: Thanks, Diego. At Fulcrum, we pursue targeted indications where we believe we can develop safe and effective small molecule therapies to rebalance gene expression. In our work across various indications, we consistently aim to address the root causes of disease to increase the potential efficacy of these treatments and, more broadly, transform the way these diseases are being treated. In spite of the challenges posed by COVID-19, we have continued to make progress with our research and early clinical portfolio. As an essential business, we continue lab operations, albeit in a more limited space.
Owen Wallace: As a result, we continue to advance the collaboration with Acceleron as well as our internal portfolio. We have also advanced our work on FulcrumSeq, a proprietary product engine designed to identify drug targets, programs, and clinical development candidates for a broad range of genetically defined diseases. By combining high-throughput RNA sequencing, cellular imaging data, and large-scale machine learning, we are monitoring more than 10,000 molecular and cellular features generated by the Small Molecule Probe and CRISPR-Perturbagen library.
Owen Wallace: Understanding their effects on gene expression is fundamental to our therapeutic strategy to modulate the genetic root cause of disease. Fulcrum-Seq is not only the core of our target identification strategy, but it also provides us with a unique understanding of how cellular function is altered in human disease. I'd like to thank our employees who have continued to work diligently through the COVID-19 crisis to advance our research programs, especially those who are coming into the lab working under social distancing and enhanced health and safety guidelines. Likewise, our hemoglobinopathy program has continued to advance towards the IND filing. Our approach has focused on the upregulation of fetal hemoglobin, which could be beneficial for both sickle cell disease and beta thalassemia. By increasing levels of HPF to compensate for the mutated hemoglobin in sickle cell patients, we believe that we can develop and deliver a potent, effective, and selective therapy for patients.
Owen Wallace: This therapeutic strategy is supported by human genetics and pharmacology data where increasing levels of HBF have been shown to be associated with improved prognosis and outcomes, suggesting that HBF may be a surrogate endpoint in future clinical trials. We're very pleased with our recent progress. Our clinical candidate, FCX6058, 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 drug concentrations that we believe will be readily achieved in humans based on pharmacokinetic profiling of the compound. We've had an abstract accepted for oral presentation at the 14th Annual Sickle Cell Disease Research and Educational Symposium scheduled for September of this year.
Owen Wallace: We have also filed our non-provisional patent application, and we've completed our IND enabling studies and toxicology work with FTX 6058. We plan to submit the IND for sickle cell disease in the second half of 2020 and initiate our phase one trial by the end of the year. With that, I will now turn the call over to Brian for an update on our financial results for the quarter.
Brian Stewart: Thanks, Owen. In these unprecedented times, Fulcrum is committed to making a difference for patients with FSHD and select hemoglobinopathies such as sickle cell disease. We are proceeding with a great sense of urgency to bring these potentially transformative therapies to patients. We ended the first quarter of 2020 with $81.2 million in cash, cash equivalents, and marketable securities. Based on our current operating plan and projections, we believe this will support our operations into the third quarter of 2021, allowing us to advance Los MapaMod and FSHD and bring STX 6058 into the clinic while continuing to invest in our discovery stage efforts. Research and development expenses for the quarter ended March 31, 2020 were $14.5 million compared to $34.6 million in the first quarter of 2019.
Brian Stewart: Included in that $34.6 million was $25.6 million of one-time costs associated with the issuance of Series B convertible preferred stock under the company's license agreement with GSK for the rights to Los Mapimais. Excluding these one-time costs. The increase of $5.5 million was primarily due to increased costs related to the advancement of Los Mapiamad for the treatment of FSHD, as well as increased personnel-related costs to support the growth of Fulcrum's research and development organization. General and Administrative expenses for the first quarter of 2020 were $5.1 million as compared to $2.6 million for the first quarter of 2019.
Brian Stewart: This increase was primarily due to increased personnel-related costs to support the growth of our organization, as well as increased costs associated with operating as a public. Overall, we remain undeterred in our mission and continue to expect several upcoming catalysts. We'll report the interim analysis from Redux 4 in the third quarter of this year. We'll initiate the phase one trial with FDX 6058 in sickle cell disease and disclose the biochemical drug target by the end of the year. And we'll continue to advance our discovery programs from our product engine while making progress with our partners at Accelerate. We're excited about the work ahead, and we will continue to execute on our plans, and we look forward to keeping you updated on our progress in the months ahead. Operator, you may now open the line for questions.
Unknown Executive: Operator, we're now ready for questions from the United States. Operator.
Operator: Ladies and gentlemen, to ask a question at this time, you need to press star, then one on your touchtone telephone. If your question has been answered or you need to remove yourself from the queue, please press the down key. Please stand by while we compile the Q&A while it's there.
Unknown Executive: Iain Fraser, Dae Ha, Joori Park, Iain Fraser, Alan Musso, Fulcrum
Operator: And our first question comes from Matthew Harrison of Morgan Stanley. Please proceed.
Unknown Caller: This is Kostas Son for Matthew. Thank you for taking our questions. A couple of questions from my side. The first one is whether you guys expect to lose any power, given that you will only have 25 subjects in the first interim analysis. Do you think you will have enough power to see a signal there, or do you expect the data only to be directional to show you an improvement or not?
Diego Cadavid: Yeah, thank you for the question. This is Diego Calabrese.
Diego Cadavid: The sample size of 80 subjects is, we believe it has appropriate power to answer the question at the end of the trial. 25 subjects, we believe, will give us an initial opportunity to look at the data and help us prepare and make some early insights into phase three planning.
Diego Cadavid: Okay, thank you. And a follow-up question. Will you need to recruit additional subjects, or do you believe you have all the subjects you need at this point?
Diego Cadavid: We have completed recruitment. We believe we have all the subjects we need.
Unknown Caller: Okay.
Diego Cadavid: And finally, I was wondering whether in the second part, when you expect all the subjects to have a biopsy at 16 or 36 weeks, given that there might be a second wave of the pandemic of additional, second wave of infections, how certain you are you can have all the subjects complete the second biopsy at 36 weeks and whether there are any actions you are taking to mitigate this risk of losing some patients there again. Thank you.
Diego Cadavid: Yes, when we amend the protocol, we carefully consider exactly what you're referring to. So we build some time windows around the 36 weeks, and Sides has flexibility as well as patience. So right now, we anticipate that we will get the data either at week 16 or at week 36, regardless.
Operator: Okay, thank you very much. And our next question comes from Joseph Schwartz with SCV Leerink. You may proceed.
Joseph Patrick Schwartz: The question would be, can you talk about how you arrived at a doubling in duration for the Redux protocol with respect to the clinical endpoints? Will patients in Redux 4 still be evaluated at 24 weeks? And how many patients are hitting this time point in the second half of this year, when it seems like social distancing might relax? And then when would most patients be hitting the 48-week time point? At this time point, have you, you know, done an analysis there to consider that, you know, this is in your best interest, given how this pandemic might evolve with respect to its different waves based on where you're enrolling these patients?
Diego Cadavid: Yes, the Reduce IV trial completed enrollment in about six months between August of last year and February of this year. Therefore, the patients are moving between all their visits over a period of six months. We decided to extend the study by an additional 24 weeks because, based on what is happening and what we expect to happen with COVID-19, this will give flexibility for the patients to collect data across a much longer period where we expect the clinics to be open, even if intermittently. Um, so overall, we believe that even if some 24-week visits are missed. Patients would come back later. And, as you know, FSHD is a slowly progressive disease. We are not counting acute events. So, as long as we are collecting data over time, we believe we'll be able to answer the efficacy questions.
Joseph Patrick Schwartz: And are you able to bring patients in and just strike while the iron's a little bit warmer? This period we seem to be entering now. Could you bring patients in for an evaluation? Can you talk about, you know, is it just that 24 and 48 weeks that the clinical assessments are being performed, or do you have any ability to do so? I think you could do in some additional sites without making additional protocol adjustments that might, you know, require you to take alpha hits.
Diego Cadavid: Yeah, this amendment builds flexibility. So all the visits of the original protocol over 24 weeks are open, sites that are open, and patients are coming. And the amendment provides additional opportunities at week 36 and week 48 with extended windows, so we really give opportunities to capture as much data regardless of what happens with COVID-19. We're very fortunate that not only the sites but the patients are very committed, and that's reflected in the high subject retention we have on the trial.
Joseph Patrick Schwartz: That's very helpful. Thank you.
Joseph Patrick Schwartz: And then have you been able to garner any insights to date from the open label trial? It sounds like you suggested it's been impacted by COVID-19. And I heard you're evaluating the next steps there. So why has that been impacted more, it sounds, than Redux 4? Can you provide any color on that?
Diego Cadavid: So multiple studies at single sites, so you don't have this opportunity we have in Redox 4 when we have many sites, and therefore, if one region, which happens to be where this site is, is heavily affected, of course, the impact will be larger. That site is in the Netherlands.
Diego Cadavid: We have always considered that a learning trial; the trial began in August, so obviously, we have had valuable learnings from that trial, which has always been the goal, to inform what we do in Redux 4. So in that sense, we believe this trial has been helpful.
Operator: And our next question comes from Tazine Amai with Bank of America. You may proceed. I just wanted to clarify your powering assumption, so you previously said that the study would be powered to show a 50% reduction of DUX4 at week 16. Just based on the changes that you're talking about, how does that affect the potential path to accelerated approval? Have you spoken with FDA about this particular item?
Robert J. Gould: Hi, Jazine. This is Robert. Just a slight correction on we. I don't believe that we powered the study for a 50% reduction in the duct flora. That was not one of the original assumptions, but I'll let Diego speak to the powering assumptions we made.
Diego Cadavid: Yeah, Robert is correct. We have never disclosed what the assumptions are for the power. This amendment is not impacting the power. The sample size is the same. It only adds some flexibility because the on-treatment muscle biopsy can be at week 16 or week 36. And we don't really expect a loss of subjects based on this amendment. Therefore, nothing has changed about the power assumption.
Unknown Caller: Okay. And how are you taking into account that you're effectively increasing the length of the study to a year? What are you seeing in compliance rates for the study so far? And does this increase, do you have any buffer, if you will, for potential dropouts in the study with the extended time of observation?
Robert J. Gould: Thanks, Chazine. This is Robert again. You know, one of the things that we've really been struck by is the cooperation of the patients and their willingness to take lost math mod. Just to remind you, as you know, it's an oral drug taken twice daily, seven and a half milligram tablets, so two tablets in the morning, two tablets in the evening, and we just had, not only a high retention rate of the patients, but we believe High Compliance as well. The original, and We're going to be able to have the original 66 patients, but at this point in time, we believe we're going to be able to retain most of the patients that are currently in the study, if not all of them.
Unknown Caller: Okay, and my last question is about taking the biopsy at 16 weeks or 36. How did you come up with 36? And how do you feel confident in the integrity of the readings at both time periods? Because there's a big gap between the two.
Diego Cadavid: Yes, this is Diego. So we have done our own preparatory study to look at the stability and variability of the dogs' gene signatures and their natural history. Also, and this was done about six, eight weeks apart. The academic group of the Wellstone collaboration had done it over a year apart, and they were very generous and shared all their data with us.
Diego Cadavid: So we know from these two studies that dogs' signature at the population level is very stable. So this interval between eight weeks or a year apart basically gives us a good argument that as long as we collect the repeated biopsies within that interval, we don't expect any impact on greater variability or loss of signature. So 36 really comes in terms of building flexibility for patients and sites who have not yet obtained a 16-week biopsy. As the pandemic moves, assuming that over time there will be a decrease in peaks, and sites will be able to reopen and bring patients in to obtain these biopsies. It's 36 weeks, but we have a window so sites and patients can be flexible, and we believe that is the best chance to collect the efficacy endpoints without losing power and keeping quality.
Operator: [inaudible] Ladies and gentlemen, if you have any questions or comments at this time, please press star, then 1. And our next question comes from Ted Tenthoff with Piper Sandler. You may proceed. Well, and thank you for the update.
Edward Andrew Tenthoff: I'm wondering what changes this additional time and data may make to a potential registrational study. And would this be something that would start at some point next year? And, you know, how, you know, it's still early, obviously, when this data set is collected, but what would you be envisioning for next steps?
Unknown Executive: Yeah, Ted. So I think first of all, the interim analysis, it's 16 weeks of data. We're doing that in order to gain insight into what our phase three trial design might look like, so we can begin that planning earlier. As you know, we had originally projected the top line date in the third quarter to begin that planning process, and that planning process, we think, can be really informed by this 16 week interim analysis data. And again, to remind you, any kind of conditional approval would require a confirmatory trial anyway, and that was the point of having the
Unknown Executive: The top line.
Diego Cadavid: Top line data is available so we can begin that planning process. Diego, do you want to add a little more detail on that?
Diego Cadavid: No, I think, if anything, as we said, having a longer duration of treatment against placebo can only make the study better and more informative.
Edward Andrew Tenthoff: Makes sense. Excellent. Looking forward to the interim update. Thanks so much for your time.
Unknown Executive: Ladies and gentlemen, it's now...
Unknown Executive: I want to thank you all for joining us today and for your interest and support of Fulcrum. Please know that we are all hoping that you and your families remain healthy and safe, and thanks again for your time today.
Operator: Ladies and gentlemen, thank you for attending today's conference. This does conclude the program. You may all disconnect. Everyone have a great day. Goodbye.