Q1 2021 Passage Bio Inc Earnings Call
[music].
Thank you from holding.
And he can walk you through the passage bio first quarter, 2021, and mutual and operating results conference call.
At this time, all participants are in listen only mode.
Following the formal remarks, we will open the call up for your questions. Please be advised that this call is being recorded at the company's request.
At this time I'd like to turn it over to Stuart Henderson, Vice President and that's relations and strategic Finance Stuart. Please proceed.
Thank you operator.
This morning, we issued a press release that outlines the topics we plan to discuss the day. This release is available and the passage bio website at investors day passage bio dot com under the news and events section.
On today's call Bruce Goldsmith, President and Chief Executive Officer, and Rich Morris Chief Financial Officer, who will review, our first quarter 2021, and financial results and discuss recent business highlights Eliseo Salinas, Our Chief Research and development Officer, Gary Romano, Our Chief Medical Officer, and Jill Quigley, Our Chief operating officer will also be.
<unk> for the Q&A portion of the call.
Before we begin please note that today's call may include a number of forward looking statements, including but not limited to comments on our expectations about timing and execution of anticipated milestones, including the initiation of clinical trials and the availability of clinical data from such trials, our expectation about our collaborators.
And partners' ability to execute key initiatives the ability of our lead product candidate to treat their respective target monogenic CNS disorder manufacturing plans and strategies trends with respect to financial performance and cash flows the company's ability to fund research and development programs impacts of the COVID-19 pandemic.
And the company's operations and its ability to manage costs along with the uses of cash and other matters.
These forward looking statements are based on assumptions that are subject to risks and uncertainties that could cause the company's actual results to differ significantly from those suggested by these statements. Given these risks and uncertainties you should not place undue reliance and these forward looking statements.
Please refer to the company's filings with the SEC.
For information concerning risk factors that could cause actual results to differ materially from expectations, including any forward looking statements made on this call.
Except as required by law the company disclaims any obligation to publicly update or revise any forward looking statements to account for or reflect events or circumstances that occur. After this call.
And my pleasure to pass the call over to CEO, Bruce Goldsmith Bruce.
Thanks, Stuart and thank you all for joining US. This morning, I will begin my remarks by highlighting our company's overall progress and just two years since the launch it passage bio I am proud to report that we have successfully transitioned to a clinical stage company with differentiated therapies and our pipeline. This is a credit to our talented.
And committed team who have successfully obtained multiple global regulatory authorizations for our three most advanced programs in the past few months.
We are driven by our mission to develop life transforming gene therapies for infants and adults, who suffer from rare and devastating neurological diseases, who desperately need our treatments.
Their journey inspires us to move with urgency and executing our ambitious strategy, which is underpinned by four strategic pillars.
One our partnership with University of Pennsylvania's gene therapy program or GTT.
Two the broad and robust pipeline that we have established.
Three the integrated manufacturing supply chain, and we are continuing to build out and for our solid corporate foundation, which includes a highly experienced team and a strong cash position.
We started 2021 with strong execution for example, and a period of less than two months, we obtained three and approvals.
On April one we also announced a major milestone for the company and for patients with the dosing of our first patient and our global imagine one trial of <unk> for infantile G M wine and Gangliosidosis.
These recent accomplishments reflect the tremendous effort of our team and our partnership with GTT.
We are continuing to focus on activating additional clinical sites for our <unk> program and initial sites for our other two programs and frontal temporal dementia and krabbe disease.
While we are diligently working to activate sites across our programs. We are experiencing some impact due to COVID-19 on site openings.
This includes meeting delays with various investigation and review bodies or the ethics committees that prioritize COVID-19 related clinical trials over ours and also staffing levels at psych hospitals.
Given the situation we have updated our expected timelines for the upcoming clinical milestones for the three clinical stage programs for GM. One we are now expecting to report initial safety and 30 dates biomarker data and the fourth quarter of this year.
We now expect to enroll the first patient in our phase one two <unk> and trial and the second or third quarter of this year and expect to enroll our first patient and our phase <unk> trial and the third quarter.
Additionally, we expect to report initial data for these programs and the first half of 2022.
Patient identification and recruitment remain key areas of focus and we have established a variety of initiatives to support this including planned clinical trial sites on three continents at centers of excellence, establishing free genetic screening and forming partnerships with advocacy groups to raise awareness of our clinical.
And programs.
Today I will review the status of each of our lead programs highlighting certain key aspects and will be important to keep in mind and the year ahead.
Before delving into each program I would like to review their commonalities, which are also important to keep in mind.
First all three lead programs address rare monogenic CNS conditions with devastating impact.
For all three conditions disease progression is rapid following symptom onset and survival is severely shortened. This is why again, we have made early patient identification of priority.
Since the severe symptoms of these disorders are driven by CNS disease manifestation and because of our strong supporting preclinical data. We are using direct CSF delivery via intra cisterna Magna or ICM administration and per our three most advanced therapies.
This direct route into the CSF achieved broad CNS distribution and it requires relatively low doses compared to IV systemic delivery and reduces the impact of neutralizing anti capsid antibodies.
ICM is administered to patients under anesthesia, while using modern neuro imaging to support a painless and precise delivery and just the cisterna magna, while avoiding blood vessels and their own structures.
For these reasons ICM administration is being increasingly used to deliver gene therapy to the CNS and is currently and used for at least seven other clinical studies and both pediatric and adult patients.
Finally, I will point out that while all three of our lead programs are in disease areas, where there are competing programs. We believe our programs are highly differentiated from.
And from our vantage point competition is raising awareness of these rare diseases, both for the need to identify patients early and bringing forward the possibility of treatments for patients.
Yeah.
Turning our attention specifically to GM, one I want to stress again, how pleased we are to have dosed the first patient and our global imagine one trial and I want to extend our gratitude to the family patient and health care providers for their support and helping us begin to realize the potential of <unk> to treat patients with GM one gang.
And I say doses.
As a reminder, our imagine one trial is focused on the infantile form of the disease, which is the most severe form with a very rapid disease course, and no current treatment options beyond supportive care.
The phase one two trial is a global open label study of <unk> administered by a single injection and just the cisterna Magna and <unk>.
And subjects with early and late onset infantile GM one.
Our study will enroll a total of four cohorts of two patients each with separate cohorts for late onset infantile and early onset infantile GM one.
Our ultimate aim of this study is to develop a transformative gene therapy that will preserve neurologic function and improved development as a potential survival and quality of life for patients with GM one.
The primary goal of the initial data from the trial is to assess safety and tolerability to allow for dose escalation and progress into our early infantile cohorts. We also plan to measure beta galactosidase enzyme activity and the CSF and serum and this is important because we know that earlier onset and greater severity of disease generally core.
Relate with lower levels of beta Gal activity.
As I mentioned earlier, we expect to report initial safety and Tolerability data and 30 day enzymatic activity of beta Gal for the first cohort of late infantile patients in the fourth quarter of 2021.
As we reported in our press release last month, our first patient has been dose and the United States. We also have received regulatory clearance and the U K, Canada and very recently, Brazil. We plan to open 10 sites globally and are also focused on countries like Brazil, and Turkey, and which there is a higher incidence of <unk>.
Due to a founder's effect, which we will believe we will will help with patient enrollment.
Additionally, we are ramping our patient identification efforts through partnerships such as the ones, we have with and VK and <unk> premium plus pilot program.
We've also built a strong network with patient advocacy groups and site coordinators and investigators at centers of excellence specializing in lysosomal storage disorders.
This comprehensive approach has been immensely useful and helping us to identify patients for our initial cohort and we will we are confident that these efforts will be able to support enrollment and our ongoing program.
Now turning our attention to the <unk> three program and Krabbe disease, we have received regulatory clearance to initiate our clinical trial for this program from FDA.
The MH L. A and you could not and Kingdom and health Canada.
Krabbe disease progresses rapidly damaging both the brain and peripheral nervous system and resulting in a life expectancy of only two years.
And our global Phase, one and two trial Galaxy will be and open label dose escalation study of PD Cara <unk> III that will use and AAV capsid to deliver the galaxy enzyme the ICM and patients with early infantile krabbe disease.
As discussed we expect that we will dose our first patient for the Galaxy study and third quarter of 2021, and we will report initial safety and 30 day biomarker data and the first half of 2022.
Our first goal of the study is to demonstrate that PD Cara III is safe for patients with early infantile krabbe disease or.
Our second goal is to demonstrate an increase and galaxy.
We hope to demonstrate an increase and this biomarker and both the CSF and serum.
The dose escalation portion of the trial will look very similar to the design for our GM one program separated by dosage and age groups. We will begin enrolling a total of four cohorts of three subjects each with separate dose escalation cohorts based on age and enrollment.
We are optimistic about the transformative potential of our therapy as a single agent based on animal models to remind you and the naturally occurring krabbe canine model a single ICM injection of an AAV vector carrying a functional canine gal sieging resulted and normalization of galaxy activity reduced CSF psychoses.
And levels normalized peripheral nerve conduction velocity improved brain myelination reduced brain inflammation and increased survival.
These beneficial effects on peripheral nerve function are especially encouraging because if it translates to humans and will potentially treat the peripheral neuropathy that causes severe disabling motor day deficits and krabbe disease.
Newborn screening is especially important for rare pediatric diseases like crap, where it is ideal to identify pre or early symptomatic babies per treatment to hopefully produce the best outcomes.
For Crabby newborn screening we are working state by state with advocacy groups and key stakeholders to support the development of additional testing and crowded newborn screening to support early and accurate identification of babies with krabbe disease.
We believe that by refining newborn screening, we can reduce the rate of false positives and aid and differentiating between newborns and high risk of developing early onset krabbe disease versus late onset <unk> disease.
We have also expanded our collaboration with <unk> to include <unk> disease, and its license almost towards disease genetic testing program, which provides access to free genetic testing and counseling as well as referrals to appropriate clinical trial programs.
Next let's discuss our third global clinical trial program for <unk> for the treatment of frontal temporal dementia with granular and mutations.
This global Phase one two clinical trial called uplift D. Now has regulatory authorizations to initiate clinical trial sites and the United States and Canada.
As many of you know STD is one of the more common causes of early onset dementia.
We are specifically focused on F. T D G are and where the disease occurs because of mutations and the GR and gene, causing a deficiency of program Ewen.
To help identify patients for the uplift the trial, we have entered into a collaboration with informed DNA and which we are offering free genetic testing and counseling to patients who have been diagnosed with F. T D.
The program will facilitate identification of STB patients with and inherited genetic mutation, providing and an important step for designing individualized treatment approaches as well as potential support for clinical trial enrollment.
It is estimated that about 5% to 10% of FTE is caused by <unk> and gene mutations.
Moving to a deficiency and pro granular and this translates to about three to 6000 patients and the United States.
Uplift D will be and open label dose escalation study of PDF T O two which utilizes and AAV one vector it's delivered to the brain functional granular and gene and coding the programming and protein administered by a single injection into the cisterna Magna and subjects with early symptomatic STD Jr and.
We now anticipate dosing our first patient later in the second or and the third quarter of this year and reporting initial safety and 30 day biomarker and the first half of 2022.
Our first goal for this study is to demonstrate that PV F. T. O. Two is safe for patients with <unk> and our second goal is to demonstrate increased pro granular levels and the CSF.
On may 17th we have scheduled and R&D webinar during which we will go into deeper role of pro granular and as it relates to Ft. D. We will also review the preclinical data supporting our clinical development plans and will discuss our clinical trial design and what we hope to see from the from the trial.
As I mentioned at the outset, we are sharply focused this year on the successful clinical development of our three most advanced programs. We are also focused on advancing and expanding our preclinical pipeline and collaborations with GTP.
To lead. These efforts we are truly excited to have recently appointed Eliseo Salinas as our Chief Research and development officer, and a sale brings deep and broad R&D experience, having worked in the pharmaceutical and biotech industry for more than three decades. He also has extensive experience and neuroscience and rare diseases, which is well aligned with our <unk>.
Companies focus on rare CNS disorders.
As we advance our robust pipeline flexible and scalable manufacturing capabilities and control of our supply chain or other important components for our company's success.
To complement our dedicated manufacturing suite of cable and and our established clinical supply distribution relationships. We look forward to opening our gene therapy manufacturing R&D site and New Jersey this quarter.
We're also pleased to have added Maxine Gowen to our company's board of directors as we continue to evolve as a clinical stage company.
Maxine brings significant public company leadership and clinical development expertise, having co founded and led a startup biotech company and served in a variety of leadership roles at Glaxosmithkline over a period of 15 years.
And with that I will turn the call over to rich to give a financial update.
Thank you Bruce.
And we're reviewing our expenses for the quarter I want to reiterate our strong cash position as a result of our follow on financing in January and.
We have reported and our press release. This morning, we ended the quarter with cash cash equivalents and marketable securities of approximately $438 million as compared to $305 million as of December 31 2020.
We expect these cash cash equivalents and marketable securities to fund our operations for at least the next 24 months.
R&D expenses increased by $12 million to $25 million for the quarter ended March 31, compared to $13 million for the first quarter of 2020.
The increase was primarily due to an increase of $5 million and clinical manufacturing costs.
400000, dollar increase and clinical development and professional services expense and a $600000 increase and facility and other costs.
We also had a $9 million increase and personnel related costs, including a one time share based compensation charge of $5 million.
These increases were offset by a $3 million decrease and preclinical research and development costs incurred associated with our IND filings for our lead indications.
We also incurred $1 $5 million of in process R&D expenses. During the three months ended March 31, 2021 and connection with the development milestone.
There were no such expenses and the first quarter of 2020.
G&A expenses increased by $7 7 million to $12 $5 million for the quarter and at March 31 2021.
And <unk> to $4 $8 million for the first quarter of 2020.
The increase was primarily due to a $4 million increase and personnel related and share based compensation expense due to increases in employee head count.
Our professional fees and facility costs also increased by $3 million, because we expanded our operations to support our research and development efforts.
Net loss was $39 million per the quarter ended March 31, 2021, compared to $18 million for the first quarter of 2020.
Now I'll turn the call back to Bruce for closing remarks.
Thanks, Rich as we look ahead to the remainder of 2021, we are focused above all on execution across our three clinical trials and.
In addition to our ongoing programs investing in R&D initiatives, and our preclinical pipeline advancement remain key imperatives for us and 2021 and beyond.
We look forward to attending <unk>.
And next week, where our partner GTP will be presenting several posters, including on medical <unk>, Lucca dystrophy, and delivering a presentation related to discovery research and gene therapy that we help support.
Looking ahead, our key anticipated milestones for our company and the upcoming year, our reporting initial safety and 30 day biomarker data and our fourth quarter of this year from the imagine one phase one two trial of <unk> for infantile Jan one.
Initiating phase one and two trials for the treatment of STD GRN and the second or third quarter of this year and for the treatment of early infantile krabbe disease and the third quarter of this year.
Opening our CMC research and development site, and the second quarter and continuing to advance preclinical programs for MLD, AOS and <unk> and our undisclosed program and.
Bring additional candidates forward.
Before taking your questions I'd like to take this opportunity to recognize and thank the team here at passage bio for their commitment to our programs and our patients as we work to change the lives of patients suffering from rare CNS disorders.
At this time, we would like to open the call up for your questions operator.
We will now take any questions. You may have if you have a question press star one and you'll be put into the Q and you would like to cancel your question. Please press the pound key.
Our first question comes from from Rama with Jpmorgan. Your line is open.
Hi, guys. Thanks, so much for taking the question.
It seems that you have for GM, one regulatory clearance and multiple countries here I count for.
Can you remind us of the time period that the second patient can enroll after the first patient.
And has enrolled and have you identified the second patient and has the site been selected as well and do you have line of sight on activating this site to get the second patient enroll and really trying to understand if there is further risk to timeline delays euro per jam on thanks, so much.
Hi, and upon.
Thanks very much for the question.
So, yes, I'll start and then I'll turn it over to Gary Romano for a few more comments, but essentially the interval between patients as we've described is mandated by the discussions with the FDA and it.
It's a 60 day window in order to ensure that there is enough and <unk>.
Proper safety follow up obviously this is a as a new agent and we are we and the FDA are just focused on and making sure that there is.
Proper safety.
And a review and then the next patient can enroll it does take several weeks for a patient to go through all of the formal testing and and then potentially be enrolled.
As we've described before.
The.
It is it is sometimes the same site or sometimes other sites that may enroll each patient.
I would just note that the investigators have been working together to.
Potentially identify patients and then we have employed a group called <unk> to facilitate any travel that might be necessary for a patient to move from one location to another for both the.
Evaluation administration and then initial follow up of course, so Gary I don't know if you want to talk a little bit more about.
The identification efforts and and.
And without getting into maybe so much detail it out.
We expect for that for the next study, but just next day patient enrollment, but maybe you could just comment on on how we've been identifying patients to date.
Yeah. Thanks, Thanks, Bruce So the answer to your question directly we haven't yet identified the next patient for enrollment, but we have identified a number of patients who are interested and enrolling and with whom we are going through eligibility. So there is a queue.
And we're not ready to disclose of course anything more about that at this time.
And regarding the sites. The first site that we enrolled our first patient is a very busy site.
That may or may not have the capacity to enrollment of patients and the next month or two.
And do have other sites that are coming on board a very soon.
And so.
And so.
Multiple sites potentially coming onboard and the next let's say.
Several months sorry.
Beginning this month next month or.
Early third quarter.
So I think to summarize.
You're absolutely right. We're focused on the same question you are which is are there are.
Are there going to be sites available or they're going to be patients available to enroll the second patient. We hope that there is not a large interval and between.
And the eligibility for <unk>.
After the 60 days.
But as Gary said, while we do have patients identified and the Q. It's important to note that those patients do need to go on site and get the final screening before they are actually dose. So we're building all of that into our timelines and projections and the site initiations may or may not play a role into that.
But we're watching all of that very carefully as we learn more about as Gary said when those sites will come on and the final identification of the patients.
Thanks, so much for taking our question and the additional detail.
And next question comes from <unk> Richter with Goldman Sachs. Your line is open.
Good morning, Thanks for taking my questions. So just following up on on our pumps question here, just maybe comment on your confidence that and it.
This <unk> 21 timeline for data for <unk>.
Yeah, and one is intact.
What's the risk outstanding rates could be here and then whether it be out their programs are on track.
And what's played out with G M one and.
And then and then secondly.
And just an update on the <unk> program with first of all with regard to kind of learnings from the competitive landscape and remote.
And that trial.
Sure. Thanks, Thanks, very much for the question.
So the reason we were.
Comfortable.
Changing the.
The guidance by approximately <unk>.
Order for the programs and also the overall timelines is really because we're getting increasing insights by further interactions with with each site that we're trying to initiate and.
Because of the.
We definitely needed the regulatory clearance first in order to dig into each of the each of the site initiation and timeline.
And also just the operational details.
Further as we to your point as we've initiated the GM. One study, we've obviously had increasing learnings about the.
Overall, COVID-19 impact.
And for these sites and how this is being played out that's why if we put all of that together.
We are comfortable with.
With the <unk> 2021 timelines for data, we absolutely understand that changing the timelines could raise questions about weather.
How confident we are and those timelines, but we've looked at when as Gary alluded to it when site Activations are now projected based on the interactions with the.
And the Ethics review committee and the sites themselves as.
And as well as as Gary said that the identification of patients and.
And Jim one.
Mirrors, I think crab to a certain extent in terms of patient identification.
And just giving us more clarity on the overall process crab.
It does have one difference and that 10 sites now are doing newborn screening and so that could change the dynamic in terms of potentially identify identifying patients more rapidly.
But its still is the site initiations that we're getting much more clarity on.
And especially in the and the COVID-19 era, and so I think those are theirs.
And the rationale why we changed the guidance.
And on the new programs.
Similarly, or once we have regulatory clearance and we were able to to really start to work with the <unk>.
Ethics review and the institutional review boards, not only in United States, but elsewhere and.
Feedback has given us much more clarity on that on those timelines.
So I think that's the first part to your question.
The second part on FTE.
And we really haven't seen very much more data at this time from other programs what we've seen.
While we do anticipate some updates over time, but we haven't really seen a significant change from the first or second quarter of this year.
Obviously, we're really focusing on the two studies that are in clinical trials. One is a humanized monoclonal antibody against <unk> and and the other is obviously a gene therapy using AAV vector and those studies are enrolling.
Our enrolling.
But we've also seen.
Similarly, I think one learning is maybe not in the electric study, but and the other gene therapy studies, we have seen similarly, a very slow opening of our clinical trial sites and Thats. One thing that we can take away is that we're not alone in this and this site initiation and Jerry.
Alright, thank you.
Our next question comes from Huron and warmer weather.
And with Cowen Your line is open.
Right good morning team and thanks for taking the questions and so I've I've a couple and the first one for Jim one maybe just give us a little bit of a sense based on the preclinical models, how fast do you see.
The stabilization from baseline to maximal reduction and the biomarker.
And I'm talking about Jim ones first and then maybe club day second.
And then secondly, the new CMC research and development side and you're Gonna have is it.
Is it is it also a CMC.
Center for optimization, and you actually made clinical material, there and turned out actually brought true to commercialization and do need to go to a different site. Thank you.
Yes, thanks, and thanks for the questions.
So first of all I'll ask Gerry to add some commentary on this but in both.
And both the <unk> and <unk>.
We're looking at multiple different biomarkers for Pharmacodynamic outcomes, and and certainly we're looking at the enzyme activity and then downstream markers.
Gary maybe you can use GMO and and and then I'll then I'll turn it over to Jill perhaps to talk a little bit about the site on the and the <unk>.
And the R&D and manufacturing site, Gary do you want to talk about the various biomarkers, we're looking at and GM on and credit and some of the kinetics, we might see.
Yes sure sure so.
And the near term, we're going to be reporting out on safety and Tolerability and our 30 day beta Gal activity and.
And that'll be mid 2021 and.
This is and.
And I'm sure that you said.
Fourth quarter.
This is in line with our first goal of demonstrating PV, Jim Owens safe and well tolerated.
And the patient population. Our second goal is again to measure effects on beta gal enzyme and CSF and serum.
We expect to able to measure that within the first day.
30 days since we have and animals.
And later on we will be measuring treatment effects on biomarkers and order generation, such as and that fall.
And also biomarkers operating structure and function, including MRI and EG.
We expect the NFL data too.
Take at least 90 days before we would see a treatment effect there given the half life of two to three months from that protein.
And we expect it will take between one and two years to share treatment effects on.
Rates of progression and.
Great and nations and MRI or on Pega deterioration.
And with longer follow up will be and assessing treatment effects from the clinical outcomes and regulation of our study is 24 months to reflect that.
And we're using variety and validated scales to measure treatment effects on patient milestones and development milestones.
And demonstrate that they have and improve developmental potential and positive protect some quality loans.
Yeah.
Youre talking about sort of rent and credit.
Yes.
And yet.
Yes so.
And credit agencies.
Again.
We're measuring a number of biomarkers there as well it will start off the Gulf Dam safety and Tolerability and looking at the enzyme galaxy.
And also one of the enzyme substrates cyclizine, which is responsible for the.
Negative effects on myelin producing cells will.
And we'll be better and galaxy at 30 days and we mentioned Cyclizine. After that probably also within we wouldn't expect to see necessarily effects as rapidly as you see effects from the enzyme activity, but later.
Probably 90 days and.
The minimum.
We have other a number of other biomarkers, which we know track and disease progression, including nerve conduction studies, where we thought the interconnection and velocities and.
And remind you that and you came on model we saw.
Preservation and improvement and peripheral nerve and then.
Automation and central Myelination.
So for brain structure, again, and MRI studies and.
And AEG and a cup and a number of other evoke responses that measure conduction and the central nervous system.
Okay, Thanks, Garrett and I think in summary, and.
It just means that we're going to have readouts.
And that our near term, which are really the enzymatic activity and then following these other markers over time and I think thats the theme for.
All of our programs.
So thanks for that summary, Gary.
Joe do mind, taking us through a little bit of the second question on the CMC R&D site.
And that's fine.
And importantly strategically.
Strategically at our manufacturing capability and our overall goal is to have this capability.
And clinical development programs running simultaneously.
What we're doing really is to establish a flexible and supply chain with dedicated manufacturing capability and global distributions from partnerships from clinical development and Kieran Chuck commercialization.
So typically with Macquarie.
And that's going to be a question, mostly with data and analytical capabilities and will allow us to ask.
And the development and validation and start with biomarker assay development and basketball and golf.
And that's all.
All of which are of course critical and as you.
And think about the development of gene therapy.
We will not be hurricanes, and clinical supply and that wholesale money and SEC.
And <unk> quarter.
And that is taking strategically down the road and.
Relocation and hope all of you guys do it will allow us to it and add additional labs for QC testing and other activities.
And or to add T GMP facility, and we start to understand the need and the supply chain with regards to write downs on Cambria look towards commercialization.
Thanks, Joe Thanks, Gary.
And next question from Nina.
<unk> Garg with Citi. Your line is open.
Hey, guys. Thanks for taking my question. So just one quick clarification on what we'll see and the fourth quarter of this year I just wanted to confirm that.
The intention would be true essentially wait until you have kind of the go ahead.
Okay for enrolling the second and third cohorts and are at the time that you would provide us with status and that's just my first clarification question and then a.
A question on FCB really quickly and.
And just given that there are.
Multiple other studies enrolling patients right now and I know I think you are using some of the same sites like UCSF and Penn that are enrolling and from a fee and the antibody study for example, I guess just if you could talk a little bit about how we should expect patient enrollment and that study to go and just given competition from from the other studies.
Thanks, Dan and thanks, Thanks for the question.
And the fourth quarter, and then I'll turn it over to Gary to talk a little bit about how we selected sites and our interactions with the investigators on SCD.
And so in fourth quarter, you're absolutely right, we're expecting to report not only the 30 day beta Gal data from the the cohort.
And so safety data and and hopefully also have the 60 day follow up and.
As we've highlighted and kind of the clinical trial charts, we do anticipate having and <unk> meeting at.
And at the and review at the end of the cohort one and that <unk> review would obviously look at all of the data that's coming out of the cohort one and also have a recommendation or discussion on advancing to cohort two and three so that's what our anticipation is at this time and at <unk>.
Certainly I think very important not only to have the data, but also have the pathway forward to your point.
So in addition to that discussion.
On an FTE, we've obviously looked at the sites very carefully and thought about.
Sites that potentially have patients identified and.
And sites that could identify patients and the network and and Gary do you want to talk a little bit more about that.
And the sites and the competition and how we are identifying patients.
Sure. Thanks, So for F T D.
We are.
Okay.
You're right.
Plenty of that to be granular and patients out there.
Not all of them have yet been identified genetically so we're taking a two pronged approach to patient identification.
First we're partnering with leading academic sites across the globe.
Who are following families with loans that mutation carriers and these are.
Some of the sites you pointed out we also have others in Europe, we're actually not.
There is less direct competition.
And this leaves and investigators and we were very enthusiastic to enroll eligible granting invitation carriers that they are currently following.
But our second approach, we're taking is that it has to do with as I said.
Many of TD patients out there.
Don't know their genetic status haven't had genetic testing, 5% to 10% and which are expected to have brand and when we paid the shoes so to.
Help identify those eligible patients with Daniel limitations.
We've recently engaged with and foreign DNA to design and support of genetic screening and counseling program. This is going to be free of charge to FTP diagnose patients.
And we're also working with other third parties to provide clinical trial information regarding debt and equity grants from studies.
And so.
And we're feeling confident of being able to enroll the study.
Yeah.
And soon as we get our sites open and we're also I should point out that we're also opening our first site.
It was later this month.
And the U S. We are also targeting sites as I mentioned globally and.
And the UK and Europe, Brazil.
Canada.
And which are advancing through IV ethics submissions at this time.
Okay. Thank you.
Okay.
Our next question comes from Google and Mr. Let's Chardan Your line is open.
Hi, good morning, and thanks for taking my call I think some of this has been answered but will operate out any houses for additional detail on your timelines.
Adjusted for the global Phase, one and twos due to COVID-19 and the.
Except that the one quarter delay roughly is par for the course.
External global forces, but could you talk a little bit more about your risk mitigation strategies that you now have in place with regards to your external partners. So.
What are the areas.
Or there is some risk and what are you doing it's sort of been sherpa.
Timelines political put forward today.
And thanks very much for the question.
So I think there is two or three primary <unk>.
<unk> that we would we would think about from a from a partnership perspective.
One is certainly manufacturing and the partnership that we have with Cadillac and it will give a lot of credit to Alex <unk>, Our chief Technical officer, and his team and I. Thank them very carefully about both the upstream.
Work that goes into securing supplies and supply chain to make sure that we can stay on track for our manufacturing and.
And.
Very pleased with the progress that he has made and building that team and then executing against that strategy to ensure.
That we can make.
The supply and our and our and our suite the dedicated suite that we brought online in December of last year and.
And got qualified even during the pandemic and I think Thats, just and we're already manufacturing and that suite and I think that demonstrates part of the commitment to owning our own destiny in terms of manufacturing.
And I will add to that that Alex and team have been very focused on downstream aspects as well.
And Thats, obviously, one of the reasons and we have established partnerships with and thinking about.
Product testing and release, but we also want to own more of that going forward and Thats why were opening the R&D site that Joe highlighted.
That's one aspect I think the second second part is clearly working and continuously.
Thinking about our partnerships with our Crows and are and work externally on regulatory partners et cetera, and that just requires very careful management.
From from our internal team and it's kind of part of the standard operating work that we're doing anticipating how.
How those how the Crs and regulatory interactions are going and then ultimately on the ethics review is our IRB is we do have a lot of activity ongoing because there are three studies that were launching simultaneously.
The regulatory approvals that we've obtained really demonstrate that that this is working very very well I think where we're getting some delays is obviously on the interactions at the site level, but those are productive they are just.
As you said kind of the new reality.
And then thirdly, and most importantly, a possibly is our relationship with the University of Pennsylvania.
And I will say that.
While the U Penn, obviously and the gene therapy program that Jim is built.
Is on.
On paper and and the relationship is moving forward to IND and then we obviously take take over for all the regulatory interactions and moving forward, but theres a continual support from people like Julia Johnson, who runs the manufacturing vector core.
From the head of regulatory et cetera, and there is a continuous.
Relationship with with Jim and his team that really provide just such great expertise that we draw and constantly so those are the three primary groups and I should mention that there are also obviously responsible for advancing our earlier pipeline as well.
Such as the.
Such as the MLD work, that's going to be highlighted a little bit of <unk> and also do participate in the and the meeting that's coming up on FTE day and highlight the work that they've done there. So I think those are the those are three external groups that we've spent a lot of time thinking about and working on and I really want to think.
Alex Gary and his team for managing all of the and complicated regulatory interactions and obviously, Jim and his team.
He's been instrumental and moving all this forward.
Great. Thank you.
Our next question comes from Laura Chico with Wedbush Securities. Your line is open.
Thanks, very much for taking my question I actually have two so.
And I'm, sorry to go back and the song, but on the day of one program I guess first if you wouldn't mind elaborating a little further on the site activation and the COVID-19 bottlenecks and I guess I just want to make sure I understand where the hang ups are coming here or is this more just kind of a buildup of activity that has not been able to guests from the queue.
And the pandemic constraints or is this.
Something more to do with the protocols training and getting through the committee is.
Just any clarity you can give there.
And.
Secondarily, then on F. T D. You mentioned and the informed DNA collaboration and I was wondering what is your sense as to the proportion of SCD patients today that are currently receiving genotype assessments. After diagnosis and also curious what led you to select and form DNA as your partner here. Thanks very much.
Absolutely. Thanks.
Thanks, very much Laura so I'll take the first question and then turn it over to Jill for Conversely, more discussion on informed DNA and why we chose them and what we know.
About the percent of Geno typing.
So on the on the programs I think.
Gary I think highlighted this.
And absolutely.
Absolutely appropriately it it's really the Q.
Adding into the Ethics Review Committee Q and <unk>.
There is there's one idiosyncrasy I think from from COVID-19, which is that.
There are many protocols that are being essentially had been delayed because of the prioritization of COVID-19.
There is also obviously and some of the hospitals.
Just in terms of virtual meetings and and.
And and Qs, it's been quite long to get into those queues.
And we definitely had to because of as you recall.
When we started the GM one study.
Did start with a protocol.
That had.
Uh huh.
A single cohort that mix, both early and late infantile and then we did change that similarly crab day also had to change that too so that was but that was part of the.
That was part of the understanding of the initial timelines. So we definitely had to submit different protocols, but thats really standard operating.
Approaches that that other companies have as well.
So I don't we don't think that Thats in particular to your question idiosyncratic to any any program. It's more about the turnaround time than at the Ethics Committee and and IRB is that has that is.
Really implement impacted the timelines.
No.
It's a long winded answer to say I think that that what we've laid out is really the majority of the of the impact.
So.
And that's why I think as we get clarity I think moving back to earlier questions Thats why as we've gotten clarity and had these interactions and understood.
And the potential timelines for the various sites openings that we have adjusted these timelines with with more confidence.
So.
Joe do you want to talk about why we chose and from DNA and then.
A little bit about the estimation.
Yes, I think.
But let's talk about the promotion.
And I think that dry and slightly wider levels from Carnegie.
And most of them.
And it has a channel that component.
And just.
And primarily family history is not always clear and.
And thats not traditionally.
And this academic centers.
And most of that loss.
And 10%.
That's true.
Darren.
And so far and.
So as we think about that and what do you think about programs coming polite and.
And so the patient and that and part one.
Q pharma partners and corn.
And going from a little tour.
Screening and our partnership with <unk> net debt.
Finally, moving on that path with very important per patient.
And I'm doing that because a lot of history and running programs and other yes.
And one of our areas for other interest partners and are now well established firm and as well and well known and.
Importantly, with her and foreign DNA program are not just not just screening per FTE with GRN and solutions.
All right.
And and that's key.
And again this is a service.
And you think about programs currently available hypomobile boats from enrolling.
Thanks very much.
Thank you.
Okay.
Our next question comes from that net <unk> with Guggenheim Securities. Your line is open.
Hi, guys. Good morning, and thanks for taking my question and this is Aaron on Alright, that's it so the first gen. One patient with US back in March and do you have any early readouts on safety.
And has a 60 day safety review been performed on the patient.
And could you talk about.
And patients therapy and screen for Jan one and has there been any screen failures.
So.
First of all thanks for the question Erin.
So we're not going to comment on any interim information that we may.
It received from the studies as we've laid out where we're talking and we're going to talk about cohort level data and.
And.
And that will come later this year as we've described.
Appreciate the question and interest.
I think we're doing this and in and just in order to make sure we have as much data as possible and house and understood.
So the second question in terms of screen screen failures. So the.
<unk>.
The way that Gary described this is that there is a network of patients that are being looked at and assessed but the screening actually occurs when the patient the form of screening in terms of the screen failure rate that you would that day.
And you get your referring to actually occurs when.
And the patient would come to the site and be at the final assessment. Because then they are actually enrolled and the final screening occurs.
What's occurring now and for patients with <unk> and other patients with rare disease and studies like this is that the.
The network and investigators and also.
Patient information forms that are filled out for example on request for information and informal way of looking at.
Patient age and whether they qualify.
<unk>.
Any genetic testing that may have occurred and whether the patient would have qualified et cetera. So that's not considered.
True.
Screen failure rate at this time, so I think what will what we will look at is when we final and finalize the cohort will provide more information and if there were any patients that that did indeed.
Fail the screening.
But we're focused right now instead on the patients that were that were rolling into the patient. It's a great question and I don't think we have enough information to comment on on that further at this time.
Okay. Yeah. It's early I appreciate the answers thanks.
Yeah.
And I'm showing no further questions in the queue at this time.
Ladies and gentlemen, thank you for participating in today's conference. This does conclude your program and you may now disconnect everyone have a great day.
Yeah.
Okay.
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