Orchard Therapeutics plc
Q1 2022 Earnings Call Transcript

Published: 12 May 2022

[Operator:]

Welcome to the Orchard Therapeutics Q1 2022 Earnings Conference Call. My name is John. I'll be operator for today's call. During the question-and-answer session, if you do have a question, pre-1 on your touchtone phone. I will now turn the call over to Bobby Gaspar.

[Bobby Gaspar:]

Hello, everyone, and welcome to Orchard Therapeutics First Quarter 2022 Financial Results and Corporate Update Webcast. I'm CEO and Co-Founder, Bobby Gaspar. Before we get started, I want to remind everyone that this presentation contains forward-looking statements. Please refer to the slide and our latest SEC filings for more information. I have 3 colleagues joining me on today's call. Braden Parker, our Chief Commercial Officer, is joining us to highlight the success we've recently had expanding commercial access for Libmeldy. Frank Thomas, President and Chief Operating Officer, will review our financial results for the quarter. Leslie Meltzer, our Chief Medical Officer, will also be joining for Q&A. In March, we spoke about our decision to strategically prioritize the focus of our platform to synergistic indications where we believe HSC gene therapy is scientifically and clinically differentiated from where it can deliver the most value. Through the insights we've gained for many years of scientific and clinical development in this field, we believe indication selection in our space is paramount, and this is what is driving our strategic approach and decision-making. Firstly, we want to focus where the HSC approach has differentiated itself scientifically and clinically, that is in neurodegenerative conditions like MLD, where the migration of gene-modified HSCs into the CNS is key to delivering the gene where it is needed. With Vamed, we have seen how focusing in this area can lead to clinical benefit, regulatory approval and increasingly commercial success. Throughout the start of 2022, Orchard has built sustained commercial momentum for Libmeldy as the first HSC gene therapy with meaningful reimbursement coverage in Europe. We are extremely pleased by the recognition of Libmeldy value commensurate with its clinical impact, which is reflected in the published net price of EUR 2.4 million attained in Germany and which is indicative of our agreements throughout the region. We're encouraged by the continued progress we're making to identify, refer and treat eligible patients with this therapy. In addition, we believe that a further focus on neurometabolic diseases such as MPS disorders, will offer a synergistic approach and enables us to leverage a common infrastructure from manufacturing and CMC to distribution, supply chain and our commercial network as well as regulatory capabilities. We've also chosen to focus on our research programs using HSC gene therapy for specific larger disease indications with genetic susceptibilities such as the progranulin form of frontotemporal dementia or the NOD2 form of Crohn's disease. As we develop these further and as the preclinical data matures, we believe these programs provide opportunities for significant value creation, either on our own or through potential partners with an interest in our platform or indications. At the upcoming ASGCT meeting, data from our neurodegenerative programs will be presented that continue to demonstrate the unique ability of our approach to enable broad distribution of gene-corrected cells and localized delivery of therapeutic enzymes and proteins in the brain. Future presentations include updated results on the OTL-203 clinical program for MPS I Hurler as well as preclinical work to advance the platform's applicability to address other neurodegenerative and CNS-related conditions, including the pro granular form of FTD. So we continue to build on the deep body of data driving our mission to develop the curative potential of HSC gene therapy and create even greater value for the communities we serve. I'll now turn the call over to Braden to review some exciting progress on the Libmeldy's commercial launch. Fred?

[Braden Parker:]

Thanks, Bobby. Since Libmeldy approval and launch, we have been building out multiple facets of our commercial infrastructure to identify and treat as many eligible MLD patients as possible. By design, this foundation can also support our next wave of neurodegenerative programs in the MPS space. These additional indications represent exciting commercial opportunities that can leverage much of the investment we are making in the Libmeldy. Since the launch, we've prioritized the activities and initiatives we believe will generate the most value for Libmeldy patients and providers. On the access and reimbursement front, we've seen our positive engagement with health technology assessment bodies and payers throughout the region, yield agreements securing reimbursement for all eligible MLD children. After announcing an agreement with NHS England in February, Italy and Germany became the second and third major European markets to recognize the value of Libmeldy commensurate with its clinical impact. The pulp's German net price of EUR 2.475 million is indicative of the level at which we've been able to secure access to VAMELDI. These agreements come after Libmeldy received the highest possible therapeutic benefit rating in presymptomatic patients by the German Federal Joint Commission, which only 4 other medicines have ever received, and the Italian Medicines Agency recognized the significant potential clinical benefit Libmeldy offers by granting innovative status. We believe the progress in Europe and the value recognized by payers has differentiated this product and our team and demonstrated a willingness to ensure access for MLD patients across the continent. We intend to continue expanding access by securing agreements in additional European markets. We are in various stages of technology assessment and reimbursement discussions with joint HTA assessment consortia such as Beneluxa and Panote as well as in Spain. We have plans to enlarge our network of treatment centers in a similar fashion by qualifying centers to administer Lenel in Sweden and Spain, in addition to our existing centers in the U.K., Netherlands, Germany, Italy and France. Over time, this same network of centers would be utilized to support future potential launches in similar indications. And in order to help ensure we are identifying as many eligible patients as possible, we are continuing to increase our support for newborn screening to drive early diagnosis. We now have 7 studies ongoing in Europe and 1 in the U.S., which are intended to generate data to support the adoption of regular screening at the state, national and regional levels. These programs could also identify MLD patients to be treated commercially if reimbursement is in place at the time of diagnosis. We are continuing to assess how to best expand our geographic footprint beyond Europe and the U.S. to regions such as the Middle East, Latin America and Asia Pacific in a capital-efficient manner. As we've mentioned previously, our partner, Genpharm in the Middle East, has already identified a patient who received Libmeldy through reimbursed international treatment abroad at our qualified treatment center in Milan, Italy. I'll hand it back to Bobby to discuss our U.S. regulatory plan and the rest of the neurometabolic portfolio. Bobby?

[Bobby Gaspar:]

Thanks, Brandon. In the U.S., we believe we have all the data needed to move forward with a submission for OTL-200, and the team is working with our clinical site and CDMO partner to prepare the package. We are planning to have a pre-BLA meeting with the FDA in the second half of this year in advance of the file, which we expect to submit in late 2022 to early 2023. The key reason we are emphasizing our focus on our neurometodic portfolio, and in particular, our next-in-line NPS programs is because our experience with MLD provides validation that we can translate to potentially transformative clinical outcomes into regulatory and commercial success. Moreover, the infrastructure we are building to support the Libmeldy launch is synergistic and directly applicable to OTL-203 in MPS I Hurler as well as our earlier-stage program for the treatment of MPS IIIA OTL-201. We the areas of clinical, regulatory, manufacturing, distribution, patient identification referral and treatment can all be utilized for potential future neurometabolic launches. We have been developing a protocol for a global MPS-I registrational study with feedback from last year's parallel scientific advice for and are focused on the importance of being able to show a meaningful difference from current standard of care, not only for regulators but ultimately for payers commercially. The regulators have been highly engaged, and we think that speaks to the opportunity we have with HSC gene therapy in this condition. As part of our ongoing interactions with regulators, we have received additional and more specific feedback related to study design and endpoints that will likely delay initiation to 2023. We while the time lines have moved into 2023, we believe the alignment we are gaining with regulators will support a stronger application in the U.S. and in the EU. I'll now turn it over to Frank to discuss in particular around Libmeldy revenue recognition and the rest of our financials.

[Frank Thomas:]

Thank you, Bobby. I'm going to spend some time reviewing the financial performance for the quarter. I'd like to open my section with some color around revenue recognition and cost of goods since it's the first time we've reported product sales for Libmeldy. Recall from our prior communications that we treated and therefore, recognized revenue from 2 commercial patients in the first quarter. Importantly, the cash flow from these patients will be paid upfront rather than over multiple years. We continue to be open to payment over time or outcome-based agreements depending on the preference of the payer. However, most payers to date have opted primarily for an upfront payment structure. Revenue from product sales of Libmeldy was $5.1 million for the 3 months ended March 31, 2022. These first 2 patients were treated under reimbursed early access programs in France and Germany. So the revenue per patient may not ultimately be indicative of the final pricing in those countries. However, with a net sales figure of about 2.5 million per patient, you'll note that it's similar to the final negotiated and published price in Germany. Cost of product sales were $1.6 million for the period, and it's worth spending a few minutes here is there are 3 primary items that make up COGS for Libmeldy. The first is the cost of manufacturing, meaning the cost to produce the drug product for the patient. The second is third-party royalties, and the third is noncash amortization of milestones that were paid previously. On the first item, the cost of manufacturing does not currently include the cost of the lentiviral vector that was used in these first patients since those vector batches were produced and expensed prior to Libmeldy approval. The royalties to third parties total about 20% of net sales in the current quarter, and that's a reasonable assumption to use going forward. Royalties may be higher in future years as we achieve higher annual sales of Libmeldy. Beyond Libmeldy revenue and COGS, you can find the full financial results from the first quarter in our press release this morning. Let me also touch on the restructuring. The changes we announced in March will extend our runway into 2024 while maintaining operational focus on several value-creating milestones, including the potential approval and launch of Libmeldy in the U.S. and additional regulatory milestones and data releases. Since the restructuring happened at the end of March, there wasn't a meaningful impact on our operating expenses in the quarter, but we do expect to start to see those benefits beginning in the second quarter. We also took onetime charges totaling about $4.7 million, which are included in their operating expenses for the first quarter related to the restructuring of our organization and certain program termination costs. Cash and investments were $199 million as of March 31, 2022. The company used about $21 million in cash during the first quarter to fund operations, which is net of $16 million in R&D tax credit refunds from the 2020 tax year. Without that credit, the burn rate for the quarter would have been roughly $37 million. Going forward, I would expect our operating expenses and quarterly burn rate to come down over the course of 2022, exiting the year closer to $20 million to $25 million per quarter, giving us runway into 2024. As we think about funding the business beyond 2024, we see many opportunities for business development across the platform. The farming deal we announced in 2021 is a good indicator of where our BD strategy might go, bringing together Orchard's expertise in HSC gene therapy with a proven partner in a particular disease or therapeutic space that has clinical and/or commercial capabilities. We think a partnership like farming could be a precursor for additional opportunities in other larger conditions with more prevalent patient populations with the potential also for deals in the Treg space and in using HSCs to deliver monoclonal antibodies to tissue-specific targets. The ideal partners would bring more than just capital but also have an existing set of capabilities, disease state knowledge, a commercial infrastructure or an idea or IP that could leverage our HSC gene therapy platform. Looking forward, we're pleased with the progress we've made and the changes we implemented to our business at the end of the first quarter. There are operational and financial benefits that should accrue to us throughout the remainder of this year. We're at an important inflection point for Orchard as we balance commercial activities for Libmeldy with an exciting pipeline of clinical and research candidates, and we are 100% dedicated to making the promise of our therapies a reality for the benefit of patients, our community and our stakeholders. With that, I'll turn the call over to the operator for questions.

[Operator:]

[Operator Instructions]. And our first question is from Gena Wang from Barclays.

[Unidentified Analyst:]

This is Harshita on for Gena. I had 2 quick ones for Libmeldy. Could you provide additional color on how many market access agreements do you expect to secure for the rest of 2022? And just additional color on how much revenue you expect per quarter in 2022, if you're able to provide that color. And then for the BLA meeting in the U.S., have you requested a meeting yet? Or when do you plan on doing that if you haven't yet? I know you said second half, but I'm curious if it was more like third quarter or fourth quarter.

[Bobby Gaspar:]

And maybe I'll just take the second one first because that's very quick. So as we've said, we are looking to hold a pre-BLA meeting in the second half of the year and with a view to -- on the basis of the interactions that we have to a late 2022 or an early 2023 file. So I really can't give you anything more than that at this time. With respect to the first question, let me take that -- turn that over to Braden

[Braden Parker:]

Thanks, Bobby, and thanks for the question. In terms of the number of agreements and/or revenue for the rest of the year, I would say that, first of all, we're extremely pleased with the progress that we've made thus far. We're in various stages of HDA assessments and reimbursement discussions across Europe. And as we noted in our prepared remarks in markets in the U.K. and Italy and in Germany. So we're -- because we're in the midst of these negotiation deck just when they might conclude. So we're going to hold off on any type of guidance in terms of the number of agreements before the end of the year, though we are in current Similarly, on the revenue front, we haven't guided to year just based on the uneven nature of these early quarters because of the timing of patient identification, the geography they may be in as well as the timing of reimbursement and treatment. So no guidance on revenue either at this point in time...

[Operator:]

And our next question is from Yaron Werber from Canon.

[Brendan Smith:]

This is Brendan on for Yaron. Just a quick one from us. First, I wanted to ask a bit about your latest regulatory interactions for MPS-I and MPS-IIIA actually. We understand you're looking or incorporate some of that feedback into study design, et cetera, for the pivotal trial. But I wanted to see if there's any more color you might be able to provide on what has maybe been especially notable or surprising there. And if there's any learnings or read-through from MPS-I to the potential Phase III pivotal study. And I guess in that same van, just wanted to see what the latest timing is for a potential MPS-IIIA pivotal study.

[Bobby Gaspar:]

Okay. Let me -- I'll take the first piece about the interactions on MPS-1 and then I can turn it over to Leslie to talk about MPS-IIIA . So just to step back a little bit. We're extremely excited about the potential of HSC gene therapy for MPS-I. It's part of our leadership and the application of this HSC gene therapy approach for neurodegenerative disorders, and we've seen the success that we've had with Libmeldy. We've also seen some very exciting data in the proof-of-concept study with stabilization of cognitive outcome and also improvement in the systemic disease parameters as well. So what we're doing is designing a global registration study. We had feedback from last year's parallel scientific advice. And the important piece of this is to be able to show a meaningful difference from the current standard of care, which is allogeneic HSCT. And that is important, not only from a regulatory perspective, but also ultimately for payers commercially. And so we've been having ongoing interactions with the regulators and we have received additional and more specific feedback related to the study design and endpoints that again, as I say, will show a meaningful difference from current standard of care. And that is what we want to incorporate into the study design, and that will likely delay the initiation to 2023. The most -- I think we've had very highly engaged interactions with the regulators, and I think that speaks to the opportunity we have with HSC gene therapy in this condition. And although the time lines have moved out, we do believe that the alignment that we're getting with the regulators will support a stronger application, both in the U.S. and in the EU. So let me then hand it over to Leslie to talk a little bit about what we might see from MPS-IIIA...

[Leslie Meltzer:]

Thanks, Bobby. So to update on MPS IIIA. That program is a little earlier than MPS-I. It's a 5-patient proof-of-concept study being conducted exclusively in the U.K. It is fully enrolled and the last patient enrolled in the latter part of last year. And MPS-IIIA is a disorder that is characterized primarily by cognitive decline. And these patients generally in the natural history was first initially developed normally and then plateau at around age 3 and ultimately starting to decline rapidly in the years after that. So like I said, this study is just recently finished enrollment, and the most recently treated patient was not treated that long ago. So we're at the point now where we're still waiting for that data set to mature a bit so that we can really start to make meaningful conclusions on those cognitive outcomes compared to what we might expect in a natural history population. So as we are evaluating potential study designs, that's really going to be informed by these observations in the proof-of-concept study as that cognitive data matures. And I think it's certainly possible to leverage the learnings from our interactions on MPS-I, which is also characterized to some extent by cognitive decline, but is also characterized by a number of systemic manifestations that may be meaningful in that disease as well.

[Operator:]

Our next question is from Dae gon Ha from Stifel...

[Dae Gon Ha:]

Just following up on the two prior questions. Maybe starting with Libmeldy, recognizing it's an uneven and somewhat unpredictable, but just to get a sense for any backlog that you currently have in terms of patients that we can be expecting as almost a guarantee for the remainder of the year? And then when we think about MPS-IH, 2023 is still a fairly broad range. So just Bobby, if you can walk us through sort of your confidence that sort of the feedback you are incorporating now is indeed going to be sort of the final iteration, if you will, before you initiate -- and would that be sort of a 1-half issue or second half initiation...

[Bobby Gaspar:]

Okay. So let me hand that over to Braden to talk about patients for Libmeldy, and then I'll pick up on the MPS-1 contraction.

[Braden Parker:]

Thanks, Bobby, and thanks for the question. I'd say that patient identification is progressing very well across the region. We've been very pleased with the number of referrals coming into the major centers. Part of the challenge of MLD is identifying patients within that treatment window of opportunity where they may benefit from Libmeldy, which is part of the reason why it's somewhat of an uneven identification process. As we've noted, we have treated 3 patients, 2 of which are representatives in this quarter, and there are a number of active cases that we're working on right now. But moving forward, we're not going to be providing intra-quarter updates on individual treated patients. We're focused really on building a sustainable commercial operation and business overall.

[Bobby Gaspar:]

And so on MPS-I. So just to reiterate here, this is a MPS-I is a systemic disease, and it does have impact on multiple different organ systems. So not only newer cognitive impairment but also on cognitive deformity, vision, hearing, cardiovascular abnormalities, et cetera. So in terms of designing specific endpoints, it's extremely important to look at that because that is the overall burden of disease in MPS-I. And not a number of those are ultimately addressed by the current standard of care. And so -- and as I said before, we want to show a meaningful difference from allogeneic transplant. And so we've got an ongoing dialogue with the regulators on the appropriate comparison and endpoint selection. Once we have clarity on the final study design once that submission is clear, then we can look at trial initiation. So as I say, we can give you further guidance later once we have that clarity from the regulators and we have a study deploying cleared by the agencies. And then as said, we can point to when the study will initiate. .

[Operator:]

Our next question is from David Hoang from SMBC...

[David Hoang:]

So I just really had one on maybe understanding the, I guess, patient journey for the commercial MLD patients. Can you just talk a little bit and provide a little bit of color as to what that patient journey looks like once you have a referral come in, what needs to be done to confirm if the patient is eligible for treatment? And then if they are confirmed, does that necessarily imply that reimbursement will follow.

[Bobby Gaspar:]

Thank you. And again, let me hand that over to Greg.

[Braden Parker:]

Sure. Thanks for the question. The patient journey is fairly consistent. It may vary somewhat based on region and exactly where the patient is identified. But generally speaking, once a patient is identified as potentially MLD, they'll be referred into one of our major treatment centers in the countries that we have treatment centers in right now, the U.K., France, Germany, Italy, the Netherlands, where they'll be assessed by the clinical experts there and confirmed diagnosis for MLD. Then part of the assessment is their eligibility based on the European marketing authorization. So ensuring that they're either presymptomatic or their symptoms have not progressed too far. And once that happens, then they'll schedule for apheresis where the cells will be collected and then sent to our manufacturing site in Milan, Italy, where they'll be transduced with Libmeldy and then cryopreserved and sent back to the center for reinfusion in the patient. So this process could take anywhere from 6-plus weeks depending on where they're coming from and whether or not reimbursement is in place at the time of the referral and diagnosis or if there's early reimbursed access available in that country as well. So the process could take a little bit longer if it's in a country where you need to get some type of authorization where there's not reimbursement in place or it could move much more quickly if it's a patient that's been identified in one of the countries where we've already secured an agreement. So hopefully, that provides a little bit of color of the process.

[David Hoang:]

Yes, that's very helpful.

[Operator:]

Our next question is from Pete Stavropoulos from Cantor Fitzgerald.

[Pete Stavropoulos:]

Bobby and team. So I know you're working to align with the FDA and the European regulators. But for the upcoming registrational study for MPS-I, when you think about the patient population you may enroll and particularly the age of the patients, how are you thinking about that? Do you think you will target only younger patients, so that clinical benefit on --- cognitive benefit can be observed or perhaps you can go for a broader range of patients that will be separated into subgroups or cohorts based on age. And also when you think about the patients who have had ERT, a number of them develop antidrug antibodies, do you see that affecting efficacy of 203 in any way?

[Bobby Gaspar:]

So maybe Leslie, if you're happy to take that question.

[Leslie Meltzer:]

Sure. I'm happy to take that. So for the first question around the target population, specifically in terms of age, we'll be able to share more detail on specific game drains when we have the final protocol. But I will say that we're looking to evaluate how this therapy compares to the current standard of care, which is allogeneic HSCT. And generally speaking, the approach is to administer current standard of care as early as possible in the disease course. So we are looking at a design where we're likely treating very young patients as early in the disease course as possible to eventually prevent manifestations of disease. So that is something we would be looking at in the final design. When it comes to antidrug antibodies, it's a great question. It's something that we actually see in our proof-of-concept study prior to patients entering the trial, 7 of those patients out of 8 total had prior exposure to ERT and did have anti-IDUA antibodies, a disease study onset. The conditioning protocol that we've used in that trial, which we would also employ in a registrational design once that final allowed us to reduce levels of anti-IDUA antibodies to nondetectable levels upon treatment with the gene therapy. So we would anticipate even if that is something that patients are presenting with an enrollment, the protocol that we're using would minimize the likelihood of that being something that would be of concern following treatment with OTL-203.

[Pete Stavropoulos:]

Thank you for taking our questions.

[Operator:]

Our next question is from Tessa Romero from JPMorgan.

[Tessa Romero:]

Just on the 201 MPS-IIIA readout that's coming up here by the end of the year. What is the size and the scope of that dataset that we'll be getting? And what would you think would be a win? And do you think that will be enough follow-up to assess clinical benefit? Or will there need to be longer duration to kind of assess that appropriately?

[Bobby Gaspar:]

And again, Leslie, I think that, that one is the...

[Leslie Meltzer:]

Sure. So what we presented so far from that study with the 5 patients that have enrolled is primarily biomarker data, expression of MCSH and clearance of GAGs in the periphery and in the CSF. And we would be in a position later this year to have 1 year of follow-up from all 5 pages that are enrolled in that on those biomarker endpoints that actually form the basis of the primary endpoint in this proof-of-concept study. We would also be in a position later this year for the investigators to share cognitive follow-up data in these patients. Like I said earlier, the disease progression of MPS-IIIA is such that patients generally flat show around the age of 3 and then start to show a drop off around the age of side. So in -- at the point where we have at least a year of follow-up from all patients, some of those patients will have more follow-up, but some of those patients will still have less follow-up in terms of getting to that point where you might start to be able to incorporate differentiation from the natural history. So we're really following this very closely and are determining how to make a decision on how to best proceed with this program once we have that additional clarity on cognitive apps. But you should expect to see by the end of the year that we would be able to present additional data because we will have at least a year follow-up from all patients.

[Operator:]

Our next question is from Vicki -- he from Oppenheimer.

[Unidentified Analyst:]

This is Jian for Kevin DeGeeter. Maybe just one for -- to follow up on the MPS-1H program. When you interact with the different regulators, do you hear kind of different feedback from the regulatory agencies? And how would that impact your timeline for initiation of the study? And then maybe you could highlight some of the ASGCT studies to look for next week.

[Bobby Gaspar:]

I'll take the first part, and then I'll hand it over to Leslie to talk about the ASGCT abstract. So just in terms of the interactions with the regulators, we did have Palo scientific advice from the FDA and the EMA last year. And in that interaction, they do give different feedback. So there is differences between the 2 agencies and what -- but at least they hear each other during that meeting. And then what we have to try and do is to address the comments both from the EMA and from the FDA. Having said that, there is some commonality in the feedback and the kind of study design that they would like to see the endpoints that they think are meaningfully important. So -- and let me just like this. In the end, we want to have one global registrational study. We don't want a study Europe and a different study for the FDA. We want one global registrational study. And so that is why these interactions that we're having are so important in order to be able to get the best study design for a single global registrational study and that will serve and get agreement for both the FDA and from the EMA. And so I'll now hand it over to Leslie to talk about the upcoming ASGCT abstract.

[Leslie Meltzer:]

Sure. Thanks, Bobby. So we're really excited about our presence at next week's ASGCT where we have seven different presentations. -- predominantly of our data from our neurodegenerative programs. And we show and are continuing to show the unique ability of gene-modified HSCs to distribute broadly throughout the body, including in the brain and other harder-to-reach tissues and enable localized delivery of therapeutic enzymes and proteins in the brain and other difficult-to-access tissues. And then specifically for MPS-I, there are 2 presentations. One is an invited lecture that is on the overall OTL-203 program, and we can expect that the investigators will be presenting the most current data available from that proof-of-concept study. I'll note that we now have nearly half of the patients with at least 3 years of follow-up. So some additional follow-up relative to earlier presentations and relative to our publication last year. We also have a poster presentation that is looking at the pathophysiological mechanisms of bone damage in Hurler syndrome and also looking at the potential of OTL-203 to enable bone cross correction in this disease. We have a number of presentations as well in our preclinical area that is looking to advance the applicability of the platform in other indications and predominantly degenerative indications, especially some work we're really excited about in the progranulin form of FTD.

[Operator:]

Sure. And we have a question from Pete Stavropoulos from Cantor Fitzgerald.

[Pete Stavropoulos:]

I know it's early stage, very early, but curiosity has been asking. One of the posters at the ASGCT. -- we'll be presenting data on a novel lentiviral promoter based on the human leukocyte antigen DR alpha promoter region. So I understand the promoter is able to induce basal levels of gene expression in microglia cells so cell-specific expression. Just wondering how the company is thinking about utilizing this novel tech? And like what kind of indications can you leverage it in?

[Bobby Gaspar:]

Yes. Thanks, -- and maybe I'll take that. So this is part of our ongoing collaboration with Dr. Alessandra Biffi at the University of Padua and our work on front of temporal dementia. So Remember, one of the important things here is that we want to get gene impression in the CNS. We can do that through the delivery of gene-modified HSCs into the CNS where they become micro clear. But the other important part here is we want the gene to be expressed in the context of neuro inflammation, which is present in this disease. And so we have been looking at promoters of what specific promoters to use and promoter selection is, again, extremely important for all kinds of reasons. And so you could have a ubiquitous promoting, you could have a macrophage-specific photo or you could have a promoter like we've thought about here, which responds to neuroinflammation. And certainly, in some Invitae studies that we've done and which will be presented, you can see that this promoter which is derived from LADR can respond to specific neuroinflammatory securitize. So FTD is one application for this type of promoter, but also if we want to use this in other neurogenetic conditions that are associated with new inflammation, it could be used in other indications as well. I mean there's still obviously quite some way to go, and we want to prove this concept both in first lien preclinical new line studies and then in a specific indication like FTD, but this is the kind of direction in which we want to move to be able to use HSCT therapy for a range of new genetic conditions.

[Operator:]

Thank you. I would like to turn the call back over to Bobby for final remarks.

[Bobby Gaspar:]

Thank you. So thank you, everyone, for your time and attention. By executing and delivering on our mission, we're confident we can create significant near-term value for our shareholders and the many other communities that we serve. Thank you...

[Operator:]

Thank you, ladies and gentlemen. That concludes today's call. Thank you for participating, and you may now disconnect.