This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk10: Good morning, everyone, and welcome to the Selecta Biosciences second quarter 2021 financial results and corporate update conference call. Currently, all participants are in a listen-only mode. This call is being webcast live on the investors and media section of Selecta's website at www.selectabio.com and is being recorded. For opening remarks, I would like to introduce Kristen Baldwin, Chief People Officer of Selecta. Please go ahead.
spk01: Thank you and good morning. Welcome to our second quarter 2021 financial results and corporate update conference call. The press release reporting our financial results is available in the investor and media section of Selecta's website, www.selectabio.com. And the quarterly report on Form 10-Q ended June 30th, 2021, which was filed today with the SEC. Joining me today are Karsten Bruhn, President and Chief Executive Officer, Peter Traber, Chief Medical Officer, and Kate, excuse me, Kai Kishimoto, Chief Scientific Officer. During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential, safety, efficacy, and regulatory and clinical progress of our product candidates, financial projections, and our future expectations, plans, partnerships, and prospects. These statements are subject to various risks that are described in the filings made with the Securities and Exchange Commission, including the most recent quarterly report on Form 10-Q. You are cautioned not to take place under reliance on these forward-looking statements, which speak only as of today, August 12th, 2021, and selected as claims any obligation to update such statements, even if management views change. I would now like to turn the call over to Carsten Bruhn.
spk12: Thank you, Kristen. Good morning. I appreciate you joining us today. To start, it's worth emphasizing our steadfast commitment to selectively mitigating unwanted immune responses through the development of next-generation antigen-specific tolerogenic therapies. Selecta continues to take a leading position in the immune tolerance field, and in the last quarter, we achieved several milestones that advanced our clinically validated intro platform across enzyme therapies, gene therapies, and autoimmune diseases. With that, I'll walk us through some of our key pipeline updates and upcoming milestones. First, a few key points on our enzyme therapy programs. SAL212, which was licensed to SOBE, is comprised of mTOR co-administered with our proprietary urocase, Fagatricase, for the treatment of chronic refractory gout. As a reminder, our phase three dissolved clinical program kicked off in the third quarter of 2020 and consists of two double-blind placebo-controlled trials of SAL212. In both trials, SAL212 will be evaluated at two doses of mTOR 0.1 milligrams per kilogram and 0.15 milligrams per kilogram. And one dose of begatricase, 0.2 milligrams per kilogram. Each trial aims to enroll 105 patients with 35 at each dose and 35 on placebo. Enrollment is progressing on schedule and top line data from DISSOLVE is expected in the second half of 2022. We intend to leverage the success of SEL212 for a second enzyme program indication in IgA nephropathy, which is a kidney disease that occurs when immune complexes of an antibody called immunoglobulin A1, or IgA1, accumulates in the kidneys. Genetic or environmental factors that cause abnormal IgA1 and its accumulation in the kidneys can result in the development of IgA nephropathy and lead to kidney disease. Although there are no approved therapies We believe our novel approach, which combines mTOR with IgA1 protease, has the potential to treat the root cause of the disease and overcome previous limitations associated with IgA protease development. Due to delay in securing a qualified CDMO to productive process development and manufacturing work, we expect to push our anticipated IND filing into 2022. Although COVID-19 and the recent surge has impacted supply chains and resulted in challenges, we've successfully secured a CDMO and ID enabling studies are currently underway. We'll provide updates on our progress later in the year. Now turning to our gene therapy programs. In the first quarter of 2021, in collaboration with Aspio, we initiated the first in-human phase one dose escalation trial of SAL399, an AV8 anti-capsid vector capsid or EMC101 containing no DNA combined with mTOR. The trial is being conducted in healthy volunteers and aims to determine the dose regimen of mTOR to mitigate the formation of antibodies to ABA capsid used in gene therapies. We're pleased with the progress made to date and remain on track. We expect to report top line data in the fourth quarter of 2021. Building on our ongoing anti-AV8 capsid study in the first quarter of 2021, we also strengthened our wholly-owned gene therapy portfolio by regaining exclusive rights to MMA-101, an AV gene therapy vector for the treatment of metabolic acidemia, or MMA, a rare metabolic disease in which the body cannot break down certain proteins and fats. The previously disclosed MMA-101 third-party manufacturing issue was resolved and we are pleased the manufacturing of a new lot has been completed and is currently undergoing final release testing. We expect to file an IND for our lead gene therapy candidate, SCL302, which is a combination of NMA101 plus mTOR in MMA during the third quarter of 2021. Further, our recent publication in the Journal of Molecular Therapy Methods and Clinical Development demonstrated our observation that mTOR enhances transgene expression after both initial and repeat dosing of an AV vector in a mouse model of MMA. The publication further validates the use of mTOR in our gene therapy pipeline and is especially relevant for the clinical development of SAL302. The Phase I-II SAL302 program, which is expected to commence in 2022, will evaluate biomarkers of the disease utilizing antibodies, safety, and tolerability. Our second wholly-owned proprietary gene therapy product candidate, SAL313, is being developed to treat ornithine transcarbamylase, or OTC deficiency. OTC deficiency is an X-linked genetic disorder caused by genetic mutations in the OTC gene, which is critical for proper function of the uracycle. Looking ahead, We expect to file a clinical trial application, or CTA, and or an IND in 2022. We submitted the Pediatric Investigation Plan, or PIP, for SEL313 to the European Medicines Agency Pediatric Committee in February 2021. Before we wrap up on gene therapy, Sarepta Therapeutics continues to conduct preclinical work looking at the combination of INTOR in certain neuromuscular disorders, including Dijon muscular dystrophy, or DMD, and limb-girdle muscular dystrophies, or LGMD, subtypes. We recently achieved a 3 million milestone payment for successfully meeting the criteria in a preclinical study under a research license and option agreement with Sarepta. This further validates the potential of INTOR's platform. Overall, we're seeing excellent progress and we look forward to building on this momentum as we move one step closer to addressing immunogenicity constraints in AV-driven gene therapy, as we strive to overcome repeat dosing limitations by preventing the formation of reducing antibodies, and as we enable more durable and robust expression of the transgene after the first dose. Now, moving on to our autoimmune program. Our recently published data in Frontiers in Immunology demonstrated that mTOR enhanced the tolerogenic environment in the liver, showed induction of a tolerogenic phenotype in all major hepatic antigen-presenting cell populations, and was protective in an acute model of autoimmune hepatitis. The publication further supports development of Selecta's mTOR platform for the treatment of liver-specific autoimmune diseases, including primary bilirucal angitis, or PBC, a chronic progressive autoimmune liver disorder that leads to inflammation damage, and scarring of the small bile ducts. PBC has a well-defined target antigen, significant unmet medical need, and is well-suited to the application of our mTOR immune tolerance platform. Our autoimmune program is advancing through IND enabling studies, and we expect to file an IND in PBC in the second half of 2022. Now I'll run through our financial results for the second quarter ended June 30th, 2021. We remain well capitalized. We had 151.5 million liquidity as of June 30th, 2021, which compares to 149.2 million liquidity as of March 31st, 2021. We believe our liquidity will be sufficient to meet our operating requirements into the third quarter of 2023. Net cash used in operating activities was 18.2 million for the six months ended June 30th, 2021, as compared to 23.5 million for the same period in 2020. Revenue recognized for the second quarter of 2021 was 19.6 million compared to no revenue recognition for the same period in 2020. Revenue was recognized under license agreement with SoBe, which began in July 2020, resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase III dissolved clinical program. Additionally, during the second quarter, we recognized less than 0.1 million for shipments under the license agreement of Sarepta and 0.1 million resulting from the expiration of the contractual audit term under the Skolkovo Foundation grant. Research and development expenses for the second quarter of 2021 were 14.5 million, which compares with 10.7 million for the same period in 2020. During the quarter ended June 30th, 2021, there was an increase in expenses incurred for consulting, salaries, and the discovery of programs offset by a decrease of ASPbio collaboration costs. General administrative expenses for the second quarter of 2021 were 4.7 million, which compares with 5.6 million for the same period in 2020. The decrease in costs was primarily the result of reduced expenses for salaries, professional fees, and patent expenses offset by increased consulting and stock compensation expenses. For the second quarter 2021, we report net income of 4.6 million or basic net income per share of 4 cents compared to a net loss of 24.1 million or basic net loss per share of 25 cents for the same period in 2020. Before concluding today's call, we have a few corporate updates to share. As we enter a critical inflection point in development, we're excited to welcome gene therapy pioneer Dr. Jude Samulski as special advisor. He's a professor of pharmacology and has been director of the University of North Carolina Gene Therapy Center for over two decades. He was awarded the first patent for AV as a viral vector and was the first recipient of the American Society of Gene and Cell Therapy Outstanding Achievement Award for Lifetime Achievements in Gene Therapy. Dr. Samolsky has advanced gene therapies in the tumor trials for hemophilia, eugenic mastoid dystrophy, giant axonal neuropathy, Pompe disease, and heart failure. He's currently the president, chief scientific officer, and co-founder of ASPIO. We're also pleased by the addition of industry leader, Nishan De Silva, to select us board of directors. Dr. De Silva has extensive leadership experience, most relevant in gene therapy development manufacturing and regulatory activities. Dr. De Silva brings over 20 years of experience in biotechnology operations, biopharmaceutical venture capital, and healthcare management consulting. He's currently Chief Executive Officer and Director of Ethics Therapeutics, a private venture-backed biotechnology company focused on addressing unmet needs in mucosal diseases. Previously, Dr. De Silva served as President Chief Operating Officer and Director of Poseida Therapeutics, a cell and gene therapy-focused biopharmaceutical company where he oversaw clinical development, regulatory, manufacturing, finance, and business development activities. Together, Dr. Samulski and Dr. De Silva's contributions will be invaluable as we continue to advance into the clinic. As mentioned earlier, we're extremely excited about the continued growth of our company and remain confident in our platform. I'd like to conclude by reiterating our gratitude to the many people who have been supportive along the way, including our patients and their families, our investigators, and our great team at Selecta. With that, we're happy to take questions. Operator?
spk10: Ladies and gentlemen, at this time we'll begin the question and answer session. To ask a question, you may press star and then one using a touchtone telephone. To withdraw your questions, you may press star and two. If you are using a speakerphone, we do ask that you please pick up the handset prior to pressing the numbers to ensure the best sound quality. Once again, that is star and then one to join the question queue. We will pause momentarily to assemble the roster. Our first question today comes from Kristen Kluska from Cancer Fitzgerald. Please go ahead with your question.
spk05: Hi, good morning, and thanks for taking my questions. So there was a recent publication which surveyed hemophilia patients, asking them to rank the most important aspects of a gene therapy treatment, where dose frequency and durability were actually found to rank as the greatest importance for heme B patients. So I know you've presented and published a lot of preclinical data this year, but I believe your recent molecular therapy publication was one of the longest studies that you've evaluated for mTOR in gene therapy. So I would like to ask if you could please discuss the key trends that you've observed on durability here, and generally speaking, the implications you think mTOR could have on durability, including through potential redosing and other aspects.
spk12: Yeah, thanks for the question, Kristen. You're right. You know, dose frequency and durability is a key issue both for physicians and patients. And we're pleased with the data we have to date. I'll let Kay comment a little bit more in detail on the findings in that study. Kay?
spk02: Good morning. Yes, so I think that that study highlighted two things. One, not only can we redose, but we're actually seeing significant enhancement of transgene expression and activity after the first dose. So we think that there's a benefit of adding mTOR to gene therapies, both at the first and second dose. Obviously, durability, as you say, is a concern. And by and large, actually, hemophilia has been so far restricted to adult patients. So, the question of durability becomes even more pressing, I think, for pediatric indication.
spk05: Okay, thanks. And then as you're currently conducting the first in-human study now, I wanted to ask what key questions you think could be helped answered with the empty capsid study and the data later this year, including the assessment of AAV8 neutralizing antibodies, and then which items do you think will be important to focus on next year with the MMA trial? And I know you're guiding to launch the trial next year, but do you also think that we will see some initial biomarker and safety data in 2022 as well?
spk12: Yeah, that's a great question. So as we guide it, we'll have results from the anti-capsid study in the fourth quarter of this year. And really what we're looking at is, you know, are we able to prevent levels of new antibodies you know, when co-administered with the AV8 capsule with mTOR. And, you know, what we expect in terms of what we've seen with a non-human primate data that, you know, we would primarily look at the 30-day data and, you know, are we able to prevent formation of the antibody. So it's a very important readout for us. But the primary goal is really to find the right dose of mTOR. It's, in essence, a dose escalation study. We're looking at two doses. In terms of the MMA trials, we haven't guided in detail, Kristen, as you know, but we're pleased that we're able to file the IND in the third quarter of this year, so a little bit ahead of the previous guidance that we've given. We'll give more detailed guidance after the FDA the IMD file, but I think it's fair to say that there is possibility that we'll be able to show some biomarker at least of the first cohort in 2022. Obviously, it's a safety study primarily, and we're also focusing obviously on the ability to prevent formation of the antibodies, but biomarkers will be something we're going to look at for sure.
spk01: Great. Thank you.
spk10: Our next question comes from Raju Prasad from William Blair. Please go ahead with your question.
spk11: Thanks for taking the question. Maybe if you could just give us a little bit of color on the different doses of mTOR that you're testing in the 399 study, and how are you going to look at that data in regards to some of the disease-specific trials that you're running next year? And I have another question.
spk12: Yeah, that's a great question, Raj. So in terms of doses, we're looking at two doses in the empty capsid study. We're looking at 0.15 milligrams per kilograms and 0.3 milligrams per kilograms. Both doses that have been in the clinic in humans As you know, we're taking the 0.15 dose forward in the Phase III currently for chronic refractory gout. We haven't guided yet on the dose we're going to use in MMA. We'll do that once we have submitted the IND application to the FDA and received feedback. I think maybe just, Raj, one additional comment around this. We, you know, in gout, we're dosing up to 12 times. So, you know, in the phase three, whereas we see in gene therapy, we likely need less doses. If you look at the non-feminine primates study, we require three doses to prevent formation of antibodies. So I think there's a possibility to use a higher dose, actually, in gene therapy, given we don't plan to give, you know, up to 12 doses. I think that's just further consideration, but we'll give guidance after we've filed the IND.
spk11: Is there anything you're thinking about with MMA and OTC primarily being more pediatric disease indications regarding the prevalent population or the incident population and the dosing?
spk12: Yeah, that's an important question, actually. I'll let Peter talk a little bit high level. I don't think we're ready to disclose details yet, but just some general understanding we have of rapamycin in pediatric use. Peter?
spk06: Sure. There is some information on the use of rapamycin in pediatric patients, including renal transplant. a number of cancer treatments. And so we do know a bit about the pharmacokinetics in pediatrics. And while we haven't dosed mTOR in children, we believe that our approach will be safe and tolerable from the standpoint of comparison of clearances between pediatrics and adults where actually children have a higher clearance rate and therefore lower levels of rapamycin in comparison to adults. So we think we'll be able to dose with the same doses that we've used in adults with a bit of a safety margin and of course then we will guide our continued dosing with rapamycin levels.
spk11: Great. And then maybe just one quick follow-up. I think at ASCCT you had a preclinical presentation on dosing in the presence of preexisting maternal antibodies. So are you still thinking about using mTOR in patients with maternal-derived antibodies versus kind of bona fide pre-existing antibodies?
spk12: Yeah, that's a good question, Raj, as well. So, you know, currently in humans, we don't think that mTOR, you know, addresses pre-existing antibodies. So we would, the current thinking is that we would use the same criteria as for other gene therapies in terms of, you know, excluding patients with pre-existing antibodies. Obviously, that population is a bit lower in kids than adults, You know, we think there are other potential treatment approaches outside of Intour to address that amid need, such as an ITG Protease, for example. But I'll let Kay maybe come and give a bit of context to that presentation we gave.
spk02: Hi. Yeah. We have seen some effect of mTOR on low levels of preexisting antibodies. But as Carson said, I think it's limited in terms of patients that would high levels. But I think that when we give mTOR with AV gene therapy for naive patients, so in other words, patients that are antibody negative, we see very robust data for enabling redosing in those animals.
spk11: Great. Thank you for the questions.
spk10: Our next question comes from John Newman from Canaccord. Please go ahead with your question.
spk03: Hi, guys. Thanks for taking my question. So, Carson, there's been a couple of questions asked already regarding the empty capsid data coming up later this year. I'm going to ask something along a different vein. So the question is, do you see much competition in this area? I'm not aware of many companies that are able, really any companies that are able to effectively redose to prevent neutralizing antibody formation at the moment. I'm just curious as to what you're seeing out on the landscape. In terms of the MMA study next year, I know you're not commenting on mTOR dosing, but would it be reasonable to assume that you would look at a multi-dose regimen of mTOR, and should we assume that the mTOR dosing would remain constant, that you wouldn't, for example, sort of step up the mTOR dosing at some of the later doses? Thanks.
spk12: Yeah, thanks, John. Great questions. Yeah, so in terms of competition, we do believe we're quite a unique position, you know, when it comes to address this issue to prevent formation of new antibodies. To our knowledge, we're the only company actually that has demonstrated the ability to reduce the formation of new antibodies and enable redosing, actually. And I think we have dosed now in mice, I think, up to three times or four times. um so to our knowledge that we're you know we're the only company that um has done this and obviously we have very uh broad clinical experience within tour and other indications like in chronic effector gal what we have now i think close to 280 290 patients dosed with um in tour up to up to six months um there's i think there's one um approach which we find quite interesting actually and which might be complementary to mTOR is the use of an IgG protease to address the pre-existing antibodies. But then the actual enzyme is quite immunogenic itself. But in terms of the ability to prevent formation, we believe we're in a unique position and obviously we'll have data in the fourth quarter. In regards to your question on MLA, Definitely, you're right. Based on the non-human primate data, it looks like three doses are required to prevent the formation of antibodies. Have not changed the dose. We've always used the dose, the same dose throughout. But as we mentioned earlier, we're not in the position yet to guide in detail on that phase 1, 2 study. We'll do this after we file the IND with the FDA.
spk03: Okay, great, thank you.
spk10: Our next question comes from DeFi Yang from Mizuho Securities. Please go ahead with your question.
spk08: Hi, good morning. This is Dan Clark on for DeFi. Just two from us. To start actually piggybacking off of John's question, we'd be curious to get your thoughts on non-viral gene therapy applications. delivery methods versus the combination of AAV and mTOR? And I have a follow-up as well, thanks.
spk12: Yeah, that's a great question. And there's a lot of excitement and noise in non-viral approaches. But I think it's also fair to say that it's fairly early in terms of just clinical evidence. There are right now, and don't quote me the exact number, but I think there's over 1,000 gene therapy trials registered on clinicaltrial.gov with AEB TAP SIDS, and obviously those will not go away. I think non-viral approaches are interesting, but I think they're very early stage.
spk08: Great, thank you. And then, do you have any data on mTOR improving transgene expression in targets other than the liver? And is this sort of part of what's going on in the Sarepta collaboration? Thank you.
spk12: Yeah, that's a great question. And I'd like to comment as well, but to my knowledge, all the work that we have done was in liver-based diseases. Unfortunately, we can't comment on the Sarepta data. Other than that, we received a 3 million milestone. for meeting the success criteria of a preclinical study, which we're obviously very thrilled about. It is obviously in a neuromuscular disease model and also in a higher dose than we've previously used, but that's as far as we can comment, unfortunately. Mr. K, would you have anything else to add?
spk02: Yeah, I don't really have anything to add to that. Thank you.
spk10: Thank you. Our next question comes from Yun Zong from BTIG, please go ahead with your question.
spk00: Great. Thanks very much for taking the question. So a question on the empty capsid study. And I just wanted to confirm that are you looking at different doses of AAV8 as well or just a single dose? And I wonder whether the effect of mTOR will be dependent on the dose of AAV8. capsid, given that for different indications for different capsid, probably companies will have to try different doses.
spk12: Yeah, thanks for the question, Yun. That's a good question. So we're using a single dose of 2E12 of AB8 anti-capsid. Obviously, it's important to keep in mind this is a healthy volunteer study. So we didn't feel it was appropriate to go with a higher dose. And we're testing two doses of mTOR the 0.15 milligrams per kilogram and the 0.3 milligrams per kilogram. But we have some, you know, we have some non-human data with higher doses of AV and showed good control of Northlander bodies. It's just in this setting, in healthy volunteers, you know, we didn't think it was a good idea to go with a higher dose for safety reasons. Okay, great. Thank you.
spk10: Our next question comes from Kill Bloom from Needham and Company.
spk09: Please go ahead with your question. Hi, and good morning, and thanks for taking our question. So as you guys are probably well aware, there's an upcoming advisory committee meeting around safety for AAVs. Do you guys think that, first of all, will redosing come up as a topic at all? And secondly, considering mTOR is an immunosuppressant, Is there potential for it to improve the safety of general administration of AAVs? Thank you.
spk12: Yeah, so I'll let Kay or Peter comment on the adcom, which we're obviously aware of. But yeah, we do have some encouraging data around safety. We have demonstrated that Intour has hyperprotective properties. Obviously, the elevated transaminases are only observed in humans, not in animal studies. So obviously, we're not able to conduct experiments specifically around that. But we have pretty, I think, compelling data that shows that mTOR is highly hyperprotective. The other, I think, safety approach is we've also shown a dose sparing effect. So with the first dose benefit having a higher higher efficacy after the first dose, which means you could potentially use a lower dose to begin with, which also is positive in terms of safety, as most of the safety events reported or deaths reported were at the very high doses of AAV. Peter, do you have anything to add on the outcome?
spk06: No, I don't have anything to add except that we, you know, are quite interested in this. And we're fortunate that Kay has had a lot of input into the FDA talking about mTOR and its ability to potentially change the game in gene therapy. And so they're well aware of Selectus technology and very interested in it. I would just mention one thing that, you know, when you made the comment, you talked about it, mTOR being an immunosuppressive. Actually, that's one of our advantages is that we really don't globally immunosuppress with mTOR. specifically immune-tolerized to the antigens that we give at the same time. So we're getting tolerance to AAV in the animal studies that we've seen, and we hope to be able to replicate that in humans. And that's a very important point because across the board, immunosuppressants have a lot of side effects because they're reducing immunogenicity to all kinds of antigens, whereas we have a rather targeted approach. I would also say that we hope, based on what Carson said about the liver approach, that mTOR may be able to spare using steroids in people who get AAV therapy. Steroids in fact are relatively contraindicated in a number of indications, such as MMA and OTCD. And so, a steroid sparing effect could also be useful in addition to reducing the hepatotoxicity.
spk02: Yeah. I might also add that, you know, one of the concerns of FDA is the liver inflammation, the liver transaminase elevation that's often seen in patients. And unfortunately, we can't study that specifically in animals because it's only been observed in humans in response to AAV. But what we have seen is that in animal studies, we've seen inhibition of T cell activation and the appearance of CD8 expressing cells in the liver. And previously, the CD8 specific, AV specific CD8 T cells have been associated with this liver enzyme elevation. And then finally, as Carson mentioned, we have shown that mTOR does mitigate inflammation in the liver and other animal models of liver inflammation.
spk10: Our next question comes from Ram Silverahu from H.C. Wainwright. Please go ahead with your question.
spk07: Hi, this is Bubal and dialing in for Ram Silverahu, and thanks for taking my question. So obviously you hired Professor Samusky. So are there particular programs where his expertise will be very, very helpful to you?
spk12: Yeah, great question. Yeah, we're very pleased that we're able to work with Dr. Samolsky. He'll support us across all our gene therapy programs that we have fully owned. And obviously, by now, the focus is clearly on MMA, a program he's very familiar with, as we have this as part of the as bio and select the agreement and as you know that returned this program so he brings a lot of expertise in that's really the initial focus um but he's also working with us um on uh you know the otc deficiency indication as well and other preclinical programs just to strengthen um you know our understanding of how intro can be used uh in the clinic great
spk07: And one more from me. So how does your IgA nephropathy program stack up against a drug like norsoplimab?
spk12: Yeah, so I think we have quite a unique approach in IgA nephropathy. And just to kind of step back, what we're trying to do here, we're really building on the learnings of our program in chronic refractory gout, SEL212, where we basically develop patients of serum acid deposits Here, we're using an IgA protease, which is also quite an immunogenic bacterial origin, to debug patients of IgA1 immune complex deposits. And to our understanding, we're the only therapeutic approach at the moment that addresses kind of the underlying root cause of the disease, the actual IgA1 complex deposit. So we think it's quite differentiated from that perspective.
spk07: Okay. That's it from me. Thank you.
spk10: And our next question is a follow-up from John Newman from Canaccord. Please go ahead with your follow-up. Hi there.
spk03: Just a follow-up regarding redosing and gene therapy. So I guess a question for the team. I just wondered if you could remind us some of the issues that are faced, I think, when we think about redosing and gene therapy. We're mainly thinking about not being able to give a second or third dose. But what are some of the other issues that that you've seen in your work in the field that are an issue, for example, in clinical trials? Thanks.
spk12: Yeah, that's a great question, John. I mean, there's a couple of applications here, right? A key challenge is often to find the right, the first dose in a phase one study. If you dose too low, you're not able to give a second dose. So that could be a potential application for mTOR, so you're able to titrate up if you were too low in your first dose. Another theoretical approach, and we haven't really studied this yet, but especially indications where you give very high viral vector doses, like in neuromuscular disorders, we're in the magnitude of E14, The potential to give multiple lower doses potentially, I think that's a very interesting approach as well, where you might be able to avoid some of the safety concerns that were discussed earlier. And we at least in animal data, we have pretty compelling data that this approach is potentially quite dose sparing as well. So that's another potential application. But I think that the biggest need right now is really The limitation of not being able to give a second dose and durability is clearly the key driver to the limitation right now.
spk10: Great. Thank you. And ladies and gentlemen, with that, we'll conclude today's question and answer portion of the call. We'd now like to turn the conference call back over to Selecta's CEO, Carson Brunn, for closing remarks. Carson?
spk12: Thank you, operator, and thank you, everyone who joined us this morning. Stay safe and healthy, and this concludes today's call. Thank you.
spk10: Ladies and gentlemen, that does conclude today's conference call. We do thank you for attending. You may now disconnect your lines.
Disclaimer