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spk05: Good morning, and welcome to the Selecta Biosciences third 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 investors and media section of Selecta's website at www.selectabio.com, and it is being recorded. For opening remarks, I would like to introduce Kevin Tan, Chief Financial Officer of Selecta. Please go ahead.
spk06: Thank you and good morning. Welcome to our third quarter 2021 financial results and corporate update conference call. The press release reporting our financial results is available in the investors and media section of Selective's website, www.selectivebio.com. And the quarterly report on Form 10Q ended September 30th, 2021, which was filed today with the Securities and Exchange Commission, or SEC. Joining me today are Carson Bruhn, President and Chief Executive Officer, Peter Traber, Chief Medical Officer, and Kay 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, in our future expectations, plans, partnerships, and prospects. These statements are subject to various risks that are described in the filings made with the SEC, including the most recent quarterly report on Form 10Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, November 9th, 2021, and selected disclaims any obligation to update such statements, even if management's views change. I would now like to turn the call over to Carson Brunn. Carson?
spk03: Thank you, Kevin. Good morning. I appreciate everyone joining us today. In the last quarter, we made significant advancements that propelled our business and our existing pipeline forward, which has the potential to overcome immunogenicity, mitigate unwanted immune responses against enzyme or gene therapies, and restore self-tolerance in patients with autoimmune diseases. We're encouraged by the numerous strategic collaborations that have further validated our mTOR platform, designed to mitigate unwanted immune responses across a range of diseases and by the opportunities to advance next-generation therapeutics. Further, these partnerships demonstrate the broad application of mTOR, and we look forward to maximizing the value of our platform as we build on this momentum. This is a truly exciting time for Selecta, and yesterday we announced top-line results from the first in-human, Phase I dose escalation trial of SEL399, which we conducted jointly with ASPbio. SEL399 is an AV8 empty capsid, or ENC101, containing no DNA combined with mTOR at doses of 0.15 mg per kg and 0.3 mg per kg. The randomized placebo-controlled and double-blind dose escalation study conducted in Healthy Volunteers was designed to determine the dose regimen of mTOR to mitigate the formation of the lesion antibodies, or NABs, against an AV8 capsid used in gene therapies. A total of 23 Healthy Volunteers were enrolled, 14 males and nine females. All subjects had an anti-AV8 NAB titer of less than 1 to 5 at baseline, The primary endpoints evaluated were safety and anti-AV8 antibody titers. We observed a strong immune response in humans administered AV8 anti-capsides. The peak median anti-AV nap titer was 1 to 6,875 at 14 days after infusion, which was maintained at high levels through day 90. The addition of mTOR to administration of anti-capsides was observed to reduce the formation of anti-AV8 NAVs in a dose-dependent manner at day 30. Median day 30 titers of anti-AV8 NAVs were 50-fold and 250-fold lower in the 0.15 mcg and 0.3 mcg into our cohorts, respectively, compared to the median titer of control subjects, those with AV8 anti-capsules alone. At 30 days, subjects who received 0.3 mcg of Intor, 6 of 6 or 100% exhibited an anti-AV8 MAP titer of 1 to 25 or less, and 4 of 6 or 67% had a titer of 1 to 5 or less. At 30 days, subjects that received 0.15 mcg of Intor, 6 of 9 or 67% exhibited an anti-AV8 MAP titer of 1 to 25 or less, and 2 of 9, or 22%, had a titer of 1 to 5 or less. At 90 days, 2 of 6 subjects in the 0.3 mcg per k cohort were observed to have sustained control of NAPs with titers of 1 to 25 or less. Consistent with preclinical data, we observed that the single-dose intro cohorts saw delayed formation of NAPs, eventually reaching similar median levels of NAPs to the control group by day 90. Based on prior animal studies, we believe that if NAFs are inhibited at day 30, administration of two additional monthly doses of Intor has the potential to maintain control of NAFs beyond day 90. From a safety perspective, there were no unexpected AEs related to Intor. The most common AE was mild to moderate stomatitis, which was ameliorated with steroid mouthwash treatment. We believe this data demonstrate in-tour's potential to address one of the biggest current limitations in gene therapy, the inability to redose lifesaving gene therapies due to the formation of NAVs against AV capsids. We look forward to leveraging these findings across our wholly-owned gene therapy pipeline and alongside our world-class gene therapy partners to achieve our goal of improving the lives of those living with monogenic disease. The press release and webcast with additional detail can be accessed in the investors and media section of our website. Next, I would like to highlight our recent business development activity and provide an overview of the key collaborations that have expanded our pipeline of novel therapeutics in combination with our IMTOR platform. We entered a strategic licensing agreement with Takeda, a global pharmaceutical leader with expertise in rare diseases, to develop targeted next-generation gene therapies for two indications within the field of lysosomal storage disorders. Together, we look forward to overcoming barriers to current efforts in AAV-driven gene therapy, as well as striving to address immunogenicity constraints to enable redosing of potentially lifesaving gene therapies. Under the terms of the agreement, Selecta is entitled to receive an undisclosed upfront payment and up to 1.124 billion in future additional payments over the course of the partnership that are contingent on the achievement of development or commercial milestones. Selecta is also eligible for tiered royalties on future commercial sales. We are encouraged by the strong endorsement from large pharma and from other major players in the gene therapy space. To further address key hurdles in gene therapy, we announced an exclusive strategic licensing agreement with Genovese to advance either SORC or ZORC, a next-generation ITG protease, to enable the dosing of transformative gene therapies in patients with preexisting AV immunity and treat certain ITG-mediated autoimmune diseases. While most ITG proteases are derived from human pathogens and have a high prevalence of preexisting antibodies, Zork is derived from a streptococcal bacterial strain that does not infect humans. The combination of Zork and Intor has the potential to both mitigate preexisting antibodies to AAV, expanding access to gene therapy to a wider range of patients, and prevents the novoimmunogenicity, keeping patients eligible for retreatment. Additionally, bacterial-derived ITG proteases are themselves immunogenic, Currently, IgG proteases can only be administered once due to the formation of high titer antibodies against the protease itself. The combination of Zork and Intor is further differentiated by the potential of Intor to mitigate the immunogenicity of Zork and enable redosing of the enzyme, an important benefit for the application of IgG proteases in autoimmune diseases mediated by pathogenic autoantibodies. In relation to our enzyme therapy program, we announced a partnership with Ginkgo Bioworks, or Ginkgo, to design novel enzymes with transformative therapeutic potential to advance treatments for orphan and rare diseases. This partnership's built on our compared trial of SCL212 in chronic refractory gout, which provides proof-of-concept data related to intours effect when combined with immunogenic enzymatic therapies. Under this agreement, with Ginkgo, Selecta gains rights to develop and commercialize select therapeutic enzymes from their advanced organism engineering platform to treat autoimmune diseases. We expect that our intro technology, in combination with Ginkgo's high-throughput enzyme discovery, design, and screening capabilities will bring us one step closer to improving the sustained efficacy of novel biologic therapeutics. Finally, we established a protein engineering collaboration with Cyrus to radically redesign protein therapeutics. The lead program in the collaboration is a proprietary interleukin-2, or IL-2, protein agonist designed to selectively promote expansion of regulatory T cells, or Tregs, for the treatment of patients with autoimmune diseases and other deleterious immune conditions. Preclinical data investigating the effects of Intor in combination with an IL-2 mutine, demonstrates substantial synergistic activity in increasing the percentage and durability of Treg expansion in the spleen. This supports the potential of mTOR in combination with IL-2 proteins to restore immune tolerance to autoantigens and forms the basis for this partnership. Collectively, these strategic partnerships provide additional validation and further demonstrate the robust value of our IMTO platform. This is truly an exciting time for Selecta, and with our unique approach and strong cash position, we're well-equipped to maintain our leadership position in the targeted immune tolerance field. I'll now take us through some of our key pipeline updates and upcoming milestones. First, a few key points on our enzyme therapy program, which has established an important framework for our clinical development path. SEL212 was licensed to SOBE and is comprised of Intor, co-administered with our proprietary uricase, Pegatricase, 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 SEL212. In both trials, SEL212 will be evaluated at two doses of Intor, 0.1 milligrams per kilogram and 0.15 milligrams per kilogram, and one dose of Bacathetase, 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 our second enzyme program indication in IgA nephropathy, or IgAM, which is a kidney disease that occurs when immune complexes of an antibody called immunoglobulin A1, or IgA1, accumulate in the kidneys. Current treatments fail to address the root cause of the disease, and we believe our novel approach, which combines mTOR with IgA1 protease, has the potential to remove injurious IgA from the kidneys, and improve markers of renal dysfunction. We remain encouraged by the strong preclinical data in IGA and expect to file an IND for IGAN in 2022. Returning to our gene therapy program, as noted, immune responses to AV gene therapy have historically precluded the ability to safely redose AV gene therapies and are a major consideration related to safety and efficacy in this space. The ability to inhibit the development of AB-specific antibodies has the potential to be transformational and shift the treatment landscape. We continue to advance our proprietary gene therapy programs and filed an INV for our lead gene therapy candidate, SEL302, which is a combination of MMA101 plus Intor. is an AV gene therapy vector for the treatment of metabolic acidemia, or MMA, a rare metabolic disease in which the body breakdowns certain proteins and fats. As of the filing of this queue, the FDA's 30-day review period for R&D to conduct the Phase 1-2 clinical trial of our SEL 3 or 2 product candidates in pediatric patients with metabolic acidemia has expired. However, we have been informed orally by FDA that they're still considering certain aspects of our filing related to chemistry, manufacturing, and control, or CMC. We intend to wait for formal clearance from FDA before initiating the proposed Phase I-II clinical trial. Our second wholly-owned proprietary gene therapy candidate, SCL313, 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 urea cycle. We expect to file a clinical trial application or CTA and or an IND in 2022. We submitted a pediatric investigation plan or PIP for SEL313 to the European Medicines Agency Pediatrics Committee in February 2021. Overall, we're seeing excellent progress across our gene therapy program, and we look forward to providing further updates later this year as we continue to address the immunogenicity constraints in AV-driven gene therapy, as we strive to overcome repeat dosing limitations by preventing the formation of NAVs, and as we enable more durable and robust expression of the transgene after the first dose. Now, moving on to our autoimmune program. Our autoimmune program is advancing through IND-enabling studies, and we expect to find IND in primary biliary cholangitis, or PBC, in the second half of 2022. PBC is a chronic progressive autoimmune liver disorder that leads to inflammation, damage, and scarring of the small bile ducts. PPC has a well-defined target antigen, significant unmet medical needs, and is well-suited to the application of our Intor platform. Autoimmune disease affects more than 24 million people in the U.S. alone, and we look forward to expanding our pipeline as we continue to explore additional applications of our Intor platform. Before we turn to the financial results, we have one final update to share. As we execute on our clinical and corporate initiatives, we continue to add talent and best to our leadership team and are excited to welcome Kevin Tan as Chief Financial Officer. Kevin brings deep financial expertise and experience in the gene therapy and rare disease landscape. His impressive track record in capital management and financing in both the biotech and investment sector will be invaluable as Selecta continues to pursue new partnership opportunities and advance multiple assets through the clinic. As mentioned earlier, we're extremely excited about the continued growth of our company, and we remain confident in our platform. Now, I'll turn the call over to Kevin to run through our financial results for the third quarter and the September 30th, 2021.
spk06: Thank you, Karsten. We remain well capitalized with $140 million in liquidity as of September 30th, 2021. which compares to 140.1 million in liquidity as of December 31st, 2020. We believe our liquidity will be sufficient to meet our operating requirements into the second quarter of 2023. Net cash used in operating activities was 28.9 million for the nine months ended September 30th, 2021, as compared to 42.1 million of cash provided by operating activities for the same period in 2020. Revenue recognized for the third quarter of 2021 was $24.4 million, compared to $4.6 million for the same period in 2020. Revenue of $24.3 million was recognized under the license agreement with SOBI, resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase III dissolved clinical program. The significant revenue increase is the result of the continued enrollment of the Phase III dissolved clinical program that was initiated in the third quarter of 2020. Additionally, during the third quarter, Selecta recognized 0.2 million for the shipment under the license grant with Sarepta. Research and development expenses for the third quarter 2021 were 21 million, which compares with 14 million for the same period in 2020. During the quarter ended September 30th, 2021, there was an increase in expenses incurred for preclinical programs salaries, headcount, and ask-buy collaboration costs. General and administrative expenses for the third quarter of 2021 were $5.4 million, which compares with $4.4 million for the same period in 2020. The increase in costs was primarily the result of salaries, professional fees, and stock compensation expenses. For the third quarter of 2021, we reported a net loss of $17.9 million, or a net loss per share of $0.16, compared to a net loss of $9.7 million, or a net loss of $0.09 per share for the same period in 2020. I will now turn the call back to Carson for closing remarks.
spk03: Thank you, Kevin. In summary, the promising results from the pioneering Phase I SEL399 clinical trial suggest that Intor, in combination with a widely used AAV8 capsid, has the potential to overcome the significant challenge of the formation of anti-AV8 maps. Reduction of capsid immunity could be transformational for the field of gene therapy by making gene therapy safer and possibly enabling repeat dosing. Reflecting on this past quarter, we've made significant steps to progress our existing pipeline candidates and establish collaborations to maximize the potential of our in-town platform. We look forward to providing additional updates on near-term catalysts as we continue to drive our business forward, unlock the power of biologics, and address unmet patient needs. I would also like to thank the entire Selecta team, our investors, and the many people who have been supportive along the way, including our patients and their families. With that, we're happy to take questions.
spk05: We will now begin the question and answer session. To ask a question, you may press star then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our roster. Our first question will come from Kristin Kluska with Cantor Fitzgerald. Please go ahead.
spk09: Hi. Good morning, everybody. Thanks for taking my questions. The first one is that yesterday's data answered a very important question related to your platform potential in gene therapies. So big picture, looking ahead into next year, what questions or areas in the pipeline do you expect to receive even more clarity on the potential of mTOR, whether it's related to your preclinical programs as well as some of the clinical work that's being conducted by both yourself and partners?
spk03: Yeah, that's a great question, Kristen. Obviously, we continue to advance our gene therapy programs, so we hope to be in a clinic with our MMA program next year and at least have some preliminary data around biomarkers of the disease and antibody titers. I think that's going to be a key readout. We have a major readout for enzyme lead program in SEL 212, where we expect phase three results in the second half of next year. And obviously, we're moving forward a number of the programs that are currently in the pipeline such as, for example, the OTC deficiency program or plan to file an IMD next year. We're also moving forward some of the exciting programs that we just struck partnerships with, specifically Zork and ITG Protease, which addresses another large unmet medical need in gene therapy. As you know, Kristen, up to 30% of patients, you know, have been exposed to a natural AV infection and have preexisting antibodies and are not eligible for treatment. So we're going to move that forward next year as well. So next year will be an exciting year for us.
spk09: Okay, thanks. And now that you have clinical evidence for both the enzymes and gene therapies, and, you know, yesterday you made it a point that the extensive preclinical work really helps with the design and understanding these results. So looking ahead into autoimmune now as those candidates near completion, going into the clinic? How have you thought about these synergies from a preclinical standpoint in order to best design a future clinical study with the greatest probability of success?
spk03: Yeah, that's a great question. And obviously, with now over 300 patients' dose with mTOR, we have very good safety database, which is always very important that we've seen that yesterday, translates very nicely to gene therapy, and I think it will be extremely helpful as well for autoimmune problems as well. We'll provide more guidance early next year, but I can tell you we're extremely excited about our partnership with Cyrus, where we released some initial data a couple of weeks ago where we saw very strong synergies between an IL-2 mutine and Intor, where we saw a higher percentage of overall Tregs when combining those two approaches. We'll provide more data next year, and I think that would be really transformational for the autoimmune fields by really enhancing the tolerogenic effects of mTOR.
spk09: Thank you.
spk05: Our next question will come from Raju Prasad with William Blair. Please go ahead.
spk02: Thanks for taking the question. I was hoping you could provide a little bit of clarity on the assay used to measure neutralizing antibodies here and when we might anticipate seeing kind of total antibody concentration and IgG levels from this study, from the 399 study. Thanks.
spk03: Yeah, thanks, Raj. I'll let Kay, our chief science officer, address the question. Kay?
spk04: Hi, good morning. Yeah, the assay to measure neutralizing antibody is a cell-based assay, so it's pretty standard within the field. Basically, you're measuring the activity of serous samples to neutralize AAV from transducing hepatocyte cell line in vitro. With respect to the other data, we haven't guided on that, but we are planning to release additional data from this study in conjunction with our partner, Aspio, at an upcoming gene therapy meeting.
spk02: Great. And then, you know, the dose here was in the 10 to the 12 range. Can you maybe just comment a little bit on, you know, how you would think about doses in like the 10 to 13 or even, you know, one times 10 to the 14th range? Do you think that, you know, the 0.3 dose might be in some larger capsid doses, or do you think that, you know, data .15 with multiple doses could potentially work for any therapeutic range of AAV that's being kind of utilized right now in clinical trials? Thanks.
spk03: Yeah, so we have, we've shown yesterday we have data in mice where we use doses of 2E13. of the AV vector. Our partner, Sarepta, has those even higher. Unfortunately, we can't disclose that data, but in the mouse study, we saw good results as well. We haven't guided, you know, which dose we plan to take into the clinic, but I think yesterday's data is a good indication we saw, which was very important to us, a good dose response curve starting at, you know, 0.15, make the pick, and then, you know, very strong efficacy at 0.3. But also, I want to remind you that we actually have even tested a higher dose of Intor in the Phase 1-2 study of SAL212 as well. So there is, you know, still some dose elasticity if you really wanted to push the dose. But I think, you know, the 0.15 is a good starting point in our view. And definitely, you know, the learning from The non-human primate studies and yesterday's empty capsule study is that, you know, three monthly doses is likely the way to move into the clinic.
spk02: Great. And then maybe just one last one. You know, I think, you know, we've got some questions on kind of the rebound in neutralizing antibodies, you know, post-Day 30. Can you maybe just address a little bit of that, you know, how from preclinical studies how you know that three doses will be enough? Is it on, like, capsid half-life or something like that to kind of enable redosing and kind of tamp down antibody levels over the long term? Thanks.
spk03: Yeah, that's an excellent question. And obviously, we saw yesterday very good comparability between the data from the non-tumor primate study and the first human study, the empty capsid study. Specifically, when we look at day 30, the distribution, the data pattern was very, very similar. And we know from the non-human primate study that three monthly doses maintain control out to day 90. We know from the mouse studies, we can maintain that control out to day 168, which is obviously very encouraging as well. So I think we have a good evidence that three-monthly doses maintain control beyond day 90. We also have done some work with outside collaborators that demonstrated that IMTO actually extends the half-life of the capsid, but we believe, you know, past day 90, there's no more capsid, no more antigen present, actually.
spk05: Our next question will come from Gil Bloom with Needham and Company. Please go ahead.
spk07: Good morning, and thanks for taking our questions. So it looks like you guys have quite a lot of strategic collaborations. Is there any particular guidelines as to who you partner with, particularly for your gene therapy side of programs?
spk03: Yeah, Gil, that's a great question. Yeah, we've been busy. We've struck four partnerships that we've been highly selective. As you know, we struck a partnership last year with Sarepta, as we see them as a leader in neuromuscular disorders, and we're making good progress in that partnership. We just, you know, last quarter received a 3 million milestone payment, so we're pleased with that. We're also excited to be working with Takeda. We're working specifically, we're exclusively licensing mTOR for two lysostomal storage disorders, so these are liver-based diseases. And Takeda is clearly a leader in this space, you know, having a couple of ERTs, enzyme replacement therapies, and really investing in their gene therapy business. So we're very excited. They're committed. They're a long-term player. That's the reason we partner with them. So that's if you like, a selective out-licensed deal of mTOR. But we've also in-licensed in the gene therapy space an ITG protease from Genovese, which we think is highly differentiated. And we really want to use Zork to address patients with pre-existing immunity, which really expands the patient pool eligible to gene therapy. So you can see we've been fairly selective, and we're trying to strike a balance here between selectively licensed into indications that we don't want to pursue ourselves, but also licensing assets in such the ITG protease from Genovese.
spk07: Maybe a related question. How do you prioritize your own internal pipeline?
spk03: That's a great question. Obviously, we're in a fairly strong financial position, and we want to have as many shots on goal. If you look at our pipeline, we have all the way from late phase phase three to about to enter the clinic to more discovery stage. So obviously there's different costs associated with that. And so I think right now we do have the means and the resources to move all those programs forward. But obviously some are more cost intensive and more resource intense once they move into the clinic. But our goal is to take advantage of the cash position and have as many shots on goal as possible.
spk07: All right. And maybe a last one on your IgG, M-Lycidase-like compound. You mentioned that there's an issue with redosing of these kind of enzymes. I know that I think M-Lycidase is a commercial product. How much of an issue is this?
spk03: Yeah, so it is a big issue. It's a bacterial enzyme, so highly immunogenic. There are really two uses, and we think it's a great fit for our platform. Our primary focus is to use the ITG protease to pretreat patients with preexisting antibodies, so have a natural AD infection to expand the patient pool. But there is, you know, a second application, autoimmune disease, As you rightly said, there is a commercial product in ITG protease in Europe that is limited to a single dose due to the immunogenicity. And I think we have the potential to redose Zork and you open up to more indications. And specifically, there are a number of ITG-mediated autoimmune diseases where we can apply Zork.
spk07: All right. That's very helpful. Thank you for taking our questions. Thank you, Gil.
spk05: Our next question will come from Xun Zhang with BTIG. Please go ahead.
spk00: Hi, this is Xun Zhang for Yun Zhang. Thank you for taking our questions. So I have a couple questions regarding your MMA program. So first is about the CMC review by the FDA. Can you give us more colors? Is that because FDA needs more time to review or you kind of foresee FDA may request more data? And also, when do you think you will give us an update on the clinical design of MMA? I know your Phase 1 study will explore inventory first dose methods. So, do you think on your Phase 1 study, you may, like, include the reducing strategies in those patients if needed?
spk03: Yeah, thanks for the question, Shu. So, unfortunately, we can't provide a lot more color. We don't have more color. As you can read in our filings, the FDA 30-day review period expired. We're orally communicated by the FDA that they're still considering certain aspects of the submission around CMC, and they'll get a formal decision by the end of November. So unfortunately, we also don't have more color. Around when do we have guidance on the clinical design? Obviously, once we have IND approval, We'll share the clinical trial design in detail and also some of the endpoints we're going to look at in the phase one trial.
spk00: Great. Thank you. I may ask one more question here. So just some competitive landscape in MMA. Just for a very few, a very rare indication, the space seems to be quite crowded. Just name a few, like the large files, AAV gene therapy, and Moderna has MRA. program and a few other auto-solutions in trials. So, I mean, it's great for the patient community, but from business perspective, just want to know your thoughts on this. Is that because the disease may be, like, significantly under-diagnosed? There may be more patients than estimated, or is it just a good indication for proof of concept? And also, do you anticipate some, like, patient enrollment challenge?
spk03: Yeah, that's a good question. We obviously think that we do have a highly differentiated approach here with the potential to redose. No other approach can offer that. So we think we're quite differentiated from that perspective. It is still, it's not an ultra-rare indication. It's a rare indication. So you're looking, you know, in the thousands of patients. And we've been very strategic about who we work with. So we have a partnership. with the NIH with Chuck Menditti, who is one of the prominent researchers in the field, and they maintain the largest patient registry in the U.S., so we'll have access to those patients. So we've been, you know, mindful around partnering with someone that has access to MMA patients. Okay. Thank you very much.
spk05: Thank you, Shubh. Again, if you have a question, please press star then 1. Our next question will come from Ram Savaraju with HCWainwright. Please go ahead.
spk08: Good morning from New York. This is Maz on for Ram. Thanks for taking our questions, and thanks for the comprehensive update. So three from us, if I may. So enzyme replacement therapy in the context of lysosomal storage diseases is kind of like a foundational treatment. From your perspective, we were wondering, what are some of the drawbacks of ERT in this context, and how are you proposing to replace the existing treatment paradigms through mTOR?
spk03: Yeah, I let Peter answer that in more detail, but obviously ERTs are limited in their use. They're usually highly immunogenic enzymes, and if you look at the overall response rates are not as high, whereas obviously gene therapy addressing the underlying monogenic, you know, issue pathology. But I'll let Peter provide a bit more color here.
spk01: Yeah, Carson, I think that you've hit the key issue. With enzyme replacement therapy, you have to give it repeatedly, and they are immunogenic compounds, so you develop anti-drug antibodies, which then reduces the efficacy. Of course, adding mTOR to ERTs could potentially improve that, but with our partnerships, particularly with Cicada, we have taken a different approach, and that is to team up with gene therapy, because gene therapy will likely reduce the long-term of the ERT and give you more long-term treatment. And furthermore, if we add mTOR to that, if it does wane in expression, we can potentially do repeat dosing of the gene therapy. Additionally, mTOR with the gene therapy could also prevent antibodies to the expressed transgene. So there are a couple of ways that mTOR combined with gene therapy is the approach that we're pursuing rather than ERT.
spk08: Thanks for that, Kala. Shifting on to the partnership with Ginkgo, are you able to expand on the logistics of bringing mTOR together with their foundry platform? For example, Will mTOR capability be installed at the foundry, or will the platforms operate independently in their current locations?
spk03: Yeah, so they'll operate independently, and we're really excited about the partnership with Ginkgo. And we're basically using their foundry to develop novel and next-generation enzymes, which we then plan to combine with mTOR. So what's important is that we will have exclusive therapeutic use for those enzymes. So in a sense, it's a strategic partnership, but it's really an inbound deal where we get access to some of the novel enzymes that we plan to combine with mTOR to enable redosing.
spk08: Fantastic. And then just finally, are you able to reveal specific design capabilities of Ginkgo's Foundry platform that you think will enhance the sustained efficacy of biologics within TOR technology. And, you know, in addition, if you're able to reveal some initial disease indications that you're pursuing with Ginkgo, that would be great too.
spk03: Yeah, so we haven't disclosed details. We just gave kind of broad brush. We're pursuing autoimmune diseases with an enzymatic therapy. And maybe I'll let Kate talk a little bit about their technical capabilities, but What really struck me is the quality and the speed they can identify enzymes and modify enzymes. You know, really, really convinced me that they're in quite a unique position in the landscape of protein design, protein engineering companies. But maybe, Kate, to provide a little more color.
spk04: Yes. Yeah, obviously, Ginkgo has made quite an impact in the protein industry. engineering world i think their foundry technology really industrializes protein design and and testing so uh i i think as carson mentioned we're really excited to be working with them and and i think at a future date we'll be able to provide you more information on on our partnership okay excellent uh that's all from us all the best thank you
spk05: This concludes our question and answer portion of the call. I will now turn the call back over to selected CEO, Karsten Bruhn, for any closing remarks. Karsten?
spk03: Yeah, thank you, operator, and thank you, everyone, for joining us this morning. Stay safe and healthy, and this concludes today's call. Thank you.
spk05: The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.
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