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spk09: And welcome to the Selecta Bio second quarter 2022 earnings release conference call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on a touch tone phone. To withdraw your question, please press star, then two. Please note, this event is being recorded. I would now like to turn the conference over to Kevin Tan, Chief Financial Officer of Selecta Bio. Please go ahead.
spk05: Thank you and good morning. Welcome to our second quarter 2022 financial results and corporate update conference call. Press relief reporting our financial results is available in the investors and media section of Selecta's website, worldwidewebselectedbio.com, and our quarterly report on Form 10-Q for the quarter ended June 30th, 2022, which we intend to file in the coming days 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 Kei 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, regulatory and clinical progress of our product candidates, our 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 SEC, including our most recent annual report on Form 10-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, August 4th, 2022, and selected as claims any obligation to update such statements, except as required by law, even if management's views change. I would now like to turn the call over to Carson Bruin. Carson?
spk02: Thank you, Kevin. Good morning. I appreciate everyone taking the time to join us today. In the second quarter of 2022, we made steady progress across our proprietary pipeline and achieved numerous key milestones. Most notably, on June 29th, We completed the enrollment of the DISSOLVE II trial, carrying a 10 million milestone payment obligation from SOBE. Our partners continue to progress the IMFOR platform in combination with their gene therapy candidates. And in June, Sarepta extended their option and license agreement for Dijon muscovistrophy and certain limb girdle muscovistrophy subtypes by nine months and achieved certain preclinical milestones. These two events resulted in total payment obligations of $6 million from Sarepta that we anticipate receiving in Q3 2022. Finally, on April 6, we priced an underwritten offering raising approximately $38.7 million. We believe that our existing cash, cash equivalents, restricted cash, and marketable securities as of June 30, 2022, will enable us to fund our operations into mid-2024. The second half of this year will be an important time for Selector as we anticipate completing the Phase III DISSOLVE trial in collaboration with our partner, SOBE. We expect to announce joint top-line data from DISSOLVE in Q1 2023. We also anticipate advancing SEL302, our proprietary gene therapy candidate to treat methylmalonic acidemia, or MMA, into the clinic and remain on track to commence the Phase I clinical trial in the fourth quarter of this year. Our team continues to advance our preclinical pipeline, most notably IND enabling studies and manufacturing scale-up for a proprietary ITG protease Zork to help unlock the power of gene therapies. IGA protease candidate selection with our partners Ginkgo Bioworks and Igon Biosciences for the treatment of IGA nephropathy and accelerating the development of IMTOR-L, which is the evolution of our Amazon Pacific Precision Immune Tolerance Platform. With an expected financial runway into mid-2024, we believe we're well positioned to reimagine immunotherapy in autoimmune disease, unlock the potential of AV gene therapy, and amplify the efficacy of biologic therapies. Let me now walk you through some of the key highlights and recent activities across all three pillars of our pipeline. Over 24 million Americans suffer from autoimmune diseases. The current standards of care utilize immunosuppressive drugs which often leave patients vulnerable to serious infections and malignancies, or symptoms-masking treatments, which fail to address the underlying cause of the disease. Our approach reimagines the treatment paradigm by addressing the underlying cause of autoimmune disease. Through our precision immune tolerance platform, we hope to restore immune system balance by inducing and expanding antigen-specific irregular T-cells, or Tregs, in vivo. As we've highlighted before, we're very excited about recent predictive data we've generated showing substantial synergistic activity when mTOR is combined with engineered IL-2 molecules that are selected for TBEX, an evolution of a platform we call mTOR-IL. A top priority for Selector in 2022 is accelerating the development of a proprietary engineered IL-2 to combine with mTOR. We have partnered with Cyrus Biotechnology, a world-leading protein engineering company spun out of David Baker's lab at the University of Washington to facilitate development of our next generation highly differentiated IL-2 mutine to combine with mTOR. Unlike other programs in development using engineered Treg selective IL-2 molecules that focus on generalized expansion of Tregs, mTOR and mTOR-L, when combined with antigen of interest, is focused on induction and expansion of TVEX specific to those autoantigens responsible for the pathogenesis of autoimmune diseases. We believe our technology has the potential to be a truly differentiated, first-in-class, antigen-specific treatment for autoimmune diseases. The first autoimmune indication in which we plan to evaluate our precision immune tolerance platform is in primary bilirucal angiitis, or PPC, a T-cell-mediated liver disease driven by a well-defined antigen, PDCE2. In PBC, the immune system mistakenly attacks tissue in the liver and damage the small bile ducts. While treatments to help slow the progression and prevent complications in PBC are available, approximately 30 to 40% of patients are intolerant to or do not respond to these treatments, leaving patients with limited alternative treatment options and a significant unmet need. Co-administering IM2RL with PDCE2, the autoantigen implicated in PVC, may result in the expansion of TVEX specific to PDCE2 and restore immune system balance. We continue to work toward additional indication selection, and we plan to expand into other autoimmune indications. We expect to provide updates on our strategic development path for IM2RL in the near future. Now moving on to our gene therapy pipelines. In Q4 2022, we anticipate starting a phase one trial of SEL302, a combination of mTOR with MMA101, an AAV gene therapy being developed for the treatment of MMA. MMA is a rare metabolic disease in which the body cannot break down certain proteins and fats. The phase one trial will evaluate the safety and efficacy of SEL302 in treating MMA and mTOR's ability to mitigate neutralizing antibodies against the MMA101 AAV capsid. We hope this trial will build on our growing body of evidence pointing towards the potentially multifaceted benefits of mTOR, enhancing the efficacy and safety of AAV gene therapies. Additionally, development of SEL302 could provide an important regulatory and clinical blueprint for our current and future gene therapy partners. potentially accelerating development of safer and redosable AEB gene therapies for patients suffering from rare genetic diseases. This past May, at the American Society of Gene and Cell Therapy, Selecta showcased six presentations, including three from our partnership with AskBio. Our CSO, Kei Kishimoto, was awarded an Outstanding Poster Presentation Award for his abstract titled, Combination of mTOR tolerogenic nanoparticles and IL-2 mutine synergistically inhibits the formation of anti-AV antibodies. This poster showed mTOR-L had the ability to induce durable immune tolerance to a co-administered AV gene therapy vector in mice and demonstrated complete inhibition of anti-AV antibody formation after multiple doses of gene therapy through 117 days. Notably, this effect was observed and would be considered sub-therapeutic doses for mTOR alone. Building on this, today we're pleased to report new data from preclinical studies in mice using gene therapy vector doses of 5E13 Vg per kick, or 10 times the dose of prior studies. This study demonstrated that a single dose of mTOR plus four monthly doses of IL-2 co-administered with AV8 CEEP produced durable mitigation of anti-AV antibodies over 131 days. When combined with our human proof of concept study, where we observed mTOR's ability to inhibit the formation of the dosing antibodies in healthy human volunteers out to 30 days, we believe these results suggest that mTOR-L has the potential to solve the redosing problem associated with AV gene therapies and transform the treatment paradigm from one and done to low and slow, whereby patients could receive multiple doses of gene therapy to titrate up to a therapeutic benefit and avoid the risks associated with high vector doses of gene therapy needed in a one-time only treatment model. Another key challenge facing the gene therapy modality is one of accessibility. Currently, 30 to 70% of patient population for gene therapy trials are ineligible for inclusion due to preexisting nucleosine anti-AEV antibodies, which are a result of natural infections. Thus, many patients in need are unable to access potentially life-altering therapies, for which there may be few or no treatment alternatives. IgG proteases have shown promise as a pretreatment to transiently clear preexisting nucleosine antibodies and create a window during which AB gene therapies could be administered. However, ITG proteases are derived from bacteria and are themselves highly immunogenic. Additionally, some ITG proteases are derived from a common human pathogen, and consequently, the vast majority of individuals have preexisting antibodies against these proteases. Zork, our proprietary ITG protease candidate, has been optimized to specifically cleave human ITG, but is derived from a non-human pathogen, and we have observed low cross-reactivity to preexisting anti-ITG protease antibodies. We believe that the combination of ZORC with mTOR could enable repeat dosing of this enzyme therapy. We continue with IND enabling studies and manufacturing scale-up. I want to take a moment to discuss how important we believe ZORC could be for the gene therapy modality. For many patients with rare genetic diseases, gene therapy could represent the most promising treatment option. Unfortunately, many patients are ineligible for gene therapy due to preexisting anti-AV antibodies. By using Zork to open a therapeutic treatment window for these patients, we have the potential to bring hope to those who may not have any other effective treatment options. At the same time, by increasing the eligible patient population, we can help companies maximize the commercial potential of their gene therapy candidates. We're taking a multi-pronged approach to tackling the immunogenicity challenges facing AAV gene therapies. mTOR and mTOR-L to mitigate the de novo formation of neutralizing antibodies and enable redosing and Zork to address those patients who due to natural AAV infections are ineligible for treatment by gene therapies. We continue to progress our gene therapy platform toward the goal of providing an industry-leading toolbox capable of unlocking the true promise of AV chin therapies. We plan to maximize the value of our platform by actively pursuing business development and outlining opportunities for both mTOR and Zork. Lastly, I want to provide an update on our Biologics pipeline, starting with SEL212, which we believe has served as clinical proof of concept for a precision immune tolerance platform with approximately 450 patients dosed to date. Many biologics can be highly immunogenic, resulting in suboptimal responses due to the development of anti-drug antibodies after multiple treatments. Patients that develop an immune response may be forced to discontinue treatment or experience adverse reactions. We believe the use of mTOR as an adjunct to biologics offers a promising approach to reduce this immune response and improve patient outcomes. SEL212 is comprised of mTOR co-administered with a proprietary urocase, the GATU case, for the treatment of chronic refractory gout and was licensed to SOBE in 2020. Our phase three dissolved clinical program picked up in the third quarter of 2020 and consists of two double-blind placebo-controlled trials of SEL212. In both trials, SEL212 is being evaluated at two dose levels of mTOR, 0.1 mgs per kg and 0.15 mgs per kg, with a single dose level of Picatricase of 0.2 mgs per kg. On December 1, 2021, we announced full enrollment for DISSOLVE-1, with 112 patients enrolled in the United States, and we recently closed enrollment at 153 subjects for DISSOLVE-2, which has been conducted in four countries across Eastern Europe and the United States. As a reminder, we increased target enrollment of Dissolve-2 from 120 subjects to mitigate any subject discontentations due to the ongoing geopolitical events in Russia and Ukraine. Achievement of full enrollment in Dissolve-2 triggered a 10 million payment obligation from SOBI, and we remain on track to complete both studies in Q4 2022 with joint top-line data anticipated in Q1 2023. We plan to work closely with our partner SOBI our clinical trial providers, and regulatory authorities to advance to a successful completion of the DISSOLVE program. With extensive clinical data in SEL212 currently in phase three, we believe our biologics pipeline is mechanistically de-risked and Selecta is well positioned to leverage these learnings into our second biologic indications in IgA nephropathy, 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 IgA protein deposits, which is the underlying pathophysiology of the disease. We believe our novel approach, which combines mTOR with an IgA1 protease, has the potential to move injurious IgA from the kidneys, improve markers of renal function, and have a transformative impact on patients' lives. We are currently working with our external partners to identify an IGA Pro Days candidate for this program and hope to finalize clinical candidate selection by year end. We're extremely excited about the advancements across all three pillars of our pipeline and the value driving milestones in the second half of 2022 and beyond. With that, I'll turn the call over to Kevin to run through our financial results for the second quarter ended June 30th, 2022. Kevin.
spk05: Thank you, Karsten. During the second quarter, we proactively took steps to bolster our balance sheet. Most notably, on April 6th, we successfully priced an underwritten offering, raising gross proceeds of approximately $38.7 million and ended Q2 2022 with approximately $143.4 million in cash, cash equivalents, restricted cash, and marketable securities. It is important to note that this cash balance does not include either the $10 million we have received in Q3 from SOBI or the $6 million from SREPTA that we anticipate receiving in Q3 2022. We believe that our existing cash, cash equivalents, restricted cash, and marketable securities as of June 30, 2022 will enable us to fund our operating needs into mid-2024. We expect multiple clinical readouts within our anticipated cash runway including the results from the Phase 3 dissolved trials in Q1 2023 and initial results from our Phase 1 trial of SEL302. Turning to our financial results in the quarter ended June 30, 2022, net cash used in operating activities was $24.1 million for the six months ended June 30, 2022, as compared to $18.2 million of cash used in operating activities for the same period in 2021. Collaboration and license revenue recognized was $39.3 million for the second quarter of 2022, as compared to $19.7 million for the same period in 2021. Revenue was primarily driven by the shipment of clinical supply and the reimbursement of costs incurred for the Phase III Dissolve program pursuant to the license agreement with SOBE and the shipment of manufactured supply under the SREPTA agreement. Research and development expenses for the second quarter of 2022 were $19.2 million as compared to $14.5 million for the same period in 2021. The increase in costs was primarily the result of expenses incurred for the SEL212 clinical program, stock compensation, and salaries. General and administrative expenses for the second quarter of 2022 were $6.2 million, as compared to $4.7 million for the same period in 2021. The increase in costs was primarily the result of expenses incurred for issuance costs for the 2022 equity offering and stock compensation. For the second quarter of 2022, Selecta reported net income of $8.6 million, or basic net income per share of $0.06, as compared to net income of $4.6 million, or basic net income per share of $0.04 for the same period in 2021. I will now turn it back to Carson for closing remarks. Carson?
spk02: Thank you, Kevin. In summary, we're pleased with our progress in Q2 across all three pillars of our pipeline. We're excited about our plans to enter the clinic with SEL 302 in Q4 2022, the anticipated completion of the DISSOLVE program with our partner SOBE, the advancement of IND-NAPING studies across our wholly-owned pipeline, supporting our numerous collaboration partners and our plans to rapidly advance our next generation precision immune tolerance technology, IMTOR-IL, into the clinic. We believe IMTOR-IL could represent a generational leap forward for the IMTOR platform, and we look forward to evaluating its full potential in PBC and beyond. We remain focused on our commitment to solving the hardest challenges in autoimmune disease and helping patients overcome autoimmunity and immunogenicity through our evolving IMTOR precision immune tolerance platform. Before we conclude today's call, I'd 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.
spk09: Thank you, Carson. We will now begin the question and answer session. To ask a question, you may press star then one 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 today comes from Joe Short of SVB Securities. Please go ahead.
spk07: Hi, this is Beth on for Joe. Thank you for taking our question today. So Horizon Therapeutics noted during their first quarter update this year that Cristexa has achieved less than 5% penetration in the refractory gout market. We were wondering what you think could be driving this low uptake and if you and your partner, Sobe, have discussed any opportunities that you could pursue to enhance SEL212's uptake, if approved. Thank you.
spk02: Yeah, hi, Beth. That's a great question. Obviously, we're not giving commercial guidance since SOBI has commercial rights, but we remain extremely excited about the commercial opportunity in general. I think, you know, Horizon has done a lot of the heavy lifting, actually, creating physician awareness, patient awareness, you know, setting a fairly high price point. But as you can tell, with the fairly low penetration at this point, there remains a tremendous commercial opportunity. And we believe one of the key differentiators, of course, is always efficacy. And we're extremely excited by the phase two results that we saw. But one of the key drivers in this patient population is also compliance. And, you know, as you know, Cristexa has to be used twice a month. with the new approval with methotrexate, even a more complex treatment measurement with daily folic acid and weekly methotrexate, whereas SGL212, if approved, would be a monthly treatment, which would be tremendous differentiation for those patients who have to come into an infusion center, which is usually a longer drive. Somebody has to take them It makes a huge difference whether this is once or twice a month.
spk09: Our next question comes from Kristin Kluska of Cansor Fitzgerald. Please go ahead.
spk08: Hi. Good morning, everybody. For the SOBE partnership, what is the total amount of milestone payments that you remain eligible for at this time? And I know that you've guided your cash runway doesn't necessarily include any potential for any of these milestones. But I would imagine that some of these might be tied in with the top line readout and a potential filing. And then has SOBE guided anything in terms of if the data does read out positively about Salesforce and steps they're taking to prepare for a potential commercialization?
spk02: Yeah, hey Kristen, great question. So we have overall guided that we're eligible to receive 630 million in milestones, which is breaking down in 80 million in regulatory and development milestones. and 550 in commercial milestones. And as we just announced, we ultimately receive 10 million for the full enrollment. So there are some payments milestones left in the current development vector phase. But maybe, Kevin, if you have the numbers top of mind. Yeah, so we have...
spk05: We received $15 million.
spk08: Sorry, Kevin, I wasn't able to hear you.
spk05: I don't know if it's my line or... Sorry, to be clear, we've already received $15 million in regulatory and development milestones, and we're eligible for the balance of $65 million.
spk08: Got it, thanks for that. And then just on this new data you had for mTOR-IL and gene therapies, wondering if you might look to share some of these additional findings at an upcoming conference or when we could expect to see the specific details.
spk02: Yes, we'll definitely share this data at an upcoming conference. We'll also include it into our corporate deck, which you actually can see on our website. So the data actually is on there already.
spk08: Perfect. Thanks. Thank you.
spk09: The next question is from Yun Zong of BTIG. Please go ahead.
spk00: Great. Thank you very much for taking the question. My question is on the mTOR IL. And I believe you indicated in the past that you were not going to use IL in the MMA study. And is that because the engineered IL2 would not be ready by the time you initiate the study, given that the new data that you just talked about, mTOR IL in gene therapy, does it make sense to maybe try to introduce IL into the planned MMA study? And do you have a plan to look for additional, sorry, in terms of gene therapy indication to potentially include IL-2?
spk02: Yeah, that's a great question, Yoon. So you're right. We don't anticipate to include IMTR-IL, at least initially in the MMA trial. And we're really encouraged by the human-proof concept study that we read out last year with an anti-capsid. where we saw good control due to the antibodies. But we can, you know, once we have an IL-2 available and went through the appropriate safety studies, we could potentially always add in m2IL. But at least for this phase one, it is not planned to include an IL-2. In terms of other indications, as you know, we have paused our OTC deficiency. indication just to preserve cash. And we really see the gene therapy modality as a partnering play. We're very committed to MMA. We want to own the regulatory pathway. So I think we set a clear precedent for our strategic partners on how to use mTOR into the clinic. I don't want to rule out we're going to pursue this program in the future, but for now we're focused on MMA.
spk00: Okay. Then on the autoimmune indications, I think that's going to be the major direction going forward. And in terms of indication selection, do you have any specific criteria in terms of the autoantigens that you would like to develop? Thank you.
spk02: Yeah, that's a great question. And as you know, we've just released the exciting inter-RL data beginning of this year. We're working through indication selection We have guided to PVC, which we like as an initial indication since it has a clearly identified autoantigen, PVC-E2. It's also a liver-directed disease as well. As you know, Intor accumulates in the liver, so we think liver-based autoimmune diseases are a focus. We'll give more guidance around this, but definitely in we have a clear focus on autoimmune diseases of the liver. Great. Thank you very much.
spk09: The next question comes from Yatin Suneja of Guggenheim Partners. Please go ahead.
spk04: Guys, thank you for taking my question. Just a couple for me. With regard to the chronic refractory cloud data coming up, could you maybe just help us understand the expectation from that study? And then also, if you can just touch on, you know, how do these data maybe serve as a proof of concept for the TUI program that you have? So that's the first question. I do have two more, which I'll ask after this.
spk02: Yeah, absolutely. So... As you know, the phase three study is a placebo-controlled study. We know from the Cristexa trials there's no placebo effect, so we're very confident here that we'll have technical success. We have run two phase two studies where we saw efficacy in the 50% range pretty consistently, and I said it, I think, the main call over 450 patients dosed. So I'm looking at this data as a baseline in terms of expectations. I mentioned earlier that we think the monthly dosing will be a key differentiator. So I think that's the expectations around efficacy. And we've done, in the past, extensive market research and feel this is an attractive and differentiated profile. In terms of proof of concept, I mean, we actually believe, just based on the phase two data, we think we have very clear proof of concepts. In the phase one study, actually, we dosed 19 patients with the enzyme alone in the GATRI case. Only three made it to week four, which shows you it's a highly immunogenic enzyme here. If you look at the phase two studies, you get a response rate. in the 50% amongst five and six. So you can clearly see that you induce tolerance and prevent the formation of ATA. So we definitely feel very strongly that we already have technical proof of concept, which we're obviously planning to use for our second enzyme program, which is an ITA protease. But of course, you know, the phase three will be additional validation. We'll have additional safety data. But overall, we're quite excited about this upcoming readout in Q1 next year.
spk04: And then with regard to the IMTOR program, first on the PBC side, are there good biomarkers to find who could respond to your IMTOR versus not? So that's the first part. And then where are you with your own ILT routine? What are the timelines there and out there? particular characteristics of an ideal IL-2 routine to be combined with IMT or if you can just comment there. Thanks.
spk02: Yeah, great question. I'll let Peter answer the first question around biomarkers in PBC. Peter?
spk10: Yeah, thanks, Karsten. In PBC, there are very good and validated, well-established biomarkers of disease that The one that's been used most frequently is alkaline phosphatase levels. And in fact, these are regulatory endpoints which have been used for approval of other drugs such as beta-cholic acid. So a reduction in alkaline phosphatase levels is an extremely good biomarker and one that can be easily monitored and has a relatively rapid response rate. So that's what we would be utilizing primarily.
spk02: Thank you, Peter. In regards to IL-2, so we haven't got an exact timing, but as you know, it's a tough day for us. We're working with our partner, Cyrus, And we'll definitely give an update in the very near future as it's a top priority. But I let Kay talk a little bit of what we're trying to achieve here in terms of differentiating with this T-Rex Selective IL-2. Kay?
spk12: Yes, hi. Yeah, so if you're familiar with the IL-2 space, one of the the goal is to expand total Tregs. And our approach is more antigen-specific because we believe antigen-specific Tregs are going to be really the key to autoimmune disease where you have a large pool of antigen-specific effector T cells. So the fact that we see this profound synergy of IL-2 with mTOR indicates that we're getting both expansion of total Tregs, which can provide bystander suppression. But more importantly, we feel we're getting this huge increase in antigen-specific Tregs. Thanks, Kay.
spk09: The next question comes from Gil Bloom from Needham. Please go ahead.
spk11: Hi, this is Chen for Gil. Thank you for taking our questions. So our first question is about mTOR for MMA study. It seems that mTOR IL, more doses can give very good inhibition of the antibodies. So are you planning to include more doses of mTOR in the MMA study? The second one is about, is there any timeline for the combination of mTOR and Zork? So it is now in the IND enabling study. Are you planning to hopefully start a trial next year? Thank you.
spk02: Yeah, great question. I'll give the first one to Peter around the MMA setup.
spk10: Yes, this is an excellent question. And in the MMA trial, because of our results in the empty capsid trial, as well as the preclinical results in non-human primates and mice, we have decided to treat with three monthly doses of mTOR following the single dose of the AAV vector. And this has been approved by the FDA and it's going to be part of our clinical trial. So subjects will receive the AAV gene therapy plus mTOR and then 56 excuse me, one month and two months later, they will receive a second and third dose of mCore. And this is a direct result of the findings in non-human primates that were able to continue to suppress antibody levels with that regimen.
spk02: Thank you, Peter. On the question on Zork, we have not guided to an IND filing date, but I think your assumption is not far off. It's not a top priority that we are pursuing. Thank you.
spk09: The next question comes from John Newman from Canaccord. Please go ahead.
spk01: Hey, guys. Thanks for taking my question. for your proprietary IL-2 that you're developing in conjunction with Cyrus, just curious about the initial indication there. I think the initial work with IL-2 will be PBC, but I believe that will be with a different IL-2. Curious as to what you're thinking for the proprietary version that you're working on.
spk02: Yeah, good question, John. We actually plan on for now, the proprietary IELTS who were developing CIRES for the PPC indication, actually. I think we have stated in the past that we are open to partnerships with existing IELTS school players, as we believe we have quite a unique value add here by differentiating by inducing air-specific air tolerance, actually. But the first indication would be with their proprietary IL-2 in PBC. Okay. Great. Thank you.
spk09: The next question comes from Raju Prasad from William Blair. Please go ahead.
spk03: Thanks for taking the question. Maybe just a little bit more color, if you can, on the gating events needed to start the Phase I MMA trial. And then just a quick follow-up, you know, thinking about the IgG protease and the potential development of that, how would you think to kind of initiate the clinical program for that asset? You know, could you kind of put it into the Phase I trial or would you have to kind of study it separately? Thanks.
spk02: Yeah, I'll let Peter comment on the gating for the MMA trial. As you know, it's a single-center study. at the NIH, and we're kind of going through motions to get this started, but I'll let Peter elaborate in more detail.
spk10: Yeah, thank you, Carson. The gating for starting the trial at the NIH are really just some administrative approvals at the NIH, which are well underway. and the setup of all the administrative and operational issues in collaboration with our CRO, which is helping to support the trial at the NIH. So there's nothing regulatory or CMC or any other issues that are gating through the initiation of that trial. So it's on track for uh, first subject, uh, uh, treated in the fourth quarter of this year.
spk02: And, and Peter, since you're on the roll, maybe, um, as you know, we haven't fully guided on the clinical development plan for Zork. Um, and obviously, you know, we'd like to take this into an indication as possible, but maybe we can talk a little bit, our thinking around, uh, you know, kind of starting this in a phase one study and, and, and healthy volunteers.
spk10: Yeah, sure. Happy to do that, Carson. The issue with Zork is that we're trying to reduce existing AAV antibodies in patients in order to be able to give them the gene therapy. Well, for that purpose, we can use healthy volunteers who have existing titers of anti-AAV vectors. And as Carson said, that can be anywhere from 40 to 70% of patients in the general population. So that's the relevant group. So our first phase one study will be looking at both the safety and tolerability of Zork alone and in combination with mTOR. and with the efficacy looking at the reduction of naturally occurring anti-AAV antibodies. So that's the first trial, and that really serves as a proof of concept for gene therapy trials. And so then following that, we would be looking to include that as a pretreatment before an actual gene therapy. Thanks, Peter.
spk09: Again, if you have a question, please press star, then 1. The next question comes from Bubalan Pachayaban of HC Wainwright. Please go ahead.
spk06: Hi, can you hear me okay? Yes, we can. All right, great. So a few questions on PBC. So you guided to us that PPC is the primary indication in the autoimmune disease space. Can you comment on the market opportunity and how you are differentiated from competitors in this space?
spk02: Yeah, and since we have a resident expert here, Peter, I'm going to give that question as well. But maybe just kind of to frame it up, obviously, we believe they're really addressing the underlying all the antigens that's driving the disease pathology actually, so really addressing the root cause of the disease mechanistically. But I'll let Peter give it more detail.
spk10: Yes, Karsten, thanks. That's correct. I mean, all of the drugs that are currently being used in PBC don't get at the root immunologic cause of the disease, and that's what we're trying to do. Now, The number of patients that respond to the current therapies is about 35% to 40% respond to ursodeoxycholic acid, and then another half of those may respond to abetacolic acid, but that's restricted to people without severe liver disease. So people are still, even with the therapies today, progressing to cirrhosis and requiring liver transplant, and they're approximately 10 to 12% of people who receive liver transplants in the United States for PBC. So I think that there is still an unmet medical need to address the underlying root cause of the immunologic damage. that's what our precision immune tolerance platform is aimed at.
spk06: Great. Thanks for the color. So it appears PBC mostly affects women than men. So do you have a reason why that's the case? And would you consider enrolling more female patients in your future clinical studies?
spk10: Yes, you're correct that as many as 90 to 95% of individuals who have PBC are women. And this, you know, it is the case for many autoimmune diseases that there's a higher percentage of women. In other autoimmune indications in the liver like autoimmune hepatitis, there's 70% of individuals that are women. So that is a common theme in autoimmune disease. So in our trials of PBC, we anticipate that the vast majority will be women that are enrolled in the trial. In terms of your question about the underlying reason why women are more affected, I don't think that that's been clearly worked out, although the animal models that are used for PBC are also much more prevalent and severe in female animals. So it does seem to be something that's replicated in the animal models of PBC.
spk06: Okay, thanks for the color. And one final question from me. It appears mTOR IL is a versatile molecule with a broad therapeutic potential. Obviously, your first indication is a RAP disease. Are there plans to pursue mass market indications within the realm of autoimmune disease space using mTOR IL?
spk02: Yeah, that's a great question. And obviously, we've just guided one indication at this point, PBC. We'll give more guidance. And we definitely have broad indications, absolutely. Whether you take all those indications into phase three is a different discussion, but we don't want to limit ourselves to rare diseases only.
spk06: Thanks so much for taking my questions.
spk09: This concludes our question and answer session. I would like to turn the conference back over to Karsten Bruhn for closing remarks.
spk02: Thank you, operator, and thank you, everyone, for joining us this morning. Stay safe and healthy. This concludes today's call. Thank you.
spk09: The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.
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