Selecta Biosciences, Inc.

Good morning and welcome to the Selecta Biosciences third quarter 2022 financial results and business update conference call. Currently, all participants are in a listen-only mode. This call is being webcast live on the investor and media section of Selecta's website at www.selectabio.com and is being recorded. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touchtone phone. And to withdraw your question, please press star then two. For opening remarks, I would like to introduce you, Mr. Kevin Tan, Chief Financial Officer of Selecta. Please go ahead, sir.

Thank you, and good morning. Welcome to our third quarter 2022 financial results and business update conference call. The press release reporting our financial results is available in the investors and media section of Selecta's website, worldwidewebselectabio.com, and our quarterly report on Form 10-Q for the quarter-ended September 30, 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, and 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 and subsequent quarterly reports on Form 10-Q. Your cautions not to place undue reliance on these forward-looking statements which speak only as of today, November 3rd, 2022, and selected disclaims any obligation to update such statements as required by law, even if management's views change. I would now like to turn the call over to Carson Brun. Carson?

Thank you, Kevin. Good morning. I appreciate everyone taking the time to join us today. In the third quarter of 2022, we continued to make steady progress across the pipeline, and with an expected financial runway into mid-2024, we believe we're well-positioned to execute on our key priorities and reach multiple near-term value-driving events. In collaboration with our partner, Sobe, we expect to both complete the SEL212 Phase 3 dissolved trial and announce joint top-line data in Q1 2023. We also remain on track to advance SEL302, our proprietary gene therapy candidates, in combination with mTOR to treat metabolic acidemia or MMA into a phase one clinical trial in this quarter. Our key priority continues to be accelerating the development of our next generation precision and tolerance platform, mTOR-IL. We've made substantial progress in identifying a proprietary IL-2 candidate and continue to believe we'll have a clinical lead candidate by year end. Additionally, Our team continues to advance our preclinical pipeline, most notably the IMD enabling studies and manufacturing scale-up for our proprietary ITG Protease Zork as a pretreatment for AV gene therapies and IgA Protease candidate selection with our partners for the treatment of IgA nephropathy. On the cusp of these key milestones, we'd like to share details on how these programs, together with recent activities, align with our mission to solve the toughest challenges associated with autoimmunity and unwanted immunogenicity. Let us begin with the applications of our precision immune tolerance platform for autoimmune disease. Currently, over 24 million Americans suffer from autoimmune diseases, and while the current standards of care utilize immunosuppressive drugs or symptom masking treatments, These treatments leave patients vulnerable to serious infection and malignancies and fail to adequately address the underlying cause of the disease, which is an imbalance of T-regulatory cells versus T-effector cells. By combining intral with autoantigens, we hope to restore natural immune system balance by inducing and expanding antigen-specific regular T-cells in vivo. As we have highlighted before, we're very encouraged by our growing body of preclinical data in which we've observed the potential to amplify the magnitude and durability of end-specific immune tolerance by combining mTOR with an engineered T-REX-selective IL-2, an evolution of a platform we call mTOR-IL. By focusing on the induction and expansion of T-REX, specific to the autoantigens responsible for the pathogenesis of autoimmune diseases, we believe mTOR-L has the potential to be a truly differentiated, first-in-class treatment for those suffering from autoimmune diseases. The first autoimmune indication in which we plan to evaluate mTOR-L is primary biliary cholangitis, or PBC, a T cell-mediated liver disease driven by a well-defined antigen Co-administering mTOR-L with PDC-E2, the autoantigen implicated in PDC may result in the expansion of Tregs specific to PDC-E2 and restore immune system balance. We continue work on identifying additional autoimmune indications to expand, and we expect to select an IL-2 candidate by year end. We also plan to provide an update on the broader strategic development path for Intor-L in the near future. Moving on to our gene therapy vertical. In Q4 2022, we expect to initiate the Phase 1-2 trial of SAL302. As a reminder, SAL302 is a combination of Intor with MLA101, an AV gene therapy being developed for the treatment of metabolic acidemia, a rare genetic metabolic disease. The Phase I-II trial will evaluate the safety and efficacy of SEL302 in treating MMA and in TOR's ability to mitigate utilizing antibodies against the MMA101 AV capsid. We believe this trial will build on the growing body of evidence pointing towards the potentially multifaceted benefits of mTOR in enhancing both the efficacy and safety of AV gene therapies. By advancing SEL302 into the clinic, we believe we can help all of our current and future gene therapy partners accelerate the use of mTOR in their gene therapy programs by providing a clear clinical and regulatory blueprint for them to follow. This past October, at the 29th Annual European Society of Gene and Cell Therapy, or ESGCT, conference, the lecture showcased three presentations, including one joint presentation with our partner, Aspire. These presentations highlighted the immunogenic nature of MTAEV capsids in healthy volunteers, and the potential of mTOR and mTOR-IL in addressing key efficacy and safety challenges in gene therapy. Our evolving precision immune tolerance platform is designed to enable AAV vector redosing by amplifying the magnitude and duration of effectively inhibiting the formation of anti-AAV antibodies, while simultaneously mitigating adverse responses associated with high AAV doses. In our human-proof concept study, we evaluated mTOR's ability to inhibit the formation of neutralizing antibodies in healthy human volunteers and observed that with a single dose of mTOR, all subjects treated with 0.3 mgs per kg of mTOR maintained NAP titers of below 1 to 25 at day 30, and two-thirds of the subjects at this level of mTOR maintained NAP titers below 1 to 5 at day 30. Our preclinical data in non-human primates and mice indicate that two additional monthly doses of mTOR has the potential to provide durable inhibition of anti-AV antibodies. We plan to use this dosing regimen in our upcoming Phase I-II trial in MMA. We're also excited by our preclinical data, which indicates that mTOR or mTOR-L may potentially transform the treatment paradigm for AV gene therapy from a one-and-done to a low-and-slow, whereby patients could receive multiple lower doses of gene therapy, tighter it up to a therapeutic benefit, and avoid the risk associated with higher-vector doses of AV gene therapy needed in a one-time-only treatment model. The area of precision genetic medicine is here, and AV-mediated gene therapies have the potential to be transformational for those who can access them. However, 30 to 70% of the patient population are not eligible for treatment or trial inclusion due to preexisting anti-AV antibodies from natural AV infections. This prevents them from gaining access to potential life-altering therapies for which there may be few or no treatment alternatives. We're developing Zork, our proprietary ITG protease candidate that is designed to specifically cleave human ITG with the goal of expanding access to gene therapies to those patients who are currently excluded due to preexisting anti-AV antibodies. Zork is derived from a non-human pathogen and has low cross-reactivity to pre-existing anti-I2G protease antibodies. In addition to potentially enabling dosing of patients with pre-existing AV antibodies, we believe that the combination of Zork within TOR could open a therapeutic treatment window and enable repeat dosing of this enzyme therapy. At the same time, by increasing the eligible prevalent patient population, we aim to bring hope to those who may not have any other effective treatment options, enable companies to maximize the commercial potential of their gene therapy candidates, and help to make otherwise uneconomic gene therapy candidates viable targets for commercial development. Finally, we continue to work with Ginkgo Bioworks to design novel AV capsids with a goal of improving transduction efficiency, liver tropism, and immunogenicity profile. The Lector will conduct all non-clinical and clinical studies with Ginkgo's uniquely designed engineered capsids. By combining mTOR, With more efficient capsids, we could potentially further reduce the doses of AAV gene therapy needed to see therapeutic benefit. As you can see, we're taking a multidimensional approach to tackling immunogenicity challenges facing AAV gene therapies. mTOR and mTOR-L to mitigate the de novo formation of re-losing antibodies and enable re-dosing. Zork to those patients who, due to natural AAV infections, are ineligible for treatment by gene therapies and next-generation AAV capsids to improve both organ tropism and transduction efficiency of gene therapies. We're actively pursuing business development and out-licensing opportunities for Zork, mTOR, and our next-generation AAV capsids in gene therapy applications. And our goal is to maximize the value of our gene therapy vertical by becoming the leading provider of solutions to manage immunogenicity to AV gene therapy developers. Now turning to our biologics pipeline. Many biologics can be highly immunogenic as well, resulting in suboptimal responses due to the development of anti-drug antibodies after treatment. Patients who develop an immune response may be forced to discontinue treatment or experience adverse reactions to continued therapy. We believe the use of mTOR as an adjunct to biologics offers a promising approach to reduce the unwanted immune response and improve patient outcomes. Our most advanced program, SEL212, has served as clinical proof of concept for a precision immune tolerance platform with over 400 patients dose to date. As a reminder, SEL212 is comprised of IMTOR, co-administered with a proprietary URO case, Pagetri case, for the treatment of chronic refractory gout, and was licensed to SOBI in 2020. Our Phase III disorganizer program kicked off 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 bagadricase at 0.2 mgs per kg. We believe SEL212 represents a potentially clinically differentiated asset for people with chronic refractory gout. In our Phase II trial, we observed a numerically higher percentage of patients responding to therapy on SEL212 versus Crostexa. A higher percentage of responders in patients with visible uric acid crystal tissue deposits, or TOFI, as well as statistically significant lower serum uric acid levels in treatment periods three and six versus Crostexa. These responses were achieved with no need for oral immunosuppressive or weekly methotrexate, and less frequent dosing of an eye infusion with monthly dosing of SEL212 versus biweekly infusions with Cristexa. Accordingly, with this tolerability profile, simplified dosing, and the avoidance of immunosuppression or methotrexate, we believe SEL212 is well positioned against the current standard of care and other drugs in the class that target this patient segment. We continue to work closely with our partners, SOBE, our clinical trial providers, and regulatory authorities to advance towards the successful completion of the DISSOLVE program, and we are on track to both complete DISSOLVE 1 and 2 and announce joint top-line data in Q1 2023. With extensive clinical data in SEL212 currently in Phase 3, we believe Selecta is well-positioned to leverage these learnings into our second biologic indication in IgA nephropathy, which is a kidney disease that occurs when immune complexes of an antibody called immunoglobulin A1, or IgA1, accumulate in the kidneys. By combining mTOR with an IgA protease to remove injurious IgA from the kidneys and improve markers of renal dysfunction, we believe our novel approach has the potential to address the underlying pathophysiology of the disease. We're currently working with our external partners to identify an IGA Proteus candidate for this program and plan to finalize clinical candidate selection by year-end. We're extremely excited about the advancements across our pipeline and the growing body of evidence showcasing the promise of our pioneering mTOR precision immune tolerance platform in a number of applications. We look forward to continuing our momentum and executing towards upcoming value-driving events. With that, I'll turn the call over to Kevin to run through our financial results for the third quarter. Kevin?