Selecta Biosciences, Inc.

Good morning, and welcome to the Selecta Biosciences fourth quarter and full year 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 it is being recorded. For opening remarks, I would like to introduce Kevin Tan, Chief Financial Officer of Selecta. Please go ahead.

Thank you and good morning. Welcome to our fourth quarter and full year 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, worldwidewebselectivebio.com, and our annual report on Form 10-K for the year to end at December 31st, 2021, which will be filed today with the Securities and Exchange Commission, or SEC. Joining me today are Carson Bruhn, President and Chief Executive Officer, and Peter Traver, Chief Medical 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 SEC, including the most recent annual report on Form 10-K. Your company should not place undue reliance on these forward-looking statements, which speak to the urgency of March 10, 2022, to select and disclaim any obligations of these such statements, even if management's views change. I would now like to turn the call over to Karsten Bruhn. Karsten?

Thank you, Kevin. Good morning. I appreciate everyone joining us today. Before we begin, I'm thrilled to announce that on March 9th, the FDA cleared the Investigational New Drug, or IMD, application for a Phase I Genotherapy Clinical Trial of SGL302 to treat metabolic acidemia, or MMA, a serious and life-threatening metabolic disorder. This clinical trial is a critical step in our efforts to treat MMA and enable redosing of AUV-mediated gene therapies. We expect to initiate the phase one trial in the second half of 2022, and we look forward to bringing hope to all those patients and families affected by this terrible disease. 2021 was a very busy and transformational year. and we're extremely pleased with the significant progress to propel our business forward. Over the past year, we advanced our pipeline of wholly owned and partnered programs. We entered a number of key strategic partnerships and are close to catalyzing an evolution of our precision immune tolerance platform. By combining mTOR with a Treg-selective IL-2 molecule, we've observed synergistic effects in the induction and expansion of antigen-specific regular T cells for Tregs. We believe this transformative combination, which we call mTOR-IL, has the potential to enhance the induction and durability of antigen-specific immune tolerance, a substantial leap forward for our mTOR platform. I would now like to walk you through key updates and recent strategic partnerships pertaining to the three pillars of our pipeline. Reimagining immunotherapy for autoimmune disease, unlocking the potential of adeno-associated virus or AAV gene therapy, and amplifying the efficacy of biologics. The current standard of care for autoimmune diseases is broad immune suppression, which is associated with side effects that often leave patients vulnerable to serious infection and malignancies. By reimagining immunotherapy for autoimmune diseases, we have taken important steps to address the significant need for antigen-specific therapies without chronic and systemic immune suppression. I want to start out with our most exciting finding from the last 12 months. In recent preclinical data generated by our scientific teams, we observed that IMTOR showed profound synergistic activity when combined with engineered IL-2 molecules that are selected for T-REX. Mice harboring transgenic antigen-specific T-cells were dosed with a target antigen and then treated with IMTOR-IL, a combination of IMTOR and a T-rex-selective IL-2. We observed IMTOR alone to induce antigen-specific T-rex. and from my extensive clinical experience with mTOR, find this level of Treg induction to be clinically meaningful. Interestingly, the administration of mTOR-IL combined with the target antigen led to a substantially greater increase in antigen-specific Tregs. In contrast, mice dosed with the engineered IL-2 plus antigen showed only an expansion of total Tregs, but little or no expansion of any specific T-Rex. We believe mTOR-IL is a transformative evolution of our precision immune tolerance platform with implications across our entire pipeline. Importantly, mTOR-IL has the potential to unlock treatments for patients with a variety of autoimmune diseases. We also tested IMTO-IL in an annual model for the ability to induce durable immune tolerance to a co-administered AAV gene therapy. In this study, IMTO-IL was co-administered with two doses of an AAV vector. we observed complete inhibition of anti-AV antibody formation after multiple vector doses through 117 days. And most excitingly, this synergistic effect was observed at doses that are considered sub-therapeutic for mTOR alone. These results suggest that the addition of a Treg-selective IL-2 to mTOR has the potential to increase the potency, durability, and potentially allow for dose sparing of mTOR. Current programs of engineered IL-2 molecules in development for autoimmune diseases focus on non-selective expansion of total existing T-Rex, but not T-Rex-specific for the autoenogens that drive the pathogenesis of the disease. IMTR-IL has the potential to be a truly differentiated, first-in-class, antigen-specific immunotherapy that restores balance in vivo to the millions of patients suffering from autoimmune disease today. On September 8, 2021, we entered into a collaboration with Cyrus Biotechnology, a world-leading protein engineering company, to design a next-generation proprietary key retroactive IL-2 molecule. A key priority for 2022 will be to identify target indications and accelerate the development of IMTOR-IL into the clinic. In parallel, we are continuing IND-enabling studies for our primary blood cholangitis, or PBC, program. Moving on to our work in gene therapy. In 2021, we reported with our partner, Aspio, on a clinical proof-of-concept study of mTOR combined with an AAV empty capsid in healthy volunteers, which I'll expand on later. We also published preclinical studies in Science Advances describing the first-dose benefits of mTOR on enhancing transient expression when co-administered with the initial dose of an A-B vector. In addition, we published a paper in Frontiers in Immunology describing the potential hepatoprotective properties of mTOR. These findings build on the growing body of evidence demonstrating the potentially multifaceted benefits of mTOR for enhancing the efficacy and safety of AV genes therapy. On October 4, 2021, we entered a strategic license agreement with Takeda, a global pharmaceutical leader with expertise in rare diseases, to combine mTOR with their targeted next-generation gene therapies for two lysosomal storage disorders. We are encouraged by the strong endorsement from one of the leaders in the lysosomal storage disorder landscape. as a validation of our approach and precision immune tolerance platform. We look forward to working closely with and supporting Takeda. We also continue to seek partnerships to expand our platform with technologies that can be applied to mitigating immunogenicity of AAV gene therapies. On October 21st, 2021, we announced an exclusive license agreement with Genovese to advance Zork, a differentiated IgG protease to enable the dosing of transformative gene therapies in patients with preexisting anti-AAV immunity. Currently, up to 50% of the potential patient population for gene therapy trials are ineligible for inclusion due to preexisting neutralizing anti-AEV antibodies that are a result of natural infection with wild-type AAV. Thus, many patients in need are unable to access potentially life-altering treatments for their genetic diseases, for which there may be few or no treatment alternatives. Zork is a bacterial protease that is designed to specifically cleave human IgG and is being developed as a pretreatment in advance of an AV gene therapy with a goal of transiently clearing preexisting neutralizing antibodies to create a treatment window during which gene therapy can be administered. Zork is differentiated from some other I2G proteases in that Zork is derived from a non-human pathogen and therefore has demonstrated very low cross-reactivity to pre-existing anti-I2G protease antibodies. The combination of Zork and IMTOR has the potential to address two of the biggest issues currently limiting AAV gene therapy. Zork to bring the power of gene therapies to those patients who would be otherwise ineligible for treatment due to preexisting antibodies, and IMTOR to mitigate the normal immune responses to AAV gene therapy and enable redosing. We believe that the combination of Zork and mTOR has the potential to provide safer and more effective gene therapies to more patients. We also announced a collaboration with Ginkgo Bioworks on January 10, 2022, to design novel AV capsids with a goal of improving transduction efficiency, liver tropism, and immunogenicity profile. Ginkgo will design and engineer the capsids, and Selector will conduct all nonclinical and clinical studies thereafter. This partnership leverages skin-co-cell engineering and high-throughput screening capabilities and Selecta's mTOR precision immune tolerance platform to advance gene therapy delivery. A major hurdle for the gene therapy field has been the toxicity associated with high AAV doses. In many cases, the toxicity is inextricably linked to immunogenicity. Our vision is to change the treatment paradigm to dose low and slow by combining mTOR with more efficient capsids to enable administration of multiple smaller doses rather than a single high AAV dose, which is often associated with serious adverse events. As mentioned earlier, in 2021, we announced top-line results from the first in-human phase one dose escalation trial of SEL399, which we conducted jointly with our partner, ASBio. SEL399 is an AV8 empty vector capsid containing no DNA combined with mTOR at doses of 0.15 mcg per kg and 0.3 mcg per kg. The randomized, placebo-controlled, double-blind dose escalation study conducted in Healthy Volunteers was designed to determine the dose regimen of mTOR to mitigate the formation of lutealizing antibodies, or NAPs, against AV8 serotype capsid used in chinotherapies. We observed a strong immune response in humans administered AAV anti-capsids alone. The addition of mTOR to the administration of anti-capsids reduced the formation of anti-AAV8 NAVs in a dose-dependent manner at day 30. Consistent with preclinical data, we observed that the single dose of intro cohorts saw delayed formation of NAFs, eventually reaching similar median levels of NAFs 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 mTOR has the potential to inhibit the formation of NAVs with improved durability. We expect that the learnings from the empty capsules clinical trials and our nonclinical studies employing three monthly doses of mTOR will guide the clinical development of our proprietary gene therapy program, SEL302. SEL302 is a combination of mTOR with MMA101, an AV gene therapy being delivered for the treatment of MMA, a rare metabolic disease in which the body cannot break down certain proteins and fats. As previously mentioned, on March 9th, the FDA cleared the IND application for our Phase I clinical trial of SEL302 to treat MMA, I want to thank our dedicated clinical, regulatory, and CMC teams here at Selecta and our external partners for all their hard work in addressing the clinical hold. The trial is expected to initiate in the second half of 2022 and will evaluate the safety and efficacy of SEL302 and the prevention of formation of utilizing antibodies against the MMA101AEV capsid. Our second wholly-owned proprietary gene therapy product candidate is SEL313 for the treatment of ornithine transcarbamylase deficiency. While we had originally anticipated a clinical trial application and IMD filing in 2022, we have decided to prioritize our resources on the MMA program for the time being. Overall, we're seeing excellent progress across our gene therapy programs and look forward to continuing to progress Intour, both in our wholly-owned gene therapies as well as in partnership with our leading gene therapy partners. We believe that the platform technologies of Intour and Zork position Selector as a leader in unlocking the true potential of AAV gene therapy. Lastly, a few key updates on our biologics programs, our most mature pipeline pillar. 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 minimize the healthcare and economic burden of anti-drug antibodies. SEL212 is comprised of IMTOR, co-administered with our proprietary EU case, the GATRI case, for the treatment of chronic refractory gout and was licensed to SOBI in 2020. As a reminder, our Phase III 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 mTOR, 0.15 mgs per kg and 0.15 mgs per kg, and one dose of Pegatricase, 0.2 mgs per kg. Each trial aims to enroll up to 120 patients with up to 40 subjects in each of the two treatment arms and up to 40 on placebo. On December 1, 2021, we announced full enrollment of DISSOLVE-1, which is being conducted in the United States. Enrollment into the DISSOLVE-2 trial is ongoing, and the study is being conducted in the United States and four countries across Eastern Europe. We are closely monitoring the evolving geopolitical situation in Ukraine and Russia and have proactively undertaken mitigation steps to prioritize the safety of our patients and investigators first and foremost, as well as address any potential disruptions. While we have some temporarily closed screening and randomization at sites in both Russia and Ukraine due to shipping constraints, We have proactively added 11 additional sites in the United States to offset and speed enrollment in Resolve 2. Of these additional enrollment sites, nine have already been activated and two are pending initiation and activation. We will continue to work closely with our licensing partners SOBI, our clinical trial providers, and regulatory authorities to assess the potential impact on the program. Before turning back to our pipeline and program updates, we want to emphasize that our hearts are with the people of Ukraine during this unprecedented humanitarian crisis. With extensive clinical data and an asset currently in Phase III, we believe our biologics pipeline is well positioned to leverage these learnings into our second biologic indication 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 underlying pathophysiology of the disease, which are the IgA immune deposits. We believe our novel approach, which combines INTOR with an IgA1 protease, has the potential to remove injurious IgA from the kidneys and improve markers of renal dysfunction. We're currently working with IGaN Biosciences on a first-generation IgA protease derived from the Haemophilus influenzae bacteria. On October 26, 2021, we entered a collaboration with Ginkgo Bioworks to discover next-generation enzyme therapies. Today, we're announcing that the first program will focus on generating a second-generation IgA protease with lower immunogenicity and potentially transformative therapy potential when combined with mTORP. We're extremely excited about these advancements and the value-driving milestones ahead. With that, I'll turn the call over to Kevin to run through our financial results for the fourth quarter and fiscal year ended December 31st, 2021. Kevin? Thank you, Karsten.