Selecta Biosciences, Inc.

Good morning, and welcome to the Selecta Biosciences first quarter 2022 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 first quarter 2022 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 quarterly report on form 10Q for the quarter ended March 31st, 2022, which will be filed today with the Securities and Exchange Commission or SEC. Joining me today are Carson Bruin, President and Chief Executive Officer, Peter Traber, Chief Medical Officer, and Kate Kishimoto, Chief Scientific Officer. During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential safety, efficacy, and regulatory and clinical progress of our product candidates, financial projections, and our future expectations plans, partnerships, and prospects. These statements are subject to various risks that are described in the filings made with the SEC, including our quarterly report on Form 10Q. Your caution is not to place undue reliance on these forward-looking statements, which speak only as of today, May 5, 2022, and select a disclaims any obligation to update such statements, even if management's views change. I would now like to turn the call over to Carson. Carson?

Good morning. I appreciate everyone taking the time to join us today. Despite geopolitical turbulence, macroeconomic volatility, and sector-specific headwinds, we believe Selecta's proactive approach to managing risk, which included opening additional SEL212 clinical trial sites in the US in the face of heightened geopolitical instability, Prioritizing our product portfolio to manage our resources and raising additional capital ensures that Selecta can build on the exciting progress made in 2021 and realize the full potential of our leading precision tolerance platform. We continue to make steady progress across our proprietary pipeline, as well as deliver on several key strategic and financial milestones. Most notably, We recently announced that the clinical hold on SEL302, our wholly-owned gene therapy candidate for medic malonic acidemia, or MMA, was lifted on March 9th, and we successfully completed an underwritten offering in April, which raised approximately $38.7 million in cross proceeds. With our focused wholly-owned portfolio and financial runway into mid-2024, We believe Selecta is well-positioned to execute on our clinical stage assets in biologics and gene therapies, advance our proprietary I2G protease Zork into the clinic, complete our I2A protease clinical candidate selection for a program and accelerate the development of IMTO-IL, our next-generation antigen-specific precision immune tolerance platform. We're incredibly excited to advance our IMTO platform and bring hope to the over 24 million Americans suffering from autoimmune diseases daily. Our sharpened strategic approach has allowed us to support and accelerate the development of our wholly-owned pipeline with a focus on autogenic therapies for autoimmune diseases and therapeutic biologics, as well as provide transformative solutions for our gene therapy partners to unlock the true potential of adeno-associated virus or AV gene therapies. I would now like to walk you through key updates and recent strategic partnerships pertaining to the three pillars of our pipeline. The current standard of care for autoimmune diseases utilizes immunosuppressive drugs, which are associated with side effects that often leave patients vulnerable to serious infection and malignancies or treatments that provide only symptomatic relief. Our approach is to reimagine the treatment paradigm for autoimmune disease by using our precision immune tolerance platform to restore natural immune system balance by inducing and expanding Anderson-specific regulatory T cells, thus avoiding the need for systemic immune suppression or chronic symptom masking treatments. Recent preclinical data generated by our scientific team showed synergistic activity when mTOR was combined with engineered IL-2 molecules that are selective for Tregs. This combination, which we call IMTR-IL, shows a substantial increase in antigen-specific Tregs when co-administered with a target antigen well beyond what we see with IMTR alone, in which we already have observed clinically meaningful benefits. We tested IMTR-IL for the ability to induce durable immune tolerance to a co-administered AV gene therapy vector in mice. We observed complete inhibition of anti-ADB antibody formation after multiple doses of gene therapy through 117 days. Most excitingly, this effect was observed and will be considered subtherapeutic doses for mTOR alone. These results suggest that this combination of a T-REX selective IL-2 with mTOR has the potential to increase the potency durability, and efficacy of the antigen-specific immune tolerance that mTOR elicits. Current programs of engineered Treg-selective IL-2 molecules focus on a generalized expansion of total existing Tregs, but not Treg-specific for the autoantigens responsible for the pathogenesis of autoimmune diseases. Thus, we believe mTOR-IL has the potential to be a truly differentiated first-in-class antigen-specific immunotherapy for autoimmune disease that restores immune system balance in vivo. We believe that our ability to induce antigen-specific T-Rex in vivo is potentially the most elegant solution to the intractable problem of restoring balance to the immune system. Further, we believe mTOR-IL represents a transformative evolution of our precision immune tolerance platform with implications across all three pillars of our pipeline, in particular, the potential to create breakthrough therapies for the treatment of autoimmune disease. A key priority for Selecta in 2022 will be to accelerate the development of a proprietary engineered IL-2 molecule. 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 speed the development of a next generation, highly differentiated IL-2 mutine to combine with mTOR. We believe our mTOR platform is ideally suited to address primary bilayer cholangitis, or PBC, a T-cell liver disease driven by a well-defined antigen. In PBC, the immune system mistakenly attacks tissue in the liver and damages the small bile ducts. Treatments to help slow the progression and prevent complication of PBC are available. However, these medications ultimately fail to control PBC, and patients often require a liver transplant. As shown in animal models of liver injury and inflammation, the ability of mTOR to target the liver coupled with the expansion of antigen-specific Tregs when co-administered with IL-2 suggests that mTOR-IL may be beneficial in the treatment of patients with PBC. We are continuing IND and APN studies for this program. In parallel, we are evaluating additional targets and indications that be well-suited for our first-in-class antigen-specific immunotherapy, and we'll update the market as we add indications to our pipeline in autoimmune disease. Moving on to our work in gene therapy, we believe Selector, with a combination of Intor and our proprietary ITG protease Zork, has the potential to solve some of the most difficult challenges facing the AAV gene therapy field. Patients who have preexisting antibodies against the capsids due to prior natural exposure to the AAV virus are often ineligible for treatment. Additionally, the anti-capsid immune response prevents the ability to re-administer AAV vectors. As a result, gene therapies are considered one-time only treatments. Currently, 30 to 70% of the patient population for gene therapy trials are ineligible for inclusion due to preexisting utilizing 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 translate clear preexisting neutralizing antibodies and create a window during which AV gene therapies could be administered. However, IgG proteases are derived from bacteria and are themselves highly immunogenic. Additionally, some IgG 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 that is designed to specifically cleave human ITG, is derived from non-human pathogen and will observe low cross-reactivity to pre-existing anti-ITG protease antibodies. We believe that the combination of Zork with mTOR could enable repeat dosing of this enzyme therapy. This combination of Zork and mTOR has the potential to simultaneously address two of the biggest issues currently limiting AAV gene therapy, XORC 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 novel immune responses to AAV gene therapy and enable redosing. We believe that the combination of XORC and IMTOR has the potential to provide safer and more effective gene therapies to more patients and truly unlock the potential of the gene therapy modality by transforming a treatment into a durable, long-term cure. Preclinical studies suggest multiple potential benefits of mTOR in AV gene therapy, including increased transient expression in the first dose, mitigation of hepatic inflammation, more durable transient expression, and inhibition of capsid-specific B and T cell responses. We are proud to have multiple presentations, both independently and in partnership with AskBio, at the upcoming annual meeting of the American Society of Gene and Cell Therapy, or ASGCT, this month. Our presentations will highlight the ability of mTOR and mTOR-IL to mitigate anti-AEV antibodies and enable repeat vector dosing. In a single-dose clinical study in Healthy Human Volunteers, conducted in partnership with AskBio, we observed the ability of mTOR to mitigate the formation of anti-AV neutralizing antibodies out to 30 days, and our preclinical data in mice and non-human primates suggest that control of antibodies can be maintained with two additional doses of mTOR. Another major challenge for the genotherapy field relates to the serious toxicities associated with vector doses of 1E14VG per kigs or higher. Solving this problem will likely require a multi-pronged approach, including engineering more efficient capsids. The ability to redose AV vectors could provide a complementary strategy by enabling the administration of multiple lower doses of capsids. We would like to see the dosing paradigm for AV gene therapy change from one and done to low and slow. By giving multiple lower doses of a gene therapy, we could potentially titrate up to the intended therapeutic level while avoiding the unfortunate adverse events that have been seen at high doses of gene therapies. Initial studies in mice suggested mTOR-L has the potential to mitigate anti-AV antibody responses at high vector doses up to 5E13 VG per kicks. We're also excited about our collaboration with Ginkgo Bioworks 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 Ginkgo's cell engineering and high throughput screening capabilities, and Selector's mTOR precision immune tolerance platform to advance gene therapy delivery. By combining mTOR with more efficient capsids, we could potentially reduce the dose of gene therapy needed to see therapeutic benefit and further mitigate the risk of serious adverse events associated with high vector doses. Moving on to our wholly owned gene therapy asset, SEL302. On March 9th, the FDA cleared the IND application for our phase one gene therapy clinical trial of SEL302, a combination of mTOR with MMA101 being developed for the treatment of MMA, a rare metabolic disease in which the body cannot break down certain proteins and fats. The trial is expected to initiate in the second half of 2022 and will evaluate the safety and efficacy of SEL302 and the mitigation of neutralizing antibodies against the MMA101 AV capsid. We are hopeful that the phase one trial of SEL302 will build on the growing body of evidence supporting the potentially multifaceted benefits of mTOR for enhancing the efficacy and safety of AV gene therapies and the learnings from our MTAV8 capsid study in healthy volunteers. We believe development of a wholly owned asset in MMA will provide an important regulatory and clinical blueprint for our leading gene therapy partners, including Takeda, Cerepsa, and Aspile. We are seeing excellent progress across our gene therapy platform, and we look forward to continuing to progress in TOR in our wholly owned gene therapy programs. To maximize the full potential of our platform, we plan to actively pursue business development and out licensing opportunities for both mTOR and ZORG for gene therapy applications. Lastly, I want to provide an update on our biologics pipeline, which houses our most mature program. SEL212 has served as an important clinical validation for a precision immune tolerance platform with over 450 patients' dose 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 that 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 mTOR, co-administer with the proprietary urocase, Pegatocase, for the treatment of chronic refractory gout and was licensed to Swedish Orphan Bivitrum, or 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, 0.1 mgs per gig, and 0.15 mgs per gig, and one dose of the Gatricase, 0.2 mgs per gig. The original enrollment target for both studies was 105 subjects. On December 1st, 2021, we closed enrollment in 112 subjects for Dissolve-1, which is being conducted in the United States. Dissolve 2 enrollment is continuing at pace and is being conducted in four countries across Eastern Europe and the United States. We have proactively undertaken steps to prioritize the safety of our patients and investigators, as well as mitigate any potential disruptions due to the evolving geopolitical situation in Ukraine and Russia. Firstly, we have temporarily suspended screening and randomization for new patients in both Russia and Ukraine. and have reserved existing clinical trial supplies in these countries for those already involved in the study. Secondly, to mitigate the risk of any delays, we proactively added 11 additional sites in the United States to offset the potential loss of subjects in Ukraine and Russia and speed enrollment in DISSOLVE-2. We now have 55 active sites and are on track to complete the study in Q4 2022. Finally, in agreement with our partner SOBI, we have increased enrollment in DISSOLVE-2 to approximately 140 subjects in an effort to replace subjects enrolled in Russia and Ukraine who may be lost to operational issues. We anticipate that these mitigation efforts will see us complete both DISSOLVE studies in Q4 2022 with joint top-line data available in Q1 2023. We will continue to work closely with our partner SOBI our clinical trial providers, and regulatory authorities to ensure the successful completion of the DISSOLVE program. With extensive clinical data and 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 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 IgA protein deposits, the underlying pathophysiology of the disease. We believe our novel approach, which combines mTOR with an IgA1 protease, has the potential to remove injurious IgA from the kidneys, improve markers of renal dysfunction, and have a transformative impact on patients' lives. We're currently working with IGEN Biosciences on the first-generation IgA protease derived from the Haemophilus influenzae bacteria. Additionally, in October 2021, we entered a collaboration with Ginkgo Bioworks to generate a second-generation IgA protease designed to have lower immunogenicity and, when combined with mTOR, have a potentially transformative therapeutic profile. We plan to finalize clinical candidate selection by the end of the year. We're extremely excited about the advancements across all three pillars of our pipeline and the value driving milestones ahead. With that, I will turn the call over to Kevin to run through our financial results for the first quarter ended March 31st, 2022. Kevin.