Selecta Biosciences, Inc.

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.

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?

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.