On March 10, 2022 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, reported financial results for the quarter and full year ended December 31, 2021 and provided a business update (Press release, Selecta Biosciences, MAR 10, 2022, View Source [SID1234609862]).

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"I am pleased to announce that on March 9th the FDA lifted the clinical hold on our SEL-302 gene therapy program to treat methylmalonic acidemia. We look forward to starting our phase 1 clinical trial expeditiously and to bring hope to those patients and families seeking a potentially durable and lifelong treatment for this terrible disease," said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. Dr. Brunn continued, "2021 was a transformative year for Selecta. We continued to grow our pipeline and achieved many significant development milestones. We also further validated and expanded our precision immune tolerance platform by entering into five important collaborations over the prior 12 months. Additionally, in January, we released preclinical data demonstrating the synergistic effects of ImmTOR in combination with a Treg selective IL-2. This potentially transformative combination, which we call ImmTOR-IL, represents an evolution of our ImmTOR platform to enhance the induction and durability of antigen-specific regulatory T cells. By comparison, Treg-selective IL-2 molecules currently in development non-specifically expand total Tregs. We believe ImmTOR-IL has the potential to be a first-in-class antigen-specific therapeutic."

Dr. Brunn continued, "With our recently presented topline data from the empty AAV8 capsid study of SEL-399 in healthy volunteers and our partnership with Genovis for Xork, Genovis’ highly differentiated IgG protease, we aim to unlock the full potential of AAV-mediated gene therapies. First, in the human volunteer clinical trial conducted with our partner AskBio, we evaluated a single dose of ImmTOR combined with an AAV8 empty capsid and observed the ability of ImmTOR to inhibit neutralizing antibodies to AAV8 empty capsids out to 30 days. Our preclinical data in mice and nonhuman primates indicate that an additional two monthly doses of ImmTOR has the potential to durably inhibit anti-AAV antibody formation, which is an important step toward enabling re-dosing and transforming gene therapies from a treatment into a cure. Secondly, by developing the Xork IgG protease with the goal of enabling treatment of those 20-50% of the population who are ineligible for gene therapy due to preexisting antibodies to AAV vectors, we aim to bring hope to those suffering from rare monogenic disease who would otherwise benefit from gene therapy treatment. Finally, we continued to prosecute our clinical pipeline, and in Q4 of 2021 we both announced completion of enrollment for DISSOLVE I, the first of two clinical studies of the Phase 3 DISSOLVE development program of SEL-212 for chronic refractory gout, and filed our IND for SEL-302, a wholly owned gene therapy program for the treatment of methylmalonic acidemia. We are incredibly excited about our future, and we are focused on continuing to prosecute our growing wholly owned pipeline, continuing to advance our technologies to enable AAV gene therapies, supporting our numerous collaboration partners and rapidly advancing our next generation ImmTOR-IL into the clinic."

Recent Highlights and Anticipated Upcoming Milestones:

Recent Strategic Collaborations:

Autoimmune:
Cyrus Biotechnology, Inc. ("Cyrus"): Protein engineering collaboration combining Selecta’s ImmTOR platform with Cyrus’ ability to radically redesign protein therapeutics. The lead program in the collaboration is a proprietary interleukin-2 (IL-2) receptor agonist designed to selectively promote expansion of regulatory T cells (Treg) for the treatment of patients with autoimmune diseases and other deleterious immune conditions. Selecta believes the combination of ImmTOR with a Treg-selective IL-2 agonist (ImmTOR-IL) has the potential to be a first-in-class therapeutic profile with antigen specific Treg expansion.
Gene Therapies:
Genovis AB (publ.) ("Genovis"): Exclusive license agreement to advance a next-generation IgG protease. This partnership leverages Genovis’ proprietary and differentiated immunoglobulin G (IgG) protease, IdeXork (Xork), and Selecta’s ImmTOR platform to enable the dosing of transformative gene therapies in patients with pre-existing adeno-associated virus (AAV) immunity and treat certain IgG-mediated autoimmune diseases. In contrast to other IgG proteases, Xork has been observed to have low cross-reactivity to pre-existing antibodies in human sera. The combination of Xork with ImmTOR has the potential to address two of the biggest immunological challenges to gene therapy – expanding access to gene therapies by overcoming pre-existing antibodies to AAV and enabling vector re-dosing.
Ginkgo Bioworks, Inc. ("Ginkgo"): Collaboration agreement to design novel AAV capsids with potentially improved transduction, enhanced tissue tropism and reduced immunogenicity. This partnership leverages Ginkgo’s high throughput screening and cell engineering capabilities and Selecta’s ImmTOR platform to advance gene therapy delivery with the goal of improving gene therapies through best in class and fit for purpose capsid design. Ginkgo plans to design and engineer the capsids and Selecta will conduct all pre-clinical and clinical studies thereafter.
Takeda Pharmaceutical Company Limited ("Takeda"): Strategic license agreement to develop next-generation gene therapies in two lysosomal storage disorders. The collaboration leverages Selecta’s ImmTOR platform to enable the redosing of transformative gene therapies.
Biologic Therapies:
Ginkgo: Partnership to design novel enzymes and proteins with transformative therapeutic potential to advance treatments for all IgA mediated diseases including IgA nephropathy. This partnership leverages Ginkgo’s cell programing platform and high throughput screening capabilities and Selecta’s ImmTOR platform with the goal of creating transformative biologic and enzymatic therapies.
Pipeline and Development Updates:
Tolerogenic Therapies for Autoimmune Disease:

ImmTOR with proprietary IL-2 protein agonist (ImmTOR-IL): ImmTOR may have profound synergistic activity with engineered IL-2 molecules that are selective for Tregs. Selecta has observed, when ImmTOR-IL was co-administered with an antigen of interest in a preclinical study, synergistic effects in further expanding antigen-specific Tregs when compared to ImmTOR alone, positioning it to be a potential first-in-class antigen-specific therapy for the treatment of autoimmune diseases.
Primary biliary cholangitis (PBC): Selecta continues IND-enabling work on an ImmTOR-based approach to treating PBC.
Gene Therapies:

SEL-399 human proof-of-concept: On November 8, 2021, in collaboration with AskBio, Selecta reported topline data for the first-in-human, dose-escalation trial of SEL-399, an adeno-associated viral serotype 8 (AAV8) empty vector capsid (EMC-101) containing no DNA combined with ImmTOR. The key objective was to determine the dose regimen of ImmTOR to effectively mitigate the formation of antibodies to AAV8 capsids used in gene therapies.
SEL-302 for methylmalonic acidemia (MMA): On March 9, 2022, the U.S. Food and Drug Administration ("FDA") removed the clinical hold on SEL-302 for the treatment of patients with methylmalonic acidemia ("MMA"). Selecta expects to start the phase 1 clinical trial in the second half of 2022.
SEL-313 for ornithine transcarbamylase deficiency (OTC deficiency): Selecta has decided to temporarily pause development in order to prioritize resources on the MMA program.
SEL-018 IgG Protease (Xork): On October 21, 2021, Selecta and Genovis entered into an exclusive license agreement to advance Xork, a next-generation IgG protease. The novel combination of Xork and ImmTOR has the potential to simultaneously address two of the key hurdles in gene therapy today: pre-existing immunity and the inability to re-dose AAV gene therapies.
IND-enabling studies are expected to commence in 2022.
Biologic Therapies:

SEL-212 for chronic refractory gout: On December 1, 2021, Selecta announced complete enrollment for DISSOLVE I, the first of two studies in our Phase 3 development program of SEL-212 (which has been licensed to Swedish Orphan Biovitrum AB (publ.) ("Sobi")) and is currently being run in the United States.
The currently enrolling DISSOLVE II trial has sites in the United States and 4 Eastern European countries (including Russia and Ukraine). We have temporarily closed screening and randomization in both Russia and Ukraine to preserve in country study supplies. We have proactively activated additional enrollment sites in the United States to offset and speed enrollment in DISSOLVE II with 9 sites having already been activated and 2 pending initiation and activation.
ImmTOR with IgA1 protease for IgA nephropathy:
Selecta continues with IND-enabling studies in IgA nephropathy.
Fourth Quarter and Full Year 2021 Financial Results:

Cash Position: Selecta had $129.4 million in cash, cash equivalents, marketable securities, and restricted cash as of December 31, 2021, as compared to cash, cash equivalents, marketable securities, and restricted cash of $140.1 million as of December 31, 2020. Selecta believes its available cash, cash equivalents, restricted cash, and marketable securities will be sufficient to meet its operating requirements into the third quarter of 2023. Net cash used in operating activities was $60.4 million for the year ended December 31, 2021, as compared to $34.9 million of cash provided by operating activities for the same period in 2020.

Collaboration and License Revenue: Revenue for the fourth quarter and full year 2021 was $29.9 million and $85.1 million, respectively, as compared to $12.0 million and $16.6 million for the same periods in 2020. Revenue was primarily driven by the license agreement with Sobi resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program. Additionally, during 2021, Selecta recognized $1.0 million for shipments of clinical supply under the license agreement with Takeda and $0.4 million for shipments under the license agreement with Sarepta Therapeutics, Inc.

Research and Development Expenses: Research and development expenses for the fourth quarter and full year 2021 were $20.3 million and $68.7 million, respectively, as compared to $15.1 million and $54.5 million for the same periods in 2020. The quarterly and annual increases were primarily driven by expenses incurred for preclinical programs, payroll costs and AskBio collaboration costs.

General and Administrative Expenses: General and administrative expenses for the fourth quarter and full year 2021 were $5.5 million and $20.9 million, respectively, as compared to $4.8 million and $18.9 million for the same periods in 2020. The quarterly and annual increases were primarily driven by increases in stock compensation expenses and consulting fees, offset by a reduction in professional fees.

Net Income (loss): For the fourth quarter and full year 2021, Selecta reported net income of $12.2 million, or basic net income per share of $0.10, and a net loss of $(25.7) million, or basic net loss per share of $(0.22), respectively. For the fourth quarter and full year 2020, Selecta reported net losses of $(15.4) million, or $(0.14) per share, and $(68.9) million, or $(0.68) per share, respectively.

Conference Call and Webcast Reminder
Selecta management will host a conference call at 8:30 AM ET today to provide a corporate update and review the company’s fourth quarter and full year 2021 financial results. Individuals may participate in the live call via telephone by dialing (844) 845-4170 (domestic) or (412) 717-9621 (international) and may access a teleconference replay for one week by dialing (877) 344-7529 (domestic) or (412) 317-0088 (international) and using confirmation code 10157869. Investors and the public can access the live and archived webcast of this call and a copy of the presentation via the Investors & Media section of the company’s website, www.selectabio.com.