Full Press Release Details
Any statements in this presentation about the future expectations, plans
and prospects of Selecta Biosciences, Inc. (the "Company"), including without limitation, statements regarding the Company's cash runway, the unique proprietary technology platform of the Company, and the unique proprietary
platform of its partners, the potential of ImmTOR to enable re-dosing of AAV gene therapy and to mitigate immunogenicity, the potential of ImmTOR and the Company's product pipeline to treat chronic refractory gout, MMA, IgAN, other autoimmune
diseases, lysosomal storage disorders, or any other disease, the anticipated timing or the outcome of ongoing and planned clinical trials, studies and data readouts, the anticipated timing or the outcome of the FDA's review of the
Company's regulatory filings, the Company's and its partners' ability to conduct its and their clinical trials and preclinical studies, the timing or making of any regulatory filings, the potential treatment applications of product
candidates utilizing the ImmTOR platform in areas such as gene therapy, gout and autoimmune disease, the ability of the Company and its partners where applicable to develop gene therapy products using ImmTOR, the novelty of treatment paradigms that
the Company is able to develop, whether the observations made in non-human study subjects will translate to studies performed with human beings, the potential of any therapies developed by the Company to fulfill unmet medical needs, the
Company's plan to apply its ImmTOR technology platform to a range of biologics for rare and orphan genetic diseases, the potential of the Company's technology to enable repeat administration in gene therapy product candidates and
products, the ability to re-dose patients and the potential of ImmTOR to allow for re-dosing, the potential to safely re-dose AAV, the ability to restore transgene expression, the potential of the ImmTOR technology platform generally and the
Company's ability to grow its strategic partnerships, and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect,"
"hypothesize," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions,
constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors,
including, but not limited to, the following: the uncertainties inherent in the initiation, completion and cost of clinical trials including proof of concept trials, including the uncertain outcomes, the availability and timing of data from ongoing
and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the
results of later clinical trials, the ability to predict results of studies performed on human beings based on results of studies performed on non-human subjects, the unproven approach of the Company's ImmTOR technology, potential delays in
enrollment of patients, undesirable side effects of the Company's product candidates, its reliance on third parties to manufacture its product candidates and to conduct its clinical trials, the Company's inability to maintain its
existing or future collaborations, licenses or contractual relationships, its inability to protect its proprietary technology and intellectual property, potential delays in regulatory approvals, the availability of funding sufficient for its
foreseeable and unforeseeable operating expenses and capital expenditure requirements, the Company's recurring losses from operations and negative cash flows, substantial fluctuation in the price of its common stock, risks related to
geopolitical conflicts and pandemics and other important factors discussed in the "Risk Factors" section of the Company's most recent Annual Report on Form 10-K, and in other filings that the Company makes with the Securities and
Exchange Commission. In addition, any forward-looking statements included in this presentation represent the Company's views only as of the date of its publication and should not be relied upon as representing its views as of any subsequent
date. The Company specifically disclaims any intention to update any forward-looking statements included in this presentation. Selecta Biosciences Corporate Presentation - April 2022 2
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Selecta Biosciences Corporate Presentation - April 2022 3
Precision immune tolerance platform has potential to restore
self tolerance in autoimmune disease and overcome ImmTOR platform has immunogenicity of gene therapies and biologics potentially broad applicability Preclinical data indicates potentially profound synergy of ImmTOR and engineered
Treg-selective IL-2 to expand antigen-specific Tregs and improve durability of immune tolerance (ImmTOR-IL) SEL-212 in chronic refractory gout potentially serves as proof of concept for ImmTOR platform with over 400 patients dosed -
Human proof of concept in Phase 3 DISSOLVE I expected read out in Q4 2022 biologics and gene therapy Empty AAV study data in healthy volunteers showed the potential ability of ImmTOR to inhibit the formation of neutralizing antibodies to AAV
capsids SEL-302: IND for gene therapy program in methylmalonic acidemia (MMA) submitted in Q3 2021 Plans to advance Xork IgG Protease to mitigate pre-existing anti-AAV antibodies through IND-enabling studies Diversified pipeline
expanding IgA nephropathy: clinical candidate selection & IND enabling studies in process to autoimmune disease Plans to advance the ImmTOR platform with IL-2 (ImmTOR-IL) for use in autoimmune disease Funding into Q4 2023
Targeted partnerships to maximize platform potential Selecta Biosciences Corporate Presentation - April 2022 4
ImmTOR Platform Precision Immune Tolerance 5
ImmTOR combines nanoparticle technology with an FDA approved
anti-inflammatory and immunomodulatory drug, and is designed to generate antigen-specific immune tolerance when combined with an antigen of interest Selecta Biosciences Corporate Presentation - April 2022 6
Autoimmune Disease Gene Therapies/Biologics Selecta Biosciences
Corporate Presentation - April 2022 7
Treg-selective IL-2 receptor agonist ImmTOR Synergistic mechanism of
ImmTOR and a Treg-selective IL- 2: Observed to greatly increase the magnitude and durability of antigen-specific Treg expansion when compared to either ImmTOR or IL-2 alone ImmTOR-IL Proof of concept human data in which we observed
ImmTOR alone and IL-2 alone lowers the translational risk and provides further confidence in the clinical utility of this potentially synergistic approach Potential to enable lower and fewer doses of ImmTOR, with applications across biologic
therapies and IL-2 mutein ImmTOR ImmTOR-IL autoimmune disease indications Induce Treg Expand existing Tregs Antigen-specific Expansion of all Induction of target Induction and pre-existing Tregs antigen-specific Tregs expansion of antigen- specific
Tregs Selecta Biosciences Corporate Presentation - April 2022 8
Tolerogenic Gene Biologic Therapies Therapies Therapies ImmTOR could
provide targeted immune ImmTOR potentially enables redosing of ImmTOR is designed to address the tolerance to auto antigens transformative gene therapies immunogenicity of biologics 80% of rare disease has a known Over 160,000 patients between IgAN
and Autoimmune disease affects more than 5 monogenic cause and most gene therapy 6 chronic refractory gout in the US 24M people in the US alone trials use AAV vectors 1,2,3,4 alone 1. https://www.orpha.net/data/patho/Pro/en/Berger-FRenPro10331.pdf
4. American journal of therapeutics, 2012-11, Vol.19 (6), p.e157-e166 2. Arthritis & Rheumatology Vol. 71, No. 6, June 2019 pp 991-999 5. https://ncats.nih.gov/trnd/projects/gene-therapy 3. ARTHRITIS & RHEUMATISM Vol. 63, No. 10, October
2011, pp 3136-3141 6. https://www.niehs.nih.gov/health/topics/conditions/autoimmune/index.cfm Selecta Biosciences Corporate Presentation - April 2022 9
Recent and Expected Commercial Rights Indication Antigen Preclinical
Phase 1 Phase 2 Phase 3 Upcoming Milestones TOLEROGENIC THERAPIES Primary biliary cholangitis (PBC) PDC-E2 Undisclosed GENE THERAPIES AAV (serotype undisclosed) SEL-302 Phase 1 start 2H 2022 Methylmalonic acidemia (MMA) AAV-hOTC Ornithine
Transcarbamylase (OTC) Deficiency SEL-313 Paused IgG protease IdeXork (Xork) Gene therapy Undisclosed Undisclosed BIOLOGIC THERAPIES IgA protease IgA nephropathy (IgAN) Candidate Selection 2022 Selecta Biosciences Corporate Presentation -
Collaboration Year 2019 2020 2020 2021 2021 2021 2021 2022 ImmTOR Gene
Therapy Biologic Gene Therapy Autoimmune Gene Therapy Gene Therapy Biologic Gene Therapy Approach Strategic licensing Strategic licensing Strategic licensing Strategic Research Option Collaboration to Strategic licensing License agreement to
agreement to agreement to Collaboration and and License engineer agreement to Agreement develop targeted, develop targeted, develop next- Agreement License Agreement proprietary IL-2 enable the dosing (Global, ex. China) next-generation
next-generation generation AAV Agreement (Global) protein agonists of gene therapies gene therapies enzyme therapies Capsids Autoimmune and Pompe/ Chronic refractory DMD and certain deleterious Lysosomal AAV mediated Undisclosed Undisclosed
Indications Undisclosed gout LGMD subtypes immune storage disorders gene therapies indications Recent/Expected Upcoming Commercial Rights Indication Antigen Preclinical Phase 1 Phase 2 Phase 3 Milestones Pegadricase SEL-212 Chronic Refractory Gout
DISSOLVE I topline data Q4 2022 Undisclosed Pompe disease Undisclosed Duchenne muscular dystrophy (DMD) Undisclosed Limb-girdle muscular dystrophy (LGMD) UndUnd isclosed isclosed Two indications for lysosomal storage disorders Selecta Biosciences
Corporate Presentation - April 2022 11
The current standard of care for autoimmune diseases is broad
immunosuppression, which is associated with side effects and leaves patients vulnerable to serious infection and malignancies THE There is a significant need for antigen-specific therapies that can induce immune tolerance to pathogenic autoantigens
without Challenges the need for chronic and systemic immune suppression. Our approach to autoimmune disease is designed to restore natural self-tolerance by administering ImmTOR with nanoparticle- encapsulated self-antigens thus avoiding the need
for chronic and systemic immune suppression THE By developing a proprietary Treg-selective IL-2 to combine with ImmTOR and autoantigens we are advancing our precision Solution immune tolerance platform with the aim of expanding antigen-specific
Tregs and enhancing durability of tolerance There are roughly 80 autoimmune conditions that affect as much as 4.5% of the world's population*. 24M+ individuals in the US alone are affected by autoimmune diseases** THE Opportunity * Autoimmune
Disease, by the Numbers in Scientific American 325, 3, 31-33 (September 2021), doi:10.1038/scientificamerican0921-31 **https://www.niehs.nih.gov/health/topics/conditions/autoimmune/index.cfm Selecta Biosciences Corporate Presentation - April
Observed synergistic activity in increasing the percentage and
durability of Treg expansion in the spleen Opportunity to restore tolerance in a wide range of autoimmune diseases Potential to create a "best in class" IL-2 therapy by combining it with ImmTOR Splenic regulatory T cells
Day 4 Day 7 Day 14 60 60 60 50 50 50 ImmTOR 40 40 40 IL-2 mutein ImmTOR + IL-2 mutein 30 30 30 Untreated control 20 20 20 10 10 10 0 0 0 C57BL/6 mice (n=7/group) were untreated or were treated with ImmTOR alone, IL-2 mutein alone, or a combination
of ImmTOR + IL-2 mutein. Expansion of CD4+, CD25+, FoxP3+ T regulatory cells in the spleen was assessed 4, 7 and 14 days after treatment. Selecta Biosciences Corporate Presentation - April 2022 14 + + + + CD4 CD25 FoxP3 (%, of CD4 ) + + + +
CD4 CD25 FoxP3 (%, of CD4 ) + + + + CD4 CD25 FoxP3 (%, of CD4 )
Antigen-specific Treg Total splenic Tregs 70 With superior expansion
and 70 durability of total Tregs, Selecta 60 60 potentially has a best in class IL-2 therapy. 50 50 40 40 However, with an approximately 3- fold increase in antigen-specific 30 30 Tregs, this data shows the 20 20 opportunity to enable a "first
in class" therapy for autoimmune 10 10 disorders 0 0 ImmTOR + + + + + + IL-2 mutein + + + + + + Ovalbumin + + + + + + + + *study conducted in wildtype mice after adoptive transfer of ovalbumin specific transgenic T-cells Selecta Biosciences
Corporate Presentation - April 2022 15 + + + + + CD4 CD25 FoxP3 (%, of CD4 CD45.1 ) + + + + + CD4 CD25 FoxP3 (%, of CD4 CD45.2 )
Day 0 2.7E12 vg/kg AAV8-SEAP +/- ImmTOR +/- IL-2 mutein Day 56 5.0E12
vg/kg AAV8-SEAP +/- ImmTOR +/- IL-2 mutein No immunotherapy 50 g ImmTOR 100 g ImmTOR 200 g ImmTOR nd nd nd 2 dose 2 dose 2 dose 2.0 2 . 0 2 . 0 2 . 0 1.5 1 . 5 1 . 5 1 . 5 1.0 1 . 0 1 . 0 1 . 0 nd 2 dose 0.5 0 . 5 0 . 5 0 . 5 0.0 0
. 0 0 . 0 0 . 0 12 19 33 47 61 75 91 104 117 1 2 1 9 3 3 4 7 6 1 7 5 9 1 1 0 4 1 1 7 1 2 1 9 3 3 4 7 6 1 7 5 9 1 1 0 4 1 1 7 1 2 1 9 3 3 4 7 6 1 7 5 9 1 1 0 4 1 1 7 50 g ImmTOR 100 g ImmTOR 200 g ImmTOR 9 g IL-2 mutein + 9
g IL-2 mutein + 9 g IL-2 mutein + 9 g IL-2 mutein nd 2.0 2.0 2.0 2.0 2 dose 1.5 1.5 1.5 1.5 1.0 1.0 1.0 1.0 nd nd nd 2 dose 2 dose 2 dose 0.5 0.5 0.5 0.5 0.0 0.0 0.0 0.0 12 19 33 47 61 75 91 104 117 12 19 33 47 61 75 91 104 117 12
19 33 47 61 75 91 104 117 12 19 33 47 61 75 91 104 117 Days post-infusion Days post-infusion Days post-infusion Days post-infusion *study conducted in wildtype mice Selecta Biosciences Corporate Presentation - April 2022 16 Anti-AAV IgG (OD )
Anti-AAV IgG (OD ) 450-570 450-570
Autoimmune disorder where the body mistakenly attacks tissue in
the liver, leading to inflammation, damage and scarring of the small bile ducts 1 More common in women, PBC is one of the most common autoimmune diseases affecting nearly 1:1000 women over the age of 40 Patients with PBC are
desperately in need of a highly-targeted, liver-directed approach to treating the root cause of the disorder We believe ImmTOR is ideally suited to address PBC Hepatoprotective in Con A Hepatic regulatory Tolerogenic liver sinusoidal liver
inflammation model endothelial cells T cells * 15 700 15 * **** 500 400 10 10 300 200 5 5 100 0 Con A Con A 0 0 + ImmTOR Rapamycin Untreated ImmTOR ImmTOR Untreated * P=0.05, ****P=0.0001 PBC is a T-cell mediated disease driven by a well-defined
antigen, ImmTOR biodistributes to the liver and induces a tolerogenic environment, ImmTOR shows hepatoprotective properties in liver injury models 1. https://rarediseases.org/rare-diseases/primary-biliary-cholangitis/ Selecta Biosciences Corporate
Presentation - April 2022 17 + low low PD-L1 CD80 CD86 (%) + Hi + CD4 CD25 PD-1 (%) ALT (U/mL)
The formation of neutralizing antibodies (NAbs) after AAV vector
administration prevents redosing due to the potentially dangerous immune response that would follow a second or third gene therapy administration. Adverse THE patient events related to high vector doses is inextricably linked to immunogenicity.*
Challenges Pre-existing immunity to AAV vectors excludes significant numbers of patients who would potentially benefit from treatment by AAV gene therapies. ImmTOR - Human proof of concept shows the possibility for ImmTOR to inhibit the
formation of neutralizing antibodies to AAV vectors. Extensive preclinical work shows the potential for improved and more durable transgene THE expression upon the first dose and potential hepatoprotective benefits of ImmTOR. Solution Xork -
Cleaves human IgG specifically and efficiently, but shows low cross reactivity to human sera potentially opening up a treatment window for those with pre-existing immunity to AAV vectors. Xork could potentially make patients with pre-existing
immunity to AAV vectors eligible for treatment. THE ImmTOR, by inhibiting the formation of neutralizing antibodies, could make redosing of gene therapies possible. Opportunity Functional benefit could be maintained or restored with additional doses.
Safer and more efficacious dosing regimens could be implemented. Selecta has partnered its technologies with leading gene therapy companies. *Flotte TR. 2020. Hum Gene Ther 31:398-399. Selecta Biosciences Corporate Presentation - April 2022 19
Selecta Biosciences Corporate Presentation - April 2022
ImmTOR Xork Potential to increase the number of patients
eligible for gene therapy by mitigating pre-existing anti-AAV antibodies + = Potential to enable re-dosing by mitigating the de novo formation of anti-AAV antibodies Pre-existing anti-IgG protease Cleavage of human IgG Antibodies in human
serum 1.75 Intact IgG 1.50 Xork is an IgG protease derived from a non- 1.25 human pathogen 1.00 Cleaved F(ab') 2 Xork cleaves human IgG specifically and efficiently, 0.75 but shows low cross reactivity to human sera 0.50 Human
IgG compared to IdeS 0.25 + + + IdeS + 0.00 Xork Xork IdeS + *IdeS is an IgG protease derived from the common human pathogen Streptococcus pyogenes Selecta Biosciences Corporate Presentation - April 2022 21 Anti-IgG protease (OD )
Day 0 Day 70 5e11 vg/kg AAV-SEAP 5e11 vg/kg AAV-SEAP 5e11 vg/kg
AAAV-SEAP + ImmTOR 5e11 vg/kg AAV-SEAP + ImmTOR ImmTOR has been 25e11 vg/kg AAV-SEAP 25e11 vg/kg AAV-SEAP observed to enhance transgene expression after Two doses of 5e11 vg/kg with first and second doses of ImmTOR provides comparable AAV 40000
expression as single dose of 25e11 vg/kg AAV dose 30000 11 (x 10 vg/kg) Repeat dosing enabled by 5 5 25 ImmTOR is dose sparing 20000 10000 0 19 61 77 151 Time after initial AAV treatment (d) *study conducted in wildtype mice Ilyinskii et al.,
Science Advances, 2021 Selecta Biosciences Corporate Presentation - April 2022 22 SEAP (RLU) 2nd dose d70
Total healthy volunteers enrolled: 23 (14 males and 9 females)
All subjects with anti-AAV8 NAb titers <1:5 at baseline Randomized, placebo controlled and double-blind study Drug Infusions Study Day 30 45 60 75 90 0 15 Placebo* + Empty Capsid (2E12 vp**/kg) n=3 Placebo + Empty Capsid (2E12