- Highlights the ability to prevent formation of vector-induced neutralizing antibodies (Nabs) and enable re-administration of AAV vectors in combination with Selecta’s ImmTOR (SVP-Rapamycin) platform
- Data show the addition of ImmTOR nanoparticles to AAV vectors provides a first dose benefit in enhancing liver-directed transgene expression
- Supports continued advancement of development pipeline in two metabolic diseases; MMA and OTC deficiency
WATERTOWN, Mass., Oct. 23, 2019 (GLOBE NEWSWIRE) -- Selecta Biosciences, Inc. (NASDAQ: SELB), a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its immune tolerance platform technology, ImmTOR™, today presented new preclinical data from its gene therapy program at the European Society of Gene and Cell Therapy (ESGCT) Annual Congress from October 22-25, 2019 in Barcelona, Spain.
"These data highlight the ability of our tolerogenic ImmTOR nanoparticles to address a key challenge in gene therapy, which is vector re-dosing limitations due to adaptive immune responses against the AAV capsid. Our data support the continued advancement of our development pipeline for MMA and OTC deficiency. We look forward to working with our partner, AskBio, to advance the MMA program into the clinic,” said Kei Kishimoto, Ph.D., Chief Scientific Officer of Selecta Biosciences. “In addition to enabling re-dosing, our data also show that ImmTOR enhances transgene expression after the first dose of an AAV vector. The cumulative benefit of enhancing both first dose transgene expression and enabling repeat dosing, can provide up to a four-fold increase in transgene expression compared to gene therapy with AAV vector alone.”
Oral Presentation Title: ImmTOR tolerogenic nanoparticles enhance transgene expression after both initial and repeat dosing in a mouse model of methylmalonic acidemia treated with AAVAnc80-Mut vector
Authors: Ilyinski
Abstract #: OR35
Presentation date: October 25, Session 4c
- Mitigation of the detrimental impact of Nabs on gene therapy: Repeated co-administration of Anc80 and ImmTOR™ was well-tolerated and led to inhibition of IgG antibodies to Anc80 in a mouse model of methylmalonic acidemia (MMA).
- Benefit in enhancing transgene expression at the initial dose: A more profound decrease of serum methylmalonic acid after initial and repeat injections was observed in mice treated with the combination of ImmTOR™ and Anc80-MUT, which correlated with higher viral genome copy number per liver cell (vg/cell) as well as higher hepatic MUT mRNA expression levels. These effects were dose-dependent, with higher doses of ImmTOR™ providing for higher vg/cell levels and lower plasma methylmalonic acid levels while also enabling therapy of juvenile mice with maternally-transferred neutralizing antibodies to Anc80.
Poster Title: Tolerogenic ImmTOR™ nanoparticles enhance vector transduction, mRNA synthesis and transgene expression after initial and repeated administrations of AAV-based gene therapy vectors
Authors: Ilyinski
Abstract #: P338
Presentation date: October 24, Poster Session ll
- The multi-pronged mechanism of action of ImmTOR™ makes it an attractive candidate to enhance systemic gene therapeutic applications: ImmTOR™ affects multiple aspects of AAV biology. In addition to mitigating the formation of anti-AAV antibodies, ImmTOR enhanced first-dose liver-directed transgene expression The data show increased vector copy numbers and transgene mRNA expression.
- Demonstrated increase in transgene expression compared to gene therapy with AAV vector alone: The rapid and enhanced transgene expression can allow for faster onset of therapeutic effects achieved at lower AAV doses and coupled with the inhibition of antibodies against AAV enable vector re-dosing.
Poster Title: The combination of ImmTOR with AAVAnc80 is therapeutically effective, safe, and repeatable in mice with methylmalonic acidemia while also being compatible with the low seroprevalence of Anc80 Nabs in the patient population.
Authors: Li
Abstract #: P453
Presentation date: October 23, Poster Session l
- ImmTOR is efficacious and well-tolerated in MMA mice, and allows therapeutic redosing of AAV by blocking the formation of anti-capsid IgG: ImmTOR was well tolerated in a murine model of MMA (Mut-/-;TgINS-MCK-Mut) that recapitulates a clinically severe disease phenotype. The first treatment of ImmTOR prevented the formation of anti-Anc80 IgG and resulted in a pronounced reduction in serum MMA levels. Pre-existing Nabs against AAVAnc80 was evaluated in plasma from MMA patients. Only 4/25 (16 percent) of non-transplanted pediatric MMA patients were seropositive for anti-AAVAnc80 antibodies. Collectively, the low Anc80 Nab seroprevalence in this patient population, coupled with ImmTOR-induced tolerance, suggests the ability to repeat treatments for MMA patients with a combination of ImmTOR and Anc80-MUT.
Poster Title: A novel AAV-based therapy in combination with tolerogenic ImmTOR nanoparticles for a sustained treatment of Ornithine Transcarbamylase
Authors: De Sabbata
Abstract #: P451
Presentation date: October 23, Session l
- Compelling opportunity to develop a therapy that has the ability to treat pediatric OTC patients with the possibility for re-dosing to maintain therapeutic levels and prevent liver damage associated with cellular immune reaction to the therapeutic virus: A novel therapeutic ssAAV8 vector was generated containing a Codon-Optimized (CO) human OTC transgene under the transcriptional control of a liver specific promoter, which is particularly efficient in correcting the OTC-spfash phenotype. A dose finding experiments was performed in the OTC-spfash mouse model, identifying the dose of 5e11 vg/kg as the therapeutic dose, resulting in restoration of physiological levels of urinary orotic acid and serum ammonia. ssAAV8-OTC vector co-administered with ImmTOR particles improved efficacy, mitigated the humoral immune response to AAV-hOTC and enabled repeated dosing of gene therapy treatments.
About Selecta Biosciences, Inc.
Selecta Biosciences, Inc. is a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its immune tolerance technology (ImmTOR) platform. Selecta plans to combine ImmTOR with a range of biologic therapies for rare and serious diseases that require new treatment options due to high immunogenicity. The company’s current proprietary pipeline includes ImmTOR-powered therapeutic enzyme and gene therapy product candidates. SEL-212, the company’s lead product candidate, is being developed to treat chronic refractory gout patients and resolve their debilitating symptoms, including flares and gouty arthritis. Selecta’s proprietary gene therapy product candidates are in preclinical development for certain rare inborn errors of metabolism and incorporate ImmTOR with the goal of addressing barriers to repeat administration. Selecta is based in Watertown, Massachusetts. For more information, please visit www.selectabio.com.
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the potential of ImmTOR to enable re-dosing of AAV gene therapy, the development of the company’s gene therapy programs, ImmTOR’s effect on transgene expression, ImmTOR’s effect on the formation of vector-induced neutralizing antibodies, the potential of the ImmTOR technology platform generally, the advancement of the company’s development pipeline, and the company’s ability to grow, develop and maintain its strategic partnerships. All such forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Such risks and uncertainties include but are not limited to those set forth in the “Risk Factors” section of Selecta’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission, or SEC, for the quarter ended June 30, 2019, and in other filings that Selecta makes with the SEC. In addition, any forward-looking statements included in this press release represent Selecta’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. Selecta specifically disclaims any obligation to update any forward-looking statements included in this press release.
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