Portfolio | Gene Therapy

Striving to make gene therapies safer and more durable
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ImmTOR™ & Gene Therapy

The potential of ImmTORin gene therapy

ImmTOR has significant potential to mitigate unwanted immune responses and induce AAV-specific tolerance to enable redosing of gene therapies. ImmTOR has the potential to administer multiple low doses to achieve therapeutic benefit without risk of overdosing, the ability to treat patients typically excluded from these treatments and is a novel approach to treating systemic diseases resulting from genetic disorders.

The potential of ImmTORin gene therapy

  • Traditional Gene Therapy

    Gene therapy has traditionally been conceptualized as a one-time, curative treatment option; however, research shows that there may be a need for subsequent doses years after initial treatment. In order to introduce a functional gene in patients, a vector is used to deliver the gene, most often derived from an adeno-associated virus (AAV). 

  • The Challenge

    While they do enable the efficacy of this powerful therapeutic approach, AAV vectors also present a key challenge in gene therapy. Neutralizing antibodies (NAbs) are formed in response to AAV vector administration, so redosing is not possible due to the potentially dangerous immune response that would follow a second or third administration of the gene therapy. 

  • ImmTOR’s Potential

    AAV vectors are non-replicating, so transgene expression is expected to wane over time, especially in children, most likely necessitating re-dosing. As many gene therapies in development are being investigated for the treatment of rare, often lethal, pediatric disorders, the inability to re-dose these therapies is of particular concern.

    ImmTOR has the potential to induce AAV-specific immune tolerance, reducing the severity of the body’s immune response to AAV gene therapies and enabling repeat administrations

    Redosing is important when determining the optimal dose

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    Establishing the optimal dose for a patient can sometimes require repeat administrations

    Redosing can help rescue therapeutic benefits over time

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    Genetic metabolic diseases often manifest early in childhood. However, AAV vectors are nonreplicating, so transgene expression is expected to wante over time as pediatric patients grow

Preclinical data

ImmTOR™ induces specific tolerance

Preclinical data show that ImmTORTM induces AAV-specific immune tolerance when co-administered with AAV8. 

Mice treated with ImmTOR co-administered with AAV8 do not develop anti-AAV8-specific antibodies. In contrast, mice treated with empty nanoparticle co-administered with AAV8 develop a significant immune response when challenged with a redose of AAV8.

When challenged with a different AAV vector (AAV5), mice treated with AAV8 + ImmTOR do develop AAV-specific neutralizing antibodies in an immune response, demonstrating that ImmTOR induces antigen-specific immune tolerance rather than broad immunosuppression.

Pipeline

ImmTOR™ + gene therapy program

Selecta’s first ImmTOR + gene therapy program for methylmalonic acidemia (MMA), being developed in partnership with AskBio, is expected to enter clinical trials in mid 2021. Selecta’s wholly owned gene therapy program for the treatment of ornithine transcarbamylase (OTC) deficiency is also expected to enter the clinic in 2022.

Additional programs in Pompe disease (also in partnership with AskBio), Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy (both in partnership with Selecta) are in preclinical development. 

Indication

Antigen

Stage of Development

Preclinical
Phase 1
Phase 2
Phase 3

Upcoming Milestone

Commercial Rights

Amplifying the efficacy of biologic therapies

Gene Therapies

Methylmalonic acidemia (MMA)

0

AAV8

0

27

MMA-101

Phase 1 trial commencing H1 2021; preliminary data expected H2 2021

0


0

Ornithine Transcarbamylase
deficiency
(OTCD)

0

AAV-hOTC

0

27

SEL-313

Enter clinic in 2022

0

0

Pompe disease

0

Undisclosed

0

20

0

0

Duchenne muscular dystrophy (DMD)

0

Undisclosed

0

20

0

0

Limb-girdle muscular dystrophy (LGMD)

0

Undisclosed

0

20

0

0

MMA-101

Selecta’s first ImmTORTM + gene therapy candidate MMA-101 for methylmalonic acidemia (MMA), being developed in partnership with AskBio, is expected to enter clinical trials in mid 2021.

MMA is a rare metabolic disease that may lead to metabolic acidosis and hyperammonemia and is associated with long-term complications including feeding problems, developmental delay, intellectual disability, and chronic kidney disease. 

SEL-313

Selecta’s wholly owned gene therapy program for the treatment of ornithine transcarbamylase (OTC) deficiency is expected to enter the clinic in 2022.

OTC deficiency is a genetic disorder urea cycle that causes ammonia to accumulate in the blood. The most severe form of the disorder presents within the first few days of life. Severe symptoms include inability to control body temperature and breathing rate, seizures, coma, developmental delays, and intellectual disability. Less severe forms of the disorder are characterized by delirium, erratic behavior, aversion to high protein foods, vomiting and seizures.

Partner with us

Learn more about partnership opportunities

Selecta has partnered with leading gene therapy companies, including AskBio and Sarepta Therapeutics to evaluate the potential of ImmTOR in combination with AAV gene therapies. 

Publications

Validated and peer-reviewed research

Our research is validated by a long track record of peer-reviewed publications in high-impact journals in collaboration with our industry and scientific partners.