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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Ultragenyx partners with GeneTx for antisense technology

Ultragenyx Pharmaceutical has entered into collaboration with GeneTx Biotherapeutics to develop GTX-102, GeneTx’s antisense oligonucleotide for the treatment of Angelman syndrome.

Ultragenyx Pharmaceutical is a biopharmaceutical company developing novel products for serious rare and ultra-rare diseases. Under the terms of the agreement, Ultragenyx will make an upfront payment of $20 million for an exclusive option to acquire GeneTx. This option may be exercised any time prior to 30 days following FDA acceptance of the IND for GTX-102.

Ultragenyx has the option to extend the option period by paying an additional $25 million incase if it wants to see the early Phase 1/2 data before proceeding. Ultragenyx may exercise this extended option any time until the earlier of 30 months from the first dosing of a patient in a planned Phase 1/2 study or 90 days after results are available from that study.

Angelman syndrome is a serious and rare neurogenetic disorder that affects approximately 1 in 15,000 people worldwide. It is caused by loss-of-function of the maternally inherited allele of the UBE3A gene, encoding ubiquitin protein ligase E3A.

Studies suggest that ubiquitin protein ligase E3A plays a critical role in the normal development and function of the nervous system. While both copies of the gene are turned on in most of the body’s tissues, in certain areas of the brain, however, only the maternal copy is active (due to a phenomenon known as genomic imprinting).

Silencing of the paternal UBE3A allele is regulated by the UBE3A antisense transcript (UBE3A-AS), the target of GTX-102. In almost all cases of Angelman syndrome the maternal UBE3A allele is either missing or mutated, resulting in limited to no protein expression.

Antisense oligonucleotide technology holds promise in addressing Angelman syndrome. GTX-102 is designed to inhibit the expression of UBE3A-AS. Preclinical studies have shown that GTX-102 reduces the levels of UBE3A-AS and reactivates expression of the paternal UBE3A allele in neurons of the central nervous system.

Reactivating paternal UBE3A expression by GTX-102 in animal models of Angelman syndrome was shown to improve some of the neurological symptoms associated with the condition.

GTX-102 is currently in late preclinical development with an investigational new drug (IND) application expected to be filed with the FDA in the first half of 2020. If IND is successful, GeneTx will initiate the trial in patients.

GeneTx Biotherapeutic is a startup biotechnology company that was launched by the Foundation for Angelman Syndrome Therapeutics (FAST), a patient advocacy organization and the largest non-governmental funder of Angelman syndrome research. The company licensed the rights to antisense technology intellectual property from The Texas A&M University System in December 2017.

During the exclusive option period, GeneTx will provide regulatory and scientific expertise and fund all development activities, while Ultragenyx will provide staff support, including strategic guidance and clinical expertise.

Both companies will together submit the IND and manage the Phase 1/2 study, which is expected to begin next year. If Ultragenyx acquires GeneTx, Ultragenyx will then be responsible for all development and commercialization activities. If Ultragenyx decides to exercise its option, it will purchase GeneTx for an initial purchase price and contingent milestones and royalties.

Source: Ultragenyx snags option on antisense startup GeneTx; News

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