Rare Daily Staff

Ultragenyx Pharmaceutical has entered into a partnership with
GeneTx Biotherapeutics to develop its GTX-102, an antisense oligonucleotide for the treatment of Angelman syndrome, a debilitating, rare neurogenetic disorder.

GTX-102 is currently in late preclinical development with an application to begin human clinical trials expected to be filed with the U.S. Food and Drug Administration in the first half of 2020.

Individuals with Angelman syndrome have developmental delay, balance issues, motor impairment, and debilitating seizures. Some individuals with Angelman syndrome are unable to walk and most do not speak. Anxiety and disturbed sleep can be serious challenges in individuals with Angelman syndrome. While individuals with Angelman syndrome have a normal lifespan, they require continuous care and are unable to live independently.

Angelman syndrome is not a degenerative disorder, but the loss of the UBE3A protein expression in neurons results in abnormal communications between neurons. The condition is often misdiagnosed as autism or cerebral palsy. There are no currently approved therapies for Angelman syndrome; however, several symptoms of this disorder can be reversed in adult animal models of Angelman syndrome suggesting that improvement of symptoms can potentially be achieved at any age.

GTX-102 is an investigational antisense oligonucleotide designed to target and inhibit expression UBE3A-AS. Studies show that GTX-102 reduces the levels of UBE3A-AS and reactivates expression of the paternal UBE3A allele in neurons of the CNS, and that reactivation of paternal UBE3A expression in animal models of Angelman syndrome improves some of the neurological symptoms associated with the condition.

The Foundation for Angelman Syndrome (FAST) formed GeneTx, which has supported preclinical research through donations the FAST community. “It is entirely fitting that GeneTx would partner with a company that not only has proven expertise in the development and commercialization of rare disease therapeutics, but truly puts the patient first in each and every step of the treatment process,” said Paula Evans, CEO of GeneTx.

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 may extend the option period by paying an option extension payment of $25 million. 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 (subject to extensions) or 90 days after results are available from that study.

During the exclusive option period, GeneTx will provide regulatory and scientific expertise as well as fund all development activities, while Ultragenyx will provide staff support, including strategic guidance and clinical expertise. The parties will collaborate on the submission of the application to begin human clinical studies and management of the phase 1/2 study in patients with Angelman syndrome. 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.


Photo: Paula Evans, CEO of GeneTx

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