RARE Daily

Ultragenyx to Acquire GeneTx

July 19, 2022

Ultragenyx Pharmaceutical said it has exercised its option to acquire GeneTx and for an upfront payment of $75 million plus future milestone and royalty payments.

The exercise of the option comes as the two companies reported encouraging interim data of their experimental gene therapy for Angelman syndrome GTX-102.

Angelman syndrome is a rare, neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. The maternal-specific inheritance pattern of Angelman syndrome is due to genomic imprinting of UBE3A in neurons of the central nervous system, a naturally occurring phenomenon in which the maternal UBE3A allele is expressed and the paternal UBE3A is not. Silencing of the paternal UBE3A allele is regulated by the UBE3A antisense transcript (UBE3A-AS), the intended 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. This condition is typically not inherited but instead occurs spontaneously.

Individuals with Angelman syndrome have developmental delay, communications issues, 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. 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 delivered via intrathecal administration and designed to target and inhibit expression of UBE3A-AS. Nonclinical studies show that GTX-102 reduces the levels of UBE3A-AS and reactivates expression of the paternal UBE3A allele in neurons of the CNS. Reactivation of paternal UBE3A expression in animal models of Angelman syndrome has been associated with improvements in some of the neurological symptoms associated with the condition. GTX-102 has been granted Orphan Drug, Rare Pediatric Disease, and Fast Track designations from the U.S. Food and Drug Administration.

“We are seeing encouraging early clinical activity across multiple domains and multiple measurements without any evidence of drug-related safety issues. The therapeutic effect should be further enhanced by starting at higher monthly loading doses that have already been shown to be tolerated,” said Emil Kakkis, CEO and president of Ultragenyx. “These data combined with the excellent science of Dr. Scott Dindot, the inventor of GTX-102, have given us the confidence to exercise our option to acquire GeneTx at an earlier timepoint so that we can take the lead on advancing GTX-102 into late-stage development for Angelman syndrome.”

Interim results on 9 patients from the U.K./Canada arm and 2 patients from the U.S. arm of the phase 1/2 study demonstrate a meaningful improvement in clinical disease and an acceptable safety profile. The company said these interim data supported a protocol amendment to the phase 1/2 study that was approved by the U.K. and Canadian health authorities in May 2022 to initiate additional, new cohorts of patients at higher monthly loading doses. The study has begun to enroll under the amended protocol and has dosed the first patient in these new cohorts.

Author: Rare Daily Staff

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