Ultragenyx and GeneTx Enter Collaboration to Develop GTX-102, an Antisense Oligonucleotide Therapy for Angelman Syndrome

On August 16, 2019, VCBeat (WeChat ID: vcbeat) learned from foreign media reports that biopharmaceutical company Ultragenyx Pharmaceutical and GeneTx jointly announced a collaboration to develop GTX-102, an antisense oligonucleotide (ASO) therapy for the treatment of Angelman syndrome.

Under the terms of the agreement, Ultragenyx will pay GeneTx $20 million to secure an exclusive option to acquire GeneTx. The transaction may be exercised at any time within 30 days after the U.S. Food and Drug Administration (FDA) accepts the Investigational New Drug (IND) application for GTX-102. Ultragenyx may extend the option period by making a payment of $25 million. The extended option may be exercised at any time within 30 months after the first dosing in the Phase I/II clinical trial of GTX-102, or within 90 days after data from such trial become available.

During this period, GeneTx will provide regulatory and scientific expertise and fund all development activities. Ultragenyx will provide personnel support as well as strategic advisory and clinical expertise. The two parties will collaborate to submit an Investigational New Drug (IND) application and jointly manage the Phase I/II clinical study in patients with Angelman syndrome. If Ultragenyx elects to acquire GeneTx, it will assume responsibility for all development and commercialization activities. It will also acquire GeneTx at an initial purchase price, which includes various milestone payments and royalties on any commercialized products.

Currently, GTX-102 is in the late stages of preclinical development, with an Investigational New Drug (IND) application to the U.S. FDA expected in the first half of 2020.

Angelman Syndrome (Angelman syndrome), also known as Angel Syndrome, is a severe developmental disorder that manifests in childhood. The incidence of Angelman syndrome is approximately 1 in 15,000. Patients exhibit severe symptoms such as epilepsy, developmental delay, speech impairment, and motor dysfunction; however, they often display a smiling demeanor with an angelic appearance, hence the name "Angel Syndrome." In 1965, British pediatrician Harry Angelman first identified and systematically described this condition, which was subsequently named after him.

Angelman syndrome is caused by a genetic defect, specifically a deletion in the q11-q13 region of chromosome 15. This condition results from a maternal monogenic inheritance defect. It occurs due to a defect in the imprinted gene region of the maternal chromosome 15q, or due to uniparental disomy where both copies of chromosome 15 carrying this defect are inherited from the father. Conversely, if the genetic defect is of paternal origin, or if both copies with the defect are inherited from the mother, it results in Prader-Willi syndrome. Currently, there are no approved therapies for the treatment of Angelman syndrome.

“Angelman syndrome is a devastating neurological disorder with no available treatment, representing a significant unmet medical need,” said Dr. Emil D. Kakkis, Chief Executive Officer and President of Ultragenyx. “GTX-102 is a novel and promising potential therapy that specifically targets the underlying disease mechanism in these patients. We are delighted that GeneTx has chosen to partner with us.”

GTX-102 is an antisense oligonucleotide designed to target and inhibit UBE3A-AS expression, aiming to address the deficits caused by the underlying genetic cause of the disease. Studies have shown that GTX-102 reduces UBE3A-AS levels and reactivates paternal UBE3A allele expression in central nervous system neurons. Expression of paternal UBE3A in Angelman syndrome animal models improves certain neurological symptoms associated with the disease. In March 2018, the U.S. FDA granted orphan drug designation to this ASO targeting UBE3A-AS.

GeneTx, founded in 2017 and headquartered in Illinois, USA, is a biopharmaceutical company dedicated to the research and development of therapies for Angelman syndrome. GeneTx was initiated by the Foundation for Angelman Syndrome Therapeutics (FAST), the largest non-governmental funder of Angelman syndrome research. In December 2017, GeneTx licensed antisense technology intellectual property from Texas A&M University.

Ultragenyx Pharmaceutical, founded in 2010 and headquartered in California, USA, is a biopharmaceutical company. The company is dedicated to providing patients with novel therapies for severe rare genetic diseases. Ultragenyx has established a diverse portfolio of approved therapies and product candidates aimed at addressing conditions with high unmet medical needs, which often lack effective treatments. The company is led by a management team with extensive experience in the development and commercialization of therapies for rare diseases.

(Compiled by Cheng Tao)