Taysha Gene Therapies has acquired exclusive global rights to TSHA-120, an intrathecally dosed AAV9 gene therapy designed to treat giant axonal neuropathy.
Taysha Gene Therapies has acquired exclusive global rights to TSHA-120, an intrathecally dosed AAV9 gene therapy designed to treat giant axonal neuropathy.
A leading patient advocacy group will receive an upfront $5.5 million payment from Taysha in exchange for Taysha’s exclusive worldwide rights to TSHA-120. The patient advocacy group will also be eligible to receive additional clinical, regulatory and commercial milestones ringing in at up to $19.3 million. Additionally, the terms of the agreement state the group will also be eligible to receive low, single-digit royalties on net sales following the product’s commercialization.
Giant axonal neuropathy is a rare genetic disorder is caused by loss-of-function mutations in the gene coding for gigaxonin. Approximately 2,400 people in the United States and Europe have this disease. The disorder affects the central and peripheral nervous systems, and symptoms related to these effects typically show before the age of five. Common symptoms and features of the disease include contractures, progressive scoliosis, spinal cord atrophy as well as white brain matter abnormalities.
Many patients with the disorder have a poor prognosis, as there are currently no approved therapies for giant axonal neuropathy. The disorder usually leads to death during patients’ late teens or early twenties.
The U.S. Food and Drug Administration (FDA) previously granted rare pediatric disease and orphan drug designations for TSHA-120 for the treatment of giant axonal neuropathy. In a statement on the acquisition, Taysha said the National Institutes of Health (NIH), in collaboration with a patient advocacy group, is currently conducting a clinical trial investigating the use of TSHA-120 in giant axonal neuropathy.
TSHA-120 was developed in a laboratory led by Taysha’s Chief Scientific Advisor Dr. Steven Gray.
“Dr. Steven Gray’s work on the GAN program was the catalyst for all the other translational research initiatives in his lab and we are very pleased to continue this important and meaningful work that has had a significant impact across the entire gene therapy landscape,” said Taysha’s Chief Executive Officer, President and Founder R.A. Session II.
The NIH’s ongoing open-label, dose-escalation trial of TSHA-120 is primarily evaluating the therapy’s safety. A secondary endpoint includes efficacy, as assessed by different pathologic, physiologic, functional as well as clinical markers. The Motor Function Measure 32 (MFM32) score is of particular importance in regard to the trial’s efficacy assessment, as the MFM32 score helps researchers evaluate the severity and progression of patients’ motor function abilities.
So far, a total of 14 patients have received one of the four TSHA-120 dose levels. Treatment with the gene therapy candidate was previously shown to feature a dose-response relationship with disease progression arrest at 1.8x1014 total vector genomes, the second-highest dose level, at one-year follow up. This finding translated into a significant eight-point improvement in the MFM32, which was considered clinically meaningful. A total of six patients treated at the therapeutic dose levels have had a sustained dose-dependent improvement in their MFM32 scores exceeding three years. The therapy has demonstrated good tolerability with no severe drug-related adverse events when administered at multiple dose levels.
“As the program that laid the foundation for our robust pipeline, we believe that TSHA-120 is a seamless strategic fit and will be immediately value-accretive for Taysha,” said Session II. “TSHA-120 clinical data generated to date is a clear validation of our scientific approach with read-through to our existing product development pipeline. We look forward to quickly working with the regulatory agencies on a path forward to approval of TSHA-120, and in parallel, accelerating the build-out of our commercial infrastructure to support patient identification, payor engagement and product distribution.”
“TSHA-120 is the first successful in-human intrathecal gene transfer in the history of gene therapy and, as such, has had a significant impact across the field,” said Taysha’s Chief Medical Officer and Head of Research and Development Suyash Prasad, MBBS, M.SC., MRCP, MRCPCH, FFPM. “We are very encouraged by TSHA-120’s halting effect on disease progression at therapeutic dose levels and long-term durability of effect in patients living with giant axonal neuropathy, and we look forward to highlighting the initial clinical data in an R&D Day in June 2021.”
Taysha said it will request an End-of-Phase meeting with the FDA and initiate talks with the European Medicines Agency and Japan’s Pharmaceuticals and Medical Devices Agency before the end of the year to discuss TSHA-120’s regulatory pathway in these regions.
