RARE Daily

Taysha Acquires Global Rights to Experimental Gene Therapy for Rare Neurodegenerative Disease

April 12, 2021

Rare Daily Staff

Taysha Gene Therapies said it acquired exclusive worldwide rights to a clinical-stage AAV9 gene therapy program, now known as TSHA-120, for the treatment of the rare neurodegenerative disease giant axonal neuropathy from the patient advocacy organization Hannah’s Hope.

Giant axonal neuropathy (GAN) is a rare inherited genetic disorder that affects both the central and peripheral nervous systems and is caused by loss-of-function mutations in the gene coding for gigaxonin. Many children with GAN show symptoms and features before the age of five, including progressive scoliosis, contractures, atrophy of the spinal cord, giant axons—also known as nerve fibers—and abnormalities of the white matter in the brain. Currently, there are no approved treatments for GAN, which often results in death for patients in their late teens or early twenties.

Under the terms of the agreement, in exchange for granting Taysha the exclusive worldwide rights to TSHA-120, GAN patient advocacy group Hannah’s Hope will receive an upfront payment of $5.5 million and will be eligible to receive clinical, regulatory, and commercial milestones totaling up to $19.3 million, as well as a low, single-digit royalty on net sales upon commercialization of the product.

TSHA-120 was originally developed in the laboratory of Steven Gray, Taysha’s chief scientific advisor. TSHA-120 is an intrathecally dosed AAV9 gene therapy currently being evaluated in a clinical trial for the treatment of GAN. The trial is being conducted by the National Institutes of Health in close collaboration with a leading patient advocacy group focused on finding treatments and cures for GAN. TSHA-120 has received rare pediatric disease and orphan drug designations from the U.S. Food and Drug Administration for the treatment of GAN.

“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 RA Session II, president, founder, and CEO of Taysha Gene Therapies. “TSHA-120 clinical data generated to date is a clear validation of our scientific approach with read-through to our existing product development pipeline.”

Sessions noted that like all of the company’s gene therapy candidates, TSHA-120 targets a monogenic CNS disease, is delivered intrathecally using a proven AAV9 vector, and utilizes a highly scalable HEK293 suspension manufacturing process. These parallels, he said, enable Taysha to leverage synergies across its core competencies to efficiently develop and commercialize TSHA-120.

Taysha plans to work with the regulatory agencies on a path forward to approval of TSHA-120, and in parallel, accelerating the build-out of its commercial infrastructure to support patient identification, payor engagement, and product distribution.

“TSHA-120 has the potential to address a significant unmet need for an estimated 2,400 patients with GAN across the United States and in Europe, potentially representing a near-term commercial opportunity of greater than $2 billion,” Sessions said.

The National Institute of Neurological Disorders and Stroke (NINDS) division of the NIH is conducting the ongoing open-label, non-randomized, dose-escalation clinical trial of TSHA-120 for the treatment of GAN. The primary endpoint is safety, with secondary endpoints measuring efficacy using pathologic, physiologic, functional, and clinical markers. A primary measure of clinical efficacy is the Motor Function Measure 32 (MFM32) score, a quantitative scale designed to assess the severity and progression of motor function abilities. There is precedent for its use in multiple clinical studies for neuromuscular diseases, including spinal muscular atrophy amongst others.

To date, 14 patients have been dosed with one of four dose levels of TSHA-120. TSHA-120 has demonstrated a dose-response relationship with arrest of disease progression at the second-highest dose level (1.8×1014 total vector genomes [vg]) at one-year post-treatment, affecting a statistically significant 8-point improvement on the MFM32 score. A 4-point change on the MFM32 score is considered clinically meaningful. Six of these patients treated at therapeutic dose levels have shown sustained dose-dependent improvements in MFM32 scores for more than three years. Long-term results demonstrated that treatment with TSHA-120 at multiple dose levels was well-tolerated with no severe drug-related adverse events. Additional data are expected later this year, including results from the highest dose cohort (3.5×1014 total vg).

“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. This program further supports our approach to treating monogenic diseases of the CNS and may enable us to pursue proof-of-concept for our redosing platform,” said Suyash Prasad, chief medical officer and head of research and development of Taysha.

Before the end of the year, Taysha intends to request an End-of-Phase meeting with the FDA and engage with the European Medicines Agency and the Pharmaceuticals and Medical Devices Agency in Japan to discuss the regulatory pathway for TSHA-120. Taysha expects to provide a regulatory and clinical update on TSHA-120, including data from the 3.5×1014 total vg cohort by year-end.

Photo: RA Session II, president, founder, and CEO of Taysha Gene Therapies

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