Taysha Gene Therapies

Signify Bio secured an oversubscribed $15 million initial financing round led by Actium Group with participation from Gates Foundation Strategic Investment Fund, Danaher Ventures, Eli Lilly, and American Cancer Society's BrightEdge.

Taysha Gene Therapies has received FDA alignment on key elements of the TSHA-102 pivotal trial design for Rett syndrome, with the agency advising direct submission of trial protocol as an IND amendment, potentially expediting study initiation.

A comprehensive 2025 pipeline analysis identifies over 20 companies developing more than 20 therapeutic candidates for Rett syndrome, highlighting significant industry investment in this rare neurological disorder.

Peter Marks, head of FDA's Center for Biologics Evaluation and Research since 2016, was forced to resign after refusing to support HHS Secretary Robert F. Kennedy Jr.'s vaccine safety claims.

• Neurogene has suspended enrollment in the high-dose arm of its NGN-401 gene therapy trial for Rett syndrome after a patient developed life-threatening systemic hyperinflammatory syndrome, a known risk with AAV vector therapies. • Despite early efficacy signals showing "meaningful gains of skills and developmental milestones" in low-dose patients, the company's shares plummeted nearly 44% following the safety concerns announcement. • The trial will continue with the low-dose cohort, though with delayed enrollment timeline, as the company works to balance promising efficacy data against serious safety considerations for this devastating neurological disorder.

• Two companies, Neurogene and Taysha Gene Therapies, are in Phase 1/2 clinical trials with gene therapies targeting the MECP2 gene for Rett syndrome. • These therapies aim to address the underlying genetic cause of Rett syndrome, unlike existing treatments that only manage symptoms. • Both companies have incorporated regulatory mechanisms to ensure precise MECP2 expression, avoiding complications from overexpression. • Preliminary data from ongoing trials are expected in late 2024 and early 2025, offering hope for a potential disease-modifying treatment.

• A patient with Rett syndrome died after receiving a high dose of Neurogene's experimental gene therapy, NGN-401, triggering a safety review. • The FDA is allowing Neurogene to continue the Phase 1/2 clinical trial with a lower dose of NGN-401, which has shown promising early results. • The adverse event underscores the risks associated with high doses of AAV vectors in gene therapy, particularly regarding immune responses. • Neurogene plans to update the clinical trial protocol to remove the high dose and expects to resume dosing in the low-dose cohort after revisions.

• Taysha Gene Therapies reported positive updates on its TSHA-102 program for Rett syndrome, with high dose treatment showing good tolerability in trials. • The FDA approved the use of pivotal TSHA-102 product in REVEAL trials and endorsed the commercial manufacturing process, marking a regulatory milestone. • Clinical data from the REVEAL trials' cohorts are expected in the first half of 2025, offering potential insights into TSHA-102's efficacy. • Taysha's strong financial position, with $157.7 million in cash, is expected to support operations into Q4 2026, ensuring continued development.

• Neurogene's stock plummeted after disclosing a serious adverse event in a patient receiving a high dose of NGN-401, its gene therapy for Rett syndrome. • The adverse event, occurring in the third patient dosed at the higher level, is consistent with known risks associated with AAV gene therapies. • Preliminary data from the low-dose cohort showed promising efficacy, with all four patients achieving 'much improved' ratings and reaching developmental milestones. • Neurogene is also discontinuing development of its gene therapy for Batten disease after the FDA denied a request for special designation.

• The gene therapy market is experiencing substantial growth, fueled by technological advancements, increased investments, and a deeper understanding of genetic diseases. • Key players are actively engaging in collaborations, mergers, and acquisitions to enhance their research and development capabilities and broaden their product portfolios. • Regulatory bodies like the FDA and EMA are expediting the approval process for gene therapies, acknowledging their potential in addressing unmet medical needs. • Ethical considerations and public perception surrounding gene editing, particularly germline modifications, remain critical factors influencing market dynamics and regulatory policies.