Cell therapy weekly: first patient dosed in cardiac gene therapy trial
This week: Roche (Basel, Switzerland) announced it plans to acquire a clinical-stage biopharmaceutical company to further develop off-the-shelf CAR-T cell therapies, Tenaya Therapeutics (CA, USA) dosed its first patient with its gene therapy for arrhythmogenic right ventricular cardiomyopathy (ARVC). Plus, the US Food and Drug Administration (FDA; MD, USA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to an investigational in vivo CRISPR-based therapy.
The news highlights:
- US$1 billion acquisition agreement for off-the-shelf CAR-T cell therapies
- First patient dosed in cardiac gene therapy trial
- RMAT designation for in vivo CRISPR-based therapy
US$1 billion acquisition agreement for off-the-shelf CAR-T cell therapies
Roche plans to acquire Poseida Therapeutics (CA, USA) for approximately US$1 billion, expanding their existing collaboration to advance off-the-shelf CAR-T cell therapies. The acquisition, expected to close in early 2025, aims to deliver next-generation CAR-T treatments with enhanced potency, improved safety profiles and scalability to reach more patients and support widespread commercial use.
Through this deal, Roche will gain access to Poseida’s GMP manufacturing capabilities, research and development portfolio and expertise, including P-MUC1C-ALLO1, an allogeneic CAR-T program in Phase I clinical trials for solid tumors and preclinical genomic medicine candidates and supporting technologies.
“This exciting acquisition will allow us to drive further progress in allogeneic cell therapy while leveraging the successful existing partnership with Poseida,” said Levi Garraway, Head of Product Development and Chief Medical Officer at Roche. “We are very encouraged by the early clinical data, and this acquisition builds on our joint progress to catalyze the development of potentially first and best-in-class cell therapies in oncology, immunology and neurology.”
First patient dosed in cardiac gene therapy trial
The first patient has been dosed in Tenaya Therapeutics’ Phase Ib RIDGE-1 trial, a dose-escalation study underway in the US and UK. The trial evaluates the safety, tolerability and preliminary efficacy of TN-401, an AAV9-based gene therapy delivered as a one-time intravenous infusion. TN-401 is designed to treat ARVC caused by mutations in the plakophilin-2 (PKP2) gene. These mutations disrupt the structural integrity and cell-to-cell signaling of heart muscle cells by reducing levels of critical proteins. TN-401 delivers a functional PKP2 gene to heart cells, restoring protein levels to address the root cause of the disease.
“People living with ARVC frequently experience dangerous arrhythmias and are at risk for developing heart failure, cardiac arrest and sudden death. To minimize their risk, ARVC patients live with significant activity restrictions, take chronic medications and require interventions that together negatively impact their quality of life but don’t address the underlying problem of a defective gene,” explained Vasanth Vedantham, an investigator for the RIDGE-1 trial. “PKP2 genetic mutations are the most common single gene cause of ARVC and unlike existing treatments for ARVC, TN-401 gene therapy seeks to directly address the underlying cause of disease by delivering a fully functional copy of PKP2 to the heart.”
The trial is enrolling up to 15 adults with PKP2-associated ARVC who have an implantable cardioverter defibrillator and are at elevated risk for arrhythmias. Initial data from RIDGE-1 is expected in 2025.
RMAT designation for in vivo CRISPR-based therapy
The FDA has granted RMAT designation to Intellia Therapeutics‘ (MA, USA) investigational in vivo CRISPR-based therapy, nexiguran ziclumeran (nex-z) for hereditary transthyretin amyloidosis with polyneuropathy. Nex-z has been designed to inactivate the TTR gene, restricting the production of TTR protein to address hereditary transthyretin amyloidosis with polyneuropathy.
This RMAT designation follows promising interim Phase I data demonstrating rapid, deep and durable TTR reduction, suggesting the potential to restrict or reverse disease progression. In addition to the RMAT designation, nex-z has received Orphan Drug Designation from both the FDA and the European Commission.
Speaking about this new designation, Intellia President and CEO John Leonard stated: “It was granted following the FDA’s review of our compelling interim Phase I data that indicated our one-time treatment led to rapid, deep and durable TTR reduction, which is expected to halt and potentially reverse the disease. We look forward to working closely with the FDA to bring this potential paradigm-shifting therapy to patients as quickly as possible.”
