Cell therapy weekly: in vivo CAR-T agreement
This week: Acuitas Therapeutics (Vancouver, Canada) and Circio (Oslo, Norway) entered an evaluation agreement for in vivo CAR-T cell therapy, the US Food and Drug Administration (FDA; MD, USA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to an investigational gene therapy for NGLY1 deficiency, and VectorBuilder (IL, USA) introduced a stable AAV vector designed to solve the issue of instability in the inverted terminal repeat (ITR) region.
The news highlights:
In vivo CAR-T agreement
Circio and Acuitas have entered into a technology evaluation agreement to assess whether Acuitas’ lipid nanoparticle technology (LNP) can be combined with Circio’s circular RNA expression platform, circVec, for novel in vivo CAR-T therapy.
Victor Levitsky, CSO of Circio, said: “Acuitas has developed a state-of-the-art LNP delivery platform to specifically deliver Circio’s circVec constructs into T-cells. By combining the unrivaled expression durability of circVec with the delivery precision of Acuitas’ LNPs, we aim to establish a novel in vivo CAR-T concept for cancer and auto-immune diseases where an extended expression window is required.”
Under the agreement, Acuitas will incorporate circVec into its proprietary LNPs, which are designed to target CD8+ or CD4+ T-cells. Circio will then evaluate the activity and durability of the modified T cells in vitro and in vivo.
RMAT designation granted to NGLY1 deficiency gene therapy
Grace Science (CA, USA) has been awarded RMAT designation by the US FDA for its investigational gene therapy for NGLY1 deficiency. The therapy, GS-100, utilizes an AAV9 vector to deliver a full-length, functional version of the human NGLY1 protein.
The FDA’s RMAT designation emphasizes the encouraging clinical data after GS-100 treatment,” said Matt Wilsey, CEO and co-founder of Grace Science. “This designation is important because it provides a clear and potentially streamlined regulatory path forward. We look forward to working with the FDA to accelerate the clinical development of GS-100.”
The RMAT designation is based on early data from an ongoing Phase I/II/III clinical trial to evaluate the long-term safety, tolerability and function of GS-100 in patients with NGLY1 deficiency.
AAV designed to tackle ITR instability
VectorBuilder has introduced MuteFree™ AAV, a stable AAV vector designed to solve the issue of instability in the ITR region, a common challenge in gene therapy development. ITR instability can lead to reduced efficiency in packaging the viral genome, inconsistent manufacturing and unreliable therapeutic performance, in some cases requiring higher doses that increase costs and toxicity risks.
“Vector design decisions made early in development often determine downstream outcomes in manufacturability, safety, and efficacy,” said Bruce Lahn, Chief Scientist at VectorBuilder. “ITR instability is a persistent challenge that can compromise AAV production and therapeutic performance. With MuteFree™, we focused on improving stability at the design level to help developers reduce variability and improve reliability across their programs.”