Quell Therapeutics Advances QEL-001 CAR-Treg Therapy to LIBERATE Phase 1/2 Efficacy Cohort for Liver Transplants

Quell Therapeutics Ltd, a pioneering company in the field of engineered T-regulatory (Treg) cell therapies, has announced significant progress in its QEL-001 therapy for liver transplant patients. The announcement was made during the American Transplant Congress held in Philadelphia, PA, USA. Quell's QEL-001 is an autologous engineered CAR-Treg cell therapy, which is now moving forward into the efficacy cohort of the LIBERATE Phase 1/2 trial after successful completion of the initial safety cohort and subsequent approval by the independent Data Safety and Monitoring Board (DSMB).

The presentation at the Congress by Prof. Alberto Sánchez-Fueyo, co-founder of Quell and Professor of Hepatology at King's College London, highlighted key findings from the study. Notably, Tregs isolated from liver transplant patients can be expanded to generate engineered CAR-Tregs with enhanced safety and therapeutic properties. These properties include the proprietary Foxp3 Phenotype Lock™ and a safety switch for clinical use. The infusion of QEL-001 was found to be safe and well-tolerated in the initial safety cohort, with engraftment and trafficking to the liver allograft observed, and persistence of infused cells for up to six months post-infusion confirmed.

These promising initial data support the further evaluation of QEL-001 in HLA-A2 mismatched liver transplant patients. The aim is to induce operational tolerance and reduce the adverse effects associated with immunosuppressive (IS) therapy. The upcoming efficacy cohort will assess tolerance induction at two and twelve months following the complete withdrawal of IS therapy. Success at the two-month checkpoint is anticipated to be a strong predictor of achieving long-term operational tolerance.

Luke Devey, Chief Medical Officer at Quell Therapeutics, expressed enthusiasm about entering this next phase of the clinical trial. He highlighted that this trial is crucial for liver transplant patients who face lifelong systemic immunosuppression and its associated complications, such as increased risks of malignancies, infections, and renal failure. The LIBERATE trial is designed to test a potentially transformative treatment paradigm aimed at achieving targeted and lasting immune tolerance, potentially eliminating the need for chronic immunosuppression.

QEL-001, Quell's lead candidate, is a first-in-class, antigen-specific CAR-Treg cell therapy developed using Quell’s unique multi-modular engineered Treg platform. The therapy features three proprietary modules: a chimeric antigen receptor (CAR) for tissue targeting, the Foxp3 Phenotype Lock™ module, and a safety switch. Specifically designed for HLA-A2 negative recipients of HLA-A2 positive donor livers, QEL-001 localizes its activity to the site of the transplanted organ.

The LIBERATE trial (NCT05234190) is a multi-center, open-label, single-arm Phase 1/2 study. It is evaluating the safety and efficacy of QEL-001 in approximately 18 HLA-A2 mismatched liver transplant patients, 1-5 years post-transplant, at sites in the UK, Belgium, and Spain. The study's safety cohort (n=3) involved no removal of immunosuppression, while the efficacy cohort (n ≈ 15) involves the administration of ATG followed by dosing with QEL-001 and the complete weaning of immunosuppression. The goal is to assess the induction and durability of operational tolerance at two and twelve months post-IS withdrawal. Immune monitoring assays will track QEL-001 CAR-Treg cells in blood and liver tissue, providing vital data for safety and efficacy assessments and supporting the advancement of Quell’s broader Treg cell therapy pipeline.

Liver transplantation remains a critical area with approximately 15,000 procedures annually in the US and EU5. Currently, liver transplant patients rely on lifelong immunosuppression, which leads to significant complications, including malignancies, infections, and renal failure. Quell Therapeutics aims to address these issues with its innovative therapies, potentially improving long-term survival and quality of life for liver transplant patients.