Syncona Limited

Quell provides updates on QEL-001 and LIBERATE trial

5 June 2024

Syncona Ltd, a leading life science investor focused on creating, building and scaling global leaders in life science, notes that its portfolio company, Quell Therapeutics (Quell), has announced that it is advancing QEL-001, its autologous, multi-modular engineered CAR-Treg cell therapy, into the efficacy cohort of the LIBERATE Phase I/II trial in liver transplant patients. Quell's decision to advance the trial follows successful completion of dosing in the initial safety cohort of three patients, from which data were presented yesterday at the American Transplant Congress. A copy of Quell's announcement is set out below, with key highlights as follows:

·      Data presented from this first-in-human study show QEL-001 to be safe and well tolerated, with no serious adverse events or dose-limiting toxicities reported to date

·      The study confirmed that QEL-001 cells migrated to the transplanted liver following infusion, with persistence of those infused cells for up to six months

·      The data support further investigation of QEL-001 CAR-Treg therapy to induce operational tolerance in liver transplant patients and decrease the side effects of immunosuppressants (IS)

·      Quell will now proceed with evaluating QEL-001 in the efficacy cohort of liver transplant patients, assessing the induction of tolerance at two and 12 months after full IS withdrawal

·      The decision to advance the trial to the efficacy cohort follows the initial data review and subsequent approval by the trial's independent Data Safety and Monitoring Board (DSMB)

Elisa Petris, Lead Partner of Syncona Investment Management Limited and Non-executive Director of Quell Therapeutics, said: "This is the first time a therapy of this kind has been assessed in humans as a potential treatment for supporting successful liver transplantation. We are encouraged by the initial data showing QEL-001 to be safe and well tolerated, and look forward to the trial advancing to efficacy evaluation. Patients undergoing liver transplantation currently face the prospect of lifelong immunosuppression, which can seriously impact quality of life, and we are excited about Quell's novel approach to address this."

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Quell Therapeutics Advances QEL-001, its Multi-modular Engineered CAR-Treg Cell Therapy, into Efficacy Cohort of LIBERATE Phase 1/2 Trial in Liver Transplant Patients

Progress in the LIBERATE trial was presented at the American Transplant Congress today

London, UK- June 4, 2024 - Quell Therapeutics Ltd ("Quell"), a leader in developing engineered T-regulatory (Treg) cell therapies for serious medical conditions driven by the immune system, announces that it is advancing QEL-001, its autologous engineered CAR-Treg cell therapy, into the efficacy cohort of the LIBERATE Phase 1/2 trial in liver transplant patients. The decision to advance the trial follows the successful completion of dosing in the initial safety cohort (n=3) and subsequent approval by the trial's independent Data Safety and Monitoring Board (DSMB) following its review of the clinical data.

Progress in the LIBERATE study was presented today at the American Transplant Congress in Philadelphia, PA, USA  by Prof. Alberto Sánchez-Fueyo, Professor of Hepatology and Academic Director of the Institute of Liver Studies at Kings College London, and co-founder of Quell. The presentation concluded:

·    Tregs from liver transplant patients can be isolated and expanded to generate engineered CAR-Tregs with improved safety and therapeutic characteristics (including the proprietary Foxp3 Phenotype Lock™ and a safety switch) for clinical use.

·    Infusion of QEL-001 was shown to be safe and well tolerated in the safety cohort (n=3)

·    Engraftment and trafficking of QEL-001 to the liver allograft and persistence of infused cells for up to six months in the periphery post infusion was confirmed.

·    These initial data support further investigation of QEL-001 CAR-Treg therapy in HLA-A2 mismatched liver transplant patients to induce operational tolerance and decrease the side-effects of immunosuppressive (IS) therapy.

Quell will now proceed with evaluating QEL-001 in the efficacy cohort of liver transplant patients, which will assess the induction of tolerance at two and 12 months after full withdrawal of IS therapy. The ability to wean patients off IS at the two-month evaluation point is expected to be highly predictive of achieving longer-term operational tolerance.

Luke Devey, Chief Medical Officer, Quell Therapeutics, said: "We are very excited to enter the next phase of this clinical trial with QEL-001 in the liver transplantation setting. This is an important trial for liver transplant patients, who still face the prospect of lifelong systemic immunosuppression and the serious complications and negative impact on quality of life that brings, including increased rates of malignancies, infections and renal failure. LIBERATE has been designed to test a new, potentially transformational paradigm for these patients, with QEL-001 designed to bring targeted and durable immune tolerance and eliminate their need for chronic immunosuppression." 

Notes to Editors

About QEL-001

QEL-001 is a first-in-class, antigen-specific CAR-Treg cell therapy, designed using Quell's unique multi-modular engineered Treg platform. QEL-001 comprises three proprietary modules: a chimeric antigen receptor (CAR) for tissue targeting, the Foxp3 Phenotype Lock™ module, and a safety switch. The QEL-001 CAR is specific for HLA-A2, which localizes its activity to the site of the transplanted organ in HLA-A2 mismatched liver transplant patients (i.e. HLA-A2 negative recipients who received an HLA-A2 positive donor liver).

About the LIBERATE Trial

The LIBERATE trial (NCT05234190) is a multi-center, first-in-human, open-label, single-arm Phase 1/2 study evaluating the safety and efficacy of QEL-001 in approximately 18 HLA-A2 mismatched liver transplant patients, 1-5yr post liver transplant, at sites in the UK, Belgium and Spain.

Safety cohort (n = 3) - No ATG conditioning and no removal of immuno-suppression to assess safety of QEL-001 therapy at 28 days post infusion.

Efficacy cohort (n = c.15) - ATG administration followed by dosing of QEL-001 and complete weaning of immunosuppression to assess the induction and durability of operational tolerance at two and 12 months after full withdrawal of immunosuppressive therapy (Endpoints 1 and 2, respectively).

In both cohorts, immune monitoring assays will be used to track QEL-001 CAR-Treg cells in whole blood and liver tissue allowing safety and efficacy assessments and providing translational information apply to the advancement of QEL-001 and Quell's broader Treg cell therapy pipeline.

About Liver Transplantation

Approximately 15,000 patients receive new liver transplants in the US and EU5 each year and the standard of care for liver transplant patients is to receive systemic immunosuppression for the rest of their lives.

Current treatments, such as calcineurin inhibitors, cause significant non-liver comorbidities including increased rates of certain malignancies and infections, diabetes and cardiovascular disease, as well as renal failure. These complications result in poor post-transplant survival with the 10-year survival outcome of liver transplant patients being around 60-65% and comparable to that of common malignancies, such as colon cancer, cancer of the uterus or Non-Hodgkin's lymphoma.

Further, long-term immunosuppressive therapy is nephrotoxic, leading to progressive and irreparable kidney damage that eventually requires dialysis and transplant.

About Quell Therapeutics

Quell Therapeutics is the world leader in developing engineered T-regulatory (Treg) cell therapies that aim to harness, direct and optimize their immune suppressive properties to address serious medical conditions driven by the immune system.

The Company is leveraging its pioneering Foxp3 Phenotype Lock™ technology, unique multi-modular platform and integrated manufacturing capabilities to design and develop a pipeline of highly engineered Treg cell therapies with greater potential for persistence, potency and stability than earlier generations of Treg cell therapy approaches.

Quell's lead candidate QEL-001 is being developed to induce operational tolerance following liver transplantation, with the potential to protect the post-transplant liver without the need for chronic immunosuppressive medications. Quell is also advancing additional programs in neuroinflammatory and autoimmune diseases internally and in partnership with AstraZeneca. www.quell-tx.com.

Contacts

Luke Henry, Chief Business Officer
Quell Therapeutics
[email protected]

Media: Mark Swallow, Frazer Hall, Sandi Greenwood
MEDiSTRAVA
[email protected]

Investors: Corey Davis, PhD
LifeSci Advisors
[email protected]