MeiraGTx Announces Poster Presentation at the 2023 American Society of Gene and Cell Therapy (ASGCT) Spotlight on Immuno-Oncology

RiboCAR-T cell activity can be precisely tuned and “remotely” controlled to improve the efficacy, durability and safety of CAR-T cell therapy

LONDON and NEW YORK, Aug. 01, 2023 (GLOBE NEWSWIRE) -- MeiraGTx Holdings plc (Nasdaq: MGTX), a vertically integrated, clinical stage gene therapy company, today announced a poster presentation at the 2023 American Society of Gene and Cell Therapy (ASGCT) Spotlight on Immuno-oncology, which is being held from August 1-2, 2023, in Seattle, WA.

“We are pleased to share data at this year's ASGCT Spotlight on Immuno-oncology on our RiboCAR technology, a synthetic riboswitch-based gene regulation system with the potential to transform CAR-T cell therapy,” said Alexandria Forbes, Ph.D., president and chief executive officer of MeiraGTx. “This innovative approach allows us to precisely and reversibly control the expression of CAR in a dose response to novel small molecule inducers, from undetectable at baseline to at least as high as levels of consitutively expressed CAR driven by the small molecule dose. This degree of control of timing and level of CAR expression is unprecedented.”

Dr. Forbes continued, “The impact of precise CAR control appears to be profound. We have demonstrated impressive improvement in CAR-T activity, cell differentiation state and durability in response to regulated RiboCAR expression as well as providing a much needed safety switch. We believe this is a game changing technology with the potential to have meaningful impact on outcomes for patients treated with CAR-T therapy.”

The poster will be available on the Posters and Publications page of the Company’s website on August 1, 2023.

The details of the poster presentation are as follows:

Poster Number: 21
Abstract Title: Riboswitch-regulated Chimeric Antigen Receptor (RiboCAR) Enhances CAR-T cell Anti-cancer Efficacy
Date: August 1-2, 2023
Time: 7:00am - 10:00am
Room: Emerald Ballroom

Chimeric antigen receptor (CAR)-T cell therapy is a promising treatment for certain cancers. However, it is increasingly evident that the level and timing of CAR molecule expression is important for CAR-T cell activation, durability and anti-cancer activities. Here, we present the development of RiboCAR, a system for precise control of CAR expression via orally available small molecule inducers. Unlike previously reported regulatable CAR platforms that utilize viral protease or chemical-induced protein dimerization, RiboCAR contains a synthetic mammalian ON riboswitch in the coding sequence of the CAR transgene, in which the aptamer functions as a sensor for a specific novel small molecule inducer. The expression level of the CAR gene is precisely dependent on the level of the riboswitch inducer. CAR is undetectable in the absence of the small molecule, and a precise dose response in CAR levels is achieved with increasing dose of small molecule, reaching levels higher than constitutively active CAR upon maximal small molecule dose. Induced CAR expression diminishes following withdrawal of the small molecule. Consistent with small molecule induced expression of the CAR molecule, we controlled CAR-T cell activity by the small molecule inducer. Additionally, T cells with low levels of CAR expression via RiboCAR show enhanced target cell-stimulated T cell activation, reduced markers of exhaustion and greater cytotoxicity when compared with T cells expressing CAR constitutively. CAR levels can be activated to the most effective levels and can be switched on and off according to the presence of the small molecules. With a bioavailable small molecule inducer, CAR-T activity can be precisely tuned and “remotely” controlled in vivo. This precise control of CAR levels with its impact on CAR-T activity and durability provides a system for significantly improving the efficacy of CAR-T therapy in comparison to current CAR-T with constitutively active CAR expression.