Uza-cel: MAGE-A4 directed TCR T-cell therapy candidate, co-expressing CD8α

In May 2024, we signed a clinical collaboration agreement with an option to exclusively license Adaptimmune’s next-generation TCR T-cell therapy (uza-cel) targeting MAGE-A4, and co-expressing the CD8α co-receptor, for head and neck cancer, and potential future solid tumor indications, using Galapagos’ cell therapy manufacturing platform. Under the terms of the agreement, Adaptimmune will receive initial payments totaling $100 million, option exercise fees of up to $100 million, additional development and sales milestone payments of up to a maximum of $465 million, plus tiered royalties on net sales.

Uza-cel (graphic) — Uza-cel has the same engineered T-cell receptor (TCR) as afamitresgene autoleucel (afami-cel), which has demonstrated efficacy in synovial sarcoma, plus an additional CD8α co-receptor that expands the immune response and improves potency against non-sarcoma MAGE-A4–expressing solid tumors (Ref.: NCT04044768; D’Angelo SP. Lancet. 2024;403:1460; Anderson VE. J lmmunother. 2023;46:132. 3. Moreno V. Presented at ESMO, FPN:1019O, October 23, 2023, Madrid)

In December 2024, we and Adaptimmune presented strong preclinical proof-of-concept data at the annual ASH meeting for uza-cel. The data demonstrated that Galapagos’ decentralized cell therapy manufacturing platform can produce uza-cel with features that may result in improved efficacy and durability of response in the clinic compared with the existing manufacturing procedure (see graphs below).

Preparations are ongoing with the goal to start clinical development in 2026.

xCELLigence cytotoxicity assay on T-cell products manufactured using Galapagos’ decentralized manufacturing (GDM) versus current centralized platform (CCP) (graphic) — xCELLigence cytotoxicity assay at GDM lab showed GDM cells had more significant killing compared with CCP cells at the lowest effector to target cell (E:T) ratio. Incucyte cytotoxicity assay at CCP lab showed similar killing patterns using both manufacturing methods at all E:T ratios tested (not shown), although 1:1 was the lowest E:T tested.

Cell therapy

Cell therapy aims to treat diseases by restoring or altering certain sets of cells or by using cells to carry a therapy through the body. With cell therapy, cells are cultivated or modified outside the body before being injected into the patient. The cells may originate from the patient (autologous cells) or a donor (allogeneic cells)

Efficacy

Effectiveness for intended use

Milestone

Major achievement in a project or program; in our alliances, this is usually associated with a payment

Preclinical

Stage of drug research development, undertaken prior to the administration of the drug to humans. Consists of in vitro and in vivo screening, pharmacokinetics, toxicology, and chemical upscaling

Take a look at our previous reports:

Annual Report 2024

Uza-cel: MAGE-A4 directed TCR T-cell therapy candidate, co-expressing CD8α

xCELLigence cytotoxicity assay on T-cell products manufactured using Galapagos’ decentralized manufacturing (GDM) versus current centralized platform (CCP)