Dr. John Mellors, who heads the cell therapy discovery team for biotechnology company Galapagos, talks about the innovations the organization is making to improve delivery speed and access to CAR T-cell therapy for those who need it.
John W. Mellors, M.D.
Head of Cell Therapy Discovery, Galapagos
Can you talk a bit about Galapagos’ history and why you are now choosing to become singularly focused on CAR T-cell therapy?
Galapagos began as a novel target and small molecule discovery company primarily focused on autoimmune and fibrotic diseases. In 2022, with a change in leadership and the arrival of Dr. Paul Stoffels as CEO, Galapagos pivoted its portfolio ambitions to more effective cancer therapies and broader access to life-saving CAR T-cell therapies through decentralized manufacturing in areas of high unmet need.
What are some of the keys to success in globalizing treatments like CAR T-cell therapy?
Some keys to success are efficient, scalable, and lower cost CAR T-cell manufacturing that can be set up in multiple locations around the globe to increase access and affordability of CAR T-cell therapy. Currently, only a small fraction of individuals with cancer who would benefit from CAR T-cell therapy are able to receive it. Galapagos’ mission is to address this shortcoming.
Why is it so important to reduce the time it takes to deliver treatments to cancer patients?
Cancer grows continuously and progressively — it does not take off weekends or holidays. The longer it takes to provide cancer therapy, the higher the tumor burden at the start of therapy, which lowers the likelihood of achieving a complete response to treatment. Put simply, cancer therapy cannot wait, and our vein-to-vein time of seven days provides CAR T-cell therapy with unprecedented and unparalleled speed.
What is “Cocoon” and how is it helping people with cancer achieve sustained remission?
The Cocoon® (from Lonza) is a functionally closed, sterile, efficient manufacturing platform, which combined with our decentralized manufacturing strategy and rapid release testing, enables delivery of fresh CAR T-cells to the patient with a vein-to-vein time of seven days.
The culture conditions used at Galapagos in the Cocoon® promote the outgrowth of CAR T-cells that have a less differentiated, naïve, and stem-like memory phenotype that show greater expansion and persistence of CAR T-cells following infusion, resulting in high efficacy and favorable safety in Phase 1-2 studies (Kersten, et al. ASH 2024, San Diego, CA).
How is Galapagos working to increase access to CAR T-cell therapy (i.e., reducing the time and cost it takes to receive this therapy no matter where you live)?
Galapagos’ decentralized manufacturing approach lowers the space, personnel, and other requirements and their associated costs that are needed to set up a CAR T-cell manufacturing site. These manufacturing sites are called decentralized manufacturing units, or DMUs. There are multiple DMUs already established in Europe and ones being set up in the United States. The first DMU in the United States, located in Boston, is manufacturing CAR T-cells for a Phase 2 study in multiple subtypes of B-cell malignancies.
How is Galapagos innovating cancer treatments to help patients achieve sustained remission?
Galapagos is pioneering cutting-edge science aimed at creating CAR T-cells that accomplish more frequent and more durable remissions of both liquid and solid cancers, through several important approaches:
- Targeting more than one cancer antigen on malignant cells to prevent down regulation of a single antigen as a mechanism of cancer escape from CAR T-cell therapy
- Arming CAR T-cells with the ability to secrete growth factors that promote expansion and persistence of CAR-T in humans, and activation of non-CAR-T endogenous immune cells, including T-cells, NK cells, and macrophages, to kill cancer cells
- Preventing CAR T-cell dysfunction and death from the hostile environment within a cancer mass
These innovations will be tested for efficacy and safety in preclinical models, and if successful, will be progressed to first in human clinical studies.
