Second quarter of 2024 and post-period update
We made regulatory, clinical, and manufacturing progress with our CD19 CAR-T candidates, GLPG5101 in relapsed/refractory non-Hodgkin lymphoma (R/R NHL) and GLPG5201 in chronic lymphocytic leukemia (R/R CLL) & Richter transformation (RT), and submitted a protocol amendment for BCMA CAR-T candidate, GLPG5301, in relapsed/refractory multiple myeloma (R/R MM) by:
- Submitting an Investigational New Drug (IND) application for the ATALANTA-1 Phase 1/2 study of GLPG5101 to the U.S. Food and Drug Administration (FDA).
- Submitting a Clinical Trial Application (CTA) to the European Medicines Agency (EMA) for the Phase 2 dose expansion study of GLPG5201. The IND for the EUPLAGIA-1 Phase 1/2 study is on track for filing in Q4 2024.
- Presenting additional encouraging safety, efficacy and translational Phase 1/2 data for GLPG5101 and GLPG5201 at scientific conferences1,2,3 demonstrating the feasibility of Galapagos’ innovative cell therapy manufacturing platform to address unmet needs of high-risk patients with median seven-day vein-to-vein delivery of fresh, fit CAR-T cells.
- Submitting a protocol amendment to EMA for the Phase 1/2 PAPILIO-1 study of GLPG5301 in R/R MM following a temporarily pause in patient enrolment due to one observed case of parkinsonism. We anticipate resuming recruitment in the coming months.
- Establishing strategic collaboration with Blood Centers of America, significantly advancing Galapagos' U.S. expansion strategy. This collaboration complements our existing collaborations with Landmark Bio and Thermo Fisher Scientific, and supports upcoming pivotal studies and potential future commercial manufacturing of cell therapies near cancer treatment centers, aiming to deliver more and faster access to potentially life-saving treatments across the U.S.
We continued to execute on our innovation strategy with license agreements and research collaborations in small molecules and cell therapies in solid tumor indications by:
- Signing a clinical collaboration agreement with an option to exclusively license Adaptimmune’s next-generation TCR T-cell therapy (uza-cel) targeting MAGE-A4 for head & neck cancer and potential future solid tumor indications, using Galapagos’ cell therapy manufacturing platform. Adaptimmune is eligible to 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.
- Expanding the strategic collaboration and licensing agreement with BridGene Biosciences, which was announced early 2024, to include the discovery of a highly selective oral SMARCA2 small molecule proteolysis targeting chimera (PROTAC) in precision oncology. This combines Galapagos’ expertise in selective ATPase small molecules with BridGene’s PROTAC discovery engine. The collaboration intends to advance the molecule into a preclinical candidate, with Galapagos holding exclusive global rights for further development and commercialization of the product candidates developed under the agreement. Under the terms of the agreement, BridGene is eligible to potentially receive up to $159 million in total payments plus tiered royalties on net sales.
We progressed our proprietary R&D pipeline of >20 clinical and preclinical small molecule and cell therapy programs in oncology and immunology by:
- Focusing on biologically validated targets to develop potential best-in-class therapeutics in areas of high unmet medical needs.
- Accelerating early-stage preclinical pipeline in oncology and immunology with the goal to initiate at least four IND/CTA enabling studies and at least one first-in-human study in 2025.
- Aiming to fuel the clinical pipeline with at least two new clinical candidates annually across cell therapies and small molecules and various indications, from 2026 onwards.
At the Annual and Extraordinary Shareholders’ Meetings held on 30 April 2024, all proposed resolutions were approved.
- Approved resolutions include the revised 2024 Remuneration Policy and 2023 Remuneration Report.
ATALANTA-1
ATALANTA-1 Phase 1/2 study with the decentralized manufactured CD19 CAR-T candidate, GLPG5101, in patients with relapsed/ refractory non-Hodgkin lymphoma (R/R NHL)
ATPase
ATPase (adenosine triphosphatase) is an enzyme that catalyzes the hydrolysis of ATP (adenosine triphosphate) into ADP (adenosine diphosphate) and an inorganic phosphate. This reaction releases energy, which the cell can use to perform various functions
CAR-T
Chimeric antigen receptor T cells (also known as CAR-T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy
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)
Discovery
Process by which new medicines are discovered and/or designed. At Galapagos, this is the department that oversees target and drug discovery research through to nomination of preclinical candidates
EMA
European Medicines Agency, in charge of European market authorization of new medications
EUPLAGIA-1
EUPLAGIA-1 Phase 1/2 study with decentralized manufactured CD19 CAR-T candidate, GLPG5201, in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) and small lymphocytic lymphoma (R/R SLL), with or without Richter transformation (RT)
Efficacy
Effectiveness for intended use
FDA
The U.S. Food and Drug Administration is an agency responsible for protecting and promoting public health and in charge of American market approval of new medications
GLPG5101
A second generation anti-CD19/4-1BB CAR-T product candidate currently in Phase 1/2 study in R/R NHL
GLPG5201
A second generation anti-CD19/4-1BB CAR-T product candidate currently in Phase 1/2 study in R/R CLL/SLL with or without RT
GLPG5301
A BCMA CAR-T product candidate
Galapagos’ cell manufacturing platform
Galapagos’ decentralized, innovative cell therapy manufacturing platform has the potential for the administration of fresh, fit cells within a median vein-to-vein time of seven days, greater physician control and improved patient experience. The platform consists of an end-to-end xCellit™ workflow management and monitoring software system, a decentralized, functionally closed, automated manufacturing platform for cell therapies (using Lonza’s Cocoon®) and a proprietary quality control testing and release strategy.
Immunology
The study of the immune system and is a very important branch of the medical and biological sciences. The immune system protects humans from infection through various lines of defence. If the immune system is not functioning as it should, it can result in disease, such as autoimmunity, allergy, and cancer
Investigational New Drug (IND) Application
An Investigational New Drug Application (IND) is a request for authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans
MAGE-A4
MAGE-A4, melanoma-associated antigen A4, is a member of the MAGE protein family of cancer-testis antigens. In healthy adult, MAGE-A4 expression is restricted to immune-privileged sites. However, in many cancers MAGE-A4 is widely expressed including lung cancer, head and neck squamous cell cancer, synovial sarcoma(SS), ovarian cancer, urothelial cancer and melanoma
Milestone
Major achievement in a project or program; in our alliances, this is usually associated with a payment
Multiple myeloma (MM)
Multiple myeloma (MM) is typically characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. The plasma cells proliferate in the bone marrow and can result in extensive skeletal destruction with osteolytic lesions, osteopenia, and/or pathologic fractures
Oncology
Field of medicine that deal with the diagnosis, treatment, prevention, and early detection of cancer
PAPILIO-1
Phase 1/2 study with GLPG5301 in patients with relapsed/refractory multiple myeloma
PROTAC
A proteolysis-targeting chimera (PROTAC) is a hetero-bifunctional molecule containing two small molecule-binding ligands joined together by a linker
Parkinsonism
Parkinsonism is a clinical syndrome characterized by a combination of motor symptoms typically associated with Parkinson's disease. Parkinsonism can be caused by Parkinson's disease itself, but it can also result from other conditions, such as neurodegenerative diseases, medication side effects, vascular changes, infections, toxins
Phase 1
First stage of clinical testing of an investigational drug designed to assess the safety and tolerability, pharmacokinetics of a drug, usually performed in a small number of healthy human volunteers
Phase 2
Second stage of clinical testing, usually performed in no more than several hundred patients, in order to determine efficacy, tolerability and the dose to use
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
Preclinical candidate (PCC)
A new molecule and potential drug that meets chemical and biological criteria to begin the development process
Product candidate
Substance that has satisfied the requirements of early preclinical testing and has been selected for development, starting with formal preclinical safety evaluation followed by clinical testing for the treatment of a certain disorder in humans
SMARCA2
SMARCA2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2) is a gene that encodes a protein involved in chromatin remodeling. This protein is a part of the SWI/SNF family of proteins, which are essential for regulating gene expression by altering the structure of chromatin (the complex of DNA and proteins that forms chromosomes). Mutations or dysregulation of SMARCA2 have been implicated in various cancers. As a part of the chromatin remodeling machinery, changes in its activity can lead to altered gene expression profiles that may contribute to tumorigenesis
uza-cel
Uza-cel is a next-generation clinical-stage engineered TCR T-cell therapy developed by Adaptimmune, targeting the MAGE-A4 cancer antigen expressed in various solid tumors. Uza-cel is engineered to express the CD8α co-receptor alongside the engineered TCR that targets MAGE-A4. Data indicate that co-expression of CD8α may broaden and increase the immune response against solid tumors
1 1EHA 2024, 13-16 June, Madrid, Spain. Kersten MJ, et al.
2 2EBMT-EHA 2024, 15-17 February, Valencia, Spain. Blum S, et al.; Tovar N, et al.; Kersten MJ, et al.
3 3EBMT 2024, 14–17 April, Glasgow, UK. Hoefsmit E, et al.; Ortiz-Maldonado V, et al.; Kersten MJ, et al.