Lakefront abandons Galapagos-developed TYK2 inhibitor after unsuccessful partnering efforts
Belgian biotech Lakefront Biotherapeutics, formerly Galapagos, has discontinued its oral TYK2 inhibitor GLPG3667 after analyzing the drug's competitive landscape and holding talks with potential partners. The autoimmune disease drug had met its primary endpoint in a Phase 2 dermatomyositis trial but missed it in lupus.
Why it matters: GLPG3667 was the last remaining clinical-stage drug candidate from Galapagos’ original small-molecule research. CEO Henry Gosebruch called it “the last remaining legacy R&D program” on an earnings call in November 2025.
Lakefront’s pipeline now lists only T-cell engagers, antibodies designed to direct T cells against disease-driving cells: gamgertamig, in Phase 1b trials for autoimmune diseases, and three preclinical programs. The latter originated at U.S. biotech Ouro Medicines, while gamgertamig was originally licensed to Ouro from Keymed Biosciences. In June, Gilead Sciences acquired Ouro, and Lakefront acquired its operating assets under a collaboration agreement.
Lakefront ties the decision to that portfolio. “The decision to terminate the program was based on an exhaustive review of strategic alternatives in light of the investment focus on our current portfolio, while remaining mindful of our responsibility to patients who depend on continued innovation and the development of new treatment options,” the company told European Biotechnology.
Zoom in: Lakefront disclosed the decision on November 11 in its third-quarter business update, saying it followed “a rigorous analysis of the competitive landscape and market opportunity.” It does not expect the cost of the discontinuation to be material. Its shares rose about 4% in Thursday morning trading in Amsterdam.
GLPG3667 is designed to block TYK2, an enzyme that relays inflammatory signals inside cells, and produced mixed results in two Phase 2 trials:
-
In GALARISSO, 21 patients with dermatomyositis, a rare autoimmune disease affecting muscles and skin, received GLPG3667 once daily on top of standard therapy and scored higher on a composite measure of improvement after 24 weeks than the 19 patients receiving placebo. The trial set its threshold for statistical significance at 10%; the result (p=0.0848) met it but would have missed the conventional 5%.
- In GALACELA, in systemic lupus erythematosus, the drug missed its primary endpoint at 32 weeks and a comparable secondary endpoint at 48 weeks.
Backstory: Galapagos said in January 2025 that it would seek partners for GLPG3667, as it announced plans to end small-molecule discovery and cut approximately 300 jobs, representing 40% of its workforce. It has since largely wound down its cell therapy activities, selling five preclinical CAR-T programs in October.
In August, Lakefront reported sustained efficacy in GALARISSO’s 24-week open-label extension, alongside the disappointing final lupus results, and said it was evaluating all strategic options for GLPG3667.
The competition: A rival reached the market while Lakefront was weighing the drug’s future. Lisraya (brepocitinib), a pill from U.S. biotech Priovant Therapeutics that blocks TYK2 and the related enzyme JAK1, won U.S. approval on August 27 as the first oral treatment for adults with dermatomyositis, based on a 241-patient Phase 3 trial. Lisraya carries a boxed warning for risks including serious infections and blood clots.
In the December 2025 results announcement, Galapagos CEO Henry Gosebruch suggested GLPG3667’s favorable safety profile could help differentiate the drug. Lakefront has not named the competitors it analyzed or said whether Lisraya’s approval influenced its decision.
What’s next: Lakefront has indicated that it remains generally open to licensing interest in discontinued programs, although it has not specified what will happen to GLPG3667’s rights. “We are generally open to licensing interest in our discontinued programs,” the company told European Biotechnology, citing the October sale to Armed Cell Therapeutics of preclinical CAR-T programs originating from AboundBio.
In the November 11 business update, Lakefront said it expects gamgertamig to enter registrational studies in 2027 and plans to present Phase 1b data at the American Society of Hematology meeting in December. It reported €2.18 billion in cash and financial investments at the end of September and forecast having at least €1.6 billion available for further transactions and other capital allocation priorities after funding its portfolio through gamgertamig’s first approval.
