GSK Abandons CD226 Cancer Therapies, Shifts Focus to ADCs and Other Promising Areas

GSK, one of the world's leading pharmaceutical companies, has announced a significant shift in its oncology strategy, abandoning its once-promising CD226 axis cancer therapies and refocusing efforts on other areas with high potential, including antibody-drug conjugates (ADCs).

CD226 Programs Discontinued

In a major setback for GSK's immuno-oncology ambitions, the company has terminated all remaining programs related to the CD226 axis. This decision comes after years of investment and high hopes for what was once considered a "particularly promising new area for next-generation immuno-oncology therapies."

The CD226 molecule, expressed on T and NK cells, was thought to stimulate an immune response against tumor cells by binding to CD155 and CD112 molecules. GSK had been developing checkpoint inhibitors targeting three immune checkpoints—CD96, PVRIG, and TIGIT—that interfere with this process.

However, the company's aspirations hit a significant roadblock earlier this year when it discontinued its anti-TIGIT antibody belrestotug, resulting in a £471 million ($629 million) impairment charge. The latest announcements in GSK's third-quarter earnings results reveal the termination of two additional CD226-related programs:

1. Nelistotug (GSK6097608): An anti-CD96 antibody developed in partnership with iTeos Therapeutics and 23andMe. It was being evaluated in a phase 2 study for recurrent/metastatic PD-L1 positive squamous cell carcinoma of the head and neck.

2. GSK4381562: An anti-PVRIG antibody licensed from Surface Oncology, which had been in phase 2 development for advanced solid tumors.

Strategic Realignment and Future Focus

Emma Walmsley, GSK's outgoing CEO, addressed the company's decision to abandon the CD226 programs, stating, "It's perfectly normal that we switch off some things. The really important thing is we do it before it becomes expensive, and then we refocus all of our energy on the things that have high potential and that can be really big."

Walmsley emphasized that the pharmaceutical industry "requires risk appetite in terms of the deployment of R&D capital, and most things don't actually work." She reaffirmed that GSK's antibody-drug conjugate (ADC) portfolio is now "one of the key things that you'll hear a lot more about over the next couple of years."

Other Pipeline Updates

Beyond oncology, GSK has also made several adjustments to its infectious disease portfolio:

• Discontinued development of a second-generation meningitis vaccine (GSK4023393) for serogroups A, B, C, W, and Y in infants.
• Terminated work on a phase 2-stage recombinant subunit vaccine for cytomegalovirus infection.
• Ended development of the TG2 inhibitor GSK3915393 for pulmonary fibrosis.
• Removed a DNMT1 inhibitor (GSK4172239) from the phase 1 pipeline, which was being assessed for sickle cell disease.

These pipeline adjustments reflect GSK's ongoing effort to optimize its research and development portfolio, focusing resources on programs with the highest potential for success and market impact.