GSK once dreamed of harnessing the CD226 axis to create a new generation of blockbuster cancer drugs. But that dream appeared to die this morning as the pharma closed the last programs related to this modality.
The CD226 molecule is expressed on the surface of T and NK cells, binding to the CD155 and CD112 molecules found on tumor cells to stimulate an immune response. Three immune checkpoints—namely CD96, PVRIG and TIGIT—are known to interfere with this process.
Back in 2022, GSK branded the CD226 axis a “particularly promising new area for next-generation immuno-oncology therapies.” As a result, the company launched a series of programs over the years to produce checkpoint inhibitors aimed at these three targets with hopes of generating billions in peak net sales.
However, these ambitions hit a major roadblock earlier this year when the pharma finally dropped its iTeos Therapeutics-partnered anti-TIGIT antibody belrestotug, resulting in a 471 million pound sterling ($629 million) impairment charge.
Then, this morning’s third-quarter earnings results brought news that other CD226-related programs have also been abandoned.
One of these is nelistotug, also known as GSK6097608, an iTeos- and 23andMe-partnered anti-CD96 antibody GSK had been evaluating in a phase 2 study of 360 patients with recurrent/metastatic PD-L1 positive squamous cell carcinoma of the head and neck. The study, which kicked off in 2023, tested nelistotug in combination with both GSK’s own immunotherapy Jemperli and its recently discontinued iTeos-partenered anti-TIGIT drug belrestotug.
GSK had also been running a phase 1 study to evaluate similar combinations as well as nelistotug as a monotherapy for patients with advanced solid tumors.
The other nail in GSK’s CD226 coffin is the pharma’s decision to halt work on its anti-PVRIG antibody GSK4381562. The drug, which GSK licensed from Surface Oncology, had previously been listed in phase 2 development, with GSK also running a phase 1 study of the asset in 141 patients with advanced solid tumors as a monotherapy and in combination with other cancer agents.
When asked by Fierce Biotech on a call with journalists this morning whether GSK has given up on its CD226 dream, outgoing CEO Emma Walmsley said it is “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,” she told Fierce.
The pharma industry “requires risk appetite in terms of the deployment of R&D capital, and most things don't actually work,” Walmsley pointed out.
Fierce recently sat down with GSK executives to map out the pharma’s antibody-drug conjugate ambitions, and Walmsley reaffirmed that this portfolio is “one of the key things that you'll hear a lot more about over the next couple of years.”
Away from oncology, GSK also dropped several infectious disease assets from its phase 2 pipeline during the quarter.
They included a second-generation meningitis vaccination for serogroups A, B, C, W and Y. GSK had been assessing the vaccine, dubbed GSK4023393, in a phase 2 study of infants.
That decision comes eight months after GSK secured FDA approval for another MenABCWY vaccine, which is marketed as Penmenvy. Unlike the infant-focused GSK4023393, Penmenvy is currently indicated for 10- to 25-year-olds.
The company also ended work on a phase 2-stage recombinant subunit vaccine for cytomegalovirus infection, as well as finally pulling the plug on a development of the TG2 inhibitor GSK3915393 for pulmonary fibrosis after already ending work in celiac disease.
In GSK’s phase 1 pipeline, the company removed a DNMT1 inhibitor called GSK4172239 the pharma had been assessing for sickle cell disease.