GSK drops celiac program acquired in Sitari buyout—and delivers blow to bid to avert antibiotic apocalypse

GSK’s decadelong involvement with the TG2 pathway has hit a setback. Ten years after helping found Sitari Pharmaceuticals and four years after buying it outright, the British Big Pharma has dropped plans to develop its drug candidate in celiac disease while leaving the door open to other indications. 

Sitari began life with the backing of GSK and Avalon Ventures, which were fresh from setting up a $495 million fund. The biotech raised a $10 million series A round and used the cash to build on what Stanford University’s Chaitan Khosla, Ph.D., had learned about TG2 inhibition. GSK bought Sitari in 2019 and took its lead candidate, GSK3915393, into the clinic the following year.

GSK completed the study in 2021, but the candidate remained part of its early-phase pipeline—until now. Wednesday, GSK punted GSK3915393 back to the research stage, ending its plans of developing the drug in celiac disease without killing off the asset altogether. The action terminates GSK’s interest in celiac disease for now, as CEO Emma Walmsley told Fierce Biotech on a call with the media this morning.

“I don't think there are any further plans to pursue celiac disease,” Walmsley said. “It will be, again, simply a question of really putting as much discipline as we can into our capital allocation. We do that now across the full portfolio of vaccines and medicines, and we just try and look to see where we're going to not only get the right impact for patients, but the right of return on that R&D investment with the right kind of portfolio mix in terms of risks and rewards.” 

GSK’s prioritization of R&D investment also delivered a blow to visions of vaccinating our way out of the antibiotic apocalypse by tossing out its phase 2 Staphylococcus aureus candidate. The Big Pharma junked the vaccine program in the same update that called time on its celiac disease work.

In its methicillin-resistant form, S. aureus is known as MRSA, a bacteria that is 64% more likely to kill than its drug-sensitive siblings. New antibiotics could improve outcomes, but, with the R&D pipeline of potential approaches currently more of a trickle than a torrent, alternative options are needed. Vaccines could be a solution, both by directly preventing infections and reducing the spread of the pathogen to cut the need for antibiotics. 

GSK applied its bioconjugation and adjuvant technologies to the problem, resulting in a vaccine designed to target five S. aureus antigens and thereby prevent recurrent skin and soft tissue infections. A phase 1/2 dose-escalation trial of the candidate, GSK3878858A, got underway in June 2020. One year later, the study hit its first snag when GSK delayed the primary completion from November 2022 to May 2023. 

The drugmaker pushed back the target completion date for the second time one year ago. The delay shunted the primary complete date out to March 2024. Now, GSK has admitted defeat. Two weeks ago, the company changed the status of the study to “active, not recruiting.” Today, GSK management included the S. aureus vaccine on the list of discontinued assets in the fourth-quarter pipeline update.