Another Roche TIGIT disappointment

Hopes for Roche’s anti-TIGIT MAb tiragolumab are already low following various failures, and the company has just sneaked another flop into its first-quarter earnings presentation. The group disclosed that it was removing tiragolumab in oesophageal cancer from its pipeline after disappointment in the Skyscraper-07 trial.

Roche also binned P-MUC1C-ALLO1, one of the Car-T projects it gained via its $1bn acquisition of Poseida in November. As for new additions, the company and its Chugai division are taking into the clinic a mystery asset known only as MINT91.

Oesophageal angst

The writing was on the wall for tiragolumab with the failure of its big trial, Skyscraper-01, in first-line non-small cell lung cancer, last year.

However, there were still a few pivotal studies to read out, including Skyscraper-07, testing Tecentriq with or without tiragolumab as first-line maintenance in unresectable oesophageal squamous cell carcinoma.

On Thursday Roche removed oesophageal cancer as a potential use for tiragolumab, and cited the end of phase 3 in locally advanced disease, without spelling out the study’s failure. When asked, a Roche spokesperson confirmed that Skyscraper-07 hadn’t met its primary endpoint.

Roche previously claimed a win in a first-line oesophageal trial, Skyscraper-08, but this used an outdated comparator, and in January the company ditched this setting, too.

At that time Roche also abandoned tiragolumab in head and neck cancer, where the phase 2 Skyscraper-09 study had been ongoing.

This leaves two phase 3 trials yet to report: Skyscraper-03, in first-line maintenance in stage III NSCLC, and Skyscraper-14, in first-line liver cancer, with results from both due later this year, according to the Roche spokesperson. But investors won’t be holding out much hope.

MUC1 & MINT91

Another first-quarter casualty is P-MUC1C-ALLO1, which had been in a phase 1 solid tumour study. The asset came via the acquisition of Poseida, and at the time it was flagged as a potential driver of the deal; more advanced Car-Ts targeting BCMA and CD19 x CD20 were already the subject of a 2022 licensing agreement.

With P-MUC1C-ALLO1 Poseida had been upping the dose of chemo for lymphodepletion in its study, with safety and biomarker data featuring at the ESMO-IO meeting in December. However, these clearly weren’t enough to tempt Roche to continue.

Roche also gained Poseida’s manufacturing capabilities, as well as two early-stage non-viral gene therapy projects in hereditary angioedema and haemophilia, although the latest discontinuation is a black mark against the group’s deal-making nous.

As for the mystery MINT91, the company declined to give more details on the project or its mechanism of action.

Selected oncology pipeline changes at Roche

Source: company presentation & OncologyPipeline.