Gritstone has a mountain to climb with Granite

After disappointing results earlier this year Gritstone needed knockout progression-free survival data with its neoantigen immunotherapy Granite – and it’s fallen well short. The company dubbed its latest update “encouraging”, but looks to be leaning towards a subgroup for a future pivotal study.

With money running low and investors deserting the group, there are big questions about how this trial might be funded. Gritstone also said on Monday that it was exploring “potential value-maximising strategies”, but it seems unlikely that a buyer would be interested in Granite based on the current evidence.

Between a rock and a hard place

Granite is a personalised neoantigen immunotherapy designed to drive a T-cell response to a patient’s tumour. Gritstone is evaluating the project in combination with checkpoint inhibitors, versus chemotherapy control, in a phase 2/3 trial in first-line microsatellite-stable colorectal cancer.

Going into a “cold” tumour like CRC was a bold move, and it hasn’t paid off. In April initial results showed the study to have failed on molecular response, the primary endpoint. At the time Gritstone pointed to an early favourable “trend” on PFS, although this was far from clear cut.

The latest update focused on PFS, and wasn’t much more promising.

In the overall evaluable population of 69 patients, at a cutoff date of 19 August 2024, there was a 21% reduction in the risk of progression or death with Granite versus chemo. However, the hazard ratio confidence interval upper bound was 1.5; Gritstone noted that the study wasn’t statistically powered for PFS.

Still, the company pointed to a subgroup analysis, involving patients with low disease burden at baseline – defined as circulating tumour DNA at or below the trial population’s median. Here, the reduction in the risk of progression or death was 38% – although, again there was a very broad confidence interval, with the upper bound at 1.7.

Gritstone didn’t provide PFS curves.

The company said the data needed time to mature, particularly in the low ctDNA group where events accrue more slowly. Overall survival data are expected in the second half of 2025.

Gritstone plans to discuss the data with the FDA; next steps include the possibility of using ctDNA levels as eligibility criteria in a potential pivotal trial.

Cash crisis

However, the group might be better off cutting its losses. As of March it had just $61.7m in the bank, and no immediate way of raising funds; its stock closed down 62% on Tuesday following the latest readout.

There isn’t much else in Gritstone’s pipeline, however: its only other cancer project is the Slate off-the-shelf neoantigen immunotherapy. A KRAS version is phase 2 ready – pending funding. The group is also developing assets for infectious diseases.

Gritstone’s neoantigen rivals include Moderna/Merck & Co and BioNTech/Roche, with mRNA-4157 and autogene cevumeran respectively; however, the lead indication for these projects is melanoma, a cancer in which PD-(L)1 inhibitors are already effective.

And development hasn’t been smooth for those companies, either: any hopes for a quick approval of mRNA-4157 in adjuvant melanoma were recently dashed, while a key readout with autogene cevumeran has been delayed.