SITC 2022 preview – cytokines and oral checkpoints

For the second year running small-molecule immune checkpoint blockade is set to take centre stage at the SITC meeting. Like in 2021 Incyte will present clinical data, this time from no fewer than three oral PD-L1 inhibitors, INCB099318, INCB099280 and INCB086550.

But Incyte will be joined by two other similarly acting small molecules: CCX559, a little-known asset in development by Chemocentryx, a company being bought by Amgen largely for its marketed vasculitis therapy, Tavneos; and HZ-G206, which appears to be owned by the Chinese group Hangzhou Hezheng Pharmaceutical. Elsewhere, there is a major focus on cytokines, plus the usual mix of novel biological targets and cell therapies.

The initial themes of SITC are emerging as the abstract titles were unveiled yesterday. Late-breaker titles remain under wraps until November 2, and five days after that the embargo lifts on the full texts of all presentations.

Chemocentryx had presented early findings from a phase 1 study of CCX559 in an Asco poster, but this comprised only safety and pharmacokinetic data. It is not yet clear whether its SITC poster will include efficacy results.

Development of oral PD-(L)1 inhibitors was once hailed as a key step towards making these therapies cheaper and more convenient, but there has been little real progress. Curis, an early leader, has reported underwhelming results for its oral PD-1/Vista inhibitor CA-170.

But Incyte made a splash at last year’s SITC with results from a phase 1 trial of INCB086550. This did yield remissions, but peripheral neuropathy put a dampener on its prospects. Thus the upcoming results with INCB099318 and INCB099280, which Mizuho analysts reckon have not been associated with that side effect, should be of great interest.

That said, oral checkpoint blockers risk missing the boat, with all the big pharma players developing subcutaneous anti-PD-(L)1 projects that promise a long patent life in addition to offering improved patient convenience.

Elsewhere, cytokine work continues at numerous biotechs despite clinical setbacks, and the private companies Medikine and Neoimmunetech have SITC presentations on approaches using IL-7.

Among other targets IO Biotech continues to plough the IDO furrow with IO102-103, though it insists that this peptide works as a vaccine, whereas the failures targeting IDO concerned small-molecule inhibitors. And a phase 1 abstract on Lava’s lead gamma-delta T-cell engager LAVA-051 will be especially interesting in light of that company’s recent validation by way of a tie-up with Seagen on a separate asset.

Therapies using gamma-delta T-cells themselves also have an SITC presence, as do those using TILs, NK cells and Car-macrophages, though much of the presentations will be preclinical.

SITC takes place in Boston, US, on November 8-12.