SITC 2022 preview – cytokines and oral checkpoints

Recently unveiled abstract titles for next month's SITC conference reveal new competition for Incyte’s small-molecule PD-L1 inhibitors.

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.

SITC 2022: small-molecule checkpoint inhibitors
Project Company Mechanism Detail Abstract
CCX559 Amgen (ex Chemocentryx) Oral PD-L1 inhibitor Ph1 769
INCB099318 Incyte Oral PD-L1 inhibitor Ph1 622
INCB099280 Incyte Oral PD-L1 inhibitor Ph1 734
INCB086550 Incyte Oral PD-L1 inhibitor Ph1 774
HZ-G206 Hangzhou Hezheng Pharmaceutical Oral PD-L1 inhibitor Characterisation 458

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.

SITC 2022: selected cytokine approaches
Project Company Mechanism Detail Abstract
MDK-703 Medikine IL-7 mimetic First ph1 results 625
Efineptakin alfa Neoimmunetech IL-7 analogue Keytruda combo in MSS-colorectal & pancreatic cancers 657
ANV419 Anaveon IL-2 fusion protein Ph1 631
CUE-101 Cue Biopharma HPV16 E7-IL-2-Fc fusion protein Ph1 +/- Keytruda in HPV16+ve head & neck cancer 681

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.

SITC 2022: selected other targets
Project Company Mechanism Detail Abstract
CUE-102 Cue Biopharma WT1-Fc fusion protein Ph1 in WT1+ve cancers 636
HMBD-002 Hummingbird Anti-Vista MAb Ph1 +/- Keytruda 623
ATRC-101 Atreca Anti-RNP complex MAb Ph1 +/- Keytruda 717
IO102-103 IO Biotech Anti-IDO & PD-L1 peptide MM1636 study, Opdivo combo in melanoma Part of session 119
LAVA-051 Lava Therapeutics Anti-CD1d gamma-delta T-cell engager Ph1 in haematological cancers 686
NC762  Nextcure Anti-B7-H4 MAb Ph1 748
NC410 Nextcure Lair-2 Fc protein Ph1 Keytruda combo 739
XmAb 819 Xencor Anti-ENPP3 T-cell engager Ph1 renal cell carcinoma 667
INCA32459 Incyte Anti-PD-1 x Lag3 MAb Ph1 723
IK-175  Ikena Oncology AHR antagonist Ph1 Opdivo combo  661
NX-1607 Nurix CBL-B inhibitor Clinical characterisation 777
EO2401  Enterome Microbiome-derived vaccine Opdivo combo in glioblastoma 642

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 2022: selected cell therapies
Project Company Mechanism Detail Abstract
CT-0508 Carisma Anti-Her2 Car-macrophage First-in-human data 634
IOV-4001 Iovance PD-1-inactivated TILs Ph1 783
AB-101 Artiva NK cell therapy (not Car-modified) Preclinical 306
ADI-xxx Adicet Bio Anti-PSMA/CD70/B7-H6 gamma-delta Car-Ts Preclinical Various
ACE1831 Acepodia CD20-conjugated gamma-delta T cells Preclinical  251
GDT002 Gadeta Gamma-delta TCR-modified T cells Preclinical 215

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

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