Table 2

Platforms targeting Cbl-b currently in development or under investigation

Platforms targeting Cbl-b
Drug/platformPharmaceuticalDevelopment and mechanism of actionInvestigational stage
NX-1607NurixComputational approach using DEL identified novel, small molecule Cbl-b inhibitorPhase I
DeTIL-0255Surgically derived TIL cultured with IL-2 plus Cbl-b inhibitor (NX-0255), then infused as adoptive TIL therapyPhase I
APN-401invIOs/ApeironCBLB specific siRNA transfected into peripheral leukocytes via electroporation and infused back into patientPhase I
bbT 3692senventy bioEnhanced cell therapy via CD79a/CD20 CAR-T with CBLB knockoutPhase I NCT05169489
HST-1011HotSpotComputational approach identified allosteric regulatory sites on Cbl-b; DEL used to identify specific allosteric inhibitorPreclinical
NTX-801NimbusStructure-based drug design identified small molecule Cbl-b inhibitor; prevents phosphorylation and activationPreclinical
Protein Targeting Chimeras (PROTAC), NOSProgenraHigh-throughput screening campaign using a homogenous TR-FRET based Tyro3 substrate ubiquitylation assay to develop hetero-bifunctional small molecules that can bind an E3 ligaseĀ±other protein for degradationPreclinical
STX-500SynthexDegrader, NOSPreclinical
APN-411invIOs/ApeironSmall molecule inhibitor, NOSPreclinical
CD70NkartaCD70 CAR-NK w/ CBLB/CISH CRISPR knockoutPreclinical
NOSSanofiCRISPR gene editing platform in T cells, NOSPreclinical
NOSJuno/Celgene/BMSCRISPR gene editing platform in T cells, NOSPreclinical
  • Cbl-b, Casitas B lymphoma-b; DEL, DNA-encoded library; DeTIL, drug enhanced tumor infiltrating lymphocyte; NOS, not otherwise specified.