Table 2

Platforms targeting Cbl-b currently in development or under investigation

Platforms targeting Cbl-b
Drug/platform	Pharmaceutical	Development and mechanism of action	Investigational stage
NX-1607	Nurix	Computational approach using DEL identified novel, small molecule Cbl-b inhibitor	Phase I NCT05107674
DeTIL-0255	Nurix	Surgically derived TIL cultured with IL-2 plus Cbl-b inhibitor (NX-0255), then infused as adoptive TIL therapy	Phase I NCT05107739
APN-401	invIOs/Apeiron	CBLB specific siRNA transfected into peripheral leukocytes via electroporation and infused back into patient	Phase I NCT03087591 NCT02166255
bbT 369	2senventy bio	Enhanced cell therapy via CD79a/CD20 CAR-T with CBLB knockout	Phase I NCT05169489
HST-1011	HotSpot	Computational approach identified allosteric regulatory sites on Cbl-b; DEL used to identify specific allosteric inhibitor	Preclinical
NTX-801	Nimbus	Structure-based drug design identified small molecule Cbl-b inhibitor; prevents phosphorylation and activation	Preclinical
Protein Targeting Chimeras (PROTAC), NOS	Progenra	High-throughput screening campaign using a homogenous TR-FRET based Tyro3 substrate ubiquitylation assay to develop hetero-bifunctional small molecules that can bind an E3 ligase±other protein for degradation	Preclinical
STX-500	Synthex	Degrader, NOS	Preclinical
APN-411	invIOs/Apeiron	Small molecule inhibitor, NOS	Preclinical
CD70	Nkarta	CD70 CAR-NK w/ CBLB/CISH CRISPR knockout	Preclinical
NOS	Sanofi	CRISPR gene editing platform in T cells, NOS	Preclinical
NOS	Juno/Celgene/BMS	CRISPR gene editing platform in T cells, NOS	Preclinical

Cbl-b, Casitas B lymphoma-b; DEL, DNA-encoded library; DeTIL, drug enhanced tumor infiltrating lymphocyte; NOS, not otherwise specified.