INNO-220 / Innovo Therap - LARVOL DELTA

The dual-target molecular glue degrader INNO-235 effectively mediates the degradation of GSPT1 and CK1α, and exhibits potent anti-tumor activity in TP53 mutant burkitt lymphoma (ASH 2025) - "Notably,compared to INNO-220 (a CK1α single-target molecular glue degrader) and MRT-2359 (a GSPT1 single-target molecular glue degrader), INNO-235 demonstrated superior anti-tumor activity and overallsurvival.To elucidate INNO-235's mechanism of action, we performed RNA-seq analysis in INNO-235 treatedDaudi cells...These findingsindicated that INNO-235 induced p53-independent apoptosis in TP53-mutated BL cells through ISRpathway activation.In conclusion, INNO-235 represents a first-in-class GSPT1/CK1α dual-target molecular glue degrader withsignificant therapeutic potential for lymphomas. By inducing both p53-dependent and TP53-independentapoptosis, INNO-235 offers a promising therapeutic strategy for TP53-mutated BL and other MYC-drivenmalignancies with limited treatment options."

IO biomarker • Burkitt Lymphoma • CNS Disorders • Hematological Malignancies • Lymphoma • Oncology • Targeted Protein Degradation • ATF4 • BCL2 • CRBN • GSPT1 • IKZF1 • IKZF3 • MYC • TP53

An orally bioavailable and dual-targeting GSPT1 and CK1α molecular glue degrader targets double-hit lymphoma cells (ASH 2025) - "Importantly INNO-235 retained robust efficacy in p53-mutant DHLDLBCL cell lines, which are resistant to INNO-220, a selective CK1α degrader. By inducing classicalapoptosis in p53 wild-type cells and p53-independent tumor cell apoptosis via the ISR pathway in p53-mutant cells, INNO-235 overcomes the limitations of single-target therapies. This dual targeting GSPT1and CK1α for degradation presents an attractive therapeutic strategy with a single-agent for DHL acrossdiverse genetic Background s. This work provides compelling rationale for clinical translation in geneticallydiverse high-grade lymphomas."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Targeted Protein Degradation • ATF4 • CRBN • GSPT1 • MYC

A Highly Selective and Orally Bioavailable CK1α Molecular Glue Degrader Targets B-Cell Lymphoma Cells (ASH 2024) - "Lenalidomide's clinical efficacy in del(5q) myelodysplastic syndrome is linked to CK1α degradation, though it more potently degrades IKZF1/3...In an OCI-Ly3 xenograft model, INNO-220 exhibits dose-dependent and more robust tumor inhibition compared to JNJ-67856633, a MALT1 inhibitor currently in clinical trials for lymphoma...In summary, our findings underscore the potential of INNO-220, a selective CK1α degrader that targets both the NF-κB and p53 pathways, in offering new treatment strategy for lymphoma, including those resistant to BTK inhibitors. The results from this study not only position INNO-220 as a promising anti-cancer agent for B-cell lymphomas but also suggest a potential strategy for patient stratification, a crucial aspect of personalized medicine."

B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • CARD11 • CRBN • GSPT1 • IKZF1 • IKZF3 • LY9 • MALT1 • NFKBIA