p300 degrader / AbbVie - LARVOL DELTA

Exceptionally selective and orally bioavailable p300 degraders for the treatment of CBP-mutant and p300-dependent cancers (AACR 2026) - "In summary, we have identified highly selective degraders of p300 with desirable profile. Efforts are in progress towards nominating a development candidate by Q1 2026."

IO biomarker • Bladder Cancer • Breast Cancer • Diffuse Large B Cell Lymphoma • Estrogen Receptor Positive Breast Cancer • Genito-urinary Cancer • Hematological Malignancies • Hormone Receptor Breast Cancer • Melanoma • Neuroblastoma • Oncology • Prostate Cancer • Solid Tumor • AR • BRCA • BRCA1 • BRD4 • CRBN • EP300 • ER • FOXP3 • GSPT1 • HIF1A • MYC • MYCN • PD-L1

Discovery and characterization of a selective p300 degrader reveals deep anti‑tumor activity in CBP mutant cancers (AACR 2026) - "Importantly, the observed growth inhibition in CBP LoF lines closely correlated with robust suppression of H3K27 acetylation and downregulation of c-Myc, reinforcing the on-target mechanism of action. These in vitro results translated into striking in vivo efficacy: once-daily oral dosing of the p300 degrader (30 mpk) led to near-complete p300 degradation in tumors and marked tumor regression (TR) across xenograft models, including SW780 (TR = 82%, bladder cancer), NCI-H1876 (TR = 100%, SCLC), PFIEFFER (TR = 98%, DLBCL), and KARPAS422 (TR = 20%, DLBCL).Furthermore, bone marrow colony-forming assays demonstrated a markedly improved safety profile, with the p300-selective degrader showing minimal hematologic toxicity (IC₅₀ >10 µM) compared to a clinical stage dual p300/CBP inhibitor (IC₅₀ = 121 nM) or dual degrader (IC₅₀ = 16 nM).Collectively, these results establish selective p300 degradation as a powerful therapeutic strategy for CBP loss-of-function cancers,..."

Bladder Cancer • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Lung Cancer • Oncology • Solid Tumor • MYC

Discovery and characterization of a selective p300 degrader reveals broad anti‑tumor activity in p300‑dependent cancers (AACR 2026) - "In a panel of multiple myeloma cell lines, p300 degraders displayed superior potency compared with dual p300/CBP inhibitors and pomalidomide. Importantly, these in vitro findings translated into efficacy in vivo. Once-daily oral administration at 30 mpk in xenograft models led to near-complete tumor p300 degradation and strong anti-tumor efficacy, with tumor growth inhibition (TGI) of 100% (VCaP, AR⁺ CRPC), 77% (LNCaP, AR⁺ CRPC), and 86% (OPM2, multiple myeloma).Furthermore, bone marrow colony‑forming assays revealed a significantly improved safety margin (IC₅₀ > 10 µM) relative to a dual p300/CBP inhibitor (IC₅₀ = 121 nM) and a dual degrader (IC₅₀ = 16 nM), supporting an enhanced therapeutic index.Collectively, these findings establish that selective p300 degradation delivers potent anti‑tumor efficacy while minimizing hematologic toxicity, offering a promising therapeutic approach for p300‑dependent cancers driven by either lineage‑specific or tumor‑intrinsic..."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer • Solid Tumor • MYC

JZY-2233: An antigen-targeted CBP/p300 degrader-antibody conjugate for advanced prostate cancer therapy (AACR 2026) - "JZY-2233 is a highly potent, antigen-targeted CBP/p300-PSMA DAC, offering prolonged tumor suppression and reduced toxicity in models of advanced prostate cancer. This approach provides a strong rationale for further evaluation in clinical studies and may be adapted for targeting additional tumor antigens across diverse cancers."

Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • MYC