Undisclosed p300-selective degrader / SK Bio - LARVOL DELTA

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

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 p300-selective degrader with potent anti-tumor activity in CBP mutant cancers (AACR 2024) - "Once daily oral administration of our compound led to almost complete degradation of p300 within H1703 xenograft tumors, resulting in a pronounced inhibition of tumor growth. Lastly, we profiled p300 degradation in human bone marrow derived myeloid progenitor colony-forming assays where we observed a significant reduction in toxicity (IC50 = 3.9uM) compared to a dual CBP/p300 inhibitor (IC50 = 121nM) or degrader (IC50 = 16nM), supporting the hypothesis that a p300-specific mechanism will offer an improved therapeutic index while maintaining anti-tumor efficacy in a biomarker population Taken together, our results suggest that a p300-selective degrader has the potential to serve as an effective therapeutic modality in CBP-mutated cancers."

Oncology

p300-selective degraders illustrate potent anti-tumor activity in a distinct subset of cancers (AACR 2025) - "Once daily oral administration of our compound led to almost complete degradation of p300 within xenograft tumors, resulting in a pronounced inhibition of tumor growth. Lastly, we profiled p300 degradation in human bone marrow derived myeloid progenitor colony-forming assays where we observed a significant reduction in toxicity (IC50 = 4µM) compared to a dual CBP/p300 inhibitor (IC50 = 121nM) or degrader (IC50 = 16nM), supporting the hypothesis that a p300-specific mechanism will offer an improved therapeutic index while maintaining anti-tumor efficacy.Taken together, these results underscore the therapeutic potential of a selective p300 degrader in both castrate-resistant prostate and CBP LoF cancers.SK Life Science Labs Proprietary / Confidential"

Late-breaking abstract • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • MYC

Late-Breaking Research from SK Life Science Labs at AACR Annual Meeting Shows p300-Selective Degraders are Potent Growth Inhibitors in Models of Aggressive Prostate Cancers and Solid Tumors (PRNewswire) - "SK Life Science Labs...presented late-breaking research at the American Association for Cancer Research (AACR) Annual Meeting 2025 in Chicago. The research identified novel orally bioavailable p300-selective degraders that have therapeutic potential for difficult-to-treat prostate cancer and multiple cancers where the protein CBP is mutated or missing....Targeted p300 degraders demonstrate superb selectivity and potency, inhibiting tumor cell growth across several indications including castrate-resistant prostate cancer and cancers where the related protein, CBP, is missing or mutated. Once daily oral administration of these potent p300-selective degraders in tumor-bearing mice results in rapid degradation of p300 and a significant reduction in tumor growth."

Late-breaking abstract • Preclinical • Castration-Resistant Prostate Cancer

SK Biopharmaceuticals’ Proteovant Therapeutics Presents Preclinical Data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - "SK Biopharmaceuticals...and its U.S. R&D subsidiary, Proteovant Therapeutics, presented data showing that selectively degrading the epigenetic protein p300, with minimal impact on its paralog CBP, results in suppression of androgen receptor signaling and inhibition of tumor growth in a mouse model of androgen receptor (AR) positive prostate cancer. Findings are being presented today at the American Association for Cancer Research (AACR), National Cancer Institute (NCI), and the European Organisation for Research and Treatment (EORTC) International Conference on Molecular Targets and Cancer Therapeutics being held in Boston."

Preclinical • Prostate Cancer