CT1113 / Chaser Therapeutics - LARVOL DELTA

PBSS1113 in Combination With Azacitidine to Treat Patients With AML/MDS (clinicaltrials.gov) - P1/2 | N=29 | Recruiting | Sponsor: Chaser Therapeutics, Inc.

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

CT1113, a dual USP25/28 inhibitor, promotes antitumor immunity by preventing YTHDF2-mediated complement activation and potentiates anti-PD-1 therapy (AACR 2025) - "As a result, both pharmacologic and genetic inhibition of USP25/28 strongly enhance anti-PD-1 therapy against two murine "cold" tumor models without discernable systemic toxicity. Together, these results provide a rationale for future clinical trials evaluating the synergy between inhibiting USP25/28 and ICI to improve the efficacy of immunotherapy."

Late-breaking abstract • Oncology • CD8 • USP25 • YTHDF2

The first-in-human trial of USP28 inhibitor CT1113 (AACR 2025) - "Importantly, preliminary efficacy was observed, validating USP28 as a therapeutic target. A phase II trial has been planned."

First-in-human • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • MYC

The deubiquitinase USP28 promotes esophageal squamous cell carcinoma proliferation by stabilizing ΔNp63 protein. (PubMed, Cell Signal) - "Importantly, CT1113 administration significantly suppressed tumor growth in ESCC xenograft models. Our study not only defines the USP28/ΔNp63 axis as a critical driver of ESCC but also validates the therapeutic strategy of pharmacologically inhibiting USP28 for the treatment of this aggressive cancer."

Journal • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • Targeted Protein Degradation

USP28 inhibition upregulates CD20 via c-myc suppression and synergizes with anti-CD20 immunotherapy in B-cell lymphomas (ASH 2025) - "These data suggest thatUSP28 inhibition upregulates CD20 through c-Myc suppression and enhances anti-CD20 therapeuticefficacy.ConclusionThese findings demonstrate that targeting of USP28 leads to c-Myc suppression and CD20 upregulation,thereby enhancing the response to anti-CD20 immunotherapy in c-Myc–driven B-cell lymphomas. Theobserved synergistic antitumor activity supports further clinical investigation of CT1113 in combinationwith Rituximab in patients with relapsed or refractory disease."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Targeted Protein Degradation • MYC • PRKDC • PTPRK

Preclinical Study of a Novel USP28 Inhibitor for the Treatment of Burkitt Lymphoma (ASH 2024) - "These experimental results suggest that SREBP1-mediated lipid synthesis plays a crucial role in BL, and that pharmacological inhibition of SREBP1 exerts cytotoxic effects on BL cell lines.In summary, our findings demonstrate that CT1113 exhibits significant efficacy against BL. Our preclinical studies of CT1113 indicate that targeting USP28 represents a highly promising and potential clinical strategy for the treatment of BL patients."

Preclinical • Acute Myelogenous Leukemia • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • MYC

CT1113, a Potent, Oral Small Molecule Inhibitor of USP25, Demonstrates Anti-Tumor Activity in Ph-Positive Acute Lymphoblastic Leukaemia (ASH 2024) - "Additionally, the proteasome-specific inhibitor MG132 blocked CT1113-induced BCR-ABL1 downregulation in human Ph+ALL cell lines. Consequently, the survival of mice treated with CT1113 was prolonged compared to those in the vehicle and TKI arms. Conclusion : Our data demonstrate the efficacy of the USP25 inhibitor CT1113 in preclinical models of Ph+ALL including that with BCR-ABL1 mutations conferring TKI resistance.These findings support the clinical investigation of CT1113 in Ph+ALL."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • ANXA5 • BCR • STAT5 • USP25