MS-553

MS-553 reduced BCR and Wnt/β-catenin signaling, overcame stromal cell mediated protection, and synergized with venetoclax in CLL samples. Furthermore, MS-553 delayed disease progression and prolonged survival in the Eµ-MTCP1 murine model of CLL. Collectively our results demonstrate that selective inhibition of PKCβ has the potential to overcome BTKi-resistant CLL.

P1, N=45, Recruiting, Shenzhen MingSight Relin Pharmaceuticals Co., Ltd. | Trial completion date: Jul 2025 --> Dec 2026 | Trial primary completion date: Jun 2025 --> Oct 2026

P1/2, N=12, Not yet recruiting, MingSight Pharmaceuticals, Inc | Trial completion date: Dec 2027 --> Dec 2028 | Initiation date: Jul 2025 --> Jul 2026 | Trial primary completion date: Sep 2027 --> Sep 2028

P1/2, N=12, Not yet recruiting, MingSight Pharmaceuticals, Inc

P1, N=45, Recruiting, Shenzhen MingSight Relin Pharmaceuticals Co., Ltd. | Suspended --> Recruiting

P1/2, N=8, Terminated, MingSight Pharmaceuticals, Inc | N=38 --> 8 | Trial completion date: Jul 2026 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: Apr 2026 --> Nov 2023; The study is terminated due to major protocol revisions.

P1, N=45, Suspended, Shenzhen MingSight Relin Pharmaceuticals Co., Ltd. | Trial completion date: Jan 2024 --> Jul 2025 | Recruiting --> Suspended | Trial primary completion date: Dec 2023 --> Jun 2025

P1/2, N=13, Terminated, Shenzhen MingSight Relin Pharmaceuticals Co., Ltd. | N=48 --> 13 | Trial completion date: Sep 2025 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: Apr 2024 --> Nov 2023; The study is terminated due to major protocol revisions.

P1/2, N=63, Terminated, MingSight Pharmaceuticals, Inc | N=117 --> 63 | Trial completion date: Jun 2024 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: Apr 2024 --> Nov 2023; The study is terminated due to major protocol revisions. A new study in CLL patients is planned.

B-cell receptor (BCR) signaling pathway inhibitors and B-cell lymphoma-2 (BCL-2) antagonist venetoclax (Ven) have transformed the treatment of chronic lymphocytic leukemia (CLL), including in high-risk patients with 17p deletion and/or TP53 mutations and complex karyotype...Patients who progress on BTKi including ibrutinib (ibr) often receive Ven but eventually relapse, underscoring an urgent need for new treatment strategies...Overall, our data provides clear evidence that MS-553 inhibits BCR signaling in vitro and in patients on MS-553 therapy. It also provides a rationale for combinations with Ven as a treatment partner based on its ability to increase survival dependence on BCL-2.

Our data demonstrate the efficacy of the PKCβ inhibitor MS-553 in preclinical models of CLL including that with BTK mutations conferring BTKi resistance. These findings support continued preclinical and clinical investigation of MS-553 in CLL, and the phase 1 trial of this agent is currently underway (NCT03492125) (Blachly et al., 2022).

Our data demonstrate the efficacy of the PKCβ inhibitor MS-553 in preclinical models of CLL, including BTK inhibitor resistant disease. These findings support continued preclinical and clinical investigation of MS-553 in CLL, and the phase 1 trial of this agent is currently underway (NCT03492125) [7].