MCL-1 selective inhibitors, global pipeline

Last Update: July 29, 2022

Company Candidate Indication Administration Phase
Novartis & Servier MIK665/S643151 DLBCL, MM, AML/MDS ± BCL-2 inhibitor (VOB560), ± Azacitidine IV I/II
AstraZeneca AZD59912 AML ± Venetoclax IV I/II
Amgen AMG 1763 MM, AML IV I
Prelude Therapeutics PRT14194 MM, AML, NHL (T, B cell lymphomas), MDS, solid tumors (sarcoma, melanoma, lung and breast cancer), monotherapy or in combination with venetoclax. ORAL & IV I
Ascentage Pharma AS00491 - IV Preclin
Ascentage Pharma APG-3526 - IV Preclin
Captor Therapeutics CT-035 - - Preclin
Anji Pharma ANJ8106 - - Preclin
Amgen AMG 3977 AML, MDS, lymphoma ORAL I
AbbVie ABBV4678 MM IV I
1. Two Ph1 completed, Ph1 in combo with Bcl2 inhibitor VOB560 began recruiting June 2021, in patients with r/r NHL, AML or MM. Ph1/2 in AML in combo with azacitidine recruiting, began Feb 2021. Ph1 in combo with venetoclax in AML recruiting
2. Phase I/II trial (NCT03218683), recruiting
3. Ph1 in AML, NHL, DLBCL was temporarily suspended for safety, (voluntary hold after issues with AMG 397). Ph1 in r/r MM and r/r AML recruiting. Data at AACR 2021, poster 1050, showed strong synergism with gilteritinib in AML xenograft model. DATA: Spencer, A., Rosenberg, A. S., Jakubowiak, A., Raje, N., Chatterjee, M., Trudel, S., … Roberts, A. (2019). A Phase 1, First-in-Human Study of AMG 176, a Selective MCL-1 Inhibitor, in Patients With Relapsed or Refractory Multiple Myeloma. Clinical Lymphoma Myeloma and Leukemia, 19(10), e53–e54. doi:10.1016/j.clml.2019.09.081
4. Phase I ongoing (hematological malignancies trial), using oral formulation. IND for IV formulation cleared March 2021 - to be used in trial for solid tumors. Read more in PRLD report here. March 2022 - Prelude plans to prioritize development of IV formulation after demonstrating desirable PK/PD and safety profile. Combination trial with venetoclax to initiate by mid-year with RP2D by 2H22.
5. Targed protein degrader. Press release.
6. Licensed from Broad Institute (MIT/Harvard). Press release.
7. Safety issues (cardiac signal) halted enrollment as well as halted AMG 176. The trial waas reinitiated in Oct 2020, but then terminated in March 2021 (not due to safety but shifted focus to AMG 176).
8. Trial was terminated early (strategic considerations), 8 patients were enrolled.

DLBCL = Diffuse large B-cell lymphoma. MM = Multiple myeloma. AML = Acute myeloid leukemia. MDS = Myelodysplastic syndromes. NHL = Non-Hodgkins lymphoma.

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