The molecules are based on connecting a known MYC binder to a VHL ligand or pomalidomide to induce MYC degradation in various cancer cells known to express MYC...Encouraging results presented herein suggest that the presented analogs may serve as prototype structures of future therapeutic agents for the treatment of MYC-dependent tumors. MYC protein degraders can well complement the more established inhibition approaches that have been presented in the past (e.g., disruption of the MYC-MAX complex formation by small-molecule inhibitors).

P1, N=50, Enrolling by invitation, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=11, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

P1/2, N=42, Recruiting, Medigen Biotechnology Corporation

P1/2, N=1, Terminated, Celularity Incorporated | N=52 --> 1 | Trial completion date: Feb 2025 --> Feb 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2023 --> Feb 2024; for business reasons

P1, N=42, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1, N=27, Terminated, Celularity Incorporated | N=94 --> 27 | Recruiting --> Terminated; Business reasons

P2, N=124, Active, not recruiting, University of Leeds | Trial completion date: Jun 2023 --> Jun 2025

P2, N=20, Recruiting, ImmunityBio, Inc. | Not yet recruiting --> Recruiting

P1/2, N=5, Terminated, 23andMe, Inc. | N=82 --> 5 | Trial completion date: Jun 2026 --> Nov 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2026 --> Nov 2024; Sponsor cancelled study

P2, N=20, Not yet recruiting, ImmunityBio, Inc.

P1, N=18, Recruiting, Medigen Biotechnology Corporation | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P1/2, N=18, Recruiting, Sanofi | Trial completion date: Feb 2029 --> Aug 2029

P1, N=0, Withdrawn, Duke University | N=12 --> 0 | Trial completion date: Sep 2027 --> Dec 2029 | Not yet recruiting --> Withdrawn | Trial primary completion date: Sep 2025 --> Dec 2027

P1, N=45, Recruiting, Masonic Cancer Center, University of Minnesota | Not yet recruiting --> Recruiting

P1, N=9, Active, not recruiting, Wugen, Inc. | Trial completion date: Dec 2025 --> Jan 2025

P1, N=6, Completed, NKGen Biotech, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Apr 2024 | Trial primary completion date: Aug 2024 --> Apr 2024

P1/2, N=101, Active, not recruiting, University of Chicago | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=54, Completed, Amgen | Active, not recruiting --> Completed

We evaluated IPH6501, a clinical-stage, tetraspecific NK cell engager (NKCE) armed with a non-alpha IL-2 variant (IL-2v), which targets CD20 and was developed for treating B cell non-Hodgkin lymphoma (B-NHL)...In vivo studies in nonhuman primates and tumor mouse models further validated its efficacy and revealed that CD20-NKCE-IL2v induces peripheral NK cell homing at the tumor site. CD20-NKCE-IL2v emerges as a potential alternative in the treatment landscape of B-NHL.

Finally, in vivo testing of PSMA TriKE showed improved tumor control and survival of mice as compared to IL-15 and untreated control groups. In conclusion, PSMA TriKE demonstrates potential as a new therapy for advanced prostate cancer by providing additional signals to NK cells to maximize their anti-tumor potential in prostate cancer, especially in the setting of a hostile TME.

P1, N=30, Recruiting, Chongqing Precision Biotech Co., Ltd

P1, N=48, Recruiting, Century Therapeutics, Inc. | N=30 --> 48

P1, N=34, Not yet recruiting, Indapta Therapeutics, INC.

P1, N=3, Terminated, Institute of Hematology & Blood Diseases Hospital, China | N=18 --> 3 | Recruiting --> Terminated; It did not reach the expected results of clinical trial

P1, N=1, Terminated, Institute of Hematology & Blood Diseases Hospital, China | N=18 --> 1 | Recruiting --> Terminated; It did not reach the expected results of clinical trial

P1, N=45, Not yet recruiting, Masonic Cancer Center, University of Minnesota | Initiation date: Oct 2024 --> Jan 2025

P1/2, N=111, Recruiting, Sanofi | Trial primary completion date: Apr 2026 --> Mar 2027

P1, N=18, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting

P1/2, N=32, Not yet recruiting, University of Aarhus

P1, N=39, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=50, Recruiting, ImmunityBio, Inc. | Trial completion date: Dec 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Mar 2025

The original molecular glue degraders (thalidomide, lenalidomide, and pomalidomide) are known to bind to cereblon (CRBN) and alter its surface to induce recruitment, ubiquitination, and degradation of therapeutically valuable neosubstrates (IKZF1, IKZF3, and CK1α). Herein, we describe the medicinal chemistry efforts that resulted in the discovery of SJ3149 as well as other potent and selective CK1α degraders. We report kinetic profiling and parameters of CK1α degradation, ternary complex, antiproliferative effects, in vitro ADME data, and in vivo pharmacokinetic studies with demonstrated oral bioavailability.

Conclusions HST-1011 was associated with dose-dependent changes in peripheral blood pharmacodynamic measures that were sustained with repeated dosing and pre-treatment tumor WTS provided preliminary suggestion of a potential enrichment approach for a study population most likely to benefit from HST-1011. Monotherapy dose-optimization and combination with anti-PD-1 are ongoing.

P1/2, N=169, Recruiting, Sanofi | N=126 --> 169 | Trial completion date: Nov 2026 --> Oct 2030

P1, N=5, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting

P=N/A, N=15, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P1, N=24, Not yet recruiting, The First Affiliated Hospital with Nanjing Medical University

These observations imply that Pomalidomide treatment influences the T-cell repertoire, particularly in the CD4 + subpopulation during the later stages of treatment, raising speculation about the potential involvement of these lymphocyte expansions in mechanisms related to antitumor immunity.

P1, N=45, Not yet recruiting, Masonic Cancer Center, University of Minnesota

P1/2, N=54, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

P1, N=11, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | N=25 --> 11