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

Our preclinical studies demonstrate that immunotherapy via the innate immune system by combining tumor-targeting CAR-NK cells with an IL-15 agonist and a CD47 blockade is a promising novel therapeutic approach to targeting MCAMhigh malignant metastatic ES.

P1, N=30, Recruiting, Interius BioTherapeutics Inc. | Not yet recruiting --> Recruiting

Persons with myeloma were randomized to receive an anti-TIGIT (T cell immunoreceptor) or anti-LAG3 (lymphocyte activation gene) antibody followed by combination with pomalidomide and dexamethasone ( NCT04150965 ). Anti-TIGIT responders had higher CD226 expression, natural killer cell activation and lower CD112 expression. These data demonstrate the clinical activity of TIGIT-LAG3 blockade and identify pathway-specific response correlates in myeloma.

P1, N=260, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting | Trial completion date: Oct 2027 --> Jul 2026 | Trial primary completion date: Oct 2027 --> Jul 2026

P1, N=12, Recruiting, Shantou University Medical College | Not yet recruiting --> Recruiting

P=N/A, N=12, Recruiting, Shantou University Medical College | Not yet recruiting --> Recruiting

P1, N=11, Completed, Radboud University Medical Center | Recruiting --> Completed

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

P1/2, N=111, Recruiting, Sanofi | Trial completion date: Aug 2027 --> Mar 2028

Pomalidomide, which degrades IKZF1 and IKZF3, induced IFN-γ overproduction in human Treg cells. Mechanistically, the Foxp3-Ikzf1-Ikzf3 complex competed with epigenetic co-activators, such as p300, for binding to target gene loci via chromatin remodeling. Therefore, the Ikzf1 association with Foxp3 is essential for the gene-repressive function of Foxp3 and could be exploited to treat autoimmune disease and cancer.

P1, N=9, Recruiting, Base Therapeutics (Shanghai) Co., Ltd.

P1, N=9, Recruiting, Base Therapeutics (Shanghai) Co., Ltd.

P1, N=26, Recruiting, Century Therapeutics, Inc. | Not yet recruiting --> Recruiting

P1, N=30, Not yet recruiting, Interius BioTherapeutics Inc.

P2, N=29, Recruiting, City of Hope Medical Center | Trial completion date: Jun 2024 --> Feb 2027 | Trial primary completion date: Jun 2024 --> Feb 2027

P1, N=42, Not yet recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Jan 2027 --> Jan 2029

P1, N=10, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University | Not yet recruiting --> Recruiting

P1/2, N=101, Active, not recruiting, University of Chicago | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2

P1, N=30, Recruiting, Zhejiang Provincial People's Hospital | Not yet recruiting --> Recruiting

P1, N=5, Not yet recruiting, Dana-Farber Cancer Institute | Initiation date: Jun 2024 --> Sep 2024 | Trial primary completion date: Feb 2025 --> Dec 2025

P1, N=166, Recruiting, Fate Therapeutics | N=322 --> 166

P1/2, N=24, Completed, Astellas Pharma Global Development, Inc. | Active, not recruiting --> Completed