timdarpacept (IMM01)

P1/2, N=104, Not yet recruiting, ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

P2, N=30, Recruiting, ImmuneOnco Biopharmaceuticals (Shanghai) Inc. | N=14 --> 30 | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Nov 2025 --> Jun 2026

P2, N=30, Recruiting, ImmuneOncia Therapeutics Inc. | Not yet recruiting --> Recruiting | Trial completion date: Dec 2027 --> Aug 2029 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=14, Recruiting, ImmuneOnco Biopharmaceuticals (Shanghai) Inc. | Not yet recruiting --> Recruiting

P3, N=170, Recruiting, ImmuneOnco Biopharmaceuticals (Shanghai) Inc. | Trial primary completion date: Oct 2026 --> Apr 2026

P2, N=14, Not yet recruiting, ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

P3, N=170, Recruiting, ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

Blockade of the CD47/SIRPα and PD-1/PD-L1 signaling pathways by the SIRPα-Fc fusion protein IMM01 and monoclonal antibody atezolizumab significantly restored the anti-MM activity of macrophages and T cells in the microenvironment, respectively. Moreover, our study clarified that DNp73 overexpression not only promotes aggressive growth of tumor cells but, more importantly, promotes immune escape of MM cells through upregulation of immune checkpoints. DNp73 could serve as a biomarker for immunotherapy targeting PD-L1 and CD47 blockade in MM patients.

The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein)...A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.

P3, N=202, Not yet recruiting, ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

IMM47 monotherapy or in combination with SIRP-Fc fusion protein (IMM01) or anti-PD-1 antibodies were used to test IMM47's anti-tumor efficacy in SCID mice with Jeko-1 or MCF-7 tumor cell xenotransplantation and hPD-1 Tg C57BL/6 mice with MC38-hCD24/hPD-L1 tumor cell homologous transplantation models...Additionally, an in vivo pharmacodynamics assay of IMM47 in combination with different PD-1 antibodies revealed that IMM47 exhibits synergistic therapeutic efficacy when combined with Tislelizumab, Opdivo, and Keytruda. Our research showed that the humanized anti-CD24 mAb IMM47 had excellent anti-tumor effect. The extracellular domain's N-glycosylation alteration has no effect on IMM47's ability to bind to CD24. The in vitro assays revealed that IMM47 exhibits significant ADCC, ADCP, ADCT, and CDC activities.

IMM01-04 showed a robust anti-tumor effectivity with a well-tolerated safety profile in prior anti-PD-1 failed classical Hodgkin Lymphoma patients. The phase 2 study is ongoing.