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DRUG:

timdarpacept (IMM01)

i
Other names: IMM01, IMM-01, IMM 01
Associations
Company:
ImmuneOnco Biopharma
Drug class:
CD47 inhibitor
Associations
1m
New P3 trial • Combination therapy
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azacitidine • timdarpacept (IMM01)
2ms
DNp73 enhances tumor progression and immune evasion in multiple myeloma by targeting the MYC and MYCN pathways. (PubMed, Front Immunol)
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.
Journal • PD(L)-1 Biomarker • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CD47 (CD47 Molecule) • CDK7 (Cyclin Dependent Kinase 7) • SIRPA (Signal Regulatory Protein Alpha)
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TP53 mutation • MYCN expression
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Tecentriq (atezolizumab) • timdarpacept (IMM01)
5ms
Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38. (PubMed, Front Immunol)
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.
Journal
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CD47 (CD47 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
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timdarpacept (IMM01)
5ms
New P3 trial
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gemcitabine • Tevimbra (tislelizumab-jsgr) • bendamustine • timdarpacept (IMM01)
12ms
Humanized Monoclonal Antibody IMM47, Targeting CD24, Exhibits Exceptional Anti-Tumor Efficacy By Blocking the CD24/Siglec-10 Interaction and Can be Used As Monotherapy or in Combination with Anti-PD1 Antibodies for Cancer Immunotherapy (ASH 2023)
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.
Clinical • Combination therapy • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD24 (CD24 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tevimbra (tislelizumab-jsgr) • IMM47 • timdarpacept (IMM01)
1year
IMM01 Plus Tislelizumab in Prior Anti-PD-1 Failed Classic Hodgkin Lymphoma: An Open Label, Multicenter, Phase 2 Study (IMM01-04) Evaluating Safety As Well As Preliminary Anti-Tumor Activity (ASH 2023)
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.
Clinical • P2 data
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SIRPA (Signal Regulatory Protein Alpha)
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Tevimbra (tislelizumab-jsgr) • timdarpacept (IMM01)
1year
Preliminary Results of a Phase 2 Study of IMM01 Combined with Azacitidine (AZA) As the First-Line Treatment in Adult Patients with Chronic Myelomonocytic Leukemia (CMML) (ASH 2023)
Preliminary data showed that IMM01 (without a low-dose priming) combined with AZA were well tolerated. The combo, when compared to the historical data of AZA alone, showed exciting efficacy result for patients with treatment-naive CMML1-2.
Clinical • P2 data
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SIRPA (Signal Regulatory Protein Alpha)
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azacitidine • timdarpacept (IMM01)
1year
Preliminary Results of a Phase 2 Study of IMM01 Combined with Azacitidine (AZA) As the First-Line Treatment in Adult Patients with Higher Risk Myelodysplastic Syndromes (MDS) (ASH 2023)
Preliminary data from IMM01 (without low-dose priming) combined with AZA were well tolerated and showed exciting efficacy results in patients with treatment-naive higher-risk MDS.
Clinical • P2 data • Tumor mutational burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SIRPA (Signal Regulatory Protein Alpha)
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TP53 mutation • U2AF1 mutation
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azacitidine • timdarpacept (IMM01)
1year
The novel high-affinity humanized antibody IMM40H targets CD70, eliminates tumors via Fc-mediated effector functions, and interrupts CD70/CD27 signaling. (PubMed, Front Oncol)
In vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively...A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt's lymphoma Raji and renal carcinoma cell A498 tumor models...IMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling.
Journal • IO biomarker
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CD70 (CD70 Molecule) • CD27 (CD27 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
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CD70 expression • CD27 expression
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cusatuzumab (ARGX-110) • IMM40H • timdarpacept (IMM01)
over1year
New P1 trial
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PD-L1 (Programmed death ligand 1) • TNFRSF8 (TNF Receptor Superfamily Member 8)
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timdarpacept (IMM01)
over1year
Preclinical development of a monoclonal antibody targeting CD70 as cancer immunotherapy (AACR 2023)
Notably, in a U266 multiple myeloma model, IMM40H, at the dose of 0.3 mg/kg, completely inhibited tumor growth in a way that therapeutic effects appeared significantly earlier than that of cusatuzumab at a higher dose of 1 mg/kg. Therapeutic effects of IMM40H at the dose of 3 mg/kg also appeared earlier than that of bortezomib at the dose of 0.5 mg/kg. Interestingly, combination of IMM40H and IMM01 (a SIRPα-IgG1 Fc fusion protein targeting CD47) generated significant therapeutic synergy in models of A498 kidney cancer and Raji lymphoma...IND of IMM40H has been approved in China and US. This antibody is now in a phase 1 study in patients with advanced malignancies expressing CD70.
Preclinical • IO biomarker
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CD47 (CD47 Molecule) • CD70 (CD70 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
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CD70 expression
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bortezomib • cusatuzumab (ARGX-110) • IMM40H • timdarpacept (IMM01)
over1year
Preclinical development of a novel bispecific mAb-Trap fusion protein, IMM2520, targeting both PD-L1 and CD47 as cancer immunotherapy (AACR 2023)
Interestingly, IMM2520 demonstrated a potent and significantly higher anti-tumor activities than IMM01 (a SIRPα-Fc fusion protein) and IMM2505 (also a CD47XPD-L1 mAb-Trap, but the variable region sequence of this PD-L1 antibody is identical to atezolizumab). In another in vivo efficacy study with MC38-hCD47/hPD-L1 colon cancer model, IMM2520 demonstrated a significant anti-tumor activity in a dose-dependent manner at doses between 2 mg/kg to 20 mg/kg. Given its potent preclinical anti-tumor activity as well as the favorable safety profile, IMM2520 may serve as a potent immunotherapy for multiple cancer types by targeting PD-L1 and CD47 on tumor cells.
Preclinical
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SIRPA (Signal Regulatory Protein Alpha)
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PD-L1 expression
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Tecentriq (atezolizumab) • IMM2505 • IMM2520 • timdarpacept (IMM01)
2years
SIRPα-Fc fusion protein IMM01 exhibits dual anti-tumor activities by targeting CD47/SIRPα signal pathway via blocking the "don't eat me" signal and activating the "eat me" signal. (PubMed, J Hematol Oncol)
Finally, IMM01 demonstrated a favorable safety profile with no human RBC binding activity or hemagglutination induction. IMM01 inhibits the growth of tumor cells by the following three possible mechanisms: (1) directly activating macrophages to phagocytize tumor cells; (2) activated macrophages degrade phagocytized tumor cells and present tumor antigens to T cells through MHC molecules to activate T cells; (3) activated macrophages can convert "cold tumors" into "hot tumors" and increase the infiltration of immune cells through chemotaxis by secreting some cytokines and chemokines.
Journal • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • SIRPA (Signal Regulatory Protein Alpha)
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timdarpacept (IMM01)