Delving into the Latest Updates on Timdarpacept with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

Recombinant human signal regulating protein alpha (SIRPalpha) fragment crystallizable (Fc)-fusion protein (ImmuneOnco)

+ [3]

Target

CD47

Action

inhibitors

Mechanism

CD47 inhibitors(Cluster of differentiation 47 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [8]

Active Indication

Chronic Myelomonocytic LeukemiaClassical Hodgkin's LymphomaRefractory Classic Hodgkin Lymphoma+ [13]

Inactive Indication

Acute Promyelocytic LeukemiaExtranodal NK-T-Cell LymphomaMultiple Myeloma+ [5]

Originator Organization

ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup

Active Organization

ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Sequence Code 942330967

Source: *****

This study is an IIT clinical study to evaluate the efficacy and safety of IMC-001 for injection on improved atherosclerotic plaque stability in patients receiving optimal medical therapy after a recent acute coronary syndrome (ACS). The study was a single-center, simple randomized, controlled study, in which the experimental group was given IMC-001 and the best drug treatment, and 8 subjects were included, and the control group was given only the best drug treatment, and 6 subjects were included.

Start Date19 Feb 2025

Sponsor / Collaborator

ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup

[+2]

NCT06647862

/ RecruitingPhase 3

A Randomized, Controlled, Double-Blind, Multicenter, Phase Ⅲ Study to Evaluate the Efficacy and Safety of IMM01 (Timdarpacept) in Combination With Azacitidine in Patients With Newly Diagnosed Chronic Myelomonocytic Leukemia (CMML1-2)

This study is a randomized, controlled, double-blind, multicenter, phase Ⅲ clinical study to evaluate the efficacy of IMM01(timdarpacept) in combination with azacitidine versus placebo in combination with azacitidine in patients with newly diagnosed chronic leukemia monocytic (CMML1-2).Primary endpoint are Complete remission rate and Overall survival.

Start Date11 Nov 2024

Sponsor / Collaborator

ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup

CTR20243920

/ RecruitingPhase 3

一项评价注射用IMM01（替达派西普）联合阿扎胞苷治疗初治的慢性粒单核细胞白血病（CMML1-2）患者的随机、对照、双盲、多中心Ⅲ期临床研究

[Translation] A randomized, controlled, double-blind, multicenter phase III clinical study evaluating IMM01 (tedapacept) for injection combined with azacitidine in the treatment of patients with previously untreated chronic myelomonocytic leukemia (CMML1-2)

1.由独立评审委员会（IRC）基于IWG2006 MDS 疗效评价标准评估初治的CMML1-2 患者的完全缓解率（CR 率）。 2.评估注射用IMM01 联合阿扎胞苷与安慰剂联合AZA 治疗初治的CMML1-2 患者的总生存期（OS）。

[Translation]

1. The independent review committee (IRC) evaluated the complete remission rate (CR rate) of CMML1-2 patients with initial treatment based on the IWG2006 MDS efficacy evaluation criteria. 2. Evaluate the overall survival (OS) of CMML1-2 patients with initial treatment treated with IMM01 for injection combined with azacitidine and placebo combined with AZA.

Start Date30 Oct 2024

Sponsor / Collaborator

ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup

100 Clinical Results associated with Timdarpacept

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100 Translational Medicine associated with Timdarpacept

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100 Patents (Medical) associated with Timdarpacept

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5

Literatures (Medical) associated with Timdarpacept

01 Nov 2004·Journal of Immunological Methods

Binding of a monoclonal antibody positively correlates with bioactivity of the F4 fimbrial adhesin FaeG associated with post-weaning diarrhoea in piglets.

Article

Author: Goddeeris, B. M. ; Cox, E. ; Verdonck, F. ; Snoeck, V.

Piglets are susceptible to F4 (K88)+ enterotoxigenic Escherichia coli (ETEC)-induced neonatal and post-weaning diarrhoea. The F4 fimbriae are composed of some minor subunits and the major subunit FaeG that also constitutes the adhesin. Parenteral vaccination of sows with an F4-containing vaccine protects the suckling piglets against neonatal F4+ ETEC-induced diarrhoea, but no commercial (mucosal) vaccine exists against F4+ ETEC-induced weaning diarrhoea. To develop a vaccine, a bioactive F4-receptor (F4R) binding FaeG molecule is required that binds to the F4R following oral immunization and induces a FaeG-specific immune response. The present study reports the altered binding of the FaeG-specific monoclonal antibody IMM01 with bioactive versus non-bioactive F4 fimbrial adhesin FaeG. The correlation of altered IMM01 binding with altered FaeG bioactivity permits the use of an IMM01-based ELISA as a fast, specific and sensitive in vitro selection for potent F4 or (recombinant) FaeG antigen formulations, useful in an F4+ ETEC vaccine.

Frontiers in Immunology

DNp73 enhances tumor progression and immune evasion in multiple myeloma by targeting the MYC and MYCN pathways

Article

Author: Lyu, Rui ; Sun, Xiyue ; Sun, Hao ; Tian, Wenzhi ; Feng, Fangshuo ; Fang, Teng ; Wang, Tingyu ; Gong, Lixin ; Xu, Jie ; Gong, Dasen ; Xu, Yan ; Hao, Mu ; Wang, Wentian ; Yu, Zhen ; An, Gang ; Liu, Lanting ; Qiu, Lugui

IntroductionMultiple myeloma (MM) is an incurable hematological malignancy with high chromosome instability and heavy dependence on the immunosuppressive bone marrow microenvironment. P53 mutations are adverse prognostic factors in MM; however, clinically, some patients without P53 mutations also exhibit aggressive disease progression. DNp73, an inhibitor of TP53 tumor suppressor family members, drives drug resistance and cancer progression in several solid malignancies. Nevertheless, the biological functions of DNp73 and the molecular mechanisms in myelomagenesis remain unclear.MethodsThe effects of DNp73 on proliferation and drug sensitivity were assessed using flow cytometry and xenograft models. To investigate the mechanisms of drug resistance, RNA-seq and ChIP-seq analyses were performed in MM cell lines, with validation by Western blot and RT-qPCR. Immunofluorescence and transwell assays were used to assess DNA damage and cell invasion in MM cells. Additionally, in vitro phagocytosis assays were conducted to confirm the role of DNp73 in immune evasion.ResultsOur study found that activation of NF-κB-p65 in multiple myeloma cells with different p53 mutation statuses upregulates DNp73 expression at the transcriptional level. Forced expression of DNp73 promoted aggressive proliferation and multidrug resistance in MM cells. Bulk RNA-seq analysis was conducted to assess the levels of MYCN, MYC, and CDK7. A ChIP-qPCR assay was used to reveal that DNp73 acts as a transcription factor regulating MYCN gene expression. Bulk RNA-seq analysis demonstrated increased levels of MYCN, MYC, and CDK7 with forced DNp73 expression in MM cells. A ChIP-qPCR assay revealed that DNp73 upregulates MYCN gene expression as a transcription factor. Additionally, DNp73 promoted immune evasion of MM cells by upregulating MYC target genes CD47 and PD-L1. 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.DiscussionIn summary, our study demonstrated for the first time that the p53 family member DNp73 remarkably induces proliferation, drug resistance, and immune escape of myeloma cells by directly targeting MYCN and regulating the MYC pathway. The oncogenic function of DNp73 is independent of p53 status in MM cells. These data contribute to a better understanding of the function of TP53 and its family members in tumorigenesis. 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.

Frontiers in Immunology

Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38

Article

Author: Tu, Xiaoping ; Zhang, Ruliang ; Li, Guanghui ; Zhao, Gui ; Wang, Kaili ; Chen, Dianze ; Guo, Huiqin ; Peng, Liang ; Liu, Dandan ; Zhang, Wei ; Sun, Nana ; Li, Tengfei ; Li, Song ; Tian, Wenzhi ; Zhang, Li ; Liu, Sijin ; Yang, Yanan ; Bai, Xing ; Yang, Chunmei

BackgroundCD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs).MethodsFive suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 “mAb-trap” platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems.ResultsUsing hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a “mAb-trap” platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. 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). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605–26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605–12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605–12C10 efficiently eradicated all established tumors in all mice.ConclusionA 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.

100 Deals associated with Timdarpacept

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Myelomonocytic Leukemia	Phase 3	China	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	30 Oct 2024
Classical Hodgkin's Lymphoma	Phase 3	-	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	01 Jun 2024
Refractory Classic Hodgkin Lymphoma	Phase 3	-	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	01 Jun 2024
Myelodysplastic Syndromes	Phase 3	China	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	-
Solid tumor	Phase 3	China	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	-
Acute Promyelocytic Leukemia	Phase 2	China	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	18 Oct 2021
Extranodal NK-T-Cell Lymphoma	Phase 2	China	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	18 Oct 2021
Multiple Myeloma	Phase 2	China	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	18 Oct 2021
Recurrent Myelodysplastic Syndrome	Phase 2	China	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	18 Oct 2021
Refractory Myelodysplastic Syndrome	Phase 2	China	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	18 Oct 2021

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Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05833984 (ESMO2024) Manual	Phase 2	Classical Hodgkin's Lymphoma	33	Timdarpacept tislelizumab	(fqvowahcoj) = qmjwjsjciy qzflydfmnx (bjfvyqopxu ) View more	Positive	15 Sep 2024
NCT05140811 (ESMO2024) Manual	Phase 2	Chronic Myelomonocytic Leukemia First line	22	Timdarpaceptazacitidine	(zvanxdghqb) = blztxdeoht ohvzaajnkq (gwutjcdajm ) View more	Positive	13 Sep 2024
NCT05140811 (phase 2 study of IMM01 combined with azacitidine (AZA), ASCO2024)	Phase 2	High Risk Myelodysplastic Syndrome First line DNMT3A \| ASXL1 \| U2AF1 ... View more	57	IMM01 + Azacitidine	ioyomrycab(tzsgqhnudu) = only 1.8% cvcmnxfdts (iocebjjrqo ) View more	Positive	24 May 2024
NCT05833984 (IMM01-04, ASH2023)	Phase 2	Classical Hodgkin's Lymphoma	32	IMM01 plus tislelizumab	(wfybmvahxx) = tabbecvenh djhwvgayft (krxalsvxsa ) View more	Positive	10 Dec 2023
NCT05140811 (ASH2023)	Phase 2	High Risk Myelodysplastic Syndrome First line	54	IMM01 + Azacitidine	(xvxbviwvcp) = leukopenia (81.5%), thrombocytopenia (68.5%), neutropenia (66.7%), lymphopenia (57.4%), anemia (44.4%) and infection(16.7%) wxvmgfjrpf (obycefqmci ) View more	-	09 Dec 2023
NCT05140811 (ASH2023)	Phase 2	Chronic Myelomonocytic Leukemia First line	24	IMM01 + AZA	(fgfjeklhnz) = 25.0% bccqflruow (oillnsfmdq ) View more	-	09 Dec 2023
CTR20220791 (ASCO 12023 \| ASCO 22023) Manual	Phase 1/2	HR-positive/HER2-low Solid Tumors \| Lymphoma	14	Tislelizumab+IMM01	(hiazywvoep) = ofliefjcif jxmeuqbogi (rnccwcegdl ) View more	Positive	26 May 2023

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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