This is a Phase 1, multi-center, open-label study of TRPH-222 monotherapy in subjects with relapsed and/or refractory B-cell NHL. The study will be conducted in two Stages: Dose-Escalation, Dose-Expansion.

Start Date15 Oct 2018

Sponsor / Collaborator

Triphase Research and Development III Corp.

100 Clinical Results associated with TRPH-222

100 Translational Medicine associated with TRPH-222

100 Patents (Medical) associated with TRPH-222

Literatures (Medical) associated with TRPH-222

01 Mar 2024·Molecular and Cellular Biochemistry

Production and characterization of a camelid single domain anti-CD22 antibody conjugated to DM1

Article

Author: Davami, Fatemeh ; Behdani, Mahdi ; Ziaei, Vahab ; Habibi-Anbouhi, Mahdi ; Azarian, Bahareh ; Ghassempour, Alireza ; Dabiri, Hamed

Antibody drug conjugates (ADCs) with twelve FDA approved drugs, known as a novel category of anti-neoplastic treatment created to merge the monoclonal antibody specificity with cytotoxicity effect of chemotherapy.However, despite many undeniable advantages, ADCs face certain problems, including insufficient internalization after binding, complex structures and large size of full antibodies especially in targeting of solid tumors.Camelid single domain antibody fragments (Nanobody) offer solutions to this challenge by providing nanoscale size, high solubility and excellent stability, recombinant expression in bacteria, in vivo enhanced tissue penetration, and conjugation advantages.Here, an anti-human CD22 Nanobody was expressed in E.coli cells and conjugated to Mertansine (DM1) as a cytotoxic payload.The anti-CD22 Nanobody was expressed and purified by Ni-NTA resin.DM1 conjugated anti-CD22 Nanobody was generated by conjugation of SMCC-DM1 to Nanobody lysine groups.The conjugates were characterized using SDS-PAGE and Capillary electrophoresis (CE-SDS), RP-HPLC, and MALDI-TOF mass spectrometry.Addnl., flow cytometry anal. and a competition ELISA were carried out for binding evaluation.Finally, cytotoxicity of conjugates on Raji and Jurkat cell lines was assessed.The drug-to-antibody ratio (DAR) of conjugates was calculated 2.04 using UV spectrometry.SDS-PAGE, CE-SDS, HPLC, and mass spectrometry confirmed conjugation of DM1 to the Nanobody.The obtained results showed the anti-CD22 Nanobody cytotoxicity was enhanced almost 80% by conjugation with DM1.The binding of conjugates was similar to the non-conjugated anti-CD22 Nanobody in flow cytometry experimentsConcludingly, this study successfully suggest that the DM1 conjugated anti-CD22 Nanobody can be used as a novel tumor specific drug delivery system.

01 Apr 2023·Glycoconjugate Journal

Improved synthesis of CD22-binding sialosides and its application for further development of potent CD22 inhibitors

Article

Author: Suganuma, Yuki ; Tsubata, Takeshi ; Ando, Hiromune ; Takematsu, Hiromu ; Kiso, Makoto ; Ishida, Hideharu ; Imamura, Akihiro

CD22, one of the sialic acid-binding immunoglobulin-like lectins (Siglecs), regulates B lymphocyte signaling via its interaction with glycan ligands bearing the sequence Neu5Ac/Gcα(2→6)Gal. We have developed the synthetic sialoside GSC-718 as a ligand mimic for CD22 and identified it as a potent CD22 inhibitor. Although the synthesis of CD22-binding sialosides including GSC-718 has been reported by our group, the synthetic route was unfortunately not suitable for large-scale synthesis. In this study, we developed an improved scalable synthetic procedure for sialosides which utilized 1,5-lactam formation as a key step. The improved procedure yielded sialosides incorporating a series of aglycones at the C2 position. Several derivatives with substituted benzyl residues as aglycones were found to bind to mouse CD22 with affinity comparable to that of GSC-718. The new procedure developed in this study affords sialosides in sufficient quantities for cell-based assays, and will facilitate the search for promising CD22 inhibitors that have therapeutic potential.

01 Jan 2018·Molecular Cancer Therapeutics

CAT-02-106, a Site-Specifically Conjugated Anti-CD22 Antibody Bearing an MDR1-Resistant Maytansine Payload Yields Excellent Efficacy and Safety in Preclinical Models

Article

Author: Kudirka, Romas ; Zmolek, Wesley ; Drake, Penelope M. ; McFarland, Jesse M. ; Barfield, Robyn M. ; Huang, Betty C.B. ; Kim, Yun Cheol ; Bañas, Stefanie ; Rabuka, David ; Carlson, Adam

AbstractHematologically derived tumors make up ∼10% of all newly diagnosed cancer cases in the United States. Of these, the non-Hodgkin lymphoma (NHL) designation describes a diverse group of cancers that collectively rank among the top 10 most commonly diagnosed cancers worldwide. Although long-term survival trends are improving, there remains a significant unmet clinical need for treatments to help patients with relapsed or refractory disease, one cause of which is drug efflux through upregulation of xenobiotic pumps, such as MDR1. CD22 is a clinically validated target for the treatment of NHL, but no anti-CD22 agents have yet been approved for this indication. Recent approval of an anti-CD22 antibody–drug conjugate (ADC) for the treatment of relapsed/refractory ALL supports the rationale for targeting this protein. An opportunity exists for a next-generation anti-CD22 antibody–drug conjugate (ADC) to address unmet medical needs in the relapsed/refractory NHL population. We describe a site-specifically conjugated antibody–drug conjugate, made using aldehyde tag technology, targeted against CD22 and bearing a noncleavable maytansine payload that is resistant to MDR1-mediated efflux. The construct was efficacious against CD22+ NHL xenografts and could be repeatedly dosed in cynomolgus monkeys at 60 mg/kg with no observed significantly adverse effects. Exposure to total ADC at these doses (as assessed by AUC0-inf) indicated that the exposure needed to achieve efficacy was below tolerable limits. Together, the data suggest that this drug has the potential to be used effectively in patients with CD22+ tumors that have developed MDR1-related resistance to prior therapies. Mol Cancer Ther; 17(1); 161–8. ©2017 AACR.

100 Deals associated with TRPH-222

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Follicular Lymphoma	Phase 1	US	Triphase Research and Development III Corp.	15 Oct 2018
Follicular Lymphoma	Phase 1	CA	Triphase Research and Development III Corp.	15 Oct 2018
Follicular Lymphoma	Phase 1	US	Triphase Accelerator Corp.	15 Oct 2018
Follicular Lymphoma	Phase 1	CA	Triphase Accelerator Corp.	15 Oct 2018
Mantle-Cell Lymphoma	Phase 1	CA	Triphase Accelerator Corp.	15 Oct 2018
Mantle-Cell Lymphoma	Phase 1	US	Triphase Accelerator Corp.	15 Oct 2018
Marginal Zone B-Cell Lymphoma	Phase 1	US	Triphase Accelerator Corp.	15 Oct 2018
Marginal Zone B-Cell Lymphoma	Phase 1	CA	Triphase Research and Development III Corp.	15 Oct 2018
Marginal Zone B-Cell Lymphoma	Phase 1	CA	Triphase Accelerator Corp.	15 Oct 2018
Marginal Zone B-Cell Lymphoma	Phase 1	US	Triphase Research and Development III Corp.	15 Oct 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03682796 (TRPH-222-100, EHA2022) Manual	Phase 1	B-cell lymphoma recurrent	32	TRPH 222 (NHL)	(imxebafbeh) = udsigvxkjd qlsoaenjip (zmsreaxlyx ) View more	Positive	12 May 2022
NCT03682796 (TRPH-222-100, EHA2022) Manual	Phase 1	B-cell lymphoma recurrent	32	TRPH 222 (FL)	(bgqypajhjm) = oitfovtdwu spuatinfxa (qgwguzwmqn ) View more	Positive	12 May 2022
NCT03682796 (ASH 12020 \| ASH 22020) Manual	Phase 1	B-cell lymphoma refractory	22	TRPH-222	(tnrjbbsqlk) = Two DLTs (Grade 3 and 4 transaminase elevations; one each at 4.2 and 10 mg/kg) have occurred tuqsdmvidg (aipukazvfg ) View more	Positive	05 Nov 2020

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