The purpose of the study is to explore the safety and efficacy of recombinant CD19xCD3 double antibody (A-319) in active/refractory systemic lupus erythematosus (SLE).

Start Date20 Jul 2024

Sponsor / Collaborator

Wuhan Xiehe Hospital Tower

[+1]

ChiCTR2100054600 / RecruitingPhase 1IIT

A-319 (a bispecific T cell engager) In Refractory/Relapse B-cell Acute Lymphoblastic Leukemia: a multicenter, open-label and dose-escalating phase I trial

Start Date06 Dec 2021

Sponsor / Collaborator-

CTR20210368 / RecruitingPhase 1

评价A-319治疗难治或者复发的前体B细胞急性淋巴细胞白血病的多中心、开放、剂量递增的I期临床研究

[Translation] A multicenter, open-label, dose-escalation phase I clinical study evaluating A-319 in the treatment of refractory or relapsed B-cell precursor acute lymphoblastic leukemia

评价A-319治疗难治或者复发的前体B细胞急性淋巴细胞白血病的安全性和耐受性。确定难治或者复发的前体B细胞急性淋巴细胞白血病对A-319的最大耐受剂量（MTD）及剂量限制性毒性（DLT）。

[Translation]

To evaluate the safety and tolerability of A-319 in the treatment of refractory or relapsed B-cell precursor acute lymphoblastic leukemia. To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of A-319 in refractory or relapsed B-cell precursor acute lymphoblastic leukemia.

Start Date07 Jun 2021

Sponsor / Collaborator

Evive Biotech Co. Ltd.

100 Clinical Results associated with A-319

100 Translational Medicine associated with A-319

100 Patents (Medical) associated with A-319

Literatures (Medical) associated with A-319

01 Feb 2022·Frontiers of medicineQ3 · MEDICINE

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific antibodies against B-cell acute lymphoblastic leukemia: targeted immunotherapy for acute lymphoblastic leukemia

Q3 · MEDICINE

Article

Author: Zhou, Yuebo ; Xu, Wenqian ; Wang, Jin ; Wang, Sisi ; Peng, Lijun ; Leung, Stewart ; Mi, Jian-Qing ; Zhu, Ziyan ; Yan, Xiaoqiang ; Kong, Yushan

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.

15 May 2000·Journal of virologyQ2 · MEDICINE

Variable Sensitivity of CCR5-Tropic Human Immunodeficiency Virus Type 1 Isolates to Inhibition by RANTES Analogs

Q2 · MEDICINE

Article

Author: Albright, Jamie L. ; Collins, Kalonji R. ; Marozsan, Andre J. ; Arts, Eric J. ; Offord, Robin E. ; Hartley, Oliver ; Torre, Vincent S. ; Quiñones-Mateu, Miguel E.

Aminooxypentane (AOP)-RANTES efficiently and specifically blocks entry of non-syncytium-inducing (NSI), CCR5-tropic (R5) human immunodeficiency virus type 1 (HIV-1) into host cells. Inhibition appears to be mediated by increased intracellular retention of the CCR5 coreceptor- AOP-RANTES complex and/or competitive binding of AOP-RANTES with NSI R5 HIV-1 isolates for CCR5. Although AOP-RANTES and other β-chemokine analogs are potent inhibitors, the extreme heterogeneity of the HIV-1 envelope glycoproteins (gp120 and gp41) and variable coreceptor usage may affect the susceptibility of variant HIV-1 strains to these drugs. Using the same peripheral blood mononuclear cells (PBMC) with all isolates, we observed a significant variation in AOP-RANTES inhibition of 13 primary NSI R5 isolates; 50% inhibitory concentrations (IC 50 ) ranged from 0.04 nM with HIV-1 A-92RW009 to 1.3 nM with HIV-1 B-BaL . Experiments performed on the same isolate (HIV-1 B-BaL ) with PBMC from different donors revealed no isolate-specific variation in AOP-RANTES IC 50 values but did show a considerable difference in virus replication efficiency. Exclusive entry via the CCR5 coreceptor by these NSI R5 isolates suggests that variable inhibition by AOP-RANTES is not due to alternative coreceptor usage but rather differential CCR5 binding. Analysis of the envelope V3 loop sequence linked a threonine or arginine at position 319 (numbering based on the HXB2 genome) with AOP-RANTES resistance. With the exception of one isolate, A319 was associated with increased sensitivity to AOP-RANTES inhibition. Distribution of AOP-RANTES IC 50 values with these isolates has promoted ongoing screens for new CCR5 agonists that show broad inhibition of HIV-1 variants.

Materials (Basel, Switzerland)

Casting and Characterization of A319 Aluminum Alloy Reinforced with Graphene Using Hybrid Semi-Solid Stirring and Ultrasonic Processing

Article

Author: Ravindran, Comondore ; Emadi, Payam ; Andilab, Bernoulli

Advanced metallurgical processing techniques are required to produce aluminum matrix composites due to the tendency of the reinforcement particles to agglomerate. In this study, graphene nano-platelet reinforcement particles were effectively incorporated into an automotive A319 aluminum alloy matrix using a liquid metallurgical route. Due to its low density, it is a highly difficult task to produce an aluminum matrix composite reinforced with graphene. Hence, this study explored a novel approach to prevent particle floating to the melt surface and agglomeration. This was achieved via a hybrid semi-solid stirring of A319, followed by ultrasonic treatment of the liquid melt using a sonication probe. The microstructure and graphene particles were characterized using optical microscopy and scanning electron microscopy. Furthermore, the interfacial products produced with the incorporation of graphene in liquid aluminum were analyzed with X-ray diffraction. The tensile test results exhibited 10, 11 and 32% improvements in ultimate tensile strength, yield strength, and ductility of A319 reinforced with 0.05 wt.% addition of graphene. Analysis of strengthening models demonstrated primary contribution from Hall-Petch followed by CTE mismatch and load bearing mechanism. The results from this research enable the potential for using cost-effective, efficient and simple liquid metallurgy methods to produce aluminum reinforced graphene composites with improved mechanical properties.

News (Medical) associated with A-319

07 Jun 2023

·www.biospace.com

ITabMed announces the IND approval from NMPA for A-337, a CD3-activating bispecific antibody targeting EpCAM to treat solid tumors

SHANGHAI--(BUSINESS WIRE)-- ITabMed Ltd., a clinical-stage biotech company in China, announced the IND approval from China National Medical Products Administration (NMPA) for A-337, a CD3-activating bi-specific antibody targeting EpCAM. This is a “Phase I, Open-label, Dose-escalation Study to Evaluate the Safety and Pharmacokinetics of A-337 in patients with advanced solid tumors”. EpCAM is one of the earliest identified tumor-associated antigens (TAA) and up-regulated and over-expressed in many solid tumors. A-337 is the second immune oncology product generated by the immunotherapy antibody (iTab™) platform to enter clinical development in China. iTab™ is a T cell engager (TCE) platform for human CD3-activating bi- and tri-specific antibodies targeting tumor associated antigens (TAA). A-337 was designed with two EpCAM targeting fragments (EpCAM x EpCAM x CD3) with significantly enhanced biological properties and improved safety pro to the competitor’s products including EpCAM x CD3 TCE, EpCAM x CD3 bispecific antibodies. In preclinical studies, A-337 demonstrated potent anti-tumor activity, favorable pharmacokinetics, and a significantly improved safety window. Dr. Xiao Qiang Yan, Chairman and CEO of ITabMed Ltd commented “A-337 is our second immunotherapeutic antibody entering clinical development in China. A-337 has the similar structural design as A-319 which is in phase I development to treat liquid tumors. Two phase I studies of A-319 are being conducted in patients with relapsed and refractory B cell acute lymphoblastic leukemia (r/r-B-ALL) and in patients with relapsed and refractory non-Hodgkin’s lymphoma (r/r-NHL). The preliminary results of the two phase I studies have demonstrated an excellent safety pro promising anti-tumor responses of A-319 during dose-escalation. Likewise, we believe that A-337 has enormous potential to treat metastatic solid tumors due to its improved safety pro its unique format design. The IND approval demonstrates our continued effort in “innovating for life” and to cure many cancer patients with our innovative medicines”. About iTab™ platform ITabMed has been developing the iTAb™ (immunotherapy antibody) platform for more than a decade. iTAb™ generates bi- and tri-specific antibodies that bind to the CD3 molecule on human T cells, and simultaneously bind to TAAs or TSA on a tumor cell. The formation of a synapse between the tumor cell and the T cell linked by the antibody leads to the activation of the T cells, and the release of mediators lysing the tumor cells. These T cell engaging bi- and tri-specific antibodies can drive the expansion of T cells, rendering T cells as serial killers of tumor cells. The iTAb™ antibodies are very potent and are manufactured in CHO cells in serum-free conditions. The iTAb drug products are very stable in liquid formulation with extra-long stability profile. About ITabMed Ltd. iTabMed Ltd. is a privately held and a clinical-stage biotech company located in Shanghai, China, focusing on development of innovative biological therapies to cure many cancer patients worldwide. For more information on please visit View source version on businesswire.com: Contacts ITabMed Ltd. Hanyang.chen@itabmed.com +86 18917873969 Source: ITabMed Ltd. View this news release online at:

ImmunotherapyPhase 1INDClinical Result

01 Dec 2021

·www.biospace.com

ITabMed Completes Series A-round Financing after Spin-off

Dec. 1, 2021 09:00 UTC SHANGHAI--(BUSINESS WIRE)-- ITabMed today announced it has completed the spin-off iTAb™ (immunotherapy antibody) platform and closed $20M Series A-round financing. Earlier in this year, Evive Biotech (formerly Generon BioMed Ltd) and Dr. Xiaoqiang Yan formed a joint venture and established ITabMed Ltd. with the full support from Evive and its shareholders. The JV company will focus on continued development of products derived from iTAb™ platform. The iTAb™ platform has been optimized over the last 10 years aiming to improve the clinical safety windows and to overcome the manufacturing-related challenges. The patented iTAb™ platform will allow the company to generate bi- or tri-specific T cell engagers. Two leading products, A-319 and A-337 are already in phase I clinical development. Multiple iTAb drug candidates are at different stages of preclinical development. ITabMed recently closed series A-round financing, co-led by 3E Bioventures Capital and Yonjin Capital, and joined by Binhai Venture Capital. 3E Bioventures and Yonjin Capital are both active biotech investors, with a focus on innovation, with a track-record of success and good reputation. ITabMed founder and CEO, Dr. Yan said: “We sincerely thank series A-round investors for supporting our continued efforts to bring safe and efficacious products to patients. We share the same mission ‘innovating for life’ and wish to grow together. We also thank the shareholders of Evive Biotech for their help and support.” Dr. Karen Liu, partner of 3E Bioventures commented: “Dr. Yan is a successful serial entrepreneur and a veteran drug developer. He is also a great scientist with a passion for innovation. T-cell engager is an important therapeutic approach in developing immune therapies. There are many drug candidates under development globally, but very few are approved because of issues relating to safety. We see the unique safety advantages of iTAb products and hope they will translate into real human drugs soon.” Mr. Wen Chen said: “We are confident in the ITabMed team led by Dr. Yan. They experienced a 20-year path in new drug R&D in China with an outstanding track-record. We are committed to support the company and to bring new immunotherapy drugs to cancer patients.” About ITabMed ITabMed is a clinical-stage biotech company located in Shanghai, China. The company was founded in 2020 and is registered in Lin Gang Sci-Tech City, Shanghai. It was a spin-off entity from the former “Generon BioMed Ltd.”. The company is focused on immunotherapy drug research and development to treat cancer. ( ) View source version on businesswire.com: Contacts Hanshen Xu Tel: +86 21 2090 7805 hanshen.xu@itabmed.com Source: ITabMed View this news release online at:

AntibodyImmunotherapy

100 Deals associated with A-319

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Systemic Lupus Erythematosus	Phase 1	CN	ITabMed Co., Ltd.	20 Jul 2024
Leukemia	Phase 1	CN	ITabMed Co., Ltd.	22 Aug 2022
Lymphoma	Phase 1	CN	ITabMed Co., Ltd.	22 Aug 2022
Pre B-cell acute lymphoblastic leukemia	Phase 1	CN	Evive Biotech Co. Ltd.	07 Jun 2021
B-cell lymphoma recurrent	Phase 1	-	Evive Biotech	15 Sep 2019
B-cell lymphoma refractory	Phase 1	-	Evive Biotech	15 Sep 2019
B-Cell Lymphoma	Phase 1	CN	Evive Biotech Co. Ltd.	10 Sep 2019
B-Cell Leukemia	IND Application	CN	Evive Biotech Co. Ltd.	08 Sep 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06400537 (ACR2024) Manual	Phase 1	Systemic Lupus Erythematosus	6	A-319	nhvxwcwwag(scddtqhajt) = All patients had grade I-II fever (drug-related) during the treatment. No other drug-related adverse events were observed. ncdhoucijd (infpmqupdu ) View more	Positive	24 Oct 2024

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