Delving into the Latest Updates on Recombinant PD-1/TIM3 bispecific antibody(L&L vision biopharmaceuticals) with Synapse

Overview

Basic Info

Drug Type

Bispecific antibody

Synonyms

Target

PD-1 x TIM3

Action

inhibitors

Mechanism

PD-1 inhibitors(Programmed cell death protein 1 inhibitors), TIM3 inhibitors(Hepatitis A virus cellular receptor 2 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [2]

Active Indication

Metastatic Solid TumorAdvanced cancerAdvanced Malignant Solid Neoplasm+ [3]

Inactive Indication-

Originator Organization

L&L Biopharma Co., Ltd.

Active Organization

L&L Biopharma Co., Ltd.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

Login to view timeline

主要目的： 1.在晚期实体瘤成人患者中，评估LB1410联合LB4330的安全性和耐受性。 2.确定剂量递增阶段LB1410联合LB4330最大耐受剂量（MTD）和/或II期推荐剂量（RP2D）。 3.评估LB1410联合LB4330的抗肿瘤疗效。次要目的： 1.评估LB1410联合LB4330在晚期实体瘤患者中的药代动力学（PK）特征。 2.评价LB1410联合LB4330的免疫原性（ADA）。 3.评价LB1410联合LB4330的ADA与PK、安全性和疗效间的关系。 4.检测基线期采集的肿瘤组织中PD-L1、TIM3、Claudin18.2（按肿瘤类型细分检测项目）。探索性目的：？LB1410联合LB4330药效学或潜在生物预测标记物：淋巴细胞亚群（含CD8+ T细胞、CD4+ T细胞等），细胞因子。

[Translation]

Primary objectives: 1. To evaluate the safety and tolerability of LB1410 combined with LB4330 in adult patients with advanced solid tumors. 2. To determine the maximum tolerated dose (MTD) and/or the recommended dose (RP2D) of LB1410 combined with LB4330 in the dose escalation phase. 3. To evaluate the anti-tumor efficacy of LB1410 combined with LB4330. Secondary objectives: 1. To evaluate the pharmacokinetic (PK) characteristics of LB1410 combined with LB4330 in patients with advanced solid tumors. 2. To evaluate the immunogenicity (ADA) of LB1410 combined with LB4330. 3. To evaluate the relationship between ADA and PK, safety and efficacy of LB1410 combined with LB4330. 4. To detect PD-L1, TIM3, and Claudin18.2 in tumor tissues collected at baseline (test items are subdivided by tumor type). Exploratory objectives: ? Pharmacodynamic or potential biological predictive markers of LB1410 combined with LB4330: lymphocyte subsets (including CD8+ T cells, CD4+ T cells, etc.), cytokines.

Start Date28 Jun 2024

Sponsor / Collaborator

L&L Biopharma Co., Ltd.

NCT06468358

/ RecruitingPhase 1/2

A Phase Ib/II, Open, Dose-escalation and Expansion Study to Evaluate LB1410 in Combination With LB4330 in Patients With Advanced or Metastatic Solid Tumors

This is a phase Ib/II, open, dose-escalation and expansion study of an anti-PD1/TIM3 bispecific antibody，LB1410 in combination with an anti-Claudin18.2/IL-10 fusion protein, LB4330 in patients with advanced or metastatic solid tumors.

Start Date19 Jun 2024

Sponsor / Collaborator

L&L Biopharma Co., Ltd.

[+1]

CTR20220704

/ RecruitingPhase 1

评价注射用LB1410在晚期恶性肿瘤患者中的安全性、耐受性、药代动力学、药效学和免疫原性的多中心、开放的Ⅰ期临床研究

[Translation] A multicenter, open-label Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of LB1410 for injection in patients with advanced malignant tumors

主要研究目的：（1）评价LB1410在晚期恶性肿瘤患者中的安全性和耐受性；（2）确定LB1410的最大耐受剂量（MTD）和/或Ⅱ期临床试验推荐剂量（RP2D）；次要研究目的：（1）评价LB1410的药代动力学（PK）；（2）初步评价LB1410在晚期恶性肿瘤患者中的抗肿瘤活性；（3）评价LB1410的免疫原性；探索性目的：探索LB1410临床活性相关的药效学（PD）生物标志物、探索接受LB1410治疗的患者的生存期等；

[Translation]

Main study objectives: (1) To evaluate the safety and tolerability of LB1410 in patients with advanced malignant tumors; (2) To determine the maximum tolerated dose (MTD) and/or recommended dose (RP2D) of LB1410 for phase II clinical trials; Secondary study objectives: (1) To evaluate the pharmacokinetics (PK) of LB1410; (2) To preliminarily evaluate the anti-tumor activity of LB1410 in patients with advanced malignant tumors; (3) To evaluate the immunogenicity of LB1410; Exploratory objectives: To explore the pharmacodynamic (PD) biomarkers related to the clinical activity of LB1410, and to explore the survival of patients treated with LB1410, etc.;

Start Date12 Aug 2022

Sponsor / Collaborator

L&L Biopharma Co., Ltd.

100 Clinical Results associated with Recombinant PD-1/TIM3 bispecific antibody(L&L vision biopharmaceuticals)

Login to view more data

100 Translational Medicine associated with Recombinant PD-1/TIM3 bispecific antibody(L&L vision biopharmaceuticals)

Login to view more data

100 Patents (Medical) associated with Recombinant PD-1/TIM3 bispecific antibody(L&L vision biopharmaceuticals)

Login to view more data

2

Literatures (Medical) associated with Recombinant PD-1/TIM3 bispecific antibody(L&L vision biopharmaceuticals)

01 Jan 2020·Journal of Pharmaceutical Sciences

Characterization of a Novel Bispecific Antibody With Improved Conformational and Chemical Stability

Article

Author: Manikwar, Prakash ; Lobo, Brian ; Rainey, Godfrey Jonah ; Mulagapati, Sri Hari Raju ; Moez, Khashayar ; Kasturirangan, Srinath

Bispecific antibodies containing single-chain variable fragment (scFv) appended to immunoglobulins G offer unique development challenges. Here, we describe the stability of a novel bispecific format, BiS5, where the scFv is tethered to the C_H3 domain. BiS5 showed an improved conformational and chemical stability compared with that of BiS4 in which the scFv is appended in the hinge region between the F_ab and F_c. By switching the location of the scFv from hinge region to the C_H3, there was an improved stabilization of C_H2 and scFv domains. Interestingly, no noticeable impact was observed on the conformational stability of C_H3 and F_ab domains. BiS4 and BiS5 showed different aggregation and fragmentation rates under accelerated temperature stress conditions. BiS4 showed higher fragmentation rates compared with BiS5 likely owing to fragmentation in the linker region on either side of the scFv while BiS5 is more resistant toward fragmentation owing to tethering of scFv to the C_H3 domain at its N and C terminus. In conclusion, the location of scFv affects both aggregation and fragmentation kinetics. These insights into the molecular structure and correlations with their physical and chemical stability will help formulation development of these novel bispecific antibodies.

01 Jul 1997·British Journal of Clinical PharmacologyQ2 · MEDICINE

Bisoprolol attenuates noradrenaline‐ and phenylephrine‐evoked venoconstriction in man in vivo

Q2 · MEDICINE

Article

Author: R. W. Langley ; A. H. Abdelmawla ; E. Szabadi ; C. M. Bradshaw

Aims The aim of this study was to examine the effects of bisoprolol (BIS), a selective β1‐adrenoceptor antagonist without partial agonistic activity, on noradrenaline‐ and phenylephrine‐evoked venoconstriction in man using the dorsal hand vein compliance technique.Methods Twelve healthy male volunteers participated in three weekly experimental sessions. Subjects were allocated to treatments and sessions on a double‐blind basis. In each session either BIS 5 mg (BIS5), or BIS 10 mg (BIS10), or placebo was administered orally, and noradrenaline acid tartrate (0.1–33.33 ng min−1 ) followed by phenylephrine hydrochloride (0.033–10 μg min−1 ) was infused into the dorsal hand vein. Systolic and diastolic blood pressure and heart rate were also measured.Results Both noradrenaline and phenylephrine produced dose‐dependent venoconstriction: the geometric mean ED50 for noradrenaline was 3.21 ng min−1 and for phenylephrine 135.04 ng min−1; the potency ratio (noradrenaline/phenylephrine) was 42. Both BIS5 and BIS10 significantly decreased the venoconstriction to noradrenaline (ANOVA; P<0.005), and to phenylephrine (ANOVA; P<0.001). The antagonism of the venoconstrictor responses was also reflected in a significant increase in logED50 values for both noradrenaline (ANOVA; P<0.005), and phenylephrine (ANOVA; P<0.0025) in the presence of both doses of BIS. Both doses of BIS significantly decreased heart rate (ANOVA; P<0.0001), and systolic blood pressure (ANOVA; P<0.0025).Conclusions Bisoprolol can antagonize α1‐adrenoceptor mediated venoconstriction in the human dorsal hand vein in vivo through a mechanism which remains to be elucidated.

100 Deals associated with Recombinant PD-1/TIM3 bispecific antibody(L&L vision biopharmaceuticals)

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Solid Tumor	Phase 2	China	L&L Biopharma Co., Ltd.	19 Jun 2024
Advanced cancer	Phase 1	China	L&L Biopharma Co., Ltd.	12 Aug 2022
Advanced Malignant Solid Neoplasm	Phase 1	China	L&L Biopharma Co., Ltd.	12 Aug 2022
Lymphoma	Phase 1	China	L&L Biopharma Co., Ltd.	12 Aug 2022
Colorectal Cancer	Phase 1	China	L&L Biopharma Co., Ltd.	-
Colorectal Cancer	Phase 1	United States	L&L Biopharma Co., Ltd.	-
Non-Small Cell Lung Cancer	Phase 1	China	L&L Biopharma Co., Ltd.	-
Non-Small Cell Lung Cancer	Phase 1	United States	L&L Biopharma Co., Ltd.	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2022	Phase 1	Non-Small Cell Lung Cancer	-	Bis5	(obdyeucuzb) = ggrcqxqkkg fxdzgihouy (ojugpqkqle ) View more	-	02 Jun 2022
				PD-1 antibody	(obdyeucuzb) = wslmyptlhe fxdzgihouy (ojugpqkqle ) View more

Login to view more data

Translational Medicine

Boost your research with our translational medicine data.

login

or

view full example data

Boost your research with our translational medicine data.

Deal

Boost your decision using our deal data.

login

or

view full example data

Boost your decision using our deal data.

Core Patent

Boost your research with our Core Patent data.

login

or

view full example data

Boost your research with our Core Patent data.

Clinical Trial

Identify the latest clinical trials across global registries.

login

or

view full example data

Identify the latest clinical trials across global registries.

Approval

Accelerate your research with the latest regulatory approval information.

login

or

view full example data

Accelerate your research with the latest regulatory approval information.

Biosimilar

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.

login

or

view full example data