学术论文及会议壁报

Updated data indicated that the combination of Osemitamab plus Nivolumab and CAPOX as first-line treatment for patients with G/GEJ cancer was safe and well tolerated.

Preliminary efficacy data indicate that the combination of Osemitamab plus CAPOX and Nivolumab as the first-line treatment for patients with G/GEJ cancer had very encouraging anti-tumor activities regardless of PD-L1 expression, especially for the patients with H/M CLDN18.2 expression compared with the historical data.

Analytical verification testing indicates Claudin 18.2 IHC 14G11 pharmDx is a sensitive, specific, precise, and robust assay for detecting Claudin 18.2 in gastric and GEJ adenocarcinoma. Claudin 18.2 IHC 14G11 pharmDx for Investigational Use Only/for Performance Evaluation Only will be used for patient selection in the phase III trial of gastric/GEJ adenocarcinoma where applicable ethics committee and regulatory approvals have been granted.

Data suggested CLDN18.2 expression levels were independent of PD-L1 status, and support the use of Transcenta 14G11 antibody for CLDN18.2 detection regardless of sample collection methods, location, and patient demographics.

Here we report safety data of Osemitamab monotherapy or in combination of other anti-tumor treatments from TranStar101 study in US population.

In preclinical studies, [177Lu]Lu-TST001 demonstrated significant antitumor efficacy with acceptable toxicity. It exhibits strong potential for clinical translation, providing a new promising treatment option for CLDN18.2-overexpressing tumors, including GC.

TST001 (Osemitamab) is a potential best-in-class antibody with improved CLDN18.2 affinity and enhanced ADCC effect, leading to anti-tumor activity in low to medium CLDN18.2 expression gastric cancer animal models.

Preliminary efficacy, safety and PK/PD data demonstrates favorable benefit risk profile and support future exploration of osemitamab at the recommended dose of 6mg/kg Q3W or 4mg/kg Q2W

The synergistic effects of Osemitamab and GC standard of care (SoC: antiPD-1 mAb + Oxa/5-FU) observed in our preclinical tumor models support Osemitamab in combination with SoC chemotherapy +/- Nivolumab in G/GEJ patients regardless of PD-L1 status.

Adding CLDN18.2 antibody to chemotherapy is a clinically validated approach to improve longterm outcomes for patients with high CLDN18.2 expressing tumors (proved by GLOW and SPOTLIGHT). Osemitamab (TST001) is a potential best-in-class humanized antibody with high affinity for CLDN18.2 and enhanced ADCC (antibody-dependent cellular cytotoxicity), delivering potent antitumor activities in both low and high CLDN18.2 expressing tumors. Osemitamab monotherapy has stronger tumor growth inhibition effect than the zolbetuximab (IMAB362)-analog at the same dose, regardless of CLDN18.2 expression levels. Preclinical studies showed that TST001 plus chemotherapy had better inhibitory effects on tumor growth than chemotherapy.

TST001 is a potential best-in-class antibody with higher CLDN18.2 binding affinity and lower fucose, resulting in enhanced antibody-dependent cellular cytotoxicity (ADCC) activity.

Claudin-18 isoform 2 (CLDN18.2) is a member of the human claudin family of tetraspan membrane proteins that are crucial structural and functional components of tight junctions. CLDN18.2 expression is strictly limited to differentiated epithelial cells of gastric mucosa. CLDN18.2 is ectopically expressed at a significant level in multiple tumor types including gastric, esophageal, pancreatic and lung cancers, making it an attractive anti-cancer target. In G/GEJ cancer, its expression is independent from PD-L1.

TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2. In this study, we constructed a solid target radionuclide zirconium-89 (89Zr) labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.

Claudin-18 isoform 2 (CLDN18.2) is a member of the human claudin family of tetraspan membrane proteins that are crucial structural and functional components of tight junctions4. Unlike other family members, CLDN18.2 expression is strictly limited to differentiated epithelial cells of gastric mucosa4, 5. Interestingly CLDN18.2 is ectopically expressed at a significant level in multiple tumor types including gastric, esophageal, pancreatic and lung cancers, making it an attractive anti-cancer target5. In G/GEJ cancer, its expression is independent from PD-L16.

This study investigated the prevalence of Claudin18.2 expression from surgical resections of G/GEJ adenocarcinoma at diagnosis and its correlation with PD-L1 expression in a cohort of Chinese patients.

TST001 is a recombinant humanized antibody. Here we report the TST001 in combination with CAPOX as the first line treatment of patients with G/GEJ cancer is well tolerated and encouraging anti-tumor activities have been observed.

TST001 is a recombinant humanized IgG1 antibody specifically against human Claudin18.2 (CLDN18.2) with high affinity and enhanced FcR engaging of NK cell.

This phase I clinical trial enrolls patients with advanced or metastatic solid tumors who progressed on or after standard treatments. In the dose escalation phase, patients without preselection of tumor CLDN18.2 expression were given increasing doses of TST001 intravenously every 3 weeks (Q3W) using a 3+3 design.

In normal conditions, Claudin (CLDN)18.2 is a tight junction protein with expression strictly confined to differentiated epithelial cells in gastric mucosa.

Claudin18.2 (CLDN18.2), a member of tight junction protein family, is strictly limited to differentiated epithelial cells of gastric mucosa and is overexpressed in multiple tumor types, such as gastric, esophageal and pancreatic cancers.

Claudin-18 isoform 2 (CLDN18.2) is a member of the human claudin family of tetraspan membrane proteins that are crucial structural and functional components of tight junctions.

硬骨抑素是一种由成骨细胞分泌的SOST蛋白，对矿化骨基质的形成和骨量有负面调节作用。我们报告了一项随机、双盲、安慰剂对照的多中心Ⅱ期临床试验的结果，blosozumab是一种针对硬骨抑素的人源化单克隆抗体，用于绝经后低骨质密度（BMD）妇女。

The enrollment is ongoing in clinical centers in the US and China. No significant safety signals were reported in the first few patients treated with TST003.

Here we identify Gremlin1 as a ligand for fibroblast growth factor receptor 1 (FGFR1), which promotes lineage plasticity and drives castration resistance. Importantly, we generate a specific anti-Gremlin1 therapeutic antibody and demonstrate synergistic effect with androgen deprivation therapy (ADT) in CRPC.

TST004 is a humanized IgG4 anti-MASP2 antibody. Here we report the in vitro characterization of TST004, as well as in vivo pharmacokinetic (PK) and pharmacodynamic (PD) and safety profiles in cynomolgus monkeys.

TST005 is a novel bi-functional fusion protein combining a high affinity PD-L1 monoclonal antibody (mAb) in a fragment crystallizable (Fc) silenced immunoglobulin G1 (IgG1) backbone and a differentiated transforming growth factor beta (TGF‑β) trap with improved stability. This study investigated the safety, tolerability and preliminary anti-tumor activity of TST005 in solid tumors.

MSB0254 is a humanized vascular endothelial growth factor receptor 2 (VEGFR-2) monoclonal antibody which inhibits angiogenesis induced by either VEGF-A or –C.This is a phase I study to evaluate MSB0254’s safety, tolerability and PK profiles, as well as preliminary anti-cancer activities in Chinese patients with advanced solid tumors.

Antibodies targeting PD1/PD-L1 are emerging as effective cancer immunotherapies, however, not all patients with PD-L1 expression respond to the treatment.

MSB2311注射液在晚期多线治疗失败的实体瘤和淋巴瘤受试者中表现出较好的抗肿瘤活性，安全性和耐受性良好，值得开展进一步的临床研究。

在中国晚期肿瘤患者中，MSB0254注射液显示出良好的安全性、耐受性和一定的抗肿瘤疗效。

MSB2311 is a novel humanized PD-L1 antibody with a unique pH-dependent antigen binding property that enables intra-tumor recycling and potentiates tumor penetration.

Treatment with immune checkpoint inhibitors, including anti-PD(L)-1 antibodies, has demonstrated durable responses in patients with PD-L1 expressing tumors. However, not all patients with PD-L1 expression respond to the treatment due to de novo or acquired resistance to checkpoint inhibitors.

MSB2311 is a novel humanized programmed death-ligand 1 (PD-L1) antibody with a unique pH-dependent antigen binding property that enables intra-tumor recycling and potentiates tumor penetration.