Transcenta announces two scientific posters at SITC 2022

Transcenta Group (06628.
HK), a clinical-stage biopharmaceutical company with integrated capabilities in the full process of biopharmaceutical discovery, R&D, process development and manufacturing, announced on November 11 that it announced two scientific studies
in poster format during the 37th Annual Meeting of the Society for Cancer Immunotherapy (SITC) held in Boston, USA, November 8-12, 2022.

One of these is related
to TST001 (Osemitamab), a high-affinity ADCC-enhanced humanized anti-Claudin18.
2 monoclonal antibody.
The expression
of Claudin18.
2 and PD-L1 in Chinese patients with gastric/oesophagogastric conjugation adenocarcinoma was studied using Transcenta's independently developed and patented Claudin18.
2-specific immunohistochemical antibody and commercial PD-L1 detection kit.

● The other is TST005, a bifunctional anti-PD-L1 and TGF-β trap fusion protein, in the treatment of subjects with locally advanced or metastatic solid tumors, as an ongoing trial (TiP) summary of a first-in-human, open-label, dose-escalation, and dose-expansion Phase I study in subjects with locally advanced or metastatic solid
tumors.

Poster summary:

Poster #105: Expression of Claudin18.
2 and PD-L1 in Chinese gastric adenocarcinoma and oesophagogastric junction adenocarcinoma

Claudin18.
2 is significantly expressed in a variety of solid tumors, including gastric cancer, and is a promising target for the treatment of gastric cancer
.
Immunotherapy with chemotherapy targeting PD-1 has been approved as first-line treatment
for gastric/oesophagogastric junction (G/GEJ) adenocarcinoma.
Understanding the expression profile of Claudin18.
2 and PD-L1 can provide guidance for the development of combination therapies for these two drugs, maximizing the benefits of each drug
.
In this study, the expression of Claudin18.
2 in surgical resection specimens of patients with G/GEJ adenocarcinoma in China and its correlation
with PD-L1 expression were investigated.

Using Transcenta's self-developed and patented Claudin18.
2-specific immunohistochemical antibody 14G11 and the commercial PD-L1 assay kit (PD-L1 IHC 28-8 pharmDx), a total of 300 surgically resected G/GEJ adenocarcinoma tissue samples, 216 (72%) tissue samples were stained positive for Claudin18.
2 (i.
e.
, Claudin18.
2 membrane staining intensity ≥1+≥10% of tumor cells)
。 For PD-L1 expression, 51 (17%) had PD-L1 combined positive fraction (CPS) ≥5
.
19% (n = 41/216) of Claudin18.
2 positive samples also showed PD-L1 CPS≥5
.
No correlation
between the expression of the two markers was observed.

Poster #771: A first-in-human, open-label, dose-escalation, and dose-extended Phase I study of TST005 in subjects with locally advanced or metastatic solid tumors

TST005 is a novel bifunctional fusion protein that combines a high-affinity PD-L1 monoclonal antibody with TGF-β trap with enhanced stability in an IgG1 backbone silent by Fc
.
This study explores the safety, tolerability, and preliminary antitumor activity
of TST005 in solid tumors.

In preclinical studies of EMT6/hPD-L1 breast tumor models (high-expression TGF-β models), TST005 showed better tumor suppression
compared to M7824 analogue, a PD-L1/TGF?β bifunctional fusion protein.

This study is being conducted
at 4 research centers in the United States and China.
As of August 24, 2022, the first three dose cohorts had completed dosing and no dose-limiting toxicity (DLT)
was observed.

The full content of the poster can be found on the company's official website:

About TST001 (Osemitamab)

TST001 (Osemitamab) is a high-affinity humanized monoclonal antibody targeting Claudin18.
2 with enhanced antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activity that shows strong antitumor activity
in xenograft trials.
TST001 (Osemitamab) is the second most advanced Claudin18.
2-targeted antibody drug developed worldwide by the Company through its Immune Tolerance Breakthrough (IMTB) technology platform
.
TST001 (Osemitamab) kills tumor cells
expressing Claudin18.
2 through ADCC and CDC mechanisms.
Using advanced bioprocessing technology, the fucose content of TST001 (Osemitamab) was greatly reduced during production, further enhancing the NK cell-mediated ADCC activity
of TST001 (Osemitamab).
Clinical trials of TST001 (Osemitamab) (NCT04396821, NCT04495296/CTR20201281)
have been ongoing in both China and the United States.
The U.
S
.
Food and Drug Administration (FDA) has granted TST001 (Osemitamab) orphan drug designation for the treatment of patients with gastric cancer and gastroesophageal junction cancer (GC/GEJ).

About TST005

TST005 is the second bifunctional anti-PD-L1 and TGF-β trap fusion protein to initiate global clinical studies, targeting two pathways commonly used by cancer cells to escape immunosuppression, namely transforming growth factor-β (TGF-β) and programmed cell death ligand-1 (PD-L1).

TST005 consists of
a high-affinity PD-L1 antibody and an engineered TGF-β receptor type II protein fused at its C-terminus.
TST005 does not bind to the Fc receptor, so the Fc receptor-mediated killing risk to effector T cells expressing the PD-L1 protein is lower
.
The high affinity binding activity of PD-L1 and enhanced TGF-β trap stability of TST005 can deliver TGF-β trap to PD-L1-expressing tumors and minimize
the systemic inhibition of TGF-β signaling off-target toxicity.
TST005 is highly effective in reversing TGF-β-induced T cell suppression
in vitro.
In multiple homologous mouse tumor models, TST005 significantly increased the invasion of CD8-positive T cells into PD-L1-expressing tumors, and showed dose-dependent tumor growth inhibition
in tumor models where TGF-β high expression was insensitive to PD-(L)1 therapy.
TST005 is well tolerated in non-human primates and shows linear PK characteristics
.
TST005 is an innovative bifunctional immunotherapy candidate with a potentially better therapeutic window
.
Clinical trials of TST005 are being conducted simultaneously in the United States and China (NCT04958434/CTR20221397).