Pipeline of Claudin 18.2-Targeted Immunotherapy

This competitive intelligence report about Claudin-18.2 Targeted Immunotherapeutics provides an up-to-date competitor evaluation in the field of therapy candidates in research and development targeting claudin 18.2 (CLDN18.2). This report will be prepared on demand within one working day upon order placement. The report lists active CLDN18.2-targeted R&D programs by R&D phase in a tabular format and describes in brief the profile of anti-CLDN18.2 immunotherapy candidates by drug modality. The report will be provided in pdf format and sent by e-mail to the customer.

As an example of this category of on demand reports, please see our free sample report of “Pipeline of 5T4-Targeted Immunotherapies”.

Claudin 18.2 (CLDN18.2) is a transmembrane, tight junction protein exclusively expressed in normal gastric mucosa cells and is retained in most gastric or gastroesophageal junction (G/GEJ) adenocarcinomas. In normal gastric mucosa, CLDN18.2 is typically buried within tight junctions. During malignant transformation, loss of gastric mucosa cell polarity may result in CLDN18.2 becoming more exposed and, thus, accessible to therapeutic antibodies.

Zolbetuximab is a first-in-class immunoglobulin G1 monoclonal antibody that targets CLDN18.2 and mediates antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in CLDN18.2-positive G/GEJ adenocarcinoma cells. VYLOY (zolbetuximab-clzb) is the only CLDN18.2 targeted therapy to be approved in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive.

Zolbetuximab has been approved in a number of countries around the world including Japan, the UK, Korea, the US, Canada, Brazil and China, plus has received marketing authorization from the European Commission which is valid in all 27 EU member states as well as Iceland, Liechtenstein, and Norway

Zolbetuximab has become the current gold standard and benchmark for all follow-on anti-CLDN18.2 immunotherapy candidates as zolbetuximab is the only candidate that has been evaluated in controlled pivotal clinical studies so far. The clinical profile of zolbetuximab showed statistically significant and clinically relevant improvements in progression free survival by 1.94 or 1.41 months and in overall survival of 2.69 or 2.23 in the SPOTLIGHT or GLOW phase III trials, respectively. Major adverse events were gastrointestinal symptoms nausea, vomiting and decreased appetite. Furthermore, only 39.1% of gastric cancer patients were eligible to treatment with zolbetuximab. One of the inclusion criteria was expression of CLDN18.2 in tumor tissue defined by moderate to strong staining in ≥75% of cancer cells.

As zolbetuximab is a chimeric naked monoclonal antibody with limited effector function, numerous next generation CLDN18.2-targeted immunotherapy candidates are being evaluated in clinical studies around the globe. Among the drug modalities applied to create CLDN18.2-targeted development candidates are naked monoclonal antibodies with enhanced target affinity and increased ADCC, CDC & ADCP, antibody-drug conjugates (ADC) with improved linker & conjugation technology and payloads, chimeric antigen receptor (CAR) T-cells and natural killer (NK) cells with improved constructs (signalling domains, armored, modular design), anti-CLDN18.2 bispecific T-cell engaging (BiTE or TCE) antibodies for recruitment of cytotoxic T-cells and anti-CLDN18.2 bispecific immune-oncology antibodies (e.g. PD-L1, 4-1BB (CD13), CD47/SIRPα or CD8).