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KDDF-201803-08 Development of a pre-clinical candidate of ACE-05 bispecific antibody with enhanced T cell activation(Oncology, Protein) [2019-10-25]

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Ongoing Project
Section Lead
Generation
Lead
Optimization
Preclinical Phase I Phase II Phase III

Development and Market Objectives

This project explores the possibility of being the final candidate for the development of the anti-PD-L1/CD3 bispecific antibody ACE-05, which was constructed using the Y-Biologic’s proprietary T cell-redirecting bispecific antibody platform, namely ALiCE (Antibody-Like Cell Engager).

 

Aim 1: To assess the mechanism of action, some imaging techniques will be applied to identify its role as a T cell engager.

Aim 2: To examine the anti-cancer effect of ACE-05, immune-humanized mouse models will be used to evaluate the anti-cancer efficacy and TIL profile analysis.

Aim 3: To assess the stability and the pre-toxicity, PK analysis will be performed in rodents and primates, and safety data will be obtained by analysis of immune cytokine profile.

Unmet Medical Need & Target Patients

Lung cancer is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. It is divided by two main types, small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). NSCLC accounts for about 85% of occupancy rate. Worldwide in 2012, lung cancer occurred in 1.8 million people and resulted in 1.6 million deaths. This makes it the most common cause of cancer-related death in men and second most common in women after breast cancer. According to 2015 Data Monitor Healthcare, the rate of NSCLC incidence in the five major European countries including the US and Japan is increasing every year from 2015 to 2035.

 

The standard therapy for NSCLC is chemotherapy commonly using platinum-based drugs (cisplatin and carboplatin) but 5-year survival rate is very poor (less than 10%). Another possible treatment is targeted therapies, which target mostly ALK, EGFR, and VEGFA. The treatment is, however, effective only for patients with adenocarcinoma, not for most of NSCLC patients. In recent years, immunotherapies such as anti-PD-1 or anti-PD-L1 mAb have shown great improvement in the treatment of NSCLC patients. But they still have high unmet medical needs because they respond only to about 30% patients.

Status

We have observed superior anti-cancer effect of ACE-05 in immune-humanized mouse xenograft model using a NSCLC cell line, HCC827, as compared to anti-PD-L1 mAb and a BiTE format bispecific Ab.

In addition, dose-finding test has been shown that the lowest dose with sufficient anti-cancer effect was 0.05 mpk in the same animal model. Currently, MoA study of ACE-05 is underway using bio-imaging equipment and T cells from PBMC.

Intellectual Property

ALiCE Patent: US Provisional application 62/655,762, Application date: 2018-04-10

Competitive Advantages

A leading format in T cell-redirecting bispecific Ab is Amgen’s BiTE, which is a ScFv-based Ab fragment. BLINCYTO, a CD19/CD3 BiTE, is now commercially available for treatment of ALL (Acute Lymphoblastic Leukemia). Compared to the BiTE format, ALiCE platform has various advantages, which are higher structural stability, bi-valency to tumor antigens, lower binding affinity to T cell, and higher productivity. Therefore, in the case of ACE-05 (anti-PD-L1/CD3 bispecific Ab) which targets PD-L1-overexpressing cancer cells, the anti-cancer effect of ACE-05 monotherapy even at lower dose is expected to be much higher than those of anti-PD-1/PD-L1 monotherapy or combination therapy. 

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