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KDDF-201709-55 Development of immuno-oncology drug PMC-309 targeting VISTA known as a negative checkpoint regulator(Oncology, Protein) [2019-06-24]

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

Development and Market Objectives

In the field of cancer immunotherapy, recent antibody therapeutics are focused on the immune checkpoint proteins, CTLA-4, PD-1/PD-L1 axis, OX-40, TIM-3, LAG-3 and 4-1BB, which are known as a major group of immune checkpoints. Although Yervoy, Keytruda, Opdivo and Tecentriq has shown to have high anti-tumor efficacy by targeting T-cells directly, however, they also have limitations to the number of patients those can be applied. Therefore, a novel antibody therapeutics development, which have distinct molecular mechanism of immune activation, may give benefit to treatment of cancer.

 

VISTA (V-domain Ig Suppressor of T cell activation) is a newly discovered negative regulator immune checkpoint which is expressed on the surface of T-cells, and also on myeloid lineage cells such as dendritic cells and myeloid-derived suppressor cells (MDSCs). Inhibiting VISTA activity by PMC-309, an anti-VISTA monoclonal antibody, may induce anti-tumor immunity in different manner to T-cell activating immune checkpoint inhibitors.

Unmet Medical Need & Target Patients

Lung cancer has the highest incidence rate in men and 85 % of lung cancer patients are classified as NSCLC.  With the highest incidence rate, the five-year survival rate of lung cancer patients is also very low (17 % compared to 65 % (colon cancer), 81 % (breast cancer)). Although anti-PD-1/PD-L1 antibodies are approved in the treatment of NSCLC, their target patient population, who express PD-L1 in high level (>50%), is under 25% of total NSCLC patients.

 

VISTA is known as a negative immune regulator which is mainly expressed on MDSC, and also on T-cells. Because anti-tumor immune response enhanced by VISTA inhibition have different mechanism compared to T-cell-mediated immune activation, the combination therapy with other immune checkpoint inhibitors can be considered as an alternative treatment for non-applicable patients to anti-PD-1/PD-L1 therapeutics.

Status

- Hit antibody targeting VISTA was screened out

- Hit antibody is on optimization stage

- The anti-tumor efficacy of hit antibody was evaluated in human PBMC-grafted human breast cancer mouse model

- The superior anti-tumor activity of hit antibody was identified

- The combination therapy with anti-PD-1 antibody was also identified

Intellectual Property

Application for Korean Patent was submitted

Competitive Advantages

- Superior anti-tumor activity compared to competitor

- For the companion diagnostics, we will stratify the relationship between VISTA expression level and anti-tumor activity

Contact & Company Overview

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