Young Woo Park, CEO of Y-Biologics, a bio startup that develops antibody drugs, revealed his aspirations to localize immune checkpoint inhibitors in an interview with Maeil Business Newspaper. What is an immune checkpoint inhibitor that makes “localization” so important?

 

 

When the immune cells in our body locate cancer cells, they immediately recognize and attack them. Problems arise, however, when the immune cells are too weak to effectively fight against cancer cells or if they attack normal cells.

 

This is why immune cells have a sort of a brake device to regulate their activity, and this is called an “immune checkpoint.” The problem is that if the brake is applied excessively, the immune cells cannot function properly or kill cancer cells in a timely manner. In recent years, immune checkpoint inhibitors that can prevent such brake malfunctions have been a hot topic in the fight against cancer in the pharmaceutical industry. Because this class of drugs uses the patient’s own immune system, it does not lead to any adverse reactions like the existing chemotherapy drugs, and if the patient responds to the drug, it can increase the survival period by up to 5 years.

 

“Recently, most pharmaceutical companies have been testing to see whether the effectiveness of anticancer drugs gets doubled when used together with immune checkpoint inhibitors,” said CEO Park who then added, “Foreign immune checkpoint inhibitors, however, are expensive, and their developers have no reason to conduct joint research with a Korean pharmaceutical company since there are companies lining up to request clinical trials on combination therapy.”

 

He then explained that localization is essential to meet the clinical demand of domestic pharmaceutical companies and to reduce the financial burden on the national health insurance scheme by providing alternatives to the costly foreign-made immune checkpoint inhibitors. 

 

There is an urgent need to develop inhibitors targeting PD-1 and PD-L1, in particular. PD-L1 found on cancer cells weakens immune cells by triggering PD-1, which is a type of a brake for immune cells. PD-L1 also disrupts the immune system by disguising cancer cells as immune cells. CEO Park said, “Cancer cells with PD-L1 can evade the attacks from immune cells by pretending to be immune cells. [...] Since PD-1 and PD-L1 are commonly found on cancer cells, it will be possible to conquer various types of cancer by developing an inhibitor targeting them.” Antibody drugs that bind to PD-1 and PD-L1 to block their functions and normalize the immune system are being developed one after another worldwide, and the prime examples of these are Opdivo and Keytruda, which have recently been registered for national health insurance coverage in Korea.

 

CEO Park further explained, “The global immuno-oncology drug market is expected to grow to KRW 30 trillion in size by 2022, and Opdivo and Keytruda have 80% share of the entire market. [...] The financial burden on the state will surge due to the registration of these two products for national health insurance coverage, but the patents for Opdivo and Keytruda will both expire in 2030, so it’s not even possible to release biosimilars until then.”

 

In order to get into this niche market, Y-Biologics is currently developing immune checkpoint inhibitors with the target launch year set as 2025 prior to the patent expiry date. CEO Park said, “There are few companies in Korea that possess PD-1 and PD-L1 antibodies. The goal is to kick off a Phase 1 clinical trial next year after entering the preclinical phase (animal testing) for an immune checkpoint inhibitor candidate this year. [...] We have been delivered research findings that it is more effective than the existing immune checkpoint inhibitors from a pharmaceutical company reviewing the joint study, so it will be an excellent alternative once it is released.”

 

Y-Biologics has already discovered PD-1 and PD-L1 antibodies using its own antibody library and high-speed antibody search system. This was possible because the company has a database on 100 billion human antibodies. CEO Park explained, “We are a R&D-oriented company that introduces new antibody drug pipelines and offers research services based on our core technologies. [...] 44 out of the 52 executives and employees at our company are R&D personnel.” The company specializes in research to find candidate substances, in particular.

 

The company even boasts its own human antibody library. “It is like a treasure trove of antibodies exhibiting great diversity, making it possible to quickly search for antibodies needed to treat specific diseases, and it differentiates us from companies that outsources the search work or obtains antibodies from foreign companies,” said CEO Park. Each antibody has a site with a unique structure and shape for recognizing and binding to a specific antigen. It is similar to the way a key can fit only in its own keyhole to lock or unlock it. Y-Biologics’ high-speed antibody search system finds the best candidate by identifying the antibody that binds best to the antigen in question and efficiently removes the disease-causing substance.

 

The company is also developing new antibody therapeutics based on ALiCE, a bispecific antibody technology.

 

It is a new drug that has overcome the shortcomings of CAR-T cell therapy, which has recently been in the spotlight. CAR-T therapy designed to attack only cancer cells by manipulating a group of immune cells called T cells has been noted for its high response rate, but the downside is that it is difficult to mass produce and its effects are relatively short-lasting. “The ALiCE platform can recognize antigens better than the existing antibodies, and it has a stronger binding affinity to antigens and stays in the blood longer,” said CEO Park who then explained that “one antibody binds to a cancer cell and the other activates a T cell.” He then revealed that there are “plans to proceed with animal testing as soon as possible.”

 

 

[By Yun Jin Kim]