MEDI:GATE NEWS Antibody-based novelty novelty with a variety of potential applications, beyond SCF/c-KIT targets, we will also catch impregnable RAS

[메디게이트뉴스 박도영 기자] Stem cell factor (SCF) mediates several cellular responses by binding and activating c-KIT (CD117), a gene encoding a receptor tyrosine kinase protein. SCF/c-KIT signaling is required for the development of hematopoietic stem cells, melanocytes and germ cells. c-KIT has been known to induce cancer proliferation for a long time, and development of anticancer drugs targeting this pathway has been attempted, but failed for various reasons.

However, it was discovered for the first time that SCF/c-KIT, which was known to have a hematopoietic function by Novelty Novelity, a domestic biotechnology company, causes swelling of blood vessels and abnormal neovascularization in a specific situation called hypoxia. Opened.

Novelty Novelity is a company founded in 2017 by CEO Sang-gyu Park, a professor at the University of Pharmacy at Ajou University, and aims to provide new treatment options through novel antibodies or antibody-based substances to patients who do not have sufficient therapeutic effect with existing treatments do. The mission of’Novelty Nobility’ embodies the corporate motto of’Research is New and Management is Dignified (Novel Science, Noble Management)’.

Medigate News met with CEO Park Sang-gyu to hear what novelty’s flagship technology is different from other technologies, and what pipeline development strategy it has in the future. Representative Park graduated from Sungkyunkwan University with a bachelor’s degree and master’s degree in biology and then completed a doctorate in medicine at Seoul National University. Afterwards, he worked as a member of the Korea Invention Promotion Association’s technology evaluation committee and experienced what kind of technology the company should have, and how the development of therapeutic antibodies proceeds in Real World.

Novelty Novelity attracted 10 billion won worth of Series A investment in January last year, and successfully completed a paid-in capital increase of 8 billion won in March this year. This is a bridge round that connects Series A and Series B, which is scheduled to be promoted in the third quarter of this year, and the cumulative investment amount to date, including Series A, of 10 billion won is about 20 billion won.

Based on this, the nonclinical development of NN2101, a first-in-class retinal disease treatment, will be accelerated, and a candidate material for the anticancer drug NN3201 (Antibody-Drug Conjugate (ADC)) will be confirmed. Currently, a total of 19 people, including 8 people from the research center and 3 people in the development team, are in charge of business development, accounting and general affairs, and plan to hire 4-5 additional people throughout the department this year.

Eye disease treatment target to start phase 1 next year… It will be helpful to patients who do not have the effect of VEGF treatment

CEO Park said, “The innovation pursued by novelty novelty is to increase patient selectivity and quality of life. To this end, innovation is to go beyond the limits of existing treatments. Refractory or resistance to existing treatments, or some rare disease,” said Park. “There is no cure at all. You have to cover that area, but there are various benefits to the patients,” he said.

The novelty novelty research team is developing a therapeutic agent that targets diseases such as eye diseases and anticancer drugs by developing a complete human antibody that inhibits SCF/c-KIT. Among them, the most advanced pipeline is NN2101, which is being developed as a treatment for macular degeneration and diabetic retinopathy.

Hypoxia is a trigger for abnormal neovascularization and is a prerequisite for ocular vascular disease. According to this study, SCF/c-KIT contributes to swelling of blood vessels and the production of neovascularization at a level similar to that of existing vascular endothelial growth factor (VEGF), but acts independently of VEGF and does not inhibit normal blood vessel growth. It showed the difference of selectively resolving abnormal blood vessels.

Novelty Novelty is 20~40 that do not see the intended therapeutic effect with VEGF inhibitors such as Lucentis (Ranibizumab) and Eylea (Aflibercept), which are conventional blockbusters, through this mechanical difference. We want to provide new treatment alternatives to% of patients. Currently, it holds target source patents for eye diseases in Korea and the United States.

CEO Park said, “NN2101 is expected to complete its non-clinical trial within this year and is planning to apply for a clinical trial approval plan (IND) to the US Food and Drug Administration (FDA) in the first quarter of next year. It is expected to enter phase 1 next year, and the same year ends. I will aim until,” he said.

ADC anticancer drug plans to apply for IND in the second half of next year… To develop indications for gastrointestinal tumor substrate and small cell lung cancer

The next substance being developed is NN3201, an ADC anticancer drug. Representative Park cited two reasons for the failure of the existing SCF/c-KIT target anticancer drug development.

The first is that even if this signal is suppressed, the effect of prolonging the life of the antibody alone is as short as 3 to 5 months because cancer cells create a bypass pathway again. Therefore, an attempt was made to develop anticancer drugs in the direction of killing cancer cells with the help of surrounding immune cells.

Representative Park said, “The characteristic of candidate substances targeting SCF/c-KIT in the past is that it was designed to require excessive help from immune cells. When administered in the form of injection, it does not only work in cancer tissues, but systemic intoxication. “There are several companies that have failed because of the side effects such as anaphylaxis in the blood.”

Second, although SCF/c-KIT induces proliferation of cancer cells, mutations occur and cancer cells proliferate even without SCF/c-KIT. Therefore, there are cases of failure because the efficacy did not come out properly.

Accordingly, bio companies are trying to develop new treatments by taking different approaches.

CEO Park said, “Magenta Therapeutics of the United States is developing a preconditioning drug for bone marrow transplantation that reverses the occurrence of side effects. Celldex Therapeutics is developing an anticancer drug with an antibody alone. Efficacy After failing at this low level, we are undergoing clinical trials by changing the indication as a treatment for itching. “We are developing an ADC that conjugates an anticancer agent to an antibody.”

CEO Park said, “NN3201 is currently in the final stage of discovery and is about to be selected for the final substance. Currently, we are preparing to sign a contract with a CDMO company, and in the second and third quarters, it will formally enter the non-clinical stage and in the second half of next year. “I expect to be able to apply for an IND.”

The first target indication for NN3201 is Gastrointestinal Tumor Substrate (GIST). According to internal data, cancer does not grow until almost 3 years when used in combination with standard treatment from the beginning. The second indication will be small cell lung cancer (SCLC), and the drug combination strategy for whether to use chemotherapy and combination therapy is planned to be completed by the first half of next year.

After ADC anticancer drugs, it also plans to develop a treatment for systemic mastocytosis, a rare disease.

Proteins that correlate with RAS mutations are also identified… To establish itself as an antibody-based therapeutic company

Novelty Novelity is currently developing SCF/c-KIT target treatments, but in the mid to long term, it aims to establish itself as an antibody-based treatment development company. Therefore, it is expected to naturally focus on anticancer drugs.

Representative Park said, “There is a RAS mutant anticancer drug that is considered to be an impregnable area among those under research and development. Because RAS has a flat surface, it is difficult to design a chemical anticancer drug, and there are candidates currently in clinical trials, but it has continued to fail.” “We have confirmed in pancreatic and colon cancers that certain undisclosed proteins correlate with RAS mutations, and we are creating a follow-up pipeline for this.”

In addition to such research and development, business development activities are also being carried out, and CEO Park is cautious, but expects to produce about one result within this year.

CEO Park said, “I think we can do an IPO in the second half of 2023. At that time, we think that the eye disease will enter the phase 2 clinical phase, and the ADC will be proceeding with phase 1. Also, RAS mutations. In relation to it, he predicted that after the candidate material is determined in the first half of next year and the cell line is created in the second half of next year, it will be conducting non-clinical studies around the expected time of IPO.”

Lastly, CEO Park said, “We are an antibody-based company and have a variety of applications. We are developing our own linkers, and we have the option to attach various anticancer drugs to them, and drugs that attach cytokines to antibodies. “I can try it,” he said, “if we have more competence, we will expand our area based on antibodies.”