DanDi Bioscience

https://www.hankyung.com/it/article/202202090320i 

This post has been translated from the original article dated 2/14/2022. 

[Exploration Note] Dandibio “applying for European phase 1 sepsis treatment next month” 

Interview with CEO Park Young-min① 

“At the end of next month, we plan to apply for the European phase 1 clinical trial of ‘DD-S052’, a treatment for sepsis and super bacteria. Clinical trials will begin in France around June, and discussions are underway for cooperative research and technology transfer contracts before and after entering phase 2.”

On the 26th of last month, Park Young-min, CEO of Dandi Bio, whom we met at the headquarters in Seongsu-dong, Seoul, said, “DD-S052 is a new concept antibiotic with the dual function of killing the causative bacteria directly and removing endotoxin (LPS) released by the causative bacteria.” It will be a first-in-class drug with a mechanism differentiated from antibiotics.”

Representative Park is currently serving as the director of Konkuk University Biomedical Science Research Institute and professor of immunology at Konkuk University Graduate School of Medicine. He is one of the few bio venture founders as a basic medical scientist. After graduating from medical school, he majored in microbiology (immunology), a branch of basic medicine. He chose the path of a basic medical researcher who studied the scientific pathogenesis of diseases and substances that could overcome them through basic medical research, rather than clinical medicine treating patients in hospitals.

In 2005, when Park was working at Pusan National University College of Medicine, he was designated as a National Research Laboratory (NRL) by the National Research Foundation and carried out the task of finding a substance that enhances the immune response. His research was to find an immune-enhancing substance among many products from Mycobacterium tuberculosis. At this time, he discovered a candidate substance for treating sepsis, and started developing a new drug for sepsis after coming to Konkuk University. In April 2016, he founded Dandi Bio. It was acquired by Next Science in 2018. Next Science has a 54.1% stake.

He said, “Sepsis is one of the diseases with a high fatality rate that causes damage to various organs by promoting an excessive immune response due to bacterial infection, but no appropriate treatment other than antibiotics has been developed so far.” We will develop drugs to treat sepsis,” he said.

Development of a fundamental treatment for sepsis 

The most common cause of sepsis is infection by microorganisms, accounting for 90% of all sepsis. It is explained that 70% of this is due to ‘gram-negative bacteria’ such as Escherichia coli, Salmonella, and Shigella. CEO Park said, “Sepsis proceeds in two stages and occurs very rapidly. In the beginning, excessive secretion of inflammatory cytokines causes an excessive inflammatory immune response, followed by an immune paralysis reaction due to the death of immune cells.” did. 

However, there is no proper treatment other than prescribing antibiotics at the right time. “In general, for the treatment of sepsis, a therapy that suppresses the immune response in the early stage and raises the immune response in the later stage is implemented,” he said. It wakes up and becomes difficult to control.”

Sepsis is difficult to treat for another reason. Even when antibiotics are properly administered, bacteria killed by antibiotics release LPS.

Dandi Bio paid attention to LPS. LPS exists in the outer cell membrane (cell wall) of Gram-negative bacteria, but is not secreted out while Gram-negative bacteria are alive. However, as the bacteria die and the cells are destroyed, toxins are leaked out.

In sepsis, LPS leaked out in this way activates the immune response excessively, causing blood coagulation in blood vessels or organ damage due to the resulting cytokine storm. It can even lead to death of the patient.

CEO Park said, "Currently, global companies such as Asahi Kasei, Ferring Pharmaceuticals, Sanofi, and Revimmune are developing sepsis treatment drugs, but all of these candidates have mechanisms of action that inhibit blood coagulation and tissue damage and regulate immune function." “We need a fundamental approach that targets bacteria and LPS secreted by bacteria, which are the cause of sepsis,” he emphasized.

DD-S052, which is being developed by Dandi Bio, is expected to have a dual function of targeting the sepsis causative bacteria and the LPS released by the causative bacteria. It is explained that it directly kills Gram-negative bacteria and binds to the LPS released at this time to neutralize it. Through this, it regulates the immune system, such as suppressing the cytokine storm. He said that it is differentiated from existing antibiotics that stop at removing the causative bacteria of sepsis.

Dandi Bio conducted a preclinical safety test with Anapass, Spain, a non-clinical testing standards certification body (GLP) specializing in preclinical testing. In addition, since 2019, it has obtained a lot of data on the pharmacokinetics, pharmacodynamics, and therapeutic efficacy of DD-S052 while carrying out the ‘Unresolved Infectious Treatment Development Research Project’, a national project of the Ministry of Health and Welfare. 

CEO Park said, “DD-S052 is a synthetic peptide composed of 11 amino acids, and safety such as low toxicity to humans has been confirmed through animal experiments.” We confirmed the treatment effect of sepsis, such as suppressing the reaction,” he said.

It also confirmed its potential as a treatment for antibiotic-resistant bacteria (super bacteria). In the process of treating sepsis, resistant bacteria proliferate excessively in the body due to excessive antibiotic prexxxscription, and more and more powerful antibiotics are used. Eventually, ‘superbugs’ that do not respond to any antibiotics are created.

Through preclinical trials, Dandi Bio confirmed that DD-S052 kills multi-resistant bacteria that are resistant to other antibiotics.

The company plans to apply for European phase 1 clinical trials for DD-S052 at the end of next month. To this end, it signed a contract with Eurofins Optimed, a French clinical commissioned organization (CRO), last year. Based on the data obtained earlier, the company plans to prepare for clinical trials with Eurofins Optimed and enter phase 1 clinical trials in France in June.

"Starting with France, we plan to start clinical trials in Europe and other countries," said CEO Park. said.

(Continued from part 2)

Reporter Kim Ye-na