In various streets of San Francisco, California, one can easily see people unsteady on their feet, acting like zombies. These individuals, dubbed "drug zombies," became addicted after using the painkiller fentanyl prescribed by doctors. The strong addictive painkiller has caused serious social problems due to its misuse and illegal distribution.
Several major pharmaceutical corporations attempted to solve the serious side effects of these narcotic painkillers by developing non-narcotic alternatives but failed repeatedly. However, the domestic corporation Vivozon Pharmaceutical succeeded in this development, specifically the locally developed new drug "Anapra Injection," which received approval from the Ministry of Food and Drug Safety last month.
Anapra Injection (ingredient name: Opiranzerin) is an injectable drug used for the control of moderate to severe acute pain after surgery, distinguishing itself from existing narcotic or non-steroidal anti-inflammatory drugs by its different mechanism of action. This includes post-surgical pain, pain from accidents, pain resulting from third-degree burns, neuropathic pain where stimuli that shouldn't be felt as pain are perceived as pain, and cancer pain experienced by patients.
Until now, the only available medication for moderate to severe pain was narcotic painkillers (opioids). However, these come with the side effects of strong addiction and tolerance. Once tolerance develops, patients cannot achieve therapeutic effects with the existing dosage, leading to treatment limitations, and there have been many cases of overdose resulting in death.
Lee Doo-hyun, chairman of Vivozon Group, met with CHOSUNBIZ at the Vivozon office in Seongsu-dong, Seongdong-gu, Seoul, on the 7th and noted, "Anapra Injection (Opiranzerin) is the world's first multi-receptor targeted non-narcotic painkiller and the first non-narcotic painkiller in the world to be used for moderate to severe pain. This has significant development value in the global market."
Vivozon Group is a biotech company established by this chairman in 2008 focused on developing new drugs for pain and central nervous system diseases. In September 2020, it acquired the current Vivozon Pharmaceutical, formerly Inist Bio-pharmaceuticals, through its subsidiary Vivozon Healthcare. Inist Bio-pharmaceuticals, which began as Kyungsung Pharmaceutical in 1938, has a factory certified by Good Manufacturing Practice (GMP), which was a consideration for the acquisition with the intention of supplying pharmaceutical products.
The chairman completed a doctoral program in psychology and biopsychology at Korea University and worked as a researcher at Amgen, Johnson & Johnson, and Eli Lilly from the late 1990s to the 2000s, participating in painkiller development. He determined that the failure of major pharmaceutical corporations to develop non-narcotic painkillers stemmed from focusing solely on drugs that act on single receptors. Simply put, the principles of pain occurrence are complex, meaning that it's impossible to effectively control pain with drugs targeting only one receptor.
Therefore, he established Vivozon to challenge the development of non-narcotic painkillers targeting multiple receptors. Anapra Injection's pain control effect is on par with existing narcotic painkillers, but it does not produce side effects like addiction or tolerance. The company noted that there are almost no side effects other than nausea and vomiting.
The chairman stated, "We believe that when Anapra Injection is launched domestically this year, we will be able to sufficiently achieve our revenue target of 115.1 billion won," and added, "2025 will mark the beginning of Vivozon Pharmaceutical’s transformation into a mid-sized pharmaceutical company selling new drugs." Plans are in place to share distribution and sales responsibilities for Anapra Injection with Boehringer. He also expressed, "We expect that collaboration with Boehringer will significantly accelerate the distribution of Anapra Injection."
According to the Korea Health Industry Development Institute, the global non-narcotic painkiller market is projected to be worth about 100 trillion won by 2030. Vivozon Pharmaceutical is developing a non-narcotic painkiller in pill form as a follow-up to Anapra Injection.
The company plans to develop VVZ-2471 as an oral pain treatment in Korea and as a treatment for drug addiction in the U.S. If successful, it is expected to be a game changer in the global pain relief and drug addiction treatment markets.
The chairman reported, "VVZ-2471 is currently undergoing phase 2 clinical trials," and added, "It is effective against substance abuse disorders like drug addiction, and we are currently collaborating with addiction experts in the U.S. to smoothly advance clinical development." The following is a Q&A session with the chairman.
–What prompted you to establish the company and pursue the development of non-narcotic painkillers?
"While working at a U.S. pharmaceutical company, I noticed the issues related to the side effects of narcotic painkillers and anti-inflammatory medications, making it essential to develop new painkillers that provide pain relief equivalent to narcotics without addiction or gastrointestinal bleeding. At that time, with the advancements in genetic engineering and molecular biology, numerous genes and receptors related to pain were discovered, but many pharmaceutical companies failed in new drug development. I led much of the research for about ten years, but we continued to encounter failures."
Then, I identified the critical reasons for the failures. The new drug development paradigm at the time focused on creating drugs that act on single receptors. However, as pain is not controlled by a single mechanism but rather by multiple pathways, it became clear that drugs acting only on one receptor could not effectively manage pain. Thus, I concluded that it was necessary to develop drugs that act simultaneously on multiple receptors. As I contemplated how to develop such multi-receptor targeting drugs, I devised a methodology to quickly screen candidate substances using electrophysiological techniques. At that time, I proposed this idea to Professor Jung Kyung-woon of the University of Southern California, and he willingly offered to help, suggesting I start a company. As a result, I returned to Korea in 2008 and established Vivozon. Professor Jung raised about 3 billion won in funding for the first three years of the business.
–How did you discover Opiranzerin?
"After establishing Vivozon in 2008, I spent about six months building an electrophysiological screening method. Collaborating with Professors Lee Eun and Lee Cheol-beom of the Department of Chemistry at Seoul National University, we synthesized substances that act on Glycine Transporter 2 and started screening them. Just acting on Glycine Transporter 2 alone did not yield the desired efficacy, so we continued synthesizing acting substances and conducting research to discover substances with superior efficacy. Through this, we secured Opiranzerin in about a year. This substance acts not only on Glycine Transporter 2 but also on the 5HT2a receptor. Individually, neither substance was effective for pain, but when administered together, it exhibited a very strong analgesic effect in animal tests, leading us to decide to develop Opiranzerin."
–Was there support from the government?
"Yes. In 2011, we were selected for the non-clinical section of the Ministry of Health and Welfare’s new drug development support project, and non-clinical development commenced. Subsequently, in 2013, we were selected for the phase 1 section and progressed swiftly through to phase 1. Later, in 2016, we were selected for the global phase 2 clinical trial project, establishing our clinical development basis in the U.S. We received a total of 7.8 billion won in national support."
–What has been the scale of funding from development to approval?
"Including government support funds, approximately 78 billion won has been invested. This is a significant amount, of which about 80% is investment for global development. About 20 billion won was invested up to entering phase 2 clinical trials. Approximately 50 billion won was invested during the clinical development phase in the U.S., but it faced setbacks due to the COVID-19 pandemic that began in early 2020. Subsequently, we quickly applied for phase 3 clinical trials in Korea, allowing us to start them in July 2021. Vivozon Pharmaceutical received exclusive rights to conduct the phase 3 trials in Korea, and so far, over 8 billion won has been invested."
–Were there any difficulties?
"There were substantial challenges in securing funding. At the time of the company's establishment, the concept of bio-investment was virtually nonexistent in the domestic market. The initial three to four years brought immense pressure financially, with times that necessitated letting go of researchers who were in the trenches with me. However, after being continuously selected for the Ministry of Health and Welfare's new drug development support project, investors began to appear, and clinical development proceeded smoothly. In 2017, we raised 100 billion won through a shareholder allocation capital increase."
A second challenge occurred during the COVID-19 pandemic, leading to the suspension of phase 3 clinical trials in the U.S. on two occasions. This resulted in substantial expenses, but more significantly, significant delays. Although we proceeded with phase 3 trials in Korea, there had been no progress in the U.S., leading to substantial fund depletion. Following this, market conditions worsened due to the war in Ukraine, negatively affecting investment environment.
–After overcoming difficulties, you succeeded in commercializing the new drug. What are your plans for entering overseas markets, including the U.S.?
"After securing funding, Vivozon plans to conduct clinical trials in the U.S. This is expected to take at least three years. For markets outside of the U.S., Vivozon Pharmaceutical is proactively preparing for exports and transfer. Since we have received product licensing domestically, discussions on export and transfer will accelerate."
–Is it true that you are also developing a non-narcotic painkiller in pill form?
"We are developing VVZ-2471 as an oral formulation. Since Anapra Injection is an injectable drug, there is discomfort with long-term use, but the oral formulation can enhance convenience. VVZ-2471 is currently undergoing phase 2 trials, and we anticipate results by the end of this year. It shows promise in addressing substance abuse disorders like drug addiction, and we are currently collaborating with U.S. addiction specialists to apply for research funding from the National Institute on Drug Abuse (NIDA) under the National Institutes of Health (NIH). We received very favorable scores in the first evaluation, which suggests that clinical development as a treatment for drug addiction is likely to proceed smoothly."
–Does VVZ-2471 have a similar mechanism of action as Anapra Injection?
"It is quite similar. Both Anapra Injection and VVZ-2471 have synergistic effects that disrupt the principles whereby pain signals generated peripherally are transmitted to the central nervous system and reduce the sensitivity of the central nervous system to pain. Pain signals are transmitted from the periphery to the central nervous system via the 'Glycine Transporter 2' and 'Glutamate Receptor 5,' with Anapra Injection targeting Glycine Transporter 2 and VVZ-2471 targeting Glutamate Receptor 5. The sensitivity to pain in the central nervous system is regulated by serotonin receptor 2a, which both Anapra Injection and VVZ-2471 target."
–What other R&D pipelines is Vivozon Group developing?
"Following Anapra Injection and VVZ-2471, the third pipeline is VVZ-3416. This substance targets three different pathways – one is a target that many global pharmaceutical companies were trying to develop as a treatment for degenerative brain diseases, another is a target currently used for Parkinson's disease treatment, and the last is an innovative target that plays a role in slowing the aging of cells or neurons. Various experiments have shown effectiveness against Parkinson's disease and senile dementia. Particularly, in animal model tests for senile dementia, we observed a remarkably promising result, completely halting the progression of the disease. Currently, non-clinical toxicology studies are nearing completion, and we anticipate entering phase 1 clinical trials within this year. A candidate substance for schizophrenia treatment is expected to undergo non-clinical research this year and enter phase 1 trials next year. Additionally, the candidate substance for treating atherosclerosis is still in the early research phase."