South Korean-based Enzychem Lifesciences (KOSDAQ: 183490) just announced that the US Food and Drug Administration (FDA) has accepted its Investigational New Drug Application (IND) to evaluate its lead therapeutic candidate EC-18, in a Phase 2 clinical trial in patients with Acute Respiratory Disease Syndrome (ARDS) due to COVID-19 pneumonia. A Phase 2 study for EC-18 in Preventing ARDS due to novel coronavirus pneumonia is currently ongoing in South Korea. Key opinion leader Dr. Cameron Robert Wolfe, from Duke University, signs on to lead the COVID-19 program in the United States. This study addresses a possible prevention of what becomes a very dangerous situation in COVID-19 patients.
A Dire Situation
The majority of individuals who get infected with SARS-CoV-2, the virus behind COVID-19, only have mild or moderate symptoms and can recover thanks to supportive care, suggests the World Health Organization. However, if someone develops a cough, fever, and difficulty breathing, this can lead to more severe problems, including a severe or critical condition called acute respiratory distress syndrome (ARDS). As Johns Hopkins Medicine lung disease expert Panagis Galiatsatos, MD, MHS notes, COVID-19 can cause various lung-related complications and long-lasting damage. In the case of ARDS, as COVID-19 can lead to a progressive pneumonia, more of the “air sacs in the lungs get filled with fluid leaking from the only blood vessels in the lungs.” This can lead to shortness of breath and ultimately to ARDS, a form of lung failure. It is an incredibly dangerous situation wherein many cases patients cannot breathe on their own and require a ventilator to help them circulate oxygen throughout the body. The death rates become high at this point. Researchers are now uncovering long-lasting pulmonary scarring and other potential long-term damages for those that pull through and survive.
What is EC-18?
EC-18 is the company’s proprietary compound originally delivered from Sika deer antlers, which act as a Pattern Recognition Receptors (PRR) (e.g., TLR4) endocytic trafficking accelerator, contributing to the swift removal of PAMPs/DAMPs.
For acute respiratory distress syndrome associated with COVID-19, dysregulation of the TLRs signaling pathway is reported to be relevant. With this unique mechanism of action, the sponsor (Enzychem) is developing EC-18 for indications including chemoradiation induced oral mucositis (CRIOM), chemotherapy induced neutropenia (CIN), and acute radiation syndrome (ARS).
EC-18 has evidenced in preclinical data to control neutrophil infiltration, thereby modulating the inflammatory cytokine and chemokine signaling that has been implicated in these severe COVID-19 cases. EC-18 has also been shown to improve lung function and reduce inflammation and fibrosis in multiple animal models of immune-mediated acute lung injury and other inflammatory diseases, such as pneumonia.
The Korean Phase 2 COVID-19 Study
In Korea, the sponsor launched a clinical trial targeting COVID-19 in May 2020. Led by Hyewon Jeong with the Chungbuk National University Hospital (CNUH), the sponsor and investigators are studying the effect of EC-18 in COVID-19 patients with pneumonia. The goal of the study is to reduce the ARDS rate.
The US-based Phase 2 study has been designed as a multi-center, randomized, double-blind, placebo-controlled trial to investigate the safety and efficacy of EC-18 in preventing the progression of COVID-19 infection to severe pneumonia or ARDS. The study duration is 12 months from the FDA approval date. The study plans to enroll 60 subjects in total—30 patients in the EC-18 arm, and 30 patients on the placebo arm. The dosing schedule will be 2000 mg QD (once daily), over a treatment period of 28 days. The Phase 2 study’s primary endpoint is the proportion of patients alive and free of respiratory failure through Day 28.
Infectious Disease Expert On-Board
Enzychem has brought on board Dr. Cameron Robert Wolfe as the lead scientific advisor for the COVID-19 program, an internationally renowned specialist in infectious diseases out of Duke University School of Medicine. Dr. Wolfe has been involved with several COVID-19 research grants, including NIAID’s ACTT/Remdesivir initiatives.
CEO Ki Young Sohn expressed his upbeat outlook based on the recent FDA action and the potential of the investigational product commenting, “We are extremely pleased with the FDA’s decision and believe there is strong scientific rationale for the development of EC-18 to treat ARDS in COVID-19 patients. This IND is the first step in Enzychem’s evolution into becoming a global biopharmaceutical leader. We look forward to advancing EC-18 as a potential new treatment option for patients with confirmed COVID-19, based on EC-18’s unique mechanism of action.”
Phase 2 Study in U.S. Current
In 2018, the company launched a Phase 2 randomized, double-blind, placebo-controlled, 2-stage clinical trial in the United States in subjects with squamous cell cancers of the mouth, oropharynx, hypopharynx, and nasopharynx planned to receive standard fractionalized IMRT-delivered radiotherapy with concomitant chemotherapy (cisplatin). This study’s primary endpoint seeks to measure the duration of severe oral mucositis (grade 3 or 4) for a seven-week duration. Several secondary measures are included as well. The study’s preliminary estimated completion date is the end of 2020. This Phase 2 study is led by Principal Investigators Dong Moon Shin, Emory University Winship Cancer Institute, and Mahesh Kudrimoti, University of Kentucky, Chandler Medical Center.
About Enzychem Life Sciences
Publicly traded on the Korean Exchange (KOSDAQ: 183490), the company was founded in 1999 to focus on developing oral small molecule therapies for patients with significant unmet needs in oncology, inflammatory, and severe respiratory diseases. Their lead candidate, EC-18, is currently in a Phase 2 clinical trial for oral mucositis and chemotherapy-induced neutropenia. The company is also developing EC-18 in metabolic disorders such as nonalcoholic steatohepatitis (NASH) in combination with cancer therapy with immune checkpoint inhibitors (ICIs) and severe respiratory diseases as a potential therapy for COVID-19. EC-18, or PLAG, is a fully synthesized substance, derived from an ingredient in Sika deer antlers.