Engensis (VM202) is a plasmid DNA designed to simultaneously express two isoforms of hepatocyte growth factor (HGF), HGF 728 and HGF 723 . Engensis is optimized to produce HGF protein at a high level when delivered to the muscle. Through simple intramuscular injections, Engensis is being studied in clinical trials to determine whether it can provide safe and efficacious treatment effects for various ischemic diseases or neurodegenerative diseases, including diabetic peripheral neuropathy (DPN), diabetic foot ulcer (DFU), and coronary artery disease (CAD).
HGF is a multifunctional protein with highly potent angiogenic and neurotrophic properties. Its biological function is mediated by its receptor called c-Met. It has been reported that HGF activates c-Met receptor to induce a variety of biological responses such as inducing the formation of new blood vessels, suppressing fibrosis and inflammation, and providing neuroprotection.
HGF has 4 naturally occurring isoforms; two of them, HGF 728 and HGF 723, are the main forms that activate the c-Met receptor. At Helixmith, we have developed a special cDNA-genome hybrid gene that guarantees the simultaneous expression of HGF 728 and HGF 723 to maximize the biological activities of HGF.
Currently, Engensis clinical programs have advanced in the US as follows:
- Diabetic peripheral neuropathy (DPN): US phase III trial ongoing, 25 sites and 500+ subjects enrolled, expected to complete and announce results in 2019
- Diabetic foot ulcer (DFU): US phase III trial ongoing, 28 sites and 300+ subjects planned
- Amyotrophic lateral sclerosis (ALS): Positive trends on efficacy and safety observed from US phase I trial, US phase II trial planned to start in 2019
- Coronary artery disease (CAD): Positive trends on efficacy and safety observed from Korea phase I trial
Engensis is the only plasmid DNA-based biopharmaceutical that simultaneously produces high levels of two isoforms of hepatocyte growth factor—HGF 728 and HGF 723. Both isoforms of HGF are simultaneously expressed then bind to the c-Met receptor, inducing multiple bioactivities that include the formation of new blood vessels, nerve regeneration, suppression of pain-related factors, and amelioration of amyotrophic conditions.
Phase III clinical trials using Engensis are currently underway in the United States for diabetic peripheral neuropathy and chronic diabetic foot ulcer, and phase II studies for amyotrophic lateral sclerosis and myocardial infarction are in preparation.