1. Engensis in DPN

Diabetic peripheral neuropathy (DPN) is one of the most commonly encountered debilitating complication of diabetes, typically presenting with burning, tingling, throbbing, and stabbing pain.

About 30 million US adults have diabetes. About 28.5% of diabetics suffer from DPN, and 40-50% of those patients suffer from painful DPN. Currently approved medications for PDPN are palliative, only managing the pain, with possible serious side effects and can be highly addictive.

With Engensis, we are trying a new approach. We believe that Engensis reverses the underlying cause of neuropathy through an angio-neurorestorative effect. Because it has this possible mechanism of action, the US FDA granted RMAT (Regenerative Medicine Advanced Therapy) designation to Engensis and we decided to look for this effect in the ongoing Phase III trial in the US.

Safety

To date, Engensis appears to be relatively safe. In the Phase I and Phase II trials conducted so far, no serious adverse events were found directly attributed to Engensis. And, because the encoded gene is indigenous, immune response concerns that may arise with other gene therapies are less likely to be an issue with Engensis.

Efficacy

Pain scores obtained during clinical trials appear to show long-lasting effects of Engensis on pain severity. Patients who were not on pregabalin or gabapentin appeared to show higher improvement rates, suggesting that Engensis may have better utility as a sole treatment.

2. Engensis in DFU

Diabetic foot ulcers (DFU) can be chronic, non-healing foot ulcers, a major complication of both diabetes and peripheral arterial disease (PAD) that is caused by impediment of the wound-healing process.

Over 6.5 million people in the US alone have chronic, non-healing foot ulcers; many of them also have peripheral neuropathy, which results in numbness or pain in the legs and arms. The market size for DFU had grown up to USD 3.6 billion in 2017. Current treatments are limited to wound care dressings or pain management, and 25% of wounds progress to the extent that amputation is required.

Engensis is currently under development as a possible fundamental treatment for chronic DFU with the hope that it that can heal the ulcer by supplying sufficient blood through new blood vessel formation around occluded or narrowed blood vessels towards the lower extremities.

Safety

To date, Engensis appears to be relatively safe. In the Phase I and Phase II trials conducted so far, no serious adverse events were found directly attributed to Engensis. And, because the encoded gene is indigenous, immune response concerns that may arise with other gene therapies are less likely to be an issue with Engensis. In addition, the drug is injected locally with no evidence of systemic exposure thus far, which should contribute to a good safety profile.

Efficacy

In the Phase I and Phase II trials, both low-dose and high-dose patients appeared to have significant changes in their ulcers – some healed completely, others decreased in size.

3. Engensis in ALS

Amyotrophic Lateral Sclerosis (ALS), more commonly known as Lou Gehrig’s disease, is a progressive and fatal neuromuscular disease. ALS is characterized by the destruction of motor neurons necessary for the mobility muscles. There is no known cause nor identified cure for ALS.

16,583 patients are identified as having definite ALS in the US and the estimated prevalence of the disease is 5.2 per 100,000. (National ALS Registry, United States, 2015)

Engensis is under development to target ALS. When Engensis is injected along the peripheral nerves and their branches, the localized production of HGF may protect nerves and promote the growth of neurons while also ameliorating atrophic conditions.

The US FDA granted orphan drug and fast track designations for Engensis for the potential treatment of ALS. With IND approved from the FDA, Phase II clinical trial of Engensis-ALS is in preparation.

Safety

There have been no serious adverse events directly attributed to Engensis in the Phase I/II trial, except for grade 1 injection site reactions, which are resolved uneventfully. Also, the encoded gene is indigenous, eliminating immune response concerns possibly attached with other gene therapies.

Efficacy

ALSFRS-R (evaluating overall ALS conditions) and MRC Scale (evaluating muscle strength) from the Phase I/II trial showed a trend that the ALS conditions were stabilized for 3 months after the 1st injection of Engensis.

4. Engensis in CAD

Coronary artery disease (CAD), also known as ischemic heart disease (IHD), occurs when one or more of the coronary arteries are narrowed or occluded, resulting in the decrease of blood supply to the heart muscle.

IHD is the third leading cause of death worldwide. The disease recurs in 30% of the patients who have received surgical procedures and medication, which are the most common treatments. Furthermore, about 10% of the patient population does not respond to medication and cannot undergo surgery.

Engensis promotes blood vessel formation in the ischemic area by HGF-based angiogenesis. HGF-based angiogenesis may also contribute to cardiac muscle function improvement through the suppression of apoptosis and cardiac fibrosis following myocardial infarction, a form of CAD.

Helixmith has completed a Phase I trial of Engensis in patients with ischemic heart disease. The company is preparing to run a Phase II clinical trial in Korea using Engensis in patients who had percutaneous coronary intervention (PCI) for an anterior wall infarction of the left ventricle following acute myocardial infarction.

Safety

No unexpected serious adverse events or deaths were observed in the Phase I trial. HGF protein levels in plasma remained stable throughout the study without any noticeable change, and antibodies to human HGF proteins expressed by injection with Engensis were not detected in serum during the follow-up period.

Efficacy

Engensis appeared to improve myocardial perfusion, wall thickness, and wall motion in patients with angina pectoris in the Phase I trial.