Strategy

The latest and most advanced candidate, GENEX-3, is among the world's first trifold effector gene-drug candidates being assessed for the treatment of heart failure, following evaluation of the initial cohort data. It is a non-viral trifold-effector plasmid created to facilitate the continuous expression of human S100A1, SDF-1a, and VEGF-165 genes, targeting multiple pathways of heart failure. Recently, a Phase 1 trial was conducted to examine the safety and practicality of GENEX-3 by retrograde coronary sinus infusion in heart failure patients with outpatient LVAD. The six-month follow-up data from the Phase 1 trial of GENEX-3 revealed that the study met the primary endpoints needed to evaluate the safety and feasibility of GENEX-3.

Scientific Platform

Gene therapy employs a transport system, called a vector, to introduce a gene that encodes a therapeutic protein into cells within the body.

• Targeted gene therapy for the heart utilizing a novel threefold effector;
• Approved for initial human clinical trials;
• No health or security risks associated with GENEX-3 have been reported so far;
• Encouraging developments in Left Ventricular Ejection Fraction (LVEF) and 6-Minute Walk Test (6MWT) performance;
• Enrollment and administration of the initial Phase I clinical trial of GENEX-3 have been accomplished;
• Investigating sources of finance for furthering GENEX-3, along with growing our range of sophisticated cardiovascular gene therapies.

Our company is pleased to furnish the six-month follow-up information from the initial testing of GENEX-3, a multi-genetic investigational therapeutic option being evaluated for gene therapy treatment of heart failure. GENEX-3 gene therapy involves a non-viral plasmid composed of human SDF-1α, VEGF165, and S100A1 gene products, which affect the recruitment of progenitor cells, angiogenesis, and calcium handling respectively. This gene therapy aims to target the underlying molecular alterations of myocardial remodeling and is conveyed to the ventricle through retrograde coronary sinus infusion (RCSI).

The primary aim of Phase I is to assess the safety of GENEX-3 infusion into the myocardium of LVAD patients and to demonstrate its safety and feasibility for RCSI. Additionally, the study will evaluate secondary outcomes, such as improvements in 6MWT duration and distance, and quality of life.

Twelve individuals with chronic heart failure received GENEX-3 as part of either Cohort 1 (70 mg/30 ml; n=6) or Cohort 2 (70 mg/70 mL; n=6). The primary endpoints of the study were to assess the safety and viability of GENEX-3, with 10 of the patients receiving a 6-month follow-up. The infusion of GENEX-3 was generally safe, with no adverse events related to the drug, but one serious event was attributed to the procedure.

In the preliminary assessment of secondary endpoints, at least a six-point rise in total score, as measured by a validated Clinical Outcome Assessment tool, was observed in half of the evaluable patients after a six-month follow-up. This group included four patients from Cohort 1 and one from Cohort 2. Additionally, half of the evaluable individuals had an improvement of more than fifty meters in the 6MWT from their pre-treatment baseline after six months of treatment.

Our cardiologists and key opinion leaders in the field of heart failure have reported that the data supports the good tolerability of GENEX-3 in patients with chronic heart failure who are on an LVAD. Furthermore, there is a positive indication that these patients had improved patient-reported outcomes after six months of treatment. We are optimistic that GENEX-3 is capable of addressing the pressing unmet medical need of those suffering from heart failure, considering that it has met the primary safety and feasibility endpoints, and the provisional assessments of the secondary endpoints have yielded encouraging results in terms of quality of life after six months of treatment.