Entos Pharmaceuticals, a clinical-stage genetic medicines company committed to using its Fusogenix PLV technology to develop cures and improve the lives of patients and their families, announced that the California Institute for Regenerative Medicine (CIRM) has awarded the company a $4 million grant. These funds will support the completion of IND-enabling activities for the development of ENTLEP001, a durable genetic medicine for the treatment of congenital generalized lipodystrophy (CGL).
CGL is a rare genetic disorder that is caused by mutations in the human leptin gene. And people with CGL are leptin-deficient and cannot make adipose tissue. This disorder is associated with severe, hard-to-treat diabetes, hypertriglyceridemia, and potential complications affecting the liver and heart.
ENTLEP001 is a systemically administered investigational gene therapy utilizing the Fusogenix PLV platform to express unmodified human leptin in the body. This treatment was designed to be durable, redosable, and provide biologically relevant levels of native human leptin expression. And preclinical studies with ENTLEP001 using a leptin-deficient mouse model resulted in clinically relevant leptin expression, disease-modifying activity including normalization of glucose and insulin levels, and decreased weight gain and food intake.
The Fusogenix PLV platform is a fusion-powered delivery system for genetic medicines combining the best aspects of viral and non-viral approaches. Utilizing a completely new mechanism for intracellular delivery of RNA, DNA and gene editing therapies, Fusogenix PLV is suitable for a wide range of best-in-class genetic medicines. Details regarding the platform’s safety, efficacy, and biodistribution in various animal models were published in Cell in September 2024.
KEY QUOTES:
“Despite advancements in CGL treatment with FDA-approved metreleptin, there are still significant unmet needs. Metreleptin requires daily subcutaneous injections and in some patients is associated with significant injection site adverse events. Although rare, there are reported cases of neutralizing anti-leptin antibody in patients receiving metreleptin. In contrast, ENTLEP001 is a genetic medicine that expresses native human leptin and may require dosing only once or twice a year, eliminating injection site reactions, simplifying patient compliance, and improving outcomes.”
- Steve Chen, MD, CMO of Entos Pharmaceuticals
“This award from CIRM is an important validation for our lead program in CGL as we work to advance our second product into the clinic using the Fusogenix PLV platform. We deeply appreciate their support and recognition of the crucial need to address rare genetic disorders like congenital generalized lipodystrophy and the potential for novel genetic medicine approaches like the Fusogenix PLV to create life-changing treatments for patients and their families.”
• ⁃ John Lewis, CEO of Entos Pharmaceuticals
