• Funding will advance the development of ENTLEP001, a durable and redosable genetic medicine for the treatment of congenital generalized lipodystrophy (CGL).

February 05, 2025 11:10 AM Eastern Standard Time

SAN DIEGO–(BUSINESS WIRE)–Entos^® Pharmaceuticals (Entos), 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 today that the California Institute for Regenerative Medicine (CIRM) has awarded the company a $4M USD grant. The 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).

“Despite advancements in CGL treatment with FDA-approved metreleptin, there are still significant unmet needs”Post this

CGL is a rare genetic disorder caused by mutations in the human leptin gene. People with CGL are leptin-deficient and cannot make adipose tissue. The 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 using the Fusogenix PLV platform to express unmodified human leptin in the body. The treatment is designed to be durable, redosable, and provide biologically relevant levels of native human leptin expression. 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 that combines the best aspects of viral and non-viral approaches. Using 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.

“Despite advancements in CGL treatment with FDA-approved metreleptin, there are still significant unmet needs,” said Steve Chen, MD, CMO of Entos Pharmaceuticals. “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.”

“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,” said John Lewis, CEO of Entos Pharmaceuticals. “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.”

About Congenital Generalized Lipodystrophy (CGL)
Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is a rare genetic disorder characterized by the near total loss of adipose tissue associated with extreme muscularity that is often present at birth or soon thereafter. CGL is associated with metabolic complications related to insulin resistance such as severe diabetes and hypertriglyceridemia. Diabetes associated with CGL is often very difficult to treat. Additional complications affecting the liver and heart can also occur. The symptoms and severity of CGL can vary greatly from one person to another. CGL is caused by mutations in the human leptin gene LEP.

About Entos Pharmaceuticals Inc.
A new reality in genetic medicine lies ahead, one that will be ushered in with the advent of safe, effective, and re-dosable nucleic acid delivery technologies. Since its inception in 2016, Entos® has been dedicated to advancing next-generation genetic medicines using our proprietary Fusogenix™ PLV™ drug delivery system. The Fusogenix PLV platform is formulated with FAST proteins to enable the delivery of nucleic acid to target cells through direct fusion. Entos is pioneering the development of life-changing medicines for patients and has partnered with global companies, such as Eli Lilly, to accelerate and expand the impact of our platform. Entos Pharmaceuticals Inc. is headquartered in Edmonton, Canada, with its wholly owned U.S. and U.K. subsidiaries based in San Diego, California and London, United Kingdom, respectively. For more information, visit www.entospharma.com, or follow Entos on LinkedIn.

About California Institute for Regenerative Medicine (CIRM)
At CIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and act with a sense of urgency to succeed in that mission.
To meet this challenge, our team of highly trained and experienced professionals actively partners with both academia and industry in a hands-on, entrepreneurial environment to fast track the development of today’s most promising stem cell technologies.
With $5.5 billion in funding and more than 150 active stem cell programs in our portfolio, CIRM is the world’s largest institution dedicated to helping people by bringing the future of cellular medicine closer to reality.
For more information go to www.cirm.ca.gov.

Forward Looking Statements
This press release contains forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements contained in this press release include statements regarding Entos and its belief as to the mode of action and potential and benefits of the Fusogenix proteolipid vehicle platform and other statements related to anticipated developments in the Company’s business and technologies. In any forward-looking statement in which Entos expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to have a reasonable basis, but there can be no assurance that the statement or expectation, or belief will be achieved. Such forward-looking statements involve known and unknown risks and uncertainties, which could cause the Company’s actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue research and development projects, the efficacy of Fusogenix as a nucleic acid delivery vehicle, uncertainties related to the research and development of pharmaceuticals, uncertainties related to the regulatory process and general changes to the economic environment. We may incur expenses or delays relating to such events outside of our control, which could have a material adverse impact on our business, operating results, and financial condition. Investors should consult with the U.S. Securities Commission for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake any obligation to update these forward-looking statements except as required by applicable laws.

Entos^® word mark and design logo, Fusogenix™ and PLV™ are registered trademarks of Entos Pharmaceuticals Inc. All other trademarks and registered trademarks are the property of their respective owners.

Contacts

Entos Pharmaceuticals Corporate Contact:
John Lewis, Ph.D., Founder and CEO
info@entospharma.com

Entos Pharmaceuticals Media Contact:
Perrin Beatty, Ph.D.
media@entospharma.com
1-800-727-0884

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