Entos Pharmaceuticals: Technology and Clinical Pipeline

Entos Pharmaceuticals, a biotechnology company based in Edmonton, Canada, develops next-generation genetic medicines to address unmet medical needs. Established in 2016, Entos focuses on creating safe, effective, and redosable nucleic acid delivery technologies.

The DOME Platform: Entos’s Core Technology

Entos Pharmaceuticals utilizes its proprietary Fusogenix™ Proteo-Lipid Vehicle (PLV) platform, also known as the Delivery Optimization and Molecule Engineering (DOME) platform. This fusion-powered delivery system for genetic medicines combines aspects of both viral and non-viral approaches. The Fusogenix PLV system delivers nucleic acids, such as RNA, DNA, or gene editing therapies, directly into the cytoplasm of target cells.

The core mechanism of the Fusogenix PLV platform involves proprietary fusogenic FAST proteins. These proteins facilitate direct fusion with the cell membrane, allowing the genetic material to bypass the endocytosis pathway. This direct delivery ensures the therapeutic payload remains intact and unmodified upon entry into the cell.

A key advantage of the Fusogenix PLV platform is its ability to enhance stability and improve targeted delivery beyond the liver. Many traditional delivery methods often result in off-target effects or preferential uptake by the liver. The Fusogenix PLV technology is inherently non-liver tropic, enabling precise delivery to various cells and tissues throughout the body.

The platform also allows for repeat dosing of genetic medicines, which is often not feasible with other delivery systems due to potential immunogenicity. Entos’s Fusogenix Optimization and CUStomization with AI (FOCUS-AI) workflow refines this process. FOCUS-AI leverages the platform’s unique features to design tailored delivery solutions for specific cell and tissue targeting, using artificial intelligence algorithms.

Therapeutic Applications of DOME

The Fusogenix PLV platform addresses a broad spectrum of therapeutic areas, including oncology, rare genetic disorders, and infectious diseases. Its ability to precisely deliver genetic material to specific cells makes it suitable for addressing underlying causes. For example, in rare genetic disorders, the platform can deliver full-length genes to correct genetic defects.

The platform’s non-immunogenic nature and capacity for repeat dosing are particularly beneficial for chronic conditions requiring ongoing treatment, allowing sustained therapeutic effects without triggering undesirable immune responses. The Fusogenix PLV has been developed as Fusogenix Systemic PLV for systemic gene therapies and gene editing, and Fusogenix Ocular PLV for eye gene editing and therapy through multiple routes of administration.

For infectious diseases, the Fusogenix Vaccine PLV enables a potent and durable immune response to antigens after intramuscular administration. The platform’s adaptability to various nucleic acid types, including mRNA, DNA, and gene editing tools, broadens its applications across diverse disease categories. Entos’s partnerships, such as with Eli Lilly, demonstrate the platform’s versatility in targeting conditions affecting the central and peripheral nervous system.

Entos’s Clinical Pipeline and Development

Entos Pharmaceuticals is actively advancing several drug candidates leveraging its Fusogenix PLV platform. One notable program is Covigenix VAX-002, a COVID-19 booster vaccine. This vaccine candidate, formulated with the Fusogenix PLV technology and plasmid DNA expressing SARS-CoV-2 antigens, has completed Phase 1 enrollment in a Phase 1/2 clinical trial in Canada.

The Phase 1 portion of the Covigenix VAX-002 study involved 50 participants, determining the optimal dose for booster vaccination. The subsequent Phase 2 will evaluate safety and immunogenicity in 250 participants. This trial is being conducted at 12 sites across Canada, including locations in Alberta, Ontario, Quebec, and Nova Scotia.

Beyond infectious diseases, Entos is developing therapies for rare genetic diseases, such as Duchenne Muscular Dystrophy (DMD) and Congenital Lipodystrophy. The company received an initial $1 million investment from CureDuchenne Ventures to develop a muscle-targeting therapy for DMD, aiming to deliver full-length dystrophin. This approach seeks to overcome limitations of current gene therapies by allowing for redosing and delivering full-length dystrophin to all necessary muscle tissues.

Entos also has partnered programs, including a collaboration with Eli Lilly and Company to research, develop, and commercialize nucleic acid products targeting the central and peripheral nervous system. This partnership, initiated with a $50 million upfront payment, allows Entos to potentially receive up to $400 million in milestone payments and royalties. Additionally, Entos is developing candidates for ophthalmic conditions and oncology.

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