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▎WuXi AppTec Content Team Editor On January 6, 2022, Eli Lilly and Company announced that it has acquired the exclusive rights to Entos Pharmaceuticals' proprietary Fusogenix nucleic acid delivery technology platform to develop and commercialize drugs targeting the central and peripheral nervous systems.
Nucleic acid therapy
.
The press release notes that Fusogenix proteo-lipid vehicles (PLVs), an innovative delivery technology, has the potential to overcome key delivery challenges for nucleic acid therapeutic modalities
.
The rapid development of nucleic acid therapy in recent years has offered hope for a cure for many previously untreatable diseases
.
A variety of gene therapies are under development with the promise of eradicating genetic diseases, halting cancer and reversing aging
.
However, these therapies all face the same challenge: how to safely and effectively deliver the payload to specific target cells
.
Researchers have attempted delivery using cationic or ionizable lipid nanoparticle (LNP) carriers, but clinical trials have shown that these approaches are highly toxic and still have limitations in targeting organs other than the liver
.
Fusogenix proteolipid carriers are composed of well-tolerated neutral lipids, and specialized fusion-associated small transmembrane proteins (FASTs), enabling efficient fusion and intracellular delivery of therapeutic nucleic acid payloads
.
This PLV platform combines the low toxicity profile of neutral lipid formulations with the high efficiency of fusion protein-mediated delivery technology
.
Entos has also developed a library of Fusogenix PLV formulations for efficient delivery of multiple therapeutic nucleic acids including gene therapy, mRNA, miRNA, RNAi and CRISPR
.
Currently, Entos' product pipeline covers oncology drugs, DNA vaccines, antiviral drugs, gene editing, immunotherapy drugs and anti-aging drugs
.
▲The Fusogenix platform catalyzes rapid lipid mixing between PLV and the cytoplasmic membrane through the FAST protein, bypassing endocytosis and delivering the payload directly into the cytoplasm (Image source: Entos official website) Clinically obtained data show that this The carrier still exhibits a good safety profile at dose levels far exceeding those expected to be effective in humans
.
Tolerability studies showed that even at very high doses, no adverse pathology was reported, either in the main organs of uptake of the therapy, or in the liver and spleen
.
In this collaboration, Entos will be responsible for generating, developing and optimizing PLVs utilizing its proprietary Fusogenix technology platform
.
Eli Lilly will select specific PLVs for further clinical development and commercialization
.
Entos will receive an up-front payment of $50 million and is eligible to receive up to $400 million in potential development and commercial milestone payments for the co-product, as well as future royalties on the product
.
"Nucleic acid-based therapies hold great promise for addressing the biological etiologies of many serious diseases with significant unmet medical needs
,
" said Andrew Adams, Vice President of Lilly Genetic Medicine .
The barrier to efficient delivery to target cells is critical to realizing its potential
.
We look forward to working with Entos to help us overcome this challenge and develop potential new therapies that may improve patient outcomes
.
"Reference: [1] Lilly and Entos Pharmaceuticals Enter into Research and Collaboration Agreement to Support the Development of Innovative Therapies in Multiple Neurologic Indications.
Retrieved January 6, 2022, from https:// lilly-and-entos-pharmaceuticals-enter-into-research-and-collaboration-agreement-to-support-the-development-of-innovative-therapies-in-multiple-neurologic-indications-301454740.
html[2] You know AAV and LNP.
What about PLV? Eli Lilly lines up new vehicle to deliver its genetic medicines.
Retrieved January 6, 2022, from https://endpts.
com/you-know-aav-and-lnp-what-about-plv -eli-lilly-lines-up-new-vehicle-to-deliver-its-genetic-medicines/Disclaimer: The WuXi AppTec content team focuses on introducing the progress of global biomedical health research
.
This article is for information exchange purposes only, and the opinions in the article It does not represent WuXi AppTec's position, nor does it represent WuXi AppTec's support or opposition to the views in this article
.
This article is not a treatment recommendation
.
For guidance on treatment options, please visit a regular hospital
.
Nucleic acid therapy
.
The press release notes that Fusogenix proteo-lipid vehicles (PLVs), an innovative delivery technology, has the potential to overcome key delivery challenges for nucleic acid therapeutic modalities
.
The rapid development of nucleic acid therapy in recent years has offered hope for a cure for many previously untreatable diseases
.
A variety of gene therapies are under development with the promise of eradicating genetic diseases, halting cancer and reversing aging
.
However, these therapies all face the same challenge: how to safely and effectively deliver the payload to specific target cells
.
Researchers have attempted delivery using cationic or ionizable lipid nanoparticle (LNP) carriers, but clinical trials have shown that these approaches are highly toxic and still have limitations in targeting organs other than the liver
.
Fusogenix proteolipid carriers are composed of well-tolerated neutral lipids, and specialized fusion-associated small transmembrane proteins (FASTs), enabling efficient fusion and intracellular delivery of therapeutic nucleic acid payloads
.
This PLV platform combines the low toxicity profile of neutral lipid formulations with the high efficiency of fusion protein-mediated delivery technology
.
Entos has also developed a library of Fusogenix PLV formulations for efficient delivery of multiple therapeutic nucleic acids including gene therapy, mRNA, miRNA, RNAi and CRISPR
.
Currently, Entos' product pipeline covers oncology drugs, DNA vaccines, antiviral drugs, gene editing, immunotherapy drugs and anti-aging drugs
.
▲The Fusogenix platform catalyzes rapid lipid mixing between PLV and the cytoplasmic membrane through the FAST protein, bypassing endocytosis and delivering the payload directly into the cytoplasm (Image source: Entos official website) Clinically obtained data show that this The carrier still exhibits a good safety profile at dose levels far exceeding those expected to be effective in humans
.
Tolerability studies showed that even at very high doses, no adverse pathology was reported, either in the main organs of uptake of the therapy, or in the liver and spleen
.
In this collaboration, Entos will be responsible for generating, developing and optimizing PLVs utilizing its proprietary Fusogenix technology platform
.
Eli Lilly will select specific PLVs for further clinical development and commercialization
.
Entos will receive an up-front payment of $50 million and is eligible to receive up to $400 million in potential development and commercial milestone payments for the co-product, as well as future royalties on the product
.
"Nucleic acid-based therapies hold great promise for addressing the biological etiologies of many serious diseases with significant unmet medical needs
,
" said Andrew Adams, Vice President of Lilly Genetic Medicine .
The barrier to efficient delivery to target cells is critical to realizing its potential
.
We look forward to working with Entos to help us overcome this challenge and develop potential new therapies that may improve patient outcomes
.
"Reference: [1] Lilly and Entos Pharmaceuticals Enter into Research and Collaboration Agreement to Support the Development of Innovative Therapies in Multiple Neurologic Indications.
Retrieved January 6, 2022, from https:// lilly-and-entos-pharmaceuticals-enter-into-research-and-collaboration-agreement-to-support-the-development-of-innovative-therapies-in-multiple-neurologic-indications-301454740.
html[2] You know AAV and LNP.
What about PLV? Eli Lilly lines up new vehicle to deliver its genetic medicines.
Retrieved January 6, 2022, from https://endpts.
com/you-know-aav-and-lnp-what-about-plv -eli-lilly-lines-up-new-vehicle-to-deliver-its-genetic-medicines/Disclaimer: The WuXi AppTec content team focuses on introducing the progress of global biomedical health research
.
This article is for information exchange purposes only, and the opinions in the article It does not represent WuXi AppTec's position, nor does it represent WuXi AppTec's support or opposition to the views in this article
.
This article is not a treatment recommendation
.
For guidance on treatment options, please visit a regular hospital
.
