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May 23, 2021, South San Francisco, California and Taipei, Taiwan (Global News)-InspirMed Inc., a subsidiary of InspirMed Inc. TLC (Nasdaq:TLC, TWO: 4152)), specializing in the development of a proprietary inhalable liposome formulation plan, and recently provided data on the potential advantages of antiviral inhalable liposome formulations on the 23rdrd International Medical Aerosol Association (ISAM) Conference. The pharmacokinetic studies of inhalable liposome GS-441524 (named ISPM21) and inhalable liposome hydroxychloroquine (named ISPM19) showed that the concentration in the lung was significantly higher than that of traditional lipid inhalants, which is The prevention and/or treatment of COVID-19 provides the potential of ISPM21 and ISPM19.
GS-441524 is the main plasma metabolite of the antiviral drug remdesivir, which has been approved for the treatment of COVID-19 in the United States. GS-441524 has many advantages over Remdesivir, with better safety and efficacy. Remdesivir shows poor stability in the blood, and is subject to a high degree of liver extraction/bioactivation, resulting in liver toxicity. SARS-CoV-2 enters the cell surface through the ACE2 protein, and preferentially infects type I/type II (AT1/2) lung cells, but remdesivir is metabolized by alveolar macrophages instead of AT1/2, so it is not applicable For the delivery of active substances. Drugs act on cells that are crucial in the pathogenesis of COVID-19. The administration of remdesivir requires cyclodextrin, which is a complex excipient that can be eliminated by the kidneys and is associated with nephrotoxicity. In contrast, GS-441524 showed similar or higher potency than remdesivir in SARS-CoV-2 infected cells, and was biologically activated by enzymes that were highly expressed in AT1/2 cells, and in human liver and It exhibits excellent safety in kidney cells. In vitro, suggesting the feasibility of higher doses without hepatotoxicity or nephrotoxicity.
The good chemical properties of GS-441524-low molecular weight, greater hydrophilicity, greater positioning of AT1/2 cells and the ability to cross the blood-brain barrier-make it a promising treatment or preventive agent for COVID-19 Candidate. However, the low oral bioavailability of GS-441524 means that extremely high oral doses are required to reach therapeutic levels. By encapsulating GS-441524 in an inhalable liposome formulation to make ISPM21, there is no need for complex excipients, cyclodextrin, thereby eliminating nephrotoxicity, and targeted delivery through inhaled liposomes can increase the active drug The utilization rate of active drugs and prolong the exposure time of active drugs in the lungs.
“We are pleased to participate in the development of antiviral drugs against the COVID-19 pandemic by applying our proprietary lipid-based drug delivery platform to the development of new direct-acting antiviral drugs,” founder and chairman Keelung Hong The doctor commented. Chief Executive Officer of TLC. “Because our inhalable liposome technology directly targets the disease site, we hope that our emerging therapies can improve on the current COVID-19 treatment.”
At the ISAM conference currently being held at the Boise Convention Center in Boise, Idaho, USA (May 22 to 26), and in fact, members of InspirMed introduced the use of ISPM21 and ISPM19 in rats. Results of a rat pharmacokinetic study. , And data from the ISPM19 lung deposition study.
The key points of the poster presentation are as follows:
- ISPM21 administered intratracheally has a longer half-life of 22.8 hours. Compared with intravenous administration of the same dose of GS-441524 solution, the concentration in the lungs is significantly higher (>200 times), and the systemic exposure level in plasma is equivalent .
- Compared with oral intravenous free hydroxychloroquine, the recommended oral dose of ISPM19 for intratracheal administration is only 1% of hydroxychloroquine for COVID-19, with a longer half-life (~2.5 times) and higher lung exposure (~30 times).
- The lung deposition rate (inhaled dose) of ISPM19 atomized into aerosol was 26.67%.
- InspirMed’s proprietary inhalable liposome formulation program can deliver antiviral drugs directly into the lungs at sustained drug levels, which may provide therapeutic effects at lower doses while avoiding systemic side effects.
This Poster display It can be accessed under “Publications” in the “Press Room” section of the TLC website at: www.tlcbio.com.
About ISPM21
ISPM21 is a proprietary inhalable liposome formulation of GS-441524. The active ingredient reaches the lungs after taking remdesivir. Initially indicated for the treatment of hepatitis, remdesivir has shown efficacy in inhibiting the viral replication of the SARS-CoV-2 virus that causes COVID-19, and has been approved by the U.S. Food and Drug Administration (FDA) for treatment COVID-19 in need of treatment. Hospitalized. The good chemical properties of GS-441524-low molecular weight, greater hydrophilicity, greater positioning of AT1/2 cells and the ability to cross the blood-brain barrier-make it a promising treatment or preventive agent for COVID-19 Candidate. However, the low oral bioavailability of GS-441524 means that extremely high oral doses are required to reach therapeutic levels. By encapsulating GS-441524 in an inhalable liposome preparation (ISPM21), complex excipients, cyclodextrin, are not required, thereby potentially eliminating nephrotoxicity, and targeted delivery by inhaling liposomes can improve activity Utilization of drugs, and prolong the exposure time of active drugs in the lungs.
About ISPM19
ISPM19, formerly known as TLC19, is a proprietary inhalable liposome formulation of hydroxychloroquine.Hydroxychloroquine has shown potential to prevent and/or treat COVID-19 in vitro And preliminary clinical trials, but oral hydroxychloroquine cannot reach the therapeutic level due to its dose-limiting toxicity. ISPM19 uses up to 1% of oral hydroxychloroquine to deliver the drug directly to the airways and lungs, potentially avoiding systemic toxicity, while providing a sustained effective concentration at the main site of infection. ISPM19 is designed to be cost-effective, easy to access, and self-manageable via a portable atomizer. An ongoing randomized, controlled, and blinded randomized study is underway to evaluate the safety, tolerability and pharmacokinetics of increasing doses of inhaled ISPM19 in healthy volunteer subjects.
About InspirMed
InspirMed is a subsidiary of TLC, specializing in the development of inhalable liposome formulations for severe acute and chronic lung diseases. TLC (Nasdaq:TLC, TWO: 4152)) is a clinical-stage specialty pharmaceutical company dedicated to research and development of new nano-drugs, so as to maximize the potential of its proprietary lipid assembly drug delivery platform (LipAD™), including BioSeizer® The slow-release technology and NanoX™ active drug loading technology have multiple uses in the selection of active pharmaceutical ingredients and are scalable in production.
Contact Dawn Chi Corporate Communications dawn@tlcbio.com
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