InspirMed highlights encouraging data on ISPM21 and ISPM19
SOUTH SAN FRANCISCO, Calif. And TAIPEI, Taiwan, May 23, 2021 (GLOBE NEWSWIRE) – InspirMed Inc., a subsidiary of TLC (Nasdaq: TLC, TWO: 4152) specializing in the development of proprietary inhalable liposome formulation programs, recently presented data on the potential benefits of inhalable liposome formulations of antiviral drugs at 23rd Congress of the International Society of Aerosols in Medicine (ISAM). Pharmacokinetic studies with inhalable liposomal GS-441524 (called ISPM21) and inhalable liposomal hydroxychloroquine (called ISPM19) have shown significantly higher concentrations in the lungs than their conventional counterparts, giving NIMP21 and ISPM19 potential as COVID-19 prophylaxis and / or treatment.
GS-441524 is the major plasma metabolite of the antiviral prodrug remdesivir, which is approved in the United States for the treatment of COVID-19. GS-441524 has several advantages over remdesivir, with better safety and efficacy profiles. Remdesivir exhibits low stability in the blood and is subject to high hepatic extraction / bioactivation, resulting in hepatotoxicity. SARS-CoV-2 enters cells via the ACE2 protein on the cell surface and preferentially infects type I / type II pneumocytes (AT1 / 2), but remdesivir is metabolized by alveolar macrophages rather than AT1 / 2, which makes it ill-suited for asset administration. drug to cells critical in the pathogenesis of COVID-19. Administration of remdesivir requires cyclodextrin, a complex excipient excreted by the kidneys and associated with nephrotoxicity. In comparison, GS-441524 demonstrated similar or superior potency to remdesivir in SARS-CoV-2 infected cells, is bioactivated by highly expressed enzymes in AT1 / 2 cells, and demonstrated an excellent safety profile. against human liver and kidney cells. vitro, suggesting the feasibility of a higher dosage without hepatotoxicity or nephrotoxicity.
The favorable chemical properties of GS-441524 – low molecular weight, greater hydrophilicity, greater localization in AT1 / 2 cells, and the ability to cross the blood-brain barrier – make it a promising candidate as a therapeutic or prophylactic agent for COVID-19. However, the low oral bioavailability of GS-441524 means that an extremely high oral dose would be required to reach therapeutic levels. By encapsulating GS-441524 in an inhalable liposome formulation to make NIMP21, there is no need for the cyclodextrin complex excipient, thereby eliminating nephrotoxicity, and targeted delivery by inhalation of liposomes allows for increased availability and efficiency. prolonged exposure of the active drug in the lungs.
“We are pleased to participate in the development of antiviral treatments in the fight against the COVID-19 pandemic by applying our proprietary lipid-based drug delivery platform to the development of new direct-acting antivirals,” commented the Dr Keelung Hong, Founder and Chairman. and CEO of TLC. “Because our inhalable liposome technology directly targets the disease site, we hope that our emerging therapies can be improved over current COVID-19 treatments.”
At the ISAM Congress, which is currently being held (May 22-26) at the Boise Conference Center in Boise, Idaho, USA, as well as virtually, InspirMed members presented the results of two pharmacokinetic studies. distinct in rats on ISPM21 and ISPM19, respectively. , as well as an ISPM19 pulmonary deposition study.
The highlights of the poster presentation are as follows:
- NIMP21 administered intratracheally had a long half-life of 22.8 hours, with significantly higher (> 200-fold) concentrations in the lungs and comparable systemic exposure in plasma compared to an equal dose of GS solution -441524 administered intravenously.
- At only 1% of the proposed oral dose of hydroxychloroquine to treat COVID-19, ISPM19 given intratracheally had a longer half-life (~ 2.5 times) and higher pulmonary exposure (~ 30 times) than free hydroxychloroquine administered intravenously.
- NIMP19 nebulized in an aerosol showed a pulmonary deposition rate (inhaled dose) of 26.67%.
- InspirMed’s proprietary inhalable liposome formulation programs can deliver antiviral drugs directly into the lungs with sustained drug levels, potentially providing efficacy at significantly lower doses while avoiding systemic side effects.
The poster presentation can be viewed under “Publications” in the Newsroom section of TLC’s website at www.tlcbio.com.
ISPM21 is a proprietary inhalable liposome formulation of GS-441524, the active ingredient that reaches the lungs after administration of remdesivir. Initially indicated for the treatment of hepatitis, remdesivir has been shown to be effective in inhibiting viral replication of the SARS-CoV-2 virus responsible for COVID-19 and is approved by the State Food & Drug Administration (FDA). -United for the treatment of COVID-19 requiring hospitalization. The favorable chemical properties of GS-441524 – low molecular weight, greater hydrophilicity, greater localization in AT1 / 2 cells, and the ability to cross the blood-brain barrier – make it a promising candidate as a therapeutic or prophylactic agent for COVID-19. However, the low oral bioavailability of GS-441524 means that an extremely high oral dose would be required to reach therapeutic levels. By encapsulating GS-441524 in an inhalable liposome formulation (NIMP21), there is no need to use the cyclodextrin complex excipient, thus potentially eliminating nephrotoxicity, and targeted delivery by inhalation of liposomes allows increased availability. and prolonged exposure of the active drug in the lungs.
ISPM19, formerly known as TLC19, is a proprietary formulation of inhalable hydroxychloroquine liposomes. Hydroxychloroquine has shown potential in the prophylaxis and / or treatment of COVID-19 in in vitro and preliminary clinical studies, but oral hydroxychloroquine cannot reach therapeutic levels due to its dose-limiting toxicities. ISPM19 uses ~ 1% of the highest oral dose of hydroxychloroquine tested and delivers the drug directly to the respiratory tract and lungs, potentially avoiding systemic toxicities while providing a sustained effective concentration at the primary site of infection. ISPM19 is designed to be cost effective, easily accessible, and can be self-administered with a portable nebulizer. A randomized, vehicle-controlled, blinded phase 1 study to evaluate the safety, tolerability and pharmacokinetics of increasing doses of inhaled ISPM19 in healthy volunteers is underway.
InspirMed is a subsidiary of TLC specializing in the development of inhalable liposome formulation programs for severe acute and chronic lung diseases. TLC (NASDAQ: TLC, TWO: 4152) is a clinical-stage specialty pharmaceutical company dedicated to the research and development of novel nanodrugs that maximize the potential of its proprietary lipid-assembled drug delivery platform (LipAD ™) , including BioSeizer® NanoX ™ sustained-release technology and active drug loading technology, which are versatile in the choice of active pharmaceutical ingredients and scalable in manufacturing.