TLC19

Coronavirus disease 2019 (COVID‑19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first identified in December 2019 in Wuhan, Hubei, China, and has resulted in an ongoing pandemic. The first confirmed case has been traced back to 17 November 2019 in Hubei. As of August 14, 2020, more than 20.6 million cases have been reported, resulting in more than 749,000 deaths.

Studies by X. Yao et al and S. Perinel et al suggest that HCQ can prevent the acidification of intracellular organelles, inhibit lysosomal release of viral genome and interfere with the glycosylation of the angiotensin-converting enzyme-2 (ACE2) receptor on the host cell, reducing the binding efficiency between the receptor and spike protein on the surface of the coronavirus and thereby reducing the chances of COVID-19 infection and replication. Therefore, on the molecular and cellular levels, HCQ has been shown to achieve antiviral activity against SARS-CoV-2, the strain of coronavirus that causes COVID-19. A study by Fan et al, a pharmacokinetics review team from the US Food and Drug Administration (FDA), emphasized the importance of translating in vitro antiviral activity to appropriate clinical dosing regimens and concluded that “antiviral effect against SARS-Cov-2 [is] not likely achievable with a safe oral dosing regimen” of HCQ due to dose confinement by potential cardiotoxicity. The FDA revoked emergency use authorization for HCQ, and recent clinical trials studying orally administered HCQ, such as SOLIDARITY and RECOVERY, which proposed the highest dosing regimen of 1600mg on day 1 and 800mg the next 9 days, were halted. Fan et al suggested that “a strategy to increase the drug exposure at the site of action (e.g., through targeted delivery) while minimizing the systemic exposure may be desirable.”


TLC19 utilizes TLC’s existing proprietary liposome technology to encapsulate ~1/100 of the oral HCQ dose into an inhalable formulation for direct deposit into the airways and lungs. A recent manuscript showed that, at equivalent doses, inhalable liposomal HCQ achieved increased exposure (~30-fold) and half-life (~2.5-fold) in the lungs than oral HCQ. Thus, TLC19 can achieve antiviral effect with a miniscule dose compared to orally administered HCQ while lowering blood and heart exposure, giving TLC19 the potential to treat COVID-19.

 

API

Hydroxychloroquine

DDS Platform

NanoX™

Indication

Coronavirus disease 2019 (COVID‑19)

Advantage

  • Direct deposit into the airways and lungs, increasing exposure
  • 1/100 of oral HCQ dose
  • Reduced cardiotoxicity
  • Inexpensive, easily accessible, user-friendly

Development Status

Phase I

Publications