News from IMI’s COVID-19 therapeutics projects, launched in the wake of the pandemic outbreak
The CARE consortium are trying to identify candidates among existing drugs that could be effective as treatments against COVID-19. Their mission also includes developing new treatments for the current outbreak and future coronavirus outbreaks. In the latest project update, it was revealed that the screening of clinically-approved drugs in a SARS-CoV-2 cell-based assay did not provide a promising drug that can quickly be positioned towards clinical development, although some repurposed compounds are still undergoing pre-clinical proof of concept testing.
They have identified advanced antibodies, compared to clinical antibodies, and their full profiling is ongoing. The first in vivo testing has started, with the first in human study to start in the second half of 2021. In terms of small molecule therapy targets, enzyme and screening assays have been developed for four SARS-CoV-2 targets, and screening of small molecule libraries has led to the identification of hits for at least three targets. Chemistry hit-to-lead optimisation is ongoing.
Animal models of SARS-CoV-2 infection have been established for safety and efficacy studies, and initial discussions have been held with the European Medicines Agency for positioning clinical trials expected in the near future (two phase 1 trials and one phase 2 trial are planned).
Another IMI project, IMPENTRI, is tasked with repurposing and rapidly developing an existing therapy, imatinib, as a new and improved therapeutic approach for acute respiratory distress syndrome (ARDS) caused by infection with SARS-CoV-2.
The project has reported that recruitment for the first clinical trial, a phase 2 trial of orally-administered imatinib in COVID-19 infected and hospitalised patients before they develop ARDS, has been completed. The second trial, a randomised, double-blind, phase 2 study to evaluate the efficacy, safety and pharmacokinetics of intravenously-administered imatinib in patients with COVID-19-associated ARDS was approved in January 2021, with recruitment set to commence. The manufacture of IV imatinib (Impentri®) has also been completed.
MAD-CoV 2 is working on developing COVID-19 antivirals against SARS-CoV-2 by targeting the ACE2 receptor, the virus’ passageway into human cells. They are doing this by engineering human tissue to test new antiviral treatments and high-throughput screening of host genetic factors (at a single amino acid resolution) which are critical for SARS-CoV-2 replication.
Several state-of-the-art advanced platforms for validation of antivirals against SARS-CoV-2 have been developed and some antivirals using this platform have been validated. The team were able to show that a low-dose combination of the antiviral remdesivir and a drug called APN01 (hrsACE2) can stop the virus from multiplying in cells.