Aluda Pharmaceuticals announced the publication of “A Vimentin-targeting oral compound with host-directed antiviral and anti-inflammatory actions addresses multiple features of COVID-19 and related diseases”
| MENLO PARK, Calif., Oct. 13, 2021 /PRNewswire/ -- Aluda Pharmaceuticals announced the publication of “A Vimentin-targeting oral compound with host-directed antiviral and anti-inflammatory actions addresses multiple features of COVID-19 and related diseases” in the peer reviewed journal mBio describing multiple actions of Aluda’s clinical candidate ALD-R491 in viral infection, lung injury and fibrosis, hyperinflammation and, more generally, autoimmune disease. The paper presents results of multiple studies, including Aluda’s NIH sponsored SARS-CoV-2 study, in which aged mice were used and drug was administered after full-blown infection (both harder than standard protocol). The treated mice showed improved general condition and reduced lung damage, both outcomes also seen in separate ALD-R491 studies of lung injury-related fibrosis. These therapeutic effects are attributed to the ability of ALD-R491 to control both viral infection and hyperinflammation. Unlike drugs that target the spike or other viral proteins to block SARS-CoV-2 infection, ALD-R491 targets a cellular protein to block the virus’s entry, movement within, and exit from the cell. In a cell-based assay, ALD-R491 protected almost all cells (>90%) from becoming infected by virus through SARS-CoV2 spike protein and its human ACE2 receptor. In addition, ALD-R491 enhanced the pathogen-killing ability of macrophages, which could facilitate the viral clearance, and therefore avoid the escalation of hyperinflammation and the persistence of disease (long COVID). Importantly, all of these actions cannot be evaded by the virus through mutations, because ALD-R491’s target protein in the host cell remains the same regardless of COVID variant. ALD-491 also has an immune balancing effect which fights hyperinflammation through a “direct” activation of regulatory T cells. This action addresses the continuing unmet need of lowering COVID’s main cause of death and damage. Since 95% of COVID cases are not severe and patients can recover by themselves, the value of an anti-COVID therapeutic drug is to prevent the remaining 5% from becoming severe or to treat them if they do. Anti-viral drugs can play a role in preventing, but not treating, severe disease because hyperinflammation, not the virus itself, drives disease progression and severity. Unfortunately, most antiviral drugs are not mechanistically safe enough for this prevention role, as seen with the risk of mutagenicity of Molnupiravir (positive Ames test for genotoxicity), which could impose substantive risks but confer no benefits to 95% of COVID patients. ALD-R491 has anti-viral and anti-inflammatory actions that offer the potential to both prevent progression and resolve severe COVID. Its oral administration and excellent safety profile would make it suitable for wide use in patients, in or out of the hospital, at any stage and under any health condition (regular, fragile, and elderly). In addition, its ability to reduce lung fibrosis would address an important unmet need in COVID. Dr. Ruihuan Chen, CEO of Aluda said, “Our approach is a perfect fit to COVID, because it addresses the multifaceted pathology of the disease. Vimentin targeting lets the cell block the virus in multiple ways that cannot be bypassed by viral mutations, and makes the immune system eliminate the virus but not overreact to it. Our findings have direct relevance to treating both infectious and non-infectious conditions that share similar pathological processes.” Steven Projan, Ph.D., an editor of mBio, noted, “Host-directed mechanisms have been underappreciated and undervalued in the fight on COVID and we feel it is important to share these findings with the community as we see a rise of variants. This program is exciting for its unique target that addresses both virus and inflammation, with actions that will be complementary to our existing set of spike protein-directed drugs.” About ALD-R491 ALD-R491 specifically targets vimentin, an intermediate filament protein that plays an essential role in the progression of various diseases, from autoimmune to fibrosis and cancer. As the first-in-class vimentin-binding small molecule, ALD-R491 has shown broad efficacy in many disease models, and an excellent safety profile in the studies required for IND filing. About Aluda Aluda discovers and develops novel small molecule drugs for unmet medical needs. Programs include both new and previously explored drug targets in the areas of inflammation, autoimmune, fibrosis and oncology. For more see www.aludapharm.com.
SOURCE Aluda Pharmaceuticals |
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