M-LIFE™ has predicted the toxicity profiles across multiple organ systems for a variety of prospective re-purposed COVID-19 drugs.
NASHVILLE, TENNESSEE – M-LIFE™ has predicted the toxicity profiles across multiple organ systems for a variety of prospective re-purposed COVID-19 drugs. The objective for identifying prospective repurposed drugs is to find on-market therapeutics having the potential to decrease the severity and duration of COVID-19 illness. However, when repurposing existing drugs for a new use, there is the possibility of adverse effects (e.g. toxicity).
M-Life™ President and CEO Ted Moskal said, “When a patient has a raging COVID-19 infection, it’s essentially a war between the virus and the clinicians fighting to save the patient’s life. The battlefield landscape merits discussion when reviewing therapeutic options. About 14 percent of COVID-19 cases require hospitalization, and once hospitalized, 39 percent succumb to the infection (Reference 1, CDC Data). The point here is that COVID-19 is a powerful and aggressive enemy once it takes hold. Aside from vaccines and cytokine storm targeting therapeutics (e.g. defensive weapons), clinicians could really use a good offensive weapon. A good ‘offensive’ therapeutic option must match the COVID-19 assault by being fast acting, and lethal to the virus. Unfortunately, aggressive therapeutics tend to have undesirable toxicities and side effects. Our toxicity algorithms identified a variety of concerns that can be weighed against therapeutic efficacy to avail the best clinical choices.”
The COVID-19 repurposed drug prospects, ketoconazole, lacidipine, pilsicainide, suramin, tirofiban, and urapidil were assessed for idiosyncratic toxicities by M-Life™ algorithms. These toxicities included agranulocytosis/neutropenia, QT prolongation, Torsades, mitochondrial damage and hepatotoxicity. The results were also compared to algorithm predictions for ‘Benchmark Drugs’, drugs known to demonstrate a particular toxicity. The tabular results are provided below:
Key: Minimal Risk 0-0.20 , Slight Risk 0.21-.39, Moderate Risk 0.40-0.70, High Risk 0.71-1.00
The Table above consists of a compilation of the six repurposed drugs (top portion of table) and failed drug ‘Benchmarks’ (bottom of table). The Benchmark Drugs algorithm predictions were accomplished after algorithm creation (i.e. these Benchmarks were not included within algorithm training). The predictive values are expressed as probabilities toward each of the referenced toxicities—wherein a ‘one’ score indicates a one hundred percent likelihood of the toxicity and a ‘zero’ indicating no probability of the toxicity. The hepatotoxicity algorithm is based on post-market drugs that cause acute liver failure or significant liver toxicity rather than long term steatosis and cholestasis. The benchmark predictions are consistent with clinical experience for all seven ‘Benchmark’ drugs.
Dr. John Panos, M-Life™ Director of Translational Discovery, said “M-Life’s novel and proprietary toxicity algorithms, including models of mitochondrial damage, provide unique insights into the toxicological effects of pharmacological compounds. First, our predictions closely align with preclinical and clinical data for, not only the Benchmark drugs listed in the table, but also for numerous blind tested drugs used to assert algorithm prediction quality. In this light, the predicted toxicities for the repurposed drugs are compelling. Second, there appears to be a linkage between mitochondrial toxicity and various organ system toxicities. Said differently, mitochondrial damage is the underlying reason for many organ system toxicities. For some time, M-Life™ has hypothesized that the mechanism for particular organ system damage ties to mitochondrial damage. This is a compelling argument since there are now published studies that show this relationship (Ref 2-5]”
The Company has further research underway relative to possible off-target effects, both toxicity and side effects, for repurposed drugs and plans on sharing additional information in the near future.
About M-Life™
M-Life™ is a life sciences, molecule discovery company focusing on the development of new drugs, agricultural and diagnostics related chemicals. Whether a new antibiotic, non-opiate analgesic or environmentally friendly herbicide, the Company aims to address gaps in the present life sciences markets making life better. To learn more about M-Life™, please visit us at www.m-lifesciences.com.
M-Life™ Cautionary Statement
This press release contains statements relative to predicted performance using proprietary algorithms. The actual performance of these drugs in treating COVID-19 cannot be fully assessed until their usefulness has been determined via treatment of the illness. The Company plans on sharing additional information relative to possible off-target effects associated with the list of repurposed drugs herein in the near future.
References
- Centers for Disease Control and Prevention, Disease 2019 Case Surveillance — United States, January 22–May 30, 2020, Erin K. Stokes, MPH1, et al.
- “Evaluation of Drugs with Specific Organ Toxicities in Organ-Specific Cell Lines”, Toxicological Sciences, 126(1), 114–127 (2012).
- “Drug-induced mitochondrial dysfunction and cardiotoxicity”, Am J Physiol Heart Circ Physiol. 2015 Nov; 309(9): H1453–H1467.
- “Hepatocyte Spheroids as Predictive In Vitro Systems for Drug-Induced Liver Injury”. Drug Metab. Dispos., 45:419–429, April 2017.
- “Evaluation of in Vitro Mitochondrial Toxicity Assays and Physicochemical Properties for Prediction of Organ Toxicity of 228 Pharmaceutical Drugs”, Chem. Res. Toxicol., 2019, 32, 1,156-167.