Gryphon Bio, Inc.
Tue Mar 24 2020 07:00:00 GMT+0000 (Coordinated Universal Time)
Gryphon Bio proposes novel antibody-drug conjugates (ADCs) to treat COVID-19.
COVID-19 Therapeutics. The effective treatment options against 2019-nCoV can either based on the use of broad-spectrum anti-viral drugs or based on specific therapeutic molecules that can directly interrupt particular stages of the viral lifecycle. Another approach is targeting the interaction between the CoV with its host cell surface receptor, thus preventing viral attachment and entry to host cells and subsequent viral proliferation. This can be achieved with peptidic fusion inhibitors, neutralizing monoclonal antibodies (mAbs), and protease inhibitors. A recent review summarized the potential for mAbs by considering the existing knowledge for the similar coronaviruses SARS-CoV and MERS-CoV 4. Unfortunately, there is evidence that some of the most potent SARS-CoV-specific neutralizing mAbs (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind the ACE2 binding site of the 2019-nCoV spike protein, implying that the difference in the receptor binding domain (RBD) of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing mAbs to mutations in the spike protein 5. Consequently, new mAbs are urgently needed to meet global medical need. ADC Therapeutics. Antibody-drug conjugates (ADCs) were developed to combine the exquisite specificity of large molecule monoclonal antibodies (mAbs) with the potency of small molecule cytotoxic drugs to improve the therapeutic index (TI) for oncology indications 6. The TI is defined as the fold difference between efficacious and maximum tolerated doses, or the toxic dose of a drug for 50% of the population (TD50) divided by the minimum effective dose for 50% of the population (ED50). Evidence for the improved TI of ADCs comes from the 7 FDA-approved ADCs, ~80 ADCs in clinical development and ~ 600 ADCs in ongoing trials. Based on the successes of ADCs for oncology indications, several ADCs are being developed for infectious diseases, particularly anti-bacterial ADCs against Staphylococcus aureus 7. ADCs vs. COVID-19. Based on the above and our strong experience with ADC development, Gryphon Bio proposes novel ADCs to treat COVID-19. Potential partners include the CDC, BARDA, NIH and DOD.