Marine-Derived Pharmaceuticals in Clinical Trials in 2022

Abstract ID 52701 Poster Board 299 Objective: Natural products contribute substantially to clinical pharmaceuticals, with an estimated 60-70% of active compounds derived from or inspired by natural products. Due to adaptation to their unique habitat, the marine environment is a rich source of biologically active primary and secondary metabolites not represented in synthetic compound libraries. To track progress of the clinical development of marine pharmaceuticals, we maintain the website www.marinepharmacology.org as a reference for those with an interest in the preclinical and clinical development of marine compounds, which has nearly 10,000 views since its redesign in 2021. In 2022, there were 15 marine-derived drugs approved by the FDA, two approved in Australia, and one approved in China. Hypothesis: There has been progress in the clinical development of marine-derived pharmaceuticals in 2022. Methodology: To identify new marine-derived compounds and track their advancements, the following websites were researched: (a) USA: https://www.accessdata.fda.gov/scripts/cder/daf/ United States Food and Drug Administration (FDA); (b) Europe: https://www.clinicaltrialsregister.eu/ctr-search/ search European Clinical Trials register; (c) China: https://www.chictr.org.cn/enindex.aspx Chinese Clinical Trials register; and (d) www.clinicaltrials.gov to determine the current status of marine-derived compounds in clinical trials. Results: Several marine-derived compounds targeting the receptors and proteins (shown in brackets), have been added to the marine-derived pharmaceutical pipeline or progressed in their development in 2022: E7130 (microtubules), and antibody-drug conjugates (ADCs) BT5528 (EPhA2 with Monomethyl Auristatin E, MMAE, which blocks tubulin polymerization) and BT8009 (Nectin-4 with MMAE) all for cancer therapy have initiated Phase I clinical trials. The ADCs MORAb-202 (FRalpha with Eribulin), MRG003 (EGFR with MMAE), A-166 (HER-2 with Duostatin 5), RC-88 (mesothelin with MMAE) for cancer therapy and STI-6129 (CD38 with Duostatin 5.2) for refractory amyloidosis therapy have ongoing Phase I and Phase II clinical trials. The ADCs ARX-788 (HER-2 with Amberstatin269) and Upifitamab rilsodotin (NaPi2b with Auristatin F- hydroxypropylamide) for cancer therapy moved from Phase I into Phase II and III clinical trials. At the end of 2022, there were 34 marine-derived compounds in active clinical trials: 6 marine-derived compounds were in Phase III, 15 compounds in Phase II, and at least 19 compounds in Phase I. Conclusions: In 2022, the clinical development of marine-derived drugs remained very active with several compounds entering Phase I, and others advancing to Phase II and Phase III. This work was supported by Midwestern University Intramural Funds.