The San Diego biotech company, ADARx Pharmaceuticals, announced a successful Series C $200 million round led by Bain Capital Life Sciences and The Column Group Crossover (TCGX) on Wednesday, August 9, 2023, to advance two clinical programs. ADARx emerged from stealth mode in the fall of 2021. So far, ADARx has successfully completed five rounds of funding, raising a total of $332 million.
ADARx is another company working on siRNA that operates within the RNA interference (RNAi) pathway. Its primary focus diseases include genetic, cardiometabolic, and central nervous system (CNS) diseases. With 9 active programs in the pipeline, currently, the company has two candidates in clinical phase I: ADX-324 and ADX-038. ADX-324 is designed for the treatment of a genetic swelling disorder, hereditary angioedema (HAE), and ADX-038 is developed for the treatment of multiple complement-mediated diseases. The ADX-324 phase I clinical study started on December 14, 2022, and primary completion is estimated to be in the beginning of 2024, followed by entry into phase II in the first half of 2024. The ADX-038 phase I clinical study started on July 3, 2023, and is expected to have the primary readout around the end of 2024. With the Series C round funding, the company plans to initiate another candidate into clinical trials in 2024, and potentially a couple more later.
The current delivery platform for both candidates in clinical trials is the GalNAc-siRNA conjugate, which was explored by other siRNA companies such as Alnylam and Silence. GalNAc, or N-acetylgalactosamine, is a sugar molecule that can recognize and bind to the cell surface asialoglycoprotein receptor (ASGPR), which is highly expressed in liver cells. However, this ASGPR receptor is not only expressed in liver cells but also in several human carcinoma cell lines, as well as glandular cells of the gallbladder and the stomach. Therefore, it has some limitations on targeted delivery and tissue/cell specificity. For CNS diseases, it is not yet clear how ADARx is targeting neurons, and it would be interesting to see the data when available.