Drugs targeting KRAS cancers co-developed by FNL to be featured at AACR Annual Meeting 

Study results of two investigational drugs that target KRAS-driven cancers co-developed by RAS Initiative investigators at the Frederick National Laboratory for Cancer Research (FNL) and now being tested in patients will be presented at the American Association for Cancer Research Annual Meeting April 25-30 at McCormick Place in Chicago.  

Both compounds, BBO-8520 and BBO-11818, were developed in partnership via Cooperative Research and Development Agreement (CRADA) with BridgeBio Oncology Therapeutics (BBOT) and Lawrence Livermore National Laboratory.  

Representatives of BBOT, sponsor of the clinical trials for both agents, will present the data during the AACR meeting.  

• James P. Stice, an associate director at BBOT, will discuss results of pre-clinical studies on BBO-8520 in a mini symposium on novel antitumor agents, Monday, April 28 in room S103. BBO-8520 targets KRAS G12C, the most common KRAS variant in lung cancer.   

• On Tuesday, April 29, BBOT Associate Director Carlos Stahlhut will present a poster on preclinical studies of BBO-11818, which shows activity against multiple KRAS mutants, and falls into the category of a pan-KRAS inhibitor.  The poster is in section 21 from 9 a.m. to noon.  

Laboratory tests show BBO-8520 blocks the active “ON” and inactive “OFF” states of KRAS G12C, resulting in rapid KRAS inhibition. While existing treatments for KRAS G12C-driven cancer have shown promising clinical efficacy, they block the KRAS G12C “OFF” state only, and patients develop resistance to the drug. The collaborators published results of pre-clinical assays in Cancer Discovery.   

There are no approved targeted therapies against other KRAS variants, which drive several major cancer types including pancreatic, colorectal and non-small cell lung cancer. BBO-11818 has shown activity against multiple KRAS mutants including KRAS G12D and KRAS G12V in their active and inactive states. 

The National Cancer Institute established the RAS Initiative in 2013 to explore and target RAS, the most frequently mutated oncogene in cancer, which at the time had no viable treatments. FNL is at the center of the hub-and-spoke model of a worldwide collaboration to investigate the complexity of RAS biology and therapy through the RAS Initiative.