Erasca is deprioritizing several applications of one of its most advanced candidates after getting a look at lackluster data and putting a KRAS inhibitor on the back burner in response to the “increasingly competitive landscape for small- and mid-cap biopharma companies.”
San Diego-based Erasca is working on treatments for cancers driven by the RAS/MAPK pathway. As part of that focus, the biotech studied its ERK inhibitor ERAS-007 in multiple settings. Companies including Celgene (now Bristol Myers Squibb), Eli Lilly, Genentech and Merck & Co. have invested in the drug class on the basis of evidence that inhibiting ERK may help patients who develop resistance to BRAF and MEK therapies.
Interest in ERK has waned in recent years, but Erasca believes it has the most potent drug in the class, thanks to factors including the long target residence time of ERAS-007 that set the candidate apart. Data from a pair of phase 1 trials have persuaded the biotech that, in some settings, the asset is worth further study. The studies assessed ERAS-007 in different settings and combinations to determine whether it can prevent or reverse in-pathway resistance and target adjacent pathways, but delivered a mixed scorecard.
Erasca is stopping assessments of the candidate in combination with AstraZeneca’s Tagrisso and Pfizer’s Ibrance after the clinical efficacy data disappointed. The biotech is also stopping tests of ERAS-007 plus its SHP2 inhibitor in light of dose-escalation safety data.
The bright spots in the data, as Erasca sees things, come from the assessments of ERAS-007 in metastatic BRAF V600E-mutated colorectal cancer. Erasca saw three partial responses, one unconfirmed, in the six patients who took ERAS-007 in combination with Pfizer’s Braftovi and Eli Lilly’s Erbitux. The patients hadn’t previously received either drug. Erasca is now doing dose expansion in the setting.
Erasca is leaving the door open to development of ERAS-007 in patients previously treated with the Lilly and Pfizer drugs, stating that the population may be explored if there's more promising data in the naive population. The biotech said it is “more challenging” to show benefits in people previously treated with the standard of care drugs.
In conjunction with the rethink on ERAS-007, Erasca disclosed changes to other parts of its pipeline. The biotech blamed the “increasingly competitive landscape” for the choice to shelve a KRAS G12C inhibitor, which the company thinks is potentially differentiated, and gave a range of research-related reasons for decisions to deprioritize three discovery programs.