Erasca and Tango Therapeutics partner on ERAS-0015 and vopimetostat combination trial

Edited by Robert McTiernan··1 min read

US biopharma companies Erasca, Inc. and Tango Therapeutics entered a clinical trial collaboration and supply agreement to evaluate a combination of ERAS-0015, a RAS-targeting molecular glue, with vopimetostat (TNG462), a PRMT5 inhibitor.

The companies plan a Phase I/II study in patients with MTAP-deleted pancreatic cancer or MTAP-deleted RAS-mutant non-small cell lung cancer (NSCLC). Tango will sponsor the trial, while Erasca will supply ERAS-0015 at no cost. The agreement is non-exclusive, and both companies retain commercial rights to their respective compounds. No financial terms were disclosed.

Scientific rationale

ERAS-0015 is an oral small molecule described by Erasca as a pan-RAS molecular glue designed to inhibit signaling across multiple RAS mutations. The compound recruits cyclophilin A to RAS proteins, disrupting downstream MAPK/ERK and PI3K/AKT signaling pathways. Erasca is currently evaluating the drug as a monotherapy in the AURORAS-1 Phase 1 trial in patients with RAS-mutant solid tumors.

Vopimetostat is a PRMT5 inhibitor designed to exploit the vulnerability of MTAP-deleted cancers. Loss of MTAP leads to accumulation of methylthioadenosine (MTA), which partially inhibits PRMT5 and sensitizes tumor cells to further PRMT5 blockade.

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MTAP deletion occurs in a large proportion of pancreatic cancers and in a subset of non-small cell lung cancers, frequently alongside RAS mutations. The companies believe this genomic overlap may create a therapeutic opportunity for combined RAS pathway inhibition and PRMT5 targeting.

Competitive landscape

Both targets are areas of active drug development. Revolution Medicines is advancing the pan-RAS inhibitor RMC-6236 in Phase I/II trials, while multiple companies are pursuing PRMT5 inhibitors, including Amgen’s AMG 193 and Tango’s TNG908.

The Erasca–Tango collaboration represents an early attempt to test whether combining these mechanisms can improve outcomes in genetically defined MTAP-deleted, RAS-mutant cancers.