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Erasca doubles down on RAS

The young company’s eighth licensing deal brings in two RAS-targeting projects from Joyo.

Erasca’s development pipeline never seems to stand still, and yesterday it underwent another transformation. The company has acquired two preclinical assets from China’s Joyo Pharmatec on the one hand, and discontinued work on three pipeline assets on the other, alongside a $160m equity offering.

The moves see Erasca doubling down on the RAF/RAS pathway – its lead remains the Novartis-derived pan-RAF inhibitor naporafenib, which recently entered phase 3 – and away from other targeted small-molecule approaches. Remarkably, the Joyo deal is at least the eighth transaction Erasca has struck to bring in R&D assets since it was founded in 2018, but most have now fallen by the wayside.

This now includes the clinical-stage ERK1/2 inhibitor ERAS-007 and EGFR inhibitor ERAS-801, both licensed in 2020, from Asana BioSciences for $20m up front and from Katmai Pharmaceuticals for $6m respectively. Erasca is cutting 18% of its staff, and says ERAS-007’s Herkules-3 trial efficacy data underwhelmed; ERAS-801 was in the Thunderbbolt-1 study, but any development will now be investigator-sponsored.

Pan-KRAS in and out

The company previously had a preclinical internal pan-KRAS programme, coded ERAS-4, but this is now being discontinued and replaced by Joyo’s ERAS-4001, another pan-KRAS approach. Pan-KRAS inhibition is becoming a hot theme, and competing assets include Revolution’s RM-6236 and BridgeBio’s BBO-11818.

The terms of Erasca’s Joyo deal call for a $12.5m up-front payment, which is in line with the company’s other deals and reflects the preclinical status of the two assets involved. An IND filing for ERAS-4001’s first-in-human Borealis-1 trial, in patients with KRAS-mutated solid tumours, is expected in the first quarter of next year.

Meanwhile, the other Joyo project now in Erasca’s hands is ERAS-0015, described as as pan-RAS molecular glue. This type of mechanism involves the bringing together of two proteins that normally wouldn’t interact, and Monte Rosa Therapeutics, for instance, is using it to cause protein degradation.

Next year Erasca also plans an IND filing to start ERAS-0015’s Auroras-1 study in RAS-mutant solid tumours. Interestingly, the company earlier used Auroras-1 as the name of a first-in-human trial of the KRAS G12C inhibitor ERAS-3490/ERAS-1, but this never got under way as the project was discontinued last June, with Erasca citing an “increasingly competitive landscape”.

At the same time the company axed three preclinical assets, including the internally discovered SOS1 inhibitor ERAS-9, and highlighted ERAS-7 as key pipeline project, along with naporafenib.

A third cull

Five months later brought another R&D cull, as three projects were discontinued, including the SHP2 inhibitor ERAS-601, which in its phase 1 Flagship-1 study was said to have achieved confirmed responses with and without Erbitux, but these were deemed insufficient to justify development.

Erasca’s Nasdaq float raised $345m in mid-2021, on the back of a focus on RAS/MAPK pathway-driven cancers – and that was before the Novartis deal brought in naporafenib. While yesterday’s deal sees Erasca doubling down on RAS inhibition, the SHP2 and SOS1 discontinuations show that the company won’t pursue this at all cost.

This is especially relevant given how crowded a space KRAS inhibition has become, something that sets a high bar for the Joyo assets to meet to warrant their continued development. But with Erasca now trading nearly 90% off its IPO price it might not have many more chances at transformation.


How Erasca has grown and shrunk its R&D pipeline

ProjectMechanism of actionSource/termsLicensed inStatus
NaporafenibPan-RAF inhibitorNovartis, $20m up front + $80m equityDec 2022Ph3 Seacraft-2 trial, Tafinlar combo in NRASm melanoma
ERAS-0015Pan-RAS molecular glueJoyo Pharmatec, $12.5m up frontMay 2024Preclinical; ph1 Auroras-1 trial in RASm solid tumours due 2025
ERAS-4001Pan-KRAS inhibitorPreclinical; ph1 Borealis-1 trial in KRASm solid tumours due 2025
ERAS-12Anti-EGFR-D2/D3 bispecific monoclonal antibodyEmerge Life Sciences, $2m up frontMar 2021Preclinical
ERAS-007ERK1/2 inhibitorAsana BioSciences, $20m up frontNov 2020Discontinued May 2024; ph1/2 Herkules-4 trial
ERAS-801EGFR inhibitorKatmai Pharmaceuticals, $5.7m up frontMar 2020Discontinued May 2024; ph1 Thunderbbolt-1 trial
ERAS-4Pan-KRAS inhibitorInternal discoveryNADiscontinued May 2024; preclinical
ERAS-601SHP2 inhibitorNiKang Therapeutics, $12m up frontFeb 2020Discontinued Nov 2023; ph1 Flagship-1 trial
ERAS-10RAS/MAPK degraderInternal discoveryNADiscontinued Nov 2023; preclinical
ERAS-5ULK1/2 inhibitorLifeArc, zero up frontApr 2020Discontinued Nov 2023; preclinical
ERAS-3490KRAS G12C inhibitorUndisclosedUndisclosedDiscontinued Jun 2023; ph1 Auroras-1 trial didn’t start
ERAS-2/3RAS-S-IIG inhibitorUniversity of California, San FranciscoDec 2018Discontinued Jun 2023; preclinical
ERAS-11MYC inhibitorInternal discoveryNADiscontinued Jun 2023; preclinical
ERAS-9SOS1 inhibitorInternal discoveryNADiscontinued Jun 2023; preclinical

Source: OncologyPipeline.


Molecular Drug Targets