Encorafenib

Most of the affected roles at Erasca are located in drug discovery functions or deprioritized programs, the company said. Erasca is spending a combined $22.5 million upfront to import fresh preclinical KRAS and molecular glue assets while clearing space in its own pipeline and laying off 18% of its employees in the process. The San Diego-based biotech, which focuses on treatments for cancers driven by the RAS/MAPK pathway, is paying Medshine Discovery $10 million upfront for the worldwide rights to the KRAS inhibitor ERAS-4001. Erasca described the candidate as having “potential to provide an improved therapeutic window relative to RAS inhibitors and prevent KRAS wildtype-mediated resistance relative to mutant-selective approaches.” Medshine will be in line for up to $160 million in milestone payments as well as a low single-digit percentage of the royalties should the drug make it to market. To make room for ERAS-4001—and working on the assumption that Medshine will also be providing some ERAS-4 molecules as backup compounds—Erasca will call time on its internal pan-KRAS program. Erasca had already amended this program a year ago, when it blamed the “increasingly competitive landscape” for its decision to shelve a KRAS G12C inhibitor despite believing that the candidate was potentially differentiated. It's not the only licensing deal Erasca announced yesterday evening. The company is also handing over $12.5 million to Joyo Pharmatech for the ex-China rights to a pan-RAS molecular glue called ERAS-0015. The candidate, which has now entered human trials, has demonstrated “5- to 10-fold greater in vitro and in vivo potency and favorable absorption, distribution, metabolism, and excretion properties and pharmacokinetic properties in multiple animal species,” Erasca explained in the release. As part of the licensing agreement, China’s Joyo will also be in line for up to $176.5 million in milestone payments. “We’re thrilled to add ERAS-0015 and ERAS-4001 to our pipeline,” Erasca CEO Jonathan Lim, M.D., said in the release. “Over the long term, we have a unique opportunity to combine these two best-in-class molecules with distinct and complementary RAS inhibitory mechanisms to ‘clamp’ RAS and shut down MAPK signaling for the benefit of patients with these common RAS mutations.” In addition to its KRAS work, Erasca will be deprioritizing two other programs to ensure it has space for both ERAS-4001 and ERAS-0015. One of these is ERAS-007, an ERK inhibitor that was in a phase 1b trial in combination with Braftovi and Erbitux in EC-naïve patients with BRAF-mutant colorectal cancer. Clinical efficacy data to date “do not support continued evaluation,” the biotech explained. The final amendment to its R&D strategy affects ERAS-801, a central nervous system-penetrant EGFR inhibitor being evaluated for recurrent glioblastoma. The biotech said that “due to the desire to focus internal resources” on its pan-RAF inhibitor naporafenib—which is due to enter a phase 3 melanoma trial in the coming weeks—as well as its broader RAS-targeting franchise, “Erasca is exploring further advancement of ERAS-801 via select investigator-sponsored trial(s).” These pipeline changes will be accompanied by a workforce reduction that will see 18% of staff heading for the exits, with most of the affected roles located in drug discovery functions or the deprioritized programs. “Erasca is deeply committed to easing this transition for its impacted colleagues and will offer comprehensive severance packages and career transition services,” the biotech added in the release. “With the in-licensing of these RAS-targeting programs, we have made the difficult but necessary decision to deprioritize or externalize resourcing of our pipeline (ERAS-007, ERAS-801, and ERAS-4),” Lim explained. “This change has unfortunately impacted certain team members. We believe that further focusing our resources will allow us to advance the programs with the highest probability of success and largest potential for patient impact.”

Erasca is undertaking some housekeeping, with a pipeline refresh that brings in two external preclinical programmes and deprioritises a number of existing assets, whilst also trimming its workforce by 18%. In addition the company priced a $160-million equity offering.“We believe that further focusing our resources will allow us to advance the programmes with the highest probability of success and largest potential for patient impact,” remarked CEO Jonathan Lim.While analysts were broadly positive on the pipeline additions, those at Mizhuo Securities said they have “come away a bit mixed on the totality of the…surprise updates.” Meanwhile, Morgan Stanley analysts noted that since going public in 2021, when it raised $345 million to fund its RAS/MAPK portfolio, Erasca’s “entire pipeline has…been replaced by externally-sourced assets.” Joyo, Medshine drugsErasca in-licensed the pan-RAS molecular glue ERAS-0015 from Joyo Pharmatech for an upfront cash payment of $12.5 million, with the latter eligible for further milestones of up to $176.5 million plus a low- to mid-single digit percentage sales royalty. Erasca initially has rights in all countries excluding China, Hong Kong and Macau, although this can be converted to a global licence for a one-time payment.It also in-licensed the pan-KRAS inhibitor ERAS-4001 from Medshine Discovery for an upfront cash payment of $10 million, with the latter eligible for up to $160 million in additional milestones, as well as a low-single digit percentage sales royalties. “Based on the compelling preclinical data generated to date, we believe both molecules have the potential to demonstrate best-in-class profiles within their respective categories of RAS inhibition,” Lim noted.To make room for the new assets, Erasca plans to discontinue its internal pan-KRAS programme, dubbed ERAS-4, while also stopping work on the ERK inhibitor ERAS-007. According to the company, data from the HERKULES-3 trial – investigating ERAS-007 in combination with Erbitux (cetuximab) and Braftovi (encorafenib) in certain patients with BRAF-mutated colorectal cancer – “do not support continued evaluation.”Erasca is also pulling back on its CNS-penetrant EGFR inhibitor ERAS-801 in recurrent glioblastoma, although it will explore options to advance the programme via investigator-sponsored trials. As a result of the reprioritisation, the company is cutting employees across drug discovery functions.ASCO Daily Digest – your go-to-source for the key developments emerging from this year's American Society of Clinical Oncology (ASCO) annual meeting. Exclusively for PLUS subscribers – sign up here!