Erasca (NASDAQ:ERAS) executives highlighted early clinical signals and the company’s strategy to differentiate its RAS-focused pipeline during a Guggenheim fireside chat featuring CEO Jonathan Lim and CFO David Chacko.
How Erasca sees differentiation in the pan-RAS field
Chacko framed the current pan-RAS landscape around Revolution Medicines’ RMC-6236, calling it “a breakthrough for the whole RAS, pan-RAS space.” He said developers are generally trying to “raise the bar” on two key dimensions: potency and pharmacokinetics (PK). Some competitors, he noted, are pursuing large potency gains over 6236, while others focus on improved PK such as higher oral bioavailability, longer half-life, and lower clearance.
ERAS-0015: potency, PK, and tumor distribution cited as potential advantages
In discussing ERAS-0015, described in the conversation as a pan-RAS molecular glue, management emphasized nonclinical data suggesting a potency edge. Chacko said that in vivo animal models indicated a five- to 10-fold potency advantage versus RMC-6236, with ERAS-0015 requiring roughly one-tenth to one-fifth of the dose to achieve similar tumor growth inhibition or regression “in most cases.” He added that in vitro, cell-based assays showed a similar five- to 10-fold potency improvement.
On PK, Chacko said ERAS-0015 has shown, in nonclinical testing across multiple species, higher oral bioavailability, a longer predicted half-life, and lower clearance. He also discussed the possibility that a lower peak-to-trough exposure profile could matter if adverse events (AEs) are driven by peak concentrations (Cmax), while cautioning the team does not know “a priori” whether on-target effects are Cmax-driven.
Chacko also described a potential biodistribution benefit: because cyclophilin A (CypA)—the binding partner referenced in the discussion—appears overexpressed in multiple solid tumors, Erasca is seeing what he characterized as preferential distribution of ERAS-0015 into tumor tissue versus the periphery in nonclinical work. If that translates clinically, he said, it could support a therapeutic window advantage. He added that CypA is endogenously and ubiquitously expressed, but cited published and internal data suggesting overexpression across multiple solid tumor types, including lung, pancreatic, and colon cancers.
AURORAS-1 phase 1: early responses at 8 mg and safety observations
Management summarized early observations from the company’s ongoing phase 1 study, AURORAS-1. Chacko said Erasca observed “multiple responses, confirmed and unconfirmed partial responses” at 8 mg, which he described as one-tenth of the dose where first responses were seen with RMC-6236. He said there were three responses as of a January data cutoff.
On tolerability, Chacko said the company had observed no dose-limiting toxicities (DLTs) as of the cutoff, with “predominantly low-grade” AEs and a generally safe and tolerated profile. He noted the company has begun dosing at 40 mg and had seen dose-proportional PK prior to that step, without signs of an exposure plateau he said has been observed with the comparator compound.
Erasca did not disclose the total number of treated patients during the discussion, but Chacko said the company expects to report data on dozens of patients in the first half of the year, covering safety, PK, and efficacy. Lim added that given the study will still have been in the clinic for less than a year at the time of the update, he expects more time will be needed to assess durability and progression-free survival (PFS), though the company will be able to report response rates and ongoing treatment status as a proxy metric.
Patient example and mutation coverage commentary
Lim provided additional detail on one responder the company has previously disclosed: a 72-year-old man with advanced non-small cell lung cancer (NSCLC) driven by KRAS G12V who had received multiple prior treatments, including chemotherapy and checkpoint inhibitors. Lim said the patient achieved an unconfirmed partial response after the first cycle that was later confirmed. He also said the patient was on supplemental oxygen and “after a week of just 8 mg daily dosing” came off oxygen and returned to work.
Management also discussed how ERAS-0015 performs across KRAS variants. In a panel including “dozens” of mutations (predominantly G12X, also G13X, and KRAS wild type), Lim said Erasca saw significantly increased potency broadly versus daraxonrasib, with “pretty similar” relative preferences across KRAS mutations. He noted one area of “equipotency against PK59,” while stating that in vivo models still showed an advantage in terms of lower dose required.
ERAS-4001: pan-KRAS program timeline and combination rationale
Chacko described ERAS-4001 as Erasca’s pan-KRAS inhibitor and a Switch II Pocket binder, positioning it as mechanistically “orthogonal” to ERAS-0015. He said the company filed and cleared an IND in Q2 of last year and that the phase 1 trial, BOREALIS-1, is advancing. Erasca has guided to data in the second half of this year from “dozens of patients,” focused on safety, PK, and initial activity. Chacko added that the company expects to initiate monotherapy dose expansions and combination dose-escalation work in calendar year 2027.
In discussing the broader rationale for pan-KRAS versus pan-RAS inhibition, management reiterated the hypothesis that sparing HRAS and NRAS could support a better therapeutic window, including potentially less rash. Chacko referenced data from another pan-KRAS molecule suggesting less rash when HRAS and NRAS are spared, while also citing a Science paper discussed in the chat that suggested sparing HRAS and NRAS may allow bypass via PI3K, supporting a possible advantage to targeting all three RAS isoforms if tolerability can be maintained.
Both executives said the company intends to be data-driven in determining whether each asset will occupy its own “swim lane” or whether one approach proves broadly superior, and they reiterated that combinations are under consideration—including combining the two agents with each other, as well as with standard-of-care and investigational therapies.
About Erasca (NASDAQ:ERAS)
Erasca, Inc is a clinical‐stage biopharmaceutical company dedicated to the discovery and development of precision medicines for patients with cancer. The company focuses on small molecule therapeutics that target critical signaling pathways involved in tumor growth and survival, with a primary emphasis on inhibitors of the MAPK pathway. Erasca’s approach is designed to deliver oral, targeted therapies that address both oncogene‐driven and immuno‐oncology indications, aiming to improve outcomes for patients with unmet medical needs.
Erasca’s pipeline comprises multiple development candidates, including small molecule inhibitors engineered to disrupt key nodes in cancer cell signaling.
