Erasca (ERAS) 3rd Annual Guggenheim Healthcare Innovation Conference summary

Pipeline and ERAS-0015 data

• Pipeline targets RAS: ERAS-0015 is a pan-RAS molecular glue aimed at KRAS, HRAS and NRAS, including key mutations and RAS wild-type; ERAS-4001 is a pan-KRAS switch II pocket inhibitor.

• Previously reported ERAS-0015 single-agent response rates were 40%-57% in pancreatic cancer, varying by treatment line and dose; lung cancer response rates were 60%+.

• At the November Triple Meeting, planned data will add patients, particularly at pancreatic recommended expansion doses of 24 mg and 32 mg; management highlighted a dose-response trend, with highest responses at 32 mg.

• Management expects longer follow-up and more confirmed responses in lung cancer; sustaining response rates at or above the previously cited 56%-59% divarasib comparator range could support pivotal development.

• Management sees potential for pan-RAS to improve pancreatic response and durability versus allele-specific approaches by also addressing wild-type RAS signaling; this remains a hypothesis.

Development plans and timing

• Three potential registration-enabling studies are planned: two in lung cancer and one in pancreatic cancer; the pancreatic Phase III start remains guided for 2027.

• A potential registration-enabling trial of ERAS-0015 monotherapy in second-line-plus RAS-mutant NSCLC is expected to start in H1 2027.

• For first-line RAS-mutant lung cancer, a Phase III trial could start in H2 2027 with pembrolizumab alone, or H1 2028 if chemotherapy is included.

• ERAS-0015 plus pembrolizumab is in dose escalation under a clinical trial collaboration with Merck; first-line lung cancer, with or without chemotherapy, is a potential focus.

Combination strategy

• Preclinical ERAS-0015 plus ERAS-4001 data at the Triple Meeting will cover in vitro and in vivo findings; the rationale is ERAS-0015-induced RAS off-state combined with ERAS-4001’s preference for that state.

• A combination study of ERAS-0015 with Tango’s PRMT5 inhibitor vopimetostat has started; rationale is dual targeting of RAS-driven, MTAP-deleted tumors.

• Management cited an 82% response rate reported at ESMO for a pan-RAS plus PRMT5 combination and said ERAS-0015 could potentially offer differentiated results.