RAMP 205 Data Update - Dose Level 1 in RAMP 205 demonstrated an 83% unconfirmed ORR (10/12 patients) and a 66.7% confirmed ORR (8/12 patients) in frontline metastatic PDAC[48] - Dose Level 1 also showed a 92% disease control rate (11/12 patients) for at least 4 cycles[48] - In RAMP 205, 92% (48/52) of patients showed tumor reduction across all dose cohorts[57] - Approximately 180,000 total incident PDAC patients globally represent a high unmet need, with a 5-year relative survival rate of 13.3%[20, 22] VS-7375 KRAS G12D Inhibitor - VS-7375 is a KRAS G12D (ON/OFF) inhibitor with IC50 values of 2 nM for GppNp-bound (ON/active) and 6 nM for GDP-bound (OFF/inactive) KRAS G12D[68] - Preclinical data indicates that VS-7375 is more efficacious than KRAS ON inhibitors in reducing tumor growth in KRAS G12D models[73] - In a KRAS G12D colorectal cancer model, the addition of Cetuximab with VS-7375 induced complete responses in all mice[78] - KRAS G12D mutations account for 26% of all KRAS mutations and are prevalent in pancreatic and colorectal cancers[84] Clinical Development Plans - The company plans to launch a Phase 3 study in 1L mPDAC in 2026[103, 113] - The company is initiating enrollment for the Phase 1/2a trial of VS-7375 in advanced solid tumors in the US, starting with an efficacious dose level of 400 mg QD[108, 113]

Core Insights - Erasca, Inc. has received FDA clearance for the IND application of ERAS-0015, a pan-RAS molecular glue, and submitted an IND application for ERAS-4001, a pan-KRAS inhibitor, both ahead of schedule [1][2] - The company has extended its cash runway guidance from H2 2027 to H2 2028 by pursuing partnership opportunities for naporafenib [1][2] Company Developments - ERAS-0015 is positioned as a potential best-in-class therapy for RAS-mutant solid tumors, with Phase 1 monotherapy data expected in 2026 [4][5] - ERAS-4001 is anticipated to be a first-in-class pan-KRAS inhibitor, with initial Phase 1 data also expected in 2026 [4][6] - The strategic decision to seek partnerships for naporafenib allows the company to focus resources on its RAS-targeting franchise [2][4] Market Potential - Approximately 2.7 million patients are diagnosed annually worldwide with RAS-mutant tumors, and over 2.2 million with KRAS-mutant tumors, indicating a significant unmet medical need [4][8] - The development of naporafenib aims to address the high unmet medical need in NRAS-mutant melanoma, a disease with no approved targeted therapies [7][8] Clinical Pipeline - ERAS-0015 has shown superior binding affinity and potency in preclinical studies compared to existing therapies, with plans for evaluation in the AURORAS-1 Phase 1 trial [5][6] - ERAS-4001 demonstrated potent activity against KRAS mutations and is set to be evaluated in the BOREALIS-1 Phase 1 trial [6][8] Financial Position - The extension of cash runway guidance to H2 2028 provides the company with over three years of cash without new capital infusion, enhancing its ability to execute clinical development plans [2][4]

Core Insights - Erasca, Inc. presented new preclinical data at the AACR Annual Meeting, highlighting the best-in-class potential of its RAS-targeting compounds ERAS-0015 and ERAS-4001, which show robust anti-tumor activity as both monotherapy and in combination therapy [1][2] Group 1: ERAS-0015 - ERAS-0015 is a pan-RAS molecular glue that demonstrated favorable pharmacokinetic properties, including longer residence time and greater tissue exposure, leading to robust anti-tumor activity at lower doses compared to leading competitors [3][5] - The compound forms a ternary complex with active state RAS and cyclophilin A (CypA), effectively blocking downstream effector complex formation and showing potent inhibition of proliferation across diverse tumor tissues and RAS mutations [5] Group 2: ERAS-4001 - ERAS-4001 is a pan-KRAS inhibitor that selectively targets both mutant and wildtype KRAS, potentially offering an expanded therapeutic index and addressing resistance mechanisms associated with mutant-selective KRAS inhibitors [4][6] - The compound exhibited significant tumor growth inhibition and anti-tumor efficacy in KRAS mutant xenograft models, with single-digit nanomolar IC50s observed in various cell lines [6][10] Group 3: SHOC2 Modulators - The company identified direct SHOC2 binders that inhibit the assembly of the SHOC2-MRAS-PP1C complex, representing a novel approach to attenuate RAS/MAPK pathway signaling [7][10] - These compounds are the first examples of direct modulators of the SMP complex, with ongoing optimization for potential protein-protein inhibitors and degrader modalities [10] Group 4: Company Overview - Erasca is a clinical-stage precision oncology company focused on developing therapies for RAS/MAPK pathway-driven cancers, with a strong pipeline and collaboration with leading experts in the field [8]