Deep modality-agnostic pipeline to shut down the RAS/MAPK pathway

We have assembled the deepest RAS/MAPK pathway-focused pipeline in the industry, consisting of modality-agnostic programs aligned with our three therapeutic strategies of: (1) targeting key upstream and downstream signaling nodes in the RAS/MAPK pathway; (2) targeting RAS directly; and (3) targeting escape routes that emerge in response to treatment. The target breadth and molecular diversity represented in our pipeline enable us to pursue a systematic, data-driven clinical development effort to identify single agent and combination approaches with the goal of prolonging survival in a wide range of patient populations with high unmet needs.

Our programs target the RAS/MAPK pathway at every turn

Phase 1
Phase 2
Phase 3
Worldwide Rights
Naporafenib (BRAF/CRAF)
Pan-RAS Q61X tissue agnostic
We initiated SEACRAFT-1, a Phase 1b clinical trial for naporafenib in combination with various agents in patients with RAS Q61X tissue agnostic solid tumors.
NRASm melanoma
SEACRAFT-2 (planned)
We plan to initiate SEACRAFT-2, a potential Phase 3 pivotal clinical trial for naporafenib in combination with various agents in patients with NRASm melanoma, in H1 2024.
ERAS-007 (ERK1/2)
We initiated HERKULES-3, a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with colorectal cancer.
EGFR altered GBM
We initiated THUNDERBBOLT-1, a Phase 1 clinical trial for ERAS-801 in patients with recurrent GBM.
KRASm G12D solid tumors
ERAS-12 (EGFR D2/D3)
EGFR & RAS/MAPK altered solid tumors
Affini-T (KRAS G12V/D)
KRASm solid tumors
Small molecule
Large molecule
TCR T cell therapy

Therapeutic Programs

Our lead product candidates are naporafenib (ERAS-254, our oral pan-RAF inhibitor), ERAS-007 (our oral ERK1/2 inhibitor), and ERAS-801 (our CNS-penetrant EGFR inhibitor). These programs are examples of our innovative strategy to target key upstream and downstream MAPK nodes. We are also advancing multiple other programs targeting key oncogenic drivers in the RAS/MAPK pathway.

Naporafenib: our PAN-RAF inhibitor

Naporafenib is a potential first-in-class pan-RAF kinase inhibitor (with high potency and selectivity against BRAF and CRAF), and has been studied in over 500 patients to date. We are planning to evaluate the molecule in indications where it has already shown promising clinical proof of concept – namely, NRASm melanoma and pan-RAS Q61X tissue agnostic solid tumors, as well as explore various combinations with other programs in our pipeline to target other RAS/MAPK pathway-driven tumors.

ERAS-007: our ERK 1/2 inhibitor

ERAS-007 is the most potent ERK inhibitor in development and has the longest target residence time among ERK inhibitors that we are aware of. ERAS-007 has been evaluated as a single agent in a Phase 1 trial in patients with advanced solid tumors. Multiple objective responses were observed in patients with various tumor types, all of which harbor alterations (BRAF, HRAS, and NRAS) in the RAS/MAPK pathway, including melanoma, salivary gland cancer, NSCLC, and thyroid cancer. The adverse event profle was reversible, manageable, and consistent with ERK inhibition. These findings support the development of ERAS-007 as a monotherapy or in combination in diverse, biomarker-selected tumor types. We are pursuing a broad clinical development plan for ERAS-007 across multiple tumor types that includes both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, and/or RAF inhibitors. The first series of trials will be proof-of-concept studies in solid tumors, NSCLC, and CRC. While providing proof-of-concept data, these trials may be expanded to enable potential accelerated approvals in their respective indications.

ERAS-801: our CNS-penetrant EGFR inhibitor

EGFR-mediated signaling plays a key role in the growth of many tumor types. Targeting of wildtype EGFR (wtEGFR) and mutant variants of EGFR (EGFRm) by small molecules and antibodies has resulted in improved patient outcomes in NSCLC, CRC, and HNSCC. However, the ability of these agents to effectively target wtEGFR and EGFRm in the CNS remains an unmet medical need. The lack of clinical activity is likely multifactorial, but we believe there are two primary reasons why approved EGFR inhibitors are not effective: (1) the molecules do not penetrate the CNS well, and (2) the molecules are weak inhibitors of the EGFRvIII mutant protein as homodimers or heterodimers that include wildtype EGFR. ERAS-801 is designed to be a potent, selective, reversible, and orally available small molecule with both: (1) highly enhanced CNS penetration (3.7:1 brain:plasma ratio in mice) and (2) the ability to target both EGFR alterations such as EGFRvIII, the most common mutant form of EGFR found in GBM, and wtEGFR, which heterodimerizes with EGFRvIII.

ERAS-4: our KRAS G12D program

Our ERAS-4 program endeavors to develop small molecules that potently and selectivity bind KRAS G12D. When bound to KRAS G12D, these inhibitors will prevent RAS-mediated signaling by locking KRAS G12D in the inactive GDP-bound state and/or obstructing KRAS G12D’s ability to bind downstream effector proteins, such as BRAF and CRAF. We are accelerating advancement of this program by leveraging our in-house chemistry, biology, and structural biology expertise gained from working on our RAS-GDP and other RAS-GTP programs. We have generated molecules with low nanomolar IC50 potency against KRAS G12D and high selectivity vs. KRAS wildtype (WT). We are optimizing the properties of these molecules utilizing SBDD and structure-activity relationships while continuing to focus on generating other highly potent and selective compounds against KRAS G12D, with the intention to nominate and advance a DevCan into IND-enabling activities.

ERAS-12: our EGFR D2/D3 bispecific antibody program

Inhibition of wildtype EGFR signaling mediated by overexpression of EGFR has shown promise in treating various tumors, including HNSCC and CRC. In tumors where overexpression of EGFR is thought to be the primary driver of EGFR signaling, an antibody-based approach is the most effective way to target the receptor, and approved antibodies have demonstrated good tolerability as well as activity by inhibiting EGFR activation and mediating antibody-dependent cellular cytotoxicity (ADCC), a process by which the antibody alerts the immune system to attack the bound tumor cell. However, all approved anti-EGFR antibodies target domain III (D3) only, which is the inactive conformation of wildtype EGFR, and no approved antibodies target domain II (D2), which is the active, ligand binding, conformation of wildtype EGFR. Antibodies targeting D2 are expected to be more effective when epidermal growth factor (EGF) or other members of the EGF family are overexpressed. We are developing a bispecific antibody that is active against both the inactive and active conformations of wildtype EGFR.

Clinical Trials

Erasca is in the process of initiating a number of clinical trials to evaluate the safety and efficacy of our therapeutic candidates—as monotherapy and in combination regimens—across a range of tumor types.

As an oncology healthcare professional, should you have a patient who may be interested in participating in such a clinical trial, consult the list below of our clinical trials currently open for enrollment—for eligibility criteria and further details. Your interest and participation is critical to the success of these trials and is instrumental in the development of desperately needed new medicines with the potential to benefit many people with cancer.

Product/Target Naporafenib (ERAS-254) / RAF

Clinical Trial

SEACRAFT-1 (ERAS-254-01) SEACRAFT-2 (ERAS-254-02)


In any nautical journey, seacraft are needed to traverse the vast blue ocean not just in their capacity as seagoing ships, but also for their important second meaning: skill in navigation. Erasca is navigating the “blue ocean” of unmet medical needs using next generation sequencing and other techniques to identify RAS/MAPK pathway-altered tumors that can be treated with naporafenib, a potent, selective, orally bioavailable pan-RAF inhibitor, in combination with other targeted therapies. The SEACRAFT series of trials, beginning with SEACRAFT-1 and SEACRAFT-2, will test whether naporafenib can improve outcomes in patients with pan-RAS Q61X solid tumors, and NRASm melanoma, respectively.

Product/Target ERAS-007/ERK

Clinical Trial

HERKULES-3 (ERAS-007-03): A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies ClinicalTrials.gov Study Identifier NCT05039177


Hercules is one of the most iconic figures in classical mythology and one of the greatest adventurers of all time. He is best recognized for his extraordinary feats of strength and durability, attributes that would be desirable for cancer treatments, as well. ERAS-007 is an investigational therapy that has exhibited similar characteristics when administered in specific clinical trial participants diagnosed with certain cancers that are caused by abnormal RAS/MAPK pathway signaling. The HERKULES-3 trial will continue to test the safety and effectiveness of ERAS-007 in trial participants with various gastrointestinal solid tumors

Product/Target ERAS-801/EGFR

Clinical Trial

THUNDERBBOLT-1: A Study to Evaluate ERAS-801 in Patients With Recurrent Glioblastoma ClinicalTrials.gov Study Identifier NCT05222802


Zeus, the great thunderbolt-wielding god of the sky in ancient Greek mythology, was once felled by an unstoppable growth in his head. Relief came only when Athena, the goddess of wisdom, was released from the confines of his skull. In THUNDERBBOLT-1, we hope to similarly unburden our patients through investigating ERAS-801 in glioblastoma (GBM), a devastating cancer of the brain. ERAS-801 is a highly brain-penetrant targeted inhibitor of EGFR, a protein programmed by the erbb1 gene. Much like the precision of Zeus’ thunderbolt, ERAS-801 is specifically designed to target GBM driven by alterations to erbb1 / EGFR. And, in the spirit of Athena, we hope that this investigation will shed more light on this disease, from predictive biomarkers to possible cures. The THUNDERBBOLT-1 trial is currently underway studying safety and activity in patients with recurrent GBM.

For any questions about our clinical trials, please contact us via email at clinicaltrials@erasca.com.