ERAS-007 / Asana BioSci, Erasca, UT MD Anderson Cancer Center - LARVOL DELTA

Updated results from ERAS-007 plus encorafenib and cetuximab (EC) in patients (pts) with EC-naïve metastatic BRAF V600E colorectal cancer (CRC) in the phase 1b/2 HERKULES-3 study. (ASCO 2024) - P1/2 | "ERAS-007 100 mg BID-QW in combination with EC was safe and well tolerated with preliminary evidence of promising clinical activity. These results support continued evaluation of this combination in EC naïve pts with BRAF V600E CRC."

Clinical • Metastases • P1/2 data • Anemia • Colorectal Cancer • Constipation • Dermatitis • Dermatology • Fatigue • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Immunology • Oncology • Pain • Respiratory Diseases • Solid Tumor • BRAF

HERKULES-1: A Study of ERAS-007 as Monotherapy or in Combination With ERAS-601 in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=85 | Completed | Sponsor: Erasca, Inc. | Active, not recruiting ➔ Completed | N=200 ➔ 85 | Trial completion date: Jan 2027 ➔ Jul 2026 | Trial primary completion date: Nov 2026 ➔ Jul 2026

Enrollment change • Monotherapy • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Erk inhibitors intercept Erk-mediated negative feedback while imposing cell-cycle arrest and activating p38. (PubMed, iScience) - "Provision of either BVD523, GDC0994, SCH772984, ASN007, or Temuterkib, led to strong phosphorylation of Erks, suggesting that all inhibitors intercepted Erks-mediated negative feedback activity...Exposure to BVD523 caused dramatic changes in the phosphoproteome. Thus, the application of Erk's inhibitors should be accompanied by agents that prevent pathway re-activation."

Journal • Oncology

Complement C3a induces synaptic elimination in the hippocampus and neurobehavioral deficits in later life of septic neonatal rats triggered by lipopolysaccharide. (PubMed, Free Radic Biol Med) - "Inhibition of ERK with ASN007 mitigated C3a-induced synaptic elimination, neuronal damage, and behavioral deficits both in vivo and in vitro. Our results suggest that astrocyte-derived C3a may contributes to hippocampal synaptic elimination and cognitive deficits through C3a/C3aR/ERK pathway in later life of neonatal septic rats. These findings highlight the C3a/C3aR/ERK axis as a potential therapeutic target for preventing synaptic and cognitive deficits in neonatal septic encephalopathy."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Infectious Disease • Inflammation • Septic Shock

HERKULES-1: A Study of ERAS-007 as Monotherapy or in Combination With ERAS-601 in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=200 | Active, not recruiting | Sponsor: Erasca, Inc. | Trial completion date: Nov 2025 ➔ Jan 2027 | Trial primary completion date: May 2025 ➔ Nov 2026

Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Decoding the molecular mechanisms related to mutations in the GNAQ/11 and BAP1 genes in ocular melanoma (AACR 2024) - "Finally, in vitro testing has been started for inhibitors targeting compensatory pathways involving beta-catenin (WIKI4) and ERK1/2 (ASN007), in combination with the GNAQ/11 inhibitor (FR900359). These tests are being conducted on various mutant UMCCs for GNAQ/11.A better understanding of the altered pathways in our GNAQ/11 or BAP1 mutant isogenic cell lines will help to identify new drugs targeting specifically UM cells."

Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BAP1 • CTNNB1 • GNA11 • GNAQ

Decoding the molecular mechanisms related to mutations in the GNAQ/11 and BAP1 genes in ocular melanoma (AACR 2024) - "Finally, in vitro testing has been started for inhibitors targeting compensatory pathways involving beta-catenin (WIKI4) and ERK1/2 (ASN007), in combination with the GNAQ/11 inhibitor (FR900359). These tests are being conducted on various mutant UMCCs for GNAQ/11.A better understanding of the altered pathways in our GNAQ/11 or BAP1 mutant isogenic cell lines will help to identify new drugs targeting specifically UM cells."

Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BAP1 • CTNNB1 • GNA11 • GNAQ

HERKULES-3: A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies (clinicaltrials.gov) - P1/2 | N=101 | Completed | Sponsor: Erasca, Inc. | Active, not recruiting ➔ Completed

Trial completion • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF • KRAS • NRAS

The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinase. (PubMed, BJA Open) - "p-ERK; miR-29a mimic + dimethyl sulfoxide vs naïve, mean difference [95% CI]: 52.00 [47.01-56.99]; miR-29a mimic + ASN007 vs naïve, mean difference [95% CI]: 47.00 [42.51-51.49]; P<0.001, n=6). Inhibiting miR-29a expression attenuates inflammatory pain by modulating IFNR1, ISG15, and p-ERK expression, highlighting the interactive roles of miR-29a and IFN-ß in the regulation of inflammatory pain."

Journal • Pain • IFNA1 • IFNAR2 • IFNB1 • ISG15 • MAPK1 • MIR29A

HERKULES-3: A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies (clinicaltrials.gov) - P1/2 | N=102 | Active, not recruiting | Sponsor: Erasca, Inc. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Aug 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • BRAF • KRAS • NRAS

HERKULES-1: A Study of ERAS-007 as Monotherapy or in Combination With ERAS-601 in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=200 | Active, not recruiting | Sponsor: Erasca, Inc. | Phase classification: P1b/2 ➔ P1/2 | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: May 2024 ➔ May 2025

Combination therapy • Metastases • Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Dr Parikh on the Rationale for Adding ERAS-007 (OncLive) - "Aparna Parikh, MD...discusses the rationale for evaluating the addition of ERAS-007 to cetuximab (Erbitux) and encorafenib (Braftovi), also known as the BEACON regimen,in BRAF V600E–mutated metastatic colorectal cancer (mCRC)."

Video

BET365 Sports: [2024 ASCO] A quick overview of the major research results in the field of digestive tumors, grasping the new trend [Google translation] (BET365 Sports) - "The American Society of Clinical Oncology (ASCO) Annual Meeting is one of the world's largest, most academically advanced and most authoritative clinical oncology conferences. The 2024 ASCO Annual Meeting will be held in Chicago, USA, from May 31 to June 4, local time....We have compiled the digestive tumor research from the Plenary Session, Oral Abstract Session, Clinical Science Symposium, Rapid Abstract Session and Education Session."

Clinical data • Colorectal Cancer • Esophageal Cancer • Hepatocellular Cancer • Oncology • Pancreatic Cancer

The Concerted Actions of MiR 29a and Type 1 Interferon Receptor Modulate Inflammatory pain (IASP 2024) - "Male rats received 4 nmole miR-29a mimic followed by injection of DMSO or 30 ug p-ERK antagonist (ASN007) 1h later... Inhibiting miR-29a expression could alleviate inflammatory pain by upregulating IFNR1 and ISG 15 while suppressing p-ERK. The concerted actions of miR-29a and IFN-? play a crucial role in modulating CFA-induced inflammatory pain by regulating the expression of IFNR1, ISG 15, and p-ERK."

Pain • IFNAR2 • ISG15 • MIR29A

Erasca Announces Strategic In-Licensing of RAS-Targeting Franchise (GlobeNewswire) - "HERKULES-3: ERAS-007 + EC in EC-naïve patients with BRAFm CRC: Deprioritized as clinical efficacy data (data to be presented at ASCO 2024) do not support continued evaluation; THUNDERBBOLT-1: ERAS-801 in recurrent glioblastoma: Due to the desire to focus internal resources on developing naporafenib and the RAS-targeting franchise, Erasca is exploring further advancement of ERAS-801 via select investigator-sponsored trial(s); ERAS-4 pan-KRAS program...Erasca will discontinue its internal pan-KRAS program; provided that certain of the existing ERAS-4 molecules are included in the Medshine agreement as potential backup compounds for ERAS-4001."

Discontinued • Pipeline update • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Oncology • Solid Tumor

Erasca Reports First Quarter 2024 Business Updates and Financial Results (GlobeNewswire) - "Key Upcoming Milestones:...HERKULES-3: Phase 1b trial for ERAS-007 (ERK inhibitor) plus encorafenib (BRAFTOVI) + cetuximab (ERBITUX) (EC) in EC-naïve patients with BRAF-mutant (BRAFm) colorectal cancer (CRC) - Phase 1b combination data expected in the second quarter of 2024."

P1 data • Colorectal Cancer

Erasca Announces Three Presentations at the 2024 ASCO Annual Meeting (GlobeNewswire) - "Erasca...announced the company will present one oral presentation and two poster presentations at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting....Oral presentation will feature updated HERKULES-3 results for ERK1/2 inhibitor ERAS-007 in combination with encorafenib and cetuximab in BRAFm colorectal cancer. Poster presentations will feature SEACRAFT-1 Phase 1 trial design for naporafenib plus trametinib in RAS Q61X mutations, and preliminary FLAGSHP-1 Phase 1 results for ERAS-601 and cetuximab in chordoma."

P1 data • P1/2 data • Trial status • Chordoma • Colorectal Cancer

Erasca Reports Fourth Quarter 2023 and Full Year 2023 Business Updates and Financial Results (GlobeNewswire) - "Key Upcoming Anticipated Milestones:...(i) HERKULES-3: Phase 1b trial for ERAS-007 (ERK inhibitor) plus encorafenib (BRAFTOVI) + cetuximab (ERBITUX) (EC) in EC-naïve patients with BRAFm CRC: Phase 1b combination data expected in the first half of 2024; (ii) THUNDERBBOLT-1: Phase 1 trial for ERAS-801 (CNS-penetrant EGFR inhibitor) in patients with GBM: Initial Phase 1 monotherapy data expected in 2024."

P1 data • Colorectal Cancer • Glioblastoma

HERKULES-3: A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies (clinicaltrials.gov) - P1/2 | N=102 | Active, not recruiting | Sponsor: Erasca, Inc. | Recruiting ➔ Active, not recruiting | Phase classification: P1b/2 ➔ P1/2 | N=200 ➔ 102

Enrollment change • Enrollment closed • Metastases • Phase classification • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • BRAF • KRAS • NRAS

Erasca Achieves Key Milestones for Naporafenib and ERAS-801 Programs and Extends Cash Runway (GlobeNewswire) - "ERAS-801 – CNS-penetrant EGFR Inhibitor: Phase 1 monotherapy dose escalation and expansion data in rGBM expected in 2024; ERAS-007 – ERK1/2 Inhibitor: Initial dose expansion data from Phase 1b/2 HERKULES-3 trial further evaluating encouraging early efficacy data with ERAS-007 in combination with EC in EC-naïve patients with BRAF mutant CRC expected between H2 2023 and H1 2024."

P1 data • P1/2 data • Brain Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Oncology • Solid Tumor

Erasca Reports Second Quarter 2023 Financial Results and Business Updates (Yahoo Finance) - "SEACRAFT-1: Phase 1b trial for naporafenib plus trametinib in patients with RAS Q61X tissue agnostic solid tumors; Dosing of the first patient expected in the second half of 2023; Initial Phase 1b combination data expected between the second and fourth quarters of 2024; SEACRAFT-2: Randomized pivotal Phase 3 trial for naporafenib plus trametinib in patients with NRASm melanoma; Dosing of the first patient expected in the first half of 2024; HERKULES-3: Phase 1b trial for ERAS-007 plus EC in EC-naïve patients with BRAFm CRC; Phase 1b combination expansion data in patients with BRAFm CRC expected between the second half of 2023 and the first half of 2024; FLAGSHP-1: Phase 1b trial for ERAS-601 in patients with advanced solid tumors; Phase 1b combination expansion data in relevant patient populations, including patients with human papillomavirus (HPV)-negative advanced head and neck squamous cell carcinoma (HNSCC), expected in the first half of 2024..."

P1 data • Trial status • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

HERKULES-2: A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC (clinicaltrials.gov) - P1b | N=24 | Completed | Sponsor: Erasca, Inc. | Active, not recruiting ➔ Completed | N=200 ➔ 24 | Trial completion date: Mar 2024 ➔ Apr 2023

Enrollment change • Metastases • Trial completion • Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Preliminary results from ERAS-007 plus encorafenib and cetuximab (EC) in patients (pts) with metastatic BRAF V600E mutated colorectal cancer (CRC) in HERKULES-3 study: A phase 1b/2 study of agents targeting the mitogen-activated protein kinase (MAPK) pathway in pts with advanced gastrointestinal malignancies (GI cancers). (ASCO 2023) - P1b/2 | "ERAS-007+EC in pts with BRAF V600E CRC shows acceptable preliminary safety/tolerability and evidence of clinical activity. The highest dose of ERAS-007 evaluated and cleared by the safety review committee to date is 100 mg BID-QW when combined with EC. Observed PK, toxicity, and preliminary activity support continued evaluation of this combination in pts with BRAF V600E CRC."

Clinical • Metastases • P1/2 data • Cardiovascular • Colorectal Cancer • Constipation • Dermatitis • Dermatology • Fatigue • Gastrointestinal Cancer • Gastrointestinal Disorder • Hypertension • Immunology • Oncology • Pain • Solid Tumor • BRAF

Preliminary results from ERAS-007 plus palbociclib (palbo) in patients (pts) with KRAS/NRAS mutant (m) colorectal cancer (CRC) or KRASm pancreatic ductal adenocarcinoma (PDAC) in HERKULES-3 study: A phase 1b/2 study of agents targeting the mitogen-activated protein kinase (MAPK) pathway in pts with advanced gastrointestinal malignancies (GI cancers). (ASCO 2023) - P1b/2 | "ERAS-007 in combination with palbo in pts with KRASm/NRASm CRC or KRASm PDAC shows expected preliminary safety with reversible and manageable AEs. The highest dose evaluated and cleared by the safety review committee to date is ERAS-007 100 mg BID-QW in combination with the approved monotherapy dose of palbo 125 mg QD. Clinical trial information: NCT05039177."

Clinical • Metastases • P1/2 data • Anemia • Cerebral Hemorrhage • Colorectal Cancer • Dermatitis • Dermatology • Fatigue • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Respiratory Diseases • Septic Shock • Solid Tumor • Thrombocytopenia • KRAS • NRAS

HERKULES-1: A Study of ERAS-007 as Monotherapy or in Combination With ERAS-601 in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1b/2 | N=200 | Active, not recruiting | Sponsor: Erasca, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Monotherapy • Oncology • Solid Tumor