ERAS-0015 / Erasca, Guangzhou JOYO Pharma - LARVOL DELTA

RCZY-690: A tri-complex molecular glue pan-RAS (ON) inhibitor exhibiting best-in-class potential for RAS-addicted solid tumors (AACR 2026) - "Compared to RMC-6236 and ERAS-0015, it shows higher degree of preferential tumor distribution in mouse models. RCZY-690 demonstrates favorable PK/PD profiles, including more durable DUSP6 suppression than RMC-6236, alongside excellent in vivo tolerability and promising safety margins in preclinical toxicity studies. Taken together, these attributes position RCZY-690 as a promising pan-RAS(ON) inhibitor and support its advancement toward an Investigational New Drug (IND) filing planned for Q2 2026."

Oncology • Solid Tumor • DUSP6 • HRAS • KRAS • NRAS

Key Upcoming Milestones (GlobeNewswire) - "AURORAS-1 and JYP0015M101: Phase 1 monotherapy data from...China expected in the first half of 2026; Initiation of AURORAS-1 monotherapy expansion cohorts and combination dose escalation cohort planned for the second half of 2026; AURORAS-1 monotherapy expansion data and combination dose escalation data planned for 2027."

P1 data • Trial status • Solid Tumor

STAR: Study of JYP0015 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Guangzhou JOYO Pharma Co., Ltd | Phase classification: P1/2 ➔ P2

Phase classification • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • RAS

Erasca is advancing ERAS-0015 in the ongoing AURORAS-1 Phase 1 dose escalation trial in patients with RAS-mutant solid tumors with initial Phase 1 monotherapy data expected in the first half of 2026 (GlobeNewswire)

P1 data • Trial status • Solid Tumor

Erasca…announced the exercise of its option to expand the existing license agreement with Joyo Pharmatech Co., Ltd. (Joyo) to include China, Hong Kong, and Macau, which will provide Erasca with worldwide rights to its potential best-in-class pan-RAS molecular glue ERAS-0015 (GlobeNewswire) - "Under the terms of the ERAS-0015 license agreement, Erasca exercised its option to convert its territory to worldwide and is obligated to make a one-time payment to Joyo based on the stage of Joyo’s development program."

Licensing / partnership • Solid Tumor

Erasca and Tango Therapeutics Enter into Clinical Collaboration to Evaluate Combination of ERAS-0015 and Vopimetostat (GlobeNewswire) - "This agreement will support a Phase 1/2 clinical trial evaluating ERAS-0015 in combination with vopimetostat in patients with MTAPdel pancreatic or MTAPdel RASm non-small cell lung cancer (NSCLC). Erasca will supply ERAS-0015 free of charge, and Tango will be the trial sponsor."

Commercial • New P1/2 trial • Non Small Cell Lung Cancer

Initial Phase 1 monotherapy data expected for ERAS-0015 in 1H and for ERAS-4001 in 2H 2026 (GlobeNewswire)

P1 data • Solid Tumor

Discovery of PSTA-2413, an oral pan-RAS inhibitor with wild type selectivity and potent in vitro and in vivo efficacy (AACR-NCI-EORTC 2025) - "PSTA-2413 retained nanomolar activity in AMG510-resistant cells, suggesting potential to overcome G12C inhibitor resistance. In contrast, PSTA-2413 showed relatively reduced activity in KRAS wild-type cells compared to RMC-6236 and ERAS-0015...A preliminary rat toxicity study indicated a 10-fold safety margin. Conclusions PSTA-2413 shows distinct advantages over existing pan-RAS inhibitors, including enhanced in vitro potency, selectivity over wild-type KRAS, robust in vivo antitumor activity with tumor regression, favorable pharmacokinetics, and a promising safety profile—supporting its potential for clinical advancement."

Preclinical • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

STAR: Study of JYP0015 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS (clinicaltrials.gov) - P1/2 | N=210 | Recruiting | Sponsor: Guangzhou JOYO Pharma Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

AURORAS-1: A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: Erasca, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Solid Tumor

AURORAS-1: A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=200 | Not yet recruiting | Sponsor: Erasca, Inc.

Monotherapy • New P1 trial • Solid Tumor

Erasca Announces Early Clinical Advancement and Prioritization of RAS-Targeting Franchise Coupled with More than 3 Years of Projected Cash Runway (GlobeNewswire) - "ERAS-0015 – Potential Best-in-Class Pan-RAS Molecular Glue: IND application cleared by the FDA; Initial AURORAS-1 Phase 1 monotherapy data in RASm solid tumors expected in 2026...ERAS-4001: Potential First-in-Class Pan-KRAS inhibitor: IND application submitted to the FDA; Initial BOREALIS-1 Phase 1 monotherapy data in KRASm solid tumors expected in 2026."

IND • New P1 trial • Oncology • Solid Tumor

Erasca Reports First Quarter 2025 Business Updates and Financial Results (GlobeNewswire) - "Key Upcoming Milestones: (i) AURORAS-1: Phase 1 trial for ERAS-0015 (pan-RAS molecular glue) in patients with RASm solid tumors: Initial Phase 1 monotherapy data expected in 2026; (ii) BOREALIS-1: Phase 1 trial for ERAS-4001 (pan-KRAS inhibitor) in patients with KRASm solid tumors: Initial Phase 1 monotherapy data expected in 2026."

P1 data • Solid Tumor

Abstract 390 - ERAS-0015 is a pan-RAS molecular glue with best-in-class potential in RAS mutant solid tumors (GlobeNewswire) - "Erasca...presented new preclinical data reinforcing the best-in-class profiles of Erasca’s RAS-targeting franchise at the American Association for Cancer Research (AACR) Annual Meeting....ERAS-0015 demonstrated favorable pharmacokinetic properties including longer residence time and greater tissue exposure that led to robust anti-tumor activity alone and in combination at doses lower than the leading pan-RAS molecular glue in development....ERAS-0015 dose-dependently formed a ternary complex with active state RAS and CypA, which blocks formation of additional downstream effector complexes. Potent inhibition of proliferation with ERAS-0015 across a panel of cell lines spanning diverse tumor tissues and RAS mutations....Promising monotherapy and combination activity across multiple RAS mutant models."

Preclinical • Solid Tumor

ERAS-0015 is a pan-RAS molecular glue with best-in-class potential in RAS mutant solid tumors (AACR 2025) - "ERAS-0015's roughly 8-20-fold higher binding affinity to cyclophilin A (CYPA) is thought to contribute to its higher in vitro cellular potency as well as favorable ADME and PK properties resulting in a longer residence time and greater exposure in tumor tissues as compared to RMC-6236. These favorable properties enabled ERAS-0015 to achieve comparable tumor growth inhibition (TGI) relative to RMC-6236 at 1/8th-1/10th the dose across multiple KRAS mutant CDX models irrespective of histology or specific mutation.ERAS-0015 demonstrated promising preclinical activity across multiple RAS mutant models supporting IND filing in 1H 2025."

Oncology • Solid Tumor • KRAS • RAS

Erasca Reports Fourth Quarter and Full Year 2024 Business Updates and Financial Results (GlobeNewswire) - "AURORAS-1: Phase 1 trial for ERAS-0015 (pan-RAS molecular glue) in patients with RASm solid tumors...IND filing expected in mid-Q2 2025...Initial Phase 1 monotherapy data in relevant tumor types expected in 2026; BOREALIS-1: Phase 1 trial for ERAS-4001 (pan-KRAS inhibitor) in patients with KRASm solid tumors...IND filing expected in Q2 2025...Initial Phase 1 monotherapy data in relevant tumor types expected in 2026"

New P1 trial • P1 data • Solid Tumor

STAR: Study of JYP0015 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS (clinicaltrials.gov) - P1/2 | N=210 | Not yet recruiting | Sponsor: Guangzhou JOYO Pharma Co., Ltd

New P1/2 trial • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Erasca Announces Three Poster Presentations at the 2025 AACR Annual Meeting (GlobeNewswire) - "Presentations will feature potential best-in-class pan-RAS molecular glue ERAS-0015 and pan-KRAS inhibitor ERAS-4001. Erasca will also present potential first-in-class examples of direct SMP complex inhibitors, representing a new approach to block the RAS/MAPK pathway."

Preclinical • Solid Tumor

Jiayue Pharmaceutical’s Class 1 new drug JYP0015 tablets were approved for clinical trial implied permission, opening a new chapter in the treatment of RAS mutation cancer [Google translation] (bydrug.pharmcube.com) - "On February 21, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that the Class 1 new drug JYP0015 tablets independently developed by Jiayue Pharmaceuticals has been approved for multiple clinical trials with implicit approval, and is intended to be used to treat hematological tumors and solid tumors with RAS mutations."

New trial • Hematological Malignancies • Oncology • Solid Tumor

Erasca Reports Third Quarter 2024 Business Updates and Financial Results (GlobeNewswire) - "Key Upcoming Milestones: (i) AURORAS-1: Phase 1 trial for ERAS-0015 (pan-RAS molecular glue) in patients with RASm solid tumors - IND filing expected in H1 2025; Initial Phase 1 monotherapy data in relevant tumor types expected to be reported in 2026; (ii) BOREALIS-1: Phase 1 trial for ERAS-4001 (pan-KRAS inhibitor) in patients with KRASm solid tumors - IND filing expected in Q1 2025; Initial Phase 1 monotherapy data in relevant tumor types expected to be reported in 2026."

IND • P1 data • Solid Tumor

RAS Targeting Franchise Update (ERAS-0015 and ERAS-4001) (GlobeNewswire) - "Nonclinical data continue to support potential best-in-class profiles, including data generated in-house; In-life portion of Good Laboratory Practice (GLP) toxicology studies tracking as anticipated: ERAS-0015 completed, ERAS-4001 near completion."

Preclinical • Oncology • Solid Tumor

Erasca Reports Second Quarter 2024 Business Updates and Financial Results (GlobeNewswire) - "Key Upcoming Milestones: AURORAS-1: IND filing expected in H1 2025; Initial Phase 1 monotherapy data in relevant tumor types expected to be reported in 2026; BOREALIS-1: IND filing expected in Q1 2025; Initial Phase 1 monotherapy data in relevant tumor types expected to be reported in 2026."

IND • P1 data • Oncology • Solid Tumor

Erasca Announces Strategic In-Licensing of RAS-Targeting Franchise (GlobeNewswire) - "Erasca, Inc...announced it has entered into exclusive license agreements for two preclinical RAS programs—a potential best-in-class pan-RAS molecular glue (ERAS-0015) and a potential first-in-class pan-KRAS inhibitor (ERAS-4001)...Under the terms of the ERAS-0015 license agreement, in exchange for an exclusive license to develop and commercialize ERAS-0015 in the Erasca territory...Erasca will pay the licensor, Joyo Pharmatech Co., Ltd. (Joyo), a one-time upfront cash payment of $12.5 million...Key Upcoming Milestones...AURORAS-1: Phase 1 trial for ERAS-0015 in patients with RASm solid tumors: IND filing expected in H1 2025...BOREALIS-1: Phase 1 trial for ERAS-4001 in patients with KRASm solid tumors....Initial Phase 1 monotherapy data in relevant tumor types expected in 2026."

IND • Licensing / partnership • P1 data • Oncology • Solid Tumor