ATX-559 / Accent Therap - LARVOL DELTA

Trial in progress: First-in-human study of ATX-559, an oral inhibitor of DHX9, in patients with advanced or metastatic solid tumors, and molecularly defined cancers. (ASCO 2025) - P1 | "A randomized cohort has also been included during dose expansion in recognition of Project Optimus. The study is open and enrollment is ongoing; clinical trial information: NCT06625515."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRCA • DHX9 • HER-2 • MSI

Accent Therapeutics Announces Trial in Progress Poster for First-in-Human Study of ATX-559 at 2025 ASCO Annual Meeting (PRNewswire) - "Initiated in late 2024, the first-in-human, Phase 1/2, open-label, dose-escalation and expansion study is designed to evaluate multiple doses of ATX-559 in solid tumor patients, with expansion cohorts of patients with advanced or metastatic BRCA-1 and/or BRCA-2-deficient breast cancer and microsatellite instability-high (MSI-H) and/or deficient mismatch repair (dMMR) solid tumors (NCT06625515). Primary endpoints include identification of the recommended Phase 2 dose (RP2D) and assessment of the safety and tolerability of ATX-559. The study additionally aims to characterize the pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity (as assessed per RECIST v1.1 criteria) of orally administered ATX-559. The study is currently open and enrolling."

dMMR • MSI-H • Trial status • Microsatellite Instability • Solid Tumor

Accent Therapeutics Presents Data Supporting Therapeutic Potential of First-in-Class DHX9 Inhibitor, ATX-559…at the AACR Annual Meeting 2025 (PRNewswire) - "The company's poster presentation includes preclinical data supporting continued clinical evaluation of ATX-559, a first-in-class potent, selective, and orally bioavailable small-molecule inhibitor of DHX9. Results within characterize the compound's activity in cancer cell lines with genomic instability and elevated replication stress spanning several indications, including dMMR/MSI-H colorectal cancer and BRCA-altered triple negative breast cancer, and in subtypes of lung, gastric, ovarian, and prostate cancers. ATX-559 was shown to be well tolerated in vivo, leading to robust and dose dependent tumor growth inhibition and regression in BRCA deficient breast cancer and dMMR/MSI-H cell- and patient-derived xenograft models."

dMMR • MSI-H • Preclinical • Colorectal Cancer • Gastric Cancer • Lung Cancer • Microsatellite Instability • Ovarian Cancer • Prostate Cancer • Triple Negative Breast Cancer

ATX-559, a first in class DHX9 inhibitor, and targeted therapeutic for molecularly defined tumors with genomic instability and replicative stress (AACR 2025) - P1 | "We previously demonstrated that DHX9 genetic loss or inhibition by the DHX9 tool compound ATX968 was efficacious in tumor types that exhibit DDRD and/or genomic instability; these include tumors with defective mismatch repair and/or high microsatellite instability (dMMR/MSI-H) or alterations in the DDR genes BRCA1 and/or BRCA2 (BRCA).Here we describe ATX-559, a potent, selective, orally bioavailable, small-molecule inhibitor of DHX9 helicase activity that is currently in clinical development. Oral treatment of 45 mg/kg BID demonstrated enriched sensitivity in BRCA altered TNBC (75%) and dMMR/MSI-H (68%) PDX models.Together, these findings represent preclinical pharmacological validation of DHX9 as a selective therapeutic target in cancers that exhibit genomic instability and replication stress. ATX-559 is currently in a first-in-human, Phase 1, open-label, dose-escalation and expansion study in patients with locally advanced or metastatic solid tumors and..."

Breast Cancer • Endometrial Cancer • Gastric Cancer • Microsatellite Instability • Oncology • Oral Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • DHX9 • MSI

Accent Therapeutics Announces First Patient Dosed in Phase 1/2 Trial of Novel KIF18A Inhibitor ATX-295 and Receives FDA Fast Track Designation for Lead Assets ATX-295 and DHX9 Inhibitor ATX-559 (PRNewswire) - "Accent Therapeutics...announced that the first patient has been dosed in a first-in-human Phase 1/2 clinical trial evaluating the safety and tolerability of ATX-295, a potential best-in-class oral KIF18A inhibitor. In addition, the company has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for ATX-295 for the treatment of adult patients with advanced/metastatic platinum-resistant or refractory ovarian cancer, and for ATX-559, a first-in-class potent and selective inhibitor of DHX9, for the treatment of adult patients with unresectable/metastatic dMMR/MSI-H colorectal cancer post checkpoint inhibitor treatment."

dMMR • Fast track • MSI-H • Platinum resistant • Trial status • Colorectal Cancer • Microsatellite Instability • Ovarian Cancer

Accent Therapeutics to Present Data on Lead Programs ATX-559 and ATX-295 at the 2025 American Association for Cancer Research Annual Meeting (PRNewswire) - "Accent Therapeutics...announced that it will present new data on its first-in-class oral DHX9 inhibitor, ATX-559, and its potentially best-in-class KIF18A inhibitor, ATX-295, at the 2025 AACR Annual Meeting taking place April 25-30 in Chicago, Illinois....Preclinical data supporting continued clinical evaluation of ATX-559 will characterize the compound's activity across in vivo models of cancers exhibiting genomic instability and replication stress, including in dMMR/MSI-H colorectal cancer and BRCA altered triple negative breast cancer. An oral presentation will discuss the preclinical activity of ATX-295 across a panel of ovarian cancer cell lines and provide rationale for whole genome doubling as a viable enrichment biomarker of ATX-295 sensitivity in ovarian cancer models....Accent's potentially best-in-class KIF18A inhibitor, ATX-295, is anticipated to enter the clinic in the first half of 2025."

New trial • Preclinical • Colorectal Cancer • Microsatellite Instability • Ovarian Cancer • Triple Negative Breast Cancer

Accent Therapeutics Announces First Patient Dosed in Phase 1/2 Trial of ATX-559... (PRNewswire) - "In addition to ATX-559, Accent anticipates initiating a Phase 1 trial in 1H 2025 for its second program targeting KIF18A in chromosomally instable tumors."

New P1 trial • Trial status • Breast Cancer • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Rectal Adenocarcinoma

Accent Therapeutics Announces FDA Clearance of IND Application for ATX-559, a First-In-Class Oral DHX9 Inhibitor (PRNewswire) - "Accent Therapeutics...today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for ATX-559, a first-in-class DHX9 inhibitor. In addition, Accent has established a Clinical Advisory Board (CAB) to help guide the Company's progress in the clinic....The newly formed Clinical Advisory Board includes...Josep Tabernero, MD, PhD."

Announcement

ATX-559-001: First-in-Human Study of ATX-559, an Oral Inhibitor of DHX9, in Patients with Advanced or Metastatic Solid Tumors, and Molecularly Defined Cancers (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Accent Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Accent Therapeutics Announces FDA Clearance of IND Application for ATX-559, a First-In-Class Oral DHX9 Inhibitor (PRNewswire) - "Accent Therapeutics...today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for ATX-559, a first-in-class DHX9 inhibitor. In addition, Accent has established a Clinical Advisory Board (CAB) to help guide the Company's progress in the clinic. The ATX-559 Phase 1/2 trial (NCT06625515) is expected to begin dosing patients with a focus on BRCA1- or BRCA2-deficient breast cancer and patients with MSI-H and/or dMMR solid tumors (including certain patients with colorectal, endometrial, gastric, and other cancers) in the fourth quarter of 2024. The clinical study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ATX-559."

Trial status • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Oncology • Solid Tumor