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APPROACH & PIPELINE

Small molecule therapies with expansive potential

Gray background with blue abstract wave intersecting a circle containing a close-up image of a cancer cell
Abstract circular graphic with connected dots representing potential cancer targets. Blue shading within the circle represents RNA modifying protein targets. Pink and blue purple shading represent adjacent high-value targets with mechanistic and biologic process similarities.
Abstract circular graphic with connected dots representing potential cancer targets. Blue shading within the circle represents RNA modifying protein targets. Pink and blue purple shading represent adjacent high-value targets with mechanistic and biologic process similarities.

Our Approach

Our deep understanding of the key biological underpinnings of cancer and ability to identify, interrogate, and successfully drug intracellular enzyme targets enables us to advance a pipeline of unique small molecule therapeutics with expansive potential. Combining our industry-leading expertise in RNA-modifying proteins (RMPs) and our systematic mapping of both the RMP space and adjacent high-value areas for drug discovery, we have built a flexible model that allows for a diversity of approaches to developing potentially transformative biomarker-driven cancer medicines. Our therapies are designed for suboptimally-addressed, novel or known high-impact oncogenic targets with the potential to benefit large patient populations.

Platform & Capabilities

Accent’s platform and integrated capabilities fuel a robust pipeline of transformative small molecule oncology therapeutics with expansive potential for individuals living with difficult-to-treat cancers. We’re combining cutting-edge approaches to identify and prioritize the most critical targets for biomarker-driven oncology indications, and to efficiently match those targets with novel small molecule inhibitors that serve as powerful starting points for our drug optimization efforts.

5-panel graphic outlining Accent integrated capabilities, including deep cancer biology, lead enzyme druggability, efficient drug discovery, strong translational medicine, and clinical development.5-panel graphic outlining Accent integrated capabilities, including deep cancer biology, lead enzyme druggability, efficient drug discovery, strong translational medicine, and clinical development.
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Pipeline

Accent is relentlessly pursuing targets with the potential to improve outcomes for broad biomarker-driven patient populations. Our pipeline offers a diversified approach of both first-in-class and best-in-class programs with the potential to address significant unmet medical needs.

For inquiries related to clinical studies, please contact us at clinicaltrials@accenttx.com

INDICATION
PRECLINICAL
IND-ENABLING
Phase 1/2
Registrational
Breast, ovarian, CRC, endometrial
PHASE 1/2

Accent’s lead program, ATX-559, is a first-in-class potent and selective inhibitor of DHX9, a novel and previously undrugged RNA and DNA/RNA helicase, shown to play a critical role in tumors with high levels of replication stress (including breast, ovarian, colorectal, endometrial, gastric, and others), representing large patient populations with significant unmet medical need. DHX9 has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability, making it a compelling novel oncology target. In addition to exploiting key tumor vulnerabilities in DNA repair deficient backgrounds (e.g. BRCA) and hyper-mutated states (e.g. MSI-H/dMMR), Accent is exploring the sensitivity of other tumor types to DHX9 inhibition, and the potential to combine DHX9 inhibitors with other cancer treatments to maximize its full potential for helping patients.

ATX-559 is currently being evaluated in a first-in-human Phase 1/2, open-label, dose-escalation and expansion study, enrolling solid tumor patients with a focus on patients with BRCA1- or BRCA2-deficient breast cancer and those with MSI-H and/or dMMR solid tumors (including certain patients with colorectal, endometrial, gastric, and other cancers). To learn more, please visit www.clinicaltrials.gov (NCT06625515).

ATX-559 has been granted Fast Track designation by the FDA for the treatment of adult patients with unresectable/metastatic dMMR/MSI-H colorectal cancer post checkpoint inhibitor treatment. Fast Track designation is designed to facilitate the development and expedite the review of novel drug candidates that address serious conditions marked by unmet medical need, with the aim of accelerating patient access to novel treatment options.

Ovarian, TNBC
PHASE 1/2

Accent’s second lead program, ATX-295, is a potential best-in-class inhibitor for KIF18A which may address a large patient population across several cancer indications, including ovarian and triple negative breast cancer (TNBC). KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability. KIF18A inhibitor treatment results in rapid cell death for cancers with an abnormal number of chromosomes (aneuploid) in vitro and in vivo, while cells with normal numbers of chromosomes (euploid) are unaffected.

ATX-295 is currently being evaluated in a first-in-human Phase 1/2, open-label, dose-escalation and expansion study, enrolling patients with locally advanced or metastatic solid tumors, including high-grade serious ovarian cancer. To learn more, please visit https://clinicaltrials.gov (NCT06799065).

ATX-295 has been granted Fast Track designation by the FDA for the treatment of adult patients with advanced/metastatic platinum-resistant or refractory ovarian cancer. Fast Track designation is designed to facilitate the development and expedite the review of novel drug candidates that address serious conditions marked by unmet medical need, with the aim of accelerating patient access to novel treatment options.

For information on clinical trials, please visit https://clinicaltrials.gov.

Our Expanded Access Policy

Expanded access, or compassionate use, is the use of an investigational medicine prior to regulatory approval and outside of a clinical trial.

We understand that for patients with serious diseases such as cancer, waiting for an approved treatment can be difficult. However, Accent Therapeutics does not currently offer expanded access to our investigational products.

​We may reevaluate the status of our Expanded Access Policy as development of our investigational products progresses. Accent Therapeutics reserves the right to revise this Expanded Access Policy at any time.

We encourage you to speak with your physician about options that may be right for you.

Presentations & Publications

Key scientific research published by the Accent team and collaborators.

4.28.25 | AACR 2025

ATX-559, a First in Class DHX9 Inhibitor, and Targeted Therapeutic for Molecularly Defined Tumors with Genomic Instability and Replicative Stress

View Presentation
4.28.25 | AACR 2025

Activity of the Novel KIF18A Inhibitor, ATX-295, is Enriched in Whole Genome Doubled Ovarian Cancer Pre-Clinical Models

View Presentation
4.8.24 | AACR 2024

Inhibition of KIF18A Leads to Mitotic Arrest and Robust Anti-Tumor Activity in Chromosomally Instable Tumors

View Presentation
4.7.24 | AACR 2024

circBRIP1 RNA as a Non-Invasive Target Engagement Pharmacodynamic Biomarker for DHX9 Inhibition

View Presentation
3.13.24 | GRC DNA Damage, Mutation and Cancer 2024

DHX9 Inhibition as a Novel Therapeutic for Cancer with Loss-of-Function Mutations in DNA Damage Repair Genes BRCA1 and BRCA2

View Presentation
10.14.23 | AACR-NCI-EORTC Symposium 2023

DHX9 Inhibition as a Novel Therapeutic Modality in Microsatellite Instable Colorectal Cancer Exhibiting Defective Mismatch Repair

View Presentation
4.29.25 | Journal of Medicinal Chemistry

Discovery of ATX968: An Orally Available Allosteric Inhibitor of DHX9

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4.14.25 | Nature

Nature Magazine Communications Biology Characterization of exoribonuclease XRN1 as a cancer target and identification of adenosine-3’,5’-bisphosphate as a potent enzyme inhibitor

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4.9.25 | Nature

Characterization of exoribonuclease XRN1 as a cancer target and identification of adenosine-3’,5’-bisphosphate as a potent enzyme inhibitor

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11.26.24 | Cancer Research

A Potent, Selective, Small-Molecule Inhibitor of DHX9 Abrogates Proliferation of Microsatellite Instable Cancers with Deficient Mismatch Repair

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9.30.24 | Epigenetic Drug Discovery Book Chapter

RNA Modifying Proteins: Emerging Targets for Drug Discovery

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10.20.23 | Acta Crystallographica Section D

Crystal structures of the DExH-box RNA helicase DHX9

View Publication

Partnerships

Our collaborations with strategic partners with deep oncology expertise enable us to further advance and achieve the rich therapeutic potential of our clinical programs. For more information about collaborations please contact us at collaboration@ACCENTTX.COM.

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Accent and AstraZeneca have a transformational partnership to discover, develop and commercialize certain novel therapeutics targeting RNA-modifying proteins (RMPs) for the treatment of cancer. The collaboration seeks to rapidly advance and achieve the rich therapeutic potential of the exciting programs under partnership by combining AstraZeneca’s proven track record in bringing forward novel oncology medicines with Accent’s industry-leading expertise in the biology, target identification and drug discovery of RMP-targeting therapies.

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