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.

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 DHX9 inhibitor with the potential to address high unmet need indications, including BRCA-deficient tumors (triple negative breast cancer (TNBC), ovarian and others), high microsatellite instable (MSI-H) and/or deficient mismatch repair (dMMR) cancers (including colorectal, endometrial, gastric and others), and additional undisclosed cancer types representing large patient populations. DHX9 is an RNA and DNA/RNA helicase that has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability. 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. Therefore, this enzyme represents a compelling novel oncology target.

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).

Ovarian, TNBC

IND-ENABLING

Accent’s second lead program 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.

Accent has advanced this program quickly and is on track to initiate Phase 1 studies in the first half of 2025.

Presentations & Publications

Key scientific research published by the Accent team and collaborators.

4.8.24 | AACR 2024

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

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4.7.24 | AACR 2024

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

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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

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10.14.23 | AACR-NCI-EORTC Symposium 2023

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

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10.13.23 | AACR-NCI-EORTC Symposium 2023

Characterization of Selective, Allosteric Inhibitors of Human XRN1

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10.12.23 | AACR-NCI-EORTC Symposium 2023

Exoribonuclease XRN1 is a Therapeutic Vulnerability in Tumors with Intrinsically Elevated Type 1 Interferon Signaling

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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.

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.

Small molecule therapies with expansive potential

Our Approach

Platform & Capabilities

Pipeline

Presentations & Publications

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

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

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

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

Characterization of Selective, Allosteric Inhibitors of Human XRN1

Exoribonuclease XRN1 is a Therapeutic Vulnerability in Tumors with Intrinsically Elevated Type 1 Interferon Signaling

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

RNA Modifying Proteins: Emerging Targets for Drug Discovery

Crystal structures of the DExH-box RNA helicase DHX9

Development of assays to support identification and characterization of modulators of DExH-box helicase DHX9

Partnerships