NB005 / XRad Therap, Newbay Pharma - LARVOL DELTA

A phase I study of NB005, a dual inhibitor of ATM and DNA-PK, in patients with metastatic tumors (ESMO 2026) - No abstract available

Clinical • Metastases • P1 data • Oncology

Phase 1a clinical trial of XRD-0394, a first-in-class dual ATM/DNA-PK inhibitor, in combination with palliative radiotherapy. (PubMed, Int J Radiat Oncol Biol Phys) - "Single-dose XRD-0394 can be safely combined with palliative RT at plasma exposures that exceeded the pre-specified target threshold, supporting fractionated multi-dose studies."

First-in-human • Journal • P1 data • Oncology

First disclosure of XRD-0394, a novel dual ATM/DNA-PK inhibitor, that potently radiosensitizes and potentiates PARP and topoisomerase inhibitors (AACR 2024) - P1 | "The median tmax (2.3 h) and mean terminal t½ (11.1 h) at the 160 mg dose in subjects support coadministration of XRD-0394 and RT within a clinically feasible time frame. These results provide a rationale for future clinical trials with XRD-0394 in combination with RT, RT and immunotherapy, PARP inhibitors and targeted delivery of topoisomerase inhibitors."

IO biomarker • Late-breaking abstract • Oncology • BRCA

Enhanced Response to Radiopharmaceutical Therapy in Preclinical Tumor Models with XRD-0394, a Dual Inhibitor of ATM Kinase and DNA-PKcs. (PubMed, Radiat Res) - "Increased expression of type I interferon response genes was observed after irradiation + XRD-0394 compared to irradiation alone, suggesting that XRD-0394 may also accentuate the immunogenic effects of radiation on tumor cells. Further investigation is warranted into treatment approaches that combine radiopharmaceutical therapies, DNA repair inhibitors, and immunotherapies."

IO biomarker • Journal • Preclinical • Ataxia • Genito-urinary Cancer • Head and Neck Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Concurrent XRD-0394 With Radiation Therapy for High Grade Gliomas (clinicaltrials.gov) - P1 | N=39 | Recruiting | Sponsor: NYU Langone Health | Not yet recruiting ➔ Recruiting | Initiation date: Apr 2025 ➔ Nov 2025

Enrollment open • Trial initiation date • Brain Cancer • Glioma • High Grade Glioma • Oncology • Solid Tumor

ATM/DNA-PK Inhibitor XRD-0394 Enhances Radiation-Induced Pro-Inflammatory Responses in Glioma Models (SNO 2025) - "We previously evaluated the radiosensitizing effect of the ATM inhibitor AZD1390 in both p53-mutant and wild-type DMGs and observed enhanced sensitivity in p53-mutant models (Mangoli et al., in press). In conclusion, a dual inhibitor of ATM and DNA-PK enhances radiation-induced cytotoxicity and pro-inflammatory signaling in GBM and DMG models. Ongoing studies will further define the therapeutic potential of this combination strategy."

IO biomarker • Ataxia • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • High Grade Glioma • Immunology • Inflammation • Movement Disorders • Primary Immunodeficiency • Solid Tumor • CCR4 • STING

ATM/DNA-PK Inhibitor XRD-0394 Enhances Radiation-Induced Pro-Inflammatory Responses in Glioma Models (WFNOS 2025) - "We previously evaluated the radiosensitizing effect of the ATM inhibitor AZD1390 in both p53-mutant and wild-type DMGs and observed enhanced sensitivity in p53-mutant models (Mangoli et al., in press). In conclusion, a dual inhibitor of ATM and DNA-PK enhances radiation-induced cytotoxicity and pro-inflammatory signaling in GBM and DMG models. Ongoing studies will further define the therapeutic potential of this combination strategy."

IO biomarker • Ataxia • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Immunology • Inflammation • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • CCR4 • STING

ATM/DNA-PK Inhibitor XRD-0394 Enhances Radiation-Induced Pro-Inflammatory Responses in Glioma Models (WFNOS 2025) - "We previously evaluated the radiosensitizing effect of the ATM inhibitor AZD1390 in both p53-mutant and wild-type DMGs and observed enhanced sensitivity in p53-mutant models (Mangoli et al., in press). In conclusion, a dual inhibitor of ATM and DNA-PK enhances radiation-induced cytotoxicity and pro-inflammatory signaling in GBM and DMG models. Ongoing studies will further define the therapeutic potential of this combination strategy."

IO biomarker • Ataxia • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • High Grade Glioma • Immunology • Inflammation • Movement Disorders • Primary Immunodeficiency • Solid Tumor • CCR4 • STING

Concurrent XRD-0394 With Radiation Therapy for High Grade Gliomas (clinicaltrials.gov) - P1 | N=39 | Not yet recruiting | Sponsor: NYU Langone Health

New P1 trial • Brain Cancer • CNS Tumor • Glioma • Malignant Glioma • Oncology • Solid Tumor

A novel dual ATM/DNA-PK inhibitor, XRD-0394, potently radiosensitizes and potentiates PARP and topoisomerase I inhibitors. (PubMed, Mol Cancer Ther) - P1 | "A Phase Ia clinical trial (NCT05002140) with XRD-0394 in combination with RT has completed. These results provide a rationale for future clinical trials with XRD-0394 in combination with RT, PARP inhibitors and targeted delivery of topoisomerase I inhibitors."

Journal • Oncology • BRCA1 • BRCA2

Trial of XRD-0394, a Kinase Inhibitor, in Combination With Palliative Radiotherapy in Advanced Cancer Patients (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: XRad Therapeutics Inc | Active, not recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Jul 2023 | Trial primary completion date: Dec 2023 ➔ Jul 2023

Combination therapy • Metastases • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Trial of XRD-0394, a Kinase Inhibitor, in Combination With Palliative Radiotherapy in Advanced Cancer Patients (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: XRad Therapeutics Inc | Recruiting ➔ Active, not recruiting | N=38 ➔ 11

Enrollment change • Enrollment closed • Oncology • Solid Tumor

Trial of XRD-0394, a Kinase Inhibitor, in Combination With Palliative Radiotherapy in Advanced Cancer Patients (clinicaltrials.gov) - P1 | N=38 | Recruiting | Sponsor: XRad Therapeutics Inc | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

XRad Therapeutics Announces First Patient Dosed in Phase 1a Clinical Trial of XRD-0394 for Metastatic, Locally-Advanced or Recurrent Solid Tumors (GlobeNewswire) - “XRad Therapeutics…announced that the first patient has been dosed in the company’s Phase 1a trial evaluating XRD-0394 in combination with radiation therapy (RT) for the treatment of metastatic, locally-advanced or recurrent solid tumors. XRD-0394 is a first-in-class, oral, dual kinase inhibitor of both ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK) and based on preclinical studies is designed to enhance the effectiveness of radiation therapies…The Phase 1a trial is an open-label, multicenter study designed to evaluate the safety and tolerability of single ascending doses of XRD-0394 administered with palliative RT in patients with metastatic, locally advanced or recurrent cancer.”

Trial status • Oncology • Solid Tumor

Trial of XRD-0394, a Kinase Inhibitor, in Combination With Palliative Radiotherapy in Advanced Cancer Patients (clinicaltrials.gov) - P1; N=38; Recruiting; Sponsor: XRad Therapeutics Inc

New P1 trial • Oncology • Solid Tumor