WSD0628 / Wayshine Biopharm - LARVOL DELTA

Radiation-induced oral mucositis to rapidly determine effective radiosensitizing dosing regimens for ATM and DNAPK inhibitors (AACR-NCI-EORTC 2025) - "Capitalizing on this normal tissue radiosensitizing effect, we determined effective radiosensitizing dosing regimens in mice for the ATM inhibitor WSD0628 and the DNAPK inhibitor WNC0901 in mice. Consistent with this prediction, co-treatment of B16 melanoma flank tumor xenografts with RT (8Gy x 1) and WNC0901 (50 mg/kg) more than doubled the median tumor control duration (median 42 [range 24-45] days; time from implantation for tumor to exceed 1500 mm3) as compared to RT alone (24 [13-30] days) or sham treatment (17 [13-17] days; overall p<0.0001). This study describes how a radiation-induced oral mucositis model can be used to identify effective radiosensitizing regimens faster and with fewer resources than relying on tumor control studies alone."

Melanoma • Oncology • Solid Tumor

ATM inhibitors in cancer radiotherapy: Mechanisms, clinical development, and future directions. (PubMed, Eur J Med Chem) - "Inhibitors such as KU-55933, KU-60019, and AZD1390 have shown the potential to sensitize cancer cells to radiotherapy by impairing DNA repair, thereby enhancing treatment efficacy...Currently, none have gained approval from the FDA or EMA, but six candidates, AZD1390, AZD0156, ZN-B-2262, SYH2051, WSD0628 and M3541 are in clinical trials, often as adjuncts to radiotherapy or in combination with PARP inhibitors. Their safety and effectiveness, however, are still under investigation. This review synthesizes ATM's dual roles and the therapeutic promise of targeting ATM in cancer radiotherapy."

Journal • Review • Ataxia • Brain Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • CDKN1A • CHEK1 • CHEK2

ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Treatment of Recurrent High-Grade Glioma (clinicaltrials.gov) - P1 | N=94 | Recruiting | Sponsor: Mayo Clinic | N=67 ➔ 94

Enrollment change • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • IDH1 • IDH2

The novel brain penetrant ATM inhibitor WSD0628 provides robust radiosensitization of brain tumor patient derived xenografts. (PubMed, Neuro Oncol) - "Collectively, these results suggest a promising role for WSD0628 in combination with RT in brain tumors and provide the rationale for an ongoing Phase 0/1A clinical trial testing this combination in recurrent GBM."

Journal • Ataxia • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor

Modeling the acute mucosal toxicity to fractionated radiotherapy combined with the ATM inhibitor WSD0628. (PubMed, Mol Cancer Ther) - "These findings were used to develop a modified biologically effective dose model to determine alternative radiation schedules with or without WSD0628 that result in similar levels of toxicity. Successful radiosensitizer dose-escalation to maximally effective therapeutic dose will require careful deliberation of tumor site and reduction of radiation dose-volume limits for organs at risk."

Journal • Oncology

Defining the spectrum of response and radiosensitizing potential of WSD0628 in brain patient-derived xenografts (PDX) models (EORTC-NCI-AACR 2024) - "We are currently developing a PK/efficacy model using PDX data to define target exposures expected to provide optimal radiosensitizing potential, which will be integrated with the PK data being collected in our ongoing dose-escalation study. Median survival (days)PDX linePlaceboWSD06282.3 Gy RT x 10WSD-0628RT x 1012.5 Gy RT x 1WSD-0628RT x 1 GBM12 19 23 55 332** 275 290 NS GBM43 23 22 41 121** 44 213* M12 14 16 16 255** 42 87NS Significance relative to comparator RT alone arm (**p<0.01, *p=0.05, NS – not significant)"

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Melanoma • Oncology • Solid Tumor • TP53

Small Molecular Inhibitors That Target ATM for Drug Discovery: Current Research and Potential Prospective. (PubMed, J Med Chem) - "Specifically, AZD1390, WSD0628, SYH2051, and ZN-B-2262 are under investigation in clinical studies pertaining to glioblastoma multiforme and advanced solid tumors, respectively. In this Perspective, we encapsulate the structure, biological functions, and disease relevance of ATM. Subsequently, we concentrate on the design concepts and structure-activity relationships (SAR) of ATM inhibitors, delineating potential avenues for the development of more efficacious ATM-targeted inhibitors."

Journal • Review • Ataxia • Brain Cancer • CNS Disorders • CNS Tumor • Glioblastoma • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor

Preclinical systemic pharmacokinetics, dose-proportionality, and CNS distribution of the ATM inhibitor WSD0628, a novel radiosensitizer for the treatment of brain tumors. (PubMed, J Pharmacol Exp Ther) - "We also observed a greater than dose-proportional increase in exposure in both the plasma and brain. These favorable pharmacokinetic properties indicate WSD0628 has potential for further exploration for use as a radiosensitizer in the treatment of brain tumors."

Journal • PK/PD data • Preclinical • Ataxia • Brain Cancer • CNS Tumor • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor

Clinical Trial of the ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Recurrent Brain Tumors (clinicaltrials.gov) - P1 | N=67 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2

Clinical Trial of the ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Recurrent Brain Tumors (clinicaltrials.gov) - P1 | N=67 | Not yet recruiting | Sponsor: Mayo Clinic | Trial completion date: Oct 2028 ➔ Feb 2029 | Trial primary completion date: Oct 2027 ➔ Feb 2028

Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2

Clinical Trial of the ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Recurrent Brain Tumors (clinicaltrials.gov) - P1 | N=67 | Not yet recruiting | Sponsor: Mayo Clinic | Trial primary completion date: Oct 2028 ➔ Oct 2027

Combination therapy • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2

The radiosensitizing effects of the novel brain penetrant and potent ATM inhibitor WSD0628 in glioblastoma and melanoma patient derived xenografts. (AACR-NCI-EORTC 2023) - No abstract available

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Melanoma • Oncology • Solid Tumor

Clinical Trial of the ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Recurrent Brain Tumors (clinicaltrials.gov) - P1 | N=67 | Not yet recruiting | Sponsor: Mayo Clinic

Combination therapy • New P1 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2