Moleculin Reports Positive Phase 1 Findings For WP1066 In Pediatric Patients Battling Recurrent Malignant Brain Tumors

Moleculin Biotech, Inc. announced positive early results from a physician-sponsored Phase 1 clinical trial evaluating its lead drug candidate, WP1066, in children with aggressive brain tumors. The study was conducted at the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta and led by Dr. Tobey MacDonald, a pediatric oncologist at Emory University. Dr. MacDonald is a Professor of Pediatrics and Director of the Pediatric Neuro-Oncology Program and is widely recognized for identifying the critical role of STAT3 in certain childhood brain cancers.

WP1066 is Moleculin’s flagship immune and transcription modulator designed to enhance the body’s immune response against tumors. The drug works by inhibiting the abnormal activity of regulatory T cells that suppress immune function, while also blocking several key transcription factors that drive cancer growth. These include phosphorylated STAT3 (p-STAT3), c-Myc, and HIF-1α, all of which play major roles in cancer cell survival, rapid tumor growth, formation of new blood vessels, tumor spread, and inflammation within the tumor environment. Because these pathways are central to many aggressive cancers, they are considered important targets for new cancer therapies.

According to Dr. MacDonald, the first-in-child trial produced encouraging signs of clinical and biological activity in highly aggressive and chemotherapy-resistant brain tumors. The results included a partial tumor response in a patient with diffuse intrinsic pontine glioma, along with clear evidence of immune changes consistent with anti-tumor activity.

The Phase 1 trial enrolled 10 pediatric patients who received WP1066 twice daily for 14 days. The primary goal of the study was to determine the maximum feasible dose of the drug in children. In addition, three children with high-grade glioma received WP1066 under compassionate use. The treatment was generally well tolerated, with no significant toxicity observed, and researchers were able to establish a maximum feasible dose. Importantly, the study showed that WP1066 successfully reduced STAT3 expression, confirming inhibition of its activity and demonstrating an associated anti-tumor immune response.

While WP1066 had previously shown strong anti-cancer activity in preclinical studies and had been evaluated in adult patients, this trial marked the first time the drug was tested in a pediatric population. The study focused on children with high-grade gliomas, including diffuse midline glioma and diffuse intrinsic pontine glioma, which account for the majority of pediatric brain tumor-related deaths. 

These diseases are associated with extremely poor outcomes, with average survival ranging from nine to 11 months after diagnosis. The trial also included patients with relapsed medulloblastoma and ependymoma, both of which lack accepted standard treatment options following disease recurrence. By including these patient groups, the study addressed a significant unmet medical need for new therapies in childhood brain cancers that currently have no effective treatments.

Walter Klemp, Chairman and Chief Executive Officer of Moleculin, said the Company is encouraged by the positive findings from the Phase 1 trial in children with recurrent malignant brain tumors. He noted that the early results demonstrate WP1066’s ability to activate meaningful anti-tumor immune responses, providing important evidence of how the drug works in a patient population with extremely limited treatment options. 

Although the data are still preliminary, he said the findings support the potential of WP1066 as a novel immunomodulatory approach for some of the most challenging pediatric brain cancers. He also expressed appreciation to Dr. MacDonald and his research team, as well as to the patients and families who participated in the study, and stated that Moleculin remains committed to advancing WP1066 as a potential treatment that could make a meaningful difference for children affected by these devastating diseases.