New Drug Shows Promise Against Incurable Pediatric Brain Cancers

HOUSTON, TX – December 17, 2025 – In a significant development for pediatric oncology, Moleculin Biotech, Inc. today announced positive results from a Phase 1 clinical trial of its drug candidate, WP1066, offering a new glimmer of hope for children with recurrent malignant brain tumors, some of the most difficult-to-treat cancers.

The physician-sponsored trial, led by Dr. Tobey MacDonald at Emory University and conducted at the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta, demonstrated that WP1066 was safe and showed clear signs of anti-tumor activity in a patient population with devastatingly few options. The findings, recently published in the peer-reviewed Journal of Clinical Investigation Insight, are substantial enough to warrant planning for a larger Phase 2 study.

A Desperate Need for New Treatments

For children diagnosed with high-grade gliomas such as diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG), the prognosis is heartbreakingly bleak. These tumors grow in critical areas of the brainstem, making surgical removal nearly impossible. They are notoriously resistant to chemotherapy, and radiation therapy, the current standard of care, only provides a temporary extension of life.

Families facing these diagnoses are often told to expect a survival time of just nine to 11 months. The aggressive nature of these tumors and their location, protected by the blood-brain barrier which blocks most drugs, has left a trail of failed clinical trials and a profound unmet medical need. The trial for WP1066 specifically recruited patients with these incurable tumors, as well as those with relapsed medulloblastoma and ependymoma, aiming to make progress where so many other attempts have fallen short.

Dr. MacDonald, a Professor of Pediatrics and Director of the Pediatric Neuro-Oncology Program, has focused his research on the critical role of a protein called STAT3 in these childhood brain tumors, a discovery that helped pave the way for this trial.

A Novel Attack on Cancer's Core Machinery

WP1066 is not a conventional chemotherapy drug. It belongs to a class of agents known as Immune/Transcription Modulators. Its power lies in its ability to launch a multi-pronged attack on the fundamental mechanisms that allow cancer cells to thrive. The drug is designed to inhibit several key oncogenic transcription factors—proteins that regulate gene expression and drive cancer growth.

One of its primary targets is p-STAT3 (phosphorylated signal transducer and activator of transcription 3). When persistently active, STAT3 helps cancer cells proliferate, survive, and evade the immune system. By shutting down this pathway, WP1066 aims to both halt tumor growth and unmask the cancer to the body's own immune defenses.

Beyond STAT3, WP1066 also inhibits c-Myc, an oncogene notorious for driving many aggressive cancers, and HIF-1α, a factor that helps tumors survive in low-oxygen environments by promoting the growth of new blood vessels. This combined assault disrupts the cancer's ability to grow, spread, and sustain itself, making it a promising strategy for tumors that have resisted other forms of treatment. Crucially, preclinical studies suggested WP1066 could cross the formidable blood-brain barrier to reach its target, a key hurdle in treating brain cancers.

Encouraging Signs from First-in-Child Trial

The Phase 1 study was designed primarily to assess the safety of WP1066 in children and to determine the maximum feasible dose. The trial enrolled 10 children who received the drug twice daily for 14 days, with three additional children treated under compassionate use. The results exceeded the typical expectations for an early-stage safety trial.

Researchers found that WP1066 was well-tolerated, with no significant toxicity preventing them from establishing a feasible dose for future studies. More importantly, the trial provided early but powerful evidence that the drug was having its intended biological effect. Analysis showed that WP1066 successfully suppressed the expression of STAT3, confirming it was hitting its target and inducing anti-tumor immune responses.

The most compelling evidence came from the clinical observations. “The results of this first-in-child trial show some encouraging signals of activity in a highly aggressive chemotherapy resistant brain cancer, such as partial tumor response in a diffuse intrinsic pontine glioma (DIPG) patient and clear anti-tumor immune changes,” said Dr. MacDonald. The observation of a partial tumor shrinkage in even one patient with DIPG—a universally fatal disease—is considered a highly significant signal in a Phase 1 setting.

From Bench to Bedside: A Path Forward

While the trial's small size necessitates caution, the combination of a strong safety profile, proven target engagement, and observable clinical activity provides a robust foundation for the next phase of development. The publication of the results in a respected scientific journal adds a layer of independent validation to the findings.

Walter Klemp, Chairman and CEO of Moleculin, expressed his optimism about the drug's potential. “We are very encouraged by the positive results from our Phase 1 clinical trial evaluating WP1066 in children with recurrent malignant brain tumors,” he stated. “These early data show that WP1066 has the ability to activate meaningful anti-tumor immune responses, an important proof of mechanism in a patient population with extremely limited treatment options.”

He continued, “While still early, these findings reinforce the potential of WP1066 as a novel immunomodulatory approach for some of the most difficult-to-treat pediatric brain cancers.”

The company and Dr. MacDonald's team are now using these results to design a follow-up Phase 2 trial, which will aim to confirm the efficacy of WP1066 in a larger group of patients. The successful initial study, funded by the Peach Bowl LegACy Fund and CURE Childhood Cancer, represents a critical step in translating a promising scientific concept into a potential therapy that could one day change the outlook for children and their families.

Strengthening Moleculin's Pipeline

The positive news on WP1066 also serves to strengthen and diversify Moleculin's overall development pipeline. The company's lead candidate, Annamycin, is currently in a pivotal Phase 3 trial for the treatment of relapsed or refractory acute myeloid leukemia (AML). Annamycin is a next-generation anthracycline designed to be more effective and less toxic to the heart than existing therapies.

With Annamycin addressing a critical need in adult leukemia and now WP1066 showing promise in pediatric neuro-oncology, Moleculin is demonstrating the potential of its multi-asset portfolio. This progress in a distinct and high-need therapeutic area like pediatric brain cancer not only de-risks the company's reliance on a single asset but also highlights the capabilities of its research and development platform. The success of WP1066 could attract further investment and potential partnerships, providing the necessary resources to advance it and other pipeline candidates, such as WP1122 for viruses and other cancers, through the lengthy and expensive clinical trial process.