Moleculin Biotech, Inc. has announced the treatment of the first patients in a Phase 2 clinical trial evaluating WP1066, a STAT3 inhibitor, in combination with radiation therapy for adults with glioblastoma. The investigator-initiated study (NU 21C06) is being conducted at Northwestern University and is funded by the National Institutes of Health (NIH) and BrainUp®.
The Phase 2 trial is an open-label, multi-arm study focusing on newly diagnosed IDH (isocitrate dehydrogenase) wild-type, MGMT-unmethylated glioblastoma patients. The primary outcome measure is progression-free survival, with secondary outcome measures including tumor microenvironment analysis.
Rationale for WP1066 in Glioblastoma
Dr. Priya Kumthekar, Associate Professor at Northwestern University and Co-Investigator for the study, emphasized the significance of the trial, stating, "The start of patient dosing is a significant step towards addressing the unmet need in the treatment of glioblastoma. We were very encouraged by the preclinical data that demonstrated by WP1066 in combination with radiation therapy increased survival and induced anti-tumor immune responses and are excited to finally be treating patients with this approach."
Dr. Amy Heimberger, Co-Investigator and Vice Chair for Research, Department of Neurological Surgery for Northwestern University, noted the rapid recruitment for the trial, indicating the urgency of addressing glioblastoma. "The significance of the unmet need can be seen in the pace of recruitment for this trial. Within the first few months of opening the trial, we have four subjects active in the study and expect to fill the safety lead-in group of six subjects soon. If treatment is well tolerated in these subjects, we will continue enrollment for the balance of the trial."
WP1066: An Immune/Transcription Modulator
WP1066 is Moleculin's primary Immune/Transcription Modulator, designed to stimulate the immune response to tumors by inhibiting regulatory T cells and key oncogenic transcription factors, including p-STAT3, c-Myc, and HIF-1α. These transcription factors play a crucial role in cancer cell survival, proliferation, angiogenesis, invasion, metastasis, and inflammation.
Glioblastoma: A Challenging Landscape
Glioblastoma is a common and aggressive brain tumor, with an average annual age-adjusted incidence rate of 3.19 per 100,000 people in the United States. It accounts for 54% of all gliomas and 16% of all primary brain tumors. The median survival is approximately 15 months, and survival rates have not significantly improved in the last three decades, underscoring the need for new therapeutic strategies.
Moleculin's Broader Pipeline
Moleculin Biotech is also developing Annamycin for relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases. The company is initiating the MIRACLE trial, a Phase 3 trial evaluating Annamycin in combination with cytarabine for relapsed or refractory AML. Additionally, Moleculin is developing WP1122 for potential treatment of viruses and certain cancer indications. Moleculin has received Orphan Drug Designation for WP1066 for the treatment of brain tumors, as well as Rare Pediatric Disease designation for three other pediatric indications.
Walter Klemp, Chairman and Chief Executive Officer of Moleculin, stated, "The NU 21C06 study is a critical next step in the development of STAT3-targeting technologies... We believe that based on the data demonstrated to date, WP1066 has the potential for significant anti-tumor activity in a wide range of hard-to-treat cancers."
