Oncopeptides confirms blood-brain-barrier penetration based on data from first patients in glioblastoma Window-of-Opportunity (WoO) study

Oncopeptides AB (publ), a biotech company specializing in difficult-to-treat cancers, today announces data from the first patients in its ongoing clinical Window-of-Opportunity (WoO) study, OP-701 (INSULA), evaluating its proprietary Peptide Drug Conjugate (PDC) platform in glioblastoma. Data from the first three treated patients demonstrate successful penetration of the human blood-brain barrier (BBB) with intra-tumoral drug concentrations in line with preclinical models, alongside good tolerability where the first patient has received five monthly doses to date without any major drug-related toxicity.

The blood-brain barrier represents one of the greatest hurdles in neuro-oncology, causing more than 90 percent of conventional systemic cancer drugs to fail because they cannot reach the brain. By confirming meaningful, BBB penetration and delivery of a cytotoxic payload into brain tumor cells in the first patients, the findings provide a strong indication of a clinical proof-of-concept for the PDC platform’s mechanism in solid brain tumors.

"Reaching our primary objective to confirm that our PDC technology successfully crosses the human blood-brain barrier is a major breakthrough for Oncopeptides," says Sofia Heigis, CEO of Oncopeptides. "For decades, the blood-brain barrier has locked out effective treatments for glioblastoma patients. Demonstrating meaningful drug penetration in resected brain tumors in patients after a single dose validates the fundamental strength and versatility of our platform, transforming our brain cancer program from an ambitious basic scientific premise into a true, clinically justified, opportunity."

The open-label INSULA study, conducted at Oslo University Hospital in Norway, utilizes the EMA approved drug melflufen from Oncopeptides’ PDC platform in patients scheduled for surgery due to recurrent glioblastoma. By administering the drug prior to surgery, researchers can directly measure drug uptake and cytotoxic activity in resected tumor tissue.

Key highlights:

• Confirmed blood-brain barrier penetration: Analysis of resected tumor tissue from three evaluated patients showed clear and consistent presence of active compound (the primary endpoint in this part of the study), indicating efficient penetration across the human blood-brain barrier.
• Safety and tolerability: The treatment has so far been well tolerated across evaluated patients with no major drug-related toxicity observed to date. The first treated patient has continued into the study’s open-label extension and received a total of five monthly doses to date, with no new tumor-related neurological symptoms observed. Postoperative paresis related to the surgical procedure was observed and is improving under ongoing treatment.
• Drug concentrations within the tumor tissue: Intra-tumoral drug concentrations in the brains of the three patients, as measured by pharmacokinetic analysis, were in line with data from our preclinical studies.
• Surgical complications: No unexpected surgical complications were observed.

Crossing the blood-brain barrier in patients diagnosed with Glioblastoma is an important step for any systemic brain cancer therapy.These initial tissue findings demonstrate that Oncopeptides’ lipophilic PDC molecules behave in human tumors just as anticipated, delivering significant concentrations in tumor cells where standard treatments historically fall short."

Prof. Petter Brandal, MD, PhD, Oslo University Hospital, and Primary Investigator, Window-of-Opportunity (WoO) study

Patient recruitment in the INSULA study continues, to reach the target of approximately 10 patients to further characterize pharmacokinetics and pharmacodynamics. The positive data from the first three patients will serve as the biological and clinical foundation to guide further clinical progression and the future development of next-generation PDC assets.

Glioblastoma is the most aggressive and common form of primary brain cancer, with a median overall survival of only 12–15 months and virtually no effective treatment options. The global glioblastoma market is characterized by severe unmet medical needs.