Cortice Biosciences Transfers Orphan Drug Designations for TPI 287 in Brain Cancer and CNS Diseases

Brain Cancer | Image Credit: ©

Sebastian Kaulitzki - stock.adobe.com

The orphan drug designations for TPI 287, which were previously granted by the FDA for the treatment of patients with gliomas, pediatric neuroblastoma, and progressive supranuclear palsy, have been acquired by CNS Pharmaceuticals from Cortice Biosciences.1

TPI 287 is an abeotaxane that has the same mechanism of action of other taxanes like paclitaxel and docetaxel. The agent stabilizes microtubules and stops cell division, resulting in apoptosis and cell death. However, unlike most taxanes, TPI 287 has shown the potential to cross the blood-brain barrier.

In July 2024, CNS Pharmaceuticals announced that they had entered into an exclusive license agreement with Cortice Biosciences, granting CNS the intellectual property rights to TPI 287, which is currently in development for the treatment of patients with glioblastoma multiforme (GBM).2

“The successful transfer of the orphan drug designations for TPI 287 demonstrates our operational efficiency as well as our ongoing commitment to the development of neuro oncology-focused, cutting-edge chemotherapies,” John Climaco, CEO of CNS Pharmaceuticals, stated in a news release.1 “As we prepare to commence patient enrollment for a phase 2 study around year-end 2025, this important step also recognizes the significant protection orphan status may confer in the form of seven years of market exclusivity.”

In a multicenter phase 1 trial, the combination of TPI 287 and bevacizumab (Avastin) led to an objective response rate of 60% and disease control rate of 96% in patients with recurrent GBM.3 The median progression-free survival and overall survival were 5.5 months (95% CI, 4.1-8.2) and 13.4 months (95% CI, 10.9-17.9), respectively. The 6- and 12-month PFS and OS rates were 40% and 64%, respectively.

The trial enrolled patients with GBM whose disease had relapsed on up to 2 prior lines of therapy. Patients received between 140 mg/m2 and 220 mg/m2 of TPI 287 every 3 weeks in combination with 10 mg/kg of bevacizumab every 2 weeks in 6-week cycles. Treatment continued until dosease progression according to Response Assessment Criteria for High-Grade Gliomas.

In addition to having a life expectancy of more than 12 weeks, a Karnofsky Performance Score of at least 70, and adequate marrow, renal, and liver function, patients had to be at least 12 weeks post-completion of radiation, 6 weeks from nitrosoureas, 3 weeks from procarbazine, 4 weeks from experimental or other cytotoxic drugs, and 1 week from noncytotoxic agents.

Patients would be excluded from the study if they had prior exposure to antiangiogenic therapy, taxanes or vinca alkaloids, enzyme-inducing anti-epileptic drugs or strong inhibitors/inducers of cytochrome P450 3A4 or P450 2C8 within 2 weeks of enrollment, a leptomeningeal tumor or gliomatosis cerebri, or were within a 4-week window from major surgery. Patients who had grade 2 or higher peripheral neuropathy or had received more than 1 course of radiation therapy or a cumulative dose exceeding 65 Gy were also prohibited.

A total of 24 patients were enrolled at 6 centers, 23 of whom were evaluable.

With respect to safety, no dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. The most frequent treatment-emergent adverse effects were fatigue (grade 1/2, n = 6; grade 3, n = 1), neutropenia (grade 1/2, n = 5; grade 3, n = 2), peripheral neuropathy (grade 1/2, n = 11), and hypoesthesia (grade 1/2, n = 6).

“Our TPI 287 program is supported by published clinical and radiologic data showing positive activity against GBM, and a favorable safety profile from testing in hundreds of patients.1 With our demonstrated commitment to defeating this deadly disease, we will be aggressively developing TPI 287 as a treatment option for GBM, where patients continue to face a near-uniformly fatal unmet clinical need,” Climaco stated.

CNS has stated that they plan to meet with the FDA to discuss the design of a registrational trial for TPI 287 in recurrent GBM, with the goal of launching the study in 2025.2

References

1. CNS Pharmaceuticals acquires orphan drug designation for novel, late stage abeotaxane, TPI 287. News release. CNS Pharmaceuticals, Inc. May 15, 2025. Accessed May 21, 2025. https://www.accessnewswire.com/newsroom/en/healthcare-and-pharmaceutical/cns-pharmaceuticals-acquires-orphan-drug-designation-for-novel-late-s-1026864
2. CNS Pharmaceuticals expands pipeline with in license of late stage novel potential blood brain barrier permeable abeotaxane for treatment of brain malignancies. News release. CNS Pharmaceuticals. July 30, 2024. Accessed May 21, 2025. https://cnspharma.com/ir/press-releases/cns-pharmaceuticals-expands-pipeline-with-in-license-of-late-stage-novel-potential-blood-brain-barrier-permeable-abeotaxane-for-treatment-of-brain-malignancies-40033084