Unmet Need: Brain tumors including aggressive Glioblastoma (GBM) remain a large societal burden due to the large number of affected patients and overall poor survival rates. A promising FDA-approved drug verteporfin (VP) was identified that directly targets transcription factors upregulated in GBM, but practical use of this drug to treat GBM is limited by its insolubility and rapid clearance.
Technical Details: Researchers at Johns Hopkins University have developed a novel drug-delivery approach to improve soluble long-lasting delivery of VP for brain tumors such as GBM and non-CNS tumors such as rare chordomas. This approach consists of conjugating VP with a hydrophilic peptide (Pep) via a biodegradable linker sequence to form self-assembling verteporfin amphiphiles (SAVA) with the composition V-Pep. The resulting molecule V-Pep has the ability to self-assemble into nanofibers in various mediums (e.g. bodily fluids) forming a localized hydrogel complex and drug depot. As shown in vitro, V-Pep micelles significantly increased cytotoxicity in GBM patient derived cell lines compared to healthy controls, and increased radiosensitivity of tumor cells, indicating its potential synergistic effects with standard-of-care radiotherapy. In addition, in vivo ectopic mouse xenograft GBM tumor models showed VP attenuated tumor growth. Due to the ability of V-Pep to self-assemble and to then be loaded into a syringe, this novel drug-delivery method can be easily translated to clinical use. Overall, this novel approach serves as a means to treat not only brain tumors such as GBM but also non-CNS tumors including rare chordomas with high-specificity, controllable release, and user-friendliness.
Value Proposition:
· Novel self-assembling hydrogel formulation increases VP solubility and long-lasting delivery
· SAVA composition is safe and non-immunostimulatory
· Delivery method allows for localized deposition and decreased need for continued drug administration
· Treatment compatible/synergistic with well-established first-line chemotherapy/radiotherapy
· Broad application of treatment method to multiple cancers including GBM, breast, lung and orphan tumors such as chordomas
Looking for Partners to: Develop & commercialize the technology as a novel composition and drug-delivery method for the treatment of cancer.
Stage of Development: Pre-Clinical
Data Availability: In vitro and in vivo mouse models
Inventors: Honggang Cui, Alfredo Quinones-Hinojosa, Sagar Shah, Alejandro Ruiz-Valls, Juan Carlos Martinez-Gutierrez, Ran Lin
Patent Status: US Pending: 16/739,956
Publication(s): Kim J et al. (2018). Verteporfin-loaded poly(ethylene glycol)-poly(beta-amino ester)-poly(ethylene glycol) triblock micelles for cancer therapy. Biomacromoleclues 19(8):3361-70. Shah S et al. (2019). Verteporfin-loaded polymeric microparticles for intratumoral treatment of brain cancer. Mol Pharmaceutics 16:1433-43. Shamul J et al. (2019). Verteporfin-loaded anisotropic poly(beta-amino ester)-based micelles demonstrate brain cancer-selective cytotoxicity and enhanced pharmacokinetics. Int J Nanomedicine 14:10047-60.Schiapparelli P et al. (2020). Self-assembling and self-formulating prodrug hydrogelator extends survival in a glioblastoma resection and recurrence model. J Control Release 10(319):311-321.
