FivepHusion, an advanced clinical-stage biotechnology company, is pleased to announce that the first patient has commenced treatment as part of the Deflexifol™ at Relapse Trial (DART). The DART Study is a phase 1b/2a clinical trial investigating Deflexifol™ monotherapy as a treatment for paediatric ependymoma and other childhood brain cancers. All major paediatric oncology centres in Australia are participating in the trial, which is being sponsored by the Australian and New Zealand Children’s Haematology / Oncology Group (ANZCHOG).

The DART Study is designed with two parts:

  • Part A, to determine Deflexifol™ safety, tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in paediatric patients with refractory or recurrent central nervous system tumours, or newly diagnosed diffuse intrinsic pontine glioma (DIPG) / diffuse midline glioma (DMG) who have completed radiotherapy.
  • Part B, a phase 2 study at the RP2D to evaluate the Deflexifol™ anti-tumour activity in patients with refractory or recurrent ependymoma. Response rate, progression free survival and overall survival will be assessed.

Deflexifol™ is an advanced clinical-stage, next-generation co-formulation of the chemotherapy drug 5-fluorouracil (5-FU) and leucovorin (LV), a drug that significantly enhances 5-FU activity. FivepHusion aims to harness the proven cytotoxic activity of 5-FU, together with the unique optimised attributes of the Deflexifol™ co-formulation, to pursue development in strategic solid tumour indications presenting with significant unmet medical needs. The priority development indications for Deflexifol™ are paediatric ependymoma and the 1st line treatment of metastatic colorectal cancer (mCRC), with a global phase III registration trial planned to start in mCRC in late 2024.

Ependymomas are rare central nervous system tumours (~4 patients per million) originating from the ependymal cells that line the ventricles of the brain and central canal of the spinal cord. Tumours can manifest at any age, with peak incidence in young children (0-4 years) and older adults. The current standard of care treatment for ependymoma is surgery and radiotherapy, though relapse occurs in approximately half of all paediatric patients and is associated with a poor prognosis. Currently, there are no drugs approved for the treatment of ependymoma, presenting a significant unmet medical need for safe and efficacious new treatments.

Previously, 5-FU has been reported to be a promising drug candidate for the treatment of paediatric ependymoma by independent labs1,2, and in a clinical trial run at the St Jude Children’s Research Hospital (Memphis, Tennessee, USA)3. Research by FivepHusion collaborators indicates that Deflexifol™ may also be efficacious against other brain cancers. Due to its improved safety, tolerability, and potentially superior anti-tumour efficacy, Deflexifol™ offers the exciting opportunity of addressing the limitations of current 5-FU formulations to enable development as the first approved drug for ependymoma and potentially other brain tumours.

The investigator-initiated DART Study is led by Principal Investigators Professor David Ziegler and Dr Marion Mateos at the Kids Cancer Centre. The trial is coordinated by the Sydney Children’s Hospital, Randwick, with support from the Cancer Institute NSW. Major funding to support the study has been provided by the Kids with Cancer Foundation and the Robert Connor Dawes Foundation.

Dr Christian Toouli, CEO and Managing Director of FivepHusion commented, “Treatment of the first patient in the DART Study is a very important milestone for the development of Deflexifol™ as a promising new therapy for paediatric brain cancers. We thank the patients and their families for their participation in this trial, and our collaborators and partners for conducting this important study.”

1 Atkinson et al. 2011, Cancer Cell 20(3):384.
2 Donson et al. 2018, Mol Cancer Ther. 17(9):1984
3 Wright et al. 2015, Neuro Oncol. 17(12):1620.

About FivepHusion

FivepHusion (www.fivephusion.com) is an advanced clinical-stage, globally focused biotechnology company whose purpose is to optimise chemotherapy to improve patient treatment outcomes and quality of life.

FivepHusion is developing Deflexifol™, a proprietary, novel, and optimised physiological pH formulation to co-administer the chemotherapeutic agent 5-fluorouracil (5-FU) and its biomodulator leucovorin (LV), a drug that significantly enhances 5-FU anti-cancer activity. These drugs are commonly used globally to treat various solid tumours including colorectal, pancreatic, gastric and breast cancers. However, due to their chemical incompatibility, current formulations of 5-FU and LV suffer from limitations in their safety, tolerability, effectiveness and pharmacological compatibility. These disadvantages contribute to limited treatment response rates, unpleasant side effects and toxicities, and a reduced quality of life experienced by cancer patients. Deflexifol™ has been designed to address these limitations through co-administration of the two agents with clinically demonstrated improvements in safety and tolerability and the potential to offer superior anti-tumour efficacy, better quality of life, and overall enhanced clinical benefit for cancer patients.

FivepHusion is developing Deflexifol™ via the FDA 505(b)(2) and EMA Article 10b regulatory pathways as a bioequivalent, chemotherapy replacement of sub-optimal standard of care formulations of 5-FU and LV for the treatment of metastatic colorectal cancer, and other tumours with a projected global incidence of greater than 6 million patients. Deflexifol™ is also being developed as a new therapy for cancers with high unmet medical need, including paediatric ependymoma; a rare and deadly brain cancer which afflicts very young children.

Deflexifol™ is a trademark of FivepHusion.

Forward-Looking Statements
This announcement (and any attachments) may contain certain forward-looking statements that are based on any number of assumptions and estimates which may prove incorrect and relate to circumstances and events that may not take place. Forward-looking statements involve known and unknown risks, uncertainties, and other factors (such as significant business, economic and competitive uncertainties and contingencies, and regulatory and clinical development risks and uncertainties) which may cause the actual future plans, results or the performance of FivepHusion and its drug Deflexifol™ to differ materially from the plans, results or performance expressed or implied by such forward-looking statements. Past performance is not a reliable indicator of future performance. There can be no assurance that any forward-looking statements will be realised. FivepHusion does not make any representation or give any warranty as to the likelihood of achievement or reasonableness of any forward-looking statements.