FivepHusion, an advanced clinical-stage biotechnology company, today announced the successful completion of the FP101A phase 1b/2a dose-escalation clinical study of Deflexifol™ in end-stage solid tumour patients.
  • Deflexifol™ is an optimised all-in-one formulation of the chemotherapeutic agent 5-fluorouracil (5-FU) and its biomodulator leucovorin (LV) for the treatment of solid tumours.
  • The FP101A phase 1b/2a clinical study was designed to confirm the pharmacokinetics (PK), safety, tolerability and maximum tolerated dose (MTD) of Deflexifol™ as a monotherapy when administered as a bolus followed by 46-hour infusion, mimicking the standard of care (SOC) ‘modified de Gramont’ regimen.
  • Nineteen end-stage patients with a variety of solid tumours were treated. Many patients that were eligible to continue treatment after the designated study treatment phase elected to do so, reflecting the enhanced safety and tolerability of Deflexifol™ reported in the trial.
  • According to the trial protocol, the MTD of Deflexifol™ was declared at Dose Level 3, at a dose of 525 mg/m2 bolus followed by a 3400 mg/m2 46-hour infusion. The MTD delivered an equivalent of ~40% more 5-FU than used in typical clinical practice.
  • PK data confirms the bioequivalence of 5-FU and LV co-formulated in Deflexifol™ to Standard of Care (SOC) individual formulations of the drugs; positioning Deflexifol™ for expedited regulatory routes in major markets.
  • Review of efficacy data, a secondary trial endpoint, demonstrated an investigator-determined disease control rate of 69% reported from evaluable patients. Deflexifol™ treatment led to stable disease in the majority of evaluable patients, with one patient achieving a partial response. Prior to recruitment into the trial, patients had typically received and failed multiple rounds of prior chemotherapy, including 5-FU and LV.
  • The FP101A data reaffirms the superior safety and tolerability of Deflexifol™ over SOC 5-FU formulations in end-stage solid tumour patients, as observed in the previously published phase 1b/2a clinical study of 40 patients (FP101).

FivepHusion is developing Deflexifol™, an optimised all-in-one formulation of the chemotherapeutic agent 5-FU and its biomodulator LV for the treatment of solid tumours. Deflexifol™ is specifically formulated to facilitate the simultaneous administration of both agents at a physiological pH, for the first time. This novel co-formulation offers reduced toxicity and significantly improved tolerability of greater 5-FU doses compared to SOC formulations. In an original forty patient phase 1b/2a clinical study in end-stage solid tumour patients1 (FP101), Deflexifol™ demonstrated superior safety and tolerability at much higher doses of 5-FU administered as either a bolus or 46-hour infusion. Higher doses of 5-FU correlate with improved response and better survival of metastatic colorectal cancer patients2, whilst the biomodulator LV potentiates 5-FU cytotoxicity to kill cancer cells3. Multiple independent phase 2 studies have reported that investigational co-administration of 5-FU and LV leads to higher response rates and better survival in mCRC4-8. However, in standard clinical practice, 5-FU and LV formulations must be administered serially due to their pharmacological incompatibility, leading to limitations in their safety, tolerability, effectiveness. These shortcomings contribute to limited treatment response rates, unpleasant side effects and toxicities, and the reduced quality of life experienced by cancer patients. Deflexifol™ has been designed to address these limitations.

The FP101A (ACTRN12619001533189) phase 1b/2a dose ranging clinical study was designed to confirm the pharmacokinetics, safety, tolerability and MTD of Deflexifol™ when administered in a regimen mimicking the SOC “modified de Gramont” regimen. Deflexifol™ monotherapy was administered to end-stage solid tumour patients as a bolus followed by a 46-hour infusion in a two-weekly cycle, for a total of four cycles of treatment. The study was performed at Cancer Care Wollongong, and led by Principal Investigator, Associate Professor Daniel Brungs. End-stage patients recruited into this study had a range of solid tumours, including metastatic colorectal cancer, breast, gastric and pancreatic cancers, and were typically heavily pre-treated, with many patients having previously failed SOC 5-FU therapy as part of multiple treatment regimens.

A total of nineteen patients were recruited into FP101A, investigating Deflexifol™ at increasing dose levels in a traditional 3+3 trial design. Deflexifol™ demonstrated favourable safety and tolerability at SOC clinical and higher dose levels, with Dose Level Three (525 mg/m2 bolus + 3400 mg/m2 infusional dose) declared the MTD. Dose Level Three delivers the equivalent of ~40% more 5-FU than is typically administered in SOC clinical practice9.

Pharmacokinetic analyses of 5-FU and LV delivered by Deflexifol™ confirmed their pharmacology is equivalent of these agents delivered independently by SOC formulations. These data support the bioequivalence of 5-FU and LV formulated in Deflexifol™, allowing for development of the drug via accelerated and de-risked regulatory routes, including the US Food & Drug Administration (FDA) 505(b)(2) and European Medicines Agency (EMA) Article 10b pathways. A December 2022 FDA Type C interaction confirmed the eligibility of Deflexifol™ for the 505(b)(2) regulatory pathway.

A review of investigator-determined tumour responses in thirteen patients evaluable via Response Evaluation Criteria in Solid Tumors (RECIST 1.1) reported an impressive disease control rate of 69%. The majority of evaluable patients achieved stable disease during the designated study treatment phase, including one patient who achieved a partial response. Moreover, these patients typically elected to continue treatment following the minimum of four cycles required by the study protocol, with multiple patients receiving greater than ten cycles of treatment. The continued participation of these patients in the trial further supports the enhanced safety and tolerability of Deflexifol™, highlighting its potential to provide an improved quality of life for cancer patients than is typically experienced with current chemotherapy formulations.

Associate Professor Daniel Brungs, Cancer Care Wollongong, Principal Investigator for FP101A commented, “The FP101A clinical trial has re-confirmed the safety and tolerability of Deflexifol™ at high doses of 5-FU in end-stage solid tumour patients. Pleasingly, we have also observed stable disease and a partial response, indicative of potentially superior efficacy provided by the Deflexifol™ formulation.”

Dr Christian Toouli, CEO and Managing Director of FivepHusion said, “The FP101A trial builds on the existing clinical experience with Deflexifol in our original FP101 phase 1b/2a study, with a cumulative total of 59 patients treated. Deflexifol has demonstrated its potential as a promising new chemotherapy for the treatment of metastatic colorectal cancer and other solid tumours.”

1Clingan et al. 2019, Asia-Pac J Clin Oncol., 15(3):151.
2Saif et al. 2009, J Natl Cancer Inst., 101(22):1543.
3Longley et al. 2003, Nat Rev Cancer, 3(5):330.
4Ardalan et al. 1991, J Clin Oncol., 9(4):625.
5Yeh et al. 1997, Anticancer Res., 17(5B):3867.
6Yang et al. 1999, Cancer, 85(9):192.
7Bleiberg et al. 2012, Acta Gastroenterol Belg., 75(1):14.
8Romano et al. 2021, Oncotarget, 12(3):221.
9www.eviq.org.au

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 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.