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FivepHusion today announces important progress in its ongoing FP101A phase 1b/2a dose-escalation clinical study of Deflexifol™ in patients with advanced solid tumours.

• Deflexifol™ is an optimised all-in-one formulation of the chemotherapeutic agents 5-fluorouracil (5-FU) and leucovorin (LV) for the treatment of solid tumours
• The ongoing FP101A phase 1b/2a clinical study is designed to confirm the pharmacokinetics (PK), safety, tolerability and maximum tolerated dose (MTD) of Deflexifol™
• Fourteen end stage solid tumour patients have been treated in FP101A to date, with a very favourable safety and tolerability profile reported. Patients that were eligible to continue treatment after the designated study treatment phase elected to do so, which is indicative of the enhanced safety and tolerability of Deflexifol™ at all doses investigated to date
• Current 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
• A review of efficacy data, a secondary trial endpoint, has demonstrated that Deflexifol™ treatment led to stable disease in the majority of evaluable patients
• The trial Independent Data Safety Monitor has reviewed the current clinical data set, and recommended Deflexifol™ dose escalation to Dose Level 4, the highest dose (525 mg/m² bolus + 3800 mg/m² infusion, administering 54% more 5-FU than SOC)
• 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 completed forty patient phase 1b/2a clinical study, 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 for the first time, the simultaneous administration of both agents at a physiological pH. This novel co-formulation offers significantly reduced toxicity, enhanced safety, and improved tolerability of greater 5-FU doses compared to SOC formulations. In FP101, an original forty patient phase 1b/2a clinical study in end stage solid tumour patients [1], Deflexifol™ demonstrated superior safety and tolerability at much higher doses of 5-FU than are typically given in the standard of care. Higher doses of 5-FU correlate with improved response and better survival of metastatic colorectal cancer patients [2], whilst the biomodulator LV potentiates 5-FU cytotoxicity to kill cancer cells [3]. Current formulations of 5-FU and LV suffer from limitations in their safety, tolerability, effectiveness and pharmacological compatibility. 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.

Deflexifol™ is currently being investigated in FP101A (ACTRN12619001533189), an ongoing phase 1b/2a dose ranging clinical study designed to confirm the pharmacokinetics, safety, tolerability and maximum tolerated dose of Deflexifol™. The drug is administered in a traditional 3+3 trial design to end stage solid tumour patients as a bolus followed by a 46-hour infusion once every two week cycle, for a total of four cycles of treatment. The study is being performed at Southern Medical Day Care Centre, and is led by Principal Investigator, Associate Professor Daniel Brungs. End stage patients recruited into this study have a range of solid tumours, including metastatic colorectal cancer, breast, gastric and pancreatic cancers, and are typically heavily pre-treated, many patients having previously failed SOC 5-FU therapy as part of multiple treatment regimens.

To date, a total of fourteen patients have been recruited into FP101A, investigating Deflexifol™ at increasing dose levels. Deflexifol™ has demonstrated favourable safety and tolerability at all doses, including at Dose Level 3 (525 mg/m² bolus + 3400 mg/m² infusional dose), delivering ~40% more 5-FU than is typically given in SOC clinical practice [4]. The Independent Data Safety Monitor has now reviewed the accumulated patient data and recommended that new patients be recruited into the study at Dose Level 4, the highest dose in this study, delivering a 525 mg/m² bolus followed by a 3800 mg/m² infusional dose of Deflexifol™, or the equivalent of ~54% more 5-FU than SOC therapy.

Pharmacokinetic analyses of 5-FU and LV delivered by Deflexifol™ have confirmed their pharmacology is typical of these agents delivered independently by SOC formulations. This data supports the bioequivalence of 5-FU and LV formulated in Deflexifol™, allowing for potentially accelerated and de-risked regulatory routes via the US FDA, European Medicines Agency and other global regulatory agencies.

A review of tumour responses at each dose has confirmed that the majority of evaluable patients receiving Deflexifol™ have recorded stable disease during the designated study treatment phase. Patients that were eligible to continue treatment after receiving the minimum of four cycles required by the study protocol elected to do so, with one patient having received up to thirteen cycles of treatment. The continued participation of these patients in the trial further supports the increased safety and tolerability of Deflexifol™ treatment, 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, Southern Day Care Clinic, Principal Investigator for FP101A commented, “The FP101A clinical trial continues to confirm the safety and tolerability of Deflexifol at high doses of 5-FU in end stage solid tumour patients. Pleasingly, we have also observed objective responses to this therapy. We are now planning to investigate the safety and tolerability of Deflexifol at Dose Level 4, the highest and final dose level in this trial.”

Dr Christian Toouli, CEO and Managing Director of FivepHusion said, “We are delighted with the progress of this important clinical study. FP101A builds on the existing clinical experience with Deflexifol in our original FP101 phase 1b/2a study, with a cumulative total of 54 patients now treated. Deflexifol continues to demonstrate its potential as a promising new chemotherapy for the treatment of metastatic colorectal cancer and other solid tumours.”

FivepHusion is aiming to complete recruitment of the FP101A clinical study in the coming months, with the goal of confirming the understanding of the pharmacokinetics, safety and MTD of Deflexifol™. In consultation with its recently announced independent, expert Clinical Advisory Board, the company is currently refining the design of a global phase III registration trial in 1^st line unresectable metastatic colorectal cancer to ensure regulatory approval in major markets and support subsequent clinical uptake as a replacement for sub-optimal SOC 5-FU/LV formulations. FivepHusion intends to finalise the phase III trial design during H1 2022, followed by consultations with global regulatory agencies, including the FDA and EMA, to facilitate initiation of the global registration study.

[1] Clingan et al. 2019, Asia-Pac J Clin Oncol., 15:151-7.
[2] Saif et al. 2009, J Natl Cancer Inst., 101:1543-52.
[3] Longley et al. 2003, Nat Rev Cancer, 3:330-8.
[4] eviq.org.au

For more information, please contact:

Dr Christian Toouli
CEO & Managing Director
c.toouli@fivephusion.com

Announcement authorised by the Board of Directors of FivepHusion

About FivepHusion and Deflexifol™

Throughout our lives, each of us will either experience the trauma of cancer first-hand, or through the experiences of a family member or friend. Unfortunately, the chemotherapy used to treat cancer often has limited therapeutic benefit, with a significant side effect burden and serious impact on quality of life.

FivepHusion is a late stage, globally focused biotechnology company whose purpose is to optimise chemotherapy to improve patient treatment and quality of life. We are developing Deflexifol™, a proprietary, novel, and optimised physiological pH formulation of the chemotherapeutic agent 5-fluorouracil (5-FU) and its biomodulator leucovorin (LV) for the treatment of solid tumours. Current formulations of 5-FU and LV are the standard of care for modern treatment of metastatic colorectal cancer (mCRC) and are also frequently utilised to treat a range of other highly incident tumours, including colorectal, breast, gastric, head & neck and pancreatic cancers. However, 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, 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™ as a bioequivalent, chemotherapy replacement of sub-optimal standard of care formulations of 5-FU and LV for the treatment of mCRC, 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, such as 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.

FivepHusion today announces the establishment of an independent, expert Clinical Advisory Board (CAB) comprising some of Australia’s leading clinical experts in oncology and pharmacology. The board will advise and guide our company on the ongoing development of Deflexifol™, an optimised formulation of the chemotherapeutic agents 5-fluoruracil (5-FU) and leucovorin (LV) for the treatment of solid tumours.

The CAB will initially be tasked with assisting FivepHusion to refine the design of our global phase III registration trial for 1^st line unresectable metastatic colorectal cancer; optimising the clinical strategy to secure regulatory approval and to generate the data set which oncologists would wish to see to use Deflexifol™ as a replacement for currently used sub-optimal formulations of 5-FU and LV in solid tumour therapy. FivepHusion intends to finalise the phase III trial design during H1 2022, followed by consultations with, and regulatory submissions to, global regulatory agencies to facilitate initiation of a global phase III clinical study.

The initial cohort of independent experts representing the core members of the FivepHusion Clinical Advisory Board are:

• Professor Stephen Clarke OAM (CAB Chairman) – Professor of Medicine, University of Sydney (USyd); Senior Staff Specialist in Medical Oncology, Royal North Shore Hospital; Chief Medical Officer, Medical Oncology, Genesis Care
• Professor John Simes AO – Senior Principal Research Fellow and Senior Associate Director, NHMRC Clinical Trials Centre, USyd; Professor of Clinical Epidemiology, NHMRC Clinical Trials Centre, Sydney Medical School, USyd; Medical Oncologist, Chris O’Brien Lifehouse and Royal Prince Alfred Hospital, Sydney
• Professor Andrew McLachlan AM – Head of School and Dean, Sydney Pharmacy School, Faculty of Medicine and Health, USyd
• Professor John Zalcberg OAM – Professor of Medicine, Head, Cancer Research Program, School of Public Health and Preventive Medicine, Monash University and Director, Division of Cancer Medicine, at the Peter MacCallum Cancer Centre for 17 years prior to taking up the position at Monash University

Professor Stephen Clarke, Chairman of the FivepHusion CAB commented, “I am delighted to join the FivepHusion CAB as Chairman and look forward to working with my CAB colleagues and FivepHusion management to optimise Deflexifol™ clinical development. Deflexifol™, a promising new drug for the treatment of metastatic colorectal cancer and other solid tumours, could be shown to provide substantial clinical benefits to cancer patients in the future.”

Dr Christian Toouli, CEO & Managing Director of FivepHusion remarked, “We are very pleased that such an expert and well-credentialed panel of professionals has agreed to serve on our Clinical Advisory Board. The willingness of these senior clinicians and scientists to contribute their expertise to our clinical program endorses the unmet medical need in metastatic colorectal cancer and other solid tumours, the inadequacy of current 5-FU-based chemotherapy, and the therapeutic potential of Deflexifol™ as an optimised chemotherapeutic formulation.”

For more information, please contact:

Dr Christian Toouli
CEO & Managing Director
c.toouli@fivephusion.com

Announcement authorised by the Board of Directors of FivepHusion

About FivepHusion and Deflexifol™

Throughout our lives, each of us will either experience the trauma of cancer first-hand, or through the experiences of a family member or friend. Unfortunately, often the chemotherapy used to treat cancer has limited therapeutic benefits, whilst causing a significant side effect burden and serious impact on quality of life.

FivepHusion is a late stage, globally focused, biotechnology company, founded by clinicians, scientists and biotechnology executives whose purpose is to optimise chemotherapy to improve patient treatment and quality of life. We are developing Deflexifol™, a proprietary, novel, optimised formulation of the chemotherapeutic agents 5-fluorouracil (5-FU) and its biomodulator leucovorin (LV), for the treatment of solid tumours. Current formulations of 5-FU and LV are the standard of care for modern treatment of metastatic colorectal cancer (mCRC) and are also frequently utilised to treat a range of other highly incident tumours, including colorectal, breast, gastric, head & neck and pancreatic cancers. However, current formulations of 5-FU and LV suffer from limitations in their safety, tolerability, effectiveness and pharmacological compatibility. These disadvantages contribute to the 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; optimising the concurrent administration of these chemotherapeutic agents in an all-in-one formulation, with clinically demonstrated improved 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™ as a bioequivalent, chemotherapy replacement of sub-optimal standard of care formulations of 5-FU and LV for the treatment of mCRC and other tumours with a projected global incidence of greater than 6 million patients, and as a new therapy for cancers with high unmet medical need, such as 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.