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FivepHusion, an advanced clinical-stage biotechnology company, today announces a commercial transaction with University of Wollongong (UOW) for an exclusive option over its ResectAssist™ Drug Delivery Platform. This innovative, drug-eluting biodegradable implant enables targeted administration of a diverse range of approved and investigational drugs directly into solid tumours with high unmet medical needs.

Key highlights of the deal and ResectAssist™ technology:

• FivepHusion has secured an exclusive option to acquire the ResectAssist™ Platform technology and IP portfolio on agreed financial terms,
• ResectAssist™ is a differentiated and adaptable next-generation drug delivery platform enabling intra-tumoural delivery of a diverse range of small molecule chemistries, biologics, antibody-drug conjugates, mRNA and other drug modalities,
• Drugs are delivered directly into solid tumours via standard endoscopy, facilitating focused high dose therapy, maximising efficacy and minimising side effects,
• The lead drug candidate, ResectAssist™-FOLFIRINOX, is in development for unresectable locally-advanced pancreatic cancer (LAPC), and is designed to downgrade these tumours to being resectable with curative intent,
• Commercial opportunities include the US$4B pancreatic cancer market, and an exciting range of upside prospects to optimally deliver other approved and biopharma-partnered investigational drugs for a broad range of solid tumour indications.

Dr Christian Toouli, CEO & Managing Director of FivepHusion said, “This transaction formalises a long-term collaboration with the University of Wollongong to secure an exciting pipeline development opportunity that will ultimately follow the development and commercialisation of Deflexifol®. We are looking forward to rapidly developing the ResectAssist™ Platform into a clinical trial program to optimise treatment for cancer patients.”

The clinical rationale and commercial strategy for the ResectAssist™ Platform is closely aligned with FivepHusion’s mission to optimise cancer therapeutics to improve patient treatment outcomes and quality of life. The UOW ResectAssist™ Program involves an expert multi-disciplinary team led by Associate Professor Kara Perrow and Professor Morteza Aghmesheh. ResectAssist™ is an innovative single-use drug-eluting implant in development for inoperable LAPC and other cancers. Using standard endoscopy procedures, the lead candidate, ResectAssist™-FOLFIRINOX, is designed to locally deliver high dose FOLFIRINOX chemotherapy (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) directly into LAPC tumours, facilitating a substantially safer, more tolerable and significantly more efficacious treatment. The intent of ResectAssist™ treatment is to convert inoperable LAPC to resectable and potentially curable.

Prof. Morteza Aghmesheh, ResectAssist™ Program Co-Founder, and an Honorary Clinical Professor at UOW said, “There is a significant unmet medical need for the treatment of pancreatic cancer patients, and in particular those with unresectable disease. The ResectAssist™ technology is designed to optimally deliver the FOLFIRINOX regimen, the most efficacious but also the most toxic therapy, facilitating maximum anti-cancer efficacy without typical systemic side effects.”

Pancreatic cancer is the 5th leading cause of cancer death in Australia and 7th worldwide, and projected to become the 2nd leading cause of cancer-related deaths by 2030. It has the lowest solid tumour survival rate, with two thirds of patients dying within the first year of diagnosis and <10% of patients surviving by 5 years. Pancreatic cancer patients have limited treatment options. While tumour resection remains the only curative option, >80% of patients present with unresectable disease, including ~30% with locally-advanced, non-metastatic disease. FivepHusion is aiming to initially develop ResectAssist™-FOLFIRINOX to treat these patients.

ResectAssist™-FOLFIRINOX represents the first of a potential pipeline of drug candidates that may be delivered via the ResectAssist™ technology for the treatment of LAPC and other solid tumours with high unmet medical need. The platform is also designed to deliver a diverse range of other drug payloads, including hydrophobic and hydrophilic compounds, biologics (including antibodies and antibody-drug conjugates), peptides and mRNA therapeutics.

A/Prof. Kara Perrow, ResectAssist™ Program Co-Founder and Program Leader commented, “The ResectAssist™ Platform enables delivery of a diverse range of drug payloads directly into solid tumours via standard endoscopy procedures. We are excited to collaborate with FivepHusion to develop this technology to treat pancreatic cancer and a broad range of other tumours.”

The market for the ResectAssist™-FOLFIRINOX drug candidate is very attractive, as there is a significant unmet medical need in pancreatic cancer and limited competition, with a projected global market of ~US$4B by 2029. The adaptability of the ResectAssist™ technology plus common use of the FOLFIRINOX drug regimen across cancer indications provides opportunities to also pursue development for other cancers, leading to upside market opportunities. Moreover, the utility of the ResectAssist™ Platform to deliver other proven and experimental drug candidates across innovative modalities and mechanisms enables exciting opportunities to develop a pipeline of drugs, and to partner with other biopharma companies, to deliver anti-cancer drugs to treat an even broader range of solid tumours.

About FivepHusion

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

The FivepHusion lead asset is Deflexifol®, a proprietary, novel, and optimised co-formulation of 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.

FivepHusion is developing Deflexifol® via the FDA 505(b)(2) and EMA Article 10b regulatory pathways as a next-generation replacement of standard of care formulations of 5-FU and LV for the first-line treatment of metastatic colorectal cancer, and other tumours with a projected global incidence of >6 million patients. Anticipated revenues for Deflexifol® reach peaks of >US$1B. 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. A phase 1b clinical trial investigating Deflexifol® as a treatment for paediatric ependymoma and other paediatric brain cancers is ongoing.

ResectAssist™ is an innovative drug delivery platform technology enabling targeted delivery of anti-cancer drugs directly into solid tumours, maximising efficacy and minimising side effects of proven and investigational drugs. The lead candidate, ResectAssist™-FOLFIRINOX, is in development to treat unresectable locally-advanced pancreatic cancer.

Deflexifol® is a trademark of FivepHusion. ResectAssist™ is a trademark of the University of Wollongong.

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 development pipeline opportunities Deflexifol® and ResectAssist™ 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, an advanced clinical-stage biotechnology company, today announces Human Regulatory Ethics Committee (HREC) approval for the next clinical trial of Deflexifol™, 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.

Bellberry Ltd, Australia’s leading independent organisation providing scientific and ethical review of human research projects, has approved the clinical trial protocol and patient consent documentation for the Deflexifol™ “FP101B” trial. HREC approval is a mandatory requirement prior to clinical trial initiation.

FP101B is a planned multi-centre phase 1b dose-escalation trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of Deflexifol™ in combination with oxaliplatin and bevacizumab as a first-line treatment in patients with unresectable metastatic colorectal cancer (mCRC). The trial design is based on US FDA advice and will be the fourth clinical study investigating Deflexifol™ as a treatment for solid tumours, and the first to study Deflexifol™ in combination with other standard of care drugs as a first-line treatment. FP101B will be conducted by FivepHusion strategic partner Syneos Health, a leading fully integrated global biopharmaceutical solutions organisation. The goal of the FP101B trial is to confirm the optimal dose of Deflexifol™ to be investigated in a planned global phase III registration study designed to confirm the superiority of Deflexifol™ over standard of care 5-FU/LV “backbone” therapy in unresectable mCRC.

This ethics approval follows strong enthusiasm from oncologists to a poster presentation describing the rationale and design of FP101B, presented at the November, 2023 Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting in Christchurch, New Zealand. Deflexifol™ is an optimised co-formulation of 5-FU and LV that requires no change in clinical practice whilst offering superior safety and efficacy for cancer patients.

Dr Christian Toouli, CEO & Managing Director, commented, “There is a significant unmet medical need to optimise standard of care 5-FU/LV therapy for solid tumour treatment. This HREC approval endorses the feedback we have received from oncologists and the US FDA on the appropriateness of investigating Deflexifol™ as an optimised replacement of 5-FU/LV in the standard of care for the 1^st line treatment of mCRC. We intend to initiate this trial as soon as possible.”

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. A phase 1b clinical trial investigating Deflexifol™ as a treatment for paediatric ependymoma and other brain cancers is ongoing.

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, an advanced clinical-stage biotechnology company, today announces that a poster of the most recently completed Deflexifol™ clinical trial was presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco (January 18-20th, 2024).

The FP101A dose-escalation clinical study of Deflexifol™ monotherapy demonstrated that concomitant delivery of 5-fluorouracil (5-FU) and its biomodulator leucovorin via Deflexifol™ is safe and tolerable in solid tumour patients at 5-FU doses up to 40% higher than typically administered by the standard “modified de Gramont” regimen. Disease control was achieved in 69% of evaluable patients, all of whom were end-stage and typically heavily pre-treated, including with prior 5-FU. The poster detailing the study results was presented by the study’s Principal Investigator, Associate Professor Daniel Brungs (Cancer Care Wollongong), who commented:

“The FP101A trial results were well received by oncologists attending the conference. It is pleasing to have the opportunity to discuss the promising Deflexifol clinical results with colleagues at one of the preeminent international conferences focused on gastrointestinal cancer treatments. There is a desperate need for new therapeutic options for the treatment of colorectal cancer and other GI cancers.”

The abstract and poster presentation are available to view online. All conference presentations and published literature relevant to Deflexifol™ can also be found on the FivepHusion website.

After receiving positive FDA Type C guidance on the clinical and regulatory paths for Deflexifol™ development, FivepHusion is now rapidly progressing plans for a follow-on  trial of Deflexifol™ in combination with oxaliplatin and bevacizumab in the first-line treatment of unresectable metastatic colorectal cancer. A clinical trial of Deflexifol™ monotherapy in paediatric brain cancers which commenced last year is also progressing as planned.

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.

FivepHusion, an advanced clinical-stage biotechnology company, is delighted to announce the appointment of Mr Iain Ross (LinkedIn profile) as a Non-Executive Director. Mr Ross is a highly experienced international biotechnology executive, currently serving as an Executive Chairman and in Non-Executive Chairman roles for UK and US publicly listed and private biotech companies. He complements and expands the current skill set of the FivepHusion Board, bringing decades of experience in corporate governance, strategy and execution, including in licensing, merger & acquisition deals and capital raising, having overseen multiple initial public offerings for his companies on the NASDAQ, LSE and ASX. Iain lives in the United Kingdom and is a frequent visitor to Australia. He has a long association with the Australian industry, having served in Board and senior management roles for a variety of Australian private and publicly listed biotech companies over many years.

Mr David Ranson, Executive Chairman of FivepHusion commented “As we pursue late clinical-stage development of our lead drug Deflexifol™, augmenting and expanding the diversity and skill set of our Board is paramount to optimally positioning our company for global development activities and commercialisation. I am thrilled that Iain has agreed to contribute his deep experience and global perspective to our company.”

Mr Iain Ross said “I am excited to join the FivepHusion Board at this important inflection in the development of Deflexifol™, which has the potential to help a very large number of cancer patients globally. Through the strategic global partnerships that FivepHusion has established, it is well placed to rapidly advance Deflexifol™ to significant development and commercial milestones. I look forward to working with the Board, and on behalf of the company’s investors, on this exciting journey.”

About Mr Iain Ross

A biochemistry graduate of London University, and an experienced businessman with >40 years experience largely in the international life sciences and technology sectors. Track record includes multiple financing transactions having raised >£600m, both publicly and privately, as well as extensive experience of divestments and strategic restructurings and >25 years in cross-border management as a Chairman and CEO. Has led and participated in 8 Initial Public Offerings/Listings , (5 LSE, 2 NASDAQ and 1 ASX) and has direct experience of M&A transactions in Europe, USA and Pacific Rim.

Following a career with multi-national companies – Sandoz AG, Hoffman La Roche, and Celltech plc for > 25 years has undertaken a number of company start-ups, turnarounds and exits as a Chairman, CEO and board member on behalf of institutional shareholders; VCs, private equity groups and banks. These include Quadrant Healthcare PLC (Drug delivery – sold to Élan); Eden BioDesign (contract manufacturing – sold to Watson Pharmaceuticals); Phadia AB (Diagnostics – acquired from Pfizer – sold to Cinven); Silence Therapeutics PLC (RNAi therapeutics platform – merged with Intradigm Inc); Allergy Therapeutics Limited (Allergy immunotherapy – prepared for IPO); Ark Therapeutics PLC (therapeutics and viral contract manufacturing) – subsidiaries sold off to private equity and a private veterinary business reversed into the LSE Main List shell to form Premier Veterinary Group plc; the 4 year turnaround of Redx Pharma plc (LSE:AIM) from administration in 2017 to in 2021 a fully funded, biotech company with big pharma validated R&D portfolio and a blue chip healthcare shareholder register and the 6 year turnaround of Kazia Therapeutics Limited (formerly Novogen) (ASX/NASDAQ) into a clinical oncology development company with a validated R&D portfolio.

Has held >25 non-executive director roles in private and public companies in Europe, US and Australia. Currently Executive Chairman of Reneuron Group plc LSE (Exosome Delivery Technology platform) and Non-Executive Chairman of Silence Therapeutics plc NASDAQ (RNAi therapeutics platform & pipeline) which he returned to in 2019; and also a Non-Executive Director of Bivictrix Therapeutics plc LSE (Oncology technology platform) he took public in 2021 . A qualified Chartered Director (UK IoD), Former Vice Chairman of the Council and Honorary Fellow of Royal Holloway, London University.

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 needs, 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.

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 labs^1,2, 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.

BOSTON and SYDNEY (July 31, 2023) — Allarity Therapeutics, Inc. (Nasdaq: ALLR) (“Allarity”), a clinical-stage pharmaceutical company developing novel oncology therapeutics together with drug-specific DRP® companion diagnostics for personalized cancer care, and Detsamma Investments Pty. Ltd. trading as “FivepHusion,” an advanced clinical-stage biotechnology company developing Deflexifol™, an optimized all-in-one formulation of the chemotherapeutic agent 5-fluorouracil (5FU) and its biomodulator leucovorin (LV), announced today that the two companies have entered into a Clinical Collaboration Agreement. Under this agreement, Allarity will support FivepHusion’s future clinical development of Deflexifol™ for the treatment of solid tumors by using certain of Allarity’s drug-specific DRP® companion diagnostics, including its validated DRP®-5FU companion diagnostic, to potentially select patients for enrollment and treatment in clinical trials of Deflexifol™ as a monotherapy and in combination with other drugs.

Deflexifol™ is a novel anti-cancer drug reformulation designed to address the safety and efficacy limitations of standard-of-care 5FU chemotherapy. It combines, in a single infusion, 5FU and LV, a drug that potentiates 5FU anti-tumor activity, to improve the therapeutic activity of 5FU. FivepHusion expects to start a phase 1b/2a study investigating Deflexifol™ in combination with oxaliplatin (“DEFLOX”) and bevacizumab in the 1^st line treatment of unresectable metastatic colorectal cancer (mCRC) patients in H2 2023. This ~50 patient trial is designed to evaluate the safety, tolerability and pharmacokinetics of Deflexifol™ in the DEFLOX plus bevacizumab regimen, to enable selection of the optimal Deflexifol™ dose to be utilized in a Phase 3 pivotal trial in 1^st line treatment of unresectable mCRC. A secondary endpoint is the assessment of objective response (eight-week scan) and overall survival of patients treated with DEFLOX plus bevacizumab.

Allarity’s DRP®-5FU is a companion diagnostic (CDx) that has been retrospectively validated and shown to predict patient response to 5FU treatment in late-stage colorectal cancer. Clinical data showing the predictive ability of the DRP®-5FU CDx in colorectal cancer were presented at the annual congress of the European Society for Medical Oncology (ESMO) in Barcelona on September 29, 2019, and were later the same year published in the scientific journal Annals of Oncology.

Dr. Christian Toouli, CEO and Managing Director of FivepHusion, said, “We are excited to collaborate with Allarity Therapeutics to evaluate the drug-specific DRP® companion diagnostic technology as part of our upcoming Deflexifol™ phase 1b/2a trial in 1st line unresectable metastatic colorectal cancer. This collaboration has the potential to develop an exciting precision medicine companion diagnostic for oncologists, facilitating administration of Deflexifol™ to likely patient responders as a superior treatment for a range of solid tumours with significant unmet medical need.”

James G. Cullem, CEO of Allarity Therapeutics, added, “Allarity is thrilled to work together with FivepHusion to support the clinical advancement of their lead Deflexifol™ program by evaluating the potential of DRP® companion diagnostics to select cancer patients most likely to respond to this novel and improved formulation of the widely-used chemotherapeutic 5FU. Together with the FivepHusion team, we look forward to advancing true personalized cancer care by using DRP® companion diagnostics to help provide Deflexifol™ to patients that will most likely benefit from this promising therapeutic candiate.”

The Clinical Collaboration Agreement

Under the terms of the Clinical Collaboration Agreement, Allarity will initially support FivepHusion’s planned Phase 1b/2a trial of DEFLOX plus bevacizumab in 1^st line treatment of unresectable mCRC, which will be conducted at trial sites in Australia. Allarity will receive patient biopsies from the trial and analyze them using the DRP® companion diagnostics technology to identify patients most likely to respond or not respond to the DEFLOX plus bevacizumab regimen. This analysis will be conducted blindly (without knowledge of any patient data and/or actual clinical response to the drug), so as to enable the retrospective analysis of the DRP® companion diagnostics predictive power following the completion of the Phase 1b/2a trial. FivepHusion will receive a first option to negotiate and obtain from Allarity a global, exclusive license to use and commercialize the DRP®-5FU CDx (together with other DRP® CDx relevant to drug combinations including Deflexifol™) through Phase 3 registration trials, regulatory approval, and to market.

Following conclusion of the Phase 1b/2a study, FivepHusion will determine whether the ability of the DRP® companion diagnostics technology to select patients responsive to DEFLOX plus bevacizumab and/or Deflexifol™ monotherapy warrants prospective use of the companion diagnostic(s), to select and enroll mCRC patients, in an international, Phase 3 registration study for the drug. Allarity will receive patient biopsies from the trial and analyze them using the DRP® companion diagnostics technology to prospectively identify patients most likely to respond or not respond to Deflexifol™. Allarity will further assist FivepHusion in the preparation and submission of any regulatory approvals, including Investigational Device Exemptions (IDEs) and Pre-Market Approvals (PMAs), required to use the DRP® companion diagnostics technology in such a Phase 3 trial and to use and market the CDx following any regulatory approval of Deflexifol™.

Financial terms of the clinical collaboration, option and potential license are not disclosed. If FivepHusion exercises its option right and receives a license to the Allarity DRP® companion diagnostic technology related to Deflexifol™, Alliarty will receive certain milestone payments triggered by regulatory approvals of Deflexifol™ and attainment of drug sales benchmarks.

About Allarity Therapeutics

Allarity Therapeutics, Inc. (Nasdaq: ALLR) develops drugs for personalized treatment of cancer guided by its proprietary and highly validated companion diagnostic technology, the DRP® platform. The Company has a mature portfolio of three drug candidates: stenoparib, a PARP inhibitor in Phase 2 development for ovarian cancer; dovitinib, a pan-tyrosine kinase inhibitor previously developed through Phase 3 in renal cancer; and IXEMPRA® (Ixabepilone), a microtubule inhibitor approved in the U.S. and marketed by R-PHARM U.S. for the treatment of second-line metastatic breast cancer, and is currently in Phase 2 development in Europe for the same indication. Additionally, the Company has rights in two secondary assets: 2X-111, a liposomal formulation of doxorubicin for metastatic breast cancer and/or glioblastoma multiforme (GBM), which is the subject of discussions for a restructured out-license to Smerud Medical Research International AS; and LiPlaCis™, a liposomal formulation of cisplatin and its accompanying DRP®, being developed via a partnership with Chosa Oncology AB for late-stage metastatic breast cancer. The Company is headquartered in the United States and maintains an R&D facility in Hoersholm, Denmark. For more information, please visit the Company’s website at www.Allarity.com.

About the Drug Response Predictor – DRP® Companion Diagnostic

Allarity uses its drug specific DRP® to select those patients who, by the genetic signature of their cancer, are found to have a high likelihood of responding to the specific drug. By screening patients before treatment, and only treating those patients with a sufficiently high DRP® score, the therapeutic response rate can be significantly increased. The DRP® method builds on the comparison of sensitive vs. resistant human cancer cell lines, including transcriptomic information from cell lines combined with clinical tumor biology filters and prior clinical trial outcomes. DRP® is based on messenger RNA from patient biopsies. The DRP® platform has proven its ability to provide a statistically significant prediction of the clinical outcome from drug treatment in cancer patients in 37 out of 47 clinical studies that were examined (both retrospective and prospective), including ongoing, prospective Phase 2 trials of Stenoparib and IXEMPRA®. The DRP® platform, which can be used in all cancer types and is patented for more than 70 anti-cancer drugs, has been extensively published in peer reviewed literature.

About FivepHusion and Deflexifol™

FivepHusion (www.fivephusion.com) is an advanced clinical-stage, globally focused biotechnology company whose purpose is to optimise chemotherapy to improve patient treatment and quality of life. Its lead program, Deflexifol™, is a proprietary, novel, and optimized physiological pH formulation of the chemotherapeutic agent 5-fluorouracil (5FU) and its biomodulator leucovorin (LV) for the treatment of solid tumours. Current formulations of 5FU and LV are the standard of care for modern treatment of metastatic colorectal cancer (mCRC) and are also frequently utilized to treat a range of other highly incident tumors, including colorectal, breast, gastric, head & neck and pancreatic cancers. However, current formulations of 5FU 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-tumor 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 5FU and LV for the treatment of mCRC, and other tumors 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 pediatric ependymoma; a rare and deadly brain cancer which afflicts very young children.

Deflexifol™ is a trademark of FivepHusion.

Follow Allarity on Social Media

LinkedIn: https://www.linkedin.com/company/allaritytx/

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LinkedIn: https://www.linkedin.com/company/fivephusion/

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Allarity Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements provide Allarity’s current expectations or forecasts of future events. The words “anticipates,” “believe,” “continue,” “could,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predicts,” “project,” “should,” “toward,” “would” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements include, but are not limited to, statements related to the Company’s ability to maintain compliance with the Nasdaq Listing Rule, use of proceeds from the offering, that the closing of offering will occur or will occur on the anticipated closing date, ability to raise capital, statements related to the expected availability capital to fund its anticipated clinical trials, statements related to advancing dovitinib in combination with another therapeutic candidate or other approved drug, any statements related to ongoing clinical trials for stenoparib as a monotherapy or in combination with another therapeutic candidate for the treatment of advanced ovarian cancer, or ongoing clinical trials (in Europe) for IXEMPRA® for the treatment of metastatic breast cancer, and statements relating to the effectiveness of the Company’s DRP® companion diagnostics platform in predicting whether a particular patient is likely to respond to a specific drug, including, but not limited to, Deflexifol™. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to multiple risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results of a clinical study do not necessarily predict final results and that one or more of the clinical outcomes may materially change following more comprehensive reviews of the data, and as more patient data become available, the risk that results of a clinical study are subject to interpretation and additional analyses may be needed and/or may contradict such results, the receipt of regulatory approval for dovitinib or any of our other therapeutic candidates or, if approved, the successful commercialization of such products, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies will not be repeated or observed in ongoing or future studies involving our therapeutic candidates, and the risk that the current COVID-19 pandemic will impact the Company’s current and future clinical trials and the timing of the Company’s preclinical studies and other operations. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our Form S-1 registration statement on file with the Securities and Exchange Commission, available at the Securities and Exchange Commission’s website at www.sec.gov, and as well as discussions of potential risks, uncertainties and other important factors in the Company’s subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information unless required by law.

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, an advanced clinical-stage biotechnology company, is pleased to announce the commencement of the investigator-initiated phase 1b/2a Deflexifol™ at Relapse Trial (DART) in paediatric brain cancer patients. This study is supported by the Kids with Cancer Foundation.

• Deflexifol™ is an optimised all-in-one formulation of the chemotherapeutic agent 5-fluorouracil (5-FU) and its biomodulator leucovorin (LV), a drug that potentiates 5-FU anti-tumour activity, for the treatment of solid tumours.
• Ependymoma is the third most common brain tumour in children. There are no drugs approved for its treatment. Currently, surgical resection and radiation therapy are the only available options. Up to half of all patients will relapse, and most of these patients will die from the disease.
• Independent pre-clinical and clinical data has demonstrated promising 5-FU activity against ependymoma. However, until the development of Deflexifol™, it has not been possible to co-administer therapeutically effective doses of 5-FU and LV in a safe and tolerable manner.
• The DART phase 1b/2a clinical 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 (CNS) 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 Deflexifol™ anti-tumour activity in patients with refractory or recurrent ependymoma. Response rate, progression free survival and overall survival will be assessed.
• The DART study is led by Professor David Ziegler and Dr Marion Mateos at the Kids Cancer Centre and coordinated by the Sydney Children’s Hospital, Randwick, with support from the Cancer Institute NSW. The study is being run at paediatric oncology centres throughout Australia and is sponsored by the Australian and New Zealand Children’s Haematology / Oncology Group (ANZCHOG) with support from the Robert Connor Dawes Foundation.

FivepHusion is developing Deflexifol™, an optimised all-in-one physiological pH formulation of the chemotherapeutic agent 5-FU and its biomodulator LV – a drug that potentiates 5-FU anti-tumour activity¹ – for the treatment of solid tumours. Deflexifol™ is specifically formulated to facilitate the simultaneous administration of both agents, for the first time. Deflexifol™ has demonstrated superior safety and tolerability at standard and higher equivalent doses of 5-FU across two clinical trials^2,3 in end-stage adult cancer patients with a variety of heavily pre-treated chemo-resistant solid tumours. Disease control was reported in the majority of patients even though they had typically previously failed multiple 5-FU treatment regimens². The most recently completed clinical trial, FP101A³, declared an MTD for Deflexifol™ at a 525 mg/m² bolus + 3400 mg/m² infusional dose when administered to mimic the standard of care (SOC) ‘modified de Gramont’ regimen. The MTD for Deflexifol™ tolerably delivered the equivalent of ~40% more 5-FU than is typically administered in clinical practice⁴; it has previously been demonstrated that higher 5-FU doses correlate with improved response and better survival⁵. Additionally, multiple independent phase 2 studies have reported that investigational co-administration of 5-FU and LV, as is achieved with Deflexifol™, leads to higher response rates and better survival compared with SOC serial administration of these agents^6-10. Deflexifol™ is therefore expected to provide superior anti-tumour efficacy.

Ependymomas are rare central nervous system tumours (~4 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^11,12. The current SOC treatment for ependymoma is surgery and radiotherapy, though relapse occurs in approximately half of all paediatric patients and is associated with a poor prognosis^13,14. Currently there are no drugs approved for the treatment of ependymoma, presenting a significant unmet medical need for safe and efficacious new treatments.

Previously, independent laboratories reported that 5-FU possesses selective cytotoxicity against ependymoma cells both in vitro and in vivo^15,16. In rodent models, intravenous 5-FU was demonstrated to significantly reduce tumour growth and prolong survival¹⁵. A St Jude Children’s Research Hospital phase 1 trial of 5-FU monotherapy in 23 patients aged ≤22 years with recurrent intracranial or spinal ependymoma reported partial responses (n=5) or stable disease (n=6) in 48% of patients¹⁷. 5-FU was administered as a bolus only, and dose limiting toxicities restricted its use and dose. Whilst the clinical potential for standard formulations of 5-FU in ependymoma showed promise, it ultimately demonstrated limited clinical utility.

Deflexifol™ is a promising new candidate for the treatment of ependymoma. Due to the improved safety, tolerability, and potentially superior anti-tumour efficacy of Deflexifol™, the drug offers the exciting opportunity of addressing the limitations of standard formulations of 5-FU to treat ependymoma and potentially other brain tumours. The higher equivalent 5-FU MTD of Deflexifol™ together with the simultaneous delivery of LV is expected to facilitate greater drug concentrations in the brain and at the tumour, leading to enhanced efficacy.

The investigator-initiated DART study is led by Professor David Ziegler and Dr Marion Mateos at the Kids Cancer Centre and coordinated by the Sydney Children’s Hospital, Randwick, with support from the Cancer Institute NSW. Professor Ziegler is the Director of the Kids Cancer Alliance. The trial will be run at all major paediatric oncology centres around Australia and is sponsored by ANZCHOG with major funding support from the Kids with Cancer Foundation and the Robert Connor Dawes Foundation. Deflexifol™ will be supplied by FivepHusion.

The DART study is designed in two sequential parts. Part A will investigate safety, including the dose-limiting toxicities, tolerability, pharmacokinetics, MTD and RP2D of Deflexifol™ in children and young adults with relapsed CNS tumours and newly diagnosed DIPG/DMG tumours that have completed radiotherapy. Part B will evaluate the anti-tumour activity, progression free survival and overall survival associated with Deflexifol™ monotherapy at the RP2D in patients with refractory or recurrent ependymoma.

Dr Christian Toouli, CEO and Managing Director of FivepHusion commented, “We are excited to collaborate with Professor Ziegler, Dr Mateos and other participating clinicians, their teams and organisations, and are very grateful of the generous charity funding support enabling the investigation of Deflexifol™ as a promising new treatment for paediatric brain cancer patients.”

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.

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 mCRC^4-8. 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.

FivepHusion, an advanced clinical-stage biotechnology company, today announced its collaboration with Treehill Partners, a New York-based strategic and financial advisory firm specializing in healthcare industry transactions, and Syneos Health® (Nasdaq: SYNH), a leading fully integrated biopharmaceutical solutions organization, to develop and bring a novel, enhanced chemotherapeutic product to market.

Treehill Partners will support FivepHusion with integrated business development, operational, strategic and transactional expertise. Syneos Health will support FivepHusion’s integrated clinical development and commercialization capabilities. This collaboration is designed to strategically and optimally progress development and commercialization of FivepHusion’s enhanced chemotherapeutic formulation Deflexifol™ in global markets.

“This is a very exciting time for FivepHusion. We are at a crucial stage in our growth strategy. By collaborating with Treehill Partners and Syneos Health, we believe we are positioned to successfully bring our development work on Deflexifol™ to global markets, including in the US, Europe and Asia,” said Dr. Christian Toouli, CEO & Managing Director, FivepHusion. “This collaboration represents a unique working model to the industry. Through the combined strength and competency of three industry leaders, we intend to maximize our progress on the development of Deflexifol™ and quickly bring innovative oncology medicines to patients in need.”

“We’re excited to collaborate with FivepHusion and Treehill Partners to help bring Deflexifol™ to patients,” said Christian Tucat, Chief Business Officer, Syneos Health. “Leveraging our deep therapeutic and global expertise, Syneos Health is pleased to contribute to accelerating the clinical development and commercialization of this important new therapy.”

“This collaboration represents a new model of integrated services across disciplines, designed to allow US and non-US emerging players to play a key role on the global stage, and we’re proud to work alongside FivepHusion and Syneos Health,” said Ali Pashazadeh, Partner & Co-founder, Treehill Partners. “By merging the scientific prowess of our clients with the clinical and commercial expertise of Syneos Health and Treehill’s healthcare advisory and execution capabilities, we are providing a unique ecosystem designed to help companies to flourish despite the current challenging market environment.”

About FivepHusion

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

FivepHusion is developing Deflexifol™, a proprietary, novel, and optimized 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 tumors 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-tumor 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 tumors 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 pediatric ependymoma; a rare and deadly brain cancer which afflicts very young children.

Deflexifol™ is a trademark of FivepHusion.

About Syneos Health

Syneos Health^® (Nasdaq: SYNH) is a leading fully integrated biopharmaceutical solutions organization built to accelerate customer success.  Syneos translates unique clinical, medical affairs and commercial insights into outcomes to address modern market realities.

Syneos brings together a talented team of professionals, who work across more than 110 countries, with a deep understanding of patient and physician behaviors and market dynamics. Together Syneos shares insights, uses the latest technologies and applies advanced business practices to speed customers’ delivery of important therapies to patients.

Syneos Health supports a diverse, equitable and inclusive culture that cares for colleagues, customers, patients, communities and the environment.

To learn more about how Syneos are Shortening the distance from lab to life^®, visit syneoshealth.com or subscribe to our podcast.

About Treehill Partners

Treehill was founded in 2014 and is led by partner and co-founder Ali Pashazadeh, who previously headed Blackstone’s healthcare advisory team and UBS’ European biotech coverage.

Treehill supports clients in the healthcare industry throughout the asset lifecycle, from buy-side acquisition and investment over value build and growth to sell-side disposal and divestment. Key areas of focus are the identifying and executing of value creative transactions and their knitting into successful corporate evolution strategies.

In delivering its advice, the firm employs a multidisciplinary senior team with impeccable pedigree that comprises medical doctors/ MDs, scientists/ PhDs, CEOs of biotechs, senior executives from large pharma, and experienced strategy consultants and investment bankers. Services provided are centered around the “principal mentality” of the team, delivering actionable strategic and transaction advice that matters to CEOs, senior leadership, their stakeholders and investors.

FivepHusion today announces an important regulatory milestone associated with the development of Deflexifol™, an enhanced chemotherapeutic formulation for patients with advanced solid tumours.

• A successful Type C Meeting interaction with the US FDA which provided valuable feedback on the Deflexifol™ clinical development, Chemistry, Manufacturing and Controls (CMC) and regulatory paths for metastatic colorectal cancer (mCRC)
• Valuable advice on the design of the next phase Ib/IIa clinical trial (FP101B) intended to confirm the Deflexifol™ dose for phase III development, when combined with oxaliplatin and bevacizumab
• Deflexifol™ able to be immediately developed for 1st line mCRC patients – no requirement to first seek approval in later lines of treatment
• Only one successfully conducted phase III pivotal trial required to support registration
• Confirmation of the FDA 505(b)(2) regulatory path for registration in mCRC
• No concerns raised about the proposed Deflexifol™ CMC pathway to registration

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. The Deflexifol™ formulation addresses significant limitations with current treatment, offering a “best in class” therapy by optimising co-administration of 5-FU and LV at a physiological pH to enhance patient treatment via greater safety, tolerability and  superior efficacy.

In December 2022, FivepHusion, together with its global regulatory consultants PharmaLex, engaged with the US Food and Drug Administration (FDA) in a Type C meeting to seek feedback on the company’s proposed clinical development program, CMC and regulatory paths for Deflexifol™. The FDA provided constructive feedback on the design of the planned next clinical trial, FP101B, a dose-ranging clinical study designed to confirm the appropriate Deflexifol™ dose to take forward into a pivotal phase III trial in mCRC patients. The Agency confirmed that Deflexifol™ can be developed in 1st line metastatic colorectal cancer patients, and that only one successfully conducted phase III trial should be sufficient for registration of Deflexifol™. The FDA stated no concerns about the FivepHusion proposed CMC pathway and also confirmed that registration of Deflexifol™ should be pursued via the 505(b)(2) regulatory path.

FivepHusion Executive Director, Dr Bill Ketelbey said, “The FDA has provided very valuable feedback on the design elements for our future clinical studies. These insights allow FivepHusion to optimise the Deflexifol clinical development program to generate the data set necessary to achieve registration of Deflexifol as an enhanced 5-FU and LV formulation for the treatment of 1st line metastatic colorectal cancer patients.”

FivepHusion CEO, Dr Christian Toouli commented, “This strategically important interaction with the FDA has confirmed our understanding of the clinical development, CMC and regulatory paths for Deflexifol. We are delighted that the Agency confirmed their requirement for one successfully conducted phase III trial and that FivepHusion can develop Deflexifol via the accelerated and de-risked 505(b)(2) regulatory path for our chosen patient population.”

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 experience the trauma of cancer first-hand, or through the experiences of family or friends. Unfortunately, the chemotherapy used to treat cancer often has limited therapeutic benefits, with a significant side effect burden and serious impact on quality of life.

FivepHusion (www.fivephusion.com) 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.