WIMR Phage NewCo March 2024

Phage NewCo

A viable sovereign capability in phage manufacture, rising to the challenge presented by antimicrobial resistance across the Asia-Pacific

The strengths and extraordinary reach of the Westmead Institute for Medical Research

MEDICAL RESEARCH has delivered significant advances in recent decades, and yet still too many people suffer the pain and anguish of unsuitable or unsuccessful treatments, bearing the consequences of solutions that work for some, but not for all.

The discovery of the ‘human genome’, the genetic material that determines how cells develop and function and is unique to each individual, has fundamentally changed the scope of healthcare, and promises to transform the lives of millions around the globe.

At WIMR, we are committed to realising the revolutionary potential of genomics, and its capacity to inform more tailored, more effective and safer interventions in the form of ‘precision medicine’.

Building on a formidable track record of research breakthroughs, WIMR is now undertaking pioneering work to make the

benefits of precision medicine available to people with serious health challenges in Australia, and around the world. Already, we are developing and implementing innovations that have made it possible to identify and deliver highly effective personalised treatments in areas such as kidney disease, liver disease, infectious diseases, mental health and autoimmune diseases.

With privileged access to the expertise and infrastructure of the Westmead Health Precinct, and deep connections into the highly diverse community of Western Sydney, WIMR will ensure that this cutting-edge work can be translated into treatments and services that deliver tangibly better health outcomes for everyone, everywhere.

Sovereign capability for health security in the Asia-Pacific

FOR OVER a decade, scientists, clinicians and health researchers have been raising the alarm about a rapid rise in antimicrobial resistance, and its potential impacts on human health.

That situation has become only more critical.

Now, drug-resistant infections kill more than 1.25 million people a year around the globe, and play a contributing role in another 4.95 million deaths. By 2050, antibioticresistant infections will become the leading cause of death worldwide, resulting in approximately 10 million deaths annually, and generating enormous social and economic cost. In 2022, a WHO report described the continued rise of antimicrobial resistance as “a global health security threat”.

Developing new antimicrobials to address drug-resistant infections as they emerge is no longer a viable option. They take too long and cost too much to develop, and struggle to maintain pace with the breakneck reproduction and mutation rates of antibiotic-resistant bacteria.

Thanks to the work of researchers at the Westmead Institute for Medical Research (WIMR), a solution is emerging in Australasia: a therapeutic alternative to antimicrobials, called ‘phage therapy’.

The WIMR Phage R&D Team, a group of researchers within the WIMR Centre for Infectious Disease and Microbiology and led by Professor Jon Iredell, has made significant contributions to the development of phage therapy in our region. The team, with the support of the Western Sydney Local Health District (WSLHD), has demonstrated both the clinical viability and commercial potential of phage therapy, successfully saving lives and limbs by defeating superbugs, and doing so quickly, efficiently and at a relatively low cost.

WIMR and the WSLHD have now committed to the development of ‘Phage NewCo’: a commercial entity that will enable the delivery of phage products and services to industry by 2026, and to healthcare settings by 2028.

‘Phage NewCo’ will address the urgent need for a sovereign capability in phage manufacture in our region, giving industry and government access to the broader capabilities of phage technologies, and delivering additional health, economic, and environmental benefits.

The promise of phage therapy

MORE THAN a decade ago, Dr Margaret Chan, then Director-General of the World Health Organization (WHO), expressed urgent concerns about the rapid rise in ‘superbugs’ capable of evading antibiotics. Speaking in Copenhagen, she memorably described a “post-antibiotic era” when common infections would once again become untreatable; when cancer treatments and transplants would become increasingly unsafe; and when even routine operations and procedures would carry high risk of untreatable infections, sepsis, and mortality. It could be, she warned, “the end of modern medicine as we know it”.

Very recently, ‘phage therapy’ has emerged as a viable alternative to antibiotics. First discovered in the early 20th century, it harnesses the superpower of phages: an evolved capability to infect and destroy targeted bacteria while remaining harmless to humans.

Phage therapy surged back into prominence in 2016 when epidemiologist Steffanie Strathdee applied it to save the life of her husband after he contracted a deadly superbug. Since then, phage research has gathered pace, with academic centres established across Europe and North America.

In recent years, phage therapy has proven capable of addressing drug-resistant infections that would otherwise lead to serious disability or death, including the superbugs of ‘E. coli’ and ‘golden staph’. It is also proving effective against mutations of

diseases previously viewed as controllable including tuberculosis, malaria, leprosy and gonorrhoeae, developments which pose significant threats, particularly in countries with under-developed health systems.

Part of the appeal of phage therapy is its speediness to develop: it takes an average of two and a half weeks to find a phage that covers a new bacteria, not previously covered. Then, add in time for genetic sequencing, manufacturing, quality control, FDA assessments, and distribution, and theoretically, within just a few of months, an answer is available to treat a superbug. By contrast, the development of a new antibiotic takes anywhere from 8 to 20 years, and costs billions of dollars for development and market access. Importantly, phage can also be synergistic with antibiotics, so even if a certain phage does not directly kill the bacteria, it can put selective pressure on the bacteria to mutate in such a way that it becomes sensitive to antibiotics again.

The global addressable phage market is now projected to reach USD1.4 billion by 2026.

Of course, phage therapy needs to be cost effective to manufacture, and regulators need to urgently broaden the scope of what can be considered an off-the-shelf medicine. Developers anticipate that the FDA and other regulators (e.g. Australia’s TGA) will approve a vast library of phages that can be continuously expanded and used for treatment of superbug infections.

Image: Sydney Children’s Health Network

Rebecca, 14, had spent more than five years in and out of hospital, struggling with repeated lung infections as a result of her cystic fibrosis. After a year of phage treatment, her lung function has improved and she is fit enough to play soccer. She is also back on the list for a life-changing lung transplant.

PHAGE BREAKTHROUGH

PHAGE BREAKTHROUGH

Dhanvi, 7, was hospitalised after a serious car accident and subsequently developed a drug-resistant pseudomonas infection. Her bones weren’t healing, and amputation was considered an option. After two weeks of phage treatment, Dhanvi’s leg was saved. She now leads an active lifestyle as a teenager.

A pioneering therapeutic alternative for a ‘post-antibiotic era’

BACTERIOPHAGES - OR ‘PHAGES’ for short – are viruses that destroy bacteria. Phage therapy involves the use of specific viruses to target bacterial infections.

Found naturally on our own bodies, in waterways, soil and from human waste in sewerage, bacteriophages are known as “hunt and kill viruses” for their ability to bind to bacteria and destroy them

P hages are the most abundant organisms on the planet, with a four-billion-year history of operating as highly targeted bacteria-killers. Over time, different phages have evolved a laser-like ability to vanquish specific bacterial strains. That ability is now being harnessed in phage therapy, for the prevention, management and cure of drug-resistant infections.

Phage therapy offers several critical advantages over antibiotic treatment.

• Phage therapy is non-toxic, given careful preparation to remove impurities

• Phage therapy is highly targeted, and less likely to cause harm to healthy microflora

• Phage therapy can be more effective, and can be used singly, in combination with other phages, or in combination with antibiotics for increased efficacy

• Phage therapy can be put into action sooner, within a matter of months, compared to the multi-year, billiondollar pipeline associated with the development of new antibiotics.

Phage therapy does not need to displace antibiotic treatment. Indeed, the two can work together, with phages applying selective pressure on a target to mutate the bacteria in such a way that it becomes sensitive to antibiotics again.

Phage therapy is part of a wave of discoveries that can bring real hope to the “post-antibiotic era”. Personalised medicine and the gene-editing powers of CRISPR-Cas are converging with phage therapy to promise a future in which malicious infections and diseases can be understood at much greater pace, and prevention and treatment can be personalised with less risk and less potential for collateral damage.

Although it is more than a century since the discovery of phages, the development of phage therapy as a mainstream therapeutic alternative has been slow - until now. In 2015, there were no clinical trials registered. In 2024, there are 71 in progress around the world.

The broader applications of phage technology

THE PHAGE R&D TEAM at WIMR has led the development of phage therapy nationally, generating transformative knowledge and translating these into reproducible clinical practice.

To date, the team has identified and ‘biobanked’ hundreds of phages, 17 of which have been successfully produced and used in the treatment of more than 30 patients, and pioneered a specialised therapeutic protocol, integrating research into real-world hospital care. As showcased throughout these pages, lives and limbs have been saved as a result.

Additionally, phage therapy has a range of nonhuman applications. These also contribute to human health by reducing the overall incidence of antimicrobial resistance and superbugs. Some specific applications are:

• Animal health. Treatments based on phage therapy are an affordable and stable solution for livestock. They can be safely stored for extended periods, and can be delivered as an additive to feed, or through gels and creams.

• Aquaculture. Phage therapeutics, irreversibly attached to the surface of feed pellets, are already in development for the treatment of Early Mortality Syndrome in prawns and shrimps,

and flavobacterial infections in salmonid species such as salmon and trout.

• Agriculture. Phage-based products are currently in development for the prevention of bacterial spoilage in root crops, particularly potatoes. The potential for phage-enhanced biodegradable carriers to extend the shelf life of fresh produce is also being explored.

• Food industry. Phages are safe and viable options for the prevention and treatment of antibiotic-resistant pathogens in a range of foods, applied as preservatives either before or after harvesting. Phage technology is also proving useful in areas including bio-sanitation and bio-detection.

• Oil and gas industries. Phages can be used in the petroleum industry to prevent the bacterial fouling that causes severe damage to gas pipelines. This will improve the safety of pipelines, and reduce the risk of environmental contamination.

• Defence industries. The Australian Defence Force is responsible for the investigation, identification and safe mitigation of biological threats. Phagebased solutions show promise as a way to mitigate the risk to both civilian and Defence personnel during these operations.

PHAGE BREAKTHROUGH

Josh , 22, had an uncontrolled golden staph infection in his heart valve. According to his care team, the likelihood of him dying from the condition was 40 percent or more. Josh was referred to the Phage R&D Team, and after four weeks of treatment, he was recovered and back at work. Three years later, he is still in excellent health.

Establishing a world-leading phage industry in Australia

IN AUSTRALIA , the foundations of a viable phage therapy industry already sit within WIMR and the WSLHD, underpinned by the work of Professor Jon Iredell and the Phage R&D team. However, regulatory uncertainties and dependence on global manufacturing pipelines mean that phage therapy is not yet safely and readily available for the treatment of patients with drugresistant infections in Australia. Nor are the wider benefits of phage technology available to the nation’s agricultural, food production, energy and defence sectors.

The critical goal now, therefore, is to move quickly to establish a sustainable and commercially viable industry in Australia, capable of serving communities and saving lives here, and across the Asia-Pacific region.

WIMR is taking the lead on this all-important venture, committed to establishing the commercial entity, Phage NewCo, in partnership with the WSLHD.

Phage NewCo will build the infrastructure and governance required to integrate capabilities in phage biobanking and diagnostics, and launch the scaled manufacture of phage products to meet the needs of government, industry and healthcare.

It will continue to work closely with the Phage R&D Team, and will license the appropriate technologies from WIMR, WSLHD and the University of Sydney. Its focus, however, will be on the efficient manufacture and delivery of quality phage products and services, underscored by revenue growth and financial sustainability.

A new venture with room to grow

WIMR lies at the heart of the Westmead Health Precinct, an area which encompasses four major hospitals, five world-leading medical research institutes, two university campuses and the largest research-intensive pathology service in NSW. The current workforce of 20,000 is expected to grow to 50,000 within the next decade, making it one of the largest health precincts in the world.

The Precinct provides WIMR with access to some of the best and brightest clinical minds in Australia, and to state-of-the-art facilities, including the nation’s first purpose-built biocontainment centre for the treatment of ‘high consequence’ infectious diseases.

Plans are now underway for a Health Enterprise Zone (HEZ) to be established on land to the north of the Precinct, accommodating a range of commercial activities which could include a scaledup phage manufacturing facility. This commitment of space and infrastructure is a fundamental enabler of Phage NewCo’s plans to meet sovereign requirements for phage manufacture in Australia, and the Asia-Pacific.

A team rich with talent and experience

ADVANCES IN phage therapy have been spearheaded by Professor Jonathan Iredell, Associate Professor Ruby Lin, Dr Ameneh Khatami and their teams since 2002 through WIMR, WSLHD and the University of Sydney.

Professor Jon Iredell is the Director of the WIMR Centre for Infectious Disease and Microbiology, the Director of Phage Australia, and leads the Phage R&D Team. He is also an infectious diseases physician at Westmead Hospital, a clinical microbiologist specialising in critical infections and the transmission of antimicrobial resistance, and Professor of Medicine and Microbiology (conjoint) at the University of Sydney. Jon’s current research projects include the world’s first FDA-approved pre-clinical intravenous phage therapy trial for the treatment of severe Staphylococcus Aureus infections, and the application of phages to eradicate high-risk bacterial clones, and biobanking.

Adjunct Professor Ruby Lin is Deputy Director of Phage Australia and the Genomics Chair of the Scientific Advisory Committee of the Westmead Precinct Hub. She has worked with numerous organisations to form academic-industry hybrid teams, and has received research grants amounting

over AUD$6.5 million for disciplines of genomics, cardiovascular diseases, obesity, cancer biology, tissue and pathogen biobanking, phage banking as well as phage therapy. She is currently on the Advisory Board for the global phage industry’s annual Phage Futures conference.

Dr Ameneh Khatami is the Phage Therapy Content Expert for the Advanced Therapeutics Steering Committee of the Sydney Children’s Hospitals Network. In 2019, she was the first clinician in Australia to treat a paediatric patient with intravenous phage therapy, supported by Professor Jon Iredell. Ameneh has received numerous awards for her research into the development of effective phage cocktails to eradicate early infection with P. aeruginosa and Staphylococcus aureus in children with cystic fibrosis. Ameneh has led the development of a Standardised Treatment and Monitoring Protocol (STAMP) for phage therapy clinical trials, endorsed nationally by adult and paediatric infectious diseases specialists.

Image: Westmead Institute for Medical Research

Your investment in a powerful sovereign capability

THE PHAGE R&D TEAM has attracted strong support from funding partners to date, Already, $7.5 million has been secured:

• In November 2023, the NSW Office of Health & Medical Research signed a funding agreement for an additional $3.5 million over the next two years to support the development of ‘good manufacturing practice’ or ‘GMP’ grade phage manufacturing at WIMR, acknowledging that a global manufacturing bottleneck was stifling access to much-needed phage therapy for Australian patients.

• Leveraging this significant government investment, a philanthropic donor has recently contributed a further $4 million to support critical research that will consolidate Australia’s position as the regional leader in biobanking and bioprospecting.

However, further investment is urgently needed to ensure that Phage NewCo can deliver a viable and sustainable sovereign capability for the manufacture and delivery of phage products and services in the region.

A gap of $6.5 million remains and must be met in order to establish a trajectory for the development of Phage NewCo as a sustainable business supplying phage products and services to customers in Australia and the Asia-Pacific.

WIMR is seeking your support

WIMR is seeking your support to raise a further $6.5 million in philanthropic funds

to launch Phage NewCo and develop the business over its first two years of operation. Your contribution will leverage the $7.5 million already contributed by the NSW government and private philanthropists.

The funds you provide will enable WIMR to:

• Incorporate Phage NewCo

• Appoint a Launch CEO

• Appoint an experienced Board of Directors and Advisory Board

• Negotiate and execute licences from WIMR, WSLHD and the University of Sydney

• Negotiate and execute contract R&D agreements with the Phage R&D Team

• Appoint key members of the Phage NewCo leadership team, including a Chief Scientific Officer

• Develop production capacity at scale, aligned with the principles and procedures of Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP)

• Commence service provision with key customers such as NSW OHMR, Sydney Water, and the Australian Defence Force

• Negotiate and execute manufacturing contracts with key customers.

A high-level budget for Phage NewCo in Years 1 and 2 is presented in Appendix C.

From Year 3 onwards, Phage NewCo will begin to raise equity capital (dilutive funding) to support ongoing product and service development and revenue growth. This dilutive funding will be leveraged with nondilutive funding (grants and R&D tax credits).

Your support for this pioneering initiative will help build sovereign capability in an industry that will equip Australia to address the global health security threat of antimicrobial resistance, and support the health and economic stability of the nation in a post-antibiotic era.

Appendix A:

Roles and responsibilities

PHAGE NEWCO will have a distinct structure and culture, tailor-made to meet the needs of customers and achieve its commercial goals, while the Phage R&D Team has restructured its operations to support the new entity. The figure below outlines the envisaged relationships and required agreements between the Phage R&D Team and Phage NewCo.

Westmead Institute for Medical Research

Professor Jon Iredell, Phage R&D Team

Scientific Advisory Services

Licensed IP, know-how, trade secrets

Contract R&D

Purpose:

1. Core R&D related to phage and antimicrobial resistance (funded by grants and philanthropy)

2. Required R&D to support the scalable delivery of phage products and services by Phage NewCo

Initial goals to enable Phage NewCo:

1. Expand existing biobank through bioprospecting

2. Develop processes to enable high throughput bioprospecting

3. Develop database, genomics, know-how, machine learning, intellectual property (IP)

4. Develop diagnostics to identify right phage for right infection

Phage NewCo

Board of Directors, Advisory Boards

Proposed Westmead GMP–Grade Manufacturing Facility

Contract manufacture

Purpose:

1. Scale production; deliver phage products/services to meet market needs for human and non-human applications

Initial goals:

1. Appoint Launch CEO

2. Establish initial governance and leadership

3. Finalise all agreements between parties

4. Contract consultants to plan for Good Manufacturing Practice (GMP) license

5. Develop Standard Operating Procedures for Good Laboratory Practice (GLP) and GMP manufacture

6. Expand Standardised Treatment and Monitoring Protocol (STAMP)

7. Develop operational plan for GMP

8. Establish Preferred Supplier status with WSLHD and NSW Health

9. Expand beyond WSLHD and NSW Health

Purpose:

1. Contract manufacture at major scale for clients across Australia and Asia-Pacific region.

Figure 1: Relationships and Responsibilities: Phage R&D Team and Phage NewCo

Appendix B: High-level milestones

BOTH THE Phage R&D Team and Phage NewCo will play critical roles in the development of Australia’s phage manufacturing sovereign capability. The diagram below outlines the high-level milestones to sustainability from the initial two-year launch phase, to 2028 and beyond.

Timeline

1

Scale-up and R&D

2024–2025

2

Spin-out commercial entity and establish ‘preferred supplier’ status

2024–2026

• Set-up GLP phage production line

• Build capacity and infrastructure for bioprospecting and biobanking

• Complete resistance and co-evolution program

• Increase IP coverage

• Incorporate commercial entity

• Secure WIMR, WSLHD and University of Sydney licences

• Secure R&D contracts

• Appoint leadership

• Establish governance

• Establish services contracts

• Secure manufacturing contracts

Funding

3

Phage for non-human applications

2026–2028+

4 Regulatory approval for human applications

2028+

• Scale manufacture from GLP to GMP

• Develop and begin selling phage products for non-human applications (non-regulated)

• Commence human clinical trials

• Secure regulatory approval for human applications in Australia and New Zealand

• Start clinical supply of phage products

Australia-wide

• Start regulatory processes for other geographic regions

• Start clinical supply to other markets

Figure 2: Milestones to sustainability: Australia’s phage sovereign capability

Appendix C: High-level budget

WIMR is seeking your support to raise a further $6.5 million for the launch and early development of Phage NewCo. Your contribution will leverage the $7.5 million of funds already secured, and will be allocated as indicated in the high-level budget below.

Figure 3: Budget for the two-year launch phase of Phage NewCo

Support our vision with a contribution

By contributing to Phage NewCo at this strategically critical time, you will be helping to ensure that Australia is leading the world in phage manufacture and therapy before the end of this decade. And you will be a partner in a pioneering initiative that will equip Australia and its near neighbours to address the existential threat of antimicrobial resistance, and support its health and economic stability into the future.

For more information about how to contribute, please contact:

Nicola Tuck

Head, The Westmead Institute for Medical Research Foundation

e: Nicola.Tuck@wimr.org.au

m: 0416 161 362