CTM CRC EXIT REPORT · CTM CRC maintains close working relationships with strategic research and...

CTM CRC E X I T REPORT

CTM CRC E X I T REPORT

CRC FOR CELL THERAPY MANUFACTURING 32 EXIT REPORT

CRC FOR CELL THERAPY MANUFACTURING

The CRC for Cell Therapy Manufacturing (CTM CRC) brings together materials scientists, cell biologists, clinicians and manufacturing experts to develop and deliver innovative and paradigm-shifting cell-based therapies to the clinic in a more cost effective manner than currently available internationally.

CTM CRC’s core platform technologies of materials and material/cell interface technologies enable improved expansion and delivery of a range of therapeutic cells.

CTM CRC’s spin-out company, Carina Biotech Pty Ltd, is developing and commercialising technologies in the field of cancer immunotherapy, including new therapeutic cells that target multiple cancer types, but do not affect normal cells. Carina also has novel modes of delivering and retaining therapeutic cells in cancer sites.

CTM CRC’s second spin-out company, TekCyte Pty Ltd, is developing specialised coated products to improve the performance of biomedical devices (such as vascular stents and wound dressings), as well as cell bioprocessing equipment.

CTM CRC maintains close working relationships with strategic research and industry partners locally and internationally to ensure Australia maximises its position in a rapidly growing global cell therapy industry.

VISIONTo develop and deliver highly effective and affordable cell therapies using novel, material-based cell manufacturing technologies.

ESSENTIAL PARTICIPANTSAthersys, Inc.

Cell Therapies Pty Ltd

Exylika Pty Ltd

NextCell Pty Ltd

MedVet Science Pty Ltd

Queensland University of Technology

Royal Adelaide Hospital – a division of Central Adelaide Local Health Network, Inc.

St Vincent’s Institute of Medical Research

SA Pathology – a division of Central Adelaide Local Health Network, Inc.

Terumo BCT Australia Pty Ltd

University of South Australia

University of Sydney

OTHER PARTICIPANTSLancaster University

Royal Prince Alfred Hospital – Sydney Local Health District

South Australian Health and Medical Research Institute Ltd

Scinogy Pty Ltd

University of Adelaide

University of Wollongong

Women’s and Children’s Health Network, Inc.

BOARDDr Leanna Read (Chair)

Dr Alexander Gosling AM

Dr Sherry Kothari (resigned 12/18)

Mr Charlie Latham

Dr Stephen Livesey

Mr Ray Wood

HEAD OFFICELevel 5Catherine Helen Spence BldgUniSA City West CampusAdelaide, South AustraliaAUSTRALIA 5000

+61 8 8302 [email protected]

ABN 92 163 117 520

twitter.com/CTMCRC

facebook.com/ctm.crc

linkedin.com/company/crc-for-cell-therapy-manufacturing

>$50M CASH & IN-KIND 2SPIN-OUT

COMPANIES

19 PARTICIPANTS

>30 PATENT APPLICATIONS

21 PHD STUDENTS

>130 PUBLICATIONS & PRESENTATIONS

>120 PEOPLE IN RESEARCH,

TECHNOLOGY AND BUSINESS DEVELOPMENT

carina b i o t e c hcellular immunotherapies

TekCyteADVANCED BIOMEDICAL COATINGS

WORLD FIRST CAR-T FOR SOLID CANCERS

BIOINVISIBLE COATED SURFACES


CEO’S MESSAGE 8

CTM CRC TIMELINE 10

SNAPSHOT SUMMARY 13

ECONOMIC IMPACT 21CASE STUDY 01 - CARINA BIOTECH 23CASE STUDY 02 - TEKCYTE 25

INDUSTRY ENGAGEMENT 27CASE STUDY 03 - ADVANCED WOUND DRESSING

28

EDUCATION & TRAINING 37CASE STUDY 04 - LIH TAN - CTM CRC PHD GRADUATE

39

CONTENTS


WE are very pleased to submit this Exit Report for CTM CRC.

Established less than six years ago, CTM CRC has made very significant contributions to an important gap in the cell therapy industry – the need to evolve towards more efficient and cost-effective methods of cell production and expansion.

Our two research programs are strategically focused on the priority commercial opportunities, and are now underpinned by a strong patent portfolio:

� Materials and Interfaces to engineer advanced surface coatings that facilitate the cost-effective manufacture and delivery of therapeutic cells; and

� Cellular Immunotherapies to develop CAR-T therapies to target solid cancers.

The Materials and Interfaces program has utilised its platform plasma polymerisation technology to create unique, thin-film coatings to optimise the performance of cultureware and biomedical materials or devices. Key outcomes have included:

� Improved cultureware performance across a range of cell types utilized by the global cell therapy industry.

� A coating that enables wound dressings to act

as carriers for therapeutic cells, significantly improving wound closure. A clinical trial is planned with a UK partner using stem cells from an Australian SME.

� An anti-thrombotic coating for vascular stents that has now entered large animal trials with a major

international stent supplier.

The Cellular Immunotherapies program was only established in 2016 but has made remarkable progress in the field of chimeric antigen receptor (CAR)-T therapy, in which a patient’s immune T-cells are engineered to recognise and destroy their cancer. In particular, CTM CRC has addressed the ‘holy grail’ of the CAR-T industry, developing a world-first, ‘universal’ CAR-T cell that attacks a wide range of solid cancers without side-effects on normal cells.

In the space of only two years, the Cellular Immunotherapies

program has:

� Demonstrated potent anti-cancer activity of the CRC’s CAR-T cells in a broad range of cancer cell lines and in several animal models of solid tumours

� Optimised engineering, production and expansion technologies to enable CAR-T cell scale-up manufacture

� Developed co-therapies to deliver and retain the CAR-T cells at the site of cancers.

A number of industry partners have been engaged to drive commercial applications of both research programs. However, the CRC Board believes its most important legacy for the Australian economy has been the establishment of two new high-growth companies that can build and retain value locally.

The first company, Carina Biotech Pty Ltd, was incorporated in 2016 to commercialise CTM CRC’s CAR-T therapy. Carina has already raised $6 million in new equity and grant funding as well as finalised plans to commence clinical trials in 2020 as the next critical commercial milestone.

The second spin out company, TekCyte Pty Ltd was established in 2018 for the commercial manufacture and supply of advanced coatings for cultureware and medical devices to the research and cell therapy industries.

Collectively, the two companies address multi-billion dollar market opportunities, and show excellent growth potential. As shareholders in Carina and TekCyte, the CTM CRC Participants will have the opportunity for ongoing benefits and return on investment.

I congratulate all of the research and commercialisation personnel in CTM CRC for their outstanding contributions to these impressive outcomes.

Turning to Education, CTM CRC has invested heavily in producing ‘industry-ready’ graduates through its flagship Entrepreneurial PhD program as well as bioprocessing training courses. These courses have been in high demand with many PhD students participating over the life of the CRC. We have also trained over 20 PhD students, who will enter the workforce with a strong understanding of industry requirements as well as excellent technical capabilities. I would like to acknowledge the quality leadership that our board and management have brought to the CRC over its 6-year life. The CRC was very ably led for almost 5 years by founding Managing Director, Dr Sherry Kothari, who helped develop a strategy that was clearly ahead of its time.

All of our board members are independent of the CRC partners, selected for the skills and experience they could bring to the Centre. The board’s expertise, cohesiveness, passion and camaraderie have contributed enormously to the success of CTM CRC.

Management and the Board had the foresight to put in place a number of important operational strategies, including:

� A very effective IP strategy, in which CTM CRC owns all new IP generated by CRC activities, and is managed by an excellent patent attorney, Dr Justin Coombs, as CTM CRC’s General Manager to ensure effective IP identification and application

� A full-time research project manager to help researchers meet milestones

� A strong emphasis on educating CTM CRC researchers in record keeping, IP and commercial imperatives

� Clear and transparent processes for CTM CRC participants to secure return on their investment through shareholding in the two spin-out companies.

Finally, the management company, CTM@CRC Ltd will continue to operate as a registered charity after termination of CRC funding. As a significant shareholder in both Carina and TekCyte, CTM@CRC will have the ongoing opportunity to support related research if the companies achieve significant capital growth. Essentially CTM@CRC will continue the purpose of the CRC.

In conclusion, I would like to thank and congratulate the Board, Audit and Risk Committee, Management, Researchers and Participants for a very successful CRC. It has been a privilege to chair CTM CRC as well as take on the additional role of CEO over the last year.

If we can achieve the planned legacies of two high-growth spin-out companies, plus a well-funded charity in CTM, we will have done the CRC program proud!

CTM CRC’s most important legacy for the Australian economy has been the establishment of two new high-growth companies that can build and retain value locally.

01

CEO’S MESSAGE


15-16 16-17 18-1917-1813-14 14-15

Project agreements executed and work commenced on all 7 first-round projects

Framework established to align CTM CRC project activities with globally recognised standards

Commercially focused IP policy developed.

First commercial deal agreed with international industry participant, Terumo BCT, Inc.

6 PhD students and 1 visiting international student commenced

Tailored entrepreneurial PhD (ePhD) program developed and launched

Key management personnel appointed and all governing documents executed

Novel surface coating for stem cell expansion technology developed at laboratory scale

Prototype devices to deliver therapeutic cells to wounds successfully developed

2 new provisional patent applications filed (surface modification of hollow fiber bioreactor cassette; Delivery of MSCs to wounds)

Royal Prince Alfred Hospital joined as an Other Participant

4 new PhD students and 1 honours student commenced

Strategic international linkages established with the Centre for Commercialization of Regenerative Medicine (Canada), University College London (UCL) and the Cell Therapy Catapult (UK)

Innaugural annual ImpaCT Day and ImpaCT Magazine for communication and collaboration initiated

Joint Playford Memorial Trust/CTMCRC PhD scholarships established

2 new research projects commenced

CAR-T therapy and gel-based delivery of cells in development

Facility established for scale-up manufacture of cell-based therapies and training

3 new provisional patent applications filed (T cell expansion; Chimeric Antigen Receptor; Antifouling medical devices)

First international PCT patent application filed (wound repair delivery system)

First spin-out company, Carina Biotech, incorporated

Over $1 million of state and federal Government grant funding attracted

Co-hosted 2015 ISCT ANZ Regional Meeting

University of Wollongong joined as an Other Participant

Positive preclinical data for wound healing using cell delivery device

Prototype technology for T cell expansion developed and evaluated in G-Rex system

Novel bioinvisible coating for vascular stents demonstrated anti-fouling properties in preclinical testing

2 collaborative projects commenced through international linkages

Collaboration established with an Australian company to advance CTM CRC’s wound healing patch towards clinical trials

Preclinical testing on bioinvisible antithrombotic vascular stent coating in collaboration with a global medical device company

Positive preliminary in vitro data in CAR-T cancer treatment for solid tumours


International phase of patent prosecution of three patent families (T cell expansion; Chimeric Antigen Receptor; Anti-fouling medical devices)

Scinogy Pty Ltd joined as an Other Participant

Collaborative agreement with the Seattle Children’s Hospital through spin-out company, Carina Biotech

Collaboration with industry growth centre, MTP Connect

Industry training delivered in conjunction with SeerPharma Pty Ltd

First cohort of 9 CTM CRC PhD sudents completed ePhD training

6 new PhD students (total 20 PhD students)

$250K seed capital raised by Carina Biotech via a grant from TechInSA

Carina Biotech website & social media launched: carinabiotech.com; CTM CRC’s launched its new website: ctmcrc.com


Bioinvisible vascular stents in advanced preclinical trials with a global medical device company

Positive preclinical data in advanced models using cell delivery device

Advanced cultureware coatings to reduce the cost of cell therapy manufacture validated in independent laboratories

in vitro proof of concept established for CAR-T cells targeting a broad range of solid tumours

Optimisation of CAR-T cell manufacture commenced and preclinical trials initiated

Adelaide-based CAR-T researcher spent two months in the Jensen laboratory at the Seattle Children’s Research Institute

Custom-built plasma reactor installed and commissioned to scale-up coating processes

15 new patent applications filed including 2 patent families entering the national phase

Carina attracted equity investment of more than $2 million

Collaborative project with the Cancer Therapeutics CRC to test proprietary T cell modulatory compounds

First cohort of PhD completions. 2 graduates employed in cell therapy/biomaterials research in Australia

50 students from Flinders University attended new bioprocessing training program

Carina was awarded a $900K BioMedTech Horizons Grant from MTP Connect

Advanced coating contract research project completed for a large multinational supplier of cell therapy equipment

Collaborations with 4 companies worldwide to develop advanced coatings for cell cultureware

Second spin-out company, TekCyte, incorporated


Carina awarded $2.1 million CRC-P grant funding

Positive data in CAR-T preclinical models for different cancer types

Promising preliminary data for T cell expansion using advanced surface coatings

in vitro proof of concept for CAR-T cells targeting further cancer cell types, including prostate cancer & rhabdomyosarcoma

Therapeutic cells shown to remain viable after freezing and thawing on cell delivery device, offering improved shelf life

TekCyte’s advanced cultureware shown to be superior to competitor products for the culture of neuronal cells

TekCyte continued its contract research services, including with repeat customers

Bioinvisible coating patent application assigned from CTM CRC to TekCyte and entered national phase

TekCyte commenced a collaboration with UniSA and SA Health to examine the long-term safety and efficacy of stents with its bioinvisible coating

Chimeric Antigen Receptor patent application assigned from CTM CRC to Carina Biotech

Completed ePhD training. 19 students graduated from the program.

05

CTM CRC TIMELINE


http://carinabiotech.com/

http://carinabiotech.com/

https://www.ctmcrc.com/

MAJOR ACHIEVEMENTS

1. Development of a world first CAR-T cell for the treatment of solid cancers

2. Design and fabrication of a patch for delivering therapeutic cells to chronic wounds

3. Development of a ‘bioinvisible’, antithrombotic coating for vascular stents

4. Surface manufacturing to reduce costs in cell expansion systems

5. Next generation bioreactor coating to promote cell expansion

6. Development of novel T cell expansion materials

7. Improved survival of pancreatic islets for transplantation

8. Construction and commissioning of a pilot-scale plasma reactor for production of advanced surfaces

9. Development and delivery of an industry-specific tailored entrepreneurial PhD (“ePhD”) Program

10. Incorporation of spin-out companies, Carina Biotech and TekCyte, to carry out CTM CRC technology development and commercialisation post funding period

RESEARCH & COMMERCIALISATION

1. Development of a world first CAR-T cell for the treatment of solid cancersCAR-T cell therapy harnesses a patient’s own immune system to fight their cancer. CTM CRC fostered the conception and development of a world-first CAR-T cell targeting a dysfunctional form of the P2X7 ion channel. This CAR-T cell has the potential to treat a broad range of cancers including common cancers such as breast or prostate cancer as well as rare or paediatric cancers.

Major CTM CRC CAR-T research outputs included:

� Development of the first chimeric antigen receptor (‘CAR’) molecular constructs targeting dysfunctional P2X7.

� Development of optimised lentivirus engineering and production techniques to facilitate CAR-T manufacture.

� Development of improved T-cell transduction and expansion methodologies to enable CAR-T cell scale-up.

� Identification of optimised variants of dysfunctional P2X7 targeting CAR-T cells, which formed the basis of Carina Biotech’s lead CAR-T cell development candidate CNA1003.

� Demonstration of dysfunctional P2X7 targeting CAR-T cell anticancer activity across a wide range of cancer cell lines in vitro.

� Pilot data showing the activity of dysfunctional P2X7 targeting CAR-T cells in animal models of human solid cancers.

� Development of high-value collaborations between Australian CAR-T researchers and global CAR-T players including pioneering CAR-T researchers at Seattle Children’s Hospital as well

as a number of corporate CAR-T industry players.

2. Design and fabrication of a patch for delivering therapeutic cells to chronic woundsChronic wounds – wounds that do not heal within three months due to a disruption of the wound healing cycle – are a major burden on individuals, healthcare budgets and societies. In the USA alone, chronic wounds are estimated to affect more than 6.5 million patients, and the cost to the healthcare system is over $50 billion annually. This includes over $15 billion spent on the treatment of diabetic foot ulcers which can markedly reduce quality of life and working capacity as well as increase social isolation.

To address this unmet medical need, CTM CRC brought together experts in biomaterials and cell biology, from research organisations, wound clinics and industry, to design and develop a wound dressing that effects rapid wound closure, reducing the risk of infection and wound management costs, and improving health outcomes for patients.

The project team used its expertise in advanced surfaces to apply a coating to a dressing that enables it to act as a carrier of therapeutic cells. Application of the dressing then delivers the cells directly and uniformly to the bed of a wound. The applied cells interact with the wound environment and modulate their activity to release multiple factors that facilitate the wound healing process and tissue regeneration.

CTM CRC projects demonstrated that the coated dressing with therapeutic cells attached has the following features:

� It significantly improves the rate of wound closure and collagen remodelling in a pre-clinical model, leading to stronger, more durable wound repair.

� The dressing has broad utility across a range of therapeutic cells (stem cells and progenitor cells) from different sources, some of which are in clinical trials for other indications.

� It is effective in the treatment of acute wounds and diabetic wounds.

� The dressing can be frozen and the attached cells remain viable upon thawing, which should allow for a cold supply chain, long-term storage and easy implementation in wound clinics.

TekCyte, which is commercialising the dressing, has determined that only a small number of cells are required which means the product can be produced at a low cost and positioned very competitively against existing advanced wound care products.

3. Development of a ‘bioinvisible’, antithrombotic coating for vascular stentsStents are tubes that help increase and maintain the inner diameter of blood vessels which previously had an obstruction, most commonly a build-up of fatty deposits. Most stents are made out of wire mesh and are permanent. But the stents currently used in clinical practice can fail, when blood clots form in the stents themselves or the vessel narrows again at the site of stent placement.

Consequently, CTM CRC combined its Participants’ expertise in vascular biology, clinical cardiology and biomaterials to design and develop a safer and more effective cardiovascular stent. We can now apply a highly biocompatible coating that effectively renders metal stents ‘bioinvisible’, evading the body’s normal immune responses to foreign bodies that cause stents to fail.

CTM CRC projects supporting the bioinvisible stent development program had the following outcomes:

� The coating significantly inhibited fouling by biomolecules and local clot formation when blood was circulated through the stent, shown with blood from 13 donors of varying age and gender

� Inflammatory responses could be detected in blood circulated through uncoated stents, but not in blood circulated through coated stents

� The coated stent has a good biocompatibility and safety profile, and is stable for at least a year after sterilisation

� Major advancements were made in the manufacturing process, such that the bioinvisible coating can now be applied to a broad range of implantable medical devices, of all shapes, sizes and materials.

02

SNAPSHOT SUMMARY


Pancreatic islet cells

SNAPSHOT SUMMARY

The intellectual property protecting the coating process and coated medical devices has now been assigned to TekCyte, which is adapting its manufacturing facility to apply the coating to stents on a commercial scale. TekCyte is also exploring new applications of the coatings on a range of medical devices which are prone to failure because of the body’s immune and inflammatory responses.

4. Surface manufacturing to reduce costs in cell expansion systemsMost therapeutic stem cells are adherent cells and therefore require an appropriate surface for attachment. Traditionally this surface is tissue culture polystyrene which is often coated with collagen and/or fibronectin to encourage adhesion. Additionally, for mesenchymal stromal cell (MSC) culture, growth factors i.e. Fibroblast Growth Factor -2 (FGF-2) are added to the media. For the culture of induced Pluripotent Stem Cells (iPSCs) different growth factors are required, as well as FGF2, FGF-10 and TGFβ1 (Transforming Growth Factor –β1) are also needed. At each media change additional growth factors need to be added into the culture due to the instability of free growth factors in solution. Sequestering growth factors onto the surfaces prior to cells being seeded means that no further growth factors need to be added into the culture daily or twice weekly.

CTM CRC brought together participants from the University of South Australia, the University of Sydney and the University of Adelaide with expertise in surface modification, glycobiology, MSC and iPSC culture. Surfaces were developed that improved MSC and iPSC growth and decreased the amount of growth factors and sera required for the culture.CTM CRC projects supporting the development of the cultureware in cell expansion systems had the following outcomes:

� The surface was comprehensively characterised with respect to its chemistry and its ability to bind

glycosaminoglycans (GAG’s) and growth factors (FGF-2 and FGF-10).

� Chemical and biological stability of the cultureware was confirmed under a range of conditions.

� Advancements were made in the coating technologies to allow for other commercially relevant 3D substrates i.e. scaffolds and microcarriers to be coated.

� Surfaces were produced that supported the growth of MSCs and iPSCs whilst significantly reducing the amount of growth factor required in their culture.

5. Next generation bioreactor coating to promote cell expansionIn line with its remit to improve the affordability and accessibility of cell therapies, CTM CRC lead a successful collaboration with an industry participant located in the USA that aimed to increase the output of therapeutic cells from the participant’s stem cell expansion technology. The collaboration aimed to develop a novel surface coating for the expansion technology that would increase the yield and versatility of the technology. The goals were to:

� Increase the yield of therapeutic cells achieved,

� Eliminate the use of animal derived products in functionalising the surface and

� Enable cells to be more easily removed.

� Successfully demonstrate application in the commercial setting, including capacity to scale-up production, be sterilisable and have an appropriate level of shelf stability.

Technology transfer of the surface coating process to the industry participant once developed was agreed with CTM CRC.

Several surface coating approaches were investigated and a process was successfully developed that gave good performance at laboratory scale. Yields of therapeutic cells achieved using coated surfaces were significantly higher than yields achieved using uncoated surfaces and comparable to yields from surfaces coated with an animal derived product. A provisional patent application was lodged on the basis of these successful results. However, when the coating was applied using production level processes in collaboration with the industry participant, technical difficulties prevented translation of the benefits seen at the laboratory scale.

Notwithstanding the failure to achieve commercial application, the commercial partner gave very positive feedback on the relationship.

6. Development of novel T cell expansion materialsT cell therapy, where a person’s immune cells are modified and grown outside the body and then re-administered, is gaining momentum as a viable treatment for patients. This applies to CAR-T therapy for cancer (being pursued by Carina Biotech), as well as Treg therapy for autoimmune diseases and transplant recipients. An important step in this process is activating T cells so that they expand outside the body in a laboratory. The most widely used method for expanding T cells in a laboratory involves the use of specially coated beads. However, these beads are protected by intellectual property and controlled by a single entity. Their removal following expansion is also problematic.

To address this, CTM CRC sought to develop a novel and patentable technology to activate T cells outside the body as a competitor to coated beads. Several approaches were investigated, exploiting CTM CRC surface chemistry expertise. A lattice arrangement constructed using a high-tech melt electrospinning process was developed and investigated for its performance in expanding T cells at the desired quality and quantity. A PCT application for the technology was lodged and the technology was subsequently transferred to an Australian company which will undertake further development to take the product to market.

A cartridge format and alternative surface chemistries were also investigated for their

performance in expanding T cells and suitability for use in a closed T cell expansion system. These technologies have shown promise at laboratory scale and warrant further investigation to determine if they can provide a commercially viable competitor to bead expansion.

7. Improved survival of pancreatic islets for transplantationDiabetes mellitus affects millions of sufferers worldwide, and its incidence is increasing. For some patients, standard therapy involving regular injection of insulin does not provide adequate treatment of the condition. An islet transplant, where islets from donated pancreatic tissue are transplanted into a recipient, has the potential to achieve adequate blood sugar control for patients where standard insulin administration has failed. Research carried out by CTM CRC researchers aimed to improve the survival and function of donor pancreatic islets for transplantation into diabetes patients.

CTM CRC researchers investigated the use of growth factors, transportation materials and implantable scaffolds to improve islet survival and function. An oxygen permeable, microwell format was developed that improved survival of mouse islets in shipping studies by providing a supportive environment. Such a device could improve the quality of islets for transplantation. Coating microwells with oxygen releasing materials and growth factors was also investigated to further enhance islet quality during transportation.

I am extremely proud of the investments that Terumo BCT have made in cell therapy...working with partners like CTM CRC is the best approach.Mr Bill Mercer Terumo BCT, Inc.


Pilot-scale plasma reactor

SNAPSHOT SUMMARY

8. Construction and commissioning of a pilot-scale plasma reactor for production of advanced surfacesA number of CTM CRC projects that showed excellent results employed a common platform technology for producing advanced surfaces: plasma polymer deposition. As the technology readiness of plasma polymer-based products progressed, and CTM CRC required samples in greater numbers for validation and beta-testing, there emerged a critical need to scale up the deposition process from laboratory scale to pilot scale.

To overcome these constraints, CTM CRC designed a plasma polymer reactor with ten times the production volume of systems previously available for projects. Researchers built and completed the validation of the new reactor within 9 months – an excellent achievement given the complexity of the design and the many input parameters that influence the deposition process. The new design retained the geometry of previous systems, reducing risk, but with a greatly increased footprint.

TekCyte will use the new reactor to scale up production of close-to-market products. TekCyte can now produce 35,000 coated tissue culture plates per annum in a single daily shift batch process. The technology also produces sufficient coated cell therapy wound dressings for large clinical studies.

ENGAGEMENT WITH SMES, NEW PARTICIPANTS & COLLABORATORS � The SME, Cell Therapies Pty Ltd, is an Essential

Participant. It provided regulatory support to several CTM CRC projects and helped define Target Product Profiles which served as key strategic documents informing various CTM CRC product development programs.

� The SME NextCell Pty Ltd – an incorporated joint venture between UniSA, Cell Therapies and Exylika Pty Ltd were Essential Participants that designed and commissioned a GMP-compliant cell manufacturing facility in Adelaide that has been a

key enabler of CTM CRC’s scale-up and translation activities.

� CTM CRC also had an overseas SME Participant in Athersys, Inc, a cell therapy company. CTM CRC researchers developed a device for delivery of a proprietary Athersys cell line to wounds.

� A collaboration with SME, Cynata Ltd, developed a stem cell-coated wound dressing, using Cynata’s proprietary stem cell, Cymerus™.

� Wilson Wolf is a leading supplier of specialised equipment for the manufacture of CAR-T cells. During the development of CTM CRC’s T cell activation technology, Wilson Wolf provided researchers with their

proprietary manufacturing equipment and appropriate training to assist with the evaluation of our technology in their systems.

� The RPA has extensive knowledge and experience in manufacturing cell and gene-based therapies. They entered CTM CRC to strengthen translational capabilities to bring manufacturing processes to the clinic, including CTM CRC’s novel CAR-T cells.

� Scinogy Pty Ltd is a successful product development company with extensive knowledge of the large-scale manufacture of cell therapies for clinical use. Its management team brings several decades of insight into the challenges facing the industry and provided CTM CRC project teams with an unparalleled level of understanding that helped frame the scope of projects to ensure outcomes were able to provide long-term benefit to the industry.

� Prof Gordon Wallace at the University of Wollongong is a global leader in the field of 3D printing of living cells. Faced with the challenge of developing novel cell delivery systems to treat disease, CTM CRC brought University of Wollongong into the centre as a participant to work with the diabetes research team at the RAH. Treating diabetic patients with living cells (islets) to manage their disease has many limitations, the most critical of these being the delivery of cells in a healthy state. This led to a collaboration to develop a new printing gels that facilitates the delivery of very fragile islets to diabetic patients.

� The University of Adelaide (UA) joined CTM CRC as an Other Participant in 2016, and it has conducted research into human regulatory T-cells, dendritic cell-target therapy and the targeting of MSCs to the central nervous system. UA researchers have also carried out much of the preclinical work which has demonstrated efficacy of Carina Biotech’s CAR-T therapies against numerous solid cancers.

� The University of Lancaster in the UK joined CTM CRC as an Other Participant in 2018, and it remains a key collaborator in advancing the product development and clinical development of the cell delivery dressing for the treatment of chronic wounds.

� CTM CRC spun out two SMEs of its own, Carina Biotech and TekCyte. The two companies will continue development and commercialisation of CTM CRC technologies past the life of the CRC. (See ‘Spin out companies & inventions’, p20)

EDUCATION 9. Development and delivery of an industry-specific tailored entrepreneurial PhD (“ePhD”) Program From its first enrolments, CTM CRC invested in producing industry-ready PhD graduates, courtesy of its flagship entrepreneurial PhD (ePhD) Program. By the end of 2018, thirteen PhD students had completed the four in-residence ePhD modules, developed and delivered by CTM CRC staff and invited industry experts, each of three to four days duration:

� Commercialising Biotechnology - examining the key issues and risks in the commercialisation of biotech inventions

� Biotechnology Enterprise and Entrepreneurship – focused on cultivating entrepreneurial and enterprising researchers

� PhDs@work – a mini MBA providing the business skills that industry seeks in new employees

� Science Communication and Engagement – equipping students with the confidence and tools to communicate their research to a wide audience.

This transferable skill set has been highly valued by employers of CTM CRC graduates in both the public and private sectors. Graduates have secured jobs in academic research, industry-sponsored research and management consulting, while others have chosen to pursue further study in science communication and medicine.

Six more PhD students will complete the Program in

2019.

Our collaboration with CTM CRC has created the opportunity to integrate different aspects of cell therapy research and manufacturing in a way we had never done before.Dr Jeff Pinxteren Athersys, Inc.


Professor Mike Jensen, SCRI

SNAPSHOT SUMMARY

INTERNATIONAL ENGAGEMENT

� Seattle Children’s Research Institute (SCRI) is providing ongoing guidance and technology transfer to Carina Biotech in relation to the manufacture and preclinical development of CAR-T cells. In addition, SCRI will undertake preclinical animal model testing of the Carina CAR-T cells in preclinical cancer models. SCRI has and will continue to host researchers and students as part of their professional development and training.

� Through the collaboration with SCRI, one of CTM CRC’s researchers had the opportunity to spend two months at SCRI in late 2017. This collaboration provided third party validation of CTM CRC’s CAR-T in vitro trials, as well as valuable new insights into engineering CAR-T cells.

� Terumo BCT worked with academic teams within CTM CRC to create a novel surface to improve the yield of expanded adult stem cells and reduce the cost and complexity of manufacturing therapeutic cells.

� Chronic diabetic wounds lead to a poor quality of life and carry a high cost burden on the healthcare budget. A collaborative project with Athersys, Inc, using their proprietary therapeutic cells led to a patent-pending cell delivery dressing with demonstrated improvements in the rate of wound healing.

� CTM CRC’s coating capabilities were sought by a multinational company to modify the surface properties of their marketed disposable polymer-based products, used to manufacture cell therapies. CTM CRC successfully demonstrated its ability to modify and impart functional properties to the surface of their polymer film. On the basis of the initial success, CTM CRC and TekCyte have received almost A$500,000 in revenue from contract research projects.

� A multinational cardiovascular device company, is collaborating with CTM CRC to evaluate its novel polymer coating for use in stents to reduce the formation of blood clots. The impact of this technology could be a reduction in catastrophic failure of implanted stents and better outcomes for treated patients.

� Merck EMD & Sarstedt are cultureware suppliers that have evaluated coated cultureware developed at CTM CRC. This cultureware is being commercialised by TekCyte.

� GE Healthcare & Wilson Wolf supplied manufacturing hardware on loan for CTM CRC’s translational facility to support pilot-scale testing of novel cell manufacturing technologies developed by CTM CRC.

SPIN-OUT COMPANIES & INVENTIONS 10. Incorporation of spin-out companies, Carina Biotech and TekCyte, to carry out CTM CRC technology development and commercialisation post funding period

Carina BiotechThe CAR-T market is growing rapidly on the back of the initial success with blood cancers. This has led to a spate of corporate investments and acquisitions, most notably the recent acquisitions of Juno Therapeutics by Celgene Corp and Kite Pharma by Gilead Sciences for $9 billion and $12 billion respectively, only seven years after their establishment. CTM CRC is capitalising on this positive market segment through the spin out of Carina Biotech Pty Ltd. Carina is focusing on engineering CAR-T cells that can target the more challenging, but also more prevalent target of solid tumours. Achievements to date include:

� CTM CRC facilitated the filing of a number of patent families covering novel CAR-T cells and solid tumour delivery systems that have been taken up by Carina. Carina has also gone on to accumulate complementary IP developed in other organisations, including IP developed in earlier CRCs.

� Within the lifetime of the CTM CRC Carina has already established financial independence and attracted several million dollars worth of equity investment as well as won two Australian Government large grants (MTPConnect and CRC-P) to fund ongoing preclinical development of the CTM CRC-originated CAR-T technology.

� Carina hopes to advance the CTM CRC-originated CAR-T technology rapidly and aspires to be ready for a first in human clinical trial by the end of 2020.

� CTM CRC is spreading benefit back to Australian Universities and SMEs through the distribution of Carina Biotech shareholding to CTM CRC Participants in recognition of the CAR-T IP developed in CTM CRC.

TekCyteCTM CRC’s second spin-out company, TekCyte Pty Ltd, has been established to develop commercial applications arising from CTM CRC’s core capabilities in coating surfaces to enhance their biological function. The markets include cultureware for use in research laboratories or for therapeutic cell expansion, as well as coatings for medical devices including vascular stents and wound dressings.

Collectively, TekCyte’s products offer a multi-million dollar market opportunity, with cultureware likely to reach market in the next few years. TekCyte has:

� Conducted an initial proof-of concept study under contract for the development of a novel cell isolation system

� Engaged companies in contract research projects which to date have totalled almost AU$500,000

� Begun establishing a strong proprietary position with patents pending in the application of CTM CRC’s coating technology. Where granted, the company will have monopoly rights across particular applications of plasma coating, including a bioinvisible coating for stents and other vascular devices, and a coated dressing that can topically deliver cells to treat chronic wounds

� Begun collaborating with a global company to commercialise its stent technology. The company has performed pre-clinical testing of TekCyte’s stent coating which demonstrated safety of TekCyte’s coating, a very positive result for any implanted device with a polymer coating.

� Started dealing with an Australian cell therapy company – Cynata Ltd, to commercialise its coated wound dressing. Preclinical results have provided strong evidence of the potential for the treatment to improve the healing of chronic wounds in diabetic patients, which costs the Australian healthcare system more than $3b annually. TekCyte is now working with Cynata and organisations in the UK to initiate a first-in-man clinical trial.


CTM CRC was formed five years ago in recognition that the cell therapy industry needed to evolve towards more efficient, cost-

effective and practical methods of cell manipulation outside the body including isolation, expansion and final packaging. It has focused on finding innovative technologies using novel materials and surface optimisation, funded with more than $50 million of cash and in-kind contributions from the government and its partner institutions.

In that time CTM CRC has conducted far-ranging projects including improving the culture surfaces for expansion of mesenchymal stem cells in closed system bioreactor, activation of T cells for immunotherapies, the delivery of therapeutic cells to treat chronic wounds and the reduction in clot formation in stents. CTM CRC was able to conduct these studies because of the unique multidisciplinary team of biomaterials scientists working closely with cell biologists, clinicians and regulatory experts that helped guide the research projects toward a commercial outcome.

The underlying capability across the majority of projects was the ability to manipulate the surface properties of materials that come in contact with living cells or tissue. The most common form of treatment used in CTM CRC was a process called plasma polymerisation that deposits a thin film polymer that can be tailored to a specific purpose or biomedical application. The capabilities and technologies that have been developed have attracted the attention of several companies in the cell therapy industry.

CTM CRC technologies will be commercialised in either of the two start-up companies, Carina Biotech and TekCyte that have been incorporated in the last two years. The two companies are a testament to the level of collaboration between the participants and the commercial focus applied to the projects within the six years of the CRC.

Carina’s Economic Impact � Carina has advanced through the technology

proof of concept stage to now be in the preclinical development stage for its immunotherapies. Analysis of comparator companies shows that preclinical development stage CAR-T companies typically have company valuations in the low-mid $10s of millions of US dollars.

� Over the next two years, Carina hopes to advance through preclinical development and toward readiness for a human Phase I human clinical trial. Once a CAR-T company has an asset in human clinical trials (phase I/II), comparators indicate that company valuations increase substantially to the range of $70 million to >$200 million.

� For CAR-T companies with products on the market or in later stage clinical trials, such as Juno Therapeutics or Kite Pharma, company valuations in the multi-billion dollar range have been seen.

� Carina has IP rights to more than $5 million of research stemming from CTM CRC. Our IP portfolio includes composition of matter patent claims to dysfunctional P2X7-targeting CAR-T cells. The most advanced claim has already entered the national phase in 11 jurisdictions including countries across North America, Europe and Asia.

� As at January 2019, Carina has raised more than $3 million equity funding as well as attracted over $3 million grant funding from the MTPConnect BioMedTech Horizons program and the CRC-P program.

� Carina has already generated four new high-value private sector jobs in Carina management, funded more than 10 research positions and supported 5 PhD and Honours student research scholarships within Australian universities.

TekCyte’s Economic ImpactTekCyte has a state-of-the-art cleanroom manufacturing facility at UniSA’s Mawson Lakes campus that will meet the quality requirements for the medical device industry. By 2025 TekCyte is expected to generate revenue in excess of $10 million and employ up to 16 staff.

BioInvisible coating � The anti-thrombotic activity of the bioInvisible

coating has the potential to reduce the frequency of the sometimes catastrophic failure of cardiovascular stents.

� The bioInvisibile stent presents an alternative to both bare metal stents and drug eluting stents – as the bioresorbable segment continues to fail.

� If clinical efficacy and safety is proven, this new stent could capture a significant percentage of the global market, currently valued at US$8-10 billion and growing at 5-6% CAGR, with several million stents implanted per year.

� Additionally, reducing the failure of cardiovascular stents can help reduce the economic burden of treating coronary artery disease, which costs the healthcare system in the US US$109 billion/year and in Europe €195 billion/year.

� The bioinvisible stent can improve outcomes for patients and extend life. Collectively, cardiovascular disease in the US accounts for 25% of all deaths and in Europe 40-50% of all deaths. In Australia coronary heart disease is the leading cause of death for males and the second leading cause of death for females.

� The bioinvisible coating can reduce the frequency of complications that arise after implantation of a broad range of medical devices that can elicit immune and inflammatory responses in the recipient. These include coronary stents, peripheral arterial stents, venous stents, grafts and shunts, mechanical heart valves, vascular access and catheter devices used in reconstructive and cosmetic surgery.

Wound patch � The fastest growing sector globally of the wound

care market is active wound care – products that promote wound healing through biological mechanisms, including tissue-engineered products, growth factors and cell therapies.

� Active wound care of diabetic foot ulcers is a US$3 billion addressable market but it is significantly underpenetrated as many currently available products have questionable efficacy, are expensive, or difficult to apply in wound clinics.

� An effective, safe, easy to apply advanced wound care dressing for treating diabetic foot ulcers could generate sales in the hundreds of millions of dollars.

Advanced cultureware � Advanced cultureware for stem cell manufacture

can improve process efficiency and reduce cost of manufacture for cell therapies.

� In just one application of the advanced cultureware for the manufacture of therapeutic stem cells, a company could achieve savings in its manufacturing costs of up to a $1 million per year.

� The market for such products is rapidly growing at >30% per annum and currently estimated to generate global sales of A$170 million.

03

ECONOMIC IMPACT


CASE STUDY01

A SPIN-OUT of the Cooperative Research Centre for Cell Therapy Manufacturing (CTM CRC), Carina is developing world-first pan-cancer CAR-T therapies to treat high-incidence cancers as well as rare and paediatric

cancers.

Chimeric antigen receptor T (CAR-T) cell therapy is a rapidly emerging treatment option that harnesses a patient’s own immune system to fight their cancer. CAR-T therapies have produced astounding results in the treatment of some blood cancers but, as yet, similar results have not been achieved against solid tumours.

As the assignee of IP stemming from over $5 million in CTM CRC research efforts, Carina has developed a world-first pan-cancer CAR-T cell targeted at solid tumours.

ECONOMIC OUTCOMESCarina Biotech is headquartered in Adelaide, South Australia, spun out of the highly successful Australian Cooperative Research Centre for Cell Therapy Manufacturing (CTM CRC).

Carina has IP rights to over $5 million of research stemming from the CTM CRC. Our IP portfolio includes composition of matter patent claims to dysfunctional P2X7-targeting CAR-T cells. The most advanced claim has already entered the national phase in 11 jurisdictions including countries across North America, Europe and Asia.

As at January 2019, Carina has raised $3million in equity funding as well as attracted over $3 million of non-dilutive grant funds from the MTPConnect BioMedTech Horizons program and the CRC-P program.

Carina has already generated four new high-value private sector jobs in Carina management, funded more than 10 research positions and provided 5 PhD and Honours student research scholarships within Australian universities.


Human triple-negative breast cancer cell line (MDA-MB-231) before (above) and after (below) exposure to Carina CAR-T CNA1003 (green). Dying cells shown in red.

carina b i o t e c hcellular immunotherapies

BROAD-SPECTRUM ANTI-CANCER ACTIVITY

FURTHER IN VITRO CYTOTOXICITY DATA across a range of

additional cancer cell lines (hematological, paediatric and rare cancers)

FURTHER IN VIVO TUMOUR GROWTH + METASTASIS DATA + INTRAVITAL MICROSCOPY showing CAR-T anti-cancer activity in an additional 3 xenograft models of human cancer

FINALISATION OF A CLINICAL PLAN to advance the lead Carina CAR-T cell into a world first pan-cancer first-in-human clinical trial in 2020 – to be conducted in Australia

IN VITRO DATA showing high levels of cancer cell cytotoxicity in 14 cancer cell lines across 9 different cancers (see table on adjacent page).

IN VITRO microscopy demonstrating real-time killing of cancer cell lines by CNA1003 (see images on adjacent page)

OUR GOAL

Complete preparation for a world-first pan-cancer CAR-T clinical trial in Australia by the end of 2020

TO GET THERE

*

*

*

IN VIVO data of animal safety + tumour growth/metastasis suppression in mouse xenograft models of human prostate cancer, breast cancer & melanoma

PATIENT TUMOUR EXPLANT DATA that shows CAR-T induced cancer cell death equal to or greater than carboplatin chemotherapy

CAR-T MANUFACTURING PROTOCOLS that are simple, inexpensive & scalable + can produce clinical-scale doses of CNA1003 within 30 days

+ +WE HAVE

CANCER CELL LINEIN VITRO CAR-T ACTIVITY

ADULT SOLID

Ovarian OVCAR3

SKOV3

Breast MDA-MB-231

BT549

Glioblastoma U87

Melanoma C32

M21

SK-Mel-05

SK-Mel-28

Pancreatic ASPC

Prostate PC3

PAEDIATRIC SOLID

Neuroblastoma SKNDZ -

Be(2)M17

Rhabdosarcoma RD

HEMATOLOGICAL

B Cell Raji

TekCyteADVANCED BIOMEDICAL COATINGS

CASE STUDY02

TEKCYTE specialises in developing and manufacturing thin-film polymer coatings that improve the performance of medical devices and cell bioprocessing equipment. A spin-out business from the Cooperative Research

Centre for Cell Therapy Manufacturing (CTM CRC), TekCyte has benefited from 5 years and A$6.2 million (A$16 million including “in-kind”) investment into R&D in plasma coating applications. TekCyte is headquartered in Adelaide where it is closely associated with infrastructure and expertise at UniSA, utilising state-of-the-art facilities at Mawson Lakes.

Effective biomedical devices � Devices used in biomedical applications

may elicit an adverse response (inflammation, immune response)

� Devices may also be compromised by fouling or formation of biofilm

� TekCyte has expertise, patented plasma coating technology and manufacturing facilities to develop and produce surface-functionalised materials

� These coatings have been proven to provide substantial value-add for the devices and materials for which they have been adapted

TekCyte can modify any biomaterial interface to:

� Enhance performance of implanted devices

� Promote efficient delivery of therapeutic cells to wound sites

� Reduce the cost of manufacturing of cell therapies

Affordable cell therapies � Delivery of therapeutic cells to the site

of tissue damage is suboptimal for some indications

� Current cell therapy manufacturing and research have a high demand on expensive reagents

INITIAL FOCUS AREAS

Initial focus is high-value-add products into large international markets

APPLICATION DESCRIPTIONADDRESSABLE MARKET SIZE STATUS

POTENTIAL OUTCOME

A novel coating for arterial or venous stents that inhibits the formation of clots.

$US 3 billion Proof-of-concept in vitro

Good safety and biocompatibility in preclinical models.

Coating unaffected by sterilisation and long term storage.

Toll manufacturing.orCo-development and licensing arrangement.

An active dressing that enables effective delivery of stem cells to chronic wounds.

$US 3 billion Proven efficacy of numerous cell lines in preclinical models.

Assembled clinical team, health economics and advanced surfaces researchers for first-in-man trial.

Co-development and licensing arrangement.

A coating applied to cell culturing equipment (plates, flasks, microcarriers, etc.) that enables improved cell growth.

$US 120 million NDA/Commercial discussions.

Manufacturing and sale through distributors.orToll manufacturing.

INTELLECTUAL PROPERTYTekCyte has a strong proprietary position – patent protection - in the application of its coating technology:

1. A novel medical device (anti-thrombotic stent) - Patent publication number WO/2017/156592 - “Anti-Fouling and/or Anti-Thrombotic Medical Devices’, National phase entry in 8 jurisdictions including countries across North America, Europe and Asia.

2. A device for the delivery of therapeutic cells to chronic wounds, Patent publication number WO/2016/131096, “Methods and Products for Delivering Cells”, National phase in Australia, US and EU

TekCyte has additional IP relating to plasma polymer coatings in the form of know-how and trade secrets.

ECONOMIC OUTCOMES

� TekCyte has trading income through the provision of contract research and development activities for international clients.

� TekCyte has secured private investment from business angels which it will use, together with its trading profits, to leverage non-dilutive grant funds to expand its business.

� TekCyte has generated five new high-value jobs in advanced manufacturing, predicted to grow to 16 new jobs by 2025.

TekCyte’s advanced biomedical coatings address major challenges in the safety, efficacy and affordability of therapies and devices

TEKCYTE SOLUTIONMARKET NEEDS

Advanced Coatings

Vascular Stents

Woundcare

Advanced Cultureware


CASE STUDY03

CTM CRC has derived enormous benefit from its participants, including the market intelligence and commercialisation opportunities from our

industry partners, and the world leading capabilities of our research partners.

Conversely, the participants have benefitted from the opportunity to come together under the effective umbrella of the CRC to design more cost-effective methods of cell therapy manufacture.Examples of the industry benefits that have been achieved through this CRC partnership include:

� CTM CRC’s unique, thin-film coatings will be incorporated into a range of commercial cultureware by Australian and international companies over the next few years.

� CTM CRC’s advanced wound dressings are being developed for commercial application using stem cells from an Australian SME

� An anti-thrombotic coating for vascular stents has now entered large animal trials with a major international stent supplier.

� CTM CRC’s ground-breaking research in the new field of CAR-T cancer therapy offers potential for curative treatments across a range of cancers.

But the CRC Board believes its most important legacy for the Australian economy has been the establishment of two new high-growth companies

that can build and retain value locally:

� Carina Biotech Pty Ltd to take the CAR-T therapies to clinical application; and

� TekCyte Pty Ltd for commercial manufacture and supply of advanced coatings for cultureware and medical devices to the research and cell therapy industries.

Collectively, the two companies address multi-billion dollar market opportunities, and show excellent growth potential.

As shareholders in Carina and TekCyte, the CTM CRM Participants will have the opportunity for ongoing benefits and return on investment.

It is great to participate in such an outcome-focused CRC. Our researchers have benefited from deep collaboration and co-location with the CTM CRC, tackling challenging interdisciplinary problems as one team.Professor Emily Hilder UniSA

ADVANCED WOUND DRESSING Participants - Athersys, University of South Australia (UniSA), University of Sydney (USyd)

CHRONIC wounds – wounds that do not heal within three months due to a disruption of the wound healing cycle – are a major burden

on individuals, healthcare budgets and societies. In the USA alone, chronic wounds are estimated to affect more than 6.5 million patients, and the cost to the healthcare system is over $50 billion annually. This includes over $15 billion spent on the treatment of diabetic foot ulcers which can markedly reduce quality of life and working capacity as well as increase social isolation.

To address this unmet medical need, CTM CRC designed and developed a wound dressing to deliver Athersys’ proprietary cells using surface technology developed by biomaterials experts at UniSA and USyd. The Athersys cells are similar to mesenchymal stem cells (MSCs) – a cell type known for its wound healing applications due to its capability for self-renewal and multilineage differentiation.

Prior to the project, the standard method of delivering MSCs was in suspension. This method works well for systemic delivery for conditions such as Graft vs Host Disease, and stroke treatments. However, Athersys wished to explore if it was possible to deliver their proprietary cells to wounds outside of the body, such as diabetic foot ulcers and other chronic wounds. For this clinical application a liquid delivery method would not be suitable. Therefore, surface modification and biomaterials expertise at UniSA and USyd worked together with stem cell experts at Athersys and their European subsidiary, ReGenersys BVBA. A bespoke surface was developed and produced positive preclinical results within the first year of the project.

The surface allows the cells to adhere to it and proliferate. However, the cells are not attached too tightly – so that they actively detach and migrate into wounds. This rapid development of the base wound dressing surface paved the way for additional advanced pre-clinical testing.

Further preclinical testing showed that the cells were delivered into the wounds, resided within the wounds for up to 7 days, and resulted in an increased rate of healing, a better-quality wound – a collagenous structure closer to that of unwounded

skin – and reduced scaring as assessed by the Manchester Scarring Scale.

Collaboration between researchers at both universities and Athersys was key to the project’s success. Over the course of the project researchers from ReGenersys regularly visited CTM CRC, with one researcher working at UniSA and USyd for 3 months. CTM CRC researchers also visited ReGenersys. Additionally, one researcher worked at ReGenersys for a 2 week period.

CTM CRC holds 3 patent applications in relation to the wound patch and the project has led to the development of further projects. One such project is with industry SME, Cynata, where the patch technology is being further developed to accommodate

mesenchymal stem cells that are grown in serum-free conditions. Cynata’s Cymerus™ cells can be manufactured cost-effectively at a large scale, from a single donor.

TekCyte and Cynata are now working with a partner in the UK towards a first-in-man trial to demonstrate the safety of this cell therapy in patients with diabetic foot ulcers.

One of the attractions of working within a CRC is the access to different partners with diverse skills, capabilities and infrastructure…Athersys continues to be supportive of CTM CRC. Dr Robert Deans Athersys, Inc.

04

INDUSTRY ENGAGEMENT


INDUSTRY ENGAGEMENT

CTM CRC PARTICIPANTSCTM CRC had 19 participants over its lifetime

PARTICIPANT PARTICIPANT TYPEORGANISATION

TYPEAthersys, Inc. Essential Participant Industry

Cell Therapies Pty ltd Essential Participant Industry

Exylika Pty Ltd Essential Participant Industry

NextCell Pty Ltd Essential Participant Industry

MedVet Science Pty Ltd Essential Participant Industry

Queensland University of Technology Essential Participant University

Royal Adelaide Hospital – a division of Central Adelaide Local Health Network Essential Participant State Government

St Vincent’s Institute of Medical Research Essential Participant Research Institute

SA Pathology – a division of Central Adelaide Local Health Network Essential Participant State Government

Terumo BCT Australia Pty Ltd Essential Participant Industry

University of South Australia (UnISA) Essential Participant University

University of Sydney Essential Participant University

Lancaster University Other Participant University

Royal Prince Alfred Hospital (Sydney Local Health District) Other Participant Hospital

South Australian Health and Medical Research Institute Limited Other Participant Research Institute

Scinogy Pty Ltd Other Participant Industry SME

University of Adelaide Other Participant University

University of Wollongong Other Participant University

Women’s and Children’s Health Network Incorporated Other Participant Hospital

COLLABORATIONSCTM CRC collaborated with many local and international companies over its lifetime. Some key collaborators included:

� Cancer Therapeutics CRC Pty Ltd

� Cell & Gene Therapy Catapult (UK)

� Centre for Commercialization of Regenerative Medicine (Canada)

� Cook Research Incorporated

� Cynata Therapeutics Ltd

� GE Healthcare

� Seattle Children’s Research Institute

� Wilson Wolf Manufacturing

* Due to confidentiality some of CTM CRC’s collaborators cannot be named.

INDUSTRY GROWTH CENTRESCTM CRC worked with the Medical Technologies and Pharmaceuticals Industry Growth Centre (MTPConnect) to:

� Explore opportunities for joint activities in Australia for cell therapy research, translation and manufacturing capabilities

� Address the skills gap that exists in the cell therapy sector in Australia through the development of training programs and workshops

� Upgrade TekCyte’s facility to enable practical training in aspects of good manufacturing practice for the cell therapy industry

� CTM CRC’s spin-out, Carina Biotech, attracted nearly $900K grant funding from the MTPConnect Biomedtech Horizons program

PUBLICATIONSBurzava, A.L.S., Jasieniak, M., Cockshell, M.P., Bonder, C.S., Harding, F.J., Griesser, H.J. and Voelcker,N.H. 2017. Affinity biding of EMR2 expressing cellsby surface-grafted chondroitin sulfate B. Biomacromolecules 18(6): 1697-1704.

Dalilottojari, A., Delalat, B., Harding, F.J., Cockshell,M.P., Bonder, C.S. and Voelcker, N.H. 2016. Poroussilicon-based cell microarrays: optimizing humanendothelial cell-material surface interactions andbioactive release. Biomacromolecules 17(11):3724-3731.

Dalilottojari, A., Delalat, B., Harding, F.J., Cockshell,M.P., Bonder, C.S. and Voelcker, N.H. 2017.Biomolecules based microarray for screening humanendothelial cells behaviour. International Journal ofBiotechnology and Bioengineering 11(1): 1-4.

Delalat, B., Rojas-Canales, D.M., Ghaemi, S.R.,Waibel, M., Harding, F.J., Penko, D., Drogemuller,C.J., Loudovaris, T., Coates, P.T.H. and Voelcker, N.H.2016. A combinatorial protein microarray forprobing materials interaction with pancreatic isletcell populations. Microarrays 5(6): 21.

Delalat, B., Harding, F., Gundsambuu, B., De-Juan-Pardo, E.M., Wunner, F.M., Wille, M.-L., Jasieniak,M., Malatesta, K.A.L., Griesser, H.J., Simula, A.,Hutmacher, D.W., Voelcker, N.H. and Barry, S.C.2017. 3D printed lattices as an activation andexpansion platform for T cell therapy. Biomaterials140: 58-68.

Ebert, L.M, Tan, L.Y., Johan, M.Z., Myo Min, K.K.,Cockshell, M.P., et al. 2016. A non-canonical role fordesmoglein-2 in endothelial cells: implications forneoangiogenesis. Angiogenesis 19(4): 463-486.

Forget, A., Burzava, A.L.S., Delalat, B., Vasilev, K.,Harding, F.J., Blencowe, A. and Voelcker, N.H. 2017.Rapid fabrication of functionalised poly(dimethylsiloxane) microwells for cell aggregateformation. Biomaterials Science 5: 828-836.

Forget, A., Waibel, M., Rojas-Canales, D.M., Chen, S.,Kawazoe, N., Harding, F.J., Loudovaris, T., Coates,P.T.H., Blencowe, A., Chen, G. and Voelcker, N.H.2017. IGF-2 coated porous collagen microwells forthe culture of pancreatic islets. Journal of Material

Forget, A., Staehly, C., Ninan, N., Harding, F.J., Vasilev, K., Voelcker, N.H. and Blencowe, A. 2017. Oxygen-releasing coatings for improved tissue preservation. ACS Biomaterials Science & Engineering, 3(10): 2384-2390; Chemistry B 5: 220-225.

Kafshgari, M.H, Voelcker, N.H. and Harding, F.J. 2015.Applications of zero-valent silicon nanostructures inbiomedicine. Nanomedicine 10(16): 2553-2571.

Kafshgari, M.H., Harding, F.J. and Voelcker, N.H. 2015. Insights into cellular uptake of nanoparticles. Current drug delivery 12(1): 63-77.

Kirby, G.T.S., Mills, S.J., Vandenpoel, L., Pinxteren,J., Ting, A., Short, R.D., Cowin, A.J., Michelmore, A.and Smith, L.E. 2017. Development of advanceddressings for the delivery of progenitor cells. ACSApplied Materials & Interfaces 9(4): 3445-3454.

Kirby, G.T.S., Michelmore, A., Smith, L.E., Whittle, J.D. and Short, R.D. 2018. Cell sheets in cell therapies. Cytotherapy, 20(2): 169-180

Kosobrodova, E., Kondyurin, A., Chrzanowski, W., McKenzie, D.R. and Bilek, M.M.M. 2016. Plasmaimmersion ion implantation of a two-phase blend ofpolysulfone and polyvinylpyrrolidone. Materials &Design 97: 381-391.

Kothari, S. 2016. Cell therapies - Australia playingcatch up? Australian Quarterly Oct-Dec: 32-39.

Maartens, J.H., De-Juan-Pardo, E., Wunner, F.M., Simula, A., Voelcker, N.H., Barry, S.C. and Hutmacher, D.W. 2017. Challenges and opportunities in the manufacture and expansion of cells for therapies. Expert opinion on biological therapy, 17(10): 1221-1233.

Moore, E., Delalat, B., Vasani, R., Thissen,H, and Voelcker, N.H. 2014. Patterning and biofunctionalisation of antifouling hyperbranchedpolyglycerol coatings. Biomacromolecules 15(7): 2735-2743.

Moore, E., Delalat, B., Vasani, R., McPhee, G.,Thissen, H. and Voelcker, N.H. 2014. Surface-initiatedhyperbranched polyglycerol as an ultra-low fouling coating on glass, silicon and porous silicon substrates. ASC Applied Materials & Interfaces 6(17): 15243-15252.


PUBLICATIONS & PRESENTATIONS

Rojas-Canales, D., Penko, D., Myo Min, K.K., Parham,K.A., Peiris, H., Haberberger, R.V., Pitson, S.M.,Drogemuller, C., Keating, D.J., Grey, S.T., Coates, P.T.,Bonder, C.S. and Jessup, C.F. 2017. Local sphingosinekinase 1 activity improves islet transplantation.Diabetes 66(5): 1301-1311.

Rojas-Canales, D.M., Waibel, M., Forget, A., Penko, D., Nitschke, J., Harding, F.J., Delalat, B., Blencowe, A., Loudovaris, T., Grey, S.T. and Thomas, H.E. 2018. Oxygen-permeable microwell device maintains islet mass and integrity during shipping. Endocrine connections, 7(3): 490-503.

Ryssy, J., Prioste-Amaral, E., Assuncao, D.F.N., Rogers,N., Kirby, G.T.S., Smith, L.E. and Michelmore,A. 2016. Chemical and physical processes in the retention of functional groups in plasma polymers studied by plasma phase mass spectroscopy. Physical Chemistry Chemical Physics 18(6): 4496-4504.

Saboohi, S., Al-Bataineh, S.A., Safizadeh Shirazi, H.,Michelmore, A. and Whittle, J.D. 2016. Continuouswave RF plasma polymerization of furfuryl methacrylate: correlation between plasma and surface chemistry. Plasma Processes and Polymers 14(3): article number 1600054.

Shirazi, H.S., Rogers, N., Michelmore, A. and Whittle,J.D. 2016. Furfuryl methacrylate plasma polymersfor biomedical applications. BioInterphases 11:031014.

Shirazi, H.S., Rogers, N., Michelmore, A. and Whittle, J.D. 2018. Particle aggregates formed during furfuryl methacrylate plasma polymerisation affect human mesenchymal stem cell behaviour. Colloids and Surfaces B: Biointerfaces, 161: 261-268.

Stead, S.O., Kireta, S., McInnes, S.J., Kette, F.D., Sivanathan, K.N., Kim, J., Cueto-Diaz, E.J., Cunin, F., Durand, J.O., Drogemuller, C.J. and Carroll, R.P. 2018. Murine and Non-Human Primate Dendritic Cell Targeting Nanoparticles for in vivo Generation of Regulatory T-Cells. ACS nano, 12(7): 6637-6647.

Stead, S.O., McInnes, S.J., Kireta, S., Rose, P.D., Jesudason, S., Rojas-Canales, D., Warther, D., Cunin, F., Durand, J.O., Drogemuller, C.J. and Carroll, R.P. 2018. Manipulating human dendritic cell phenotype and function with targeted porous silicon nanoparticles. Biomaterials, 155: 92-102.

Tan, L.Y., Mintoff, C., Johan, M.Z. and Ebert, B.W.,Fedele, C., Zhang, Y.F., Szeto, P., Sheppard, K.E.,McArthur, G.A., Foster-Smith, E., Ruszkiewicz, A.,Brown, M.P., Bonder, C.S., Shackleton, M. and Ebert,L.M. 2016. Desmoglein 2 promotes vasculogenicmimicry in melanoma and is associated with poorclinical outcome. Oncotarget 7(9): 46492-46508.

Tan, L.Y., Martini, C., Fridlender, Z.G., Bonder, C.S.,Brown, M.P. and Ebert, L.M. 2017. Control of immune cell entry through the tumour vasculature:the missing link in optimising melanomaimmunotherapy? Clinical & TranslationalImmunology 6(3): e134.

Thomas, H.M., Cowin, A.J. and Mills, S.J. 2017. Theimportance of pericytes in healing: wounds andother pathologies. International Journal of MolecularSciences 18(6): 1129.

Wunner, F.M., Bas, O., Saidy, N.T., Dalton, P.D., De-Juan-Pardo, E., and Hutmacher, D.W. 2017. Melt Electrospinning Writing of Three-dimensional Poly (e-caprolactone) Scaffolds with Controllable Morphologies for Tissue Engineering Applications. Journal of visualized experiments 130: e56289.

Wunner, F.M., Maartens, J., Bas, O., Gottschalk, K., De-Juan-Pardo, E. and Hutmacher, D.W. 2017. Electrospinning writing with molten poly (e-caprolactone) from different directions-examining the effects of gravity. Materials Letters, 216: 114-118

Wunner, F.M., Wille, M.L, Noonan, T.G., Bas, O., Dalton, P.D, De-Juan-Pardo, E. and Hutmacher, D.W. 2018. Melt Electrospinning Writing of Highly Ordered Large Volume Scaffold Architectures. Advanced Materials, 30(20): 1706570

Yang, G.N., Kopecki, Z. and Cowin, A.J. 2016. Role ofactin cytoskeleton in the regulation of epithelialcutaneous stem cells. Stem Cells and Development25(10): 749-59.

Yeo, G.C., Kondyurin, A., Kosobrodova, E., Weiss, A.S. and Bilek, M.M.M. 2017. A sterilizable, biocompatible, tropoelastin surface coating immobilised by energetic ion activation. J. R. Soc. Interface 14(127)

PRESENTATIONSAhangar, P., Hofma, B., Kirby, G., Smith, L., Mills, S. and Cowin, A. Delivery of multipotent stem cells using plasma-polymerised patch surfaces. ScarCon European Tissue Repair Society Congress, Amsterdam 2018

Al-Bataineh, S., Cavallaro, A., Ramiasa, M., Whittle, J. and Vasilev, K. Deposition of 2-oxazoline-based plasma coatings using atmospheric pressure DBD helium plasma jet. Gaseous Electronics Meeting XX, Townsville 2018

Barry, S. Unravelling the FoxP3 interactome in human Treg cells. Australasian Society of Immunology Conference, Wollongong 2014

Barry, S. Molecular identification of human FOXP3+Treg. China Tregs/TH Subsets Conference, Shanghai 2014

Barry, S. Tools for isolation, biomarkers of stable function and affordable manufacturing. Regional ISCT Meeting, Adelaide 2015

Barry, S. Immunotherapies. Australian Institute of Medical Scientists, 2017

Barry, S. Making immunotherapy simpler and cheaper to deliver using 3D lattices. Miltenyi Biotech Cell Therapy Day, Melbourne 2017

Barry, S. Melt electrospun 3D lattices for the clinical scale expansion of immunomodulatory cells including human regulatory T cells (Tregs). Eradicate Cancer, Melbourne 2018

Barry, S., Sadlon, T. and Bandara, V. New technology to deliver immunotherapies. Adelaide Society of Immunology-Day of Immunology: Using your immune system to fight cancer, Adelaide 2018

Barry, S., Sadlon, T. and Bandara, V. Validation of a novel CAR-T cell targeting non-functional P2X7. Eradicate Cancer, Melbourne 2018

Benveniste, G., et al. A novel low-fouling thin film technology for improved stent patency. VERVE Symposium, 2016

Bilek, M. Practical bioactive interfaces for biomedicine: recent advances towards translation to applications in biomedical implants and microarrays. 5th International Symposium of Surface and Interface of Biomaterials and the 24th Australasian Society for Biomaterials and Tissue Engineering, Sydney 2015

Burzava, A., et al. A low-fouling polymer coating combined with key biomolecules as an endothelial cell selective platform for stents. ASBTE Conference, 2017

Burzava, A., Griesser, H., Jasieniak, M., Bonder, C., Voelcker, N. and Moore, E. Selective capture of endothelial cells by CD34 grafted onto a low-fouling hyperbranched polyglycerol coating. Biointerfaces International, Zurich 2018

Burzava, A., Moore, E., Jasieniak, M., Cockshell, M., Harding, F., Voelcker, N., Bonder, C. and Griesser, H. A bioactive hyperbranched polyglycerol polymer coating as an endothelial cell selective platform for vascular implants. Australasian Society for Biomaterials and Tissue Engineering, Fremantle 2018

Chakraborty, A., Jasieniak, M., Moore, E. and Griesser, H. Glycidol plasma polymer: A platform for a covalent grafting of biomolecules. Australasian Society for Biomaterials and Tissue Engineering, Fremantle 2018

Cockshell, M., Moldenhauera, L., Dalilottojari, A., Harding, F., Voelcker, N. and Bonder, C. Rapid and large-scale expansion of human endothelial progenitor cells with therapeutic potential. ISCT Conference, Singapore 2016; Australian Vascular Biology Society Meeting, 2016

Dalilottojari, A., et al. Cell microarrays for the design of biomaterials to support human endothelial cell growth. 17th International Conference on Bionanotechnology, Biomaterials and Advanced Biomechanics, 2017

Delalat, B., et al. 3D printed lattices as an activation and expansion platform for T cell therapy. ASBTE Conference, 2017



Forget, A. Microwells as a screening platform for matrix interactions with cell spheroids. 5th International Symposium of Surface and Interface of Biomaterials and the 24th Australasian Society for Biomaterials and Tissue Engineering, Sydney 2015

Forget, A., et al. Rapid prototyping of microwells for the formation of cell spheroids and the study of ECM-cell interactions. TERMIS-AP, 2016

Forget, A., et al. Oxygen releasing plasma polymer sandwiches. ASBTE Conference, 2017

Harding, F., Delalat, B., Gumdsambuu, B., Mohandas, A., Hill, D., Walsh, J., Pederson, S., Grose, R., Krumbiegel, D., Couper, J., Brown, C., Sadlon, T., Hutmacher, D., Voelcker, N. and Barry, S. Scalable functionalised scaffolds for clinical expansion of human T cells. ISCT Conference, Singapore 2016

Ibrahim, J., Al-Bataineh, S., Michelmore, A. and Whittle, J. A diagnostic study of atmospheric pressure dielectric barrier discharge (DBD) helium and argon plasma by optical emission spectroscropy. Gaseous Electronics Meeting XX, Townsville 2018

Kirby, G., Vandenpoell, L., Pinxteren, J., Short, R., Michelmore, A. and Smith, L. Delivering a cell therapy. 21st International Society for Cell Therapy Conference, Las Vegas 2015

Kosobrodova, E. Immobilisation of tropoelastin on plasma immersion ion implanted polymer surfaces. 5th International Symposium of Surface and Interface of Biomaterials and the 24th Australasian Society for Biomaterials and Tissue Engineering, Sydney 2015

Kothari, S. Integrated solutions for affordable and accessible cell therapies. World Stem Cells & Regenerative Medicine Congress, London 2015

Kothari, S. Cell Therapy Down Under: Growing Australia’s cell therapy industry. 11th Phacilitate Cell & Gene Therapy Forum, Washington DC 2015

Kothari, S. Cell therapy in Australia. Regional ISCT Meeting, Adelaide 2015

Kothari, S. Opportunities and challenges in Australia. ISCT Conference, Singapore 2016

Kothari, S. Ritchie Centre Public Forum. Translational Research Facility, Monash Medical Centre, Clayton 2016

Kothari, S. Bench to bedside. Bellberry, HREC Education Weekend, Stem Cells, Manufacture and Commercialisation, 2016

Martin, L. Computer simulations of biometric peptides for immobilisation on plasma-activated surfaces. 5th International Symposium of Surface and Interface of Biomaterials and the 24th Australasian Society for Biomaterials and Tissue Engineering, Sydney 2015

Michelmore, A. Plasma polymers for biomedical devices: Fabrication of stable functionalised surfaces. Gaseous Electronics Meeting, Geelong 2016

Moore, E., Burzava, A., Cockshell, M., Benveniste, G., Voelcker, N. and Bonder, C. Antithrombotic polymer coating displaying pro-healing biomarkers for implantable vascular devices. South Australian Cardiovascular Research Showcase, Adelaide 2017; ASBTE Conference, 2017

Moore, E., et al. A smart surface approach to improving outcomes for patients with vascular devices. CCB presentation, Adelaide 2017

Moore, E., Burzava, A., Cockshell, M., Jasieniak, M., Griesser, H. and Bonder, C. Antifouling properties of HPG coated bare metal stents. Northern American Vascular Biology Organization’s Vascular Biology meeting, 2018

Myo Min, K., Parham, K. and Bonder, C. Revealing a critical cross-talk between beta islet cells and the vasculature in diabetes. 21st annual student meeting of the Australasian Society for Immunology SA/NT branch; Australian Society for Medical Research (ASMR) SA Annual Scientific Meeting, Adelaide 2015

Myo Min, K., Parham, K., Rojas-Canales, D., Penko, D., Drogemuller, C., Coates, PT. and Bonder, C. Revealing a critical cross-talk between beta islet cells and the vasculature in diabetes (poster). Joint IPITA-IXA-CTS (International pancreas and islet transplant association, International xenotransplantation association, Cell transplant society) Congress, Melbourne 2015

Ozsvar, J.and Weiss, A. Ozsvar, J.and Weiss, A. Computational modelling of tropoelastin interactions. Annual Meeting of Matrix Biology Society of Australia and New Zealand, Melbourne 2017

Ozsvar, J. and Weiss, A. Allysine in tropoelastin dynamics and assembly. 10th European Elastin Meeting, Nijmegen 2018

Ozsvar, J. and Weiss, A. Allysine in tropoelastin dynamics and assembly. 10th European Elastin Meeting, Nijmegen 2018

Palaniappan, C. Affordable cell therapies - FACT or FICTION! Affordable Cell Therapies - FACT or FICTION, Adelaide 2014

Penko, D., Rojas-Canales, D., Forget, A., Harding, F., Delalat, B., Waibel, M., Loudovaris, T., Blencowe, A., Drogemuller, C., Voelcker, N. and Coates, P. Covalently bound islet survival factors to tissue culture surfaces maintain their biological activity. International Pancreas and Islet Transplantation Association Congress, Melbourne 2015

Rasko, J. Cell and gene therapy; coming to terms with it all. 5th Malaysian Tissue Engineering and Regenerative Medicine Scientific Meeting, Malaysia 2014

Rasko, J. Stem Cell Research. Menzies Research Institute, 10th Annual Symposium, Hobart 2014

Rasko, J. Stem cells now and in the future - where are we on the road to translation? ARCS Scientific Congress, Sydney 2015

Rasko, J. and Macpherson, J. Down Under where? Overcoming the challenges of an international multicentre B-thalassemia major study of LentiGlobin BB305-gene-modified autologous CD34+ cells with centralised manufacturing. International Society for Cellulary Therapy 21st Annual Meeting, Las Vegas 2015

Rasko, J. and Macpherson, J. From bench to bedside: gene therapy for the beta-hemoglobinopathies. Australasian Gene & Cell Therapy Society 9th Scientific Conference, Melbourne 2015

Rasko, J. and Macpherson, J. Designing and validating an environmental monitoring program. International Society for Cellulary Therapy 21st Annual Meeting, Las Vegas 2015

Rojas-Canales, D., et al. NRG mice provide a stable and functional host for human islets in an allogeneic transplant model. Transplantation Society of Australia and New Zealand meeting, 2017

Rojas-Canales, D., et al. Novel PDMS microwell device protects islets from conventional shipping stress. IPITA Conference, 2017

Schiesser, J. Creation of immature Beta Cells from human pluripotent stem cells. 27th Stem Cell Network Workshop: Stem Cells and Diabetes Therapies, Sydney 2018

Short, R. Opportunities for material science in cell therapy manufacturing. Regional ISCT Meeting, Adelaide 2015

Short, R. Advanced materials in cell therapy. 11th Phacilitate Cell & Gene Therapy Forum, Washington DC 2015

Simula, A. New economy, new manufacturing. AusBiotech National Conference, Gold Coast 2014

Simula, A. Rapid development and translation of affordable cell therapies. 5th International Symposium of Surface and Interface of Biomaterials and the 24th Australasian Society for Biomaterials and Tissue Engineering, Sydney 2015

Simula, A. Managing the manufacturing costs of cell-based therapies - A tale of three surfaces. QEH Research Seminar Series, 2016

Simula, A. A ‘material’ improvement to COGS. Cell & Gene Therapy World Conference, Washington DC 2016

Simula, A. Improved COGS - A tale of three surfaces. World Stem Cells & Regenerative Medicine Congress, London 2016

Simula, A. Advanced surfaces: An alternative for more affordable and effective cell therapies. World Advanced Therapies & Regenerative Medicine Congress, 2017


CTM CRC researcher, Nick Rogers


Sivanathan, K., Manaph, N., Nitschke, J., Drogemuller, C., Zhou, X. and Coates, P. DNA demethylation agents promote pancreatic endodermal differentiation of Mesenchymal Stem Cells. 27th International Congress of The Transplantation Society, Madrid 2018

Stead, S. In vivo regulatory T-cell generation with dendritic cell targeting nanoparticles. The Transplantation Society of Australia and New Zealand 26th Annual Scientific Meeting, Melbourne 2018

Tan, L. When benign moles go bad. Three Minute Thesis Grand Final (University of South Australia), 2015

Tan, L., Brown, M., Thompson, E., Shackleton, M., Bonder, C. and Ebert, L. A critical role for desmoglein-2 in melanoma vasculogenic mimicry. Australasian Society for Immunology student retreat, 2015; Australian Society for Medical Research SA Annual Scientific Meeting, 2015; 22nd Australian Vascular Biology Society Annual Scientific Meeting, 2014; Adelaide Immunology Retreat - 10, 2014; Adelaide Protein Group Student Awards, 2016

Tan, L., Thompson, E., Sheppard, K., Mintoff, C., Shackleton, M., MacArthur, G., Ruszkiewicz, A., Brown, M., Bonder, C. and Ebert. L. A critical role for desmoglein-2 in melanoma vasculogenic mimicry. Adelaide Immunology Retreat (AIR-11); Barossa Cell Signaling Meeting 2015; Medical Research Week South Australian Scientific Meeting, ASMR 2016

Tan, L., et al. Role of vasculogenic mimicry vessels in mediating leukocyte recruitment to melanoma. ASMR Annual Meeting SA Branch, 2017

Thompson, E. The potential role of interleukin-3 (IL-3) in blood vessel development in breast cancer. Adelaide Immunology Retreat 10, 2014; 22nd Australian Vascular Biology Society Annual Scientific Meeting, 2014; Australian Society for Medical Research SA Annual Scientific Meeting, 2015

Thompson, E., Tvogorov, D., Khew-Goodall, Y., Lopez, A. and Bonder, C. A novel growth factor in breast cancer progression. Australian Society for Medical Research SA Annual Scientific Meeting, 2015

Thompson, E., Khew-Goodall, Y., Lindeman, G., Lopez, A. and Bonder, C. The potential role of interleukin-3 (IL-3) in blood vessel development in breast cancer. Barossa Cell Signaling Meeting 2015

Thompson, E., Khew-Goodall, Y., Lopez, A. and Bonder, C. The potential role of interleukin-3 (IL-3) in blood vessel development in breast cancer. Centre for Cancer Biology internal seminar series, 2016; ASMR Annual Meeting SA Branch, 2016

Thompson, E., Khew-Goodall, Y., Lopez, A. and Bonder, C. A role for interleukin-3 (IL-3) in breast cancer progression. University of South Australia 4th school of Pharmacy and Medical Sciences seminar

Thomas, H., et al. Flightless I regulation of pericyte function in diabetic wound healing. ASMR Annual Meeting SA Branch, 2017

Thomas, H., et al. Flightless I regulates pericytes action on angiogenesis and inflammation during chronic wound healing. AWTRS, 2017

Thomas, H., Hoffman, B., Strudwick, X., Mills, S. and Cowin, A. Flightless 1 regulation of pericyte function in diabetic wounds. ScarCon European Tissue Repair Society Congress, Amsterdam 2018; International Vascular Biology Meeting, Helsinki 2018

Thompson, E., et al. Understanding the molecular mechanisms underpinning tumour vascularisation in breast cancer. ASMR Annual Meeting SA Branch 2017

Thompson, E., Duluc, C., Farshid, G., Khew-Goodall, Y., Lopez, A. and Bonder, C. The potential role of interleukin-3 (IL-3) in blood vessel development in breast cancer. 8th Centre for Cancer Biology meeting - Cell Signalling in Cancer Medicine, Barossa Valley, 2017

Weiss, A. Molecular positioning of nature’s elastic assembly modules to build complex multi-dimensional vascular and microvascular structures. 5th International Symposium of Surface and Interface of Biomaterials and the 24th Australasian Society for Biomaterials and Tissue Engineering, Sydney 2015

Wunner, F., et al. Melt electrospinning writing of well-ordered multi-layered poly (e-caprolactone) scaffolds by implementing a dynamic control over the electrostatic forces. ASBTE Conference, 2017

Yang, G. Regulation of epidermal stem cells by Flightless I protein during wound repair. European Tissue Repair Society - (T)issues of War & Peace, Brussels, 2017

Yang, G. Regulation of epidermal stem cells by Flightless I protein during wound repair. German Stem Cell Network, Jena 2017

Yang, G., et al. Flightless I regulates proliferation of cutaneous epithelial stem cells during wound repair. AWTRS, 2017

Yang, G., et al. Regulation of epidermal stem cells by Flightless I protein during wound repair. SMAR SA Branch Meeting, 2017


PhD students, Hannah Thomas & Hanieh Safizadeh

CTM CRC provided scholarships to twenty-one PhD students and five Honours students enrolled at universities in three states.

From its first enrolments, CTM CRC invested in producing 'industry-ready' PhD graduates, courtesy of its flagship entrepreneurial PhD (ePhD) Program. Developed and delivered by CTM CRC staff and invited industry experts, ePhD training focused on creating an industry-ready workforce possessing valuable transferrable skills, an understanding of research translation and commercialisation, and an entrepreneurial mindset. Students attended four in-residence sessions, each of three to four days duration.

Commercialising BiotechnologyIn this module, students gained an awareness of the key issues and risks in the commercialisation of biotech inventions. Industry experts shared their perspectives on various stages of the path to market, including university technology transfer, the patenting process, product development, regulatory pathways, financing of startups, and licensing and partnering. Students were also made aware of the specific challenges faced by the cell therapy sector, including cost of manufacturing, the supply chain and re-imbursement.

Biotechnology Enterprise and Entrepreneurship (BEE)BEE focussed on cultivating entrepreneurial and enterprising researchers, learning from the successes and failures of healthcare startups. Students analysed the environment in which healthcare businesses operate and the key external forces that influence business models. They designed

a compelling story or pitch to communicate the value of a business model idea, and learnt about the different ways to raise money to finance a new venture. Guest speakers with real-world experience as innovators and entrepreneurs, including researcher-inventors, CEOs and venture capitalists, joined us to help connect students to the broader entrepreneurial community.

PhDs@work – a mini MBAPhDs@work focussed on the employable business skills that industry seeks in new employees. Students explored preferred learning styles, group dynamics and effective teamwork, the concept of emotional intelligence, and different leadership styles and models. There were also introductions to project management and financial management (making sense of the balance sheet and profit & loss statement). Finally, students were taught about the importance of personal brand and how to build and maintain a professional network.

Science Communication and EngagementIn this module students developed their confidence for public speaking, and were provided with the tools to make their presentations more engaging, entertaining and informative. With respect to writing, students were coached in writing science in plain English, in order to engage with a broad audience. Finally, students learnt how to build their profiles on various social media platforms, how to develop a social media communications strategy, and how to use various content types for effective communication on the web.

Twenty-three university staff were involved in supervising postgraduate students, along with 13 non-university staff who contributed an end user perspective to projects.

Students were included in other CTM CRC-led professional and social opportunities to increase face-to-face engagement, enhance linkages to CTM CRC Participants, and develop professional networks. In addition, CTM CRC’s links with industry organisations enabled various external training opportunities for our students, including:

� Participation in 'Summer by Design', an international two-week workshop hosted in Toronto by the Centre for Commercialization of Regenerative Medicine (CCRM) and the Rotman School of Management

� Internships at CCRM in Toronto in September 2018 and Cell Therapies Ltd in Melbourne in February 2019

� Participation by two PhD students in the CCRM Australia/IMNIS Regenerative Medicine International Mentoring Program

Of the ePhD Program, a CTM CRC PhD graduate, Lewis Martin of the University of Sydney, typified the positive response by saying: “I’ve learnt to think more strategically about my work and to plan from an early stage how the outputs of my project can be translated to real world situations and

deliver benefits to patients. I’ve also been exposed to professionals and executives from biotechnology and a host of supporting professions, and that has been really useful in thinking about future careers.”

As of 31 December 2018, three PhD students had graduated and progressed to careers in research or industry.

Bridging the gap between industry and researchers, and identifying and addressing skills gaps in the emerging industry of cell therapies, have been important facets of CTM CRC’s broader training programs. For SMEs and larger end user organisations, CTM CRC developed a series of training modules in cell therapy development, manufacturing and regulation in conjunction with SeerPharma Pty Ltd.

CTM CRC has also developed and incorporated lectures and practicals in cell therapies and bioprocessing into courses run by Flinders University (BSc and MSc in Biotechnology), delivered to over fifty students, and this will continue in 2019. Collectively, the ePhD and industry training programs foster the commercialisation and growth of Australia’s

expanding biomedical and cell therapy industries.

I’ve learnt to think more strategically about my work and plan from an early stage how my project outputs can be translated to real world situations and deliver benefits to patients. I’ve also been exposed to professionals and executives from biotechnology; this has been really useful in thinking about future careers.Lewis Martin CTM CRC PhD Graduate

05

EDUCATION & TRAINING


Dr Lih Yin Tan CTM CRC PhD Graduate

CASE STUDY01

CASE STUDY

04DR LIH TAN - CTM CRC PHD GRADUATE

DR Lih Yin Tan attended high school in Malaysia before coming to Australia to study Biomedical Science at the University

of Adelaide where she attained Bachelors and Honours degrees. Lih then worked as a Research Assistant at the Centre for Cancer Biology for one year, before undertaking a PhD at the University of South Australia in CTM CRC Project 1-04 “Endothelial Progenitor Cells Expansion Surfaces”. Lih received from CTM CRC a top-up scholarship of $8,000 p.a. plus operating funds of $25,000 p.a. to support her research.

In her PhD project, Lih studied the process in melanoma tumours of vasculogenic mimicry (VM), which is a phenomenon where cancer cells acquire the ability to form vessel-like structures behind which they can hide from the body’s immune cells. With collaborators in Melbourne, Lih identified that blocking an adhesion protein called DSG2 disrupts melanoma cell-cell adhesion and VM, and ultimately slows tumour growth. This mechanism of action can thus be exploited in new cancer treatments that enhance the body’s own immune response to kill cancer cells.

To supplement her technical training, Lih completed CTM CRC’s ePhD training modules covering biotechnology translation and commercialisation, entrepreneurism, business skills, and scientific communication and engagement. She put the last of these into practice most effectively when she gave a presentation in 2016 at the UniSA Three Minute Thesis Competition entitled Mission Immune Impossible. Lih won the People’s Choice Award, as voted by the audience.

Since completing her PhD in 2018, Lih has been employed as a Research Associate at UniSA where she now works on a project sponsored by the biotechnology company Carina Biotech, a spinout of CTM CRC. Lih is using intravital microscopy, an extremely powerful tool that enables imaging of several biological processes to examine post-infusion the distribution of CAR-T cells and how

they interact with tumour cells. CAR T-cell therapy is a new form of immunotherapy that uses specially altered T cells to directly and precisely target cancer cells.

“Undertaking a PhD in research has equipped me with the skills to design and perform experiments to better understand how cancers behave. The ePhD program builds on this foundation and expands my knowledge beyond the lab and into the commercial reality of the industry. As part of this program, we learnt basics about company startups, how to read and write patents, techniques in studying and identifying opportunities in the market, and skills in how to pitch ideas to investors. We also had the opportunity to learn first-hand from entrepreneurs about their experience and insight in the industry. It gave me an appreciation of what steps, efforts, and motivations are required to turn an idea or finding into a publicly available product that can change or even save lives.

I am grateful for the ePhD program, as it has shown me

the big picture industry beyond the lab and how it translates and affects what happens in my day to day lab work.” Dr Lih Yin Tan.

Undertaking a PhD in research has equipped me with the skills to design and perform experiments to better understand how cancers behave. The ePhD program builds on this foundation and expands my knowledge beyond the lab and into the commercial reality of the industry. Dr Lih Yin Tan CTM CRC PhD Graduate


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