CTM CRC HOSTS IMMUNOTHERAPY EXPERT - PROFESSOR JENSENHighlights - ImpaCT Day & public lecture

SCINOGY JOINS CTM CRCAccelerating development of next-gen cell therapy manufacturing

ePhD GRADUATIONCTM CRC congratulates its first ePhD Programme graduates

ImpaCTCTM

CRC

May‘17

2| CTM CRC ImpaCT

THE last year has been one of transition, change and renewal. With the end of CTM CRC’s funding term looming in June 2019, we

forge ahead with a renewed focus on sustainability; to maximise our outputs and opportunities, leave behind a lasting legacy, and ensure that our excellence continues to thrive post-funding.

Two recommendations from the recent Miles Review were important factors in CTM CRC’s strategic focus moving forward:

� Putting industry ‘front and centre’, with a focus on solving problems

� No extension funding

CTM CRC has responded to discussions with key stakeholders from across the cell therapy landscape - large research consortia, key opinion leaders and industry experts – to identify opportunities and gaps and align these with CTM CRC’s strengths and capabilities to propose three major areas of focus.

Materials and InterfacesThis area contributes to improvement in expansion, formulation and delivery of ‘therapeutic’ cells. CTM CRC is ‘cell agnostic’ in its approach to reducing the cost of goods, providing a strategic advantage and focusing on industry-relevant cells. Our active programs with MSCs and iPSCs demonstrate a positive impact on efficiency and COGS through surface optimisation of existing process tools and/or immobilisation of expensive biomolecules.

Cellular ImmunotherapiesThere is currently a dominant focus on immunotherapy developments within the industry. Given the almost singular focus of many large pharma in this area, it is evident that the market is ready and eager for novel developments and

further cell therapy offerings in this space. CTM CRC has recently formed its first spin out company, Carina Biotech Pty Ltd, to further develop and commercialise CTM CRC’s suite of complementary cellular immunotherapy technologies. These range from a new Chimeric Antigen Receptor (CAR) T cell to target solid tumours to a novel T cell expansion platform.

Pilot Manufacturing & TrainingCTM CRC has established a new translational facility, TekCyte, that will facilitate demonstration of scalability and regulatory compliance for products and devices as they progress toward human clinical testing. In response to industry feedback, TekCyte will also function as a training facility to address the predicted shortage in appropriately qualified personnel for the cell therapy industry.

This renewed focus and targeted approach allows for overlap in platform technologies, therapeutic applications and commercial objectives and provides CTM CRC with a strong foundation for solution-driven industry collaborations. With a fast maturing cell and gene therapy industry and unprecedented clinical success, there has never been a better time to focus on the commercial feasibility and viability of products. CTM CRC’s innovative approach to using materials and surface functionalisation technologies is proving to be a valuable asset to help realise CTM CRC’s vision to make cell therapies more affordable and accessible.

CTM CRC held its 2017 ImpaCT Day in February at the Adelaide Convention Centre. The theme for this year was translation and

scale up, with guest presentations by Professor Michael Jensen, Seattle Children’s Research Institute and David James, Scinogy Ltd.

Professor Jensen, a pioneer of cellular immunotherapies for paediatric cancers, presented the day's keynote lecture, sharing his research group's ground breaking work translating chimeric antigen receptor (CAR) T cell therapy into the clinic for the treatment of childhood leukaemia.

Following Professor Jensen’s presentation, David James provided an interesting perspective on scale-up challenges for cell manufacture and the impact of automation on driving down cost and improving accessibility.

The day culminated in a fun, interactive session addressing philosophical debates on the cell therapy industry as a whole. Questions provoked discussion on issues such as affordability, accessibility, and whether cell therapies should be the preserve of the ‘young’ and/or ‘wealthy’. The adjudicator panel comprised Professor Jensen, David James and Dr Stephen Livesey and the winning team successfully argued that cell therapies should only be available to the young. Fortunately, the adjudication focused only on how persuasive teams were, rather than topic content.

Professor Jensen was in Adelaide at the invitation of CTM CRC and Carina Biotech to participate in a week long program of events. This included a public lecture ‘No chemo. No radiation. No

childhood cancer,’ sponsored by TechInSA at the Science Exchange, and various fund-raising events and networking meetings to raise awareness of CAR-T cell therapies and discuss opportunities for collaboration. During a meeting with the Hon. Jay Weatherill MP, Premier for South Australia, Professor Jensen was able to illustrate the potential role South Australia could play in the advancement of CAR-T therapies for the treatment of paediatric cancers.

CTM CRC and Carina acknowledge the support and hospitality provided by Team Kids and the Women’s and Children’s Hospital in organising satellite meetings and events around South Australia during Professor Jensen’s visit.

Professor Jensen presenting at ‘No chemo. No radiation. No childhood cancer’ public lecture

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MESSAGE FROM THE CEOCTM CRC’s evolving strategy

CTM CRC HOSTS IMMUNOTHERAPY EXPERT - PROFESSOR JENSENHighlights - ImpaCT Day & public lecture

highlights

4| CTM CRC ImpaCT

ADVANCED therapy manufacturing technology and scale-up specialist, Scinogy has joined CTM CRC.

The addition of Scinogy’s experience in manufacturing systems for cell therapy, complements CTM CRC’s expertise in surface functionalisation and new materials technologies. This powerful combination of capabilities will better address current manufacturing challenges, such as scalability and cost.

“With the clinical progress and rapid growth in advanced therapies, the time is right to address the challenges facing commercial success. As processes for the manufacture of these products are locked in at a very early stage of development, early adoption of technologies that are scalable, reproducible, transferable and commercially viable is critically important. Integration of CTM CRC’s surface optimisation with Scinogy’s automated closed systems will provide a powerful tool towards more cost effective and scalable approaches to manufacturing.” Dr Sherry Kothari, CEO of CTM CRC, said.

Advanced therapy companies must have confidence in their clinical data and products. Process integrity ensures that the same process has been performed for every patient, every batch, every site, every time.

“The combination of Scinogy’s expertise in the development of closed, automated manufacturing systems and single-use kits, in addition to CTM CRC’s surface functionalisation capabilities provides an ideal opportunity to create next-gen manufacturing processes that are reproducible, scalable and cost effective from the outset.”Mr David James, CEO of ScinogyThe collaboration between the two companies will begin with a focus on T cells, initially tailored to simplify chimeric antigen receptor (CAR) T cell manufacture, currently of interest in the field for the development of immunotherapies for the treatment of cancer. A significant advantage of the collaboration is that both companies are developing platform technologies, which can be adapted to provide flexible, configurable systems, tailored to suit different processes for a range of cell types.

This is an exciting time for the industry and the CTM CRC/Scinogy partnership dovetails with CTM CRC’s new translational facility, TekCyte, for the seamless and efficient scale-up of manufacturing processes from the lab to commercial scale. This also provides an opportunity to establish a unique cell therapy capability in Australia.

CTM CRC continues to expand its collaborative base and strengthen its capability portfolio and it is ideally positioned to address the

manufacturing challenges facing the rapidly growing cell therapy industry.

Exciting technologies CTM CRC has created and is continuing to develop include:

� A coated wound dressing to deliver pluripotent stem cells that promote rapid wound healing

� Advanced surfaces that significantly reduce the quantity of expensive reagents, and therefore cost, when expanding therapeutic cells

� An antithrombotic coating that reduces the risk of stent failure and the need for repeat surgery

� Lattices for the activation and efficient expansion of T cells for the treatment of cancer and immune-related conditions

� Novel gel-formulations for the targeted delivery of cellular immunotherapies

CTM CRC is now in discussions with companies interested in further development and potential commercialisation of the above technologies. This interest from industry is a resounding endorsement of CTM CRC’s novel use of materials and surface chemistry interventions to optimise manufacturing processes and tools for the cell therapy industry.

CTM CRC’s newly established translational facility, TekCyte™, provides the necessary infrastructure to facilitate the translation and scale up of its technologies in order to deliver commercially feasible advancements. TekCyte™ includes cleanrooms for cell expansion, equipped with

a range of pilot-scale equipment for both the manufacture of advanced coated materials and their testing in a range of pilot-scale cell expansion bioreactors.

With strong demand from cell therapy tools providers looking to create out-of-the-box solutions for manufacturing challenges, the establishment of TekCyte™ ideally positions CTM CRC to offer its expertise to the industry in the form of contract research and development. TekCyte™ will also provide training to cell therapy companies and research organisations in cell processing, including hands-on training in various cell expansion platforms, quality control and cGMP manufacture. Various TekCyte™ training and education programs will also be progressively offered online.

The TekCyte™ initiative represents a very exciting time for the cell therapy industry in Australia and provides an opportunity to make a significant impact on the manufacture and delivery of next generation advanced therapeutics for intractable diseases.

Concept drawing of Scinogy’s ‘Proteus’

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SCINOGY JOINS CTM CRCAccelerating development of next-gen cell therapy manufacturing

NEW TRANSLATIONAL FACILITYCommercialisation update & newly established TekCyte™ facility

highlights

CTM CRC’s first cohort of students were presented with their completion certificates for the ePhD programme in February 2017,

two years after it was launched. The programme, designed to equip students with entrepreneurial and business skills to better prepare them for careers in industry, has been very well received. Presenting the certificates, Dr Leanna Read, CTM CRC Chair and and Chief Scientist of South Australia, commented, “This is exactly the type of training that all PhD students should have, regardless of their future directions. Entrepreneurial thinking underpins innovation in any technology-related career." The core of the ePhD Program is a series of four multi-day residential training modules delivered over two years focussing on the most important transferable skills sought by industry.

The inaugural module, held in April 2015, introduced students to the process for turning a biomedical invention into a successful commercial product. Subsequent modules covered entrepreneurship, business skills, effective communication, building and maintaining a professional network, using social media to build a profile, and individual development plans for career advancement. The courses, a combination of lectures, case studies and workshop exercises, were delivered by members of the CTM CRC team as well as guest speakers from the biotech and business communities. Lewis Martin, one of CTM CRC’s ePhD graduates from the University of Sydney spoke about the benefits of the ePhD program.

“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.”Lewis Martin, ePhD graduate“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."

CTM CRC congratulates its class of 2017:Adel Dalilottojari, University of South AustraliaKristen Malatesta, University of AdelaideLewis Martin, University of SydneyHanieh Shirazi, University of South AustraliaSebastien Stead, University of AdelaideLih Tan, University of South AustraliaHannah Thomas, University of South AustraliaEmma Thompson, University of South AustraliaFelix Wunner, Queensland University of Technology

6| CTM CRC ImpaCT

IN June 2016, CTM CRC incorporated

its first spin-out company, Carina Biotech.

Carina aims to develop technologies that expand the application of chimeric antigen receptor (CAR) T cell therapies, making them more affordable and more effective against a broad range of cancers. Carina’s work will focus on new solid tumour targeting CAR-T cell technologies as well as T-cell manufacturing and delivery technologies.

Led by founding CEO, Dr Justin Coombs, Carina has already been successful in:

� Securing seed funding from TechInSA

� Being a key partner of Team Kids in their philanthropic fundraising efforts for CAR-T research

� Establishing collaborative relationships with national and international CAR-T industry players including the Jensen laboratory at Seattle Children’s Research Institute, who are world leaders in the development and clinical trials of CAR-T therapies

ANTITHROMBOTIC STENTAdvanced coating for coronary stents

HEALTHCARE costs associated with cardiovascular disease in Australia were estimated at $12bn in 2013 and are

expected to double by 2033. Approximately 26,000 stents are deployed annually in Australia to treat vascular occlusions. Bare metal stents (BMS) are the most common form of stent used. Despite recent technology developments, costs to healthcare remain high due to continuing issues with thrombosis and re-stenosis.

CTM CRC has developed and patented a unique coating with excellent antifouling and antithrombotic properties and potential to improve the performance of BMS.

The technology allows for further functionalisation of the antithrombotic stent surface to create a coating capable of attracting endothelial cells that will promote repair of the vascular cell wall, to reduce re-stenosis.

CTM CRC is collaborating with a major manufacturer and supplier of commercial stents to evaluate the promising data generated to date.

ePHD GRADUATIONCTM CRC congratulates its first ePhD Programme graduates

Antithrombotic properties show dramatic reduction in clot formation (Using in vitro model of blood flow through a stent, using the Chandler Loop)

carina b i o t e c h

A CELL THERAPY CRC COMPANY

2017 ePhD Programme graduates

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CARINA BIOTECHCTM CRC creates its first spin-out company

highlights

Athersys, Inc.Cell Therapies Pty LtdQueensland University of TechnologyRoyal Prince Alfred HospitalThe Royal Adelaide Hospital - a division of Central Adelaide Local Health Network, Inc.St Vincent’s Institute of Medical ResearchSA Pathology - a division of Central Adelaide Local Health Network, Inc.

Scinogy Pty LtdSouth Australian Health and Medical Research Institute (SAHMRI) LtdTerumo BCT, Inc.The University of AdelaideUniversity of South AustraliaUniversity of SydneyUniversity of Wollongong AustraliaWomen’s and Children’s Health Network Inc.

Participants

T +61 8 8302 3503info@ctmcrc.com ct

mcr

c.co

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EditorNatalie WatkinsMarketing & Communications Manager

Cell Therapy ManufacturingCooperative Research Centre

twitter.com/CTMCRCfacebook.com/ctm.crc linkedin.com/company/crc-for-cell-therapy-manufacturing

Level 5Catherine Helen Spence BldgUniSA, City West CampusADELAIDE, South AustraliaAUSTRALIA 5000

What is CTM CRC?The CRC for Cell Therapy Manufacturing (CTM CRC) is an international collaboration focused on the development of integrated solutions for cost effective, accessible cell therapies.

A $60M investment from CTM CRC’s participants and the Australian Government enables CTM CRC to connect cell biology with advanced materials in a unique approach to address the challenges in regenerative medicine today.

tailored entrepreneurial PhD

program creating industry-ready

graduates

cost-effective manufacture and

rapid translation of cell therapies into clinical

practice

international collaboration between

research providers, industry, hospitals and

charities