CTM CRC The CRC for Cell Therapy Manufacturing (CTM CRC) is a $60M collaboration between industry, academia and health providers Vision: To increase the accessibility, affordability and efficacy of cell therapies Mission: CTM CRC’s mission is to ensure more efficient and cost-effective cell isolation, expansion and delivery by: Developing novel technologies that integrate smart materials and interfaces for improved cell processes Facilitating the pilot scale-up and translation of technologies

CTM CRC Capabilities Technology Applications Manipulate cellular behaviour through interaction with functionalised surfaces Development and optimisation of advanced surfaces and analysis Biomaterials design Bioanalytical expertise Regulatory expertise Preclinical experience Pilot-scale expansion and manufacturing Adult progenitor cell expansion – Functionalised surfaces for more efficient large-scale expansion of cells, such as MSCs Controlled delivery of ancillary reagents – Specialised surfaces for more efficient supply of critical and expensive reagents for cell growth Topical delivery of adult progenitor cells – Surfaces that allow targeted delivery of cell therapies to specific sites of action for improved efficacy Antifouling surfaces – Reducing incidence of thrombosis and restenosis of vascular/coronary stents Pluripotent stem cells – Surfaces to promote expansion and targeted differentiation of cells, such as iPS cells T cells – Activation, expansion and delivery

Development Themes CTM CRC Materials & Interfaces Cellular Immunotherapies Pilot Manufacturing Addresses the efficacy, manufacturing and delivery challenges facing the T cell therapy industry Cheaper and more practical cell isolation, expansion and delivery technologies, through the use of smart materials and functionalised surfaces Scale-up of surface-functionalisation and cell expansion capabilities for proof-of-concept studies and rapid translation of technologies

Biomaterials Plasma treatment (chemical coating) Electrospun scaffolds Hydrophobic scaffolds Hydrogel scaffolds 3D Lattices Materials capabilities can be tailored to suit a range of expansion technologies and cell types: Adult progenitor cells T cells iPS cells

Topical Delivery of Progenitor Cells #2 Product concept: Delivering cells from a dressing adult progenitor cells PP treated surface medical grade backing Product concept is a simple one and very similar to Apligraf: Cells are seeded onto the plasma polymer coated medical grade dressing The cells and dressing are frozen and stored Frozen cell-based dressing is shipped to wound clinics and hospitals as an off-the-shelf product to treat a variety of wounds. Cells do not need to be expanded on the dressing, but simply seeded and then frozen. COGs for such a product can be maintained to under $1000 per treatment frozen and stored wound treatment PATENT PENDING

Antifouling & Cell-attracting Surfaces #3 Functionalised surfaces for improved vascular repair Improvement in performance of vascular stents by Reducing incidence of thrombosis/re-stenosis Increasing re-endothelialisation of vessel walls Patented process for coating bare metal stents Reduces fouling of stent struts Allows for functionalisation of stent with biomolecules to promote re-endothelialisation Ancillary materials can be a proportionally large component of COGs for allogeneic therapies. Growth factors and cytokines are routinely added and the cost at the required standard can be at least $1M/g Their use is very often sub-optimal; simply adding it to the medium at a specific concentration. As processes are scaled up the requirement for medium and therefore, these components, can become a large proportion of the cost of manufacture. Scale non-optimal process →inefficiency increases We know that many such bioactive molecules interact with the ECM and are delivered to the tissue in a spatio-temporal manner. We are trying to emulate this somewhat through the development of coated surfaces suitable for the correct delivery of GFs to cells. In most cases cells are attached to a surface or matrix so why not provide the factors on this surface? This approach is applicable to a large number of factors used to expand CTs (FGF2, VEGF, IL2) with spatially and temporally control and to a large number of cell types.

Cellular Immunotherapies T cell expansion- Novel material for the ex vivo expansion of T cells, designed to integrate into existing T cell expansion platforms Cancer target for CAR-T therapy –Specific cancer antigen as a potential CAR-T cell target for the treatment of solid tumours Tregs for immunomodulation – Expansion protocols for a more stable Treg phenotype Targeted delivery – Surfaces and gels to allow targeted delivery of cells to sites of action for improved efficacy and reduced dose Gene delivery – Devices and technologies to improve delivery of DNA/RNA into cells, for cell and gene therapies Ancillary materials can be a proportionally large component of COGs for allogeneic therapies. Growth factors and cytokines are routinely added and the cost at the required standard can be at least $1M/g Their use is very often sub-optimal; simply adding it to the medium at a specific concentration. As processes are scaled up the requirement for medium and therefore, these components, can become a large proportion of the cost of manufacture. Scale non-optimal process →inefficiency increases We know that many such bioactive molecules interact with the ECM and are delivered to the tissue in a spatio-temporal manner. We are trying to emulate this somewhat through the development of coated surfaces suitable for the correct delivery of GFs to cells. In most cases cells are attached to a surface or matrix so why not provide the factors on this surface? This approach is applicable to a large number of factors used to expand CTs (FGF2, VEGF, IL2) with spatially and temporally control and to a large number of cell types.

Cellular Immunotherapies #4 CTM CRC capabilities utilised across immunotherapy manufacturing Novel CAR-T cell target PATENT PENDING Leukapheresis 1 Selection & Activation 2 Gene Transfer 3 Cell Expansion 4 Delivery 5 3D lattice for T-cell activation High efficiency (>90%) T-cell transformation methods which can be automated 3D lattice for T-cell expansion which matches or exceeds magnetic bead performance & suitable for automation Phase-shifting gel for delivery of CAR-T to tumour resection sites PATENT PENDING

Pilot Manufacturing TekCyteTM TekCyteTM is a CTM CRC translational and pilot-scale manufacturing facility to facilitate new technology development and translation into the clinic Validation of lab-based technologies at a larger scale, prior to more expensive product development and commercial scale-up More accurate modelling and comparison of impact on manufacturing costs Critical infrastructure to deliver specialist training in cGMP manufacturing of advanced therapies to private- and public-sector organisations 71% 79% Ancillary materials can be a proportionally large component of COGs for allogeneic therapies. Growth factors and cytokines are routinely added and the cost at the required standard can be at least $1M/g Their use is very often sub-optimal; simply adding it to the medium at a specific concentration. As processes are scaled up the requirement for medium and therefore, these components, can become a large proportion of the cost of manufacture. Scale non-optimal process →inefficiency increases We know that many such bioactive molecules interact with the ECM and are delivered to the tissue in a spatio-temporal manner. We are trying to emulate this somewhat through the development of coated surfaces suitable for the correct delivery of GFs to cells. In most cases cells are attached to a surface or matrix so why not provide the factors on this surface? This approach is applicable to a large number of factors used to expand CTs (FGF2, VEGF, IL2) with spatially and temporally control and to a large number of cell types. 86% 97%

Pilot Manufacturing TekCyteTM Systems to test CTM CRC technologies Dedicated cleanroom suite including two Grade B cGMP-standard manufacturing suites Designed to meet international standard ISO 14644 and follow the PIC/S guide to GMP of medicinal products, Annex 1 Separate AHU supply allowing for two simultaneous manufacturing activities Transparent glass wall and AV facilities provide view into clean room for training purposes 71% 79% Ancillary materials can be a proportionally large component of COGs for allogeneic therapies. Growth factors and cytokines are routinely added and the cost at the required standard can be at least $1M/g Their use is very often sub-optimal; simply adding it to the medium at a specific concentration. As processes are scaled up the requirement for medium and therefore, these components, can become a large proportion of the cost of manufacture. Scale non-optimal process →inefficiency increases We know that many such bioactive molecules interact with the ECM and are delivered to the tissue in a spatio-temporal manner. We are trying to emulate this somewhat through the development of coated surfaces suitable for the correct delivery of GFs to cells. In most cases cells are attached to a surface or matrix so why not provide the factors on this surface? This approach is applicable to a large number of factors used to expand CTs (FGF2, VEGF, IL2) with spatially and temporally control and to a large number of cell types. 86% 97%

Contact CTM CRC T +61 8 8302 3503 E info@ctmcrc.com