Cell Medica is a UK-based company developing cancer medicines in the area of “immunotherapy”. Immunotherapy involves enhancing or targeting the body’s immune system to recognise and fight various diseases. Immunotherapy has the potential to be transformational in the way certain cancers are treated. The Biomedical Catalyst grant will enable Cell Medica to run a clinical study in the UK to assess the safety and effectiveness of a targeted immunotherapy product in patients with certain types of leukaemia. Despite good responses to induction chemotherapy, approximately 50% of adult patients with leukaemia do not achieve durable responses and subsequently relapse. In patients over 60 years at the time of diagnosis, the prognosis is particularly poor and many do not live beyond 12 months. It is clear that safer and more effective cancer treatments are needed; Cell Medica’s immunotherapy product has the potential to be of significant benefit to these patients. Assuming successful completion of this study, Cell Medica will conduct further clinical studies to confirm the safety and anti-cancer activity of the immunotherapy product. Studies will be run in leukaemia and other types of cancer. These data can then be used to register the therapy in the UK and Europe – in addition to other territories such as the US - as an approved medicine, a step which will allow Cell Medica to provide this therapy commercially to patients in need, throughout the UK and other countries.

"The Northern Alliance Advanced Therapies Treatment Centre (NAATTC) is a group of NHS hospitals and services. NAATTC has a wide geographical reach across Scotland and the North of England and is responsible for the health care of 15 million NHS patients. Advanced therapies are becoming increasingly available with a growing number of companies developing them both in the UK and worldwide. They are based on the administration of gene- and cell-based products in specialities such as haematology, autoimmunity, hepatology, cardiology and ophthalmology. They are thought to be more effective than existing treatments and provide treatments for diseases where currently no effective therapy exists. However most are still in clinical trials. Advanced therapies present significant challenges to healthcare providers compared with existing treatments. Addressing these challenges in the NHS will require development and dissemination of new skills for nurses, doctors, hospital pharmacists, NHS managers, and commissioners such as NHS England and the clinical commissioning groups (CCGs). It will also require changes in the way treatment is delivered. The changes required in the NHS can only be properly implemented through partnership with the companies that are developing and providing advanced therapies to the NHS. Manufacturers will need assistance with clinical trials to ensure optimal trial design, effective recruitment into clinical trials, and long term follow up of outcomes. The manufacturing and distributing processes are complex and it is critical that these systems are integrated effectively with those within the NHS. The NAATTC already has considerable experience of delivering advanced therapies and clinical trials and will use this experience to work with manufacturers (and their supply chains) to significantly increase their capacity to deliver advanced therapies effectively, safely, and seamlessly to patients within the NHS. It will identify gaps in our existing provision and develop solutions to narrow and eliminate the gaps. It will share the best practice that it develops to other ATTCs and to other NHS organisations. The outcomes will be to deliver these promising therapies to NHS patients and to make the NHS a global leader in their delivery, creating health and wealth for the UK."

Cell Medica develops novel cellular immunotherapy products for treating cancer. These therapies rely on harnessing the human immune system to treat cancer and represent a significant advance over traditional chemotherapy because the immune cells are activated to attack the malignant cells and not the healthy cells of the body. This project is a collaboration between Cell Medica, a company founded in the UK in 2007, and the Cell and Gene Therapy Catapult (CGTC). It will support increased knowledge about the functionality of these products and how to manufacture them at an acceptable cost to ensure widespread availability within the UK healthcare system. The teams will also work on ways to measure how the cells act to kill cancer cells which will then inform us how to manufacture these products for maximal patient specific benefit. We will be working closely with regulatory bodies to understand requirements to supply multiple different products in parallel from the same facility, thereby reducing further reducing costs. The experience with this project will allow the training of two ‘Qualified Persons' who will become experts in the approval of products for use in humans.

Cell Medica and UCL Institute of Child Health Great Ormond Street Hospital for Children NHS Trust will undertake a Phase I/II clinical trial - ASPIRE (Adenovirus-Specific Paediatric Immune REconstitution). The study is designed to demonstrate the safety and efficacy of Cytovir ADV - Cell Medica’s adoptive cellular therapy for the treatment of adenovirus infections in paediatric patients following bone marrow transplant (allogeneic haematopoietic stem cell transplant or allo-HSCT). Adenovirus infections cause mortality in up to 30% of children in high risk patient populations following allo-HSCT and current antiviral drug therapies are of limited benefit. Adoptive cellular therapy has already shown promising results in preventing viral disease in patients receiving a bone marrow transplant Cell Medica will be study sponsor and will prepare their adenovirus specific T cell therapy products (Cytovir ADV) for patients being treated. Dr Waseem Qasim and Prof Bobby Gaspar of the UCL Institute of Child Health Great Ormond Street Hospital for Children NHS Trust are the study investigators.

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Delivery of tools to navigate the regen med uncertainties. VALUE has delivered tools for developers, manufactures and funders to understand regulatory requirements, supply chain logistics and reimbursement decision processes. It has also developed innovative models for investment and manufacturing. Progress of the regenerative medicine industry is currently hindered by a series of uncertainties. The VALUE consortium is a microcosm of the sector and over the past two years has gained an in-depth understanding of, and developed solutions to, many of the market barriers. These relate to uncertainties regarding the regulatory requirements, how regenerative medicines are adopted by the NHS and Bupa, the need for adequate levels of funding and the need to understand the impact of the costs associated with manufacturing and product supply. The VALUE Consortium has delivered the following tools and models: • PAS83 – legislation and guidance for developers • PAS84 – glossary of terms • PAS94 – Characterization of human cells for clinical applications • Navigation tools that aid the teaching and explanation of concepts and issues to the developers • Bupa has developed and adopted a clinical decision process for regenerative medicines that is also available for adoption by all medical insurers • Publication of a new ‘How To Why To Guides’ to increase awareness of the NHS adoption pathway for cell therapies • Recognition of the potential value of regenerative medicines on an additional major industry sector and the potential to raise new finance based on an innovative investment and business model • A computational model that predicts the cost, associate-risks and bottlenecks inherent in the CBMP development process. This facilitates the ‘’make or buy” decision for developers • A tool/algorithm to clarify supply chain requirements for all types of cell therapies • NHSBT has been able to develop a CMO business strategy to optimally serve the national and international regenerative medicine industry Quote • “Bringing together key opinion leaders from across the regenerative medicine value chain has been invaluable to understand the issues and constraints and so enable solutions to be developed within a real context” Cathy Prescott Biolatris • “Having the first ATMP approval makes market adoption challenging. The outputs from VALUE will empower other players in the RM industry to make it too” James Blann TiGenix

Cell Medica, develops, manufactures and provides cellular immunotherapy products for the treatment of infectious disease and cancer. Cell Medica Ltd collaborated with eXmoor Pharma Concepts Ltd and University College London (UCL) on this project, with the aim of the development of a scaled-up manufacturing process for production of virus specific T cell therapies. Cell Medica’s lead product is Cytovir CMV, a T cell therapy targeting Cytomegalovirus (CMV) in patients who have undergone bone marrow transplants or allogeneic haematopoietic stem cell transplants (allo-HSCT). The project developed new cell processing methods and achieved step change improvements in the key production parameters of cost, time, quality and flexibility. A modular closed cell processing system was developed and manufacturing costs savings were identified. An advanced manufacturing system was designed and successfully prototyped. A transition plan and supporting documentation is in place to enable Cell Medica to operate within a facility that will support production targets of 5,000+ cell products per annum. eXmoor Pharma Concepts have gained insight and understanding into individualised cellular therapy manufacturing issues and this will allow their support of the development of processes by other groups in the UK and hence the consulting activities of eXmoor. UCL were able evaluate selection of target cells from mobilised aphaeresis, evaluate alternative cell selection targets and develop identity and potency assays, forming a significant part of the UCL researcher’s PhD.