Professor Ivan Wall has been appointed as Professor of Regenerative Medicine with the Institute of Immunology and Immunotherapy at BHP founder-member the University of Birmingham.

Professor Wall joins us from Aston University and has a well-established relationship with the University of Birmingham as the Lead for the Centre for Advanced Therapies Manufacturing Training. His research group works on stem cells and extracellular vesicles, with emphasis on industrial translation and scale up production – his ambition is to see Birmingham become a hub manufacturing cell and gene therapies that local patients can benefit from.

To mark Professor Wall’s latest appointment with the University, the Institute of Immunology and Immunotherapy sat down with him to learn more about his background and expertise:

What research and industry work do you currently undertake?

My academic research spans stem cells, tissue engineering and bioprocessing. I am particularly interested in the role of mesenchymal stem cells in regenerative medicine, both via direct differentiation towards regenerative cell types but also via their secretion of paracrine signalling vehicles such as exosomes. Exosomes enable cells to communicate with each other and current research points to stem cell-secreted exosomes as important cues for regeneration of injured tissues. My research team has created novel cell lines, demonstrated scalable production and examined cell stimulation methods to enhance potency. Outside of academia I have co-founded two companies: FourPlus Immersive, which creates virtual reality training simulations for GMP cell and gene therapy manufacturing; and Quest Meat. Both companies are based in Birmingham.

What made you become interested in regenerative medicine?

I undertook a PhD in wound healing and my early research focussed on understanding why some wounds in aged or diabetic patients do not heal very well. This spurred an interest in how stem cells are the building blocks for tissue and organ formation, with the aim of understanding how stem cells might be used to drive regeneration of aged or injured tissues. In 2009 I became a lecturer at UCL, working in regenerative medicine bioprocessing, which enabled me to bring together my interest in working with stem cells to treat disease with industrialisation strategies to scale up production for clinical applications.

What is Quest Meat and how did you come about co-founding this organisation?

Quest Meat is a startup that is creating cultivated meat. I co-founded this company with Dr Petra Hanga (now UCL) and former board members of a UK regenerative medicine company and we are based here in Birmingham. We have been able to take our knowledge of scaling up stem cells for medicine and apply it to future meat production. We are doing this because global food production in its current form is not sustainable and, with a growing global population and climate change creating pressure on existing food systems, we need a radical new approach to food production. As a parent I want my children to eat nutritious food that has not been intensively farmed, used antibiotics that may cause health problems, or will accelerate environmental damage. As a scientist and CEO of Quest, I can work with a brilliant team to create a healthy and sustainable alternative.

What are the opportunities and challenges facing future cell and gene therapies?

Cell and gene therapies are transforming healthcare and we are now seeing some truly remarkable treatments emerging that are curing patients of rare and life-threatening diseases, including rare forms of cancer that have not responded to conventional treatments.

Even though these medicines are still in their early days, the rate of development of new treatments means they are becoming more and more prevalent in hospitals and so over time more patients will benefit from them. The main challenge is in being able to manufacture them consistently and affordably, especially as some manufacturing batches only treat a single patient. A second critical challenge is in training enough people to grow the workforce needed for this rapidly growing industry – there is a huge skills shortage. University of Birmingham is at the forefront of addressing these challenges, with the National Training Centre for Advanced Therapies Manufacturing and also excellent advanced therapy manufacturing cleanroom capabilities.

What key advice would you give to researchers considering scaling their research into industry?

Think about what manufacturing for your final product would look like early in the translation cycle. A lot of effort is required to manufacture medicines that will be administered to patients. For example, regulatory guidelines around good manufacturing practice (GMP) must be adhered to, to show that those manufacturing processes consistently deliver the required product quality. Everything from the cleanroom environment, manufacturing equipment, processes and personnel must be monitored and documented. Any changes to manufacturing later on will require re-validation which can cause significant delays to the product development cycle.

BHP founder-member the University of Birmingham has created a new spinout, Healome Therapeutics Ltd, to commercially deploy a platform that delivers a ‘pro-healing’ microenvironment for the leading causes of preventable blindness.

The company’s leading application will be in ocular surface diseases, which are notoriously challenging conditions to treat, and have progressively larger impacts on quality of life as the diseases run their course.

The Healome technology is a novel fluid-gel material that flows like a liquid, and self-structures into a thin, clear, protective layer over the surface of the eye which is gradually dispersed and cleared away by blinking over 2-8 hours (customisable depending on application).

The gel can be used alone, or as a ‘carrier molecule’ to deliver other therapeutics.

Studies have already shown that one of Healome’s formulations has anti-fibrotic (anti-scarring) activity and these healing properties are augmented by combining it with other therapeutics.

The technology was developed by a team led by Professor Liam Grover who is Director of the University’s Healthcare Technologies Institute (HTI).  It is envisaged that treatments developed from this platform will come in the form of clear degradable ‘ocular bandages’ that can be applied like normal eye drops.

Professor Grover, who is also a co-founder of Healome Therapeutics, commented: “There are many cutting edge drugs on the market or in development for diseases that affect the surface of the eye. One of the biggest challenges is to keep therapeutics on the surface of the eye for sufficient time for them to have an effect and more generally to regain or replace all the functions of the tear film.”

The company’s founding directors already have prior experience in commercialisation and advancing therapies towards Phase I-III clinical trials and include Professor Anthony Metcalfe, Industrial Professor of Wound Healing, formulation engineer Dr Richard Moakes, and Dr Richard Williams, whose work at the HTI involves translating healthcare technology concepts to finished products ready to enter clinical trials.

Although Healome will initially concentrate on Dry Eye Disease, in the long-term the company aims to partner with healthcare companies to co-develop new therapeutics for delivery to the surface of the eye.

The gels respond to shear stress, which allows it to change back and forth from a liquid to a soft-solid consistency according to the physical forces applied to it, such as extrusion from a container, or blinking.

Its mechanical and drug diffusion properties can be ‘tuned’ by physical rather than chemical changes to the base polymers.  These attributes mean that pre-clinical or early clinical safety studies for new formulations will not need to be repeated and will reduce the time and cost to bring new products to market.

CEO of Healome, Dr Richard Williams, commented: “Ocular surface diseases leading to Dry Eye have a disproportionately large impact on health, well-being and the ability to enjoy life. These conditions can also be very expensive for patients to manage. There are many unmet patient, clinical and industrial needs in this area, which Healome Therapeutics is well-placed to address. Pre-clinical safety of the platform is well-established, GMP manufacturing has been set up to supply planned phase 1 trials and we have brought in significant executive experience in eye care to accelerate plans.”

The researchers behind Healome have already raised £2.8m grant funding from the Medical Research Council (MRC) to progress the original concept from lab bench to completing phase 1 human trials. The developed platform and supply chain was then applied to help tackle challenges in ocular surface diseases via a £1.3m grant from the National Institute of Health and Care Research (NIHR) Invention for Innovation programme. The platform has also shown early promise in dermal and orthopaedic applications.

Healome Therapeutics has already raised £400k funding from Innovate UK and SFC Capital, and is now establishing its own laboratories at the Birmingham Research Park, which has been nurturing high-growth biomedical companies since 1986.

Phase I human trials to test the core technology in combination with therapeutics known to prevent corneal scarring and manage severe dry eye will commence in Q2 2022, supported by the University of Birmingham GMP manufacturing facility.