Introduction

Cellesce has sponsored 2 awards for “Science and Innovation” for pupils of Cardiff West Community High School.  The recipients were nominated by their teachers to recognise their diligence, application and enthusiasm for science during a very difficult year. The awards shine a spotlight on those pupils whose enquiring minds, desire for understanding and dedication to their work, align with Cellesce’s standards of excellence. We are very happy that the school has highlighted these individuals to celebrate their achievements and we congratulate them on their success.

The awards were presented at an “Evening of Celebration” on Thursday 7th July 2022.  Jason Mohammed, star of radio and television (and an alumnus of the school that was previously known as the Glyn Derw High School) gave an inspiring and motivational welcome speech. He used Mohammed Ali’s famous quote that includes the line “the will must be stronger than the skill” and encouraged the students to work hard towards their dreams.

Jason Mohammed, an alumnus of Cardiff West chs introduced the awards evening

Award winners

The inaugural winner of the Key Stage 3 award (ages 11-14) was Jana Deeb. Her teacher described her as “an extremely conscientious student who completes all her work to a high standard with extra work at home. Jana goes above and beyond in terms of the amount of effort she puts into her science classes. She never accepts anything at face value and always needs further detail and clarification”. Her achievement is even more impressive considering that English is not her first language.

The winner of the Key Stage 4 award (ages 14 – 16) was Cameron Marchant for his natural ability in science and hard work at school and at home. He was described as a high achiever who participated fully in the lessons.

Award winners of the Science and Innovation Award. From left to right are Cameron Marchant, Elizabeth Fraser (Alliance Manager, Cellesce), Jana Deeb, Trevor Dale (Professor at Cardiff University and Cellesce co-founder) and Science Teacher Esther Lewis.

There were many other prize winners for excellence in specific subjects, pastoral and community work, achievement in sport and the performance arts. Rhys Priestland, the Cardiff Blues and Wales rugby player was at the event to present the Admiral “CREATE YOUR WORLD” awards.

A picture of the award winners and presenters outside Cardiff West Community High School. Head teacher Martin Hulland is fourth from the right and Deputy Head Natalie Richards, is third from the left.

Cellesce is committed to promoting and encouraging students to study the STEM disciplines of Science, Technology, Engineering and Mathematics, to help address the current skills shortage in these areas in the UK.

Cellesce is delighted to confirm that our first patent family (EP 3 481 942 B1) has been granted, and we expect this family to continue to grant globally (USA, China, Japan etc.). Two other patent families have been filed and are going through normal examination processes which we expect will lead to granted status. A fourth filing is imminent (Q1 2022).

The granted patent confirms Cellesce’s ownership of this unique organoid manufacturing process that works at both industrial scale and delivers the exceptionally high quality required for commercial organoid deployment.

Cellesce invests in research, and we expect to continue to invent and file patents. IP ownership continues to strengthen our position as the only global industrial producer of organoids.

Cellesce has announced the promotion of Vicky Marsh-Durban as the company’s first full time CEO. Vicky joined Cellesce in 2019 as Lead Scientist and was promoted to COO and the Board in Jan ’21. 
Victoria Marsh Durban
Vicky completed her Ph.D. at Cardiff University in 2008 in the field of cancer genetics. Subsequently she moved to University of California, San Francisco (UCSF), where she held a post-doctoral research scholarship investigating targeted therapeutic approaches in malignant melanomas. In 2014 she was enticed back to Cardiff to take up a Research Fellowship at the European Cancer Stem Cell Research Institute. In 2016 Vicky joined ReNeuron in her first commercial role, as Principal Investigator and Head of Cell Biology.
 
Vicky has played a vital role in helping the Company to make significant commercial and scientific progress despite the challenges of the CV-19 global pandemic and we are all excited that she will now take full responsibility for running the company as it enters the next phase of its development.
 
At the same time Paul Jenkins will be stepping down from the Board. Paul has made an invaluable contribution to Cellesce and the Board would like to place on record its thanks for all his hard work over the last 2 years. We are delighted that he will continue to support the Company in a consultancy capacity going forward.

Tim Watts has been appointed as an Independent Non-Executive Director of the Company.

Tim Watts

Tim has worked in the pharmaceutical and biotech sectors since 1990 with experience in both Big Pharma and public/private SMEs. From August 2018 to September 2021 he was initially CFO before latterly becoming CEO at AIM-listed Shield Therapeutics plc, a company focused on commercialising its innovative iron deficiency therapy. From 2012 to 2017 Tim was CFO of Oxford BioMedica plc , a world-leading cell and gene therapy company, when the management team grew the Group’s market capitalisation from £30 million to £330 million and laid the foundations for the business it is today. Prior to Oxford BioMedica, from 2007 to 2011 Tim was CFO of Archimedes Pharma, a private equity backed specialty pharma company, and before that from 1990 to 2007 he held a variety of increasingly senior roles at AstraZeneca, including Group Financial Controller from 2002 to 2006.

Since December 2017 Tim has been a non-executive director at Fusion Antibodies plc, an AIM-listed company specialising in providing pre-clinical antibody discovery, engineering and services for both therapeutic drug and diagnostic applications. He was also a director of the UK’s BioIndustry Association from 2013 to 2017.

Tim’s appointment follows the resignation of Professor Julian Chaudhuri from the board following his recent appointment as Pro-Vice-Chancellor (Education) at the University of Bath. Professor Chaudhuri, a founder of Cellesce will remain on Cellesce’s Scientific Advisory Board.

John Allbrook (Chairman of Cellesce) said:
“It is impossible to exaggerate the enormous contribution that Julian has made over the last eight years. One of the founders of Cellesce, I am pleased that we will continue to benefit from Julian’s experience and expertise on our Scientific Advisory Board. I am delighted to welcome Tim Watts to the Board. Tim’s industry knowledge and experience will be invaluable to Cellesce as we seek to establish the company as the market leading CDMO of organoids.”

Cellesce has carried out a study in collaboration with Cardiff University to assess organoid size and cell count from 3D image analysis. Whilst the improved predictive power of patient-derived organoids (PDOs) have the potential to replace 2D  assays in drug discovery the challenge for organoid users is to fully extract, exploit and understand the increased complexity of 3D in vitro models. 3D image analysis may well provide a means to address that challenge.

Many of the practical limitations have already been overcome by recent advances in microscopy, leading to improvements in 3D image resolution, speed of imaging, data acquisition and dedicated software for high-content, high throughput assays. This technology can be used to quantify changes in gross organoid morphology, such as size and shape and also detect subtle, cellular, drug-induced alterations. Multi-parametric, image-based analysis can lead to an understanding of the relationship between the morphology of 3D PDOs and the underlying cell biology Badder et al. 2020, PLOS ONE.

Comparison of the morphology of untreated and treated patient-derived colorectal cancer organoids

To find out more about this study please view the Application Note.

Dr Kate Rowley has been appointed as an Independent Non-Executive Director of the Company.

Kate is an Independent Consultant for Symmetrist and a Venture Partner at Global Bio Fund. She advises companies developing innovative science and technology with the potential to transform healthcare. Kate supports companies from across the UK, West Coast US and Australia and works with them on project, executive and non-executive roles as meets their needs.

Kate has a deep history of commercialisation of Life Sciences with experience in Investor, Founder and Non-Executive Director roles across a variety of businesses in med tech, digital health and drug discovery/development. She has more than 7 years’ experience of investing as an Investor Director working at IP Group and then Bioscience Managers, where she led the team supporting Downing with their EIS/VCT investments. Prior to this Kate held a number of commercially focussed roles at Quotient Clinical (now Quotient Sciences) Nexxus, the West of Scotland Bioscience Network and SAMS.

Vicky Marsh-Durban has been promoted to the position of Chief Operating Officer and will take a seat on the Board.

Vicky completed her Ph.D. at Cardiff University in 2008 in the field of cancer genetics with a focus on models of gastrointestinal tract cancers. She subsequently moved to the University of California, San Francisco (UCSF) where she held a post-doctoral research scholarship investigating targeted therapeutic approaches in malignant melanomas. In 2014 she returned to Cardiff to take up a Research Fellowship at the European Cancer Stem Cell Research Institute.

Vicky took up her first commercial role as Head of Cell Biology at ReNeuron in 2016 before joining Cellesce as Lead Scientist in 2019. Vicky has played a significant role in helping the Company to navigate the CV-19 global pandemic whilst ensuring that key commercial and scientific progress has been maintained.

Paul Jenkins (CEO of Cellesce) said:
“I am delighted that we have been able to make these important appointments during this critical period for the Company. Kate’s industry experience and connections make her an invaluable addition to our Board, whilst the quality of Vicky’s input over the last 12 months has resulted in a well-earned promotion and extension to her responsibilities.”

Concurrent with these appointments Dr. Marianne Ellis and Prof. Trevor Dale will be stepping down from their Board roles and joining the Company’s Scientific Advisory Board. Both Marianne and Trevor have been instrumental in helping Cellesce develop its patented bioprocess for the expansion of Patient Derived Organoids and both will still be involved in the ongoing management of the company.

John Allbrook (Chairman of Cellesce) said:
“It is impossible to exaggerate the enormous contribution that both Marianne and Trevor have made over the last 7 years. They were here when it all began and I know that through their contribution to our Scientific Advisory Board we can look forward to enjoying the benefits of their input and expertise in the future as the Company embarks on the next phase of its development.”

Cellesce, together with peptide 3D scaffold specialists, Manchester BIOGEL, and complex protein manufacturer, Qkine, have been awarded Innovate UK Sustainable Innovation Funding to develop fully synthetic, chemically-defined three-dimensional (3D) scaffolds that mimic more accurately the physiological environment in the human body and enable manufacture, scale up and improved reproducibility of patient-derived organoids.

Organoids are three-dimensional (3D) structures derived from stem cells that mimic mammalian organs. These have transformative potential as new platforms for faster drug discovery and better model systems for determining drug efficacy and toxicity. As well as pushing forwards basic biological understanding by more accurately replicating the responses seen in humans and reducing the need for animal use in research. However, existing methods for growing organoids rely predominantly on a 3D growth matrix extracted from mouse tumours to provide a supporting structure, this material is complex and poorly defined, leading to challenges with scale-up and limiting use in drug discovery platforms and other research applications.

This project seeks to address these issues by combining the existing technologies of Manchester BIOGEL’s tuneable peptide hydrogel scaffolds with Qkine’s optimised high purity growth factors to build a new 3D cell culture scaffold that will mimic the natural environment of the body. Importantly, all the components will be chemically-defined and animal product free, enabling greater experimental reproducibility. Working together with the leaders in patient-derived organoid scale-up, Cellesce, they will develop and tailor these new materials for scalable and reproducible organoid culture.

Commenting on the grant award, Professor Aline Miller, CEO of Manchester BIOGEL said “I am very excited about this project – not only will we establish a new collaborative consortium, but we will also bring together our significant expertise to contribute to the development of an enabling platform technology with pressing scientific need, and with strong commercial potential.”

A successful outcome from the collaboration will lead to the development of improved human cell-based models. This addresses key scientific challenges in the stem cell and drug discovery sector, reduces animal use in research, and strengthens UK life science manufacturing to provide a long-term sustainable return on investment for UK PLC.

colorectal cancer organoids

Colorectal cancer organoids ©National Physical Laboratory

About Manchester BIOGEL
Manchester BIOGEL is a global leader in the design and manufacture of synthetic self-assembling peptide hydrogels that provide a natural physiological extracellular matrix to support long term culture. Their biologically relevant hydrogels mimic the cell micro-environment and their stiffness and functionality can be modulated to simulate the natural environment of all human tissues. Manchester BIOGEL’s proprietary technology is 100% ethical, animal free and chemically defined. It opens up opportunities and offers clinically translatable solutions to meet current healthcare challenges within the growing fields of 3D cell culture, 3D bioprinting, tissue regeneration and drug discovery.

manchesterbiogel.com

About Qkine
Qkine is a Cambridge, UK-based manufacturer of high purity, animal-free growth factors, cytokines and other complex proteins. Qkine combines proprietary production processes with protein engineering technology to tackle fundamental biological and scale-up challenges for the fast-growing stem cell, organoid, regenerative medicine and cultured meat sectors.

qkine.com

We recently announced the impending arrival of new patient-derived Breast Cancer organoid lines. These new lines have been fully validated for compatibility with our proprietary organoid expansion process. We have recently published a new Application Note which describes the process and demonstrates the stability of breast cancer organoid phenotype, genotype and drug response following bioreactor expansion.

manual v bioreactor organoid expansion

Excitingly, our bioreactor-expanded organoids demonstrate reduced variability and greater batch-to-batch reproducibility than their manually grown counterparts in drug response assays, thus reinforcing their compatibility with drug screening applications. Go to the App Note.

Breast cancer is one of the most common types of cancer. Cellesce has invented and patented a unique bioprocess for the expansion of human-derived, cancer organoids for applications in cancer drug discovery and in collaboration with Cardiff University, is finalising the development of a range of breast cancer organoid lines. These will be available off-the-shelf towards the end of 2020.

Cellesce’s organoid expansion technologies minimise manual handling time and maximise reproducibility, to position organoid technology as a cost-effective and accurate tool in early-stage drug discovery.

Organoid drug assay workflow

A number of new and unique breast cancer organoid lines representing the key molecular subtypes of breast cancer have been established from primary patient biopsies or from Patient-Derived Xenograft (PDX) tissue.

The organoid lines have never been cultured in 2D adherent conditions, and faithfully represent the tumour from which they were derived.

Breast cancer organoids expanded at scale by Cellesce have been shown in pilot studies to generate more reproducible data than their manually grown counterparts, while maintaining the phenotype and genotype of the starting tissue.

Find out more.

A new paper exploring the application of patient-derived organoids (PDOs) in the study of novel inhibitors of stem cell activity has recently been published in the journal PLOS ONE (Badder et al., 2020).

The study utilised 3D image-based morphometric analysis to quantify over 600 different features from individual organoids following treatment with TNKSi. While the morphometric analysis approach mirrored the trend seen in traditional biochemical assays, importantly this more sophisticated method was able to detect subtle alterations in growth and morphology in response to TNKSi with much greater accuracy. This leads to the conclusion that whilst traditional biochemical assays still have value in detecting compounds that merit further investigation in early stage drug discovery, combining these with 3D morphological analysis could be the key to unlocking the full potential of organoids in predictive drug testing at a much larger scale.

The study was led by Cellesce founding director Professor Trevor Dale’s Cardiff University-based academic research group working together with Cellesce and other partners. It describes the derivation of a novel set of colorectal cancer PDOs. The PDO models are then used as a platform to test the response of colorectal cancer to Wnt pathway modulation using small molecule inhibitors of the tankyrase protein (TNKSi). The work utilises a range of analysis techniques and highlights 3D quantitative image analysis in particular as having the potential to greatly enhance the high throughput prediction of compound efficacy in pre-clinical testing.

In recent years, there has been a shift within the drug discovery industry to focus on the development of compounds targeting ‘cancer stem cell’ populations within tumours. Historically, conventional chemotherapeutics have aimed to target the tumour bulk, to kill as many tumour cells as possible; the effects of which are usually to drive tumour regression in the short-term, albeit with greater side-effects – and a high chance of patient relapse. It is now widely understood that, in order to permanently prevent tumour growth, the initiating cancer stem cell population must be removed or inhibited. In the patient, this might have a relatively small impact initially on overall tumour size, but a longer term more effective treatment caused not by killing the cells, but by a more subtle change in the behaviour of the cells within the tumour.

The study of such targeted compounds has led to demand for better predictive model systems. While historical drug discovery has relied heavily on the predictive power of 2D cancer cell lines, their lack of cellular heterogeneity and relevant phenotypic behaviour leaves them largely unsuited for the study of cancer stem cell inhibitors, and far from ideally placed for anti-cancer drug development in general.

PDOs – which retain intra-tumoral complexity and, crucially, stem cell function – are now gaining increasing momentum as predictive in vitro models in the drug discovery field, with the potential to reduce compound attrition rates and development costs, ultimately increasing the number of successful compounds available for use in the clinic. A more complex model, the study argues, demands a more comprehensive method of analysis that is capable of capturing the complete range of changes that may occur in response to treatment.

The organoid lines generated for this study are licensed for sale by Cellesce in large scale validated batches produced using Cellesce’s patented bioprocess. Cellesce PDOs:

  • Are vialled ready for plating straight into the desired format
  • Come with full protocols and technical support
  • A custom expansion service is available with:
    • Culture optimisation and banking options
    • Large scale expansion with custom vialling

Cellesce has produced an Application Note that summarises the paper’s findings.