BioScience Today 25 by Distinctive Media Group Ltd

SCIENCETODAY

BIO

cancer research • biosample provenance • biology of ageing • healthcare diagnostics • european biotech

ISSUE25

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www.biosciencetoday.co.uk

| foreword |

foreword Karen Southern Editor in chief

Editor Karen Southern karen.southern@distinctivegroup.co.uk

Design Distinctive Publishing, 3rd Floor, Tru Knit House, 9-11 Carliol Square, Newcastle, NE1 6UF Tel: 0191 580 5990 www.distinctivepublishing.co.uk

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Biotech stands at the brink of a new revolution It’s almost impossible to keep up with the breathtaking pace of progress in the field of bioscience, particularly biotech. Advances that seemed impossible only five short years ago are now mainstream, and revolutionary breakthroughs seem to pop up almost daily in my newsfeed. There’s no doubt that biotech is poised on the edge of a glittering golden era, and there’s much to celebrate, as evidenced by the pioneering longevity work of scientists such as Dr Eric Leire at Genflow Biosciences. His view - that age is just a number after all, and can be treated like any other disease – has ground-breaking implications for the health and wealth of our ageing societies. His work on transformative gene therapy seeks to repair the DNA damage which influences ‘bad’ ageing, and make growing older a happier, healthier experience for everyone. Good news indeed. The work of Dr Fiona McLaughlin at Avacta also addresses a critical healthcare gap – the lack of a durable response to current immunotherapies experienced by many cancer patients. Recently appointed to the role of Chief Scientific Officer

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in Avacta’s Therapeutics Division, Fiona and her colleagues have already laid the groundwork for first-in-class oncology treatments. Now for the downside (temporarily, at least). Biotech in Europe faces a number of challenges which hinder its deserved rise to the top of the global league. While the continent continues to forge ahead with brilliant R&D and entrepreneurship, well on par with its U.S. counterparts, it still lags behind when converting this priceless research treasure chest into tangible products. Thankfully, this lack of commercialisation is well recognised, and governments and industry are taking urgent steps to redress the balance. These include initiating stronger links between academia and industry, better access to funding and investment in Europe’s excellent pool of talent, and setting up innovative support frameworks such as the UK’s Industrial Biotechnology Strategy. With a sustained focus on growth, the future looks bright.

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features

Biotech pioneer tackles the biology of ageing

20 12 Shaping the science of oncology Biosample provenance: what researchers need to know

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contents / www.biosciencetoday.co.uk / issue 25 /

Foreword

4-5

Contents

7-13

NEWS

intellectual property Protecting Digital Medtech Innovation

12-15

cancer research Dr Fiona McLaughlin is the new Chief Scientific Officer of Avacta’s Therapeutics Division. She talks to Karen Southern about her mission to develop first and best-in-class cancer drugs.

20-21

biosample provenance Why is the current system for sourcing samples broken? And what does this mean for researchers who use biosamples? Robert Hewitt, MB BS, PhD, of Biosample Hub, investigates.

22-25

biology of ageing Living to a ripe old age is one thing. Enjoying a healthy, ripe old age is the challenge. Biotech veteran Dr Eric Leire aims to slow ageing by design, as he explains to Karen Southern.

26-27

healthcare diagnostics An innovative ultrapure water system has successfully tapped into healthcare diagnostics.

32-34

european biotech Converting cutting-edge research into viable products remains a challenge for the European biotech sector. Jonathan Hay of Delin Ventures investigates how ambition can translate to reality.

26 Ultrapure water system passes big test

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Dr. Leire has a solid biotechnology expertise through his experience in the pharmaceutical industry (Pfizer, Schering Plough, Pharmacia), biotechnology (CEO of several private and public biotech companies such as APT Therapeutics, Paringenix), academia (Research Associate at the Harvard AIDS Institute) and Private Equity (partner at Biofund Venture Capital). He is the inventor of several medical patents. He also serves on the board of several biotechnology companies (Immunethep, BSIM, Inhatarget). Furthermore, Eric has been CEO of several gene and cell therapy companies such as Enochian Biosciences (Nasdaq: ENOB) and DanDrit Biotechnologies (OTC.QB:DDRT). He holds an MD from Grenoble University and an MBA from HEC, Paris and Kellogg, Northwestern University.

Dr Fiona McLaughlin Chief Scientific Officer of Avacta’s Therapeutics Division Dr McLaughlin is a highly experienced oncology drug developer, bringing over 25 years’ experience in research and translational drug development in the pharmaceutical and biotech sectors, having led teams from early research through to clinical development. Fiona started her career at GlaxoSmithKline and has subsequently held leadership positions in multiple biotech companies including Vice President, Translational Research at Antisoma plc and Director of Preclinical Development at BTG plc (now part of Boston Scientific).

Alex Bone Patent Attorney, Partner, AA Thornton Alex is a UK and European qualified patent attorney with extensive experience in identifying and protecting innovations, and has spent many years working in-house in the medical device and diagnostic field. Through his work with big corporates and multinationals Alex is able to bring a wealth of knowledge to his work with SMEs and start-ups to provide leading strategic IP advice.

to advertise or contribute to the next edition advertising: liz.hughes@ distinctivegroup.co.uk editorial: karen.southern@ distinctivegroup.co.uk

BIO

SCIENCETODAY

Dr Eric Leire Founder & CEO, Genflow Biosciences Ltd

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Artificial heart is successfully implanted A bioprosthetic artificial heart has been implanted in a critically ill patient for only the third time ever in a commercial setting. The Aeson® device – heralded as the world’s most advanced total artificial heart - offers a therapeutic alternative for people suffering from end-stage biventricular heart failure. The implant was performed at the Department of Cardiovascular Surgery, in University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany. Designed and developed by Carmat, this implantable bioprosthesis is continuously connected to a portable external power supply system. It was developed in response to the well-documented shortfall in heart transplants for tens of thousands of people suffering from irreversible endstage heart failure. It is also classed as the first physiologic heart replacement therapy, given the use of highly biocompatible materials, its unique self-regulation system and its pulsatile nature. It is hoped that the Aeson® heart could save thousands of lives without risk of rejection and with a good quality of life. The device is the result of a collaboration between Professor Carpentier, the renowned inventor of Carpentier-Edwards® heart valves - the most used in the world - and aerospace giant Airbus Group. It is currently commercially available in the bridge-totransplant indication in Europe and other countries that

recognise the CE mark. Aeson® is also currently being evaluated in an Early Feasibility Study in the United-States. UKSH in Kiel, where the surgery was carried out, is one of Germany’s leading heart centres with a long history of thoracic transplantation. Prof. Assad Haneya, who performed the implant with his team, said: “We are pleased to have successfully implanted the CARMAT TAH in our centre. “The patient who received the device suffered from severe end-stage biventricular heart failure and he was eligible for an urgent heart transplant. During the last weeks, we noticed a further deterioration with signs of a beginning multi-organ failure and the use of Aeson® was a natural choice.” Dr. Bernd Panholzer, Director of Cardiovascular Intensive Care Unit, added: “A few days after the procedure, the device is providing all the necessary support and the patient is recovering well. Since the device has some key characteristics similar to a real heart, such as pulsatility, hemo-compatibility and self-regulation, we expect to meet the needs of many other patients placed on the waiting lists with this new type of therapy.” Find out more at carmatsa.com.

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Large-scale drug analysis reveals potential new COVID-19 antivirals Researchers at the Francis Crick Institute and University of Dundee have screened thousands of drug and chemical molecules and identified a range of potential antivirals that could be developed into new treatments for COVID-19 or in preparation for future coronavirus outbreaks. While COVID-19 vaccines are being rolled out, there are still few drug options that can be used to treat patients with the virus, to reduce symptoms and speed up recovery time. These treatments are especially important for groups where the vaccines are less effective, such as some patients with blood cancers. In a series of seven papers, published in the Biochemical Journal, the scientists identified 15 molecules which inhibit the growth of SARS-CoV-2 by blocking different enzymes involved in its replication. The researchers developed and ran tests for around 5,000 molecules provided by the Crick’s High Throughput Screening team to see if any of these effectively blocked the functioning of any of seven SARS-CoV-2 enzymes. The tests were based on fluorescent changes with a special imaging tool detecting if enzymes had been affected. They then validated and tested the potential inhibitors against SARS-CoV-2 in the lab, to determine if they effectively slowed viral growth. The team found at least one inhibitor for all seven enzymes. Three of the molecules identified are existing drugs, used to treat other diseases. Lomeguatrib is used in melanoma and has few side-effects, suramin is a treatment for African sleeping sickness and river blindness and trifluperidol is used in cases of mania and schizophrenia. As there is existing safety data on these drugs, it may be possible to

more quickly develop these into SARS-CoV-2 antivirals. John Diffley, lead author of the papers and associate research director and head of the Chromosome Replication Laboratory at the Crick, said: “We’ve developed a chemical toolbox of information about potential new COVID-19 drugs. We hope this attracts attention from scientists with the drug development and clinical expertise needed to test these further, and ultimately see if any could become safe and effective treatments for COVID-19 patients.” The 15 molecules were also tested in combination with remdesivir, an antiviral being used to treat patients with COVID-19. Four of these, all which target the SARS-CoV-2 enzyme Nsp14 mRNA Cap methyltransferase, were found to improve the effectiveness of this antiviral in lab tests. The scientists now plan to run tests to see if any pairing of the 15 molecules they identified decrease the virus’ growth more than if they are used alone. Targeting enzymes involved in virus replication could also help prepare for future viral pandemics. “Proteins on the outside of viruses evolve rapidly but within different classes of viruses are well conserved proteins that change very little with time,” adds John. “If we can develop drugs that inhibit these proteins, in the situation of a future pandemic, they could provide a valuable first line of defence, before vaccines become available.”

“We’ve developed a chemical toolbox of information about potential new COVID-19 drugs. We hope this attracts attention from scientists with the drug development and clinical expertise needed to test these further, and ultimately see if any could become safe and effective treatments for COVID-19 patients.” John Diffley, head of the Chromosome Replication Laboratory at the Crick

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Breakthrough on horizon for superior bovine mastitis cure Advanced studies into adjunct therapy in bovine mastitis are set to start. The condition is a significant economic and animal welfare issue for global dairy farmers, and this study, by Anifera, will build on promising initial data. It follows a substantial boost from Stonehaven Incubate, which invests in new, innovative animal health companies and is a co-founder of Anifera. Anifera is developing compounds which can improve the efficacy of antibiotics, with the goal of ultimately reducing their use in animals. Anifera’s small molecule compounds seek to potentiate the effects of the antibiotic through a unique mechanism of action which have been shown to increase the susceptibility of resistant strains of bacteria to antibiotics. With an initial focus on bovine mastitis, significant benefits are expected if the compounds produce a superior bacterial cure.

“Bovine mastitis is a huge economic challenge for the dairy industry, affecting the yield and quality of milk and impacting animal welfare. With increasing concerns and restrictions on the use of antibiotics in farm animals, Anifera’s innovative approach could help improve health and productivity for dairy farmers worldwide.” Dr Simon Wheeler, a member of Anifera’s Board

Dr Gwynneth Thomas, CEO of Anifera, commented: “We have seen very encouraging results in early studies focused on bovine mastitis, utilising our lead compound as an adjunct therapy to a commercial intramammary antibiotic. We look forward to moving ahead with additional development work aimed at further exploring improvements in the efficacy of existing antibiotics when used in combination with our compound, helping to advance sustainability in animal health. We are grateful for the continued commitment of Stonehaven Incubate as we seek to bring these potentially ground-breaking compounds to market as soon as possible.” Dr Simon Wheeler, a member of Anifera’s Board, said: “Bovine mastitis is a huge economic challenge for the dairy industry, affecting the yield and quality of milk and impacting animal welfare. With increasing concerns and restrictions on the use of antibiotics in farm animals, Anifera’s innovative approach could help improve health and productivity for dairy farmers worldwide.” Bovine mastitis is an inflammatory response of the udder tissue in the mammary gland caused by microorganisms that most often gain entry via the teat canal. It is widely considered to be the most common cause of economic loss in the dairy industry from disease due to reduced yield and lower milk quality. Overall, mastitis is estimated to cost the global dairy industry up to USD 32 billion annually1. Annual losses in the US alone are estimated at USD 2 billion2. Dairy farmers are expected to face additional challenges as greater restrictions are imposed on veterinary use of multiple antibiotics in major markets including Europe. Jarne Elleholm, CEO of Stonehaven Incubate, added: “Anifera has the potential to pioneer new ways of treating bovine mastitis, offering immediate financial and welfare benefits to dairy farmers. We are committed to helping Anifera advance these important studies and drive innovation to improve the efficacy of antibiotics. We share their goal of ultimately reducing the usage of antibiotics in disease states across animal health where they are the first line of treatment.” Anifera was formed by Stonehaven Incubate and Agile Sciences in 2020.

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Antimicrobial resistance ‘arms race’ heats up An advanced interventional microbiomics company, which is developing non-antibiotic methods for the control of multiple-drug resistant superbugs and other infectious disease, is stepping up development of a cure for antibiotic resistant bacteria. BioPlx has set out to control and combat the rise of superbugs by using targeted microbiological and immunological agents to decolonise (eliminate) undesirable or pathogenic organisms, and recolonise with safe replacement organisms that durably occupy the same microbiomic niches, and prevent pathogen recurrence and re-infection. Antimicrobial Resistance (AMR) has been characterised by the WHO as “one of the biggest threats to global health, food security, and development today”, with the stark warning that “the rapid global spread of multi- and pan-resistant bacteria (also known as “superbugs”) causing infections are not treatable with existing antimicrobial medicines such as antibiotics.” Amid WHO’s ominous outlook and other unequivocal warnings on the implications of AMR, one SciTech industry insider weighs in on what’s needed to stem this phenomenon that is killing people in increasing numbers and vastly changing the world we live in - today and for the years ahead. Tim Starzl is the son of Thomas E. Starzl, MD, PhD (known as the ‘father of modern transplantation’) and co-founder and President/Chairman of BioPlx. This advanced interventional microbiomics company is developing nonantibiotic methods for the control of multiple-drug resistant superbugs and other infectious diseases. Tim explains, “Both the medical community and the masses need to understand AMR with a better conceptual framework than the often-misused concept of ‘mutation’. “We’re living in an era when pandemics like the current COVID-19 contagion are increasingly posing a significant risk of mortality, as bacterial infections do not have the level of herd resistance that was present even a few decades ago.”

is being exacerbated in kind. It cites: “Bacterial infections unsuccessfully treated due to AMR claim at least 700 000 lives per year worldwide and are projected to be associated with the deaths of 10 million people per year by 2050, at a cost of US$100 trillion to the global economy through loss of productivity. In the USA, more than 2.8 million multidrugresistant bacterial infections occur annually, causing at least 35,000 deaths and $20 billion in health-care expenditures.” Starzl’s research, and that of his son, Ravi, who is co-founder of BioPlx, is focused on developing a cure for antibiotic resistant bacteria. He says, “We are in an ‘arms race’ to develop effective tools to attack AMR—one of the primary threats to the human race. “A paradigm shift in the science is needed relative to the basic concepts of microbiome management and ecology— one that facilitates highly selective antibody-based decolonisation methods to remove specific pathogens from their embedded microbiomic niches. This with durable, niche-specific, protective recolonisation using safe engineered ‘Kill-Switch’ replacement organisms that cannot infect their host. “Optimally, this science also proffers solutions that concurrently satisfy medical practice, reimbursement, patient requirement and public health objectives while also reducing disease recurrence and care provider liability, risk and matrix strategies. Fortunately, today’s technology—and those on the near horizon—allow for all of this.” Speaking at the virtual World Anti-Microbial Resistance Congress, attended by experts from over 50 countries, Dr. Ravi Starzl shared key findings of his groundbreaking research, discussing “Pangenomic Microbial Memory: The Origin of the AMR Crisis”; and “Kill Switch: A Critical Tool in the Fight Against AMR’.

In fact, with the COVID-19 Delta variant raging across the world, one peer reviewed medical journal reports that AMR

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Protecting Digital Medtech Innovation For many years the medical technology (medtech) sector has been at the forefront of innovation and the Covid-19 pandemic has not slowed it down, with new technology quickly being developed to test for, prevent and treat the virus. Protecting medtech innovations can be crucial to the commercial viability of a new development project. A protection strategy that indicates the potential for securing patents can drive investment because patents can help to secure a market position and / or can be licensed for use by others to provide additional revenue. The most recent data from the European Patent Office shows that the top ten technical fields for patent filings by number in 2020 include “medical technology” at number one, “pharmaceuticals” at six and “biotechnology” at eight, with each showing an increase in filings from the previous year. Some of this increase may have been due to the crisis, but it seems likely that the upward trend for this sector will continue, particularly in the digital space. Digital technology is already well integrated into medtech, with electronic delivery, testing, diagnostic and monitoring devices improving all the time. Digital technology also facilitates the analysis of images and data, identifying trends and spotting abnormalities. Incorporating Artificial Intelligence (AI) is becoming more common as it is hoped that this will result in systems that are faster and more accurate than digital, but nonAI, versions. The recent data already shows a significant increase in FDA approvals for AI algorithms with medical applications. During the pandemic, AI has also proven that it can help with drug discovery. In early 2020 an AI tool was used to review data (including patents, papers and the like) and predicted that an existing drug for rheumatoid arthritis, baricitinib, might be beneficial in treating critically ill Covid-19 patients. That prediction was tested and ultimately resulted in some emergency regulatory approvals of the drug to treat that patient population. Traditional developments continue, but the additional focus on digital innovation means that protection strategies need to evolve. Patent applicants for medical technology have always had to deal with the exclusion from patentability in some territories for methods of medical treatment or diagnosis carried out on the human body. Since many digital and AI medtech innovations involve software, and software “as such” is excluded from patentability in

some territories, they must now deal with an additional exclusion. Given these exclusions, can these innovations be patented, and is it worth it when the actual software code is automatically protected by copyright? Given the limited protection afforded by copyright, and the potential importance of protection for such innovations, the good news is that, “YES”, in many cases, patent protection can be obtained. However, AI is a new and fast evolving technology and the potential for obtaining patent protection is not always clear. The major patent offices have, over recent years, worked with applicants and attorneys to understand the needs of industry and to issue guidance on protecting AI inventions. The general guidance is that a non-obvious technical solution to a technical problem should be patentable. AI and software inventions may be considered technical as a result of their technical application, or their technical implementation on a computer system, for example, improving that computer system. Patents are not the only form of protection available for AI or software. Some technical aspects of an innovation may not be visible to an end user. A user may interact with a graphical user interface to access a cloud based AI, or they may interact only with an end product which has been developed using input from an AI device. In such cases end users do not gain direct access to, and cannot easily analyse, the AI or software. The disclosure required to obtain a patent may not be an attractive option. Protecting such innovations using trade secrets may be a commercially appropriate option. A trade secret is information that (a) is not generally known, (b) has commercial value and (c) is treated by its holder as secret. A trade secret should be known to as few people as possible and, preferably, only to those who need to know it. There is no single IP right that is best for protecting digital innovations in the medtech field. It is important to have a flexible strategy that can take advantage of the benefits of different rights for aspects of the innovation. If you have any queries regarding this topic, or other medtech, pharmaceutical or biotechnological matters, please contact Alex Bone at amtb@aathornton.com or visit aathornton.com.

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Shaping the science of oncology Dr Fiona McLaughlin is the new Chief Scientific Officer of Avacta’s Therapeutics Division. She talks to Karen Southern about her mission to develop first and best-in-class cancer drugs.

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rom the day that Dr McLaughlin – then a biochemistry student – volunteered for a one-off industrial placement at ICI, her ‘fate’ was sealed.

“I have worked in cancer research throughout my career,” she explains, “including at university, where my final year project was conducted at The Beatson Institute working on a metabolism project, now a very hot area of research. “My PhD was in Stem Cell Leukaemia, and in industry I have worked throughout in oncology (and inflammatory) drug development, covering small molecules, biologics, and radiopharmaceuticals. “I am very fortunate to have always loved science and biological sciences in particular. Working with worldclass physicians and scientists is always inspirational because you know that what you do is going to contribute towards either greater understanding of disease biology, or ultimately in a new oncology therapeutic.” After completing a year at ICI (now AZ), she finished her BSc at Glasgow University, and a PhD in Haematology at Cambridge. Twenty-five years on, her impressive pharma and biotech portfolio in research and translational drug development includes stints at GlaxoSmithKline, and leadership positions such as vice-president, Translational Research at Antisoma plc and director of Pre-clinical Development at BTG plc (now part of Boston Scientific). Other roles include Head of Biology at TopoTarget A/S, where she was responsible for the pre-clinical development of belinostat which went on to gain FDA approval to treat peripheral T-cell lymphoma. Most recently, she was vicepresident of New Opportunities at Algeta ASA (acquired by Bayer), a Norwegian biotech developing alpha radiopharmaceuticals, that gained FDA approval of Xofigo to treat castration resistant prostate cancer. Now she is responsible for helping to develop innovative cancer therapies and powerful diagnostics at Avacta, as Chief Scientific Officer of the Company’s Therapeutics Division. This intensive body of work focuses on addressing a critical gap in cancer treatment - the lack of a durable response to current immunotherapies experienced by most patients. By combining its two platforms, Affimer® and pre|CISION™, the Group is building a pipeline of novel cancer therapies. The Affimer® platform is an alternative to antibodies derived from a small human protein. Despite their shortcomings, antibodies currently dominate markets, such

as diagnostics and therapeutics, worth in excess of $100bn. Affimer® technology has been designed to address many of their negative performance issues, principally: the time taken to generate new antibodies and the reliance on an animal’s immune response; poor specificity in many cases; their large size, complexity and high cost of manufacture. Avacta’s pre|CISION™ targeted chemotherapy platform releases active chemotherapy in the tumour, which limits the systemic exposure that causes damage to healthy tissues, and improves the safety and therapeutic potential of these powerful anti-cancer treatments. So what attracted Fiona to the role? “I had been working as a consultant for the last few years, which gave me a great amount of flexibility to work with a number of different types of organisations, from biotechs, to venture capitalists and not for profit organisations such as Cancer Research UK. “Working as a consultant, you build up a fantastic network, especially in the Cambridge area. As a next step, I wanted to move to an Oncology-focused biotech, where I could take my expertise gained over 25 years in drug development, together with my strong network in the oncology field, to really develop the science and bring new, innovative drugs to the market. “Avacta is a company that is just starting its journey as a clinical development organisation, and I could see the potential to really shape the portfolio and help steer the company into a new phase.” There is also however, a more personal element for Fiona: “I have an identical twin sister who was diagnosed with breast cancer in 2018, while still in her 40’s. I have known many people who have had cancer, but not anyone this close. She was diagnosed with a type of tumour for which there was an antibody therapy, and we hoped that meant she would be spared from the side-effects of chemotherapy. Unfortunately, the best result in trials came from the antibody given in combination with chemotherapy and so she underwent 12 months of chemo, antibody treatment, surgery and radiotherapy. “I saw first-hand the side effects of having three chemotherapeutic drugs given at the same time, and I appreciated more than ever the need to get better tolerated drugs to patients. One of the drugs she was given is called an anthracycline, and I am now working on developing a better tolerated version of an anthracycline in my new role at Avacta.”

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“This means we can collaborate with first class academic labs to help translate our research (for example exploratory biomarker analysis) to the clinic and back to the bench. We design our clinical trials to be as data rich as possible, so that we get a better understanding of our drugs and how they work and identify which patients are likely to respond, using state of the art methodology.” Fiona and her team have already prioritised assets in their portfolio, driving them faster towards the clinic. “We have also built up the translational science team to ensure we design the most effective clinical studies, expand the pipeline using our two platform technologies and increase our interactions with world-class academic labs and industries, to deliver first-in-class therapeutics.” However, she is also pragmatic about the challenges ahead: “There are more than 100 different types of cancer, some are solid and some are liquid (haematological) which makes our work incredibly challenging. Each tumour type has a different genetic background, and that genetic background can change over time and with treatment. Gaining an understanding of this complex environment such that we then understand which targets to go after is a massive challenge. “I think one of my greatest frustrations, so to speak, is that there are still so many potential drug targets that are un-druggable using current technologies, for example transcription factors.

Dr Fiona McLaughlin Chief Scientific Officer of avacta’s Therapeutics Division

“When my twin sister was diagnosed with breast cancer, I saw first-hand the side effects of having three chemotherapeutic drugs given at the same time, and I appreciated more than ever the need to get better tolerated drugs to patients. One of the drugs she was given is called an anthracycline, and I am now working on developing a better tolerated version of an anthracycline in my new role at Avacta.” For now, Fiona sees her main challenge being access to high quality patient material and “the heterogeneity of tumours which makes statistically significant comparisons challenging.” However, she singles out the timely advances in AI for rapid breakthroughs in oncology drug development, diagnosis, precision oncology and ultimately prevention. “The ability to process huge amounts of data, and recognise patterns in the data, allows us to potentially identify novel areas of research and new drug targets, but also to repurpose existing therapeutics. “Furthermore, in advancing these therapies in the past five years, cutting-edge research areas have been established that hold huge potential to expand the efficacy and safety of current therapy options. By harnessing these discoveries, the benefits of standard chemotherapies can be expanded to more patients, without the debilitating side-effects.

“This is why everything that we do in the lab has to be tangible. We are making drugs to deliver to patients, or developing companion diagnostics to help deliver a precision medicine approach to cancer treatment. Our ultimate goal is to continue bringing novel, effective therapies to patients, in particular in areas of high unmet need such as pancreatic cancer and to help make cancer a disease that people die with, not from.” How does Dr McLaughlin see treatment progressing in the next few years? “Immuno-oncology agents have been transformational for many patients, but sadly not all. A number of disruptive technologies, such as in the cell and gene therapy area, could significantly alter cancer outcomes, but I suspect chemotherapy will still have a role to play in patient care for many years to come.” And finally, any advice for aspiring R&D graduates? “Don’t give up! Attrition in early stage drug development is high, because of the complexities of what we do. You need to be able to problem solve constantly, but the more experience you gain, the more you are able to bring that experience to bear on the problem in hand.” avacta.com

About Avacta Avacta’s Therapeutics development programme is based in Cambridge, with the Diagnostics division in Wetherby. The Group is working with global partners to develop bespoke Affimer® reagents for third party products, and is also developing an inhouse pipeline of Affimer-based diagnostic assays including the AffiDX® SARS-CoV-2 Lateral Flow Rapid Antigen Test. This year, it transitioned to a clinical stage biopharmaceutical company, with a phase I study of AVA6000 Pro-doxorubicin, its lead pre|CISION™ prodrug, in patients with locally advanced or metastatic selected solid tumours.

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New approach will help identify drugs that can ‘glue’ proteins together A new screening method that can test the effectiveness of therapeutic molecules designed to ‘glue’ proteins together in the body has been developed by researchers at the University of Birmingham and the University of Leicester. The research paves the way for drug developers to screen large numbers of potential new drug compounds to discover new treatments for diseases such as breast cancer and Parkinson’s disease. The ways in which proteins interact with each other are fundamental to all cell functions. These interactions underpin every function of a healthy body, with any slight change in these interactions resulting in disease. A handful of drugs have been designed that can break apart these interactions, and this serves to disrupt the progress of the disease. However, in some diseases, the problem is caused by protein interactions not happening, or not happening in the right way. So new drugs that work by ‘gluing’ these proteins together would be highly effective, but finding them is not straightforward. In this study, researchers in the University of Birmingham’s School of Biosciences have designed a system that uses mass spectrometry to measure the precise mass of a pair of proteins, plus the ‘glue’, to identify which ‘glue’ is the strongest and thus will likely be the most successful in treating the disease. Lead author Dr Aneika Leney said: “A healthy body depends very much on the cells’ proteins being able to signal effectively. Any wrong signal can lead to disease and that could be the wrong proteins sticking together – or proteins not joining up as they should. We want a drug that corrects for this. Our methods provide a ‘snapshot’

of what is happening to the proteins when we add a potential drug so we can see quickly whether the ‘glue’ is working” The team worked with chemical biologists at the University of Leicester to test the method on therapeutic compounds being studied by co-lead author Dr Richard Doveston and his team. Dr Doveston says: Looking for molecules that act as glues is not easy because things are complicated by having two proteins in the mix. At the early stage of development we often just want to find molecules that are good starting points for development, so they might not be that good as glues at this stage. The current high-throughput screening methods available to us are usually not very effective in this context. The mass spectrometry method is great because we can learn so much from the data and it can be gathered relatively easily and quickly. Because the glue compounds are highly specific to the identified proteins, interactions with other proteins are rare, so the therapy is unlikely to produce any unlookedfor effects.” Dr Leney adds: “We hope our approach will be taken up by pharmaceutical companies and used to rapidly screen and test promising drug compounds that can bind proteins together to deliver a therapeutic benefit.” This research is published in Chemical Science, the Royal Society of Chemistry’s peer-reviewed flagship journal, and is free to read.

“A healthy body depends very much on the cells’ proteins being able to signal effectively. Any wrong signal can lead to disease and that could be the wrong proteins sticking together – or proteins not joining up as they should. We want a drug that corrects for this. Our methods provide a ‘snapshot’ of what is happening to the proteins when we add a potential drug so we can see quickly whether the ‘glue’ is working” Dr Aneika Leney

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Novel mechanism links IBD genetic defect to gut leakiness A study into ‘leaky gut’ is the first to show how a disease mutation increases the risk of developing Inflammatory Bowel Disease (IBD). Researchers led by a biomedical scientist at the University of California, Riverside, have identified a novel mechanism by which loss-of-function mutations in the gene PTPN2 – found in many patients with IBD – affect how intestinal epithelial cells maintain a barrier. The intestinal epithelium, a single layer of cells, plays a critical role in human health by providing a barrier while also allowing nutrient and water absorption. Intestinal epithelial cells are needed for regulating immune function, communicating with the intestinal microbiota, and protecting the gut from pathogen infection — all of which critically depend on an intact epithelial barrier.

how claudin-2 expression increases and contributes to fluid loss. PTPN2 typically acts as a brake on the expression of claudin-2, McCole explained. The loss-of-function mutation in PTPN2 that occurs in IBD removes this brake and allows increased fluid loss. “In addition, PTPN2 also promotes an endogenous factor, called matriptase, that removes claudin-2 from the area of the cell membrane where it mediates its effects in allowing fluid loss to occur,” McCole said. The cumulative effect of reduced PTPN2 activity on both mechanisms was elevated fluid loss. The researchers proved this defect could be reversed by treating cells lacking PTPN2 with recombinant — or synthetic — matriptase.

Affecting millions around the world, IBD is a set of chronic intestinal diseases in which the lining of the gut becomes inflamed and leaky. Increased gut leakiness has recently been confirmed to increase the risk of developing IBD.

“Our work improves understanding of how the genetics of IBD can contribute to the altered physiology in patients that drives their symptoms,” McCole said. “It also supports our related work identifying how the class of drugs, called JAK inhibitors, may be used to rescue ‘leaky gut,’ particularly in patients with loss-of-function mutations in the PTPN2 gene.”

“This new publication is a culmination of a body of work from my lab identifying how loss-of-function mutations in PTPN2 can increase gut permeability or leakiness,” said Declan F. McCole, a professor of biomedical sciences in the UCR School of Medicine, who led the study published in the Journal of Clinical Investigation. In the study, which was conducted in mice, human cells, and tissue from IBD patients, McCole and his colleagues showed that in IBD patients carrying a loss-offunction PTPN2 mutation, the expression of claudin-2, a protein that causes loss of water and sodium into the gut and promotes diarrhea, is increased. Using mouse models, the McCole lab identified a dual mechanism that explains

The study also showed that a recently identified and rare novel mutation in PTPN2, which causes gut epithelial damage in children, also increases gut epithelial leakiness — but without causing epithelial cell death. “This suggests that patients who develop this condition may exhibit ‘leaky gut’ before full-blown disease occurs,” McCole said.

“Our work improves understanding of how the genetics of IBD can contribute to the altered physiology in patients that drives their symptoms. It also supports our related work identifying how the class of drugs, called JAK inhibitors, may be used to rescue ‘leaky gut,’ particularly in patients with loss-of-function mutations in the PTPN2 gene.”” Declan F. McCole, professor of biomedical sciences in the UCR School of Medicine

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The Elekta MR-linac machine

Lung cancer treatment is a UK first A grandfather has become the UK’s first lung cancer patient to benefit from a state-of-art radiotherapy treatment at The Christie NHS Foundation Trust. Barry Staniforth, 81, was treated using the Elekta MRguided linear accelerator (MR-linac) machine that performs real-time MRI scans while X-ray beams target the tumour, making it more accurate and reducing side effects. Despite the COVID-19 pandemic Barry was quickly referred to The Christie in Manchester for treatment. He then received four weeks of radiotherapy to treat his lung cancer using the pioneering Elekta MR-linac machine. The MR-guided linear accelerator (MR-linac) combines magnetic resonance (MR) scanning and tumour-busting radiotherapy to deliver magnetic resonance radiotherapy in one hi-tech package. Barry’s treatment was part of the MOMENTUM trial which is a worldwide radiotherapy trial using the MR-linac. It aims to target a wide range of cancers to find out which ones react best to the treatment before it is hopefully rolled out across the globe. The trial is being overseen by Dr Cynthia Eccles and the MR-linac team at The Christie and supported by the NIHR Manchester Biomedical Research Centre. Barry, from Sandbach, had only just retired, aged 79, before his diagnosis. He was treated by specialist lung oncology team headed up by Dr Ahmed Salem and Professor Corinne Faivre-Finn, with support from the MR-Linac clinical lead Professor Ananya Choudhury, consultant research radiographer, Dr Cynthia Eccles and physics lead Dr Rob Chuter. The research team are also based at The University of Manchester. Dr Ahmed Salem said: “The MR-linac’s unique ability to provide real time scans of the tumour and healthy tissues while treatment is being delivered provides an opportunity

Barry Staniforth and the MR-linac team at The Christie to improve radiotherapy accuracy & reduce side-effects in selected patients. “We hope that Barry will be the first of many lung cancer patients to have treatment on this innovative machine. It is a privilege to be part of the team that made this possible”. Being able to more specifically target tumours and avoid more healthy tissue around them means the machine can use target X-rays better. The £5.3m machine was partfunded by donations to The Christie charity. Since the opening of the UK’s first NHS high energy proton beam centre in 2018, The Christie is now one of only two sites worldwide to offer both these pioneering radiotherapy treatments.

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Gut bacteria influence brain injury in pre-term babies Extremely premature infants are at a high risk of brain damage. Researchers at the University of Vienna and the Medical University of Vienna have now found possible targets for the early treatment of such damage outside the brain: bacteria in the gut of pre-term babies. The research team found that the overgrowth of the gastrointestinal tract with the bacterium Klebsiella is associated with an increased presence of certain immune cells and the development of neurological damage in premature babies. The study is now published in journal Cell Host & Microbe. The early development of the gut, the brain and the immune system are closely interrelated. Referred to as the gut-immune-brain axis, bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve and the immune system. “We investigated the role this axis plays in the brain development of extreme pre-term infants,” says microbiologist and immunologist David Seki, one of the study authors. He added: “The micro-organisms of the gut microbiome - which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes - are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain.”

MICROBIOME PATTERN CLUES “In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury,” said David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna. “Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided.”

EXTREMELY PREMATURE STUDY Starting points for the development of appropriate therapies are provided by the biomarkers that the

interdisciplinary team was able to identify. “Our data show that excessive growth of the bacterium Klebsiella and the associated elevated-T-cell levels can apparently exacerbate brain damage,” explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Medical University of Vienna. “We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process,” he adds. The study monitored a total of 60 premature infants, born before 28 weeks’ gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods – the team examined the microbiome using 16S rRNA gene sequencing, among other methods – the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants’ brains.

RESEARCH CONTINUES The study, which is an inter-university cluster project under the joint leadership of Angelika Berger (Medical University of Vienna) and David Berry (University of Vienna), is the starting point for a research project that will investigate the microbiome and its significance for the neurological development of prematurely born children even more thoroughly. In addition, the researchers will continue to follow the children of the initial study. “How the children’s motoric and cognitive skills develop only becomes apparent over several years,” explains Angelika. “We aim to understand how this very early development of the gut-immunebrain axis plays out in the long term. “ The most important cooperation partners for the project are already on board: “The children’s parents have supported us in the study with great interest and openness,” says David Seki. “Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that.”

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| biosample provenance |

Biosample provenance: what researchers need to know Why is the current system for sourcing samples broken? And what does this mean for researchers who use biosamples? Robert Hewitt, MB BS, PhD, of Biosample Hub, investigates. The journey for every biospecimen used for medical research is different. It all begins when the sample is donated by an individual and it ends when the sample reaches the research laboratory where it is analysed. Between these two points, there is a wide variety of possible routes, events and timelines, any of which may have the potential to affect the quality of the sample. Because of this it is vitally important that researchers know the provenance details of everyone of the biospecimens they use in their work. Unfortunately, for researchers working in industry, this information is often lacking, and this will affect the reliability of the resulting research they conduct. Why is this? The reason is that researchers in industry very often obtain biospecimens through the services of a commercial broker. These brokers act as an intermediary between the client in industry and the hospital biobank where the sample was originally collected and preserved. Brokers source the samples that their client require and charge a fee for doing this. They prefer not to allow free and unconditional communication between the researcher and

the hospital biobank, because this would risk their own circumvention and potential loss of profits. So, in general, brokers keep the source of their samples to themselves. The result of this is that the researchers may then lack biospecimen provenance information they need. For the industry scientists who are the end-users of the samples, the provenance information that is important to know includes: (a) sample processing history, (b) information about the donor and their medical history, (c) the geographic origin of the sample which provides information about environment and ethnicity, and (d) previous custodians, which may include one or several commercial brokers. Even in simple cases there is great potential for variation in sample processing. To take one example: diseased tissue removed during an operation by a surgeon. This type of sample needs to be preserved rapidly to minimise damage caused by anoxia which begins once tissue is separated from its blood supply. The speed with which preservation

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| biosample provenance |

is started, by cooling and freezing, is highly variable and dependent on the efficiency of the biobank staff. Another example, is where blood samples need to be processed by fractionation into different components (blood cells, plasma, and serum) and again the efficiency of this process can vary between different sources. At the most basic level, knowing the identity of the source biobank allows researchers to decide whether samples are likely to be reliable, based on past experience. If a particular biobank has obtained appropriate licencing, certification or accreditation, this will give confidence about sample quality and reliability. This includes licensing by the Human Tissue Authority in the UK, ISO certification (ISO9001 and ISO20387), US CAP Accreditation and CTRNet Certification. Researchers who are unable to assess the reliability of their samples are in danger of producing research that is irreproducible. This is not only a waste of research funding on a huge scale, but it also delays the development of lifesaving therapies. Industry scientists need information about the sample donor, including demographic information and medical history. To be sure that this information is correct, it is best for the scientists to be in direct contact with the source biobank. If additional information is required subsequently, for example the response to treatment or survival time, then it will be necessary to get back in touch with the source biobank. All of this is made significantly more difficult if a broker will not comply with a request to reveal the source of the samples. Knowing the geographic origin of a sample is essential because this may provide information about environmental, socio-economic and genetic factors that will help make sense of research findings. This is particularly important because the international sourcing of samples for industry is highly prevalent. In a recent survey by Medicines Discovery Catapult found that diagnostics SMEs in the UK obtained 75% of their samples from other countries. Part of the reason is that in the UK and other countries in Western Europe, there is a high level of concern about the ethics of trade in human tissue, so brokers find it much easier to source samples in other parts of the world, like eastern Europe, Asia and the USA. It is important to note that some countries like China, India and Russia have legal restrictions on the export of samples, so another reason to be sure of geographic origin is to avoid the use of illegally sourced samples. The international sourcing of clinical samples may involve a number of commercial entities operating in different countries, which adds additional degrees of separation between the source and the end-user. It is important for end-users to be aware of this and the possible effect on the reliability of information provided about patient consent and sample provenance. Information about sample provenance is clearly vital for a range of scientific, ethical and legal reasons, so what can be done to make sure that when industry obtains samples, they always come with reliable provenance information? One option is for brokers to allow direct communication between the hospital source of samples and the enduser, but to require both parties to sign a contractual agreement to the effect that they will not circumvent the broker. Such contracts are indeed being used effectively by several commercial brokers. However, the fact they place restrictions on the freedom of companies and biobanks to form partnerships is not always acceptable to one or other of the potential partners. Another option is for companies to develop their own networks of biobanks to supply the samples that they need. In the long term this may be feasible, however in the short term it can be very difficult to find suitable hospital

About the author Robert Hewitt, MB BS, PhD, is the founder of Biosample Hub, a new platform that connects Biotech companies looking for samples, with Biobanks that have ethically sourced samples available. Web: biosamplehub.org LinkedIn: linkedin.com/in/hewittr/ Twitter: twitter.com/rhbio

biobanks with the necessary samples in stock. Companies can consult the publicly available biobank directories, but these are generally designed with academic researchers in mind and may not indicate whether the biobanks are willing or indeed motivated to work with industry. This means that for start-up companies and those with urgent sample needs, there is often little alternative but to obtain samples through brokers. A recently established not-for-profit company provides a possible solution. This company called Biosample Hub provides an online platform dedicated to partnering industry with academic biobanks. The platform includes directories of biobanks, companies and requests as well as networking features to allow members to communicate. So far this has been well received by academic biobanks in western Europe, providing industry with a route to previously inaccessible sources of clinical samples. Looking ahead, regulatory requirements for the approval of drugs and diagnostics will enforce the need for reliable sample provenance information. For makers of medical devices the European IVDR regulations already require this. In addition to the introduction of new legal and regulatory requirements, there are promising technological developments on the horizon that will help ensure reliable sample provenance information going forward. To take one example, Blockchain with its distributed virtual leger technology offers the potential to track samples with absolute confidence while also protecting patient confidentiality. Given this we can say that prospects for improving biosample provenance in the future look very promising.

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| big interview |

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| big interview |

Biotech pioneer tackles the biology of ageing

Living to a ripe old age is one thing. Enjoying a healthy, ripe old age is the challenge. Biotech veteran Dr Eric Leire aims to slow ageing by design, as he explains to Karen Southern.

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he quest for immortality (or at least eternal youth) is an ancient concept – and nothing has made us question our own mortality more than the events of the last 18 months. But, to quote Freddie Mercury’s swansong, ‘Who wants to Live Forever? if it means enduring crippling age-related illnesses in later life. The problem of ageing populations, especially in developed nations, has brought longevity acutely to the fore. According to OECD, health expenditure will rise from 8.8% of GDP in 2015 to 10.2% by 2030, with demographic pressures driving a quarter of this increase. For the US it has been estimated slowing aging and increasing healthy life expectancy by between one and two years is worth between $7 trillion and $38 trillion. Dr Leire has made health span, not life span, the main focus of his work (although he admits better life expectancy would be the cherry on the cake). He is the founder and CEO of British-based pre-clinical biotech company Genflow, which is looking at ways to slow the ageing process through transformative gene therapy. The company is working on a variant of the Sirtuin 6 (SIRT6) gene, found in centenarians, to develop a product which will repair DNA damage, boost genes and extend individual health spans by up to 25%. Clinical trials will be carried out within the next few years, and, subject to regulatory approval and successful patient outcomes, the product could be ‘on the shelf’ within a decade. Dr. Leire has an accomplished career in scientific research and development spanning 40 years. Having held positions at Pfizer, Schering Plough and Pharmacia, he went on to be CEO at several biotechnology companies, including APT Therapeutics and Paringenix. Today he serves on the board of Immunethep, BSIM and Inhatarget. He has invented several medical patents and spent time as a research associate at the Harvard AIDS Institute. He has specialised in gene therapy for 15 years. In a breakaway from conventional medical thinking, Dr Leire regards ageing as a disease rather than the inevitable consequence of accumulated years. As he explains: ‘Ageing is plastic, we can slow it, and reverse it. “I believe it is unethical to view ageing as a biological process that we can’t act upon. For example, if you go to a cardiologist, you don’t expect him to say ‘You have high cholesterol or blood pressure, but we won’t treat it as a disease’. “Yet if you tell your GP, ‘I keep losing my keys, I can’t see too well, I can’t run so fast any more,’ it’s perfectly acceptable for them to say ‘It’s just ageing, there’s nothing you can do!’ Dr Leire hopes this mindset will change, now that the biology and the nine driving factors of ageing – as identified in a 2012 study by Carlos Lopez - are better understood. “Age will then become a risk factor to treat, much like, say, statins are used to treat high cholesterol. “Lots of companies have been set up to tackle just one of the drivers of ageing. But if you only fix 1/9th of the problem, the impact will be modest at best. We seek to tackle at least half the drivers, extend health span by delaying the diseases of old age, and also prevent loss of muscle mass, weakened immune systems, and the decline of cognitive functions.” DNA damage is identified as the most upstream, common factor for poor ageing. Dr Leire acknowledges the role of diet and fasting in ageing well, but says the key to healthy longevity ultimately lies in DNA repair. “You only have to look at Jeanne Calment, the world’s oldest documented

Dr Leire founder and CEO of Genflow

“You only have to look at Jeanne Calment, the world’s oldest documented person. She lived to be over 122, but loved her wine and cigarettes. The key to her longevity lay in her genetic make-up. So, we need to find the genetic drivers that impact the hallmarks of ageing.” person. She lived to be over 122, but loved her wine and cigarettes. The key to her longevity lay in her genetic makeup. So, we need to find the genetic drivers that impact the hallmarks of ageing. “DNA breaks easily, and constantly. It becomes a vicious circle for the genetic system, which gets overwhelmed. “To counter this, we are currently doing trials with enhanced AAVs (adeno-associated viruses), which are easy to administer and cost-effective. We will look next at working with patients with accelerated ageing disease, (subject to regulatory acceptance). Our treatment will involve IV infusions of AAVs that can express SIRT6 into specific cells, to slow down these patients’ symptoms, such as cataracts and diabetes, and repair DNA damage.” Gene therapy has made huge progress in the last five years. In fact, five years ago, Genflow’s work would not have been possible because the tools for the work were not available.

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In parallel, huge strides have been made in understanding the process of ageing. But up until very recently, the cost of therapy was hugely prohibitive. Dr Leire explained: “Longevity gene therapy originated in California, as a very high cost treatment for Silicon Valley types. “This is the opposite of what we want. We don’t want to give 30 extra years complete with cancers, Alzheimer’s and such like. We want to prevent the slow decay of biology that comes with age in a cost-effective, safe, ethical and userfriendly way.” The company’s pre-clinical studies have already yielded promising results, by expressing the DNA of the Centenarian Variant of the Sirtuin 6 gene using the vector for GF-1002, which establishes that it is possible to deliver extra copies of the Variant into cells. The Centenarian Variant has also already been shown to have improved capabilities to repair DNA damage both by homologous recombination and nonhomologous end-joining. Ultimately, the company hopes their therapies could act upstream on several drivers of ageing. Trials have already proven to increase lifespan in mice by up to 30 per cent. Dr Leire added: “Our treatments are preventative, rather than a cure. We would look to start treating people in their 50s, as age-related diseases tend to start in the 60s.

“It’s envisaged our products would be off the shelf, and patient-friendly, topically administered to the skin or injected via IV. Treatment wouldn’t need to be regular, perhaps every one or two years, at a cost of perhaps £10£15,000. To date, research has primarily centred on the USA, where billionaires such as Jeff Bezos and PayPal founder Peter Thiel have invested heavily in biotech research. While this investment has spurred the proliferation of firms in the longevity space across the Atlantic, in Europe a leader is yet to emerge. Genflow, based in the UK with research facilities on the continent, aims to fill this gap. “Dr Leire explained: “My treatments aren’t aimed at the super-rich in the way they are being developed in the USA – they aren’t meant to bring back youth. We want to create therapeutic interventions, with all the ensuing benefits for the economy and society at large.” To this end, Genflow has settled in London, “where investors are better quality”, close to the world-class genetics therapy hub of Cambridge and Oxford. “There’s a huge appetite for biotechs right now,” Dr Leire concluded, “and Genflow hopes to become the market leader for longevity tech in Europe.” Visit genflowbio.com for more information.

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| healthcare diagnostics |

Ultrapure water system passes big test An innovative ultrapure water system has successfully tapped into healthcare diagnostics. The pharmaceutical industry is embracing new technology that can reduce costs and simplify installation. At the production site of a multinational healthcare diagnostic test manufacturer, Bürkert’s FLOWave has proven highly successful in measuring the flow of ultrapure water. In fact, recent expansion has placed a repeat order for the versatile flowmeter, having provided four years of faultless service in the initial installation. Pharmaceutical manufacturing requires many stringent specifications to be met by all the components used in a production facility. Not least among these are hygiene and accuracy, but when dealing with ultrapure water, the choices for a precision flowmeter can be limited. The main reason is that this liquid has very low conductivity, which rules out mag-flow meters, and until recently, there was only one viable option for a flowmeter.

PHARMACEUTICAL ADVANTAGES Using Surface Acoustic Wave (SAW) technology, fluid control systems specialist Bürkert has developed a flowmeter in which none of the components are in direct contact with the fluid and which causes no restriction to flow. Furthermore, the internal surface of the tube can be manufactured to the same surface finish as the rest of the pipeline, meaning that in terms of hygiene, cleaning and flow conditions, there is no difference to any other piece of straight pipe within the process. The FLOWave also solves many of the issues associated with some high-end flowmeters, such as system vibration in the plant, magnetic and electrical effects as well as the conductivity of the liquid - none of these factors have any effect on the accuracy or reliability of the flow measurements. One of the early adoptions of the FLOWave in a pharmaceutical setting was in the healthcare diagnostics manufacturing plant, where it was used to measure ultrapure water volumes being used by a set of laboratories. The project included the installation of two FLOWaves as part of a new process build.

PRODUCTION EXPANSION The recent pandemic has led to increased demand for laboratory diagnostic products and the decision to install a second production line that will manufacture a key component used in Covid diagnostic testing. Part of this project was awarded to KJB Water & Process Engineering, which has been responsible for the overall design of the ultrapure water system. Within each laboratory, there are take-off points for ultrapure water, which is supplied by a ring-main. In order to ensure sufficient volumes of ultrapure water, the flowmeters are installed on the supply and return legs of the ring main; the calculated difference in flows enables the ultrapure water production system to match demand. Dr Corby Lee, technical consultant at KJB Water & Process Engineering, put together the supporting evidence that demonstrated the isolution could provide the required data in a hygienic setting without the drawbacks associated with more traditional instruments.

CONTINUED PERFORMANCE Dr Lee explains: “Now, having selected the Bürkert product for flow measurement four years previous, the latest project to install a second production line will include two more FLOWave components. Since the initial project, the customer has had no issues with the performance of the flowmeters and we were confident this latest installation would offer the same.” Dr Lee concludes: “In terms of installation, the process is significantly less complicated when using a FLOWave device as it can be mounted in any orientation and its compact design makes it easy to integrate into the overall design of the plant. Furthermore, the connectivity makes the control integration very easy and with Bürkert’s support we were able to meet the tight delivery deadlines that were set for this project.”

“Now, having selected the Bürkert product for flow measurement four years previous, the latest project to install a second production line will include two more FLOWave components. Since the initial project, the customer has had no issues with the performance of the flowmeters and we were confident this latest installation would offer the same.” Dr Corby Lee, technical consultant at KJB Water & Process Engineering

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| healthcare diagnostics |

Image above: Bürkert’s FLOWave measures the flow of ultrapure water Image right: In order to ensure sufficient volumes of ultrapure water, the flowmeters are installed on the supply and return legs of the ring main; the calculated difference in flows enables the ultrapure water production system to match demand

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| life science reagents |

The scientific, political and economic implications of COVID-19: an insider’s perspective It is widely assumed that the life science industry performed well off the back of the COVID-19 pandemic, with the demand for assays and molecular tools driving unprecedented sales to support global research. This may be true in the short term, but a broader vision must be applied to business models to ensure that appropriate measures are in place for future success. In this issue of BioScience Today, we talk to Dr Tillmann Ziegert, Managing Director of Biorbyt Ltd, about how the company weathered the initial storm of the COVID-19 pandemic, the importance of business agility to grasp the opportunities that arise during such turbulent times, and the subsequent economic and political landscapes. REMAINING AGILE The COVID-19 pandemic presented many challenges for business operations, especially for companies like Biorbyt that supply essential consumables and reagents – including antibodies, proteins and molecular tools – to life sciences labs around the world. Throw in the mix the Brexit debacle and, if you weren’t prepared or ready to rapidly evolve, then the train was leaving the station without you. Tillmann explained: “We’re a global company based in Cambridge, UK, with offices in Wuhan, China, and St. Louis, USA. Our logistics hub and one of our labs are located in Wuhan, so obviously, we had to re-jig our transportation routes fairly quickly when the pandemic hit. However, as almost all the labs we supply were closed during the first global lockdown, logistics wasn’t really an issue; people literally couldn’t do their scientific research. This obviously resulted in a huge drop in business, and forced us to carefully plan our next move. People were

under the illusion that it was a great opportunity for reagent suppliers, but initially, when all the labs were closed, it was the opposite, and many smaller businesses suffered.” “We endured those months and managed to hold on to all of our employees, which was crucial to be able to hit the ground running when labs reopened. Business is nearly back to pre-pandemic levels, but the logistical environment has changed with new – unforeseen – global challenges. Overall, COVID-19 has made customs officials more suspicious of anything life sciences related, which means increased paperwork, greater uncertainty and, ultimately, delays in delivery times.” “Brexit has obviously not helped the situation, and made shipping into Europe a real challenge, resulting in even more paperwork, changes to certification requirements, and additional tariffs – causing even longer delays. One solution we explored was to invest in a European hub, like we have in the USA and China. But, although we

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| life science reagents |

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| life science reagents |

may not entirely agree with what has happened, we are committed to Britain. We have built our lives and careers here, and have many employees we care about and have a certain responsibility for. We therefore didn’t want to do anything radical, and will continue working with our strong partnership network inside the EU.” “For small companies, it’s a balancing act, and these issues need to be integrated into long-term business planning. It’s not going to get easier, which means you need the resources in IT, logistics and operations to deal with the problems in a more efficient way. And this is where business agility truly comes into play. One of the major initiatives we have implemented during this time is in our stock management. Our portfolio includes over 500,000 research reagents, which obviously can’t all be stocked, but we are continuously analysing our top sellers and increasing their baseline stock levels. This strategy adds to our overheads and risk, but in a time where the customer expectation is at ‘Amazon’ levels – ‘I ordered it yesterday, why hasn’t it arrived today?’ – we will be well positioned to meet their needs.”

OPPORTUNITIES AMID A CRISIS In 2021, Biorbyt celebrated its 10th year as a trusted member of the scientific community. The company could have never forecast the recent events but, because of the entrepreneurial blood running through its veins, it was able to sniff out the opportunities and pave a clear path for the future ahead. Tillmann continued: “There have been many business positives to arise from these otherwise difficult times. We have expanded our portfolio to include various SARS-CoV-2 related reagents – including spike proteins, variant proteins, antibodies and ELISA kits – to support researchers working on COVID-19 vaccines. We are also looking to develop a more accurate and robust research diagnostic tool for COVID-19. Currently, most tests are based on a lateral flow assay, where you have one antibody with a colourimetric output. This method is acceptable, but prone to returning false-negative results, meaning it needs a follow-up PCR test. A more accurate technique is no doubt required, so we are engaging in some early R&D into building a more robust kit, with the goal of making it ‘future proof’.” “We are also collaborating with a fellow British company to develop an assay that includes the trimeric spike protein for the Alpha variant. This company has managed to successfully express the complete viral protein, which is quite a scientific achievement, because of its immense size.

There have been many business positives to arise from these otherwise difficult times. We have expanded our portfolio to include various SARS-CoV-2 related reagents – including spike proteins, variant proteins, antibodies and ELISA kits – to support researchers working on COVID-19 vaccines. Dr Tillmann Ziegert, Managing Director of Biorbyt Ltd

This could be a great product for the current market, and early results show good specificity and sensitivity. But, as we have learned, SARS-CoV-2 is rapidly evolving, so there are a lot of additional reagents that customers will need, which is why we are forming additional partnerships to develop more of these proteins and continue our support of research worldwide.”

THE WIDER IMPLICATIONS “Scientific and technological advancements have been pivotal to vaccine development and tracking SARS-CoV-2 during the pandemic, improving the profile of science to not only the general population, but also to governments and political parties. Scientific R&D has proven, once again, it is a crucial part of our society. This has already resulted in more funding and support for companies looking to innovate technologies to improve research so that, next time, we will have a more rapid response to improve health outcomes, and to minimise the economic and social fallout.” “COVID-19 united the scientific community with a common cause, rallying resources and personnel to propel research in this field years in advance. The virus had a spotlight, and a lot of superb technology has been developed as a result. It doesn’t necessarily mean you get a perfect diagnostic kit or a cure, but gradual – sometimes giant – improvements. mRNA vaccines are a prime example. We have never had anything like this before, but we can now sequence a virus, copy the relevant genetic material, and stimulate an immune response by mimicking certain characteristics. Previously, this would have taken years to get through clinical trials, because the focus and, therefore, the funding just wouldn’t have been there. But now we have a new tool in our armamentarium, with efficacy and safety data available for future vaccines or treatments.” “This fast-tracked emergency response was accepted – and necessary – because of the acute health, social and economic impacts that the virus was having on all of us. Looking further afield, where does the next priority lay? One could easily argue cancer research: surely cancer could be cured if we focus our funding and attention there? But the nature of that challenge is a different beast; cancer isn’t an infectious disease caused by a single pathogen. The plurality of the disease, and its genetic and environmental links – combined with the many different stages – make it a complicated challenge. And who’s to say that cancer is the priority? Do absolute poverty and preventable diseases kill and impact more people in developing nations? Or should we focus more on environmental issues or depression? These questions run deep into the ethical and political spectrum, which is why – in a democratic society – funding is divided, and not normally bundled into one area.”

BIORBYT AND BEYOND “Qun Yang, Biorbyt’s COO, and I founded this company to provide the best possible service to the scientific community, and with the landscape continually changing, the company must be flexible to fulfil its mission. We are adjusting to the new global geopolitical realities established by the COVID-19 pandemic and Brexit, and acknowledged that this is the new norm. The ‘seasonal’ opportunities born out of recent times will fade, which is why we are exploring other innovative ventures to ensure we continue supporting ground-breaking scientific research well into the future,” Tillmann concluded. www.biorbyt.com

Pathways to great research About us

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As a team of expert scientists, we know first-hand the issues you face every day. Trusted by the global life science community, Biorbyt manufactures and validates thousands of research use reagents. From antibodies to ELISA kits, we have an extensive catalog of products to suit your needs.

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| european biotech |

Euro biotech: breaking down the barriers to a golden age Converting cutting-edge research into viable products remains a challenge for the European biotech sector. Jonathan Hay of Delin Ventures investigates how ambition can translate to reality.

Europe’s tech sector is going from strength to strength. The Covid-19 pandemic – and the world’s resulting reliance on technology to survive lockdowns – meant it enjoyed a record year of investment and growth. It raised in the region of US$40 billion and valuations of tech companies grew 46 per cent in 2020. This was the strongest 12 months in a five-year gallop, during which the sector grew fourfold.

to raise US$52.2 billion. This dwarfs the total figure for last year and is a clear signal of the challenge the European tech sector is starting to mount on the other industry behemoths in America and China. Thirty-five per cent of global seed stage capital has been raised by European start-ups and it is expected that 3.2 million people will be employed in European tech by 2025, according to new data produced by Dealroom.

The good times have continued in 2021 and in the first six months of this year Europe’s tech start-ups managed

The European biotech sector is not nearly as advanced when it comes to closing the gap with its counterparts

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| european biotech |

in China and America. In 2018, China and the US accounted for 43.3 per cent of all biotechnology patents filed. Figures from the World Intellectual Property Organization show that Chinese and American depositary authorities, which collect deposits of microorganisms for biotech patent procedures, were collecting thousands more deposits than European authorities. The main challenge for the European biotech industry is translating research into medicines. According to a study by management consultancy McKinsey & Co., Europe is on par with its American counterparts during the discovery phase, but it falls significantly short when converting research into products. European discoveries too frequently end up providing the foundation for great American companies. Illumina, for example, is headquartered in California, but it was built on the back of research into a new approach to DNA sequencing by Solexa a company spinout from the Chemistry Department of the University of Cambridge. The invention of the monoclonal antibody by Cesar Milstein in Cambridge was never even patented. There are unfortunately many such examples of failures to commercialise European inventions. This problem also used to hamper the European tech sector and is not a new issue. In a 1995 report on innovation, the European Commission acknowledged that companies and governments should ‘redeploy their efforts and improve capability to translate research into commercial success’. Emphasis was subsequently placed on strengthening the management of knowledge and intellectual property by European universities. Strengthening the links between academia and industry would go some way to narrowing the gap with rival countries. Developing an environment that encourages entrepreneurial pursuits is equally important. Policies supporting this, like improving access to finance and tax credits, would foster domestic growth and production. If we look to France as a test case of a country that implemented such supportive policies, we can see the entire health ecosystem benefitted. The sector as a whole doubled in size over the last five years, with 41 per cent of companies launched between 2014 and 2018 – one of which is DNA Script. Its plan to equip labs with their own DNA printers attracted €80 million in Series B funding from European investors. In the UK, the Industrial Biotechnology Strategy is being rolled out in the hope of positioning the UK as an international industrial biotech innovation and commercialization hub by 2030. Steve Bagshaw, Chair of the Industrial Biotechnology Leadership Forum, says the UK is a world leader in bioscience research but adds that the country needs supportive government policies and

“The UK is a world leader in bioscience research but the country needs supportive government policies and simplified, yet rigorous, regulatory frameworks to make it a world leader in practice.” Steve Bagshaw, Chair of the Industrial Biotechnology Leadership Forum

Jonathan Hay

Partner at Delin Ventures, a UK-based VC firm which invests in breakthrough life science and technology businesses.

simplified, yet rigorous, regulatory frameworks to make it a world leader in practice. Supportive policies alone will not be enough to improve the fortunes of the European biotech sector; it also needs access to capital. Initial public offerings (IPOs) are four to five times larger in America than in Europe, which is a fragmented market. European biotechs are listed on 15 different European stock exchanges, with 90 per cent listed in their home countries. This will take a long time to change. The real solution is to nurture the entrepreneurial ecosystem and build on the European talent pool that is emerging. The European tech sector is leading the way on this. The UK’s Alex Chesterman, of LoveFilm, Zoopla and now Cazoo fame, Sweden’s Daniel Ek and Martin Lorentzon, who founded Spotify, and Sebastian Siemiatkowski, Niklas Adalberth and Victor Jacobsson, who founded Klarna, are all part of a rich ecosystem of entrepreneurs who want to stay in Europe and are nurturing the next generation. Their success fuels the growth and sustainability of other tech companies and the industry across the continent. They can recycle existing talent, leverage established networks and attract the attention of funds more easily. We are beginning to see the same trend appear in the European biotech sector. In 2019 Denmark’s Genmab raised $580 million on NASDAQ and is now worth close to $30 billion. More recently the founders of BioNTech, Ugur Sahin, OzlemTureci, and the Strungman brothers set examples for what can be achieved. We need to build on such successes and support Europe’s entrepreneurial ecosystem. Entering the golden age of biotechnology, Europe trails the heavy hitters in translating discoveries into products. But with supportive government policies, sufficient capital and a strong talent pool, the outlook is bright, even if the road between innovation and commercialisation remains somewhat rocky.

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New research database goes live A new platform for life sciences and chemistry researchers has gone live. Dimensions L&C analyses over 120 million scientific publications, millions of patents, grants and clinical trial documents, enabling researchers to get complex and diverse answers directly from the source content.

Digital Science recently announced a collaboration with OntoChem (ontochem.com). Dimensions L&C uses the ontologies from OntoChem, which include around 40 million concepts and 100 million synonyms from more than 35 knowledge domains such as compounds, proteins, diseases, drugs, materials, methods, devices or species, enabling a high quality, context sensitive knowledge discovery tool.

Users can search for small molecules, chemical reactions and gene sequences, validate biomarkers, understand disease mechanisms and identify drug targets.

Christian Herzog, CEO Dimensions, said: “There is an ever growing publication haystack and researchers need to find the needles of information quickly and efficiently.

They can also quickly discover relevant chemical information in broader life sciences and chemistry research areas working with a chemistry structure editor and a biosequence search for nucleotides and proteins. Different from other products, data is identified in full-text documents on a daily basis, creating a highly comprehensive and up-to-date resource.

“In the past you needed to know what to ask the search engine in order to find it, but with Dimensions L&C, we are now providing next generation discoverability for life sciences and chemistry researchers: an ontology driven retrieval engine which identifies relationships and links in more than 120m publications - allowing the researcher to move on from search to AI-supported discovery.”

Medical cannabis crowdfund raises millions A British company has raised over £3.4million in Europe’s largest ever medical cannabis crowdfund. Grow will use the crowdfund investment to expand operations in the UK and Europe and support R&D. The medical cannabis sector is tipped for significant growth in the coming years, with medicines prescribed for symptoms related to health issues such as epilepsy, insomnia and chronic pain. Europe’s medical cannabis sector is expected to be worth $3.1bn by 2025. The company recently bought Sanoid Isolates, a production facility in Andalusia, Spain. This will allow

Grow to produce cannabis in climates similar to the cannabis-growing regions of California, and process in-house to produce a wide range of cannabis-active pharmaceutical ingredients and cannabis medicines.

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Advances in longitudinal RWD and genomics access for drug development in Africa A new partnership aims to build the largest integrated clinical and genomics data biobank in Africa, representing a major boost for RWD research across the continent. The collaboration is between BC Platforms (BCP), a global leader in genomics research, analytics and global data access, and the African Institute of Everyone Genome (AiEG), a South African genomic company which is 100% black-owned and controlled. AiEG is supported by the African Institute of Biomedical Science and Technology, based in Zimbabwe and South Africa. EveryoneGenome project hopes to begin successfully impacting the lives of millions of Africans under the slogan “Black DNA matters.” The company seeks to foster a progressive movement that will empower African research participants, communities and researchers to engage with, and benefit from, genomic research and biobanking in a fair and mutually beneficial manner. As part of the collaboration, BCP’s platform will enable RWD research, involving 10M+ consenting patient genomes from all 54 African countries, to be collected by AiEG over a period of 10-15 years. The main goal of the research will be to enable drug development and clinical research for patients in sub-Saharan Africa. To date, global investment in African genome research has been lacking, with only 1% of total funding directed towards genomics research and clinical studies in Africa. [1] In terms of human genomic analyses, only around 5000 to 10,000 whole African genomes have been studied, in contrast to up to 1 million genomes globally. This

“Supporting regional genomics initiatives and RWE research is an important part of our vision to build the world’s leading analytics platform enabling rapid drug development.” Tero Silvola, CEO, BCP’s

contrasts with the fact that 25 per cent of the world’s population is expected to be based on the African continent by 2050. This significant growth sits alongside a current and ongoing increase in pharmaceutical expansion, with the estimated value of Africa’s pharmaceutical market growing to $20 billion in 2018. The importance of understanding the full genetic diversity of patients in sub-Saharan Africa is critical for drug development: novel target identification, validation and early insights into adverse events. It has been well described that the genetic diversity represented by patients from the African continent is the greatest in the world. [2] As part of the Strategic Data Partnership with AiEG, BC Platforms is providing a cloud-based, scalable Discovery and Research Platform, made available to AiEG and commercial researchers via Microsoft Azure. AiEG has built a large footprint of public and private healthcare entities and experienced research clinicians who consent patients for sharing clinical and genomic data for research. The first pilot cohort of patients is anticipated to be engaged in October 2021. BCP’s role will enable research collaborations with drug developers, data management and preparation of analysis-ready datasets and leading with global best practices in patient data privacy and security. BCP’s CEO Tero Silvola said: “Supporting regional genomics initiatives and RWE research is an important part of our vision to build the world’s leading analytics platform enabling rapid drug development. “We understand the importance and significant opportunity involved in ensuring that African data is represented in Life Sciences research in the near to long term.” Joe Mojapelo, CEO at AiEG, added: “Our goal is for African DNA to be studied on its own and be part of clinical trials for new and novel therapies treating a truly global population. Through the RWE that will be produced by future studies in collaboration with BCP, leveraging their integrated cloud-based platform alongside our region-leading database, we are keen to contribute to a new world of research equity. This means promoting access to African genomic data and one day eradicating unnecessary side effects for the people of South Africa, the African continent and eventually the global African diaspora.”

REFERENCES 1. Pennisi, E. Africans begin to take the reins of research into their own genomes. Science, 4 February 2021. https://www.science.org/ news/2021/02/africans-begin-take-reins-research-their-own-genomes 2. Ning Yu, Feng-Chi Chen. Larger Genetic Differences Within Africans Than Between Africans and Eurasians. GENETICS, May 1, 200.2. https://www.genetics.org/content/161/1/269

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Pioneering breakthrough in treatment of ‘devastating’ neurological disorder IntraBio Inc has announced positive data from its multinational clinical trial of IB1001 for the treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff disease). IB1001 demonstrated a statistically significant and clinically meaningful improvement in symptoms, functioning, and quality of life in both the primary and secondary endpoints for pediatric and adult patients with GM2 Gangliosidosis. The trial met its primary endpoint, the Clinical Impression of Change in Severity (CI-CS), which was assessed by blinded, centralised raters (professors of neurology with expertise in movement and neurological disorders). The trial also met secondary endpoints including the Scale for the Assessment and Rating of Ataxia (SARA), the Modified Disability Rating Scale (mDRS), the Investigators’, Caregivers’, and Patients’ Clinical Global Impression of Change (CGI-C) assessment. IB1001 was observed to be safe and well-tolerated, with no drug-related serious adverse events. “The results of this study are hugely important for the GM2 community,” said Dr. Susanne Schneider, principal investigator and Professor of Neurology from Ludwig Maximilian University of Munich. “IB1001 is the first drug to demonstrate a statistically significant and clinically meaningful effect for the treatment of GM2 Gangliosidosis. IB1001 has a very compelling safety profile, easy oral administration [sachet mixed with water], affirming its very favourable risk/benefit profile as a treatment for this devastating disease.” Professor Antony Galione, FRS, FMedSci, Statutory Professor of Pharmacology, University of Oxford commented: “GM2 Gangliosidosis (Tay-Sachs and Sandhoff disease) is a devastating disease that has never had any available treatment. We are very excited that IB1001 is the first drug that is effective for this disorder and will improve the lives of so many patients and their families. Given what is known about IB1001’s mechanism, and its multiple successful clinical trials, we will continue to investigate this drug for other rare genetic neurological diseases and for more common neurodegenerative diseases prevalent in society with large unmet medical needs.” In a joint statement, Rick Karl, President of the Cure Tay-Sachs Foundation and Dan Lewi, Chief Executive Officer of the Cure Action for Tay-Sachs Foundation, said: “This treatment is a major breakthrough for the GM2 Gangliosidosis community that includes Tay-Sachs and Sandhoff. It is the first drug to offer hope to the patients and families affected by these devastating diseases. They are progressive, life-threatening conditions with no approved medicinal treatments. There is an urgent need for this effective treatment to be approved and made available for patients in our community before the window of therapeutic opportunity is lost.” The positive results of this IB1001-202 study are reinforced by the efficacy and safety profile of IB1001 already demonstrated in IntraBio’s successful IB1001-201 study for Niemann-Pick disease Type C (NPC). As is the case in the IB1001-202 clinical trial for GM2 Gangliosidosis, IB1001201 was the first clinical trial to demonstrate statistical significance and a clinically meaningful effect in patients

with NPC. These results provide further momentum for the broad clinical development program planned for IB1001 which will address high unmet medical needs for the treatment of both rare and common neurological disorders.

ABOUT THE IB1001-202 TRIAL IB1001-202 (NCT03759665) is a multinational clinical trial evaluating IB1001 for both symptomatic and neuroprotective, disease-modifying treatment for adult and pediatric patients with GM2 Gangliosidosis. Patients aged 6 years and older were enrolled at trial sites in the United States, the United Kingdom, the European Union. To investigate its symptomatic effects, IB1001 was assessed during a “Parent Study” consisting of a baseline period (with or without a study-run in), a 6-week treatment period, followed by a 6-week post-treatment washout period for examining symptomatic relief. In the “Extension Phase”, patients receive treatment with IB1001 for 1 year to study the neuroprotective, disease-modifying effects. Both the symptomatic and long-term benefits of treatment have previously been observed in observational clinical studies and are consistent with the pharmacological action of IB1001 demonstrated in in vitro and in vivo non-clinical studies. In addition to Clinical Study IB1001-202, IntraBio has completed a parallel multinational clinical trial with IB1001 for the treatment of Niemann-Pick disease Type C (NPC; NCT03759639). In September 2020, IntraBio announced the positive results of this trial (IB1001-201), which met both its primary and secondary endpoints and demonstrated a statistically significant and meaningful improvement in patients with NPC. IntraBio is currently conducting a parallel clinical trial for IB1001 for Ataxia-Telangiectasia (A-T; NCT03759678).

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Clive Minihan (left) and Andrew Halliday (right), founders of Personalised Diagnostics

Covid portal start-up exceeds 1 million tests and creates offshoot venture As the UK continues learning how to live with the pandemic, some key questions remain. Chiefly, how will the NHS grapple with the huge diagnosis and treatment backlog that has built up, and will the NHS become even more open to new technologies? The existential crisis caused by Covid-19 forced the whole healthcare industry to learn new ways of working almost overnight. Softward entrepreneurs Clive Minihan and Andrew Halliday are among the healthcare specialists who have had a busy 16 months. Predicting that the need to process Covid tests at scale would require the process to be digitised, the pair formed the startup Recova-19 in May 2020. To date, their testing portal has facilitated the processing of more than 1.2 million tests and their team has grown to 10. The cloud-based SaaS platform application has proved so successful that the duo plan to use it to further support resilience in the health care system in the crucial areas of point of care testing and remote diagnostics with a new venture, called Personalised Diagnostics Limited (PDX). It is intended that the new technology will be available to improve the ease of data collection and processing in clinical trials, innovative point of care diagnostic products and – building on the company founders’ existing strong connections with pharmacies and laboratories – personal genetic based tests in oncology, fertility and gastric health. The platform has been some time in the making, being originally designed in 2012 to allow remote data collection and diagnosis for the NHS and was successfully adopted in Dermatology and Sexual Health by NHS Wales. Last spring the pair quickly recognised that the platform’s ability to gather data remotely, store it securely, and deliver results electronically would be crucial in dealing with Covid testing. Fifteen months on, the company’s software

is used by two of the top three high street pharmacy chains, employers such as Cambridge University, and most of the UK’s UKAS accredited laboratories. The company sends all Covid testing results to Public Health England every morning. The portal has also recently been launched in Ireland. Clive says, “The success of the portal is based on Andrew’s total commitment that software has to work, be user friendly, and be constructed using agile methodology to enable adaptation for customer needs in an accelerated timeframe.” Dr. Tony Cooke, Chief Executive of Cambridge Clinical Laboratories, explained: “Using the Recova portal has transformed the time and potential mistakes in transcribing test details. We simply check samples in using a barcode scanner and upload the results from our Laboratory Information Management System once processing is complete. “The simplicity of the process, plus the added bonus of using the Recova software to facilitate our reporting to PHE, allows us to focus on what we do best – processing clinical samples. Without Recova we could not have successfully scaled our operations to cope with Covid as we have.” Additionally, given the concerns around the inevitable delay in addressing the backlog, individuals may be more willing to manage their healthcare privately through accessing clinical testing in the private market and accessing their own data in a secure and confidential portal under their own control. These are all areas that Clive and Andrew, are keen to explore and they are currently in discussion with clinical researchers, healthcare professionals and laboratories for whom remote data capture and reporting is crucial. Clive concludes: “With a million results behind us, we’ve shown our technology can reach scale and. with Personalised Diagnostics we aim to transform outcomes in healthcare for the future. It’s a really exciting prospect for everyone.” More details at pd2x.com

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New clinical study into R-ketamine use for Treatment Resistant Depression A clinical study to evaluate the safety and efficacy of PCN-101 (R-ketamine) has entered a new phase. R-ketamine is a stereoisomer of ketamine being developed for therapeutic treatment of psychiatric disorders such as Treatment Resistant Depression (TRD). The Phase 2a clinical trial has received the necessary regulatory and ethics approvals, and is led by Perception Neuroscience, a biopharmaceutical company developing innovative therapies in neuropsychiatric diseases. The trial is a double blind, placebo-controlled study in patients with TRD. Each of the 3 parallel arms will enroll 31 patients at multiple locations. Patients will receive either placebo, a 30 mg dose, or a 60 mg dose of R-ketamine intravenously. Patients will be assessed for depressive symptomology over the subsequent 14 days using the MontgomeryAsberg Depression Rate Scale, or MADRS. Topline data from the study is expected to be reported at the end of 2022. “We’re excited to take the next key step with this clinical trial to show the potential of PCN-101 for people living with TRD,” said Terence Kelly, PhD, CEO of Perception Neuroscience. “TRD impacts nearly 100 million people around the world, making up a third of patients living with depression; currently they are either undertreated

or unresponsive to existing treatment options. We believe PCN-101 holds promise in helping such treatment-resistant patients, as a potential rapidlyacting antidepressant which can be administered at home.” “We believe insight into the molecular properties of the single isomer, R-ketamine, has the potential to offer a highly differentiated profile from current treatment options,” added Florian Brand, CEO & Co-founder of atai Life Sciences. “Initiating this Phase 2 clinical study is a major step for our teams at Perception and atai and is a great achievement. We believe this work has the potential to deliver a novel option with diversified delivery capabilities that could decrease overall healthcare utilization, which may help us move toward our greater mission to improve care for patients who suffer from TRD.”

ABOUT PCN-101 Perception Neuroscience is developing PCN-101 (R-ketamine) for the treatment of Treatment Resistant Depression (TRD). PCN-101 is a single isomer of ketamine and belongs to a new generation of glutamate receptor modulators with the potential for rapid acting antidepressant (RAAD) activity and anti-suicidal effects. Pharmacologically, PCN-101 is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Nonclinical depression model studies in rodents suggest that R-ketamine could possess more durable and potent effects than S-ketamine despite a lower affinity to the NDMA receptor and potentially a more favorable safety and tolerability profile.

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Cleaning breakthrough for listeria elimination All traces of listeria spp in a highly sensitive food production environment have been successfully eliminated in a breakthrough pilot. The 11-week proof of concept saw Bio-Fence antimicrobial coatings applied to the floor and lower part of walls of a hot dog peeling room in a major sausage manufacturing facility in Israel. Despite repeated, strict cleaning and disinfection routines, the facility had a continuous pre-pilot presence of listeria sp, particularly on the production floor. During the three-week control phase prior to the application of the Bio-Fence coating, listeria was detected in 21 out of 23 (91%) daily floor samples; following the application of the Bio-Fence coating, listeria was completely undetectable on the floor surface during day-to-day production.* Results from the pilot also show a dramatic reduction of up to 99.9999% in the level of gram-negative bacteria as demonstrated by Enterobacteria (EB) readings, and a considerably improvement in hygiene levels as demonstrated by Total Count (TC) readings. Exactly the same cleaning and hygiene routines, involving a chlorinebased product, were practiced before and after the Bio Fence application. Environmental pathogens within the food production process remains one of the greatest risks to food safety, with the presence of these bacteria in the production environment directly linked to the contamination of food. The hot dog peeling room was specifically selected for the pilot as it poses a series of complex challenges to maintaining hygiene levels; the production environment includes low temperatures, humidity, condensation and heavy movement of workers and equipment – all conditions under which listeria can thrive.

Despite the pilot taking place under heavy organic load and wet conditions, the results demonstrate that Bio-Fence technology, when embedded in an industrial topcoat, can serve as a powerful anti-microbial solution that stabilises and prolongs the activity of standard sanitizers, thereby helping dramatically reduce the spread of listeria. As a result of the successful proof of concept, the manufacturing facility has continued to use Bio-Fence’s antimicrobial coatings and is now looking to expand the use of the coating in other areas of the facility. * Positive post-application listeria results were established on one weekend during the trial, as chlorine was not used in that weekend’s sanitation. Ofer Shoham, CEO of Bio-Fence, said: “Dealing with environmental pathogens like listeria, salmonella and others in food production processes is a continuous struggle for food manufacturers, especially in the production of sensitive food defined as RTE. “There is a direct link between the presence of these bacteria in the immediate environment of production equipment and the contamination of food products. Sadly, thousands of people are still infected by listeria every year, causing a mortality rate of more than 25%. “We are hugely encouraged by the breakthrough results of this pilot, which independently demonstrates the efficacy of the Bio-Fence product in helping eliminate listeria.” Bio-Fence is an Israeli health and food tech start-up, which develops antimicrobial coatings and paints to destroy micro-organisms on contact and create a contamination-free environment. Bio-Fence’s polymer is added to a topcoat that is then applied to surfaces for better sanitisation.

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AI could improve diagnosis for over 100,000 prostate patients in UK The use of AI to identify prostate cancer is currently being validated in the first retrospective study of its kind in the UK. Real-world data from hospitals and scanner types is being scrutinised, to show how the technology could improve accuracy of diagnosis, and potentially help over 100,000 patients per year in the UK alone. Prostate cancer is the most common cancer in men in Europe, Africa and the Americas, with 1.4 million diagnosed worldwide each year and 375,000 deaths. In the UK, prostate cancer now kills more patients each year than breast cancer, and 56% of cases in England are detected late, when the disease is high-risk or advanced. Improved ways of screening for and diagnosing the disease are needed to help detect the disease earlier and offer patients better treatment and outcomes. The study is a collaboration between Hampshire Hospitals NHS Foundation Trust (HHFT) and Lucida Medical Ltd, whose (Prostate Intelligence) technology uses radiogenomics, machine learning and image processing to analyse magnetic resonance imaging (MRI) scans. Results presented at the European Congress of Radiology (ECR) in March 2021 indicate that it can help automate labour-intensive tasks such as marking out lesions, and avoid unnecessary invasive biopsies, with unprecedented accuracy and consistency. The technology recently received the CE mark, allowing for use in hospitals. For the NHS to adopt this technology, its accuracy needs to be proven in a range of settings. Most studies on AI for radiology to date have used data from single centres, but it is known that performance can vary between hospitals and with equipment from different scanner types. This collaborative research led by HHFT will specifically test how the software would work at a range of different NHS hospitals and with all major MRI scanner manufacturers.

The PAIR-1 (Prostate AI Research – 1) study will collect data on 2100 patients who were diagnosed at seven different centres. All data will be de-identified so that the researchers will not be able to link it to individuals, following a strict protocol approved by the UK Health Research Authority. This work is especially valuable because it will allow the software to be tested with the same types of patients, scanners and hospitals that would be encountered in practical clinical use, but without impacting on patients’ care. Prof Richard Hindley, consultant urologist and lead for innovation at HHFT, said: “We are delighted that HHFT is able to work with Lucida Medical on this collaborative study. It will gather real-world information on the prostate cancer diagnostic pathway across a range of NHS Hospitals, and is a natural evolution for our trust having been leading participants in the PROMIS trial (2015-2017) which provided the evidence to support the incorporation of prostate MRI into the assessment of any man with suspected prostate cancer.” Dr Aarti Shah, consultant radiologist at HHFT and chief investigator for the PAIR-1 study, added: “Reviewing prostate MRI requires experience and expertise to ensure that the right patients have a biopsy as well as to help target biopsies to maximise the chances of finding significant cancers. AI has exciting potential to enhance the processes of screening and treating patients, and this study will provide strong evidence on its performance.” Lucida Medical co-founder and Chief Medical Officer Prof Evis Sala, Professor of Oncological Imaging at the University of Cambridge, said: “Now Pi has CE marking, clinical studies such as this are crucial to demonstrate the performance of the system in real-world clinical use. HHFT has brought together a group of Trusts representative of the wide range of settings across the NHS, from major teaching centres to district general hospitals.”

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palladium catalysts nickel foam

thin film 1

surface functionalized nanoparticles

organometallics

1.00794

Hydrogen

zeolites 11

anode

2 1

99.999% ruthenium spheres

6.941

2 8 1

22.98976928

24.305

Sodium

Magnesium 2 8 8 1

osmium

MOFs ZnS

40.078

2 8 18 8 1

85.4678

(223)

2 8 18 18 8 2

Francium

(226)

2 8 18 9 2

Ac (227)

Radium

2 8 18 10 2

91.224

2 8 18 18 9 2

138.90547

2 8 18 32 10 2

104

Rf (267)

2 8 18 19 9 2

140.116

Th 232.03806

2 8 18 32 32 10 2

2 8 18 21 8 2

140.90765

Thorium

Pa 231.03588

2 8 18 32 20 9 2

Protactinium

transparent ceramics EuFOD

spintronics

105

Db (268)

optical glass

2 8 18 13 1

2 8 18 32 11 2

2 8 18 32 12 2

183.84

2 8 18 32 32 11 2

106

Sg (271)

(98.0)

2 8 15 2

2 8 16 2

2 8 18 32 13 2

107

Bh (272)

Seaborgium

2 8 18 15 1

2 8 18 1

190.23

108

Hs (270)

Bohrium

2 8 18 16 1

102.9055

2 8 18 32 14 2

Mt (276)

Hassium

2 8 18 23 8 2

(145)

Np (237)

Neptunium

150.36

Promethium 2 8 18 32 21 9 2

2 8 18 24 8 2

2 8 18 32 15 2

151.964

Samarium

2 8 18 32 22 9 2

2 8 18 32 24 8 2

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110

Ds (281)

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111

Rg (280)

(244)

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200.59

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Roentgenium

(247)

Americium

Curium

(247)

Berkelium

112

Cn (285)

Ge 72.64

204.3833

113

Nh (284)

Copernicium

2 8 18 18 4

207.2

114

Fl (289)

Nihonium

2 8 18 28 8 2

2 8 18 29 8 2

Mc (288)

Flerovium

164.93032

Er 167.259

Holmium 2 8 18 32 28 8 2

(251)

(252)

100

(257)

Fermium

2 8 18 31 8 2

101

Md (258)

laser crystals

2 8 18 32 32 18 5

116

102

No (259)

Mendelevium

Lv (293)

2 8 18 32 8 2

2 8 18 32 32 8 2

103

2 8 18 32 18 6

pharmacoanalysis

(262)

2 8 18 32 18 7

2 8 18 32 32 18 6

117

(294)

Lawrencium

calcium wires

process synthesis

2 8 18 32 18 8

(222)

Radon 2 8 18 32 32 18 7

118

Og (294)

Oganesson

2 8 18 32 32 18 8

h-BN

InGaAs AuNPs

spectroscopy

superconducto

chalcogenides excipients CVD precursors deposition slugs YBCO

refractory metals

metamateri Fe3O4

shift reagents

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2 8 18 18 8

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2 8 18 8

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fluorescent microparticles

Nd:YAG

83.798

Tennessine

2 8 18 32 9 2

2 8 18 32 32 8 3

2 8 8

Krypton

cryo-electron microscopy

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ferrofluid dielectrics

2 8 18 18 7

Astatine

174.9668

Iodine

Lutetium

Nobelium

39.948

Argon 2 8 18 7

126.90447

Livermorium

Ytterbium 2 8 18 32 31 8 2

(209)

173.054

Thulium

2 8 18 32 30 8 2

2 8 18 18 6

Polonium

Moscovium

168.93421

Erbium 2 8 18 32 29 8 2

Einsteinium

2 8 18 30 8 2

79.904

127.6

2 8 18 32 18 5

Neon

Bromine

Tellurium

208.9804

115

ITO

20.1797

2 8 7

35.453

2 8

nano ribbons

Chlorine 2 8 18 6

78.96

Bismuth 2 8 18 32 32 18 4

32.065

121.76

2 8 18 32 18 4

2 8 6

Selenium 2 8 18 18 5

Fluorine

Sulfur 34

2 7

18.9984032

Antimony

Lead 2 8 18 32 32 18 3

2 8 18 5

74.9216

Tin

2 8 18 32 18 3

Arsenic

118.71

Thallium 2 8 18 32 32 18 2

Germanium 2 8 18 18 3

2 8 5

30.973762

15.9994

Phosphorus 2 8 18 4

Oxygen

silver nanoparticles

Californium

rhodium sponge

28.0855

114.818

2 8 18 32 18 2

2 8 4

2 6

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graphene oxide

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14.0067

Indium

Mercury

Dysprosium 2 8 18 32 27 8 2

2 8 18 18 2

Pu Am Cm Bk Cf Es Fm enantioselective catalysts Plutonium

2 5

Nitrogen

Silicon 2 8 18 3

69.723

112.411

162.5

Terbium

Cadmium 2 8 18 32 18 1

Gallium

Gold

158.92535

2 8 18 32 25 9 2

196.966569

Darmstadtium

Gadolinium 2 8 18 32 25 8 2

2 8 18 32 17 1

Zinc

Silver

195.084

157.25

Europium

2 8 18 18 1

2 8 3

26.9815386

2 8 18 2

65.38

107.8682

Platinum

Meitnerium

2 8 18 25 8 2

106.42

192.217

109

2 8 18 18

Palladium

macromolecules 61

12.0107

Carbon

Aluminum

Copper

Iridium 2 8 18 32 32 14 2

63.546

Nickel

Rhodium

Osmium 2 8 18 32 32 13 2

58.6934

Cobalt

101.07

Rhenium 2 8 18 32 32 12 2

58.933195

Ruthenium

186.207

Tungsten

144.242

Iron

Technetium

Nd Pm Sm

Uranium

55.845

2 8 18 13 2

2 4

Now Invent.

indicator dyes

MOCVD

95.96

2 8 18 22 8 2

238.02891

54.938045

Manganese

Molybdenum

Neodymium 92

2 8 14 2

sputtering targets tungsten carbide

2 8 18 12 1

Dubnium

2 8 13 2

rare earth metals

mesoporous silica MBE

51.9961

180.9488

Praseodymium 2 8 18 32 18 10 2

Chromium

Tantalum

Rutherfordium

Cerium 90

quantum dots

2 8 13 1

ultralight aerospace alloys

92.90638

178.48

2 8 18 32 18 9 2

2 8 11 2

Niobium

epitaxial crystal growth drug discovery

Hafnium

Actinium

50.9415

Vanadium

Zirconium

Lanthanum 2 8 18 32 18 8 2

47.867

Yttrium

Barium 2 8 18 32 18 8 1

2 8 10 2

Titanium

88.90585

137.327

Cesium

2 8 18 8 2

87.62

132.9054

Scandium

Strontium 2 8 18 18 8 1

44.955912

Calcium

Rubidium 55

2 8 9 2

isotopes

39.0983

Potassium

3D graphene foam

nanodispersions

He Helium

2 3

Boron

2 8 2

2 8 8 2

4.002602

10.811

Beryllium

nanogels

metal carbenes

bioactive compounds

9.012182

Lithium

2 2

gold nanoparticles

III-IV semiconductors

screening chemicals

buckyballs

janus particles

glassy carbon alternative energy

diamond micropowder

Now Invent!

metallocenes BINAP

conjugated nanostructure

BioScience Today 25

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