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University of 91ֱ�� spinout company, Crucible Therapeutics, a biotechnology company developing novel therapies to treat the most common genetic form of motor neurone disease (MND), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), has secured £5 million financing from Northern Gritstone and Argobio Studio.

MND is a neurodegenerative disease which causes nerve cells to progressively stop working throughout the spinal cord and the brain. The disease, which predominantly affects people aged 60-65, leads to progressive paralysis and death usually within three to six years from the onset of symptoms. 

FTD involves the degeneration of frontal and temporal lobes of the brain causing altered personality features. It most commonly affects people aged 45-65 and can affect behaviour, personality, language and movement. There is currently no effective treatment for MND or for FTD.  

Crucible Therapeutics was developed based on research from three leading experts in the internationally renowned Neuroscience Institute at the University of 91ֱ��. The collaborative team consists of Professor Guillaume Hautbergue, Professor of Translational RNA Biology, Professor Mimoun Azzouz, Chair of Translational Neuroscience and Professor Dame Pamela Shaw, Professor of Neurology and Director of the 91ֱ�� Institute for Translational Neuroscience (SITraN). 

Professor Guillaume Hautbergue, Director of Crucible Therapeutics, led the development of earlier research funded by the MND Association. Working alongside Professor Dame Pamela Shaw and Professor Mimoun Azzouz, the team identified a particular protein called SRSF1 which binds to the pathological repeated RNA molecules and transports them out of the cell centre, effectively overriding the gatekeeping machinery within the nucleus by opening a back door. The researchers have further shown that by reducing the SRSF1 protein or altering its makeup so that it is unable to interact with the cell’s export machinery, it is possible to reduce the amount of rogue RNA molecules escaping into the cell’s cytoplasm.

Building on this research, the team have developed a pioneering gene therapy technology aimed at interacting with the SRSF1 pathway to bring about a therapeutic effect in MND and FTD patients. 

Following the demonstration of the mechanism of action of SRSF1 and further proof of concept work, the Cell and Gene Therapy Catapult (CGT Catapult) provided translational development support to the programme through medicines development planning, analytical method development and preclinical safety testing advice. Alongside this collaboration between 91ֱ�� and CGT Catapult, further research at 91ֱ�� into the development and testing of the gene therapy was funded by LifeArc and the MND Association, through the LifeArc Philanthropic Fund. 

Crucible is receiving financing and support from Northern Gritstone and Argobio Studio to fund essential development and manufacturing work, which will take the company up to its first clinical trial.

It is the first spinout focusing on advanced therapeutics to receive investment from Northern Gritstone, the investment business focused on university spinouts and technology-enabled businesses in the North of England. Argobio Studio is a pan-European biotech company start-up vehicle whose experienced team of entrepreneurs and scientific directors has supported multiple advanced therapeutics start-ups across Europe since inception. Demonstrating its ongoing commitment, Argobio Studio continues to offer operational guidance to Crucible throughout its spinout phase and will persist in providing support during the upcoming preclinical development stage.

Neill Moray Mackenzie and Jonathan Foley from Argobio Studio will support the development of the company’s novel therapies. Together their considerable R&D, commercial and manufacturing experience in multiple gene therapy companies will be brought to bear at this critical time for Crucible. Professor Guillaume Hautbergue will join them as Non-Executive Director on the board of Crucible Therapeutics representing the founders.

Professor Guillaume Hautbergue, Founding Director of Crucible Therapeutics, Professor of Translational RNA Biology at the University of 91ֱ��, said: “I worked on the therapeutic target for more than 15 years, initially to study its roles from a discovery perspective, prior to realising its promising potential for the development of a novel gene therapeutics in close collaboration with the other founders. What an incredible journey! I feel blessed and honoured to be working with them and moving forward a bench discovery onto the translational path. I am now delighted to continue our preclinical development programme in partnership with Argobio Studio and Northern Gritstone who bring very significant levels of expertise and support."

Professor Mimoun Azzouz, Co-Founder of Crucible Therapeutics, Professor and Chair of Translational Neuroscience at the University of 91ֱ��, Founder and Director of Gene Therapy Innovation and Manufacturing Centre (GTIMC), said: “I am delighted with the support received today from Northern Gritstone and Argobio Studio. Crucible Therapeutics is a great addition to the favourable and dynamic gene therapy ecosystem at the University of 91ֱ��. This is a massive deliverable which would enable the progress of the translational pipeline being developed by the company towards potential life-changing therapies for patients with MND and FTD.”

Professor Dame Pamela Shaw, Co-Founder of Crucible Therapeutics, Professor of Neurology at the University of 91ֱ�� and Director of the 91ֱ�� Institute for Translational Neuroscience (SITraN), said: “Our novel therapeutic approach has made significant strides in our pursuit of transforming how these devastating diseases are treated and potentially achieving meaningful therapeutic impact. Today marks an important milestone, which brings us closer to supplying transformative treatments to people with neurological diseases like MND and FTD. The significant experience and support that Northern Gritstone and Argobio Studio bring to Crucible further enables our pre-clinical development while allowing us to strategically build our team.”  

Duncan Johnson, CEO of Northern Gritstone, said: “I’m pleased to say that the Crucible’s founders, Professors Dame Pamela Shaw, Guillaume Hautbergue and Mimoun Azzouz, exemplify the world-leading research and medical expertise already present in the North of England and we look forward to working with them as they prepare to bring Crucible's therapeutic candidate closer to clinical trials. We also welcome the opportunity to invest alongside the team at Argobio Studio whose invaluable experience in gene therapy will be critical as Crucible takes the first important step in its journey.”  

Neill Moray Mackenzie, Entrepreneur in Residence, Partner at Argobio Studio, said: “Ever since I had tea with Stephen Hawking in Cambridge many years ago, I have been searching for a realistic hope of a cure for this devastating disease out of respect for him. At Argobio Studio, we have the opportunity at looking all the technologies with unbiased view and I can honestly say the 91ֱ�� approach was the most compelling for us. While the therapy is still in early stages of development, we look forward to working alongside Northern Gritstone to bring the programme to fruition.”

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Additional information

91ֱ�� the Founders

Professor Guillaume Hautbergue is a distinguished researcher renowned for his contributions in the field of RNA biology and molecular neuroscience. With an impressive academic background, he has made significant strides in understanding the molecular mechanisms underlying neurodegenerative diseases. His expertise lies in investigating RNA metabolism and its implications in conditions such as Motor Neurone Disease (MND). Professor Hautbergue’s groundbreaking research has garnered international recognition, and his findings hold promise for the development of novel therapeutic strategies. Through his unwavering dedication to advancing neuroscience knowledge, Professor Guillaume Hautbergue continues to shape the field and inspire future generations of researchers. In 2019, he was invited and elected Fellow of the Royal Society of Biology (FRSB) in recognition of “a prominent contribution to the advancement of the Biological Sciences”.

Professor Mimoun Azzouz is a highly accomplished researcher and international expert in the field of gene therapy. With an extensive background in neuroscience and gene therapeutics, he has made significant contributions to the development of innovative gene-based treatments for neurological disorders. His research focuses on the delivery of therapeutic genes to the central nervous system, particularly in the context of neurodegenerative diseases like Parkinson’s and MND. Driven by a passion for translational science, Mimoun Azzouz’s work bridges the gap between bench and bedside, aiming to bring promising therapies from the laboratory to clinical application. Through his pioneering efforts, he has emerged as a leading figure in the field of gene therapy for neurological conditions, offering hope for patients worldwide. Azzouz has also won prestigious awards in keeping with the excellence of his science, including the ERC Advanced Investigator (2011), ERC Proof-of-Concept (2017) and IMI award (2020).

Professor Dame Pamela Shaw is an internationally renowned clinician and academic researcher known for her work in the field of ALS/MND. Pamela is a Consultant Neurologist at the 91ֱ�� Teaching Hospitals NHS Foundation Trust and Professor of Neurology and Director of the 91ֱ�� Institute of Translational Neuroscience (SITraN), where the academic research underpinning Crucible’s therapeutic candidate was developed. The range of Pamela’s molecular, genetic and clinical contributions has attracted international recognition and the award of multiple prizes, including the Wellcome Senior Fellowship in Clinical Science between 1991 and 2000. In 2014, she was made a Dame

Commander of the Order of the British Empire (DBE) and in 2022 she received the British Neuroscience Association award for an outstanding contribution to Neuroscience. Her translational research had led to several improved outcomes for patients with MND.

Neill Moray Mackenzie is a seasoned veteran in the biotech industry, boasting a wealth of

experience and expertise. With a career spanning several decades, he has played a pivotal role in shaping and advancing the field of biotechnology. Throughout his professional journey, Mackenzie has held key leadership positions in prominent biotech companies, overseeing strategic initiatives, business development, and successful commercialization of innovative therapies. His keen business acumen, combined with his in-depth understanding of scientific advancements, has contributed to his reputation as a visionary leader in the biotech sector. Neill Moray Mackenzie continues to drive growth and innovation, propelling the industry forward with his remarkable contributions.

Jonathan Foley is Scientific Director at Argobio with 20 years of experience in drug discovery, analytical development, and rare disease research. Most recently, Jonathan was a Senior Director and Head of Discovery at Freeline (Nasdaq: FRLN). Prior to Freeline, he was a Lecturer at University College London in the group of gene therapy pioneer Professor Amit Nathwani and was a member of the first research team that spun Freeline out of academia. During his academic career he published extensively in the areas of biochemistry, bleeding disorders and complement-mediated disease.

91ֱ�� Crucible Therapeutics

In 2023, Crucible emerged as a spinout from the University of 91ֱ��, focusing on the development of groundbreaking therapies aimed at addressing the significant unmet medical needs in neurological diseases. The foundation of Crucible is built upon the groundbreaking research conducted by world-renowned scientists at SITraN (91ֱ�� Institute for Translational Neuroscience). As a pre-clinical stage biotech company, Crucible is diligently advancing therapeutic candidates specifically designed to tackle conditions such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Through their innovative approach, Crucible aims to revolutionise the treatment landscape and bring hope to those affected by these debilitating conditions.

For more information please go to: www.sheffield.ac.uk/rpi/commercialisation/commercial-portfolio/crucible-gene-therapeutics

91ֱ�� Argobio Studio

Argobio is a start-up studio based in Paris, France, dedicated to turning cutting-edge innovations into breakthrough biotech companies. Argobio sources innovative early-stage projects on therapeutics from renowned European academic research institutions with a focus on rare diseases, neurological disorders, oncology, and immunology. 

Argobio selects and incubates these projects with the goal to create biotech companies and develop them up to a significant Series A financing. Argobio provides broad expertise in the discovery and development of novel drugs with a team of highly experienced Biotech entrepreneurs.

For more information please go to:

91ֱ�� Northern Gritstone

Northern Gritstone is a groundbreaking investment company, which is dedicated to supporting the commercialisation of academic spin-outs and IP-rich businesses based in the North of England.

Launched in July 2021 by the Universities of Leeds, Manchester and 91ֱ��, it was founded with the philosophy of Profit with Purpose, combining strong returns for investors with wider positive, societal and economic impact, including supporting Levelling Up and high-skilled job creation in the North of England.

The company is deploying more than £300m of capital, having secured commitments from a broad and diverse base of investors including British Patient Capital, Greater Manchester Pension Fund, West Yorkshire Pension Fund, M&G and Columbia Threadneedle, among others. It is dedicated to financing companies in some of the UK’s fastest growing sectors such as advanced materials, energy, health technology and cognitive computation and has already made 11 investments in some of the UK’s most exciting future science and technology-enabled businesses.

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