Success stories of projects funded by Translation Manchester: Link Biologics

by | Jun 26, 2024 | Case studies | 0 comments

Harnessing the body’s own protective pathways to treat chronic diseases

 

The problem

More than a billion people suffer from chronic diseases where inflammation and tissue degeneration significantly limit daily activities and reduce quality of life. For example, loss of joint mobility due to arthritis causes disability, affecting walking and climbing stairs, whilst eye conditions can affect reading, driving and recognising faces. This places an enormous burden on the healthcare system and has a huge socioeconomic impact by reducing the productivity of people living with these conditions and those caring for them. Thus, there is a great need for solutions that can tackle the core of these diseases and mitigate their impacts on patients and society.

 

Introducing Tony Day and Caroline Milner

Tony Day is a Professor of Biochemistry and Caroline Milner is a Senior Lecturer, in the Division of Cell Matrix Biology and Regenerative Medicine within the Faculty of Biology, Medicine and Health at the University of Manchester. Both Tony and Caroline have backgrounds in Biochemistry and Chemistry. They were both Versus Arthritis Research Fellows at the University of Oxford; it was during Tony’s fellowship (1991-1998) that he began to work on osteoarthritis (OA), with their first grant together on OA in 2000. They moved to the University of Manchester in 2005/2006 where they further developed their work and expanded into additional translational research areas including Dry Eye Disease (DED). This led to the formation a spin-out company in 2021 to commercialise and maximise the potential of their work for the benefit of patients with DED and OA.

 

The translational journey: From concept to implementation

The translational journey for Tony and Caroline started in 2005, around the time they moved to the University of Manchester from Oxford. The team had recently discovered that a protein called TSG-6, which is made in our bodies in response to inflammation, can prevent specialised cells called osteoclasts, from breaking down bone tissue. This paved the way for them to explore the potential of TSG-6 as a treatment for osteoporosis, a health condition that makes the bones fragile and more likely to break. Funding from various sources including Isis Innovation (Oxford), Versus Arthritis, GalaxoSmithKline (GSK) and a prestigious “Developmental Pathway Funding Scheme” (DPFS) award from the Medical Research Council (MRC) allowed the development of ‘Link_TSG6’ as a new therapeutic. Link_TSG6 is a biological drug that uses part of the human TSG-6 protein (the Link domain). Link_TSG6  has greater activity than the full-length protein and is easier to produce at scale.

Further research into TSG-6 and Link_TSG6, provided wider insights and the team shifted their focus to explore the therapeutic potential of Link_TSG6 in OA and, later, in DED. The team secured additional funds from Versus Arthritis as well as from internal funding schemes at the University of Manchester, including three MRC “Confidence in Concept” (CiC) awards, a “Proximity to Discovery” (P2D) award, and two Wellcome Translational Partnership Award (TPA) grants. This further enabled them to develop the project and retain key staff members, leading to numerous publications and the filing of two patents (one for OA and one for DED).

 

The Founding Team of Link Biologics (May 2022): Tony Day (left), Caroline Milner (centre), Reuben Dawkins (right). Picture (Tony Day ©) taken near Oxford following Creative Destructive Labs (CDL) Oxford Health, Session 4, where Link Biologics graduated from the CDL accelerator programme.

 

 

The “push” to spin-out

The wealth of research demonstrating the immunomodulatory and tissue-protective effects of TSG-6, and their exciting data showing therapeutic effects of Link_TSG6 in models of DED and OA, fuelled Tony and Caroline’s determination to progress Link_TSG6 to the clinic for patient benefit. Attempts to licence the technology to biopharmaceutical companies were unsuccessful, thus spinning-out was the obvious next step.

However, it was not until 2018 that the team, in conjunction with Reuben Dawkins (at the time the Global Product Director for Early-Stage Assets at Novo Nordisk), decided to form a company, and Link Biologics was spun out from the University in 2021. Reuben’s knowledge of drug development and his business background provided the confidence and reassurance to found Link Biologics, with Reuben as an invaluable member of the team.

Two years later, in 2023, Link Biologics announced a £216 million partnership deal with Théa Open Innovation (TOI), part of Théa group (the leading independent eyecare company in Europe), to further develop Link_TSG6 eye drops for DED.

 

“When spinning out, building an excellent team and network is essential”

Tony Day and Caroline Milner 

How the Translation Manchester Access to Expertise (A2E) award facilitated the translational potential of Link_TSG6

The funding received from Translation Manchester, as well as other internal schemes from the University, were instrumental in moving the translational work forward, initiating new activities and de-risking elements of the team’s strategy. In particular, the Translation Manchester “Access to Expertise” (A2E) (2019) and  “Projects for Translation” (P4T) (2018) awards enabled the team to refine their manufacturing process for Link_TSG6, which was originally developed through a BBSRC CASE PhD studentship. The data/insights obtained during this project are proving very useful in the ongoing transfer of the process to scale.

 

Reflecting on challenges

Despite the promise of their technology, the road to commercialisation was not easy. Discussions and negotiations with biopharma companies and venture capitalists (VC) regarding investment proved lengthy and complex, exacerbated by the COVID-19 pandemic, which led to significant delays in obtaining funding for the company. With hindsight, utilising a strategy to create a sense of urgency and “fear of missing” out, might have resulted in VC success.

Excitingly, Link Biologics was able to find a pharmaceutical company that was enthusiastic to invest. The team quoted “Every start-up should prepare to contact 100+ suitable investors, while hoping you only need to pitch to about 20 to get a deal over the line”.

 

Advice for those venturing to form a spin-out

Entrepreneurs at the start of their journey need to understand that translation/commercialisation is often not a straight path, and it can take much longer than one might imagine, as there are constant challenges to overcome. The team’s advice to those aspiring to spin-out is to have sound evidence that their technology meets a major unmet need. They quote “When spinning out, building an excellent team and network is essential. Make sure you get the best legal advice you can afford. Seek external validation and mentorship from seasoned entrepreneurs and business experts to gain insights and confidence in your ability to progress this along the translational pathway. Finally, use every opportunity to market your technology and develop a compelling pitch, as this is critical in securing investors.”

 

What’s next for Link Biologics?

The company is currently focussed on advancing their DED and OA programmes towards clinical trials. To do this they are moving forward with activities in three main areas: 1) non-clinical development (e.g., in vivo toxicology studies); 2) optimising formulation and transferring their manufacturing process to scale; and 3) clinical development (creating robust clinical trial protocols). Within the next 10 years the team hopes to see Link_TSG6 being approved for DED and look forward to continuing to develop this protein biological with the aim of setting a new standard of care in multiple inflammatory and tissue degenerative conditions.

 

People who have contributed to making Link Biologics a reality

The team is thankful to all colleagues and collaborators who have contributed to their translational journey. In particular, members of their research group in Manchester (in alphabetical order): Becky Dodd, Sheona Drummond, Doug Dyer, Giles Hassall, Nikos Kouvatsos, Sophie Powell, Jenny Scott and Jen Thomson), colleagues and collaborators in Manchester (Clair Baldock, Christoph Ballestrem, Diane Escott, Sasha Golovanov, Tim Hardingham, Matt Hardman, Judith Hoyland, Sue Kimber, Craig Lawless, Qing-Jun Meng, Julian Selley and Richard Unwin), clinical colleagues who provided human joint tissues for the OA work (Sanjay Anand, Leela Biant and Andrew Price), collaborators who tested Link_TSG6 in models of OA (Eckart Bartnik (and research team), Matthias Herrmann and Thomas Leeuw at Sanofi Aventis (Frankfurt)) and models of joint pain (Stuart Bevan and Clive Gentry (KCL)), Ian Evetts and David Simpson for their advice along the way, Joo Youn Oh and her team at Seoul National University Hospital for the work on DED, Afsie Sabokbar and Dave Mahoney (University of Oxford) for the early work on the development of TSG-6 as a treatment for osteoporosis and last but not least, Reuben Dawkins, the CEO and co-founder of Link Biologics.

The team is also grateful for the funding they received from BBSRC (including CASE Awards with Eden Biodesign (supervisor: Jenny Thirlway) and Merck Serono (supervisor: the late Amanda Proudfoot)), GSK, MRC, Translation Manchester, Versus Arthritis and the Wellcome Trust.

This blog post is based on an interview with Tony Day and Caroline Milner, you can read the full Interview below.

Click to read the full interview

Could you provide a brief summary of the project to date, describing the translational journey from lab to spin-out and further investments?

Our translational journey started a long time ago – around the time we moved to the University Manchester (UoM) from Oxford in 2005.

Caroline/Tony:

We had just discovered that TSG-6 was an inhibitor of osteoclast-mediated bone resorption and (initially with collaborators in Oxford) set out to develop recombinant human TSG-6 (rhTSG-6) as a treatment for osteoporosis. We attracted substantial funding along the way from Isis Innovation, Oxford (2006-2007), Versus Arthritis (2007-2010) and an MRC DPFS (2013-2015) award; it was prior to obtaining the DPFS grant that we decided to focus on Link_TSG6, which is the isolated Link module domain of human TSG-6, rather than the full-length protein since our preliminary studies indicated that this was equally efficacious as well as being easier to produce at scale. During this period, we also made a start of developing a manufacturing process for Link_TSG6 (with a BBSRC CASE studentship from Eden Biodesign; 2010-2013). Following the DPFS grant we obtained funding from GSK (from their Biopharmaceuticals R&D Innovation Fund 2014) to investigate the use of a proprietary technology to extend the half-life of Link_TSG6 (2015-2017).

As well as our translational work on osteoporosis, we had also been investigating the role of TSG-6 in osteoarthritis (OA); research Tony initiated as a Versus Arthritis Research Fellow (1991-1998). Findings from our Versus Arthritis Programme grant (2009-2015) and work in collaboration with Sanofi-Aventis (2010-2011) indicated that Link_TSG6 might have utility as a Disease Modifying OA Drug (DMOAD) along with additional analgesic effects.

Given there appeared to be limited interest in Link_TSG6 as an anti-catabolic therapy for osteoporosis we refocused our translational efforts onto OA, with the filing of a US patent in 2014 (a ‘continuation in part’ to our pending US patent for a “method of treating bone disorders using TSG-6”).

The ensuing development of Link_TSG6 for OA was funded from several sources, including a project grant from Versus Arthritis (2015-2018) and bespoke funding provided by the charity in 2018-2019 (in response to a ‘translational business case’). In addition, we obtained valuable internal support from the UoM’s MRC CiC (2015-2016; 2018-2019), P2D (2018-2019) and Wellcome TPA (P4T: 2019; A2E: 2019-2020) schemes that allowed us to develop particular aspects of the project, and helped us retain key staff. The ‘translational award’ from Versus Arthritis included a collaboration with Stuart Bevan and Clive Gentry at KCL, revealing that Link_TSG6 has a potent inhibitory effect on the development of pain in a model of surgically induced OA (with paten filing in 2021). Following this, we were successful in obtaining another Programme grant from Versus Arthritis (2020-2024). This is largely a basic science grant, aimed at understanding the role of endogenous TSG-6 in joint protection, but also includes some translational research.

We initiated work on a new indication for Link_TSG6 in 2016 – Dry Eye Disease (DED) – in collaboration with Joo Youn Oh in Seoul. Dr Oh had published a couple of papers on rhTSG-6 in models of DED and agreed to test Link_TSG6. Over the next few years this led to a large body of data showing that Link_TSG6 has a potent effect on multiple aspects of DED. A patent was filed in 2019 with our paper published in 2022 (Oh et al., 2022 10.1016/j.jtos.2021.12.012).

It was in the summer of 2018 that we were contacted by Reuben Dawkins (at the time working for Novo Nordisk in Zurich) to see if we had considered forming a company to develop our Link_TSG6 technology. Reuben had seen our non-confidential flyer posted on the UMIP website describing the potential of Link_TSG6 as a novel disease modifying therapeutic for osteoarthritis. Following extensive discussions and a face-to-face meeting with Reuben in November 2018, we decided to form a company together with DED and OA as our initial indications. Link Biologics was finally spun out from the University of Manchester in June 2021.

In September 2023 a partnership agreement was announced between Link Biologics and Théa Open Innovation (TOI; part of Théa Group – the leading independent European pharmaceutical company specialising in the research, development, and commercialisation of eye care products). The disclosed deal was £216m, excluding an equity investment in Link Biologics, R&D reimbursement costs and tiered royalties on future net sales of Link_TSG6 products within the ophthalmology field (all of undisclosed values).

The partnership provides TOI with an exclusive licence to develop, manufacture and commercialise Link_TSG6 eye drops worldwide (excluding Asia), where Link Biologics is responsible for advancing the Dry Eye Disease programme up until the end of Phase 2 clinical trials, while retaining rights to all our other programmes (including OA).

 

Can you give us an idea of how this project came about? Why this specific research area?

Tony:

Much of the history of the project is described in the summary above.

In 1991, I obtained a Research Fellowship from Versus Arthritis (the Arthritis Research Campaign as it was then) to determine the 3D structure of L-selectin, a cell surface receptor involved in leukocyte adhesion and migration; this was based in the NMR group of Iain Campbell at the University of Oxford. Following the first paper on TSG-6 being published in 1992 by researchers at NYU (brought to my attention by Bob Sim, with whom I had done my DPhil; for further details see Day, 2021 10.3390/v13071256) I started working on this protein as a side project, generating the recombinant Link module from human TSG-6 (i.e., Link_TSG6) for structural analysis. The only real success of my fellowship was the determination of the solution structure of the TSG-6 Link module. This work was published in Cell in 1996, where this paper (Kohda et al., 1996 10.1016/s0092-8674(00)80151-8) was instrumental in getting renewal of my Fellowship (in 1996), obtaining a staff position within the MRC Immunochemistry Unit, Oxford (1998-2005), and pretty much every grant I applied for over the next 5 years. This rather committed me to working on TSG-6 as a major focus going forward!

Having funding from Versus Arthritis brought me into contact with scientists working on OA (e.g., through Fellowship meetings), in particular Mike Bayliss (Royal Veterinary College, London) and Jill Urban (University of Oxford) who both became important mentors. This initiated a long-term interest in osteoarthritis, and the musculoskeletal system in general, ultimately led to our development of Link_TSG6, first as an anti-osteoporotic agent then as a DMOAD.

Caroline was also a Versus Arthritis Research Fellow (1994-2000), and we started collaborating around 1999 when sharing lab facilities in the MRC Immunochemistry Unit, with our first joint funding on TSG-6 and OA being from the Oliver Bird Fund in 2000 (2000-2003).

The work on Dry Eye Disease had an equally complex beginning! I started working on a major form of blindness – Age-related Macular Degeneration (AMD) – following my move to Manchester in 2005. This work (with Paul Bishop) was built upon research I had done during my DPhil (on Complement Factor H; see Day, 2021) along with collaborative studies with Bob Sim carried out by our joint DPhil student Simon Clark (who eventually span out Complement Therapeutics with Paul Bishop in 2021). While this is not relevant to the current story, it was because of my interest in AMD that I was attending the annual ARVO (Association for Research in Vision in Ophthalmology) meeting in Seattle in 2016, where Joo Youn Oh was also an attendee. During a brief meeting we agreed to collaborate on Dry Eye Disease. As noted above Dr Oh had already investigated rhTSG-6 in DED models, and while some interesting data had been obtained, she did not think the full-length protein was suitable to be developed as a therapeutic. Joo Youn was aware of our work and very keen to investigate whether Link_TSG6 was a better drug target.

 

At what point in the programme of work did you decide that forming a spin-out was the best option to take your innovation forward and why?

Caroline/Tony:

A wealth of data has been published (e.g., over the last 15 years) indicating that the TSG-6 protein is responsible for mediating the beneficial effects of human mesenchymal stem cells in a broad range of disease models (see Day & Milner, 2019 10.1016/j.matbio.2018.01.011). This has underpinned the concept that TSG-6 has an important role as an intrinsic protector of tissues during inflammation. Our work in models of DED, OA and osteoporosis convinced us that Link_TSG6 had considerable potential to be developed as a protein biological drug based on its immunomodulatory and tissue-protective effects and that it was a more suitable translational target than full-length TSG-6. Thus, our aim has been to progress Link_TSG6 towards the clinic for patient benefit.

While we had considered the possibility of forming a spin-out company, it was Reuben Dawkins’ involvement that provided the catalyst for this. When we met Reuben in 2018, he was the Global Product Director for Early-Stage Assets at Novo Nordisk, and it was clear that his knowledge of drug development and his business knowhow was highly complementary to our expertise. Reuben’s enthusiasm for our data (and the Link_TSG6 technology in general) gave us the confidence to found Link Biologics.

As noted above we had already attracted a lot of funding for research on TSG-6 and the development of Link_TSG6 as a biological drug. Given we had been unable to identify a biopharma company to license our technology (something we had actively pursued over many years), forming a spin out was the obvious next step, especially since obtaining sufficient funding to continue the development in an academic setting seemed unlikely. So, Reuben’s contacting us came at exactly the right time.

It’s hard to imagine we could have found a better partner that Reuben with whom to have co-founded Link Biologics. His commitment to the company has been extraordinary and working closely with Reuben over the last 5+ years has been an incredibly enjoyable and rewarding experience. We are excited by the journey ahead.

 

Looking back, can you tell us about any bottlenecks/challenges you have faced along the way and things you would have done differently?

Caroline/Tony:

The relationship with colleagues at UMIP/UMIF is important for a smooth translational journey. We were fortunate to work with a couple of excellent Project Managers at UMIP over many years (Emma Wood (2008-2010) and Sonia Nikolovski (2013-2019)) who provided very valuable input, support and encouragement. Unfortunately, we ran into difficulties during the spin out process (2019-2021) and during the negotiation of the investment deal (2021-2023). As a result, launching the company and subsequently negotiating the partnership deal took longer and cost more (e.g., in legal fees) than it should have done. It was also extremely stressful at times. The difficulties experienced in the lead up to spinning out were exacerbated by the COVID-19 pandemic, which meant that many of the discussions occurred online rather than face-to-face.

The fundraising for the company also took much longer than we had anticipated. In this regard, finding a lead investor, as opposed to just ‘potentially interested’ parties, was a challenge we faced. Ultimately, we got around this by finding a pharma partner, rather than a VC, to invest in the company. In hindsight, we (Link Biologics) could have done a better job at creating a sense of urgency and a ‘fear of missing out’ amongst potential VC investors. In addition, we should have been more aware of the number of investors we would need to contact. Every start-up should prepare to contact 100+ suitable investors (while hoping you only need to contact 20 to get a deal over the line).

 

Do you have any advice for anyone who is about to undertake a similar journey?

Caroline/Tony:

Translation/commercialisation is often not a straight path and can take much longer than you might imagine at the outset. There are constant challenges to overcome. As described above, we started developing rhTSG-6 as treatment for osteoporosis in 2006. So, you don’t necessarily end up where you expected to!

Be highly critical of ones’ own data, since you don’t want to embark on a translational journey unless you are absolutely certain you have something worth translating. This also means that you must be addressing a major unmet need and that your technology provides a clear solution. If you are sure that you have something good to translate, then don’t be deterred by others (who will not be as excited/convinced by your technology as you are). Don’t be put off or get demoralised by rejection, and be prepared to ‘fight’ to keep the dream alive.

When spinning out, building an excellent team and network is essential. There is no doubt that Reuben’s business experience was key to obtaining the deal with TOI.

Getting external validation/mentorship from seasoned entrepreneurs and business experts is valuable (e.g., to pressure test your business plan and identify any gaps in approach). For example, Caroline took part in PULSE in 2020 (a training Programme for Up and coming Life Science Entrepreneurs) and Link Biologics participated in an international accelerator programme (Creative Destruction Lab (CDL)) in 2021/2022; both of these were recommended to us by UMIF. Link Biologics was selected for CDL Oxford Health from a large number of applicants and progressed through the entire programme, graduating in June 2022. We obtained a lot of confidence in the ability and expertise of the Link Biologics’ team through being in CDL. The advice and insights we obtained during the CDL programme was invaluable and we are still in touch with several mentors who continue to provide very helpful input.

It’s important to develop a simple and compelling narrative when pitching to VCs, biopharma companies etc. This is something we improved over time and fine-tuned while taking part in CDL.

Use every opportunity to market your technology. For example, Reuben found us through a UoM flyer.

Get the best legal advice you can afford. We were fortunate to work with the international law firm Fieldfisher during the spinout and deal negotiation process and are delighted to continue this relationship now that Link Biologics is up-and-running. In addition, Fran Salisbury and her team at Mewburn Ellis have provided excellent support for all of our IP needs for a considerable period of time, and again this is a partnership we hope to continue for many years to come.

Getting funding from VCs can be difficult depending on technology area (gene therapy is in vogue). Biopharma is looking for reasons to invest (for companies to complement their portfolio) whereas VCs are looking for red flags and reasons not to invest.

 

How did the Translation Manchester internal funding help you?

Caroline/Tony:

MRC Confidence in Concept (CiC), MRC Proximity to Discovery (P2D) and Wellcome Translational Partnership Award (TPA) funding has been extremely useful in allowing us to obtain support for specific targeted activities.

We have been awarded 3 MRC CiC grants between 2015 and 2020. The first of these (2015-2016) was aimed at generating novel composition of matter IP, however, this project was beset with technical difficulties (largely outside of our control) and did not generate data suitable for patent filing. The second CiC project (2018-2019) focused on understanding the mechanism of action (MOA) underlying Link_TSG6’s inhibition of cartilage breakdown (i.e., its disease modifying effect) and initiated studies to stratify patients based on their response to Link_TSG6 treatment. Both aims were partially successful, with continuation of the work during our Versus Arthritis translational award (2018-2019), our TPA Access to Experts (A2E) grant (2019-2020) and our Versus Arthritis Programme grant (2020-2024). Much of the resulting data, e.g., identifying Responders and Non-Responders to Link_TSG6 treatment and the MOA of Link_TSG6, were published last year (Drummond et al., 2023 10.1016/j.joca.2023.05.013); moreover, Link Biologics is continuing to develop a personalised medicine approach for OA. The CiC project was also important since it allowed us to retain a key member of our team. In this regard, Anu Soukas (Strategic Funding Team, FBMH) was instrumental in our obtaining this grant in conjunction with support from Tim Hardingham and Qing Jun Meng. The third CiC grant (2019-2020) was focused on a new indication for Link_TSG6 and, because of the encouraging results, this is something that Link Biologics is currently taking forward.

The MRC P2D (2018-2019) ‘Relationship Incubator Award’ allowed us to fund a consultant to evaluate the DED market and identify prospective industry partners, i.e., providing useful information during the initial development of our business plan. We also obtained a Wellcome TPA ‘Projects 4 Translation’ (P4T) award (2019) that allowed us to further develop our manufacturing process for Link_TSG6, i.e., with regard to the methodology for downstream processing. The data/insights obtained during this project are proving very useful in the context of ongoing work being carried out by a CDMO (on behalf of Link Biologics) to transfer our process to scale.

We are immensely grateful for the translational funding support we have received through the internal UoM schemes. While these represent relatively small amounts of money, they have been very useful in moving our translational work forward, initiating new activities and de-risking elements of our strategy.

 

What’s next for your company/research and where do you see this work going in the next 10 years?

Caroline/Tony:

Now that Link Biologics has funding (through our partnership with TOI and their equity investment in the company) we are heavily focussed on advancing our DED and OA programmes towards clinical trials. To do this we are moving forward with activities in three main areas: non-clinical development (e.g., in vivo toxicology studies), CMC (e.g., formulation and transferring our manufacturing process to scale) and clinical development (creating robust clinical trial protocols).

In the next 10 years we hope to see Link_TSG6 being approved for DED and to continue to develop this protein biological with the aim of setting a new standard of care in multiple inflammatory and degenerative conditions.

 

Do you have a list of collaborators/funders that you would like to acknowledge? 

Caroline/Tony:

There are so many people to thank!

Colleagues and collaborators

Firstly, members of our research group in Manchester who have contributed to our translational story (in alphabetical order: Becky Dodd, Sheona Drummond, Doug Dyer, Giles Hassall, Nikos Kouvatsos, Sophie Powell, Jenny Scott and Jen Thomson).

We would also like to thank colleagues and collaborators in Manchester for their input and support: Clair Baldock, Christoph Ballestrem, Diane Escott, Sasha Golovanov, Tim Hardingham, Matt Hardman, Judith Hoyland, Sue Kimber, Craig Lawless, Qing-Jun Meng, Julian Selley and Richard Unwin.

We are particularly grateful to Sanjay Anand, Leela Biant and Andrew Price (orthopaedic surgeons in Manchester and Oxford) who have provided human joint tissues for our work on OA.

Eckart Bartnik (and research team), Matthias Herrmann and Thomas Leeuw at Sanofi Aventis (Frankfurt) for the testing of Link_TSG6 in models of OA.

Stuart Bevan and Clive Gentry (KCL) for testing Link_TSG6 in models of joint pain.

Ian Evetts and David Simpson who gave us much free (but very helpful) advice along the way.

Joo Youn Oh and her team at Seoul National University Hospital for the work on DED.

Afsie Sabokbar and Dave Mahoney (University of Oxford) for the early work on the development of TSG-6 as a treatment for osteoporosis.

And last but by no means least, Reuben Dawkins, CEO and co-founder of Link Biologics.

Funding

BBSRC, including CASE Awards with Eden Biodesign (supervisor: Jenny Thirlway) and Merck Serono (supervisor: Amanda Proudfoot).

GalaxoSmithKline

Medical Research Council

Translation Manchester

Versus Arthritis

Wellcome Trust

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