UCL Proximity to Discovery: Industry Engagement Fund (PtoD) 2016

Lead Research Organisation: University College London

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

The MRC Proximity to Discovery scheme awards universities funds to help develop new collaborations, and ways of exchanging knowledge and skills.  The awards can be used to support activities that promote the value of academic-industry partnership, and enhance academic and industry researchers’ understanding of each other’s needs and capabilities.  This may be through people exchanges, creation of technology demonstrators, showcase events, commercialisation workshops and ‘entrepreneurs in residence’ schemes.  Such exchanges of knowledge and skills will boost the most fruitful collaborations between UK universities and life science companies.

Publications

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Description Ben Allsop secondment to Luxcell 
Organisation BMG LABTECH
Country Germany 
Sector Private 
PI Contribution The development of novel therapies for the treatment of ischemia reperfusion injury have been hampered by poor translation to the clinical setting. A major factor has been an inability to accurately model the reperfusion event in appropriate cell systems. The team at UCL are developing low molecular weight compounds aimed at reducing cardiovascular damage from IR injury and improving recovery from myocardial infarction. Current in vitro models of IR injury do not appropriately model the speed of re-oxygenation and hence underestimate the injury caused during reperfusion. The models the partner organisations are developing enable faster reperfusion which more accurately simulate the in vivo process and also allow continual monitoring of the cells during all stages of the IR injury. Combined, these would enable UCL to develop a model to assess IR damage and a medium throughput assay that is more disease relevant that current methods of measuring IR injury. A more disease relevant model, would aid drug discovery and enable development of better drug candidate molecules. It would also reduce the number of in vivo experiments required to develop a compound, reducing animal use and demonstrating UCL commitment to the 3R's. Implementation of this system in our drug discovery group would place UCL in a world-leading position for modelling cardiovascular IRI and build expertise in support of our collaboration with AstraZeneca.
Collaborator Contribution Ben Allsop would gain the experience of developing an in vitro disease relevant cell model of cardiac IR injury for use in drug screening. Being able to visit the partner organisations he would gain the direct experience of how the probes have been developed and can be used in similar models. He would also gain experience and knowledge of IPSC culture direct from the experts in Ncardia.
Impact Our proposal brings together three SMEs (Luxcel, Ncardia & BMG Labtech), experts in cardiovascular disease (Prof Derek Yellon & Dr Sean Davidson), PI3 Kinase signalling pathways (Prof Bart Vanhaesebroeck & Dr Benoit Bilanges) and small molecule drug discovery (Dr Richard Angell, Dr Trevor Askwith, Dr Sally Oxenford). The data generated by this collaboration serves to further build the UCL-AZ collaboration in cardiovascular disease. The output was presented by Ben at Conference of the Society for Laboratory Automation and Screening (SLAS) 2019 - Speaker: Ben Allsop (Research Associate, Drug Discovery Group, University College London), Catherine Wark (Applications Manager, BMG LABTECH Ltd.) Tuesday, February 5
Start Year 2017
 
Description Ben Allsop secondment to Luxcell 
Organisation Luxel Biosciences
Country Ireland 
Sector Private 
PI Contribution The development of novel therapies for the treatment of ischemia reperfusion injury have been hampered by poor translation to the clinical setting. A major factor has been an inability to accurately model the reperfusion event in appropriate cell systems. The team at UCL are developing low molecular weight compounds aimed at reducing cardiovascular damage from IR injury and improving recovery from myocardial infarction. Current in vitro models of IR injury do not appropriately model the speed of re-oxygenation and hence underestimate the injury caused during reperfusion. The models the partner organisations are developing enable faster reperfusion which more accurately simulate the in vivo process and also allow continual monitoring of the cells during all stages of the IR injury. Combined, these would enable UCL to develop a model to assess IR damage and a medium throughput assay that is more disease relevant that current methods of measuring IR injury. A more disease relevant model, would aid drug discovery and enable development of better drug candidate molecules. It would also reduce the number of in vivo experiments required to develop a compound, reducing animal use and demonstrating UCL commitment to the 3R's. Implementation of this system in our drug discovery group would place UCL in a world-leading position for modelling cardiovascular IRI and build expertise in support of our collaboration with AstraZeneca.
Collaborator Contribution Ben Allsop would gain the experience of developing an in vitro disease relevant cell model of cardiac IR injury for use in drug screening. Being able to visit the partner organisations he would gain the direct experience of how the probes have been developed and can be used in similar models. He would also gain experience and knowledge of IPSC culture direct from the experts in Ncardia.
Impact Our proposal brings together three SMEs (Luxcel, Ncardia & BMG Labtech), experts in cardiovascular disease (Prof Derek Yellon & Dr Sean Davidson), PI3 Kinase signalling pathways (Prof Bart Vanhaesebroeck & Dr Benoit Bilanges) and small molecule drug discovery (Dr Richard Angell, Dr Trevor Askwith, Dr Sally Oxenford). The data generated by this collaboration serves to further build the UCL-AZ collaboration in cardiovascular disease. The output was presented by Ben at Conference of the Society for Laboratory Automation and Screening (SLAS) 2019 - Speaker: Ben Allsop (Research Associate, Drug Discovery Group, University College London), Catherine Wark (Applications Manager, BMG LABTECH Ltd.) Tuesday, February 5
Start Year 2017
 
Description Ben Allsop secondment to Luxcell 
Organisation Ncardia
Country Belgium 
Sector Private 
PI Contribution The development of novel therapies for the treatment of ischemia reperfusion injury have been hampered by poor translation to the clinical setting. A major factor has been an inability to accurately model the reperfusion event in appropriate cell systems. The team at UCL are developing low molecular weight compounds aimed at reducing cardiovascular damage from IR injury and improving recovery from myocardial infarction. Current in vitro models of IR injury do not appropriately model the speed of re-oxygenation and hence underestimate the injury caused during reperfusion. The models the partner organisations are developing enable faster reperfusion which more accurately simulate the in vivo process and also allow continual monitoring of the cells during all stages of the IR injury. Combined, these would enable UCL to develop a model to assess IR damage and a medium throughput assay that is more disease relevant that current methods of measuring IR injury. A more disease relevant model, would aid drug discovery and enable development of better drug candidate molecules. It would also reduce the number of in vivo experiments required to develop a compound, reducing animal use and demonstrating UCL commitment to the 3R's. Implementation of this system in our drug discovery group would place UCL in a world-leading position for modelling cardiovascular IRI and build expertise in support of our collaboration with AstraZeneca.
Collaborator Contribution Ben Allsop would gain the experience of developing an in vitro disease relevant cell model of cardiac IR injury for use in drug screening. Being able to visit the partner organisations he would gain the direct experience of how the probes have been developed and can be used in similar models. He would also gain experience and knowledge of IPSC culture direct from the experts in Ncardia.
Impact Our proposal brings together three SMEs (Luxcel, Ncardia & BMG Labtech), experts in cardiovascular disease (Prof Derek Yellon & Dr Sean Davidson), PI3 Kinase signalling pathways (Prof Bart Vanhaesebroeck & Dr Benoit Bilanges) and small molecule drug discovery (Dr Richard Angell, Dr Trevor Askwith, Dr Sally Oxenford). The data generated by this collaboration serves to further build the UCL-AZ collaboration in cardiovascular disease. The output was presented by Ben at Conference of the Society for Laboratory Automation and Screening (SLAS) 2019 - Speaker: Ben Allsop (Research Associate, Drug Discovery Group, University College London), Catherine Wark (Applications Manager, BMG LABTECH Ltd.) Tuesday, February 5
Start Year 2017
 
Description Dr Anna Poon secondment to UCL from Astex 
Organisation Astex Pharmaceuticals
Department Astex Therapeutics Ltd
Country United Kingdom 
Sector Private 
PI Contribution Access to UCL knowledge and biomedical expertise. transfer of neuronal differentiation techniques and the mitophagy detection methods from UCL to Astex. Marc Soutar (postdoc in the HPF lab) has optimised the methods for detecting mitophagy in iPSC-derived neurons (paper in revision in Sci. Rep), he will transfer his knowledge skills to Anna Poon, the postdoc based at Astex. ? The opportunity to collaborate on a long-term basis with UCL: Such as identification of the key modulators of mitophagy and the specific protein domains important for this modulation would potentially allow the resolution of novel crystal structures, or optimisation of existing structures. This would allow the design of novel small molecule protein modulators of p62 structure and function. The potential biological consequence of these molecules can then be assessed and the potentially therapeutic utility alterations can then be established with the ultimate aim of altering / correcting the pathogenic processes involved in diseases such as FTD and Parkinson's disease.
Collaborator Contribution Access to Astex expertise and skills in CRISPR technology ? Development of a long-term collaboration with a leading company at the forefront of innovative drug discovery and development for CNS disease ? The immediate impact of this proposal will be on laboratories directly involved in researching mitophagy/macroautophagy at a basic and translational level. This project will lead to a number of new collaborations from various fields of research in the next several years. p62 is a multidomain protein which exerts multiple functions by interacting with different binding partners. Thus the knowledge acquired in this proposal has the potential to translate into the development of new innovative tools and biological assays that will not only benefit the mitophagy research community, but will benefit the larger scientific community, more generally.
Impact Dr Anna Poon has learned all the mitophagy methods from the HPF lab, and has generated interesting data in her p62 CRISPR KO iPSC-neurons as a result. She presented her data at a meeting between Astex, HPF and Selina Wray on the 27th September 2018, at AStex in Cambridge. The data generated by Anna in collaboration with the HPF lab will be the basis of a joint publication between Astex and UCL in the next few months.
Start Year 2018
 
Description Francisco Vasconcelos secondment to Trendalyze 
Organisation Trendalyze Decisions Ltd
Country United Kingdom 
Sector Private 
PI Contribution Development of algorithms that combine deep learning models built at UCL and Trendalyze's time-series motifs software in order to perform analysis of eye trajectories recorded during interventional training and procedures. In addition to eye trajectories other signals have been analysed including probe and instrument motion trajectories. The Partner will benefit from having an expert in eye tracking and skill analysis utilise their platform and provide insight into its application against the state of the art. This could be an important area for business development for the company and the pilot study would provide both expertise and experimental data for the proof of concept. The Partner will also benefit from the opportunity to collaborate on a long-term basis with UCL and gain insight into unique data streams in order to validate their technology within health applications.
Collaborator Contribution We will gain access to Trendalyze expertise and skills of how to implement their innovative technology - a Google-like search approach based on pattern shapes within time series and deep learning. We will share our knowledge in this field and work together to optimise this commercial technology. During the course of the project, we will explore how these quantitative tools can be used to improve the clinical training programmes at UCL. Other benefits include the development of a long-term collaboration with a leading company with the first pattern and motif discovery platform in IoT and Big Data, including access to joint-industry funding routes.
Impact The project will produce outputs showing the capability of the time-series motifs to be used in a diverse range of applications, in this case interventional analysis and training. This will be used by Trendalyze during investment rounds and to showcase capability while trying to secure new business.
Start Year 2017
 
Description James Fullerton secondment to GSK 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Knowledge exchange to facilitate the safe establishment of, and protocol optimisation for, the IV endotoxin model in healthy volunteers at GSK. This will include the secondee gaining experience of dose escalation and toxicity studies as a new batch of endotoxin for use in humans has been generated but is yet to be widely employed or reported on - Knowledge exchange regarding integration of interventional challenge models into existing experimental medicine (pre-clinical) study and Phase 1 trial protocols. - Conduct and analysis of studies employing novel Immune Modifying Particles (IMPs) targeted at cells of the myeloid lineage, in particular monocytes and macrophages. Knowledge exchange around these cell type's identification, phenotyping and functional assessment. - Exploration of the role different human models of inflammation may play in future translational research and drug development including established (e.g. cantharidin blister) and novel (e.g. intradermal UV-killed E.coli) techniques - UCL to host a series of talks and/or workshops by GSK staff to promote the conduct and quality of translational research
Collaborator Contribution Inform starting dose of IV endotoxin, input into dose escalation decisions, establish and deploy a safe dose of IV endotoxin 'sufficient for purpose': Literature review; liaison with manufacturer of GMP endotoxin; discussion with leading experts on the IV endotoxin model; review the clinical, cellular and biochemical data obtained from initial healthy volunteer studies - Employ the model as a 'test-bed' for novel IMPs: Review pre-determined end-points; assess the adequacy of the model; comment on the timing, dose and efficacy of novel IMPs. - Contribute to on-going immunomodulatory pre-clinical and Phase 1 studies in the Clinical Unit Cambridge: Assist in the processing, analysis and interpretation of samples derived from studies exploring the modulation of monocyte and macrophage function - Observe on-going work employing cutaneous models of inflammation in man. Assist with their interpretation, comment on their validity and role - Learn from GSKs commercial environment: Observe decision making around target identification and drug development. Understand the academic-industry interaction established between Cambridge and GSK - Arrange a series of educational events: Develop a list of topics and potential speakers who may contribute to a series of lectures/workshops at UCL. Arrange the logistics around these
Impact GSK will benefit from having a clinician experienced in the use of the IV endotoxin model present as they seek to operationalise the model, run dose escalation studies and optimise it as a 'test-bed' for novel compounds. This should provide increased safety for healthy volunteer participants and afford assurance to GSK that their observations and results are in-keeping with those obtained by previous investigators (acting as a quality check). - GSK will gain an individual who can bring expertise in a) models of inflammation in humans b) the clinical context of innate immune dysfunction and c) assessment of the phenotype and functional status of monocytes and macrophages - the principle target of their IMPs - Establishment of a longer-term relationship with the Department of Clinical Pharmacology which has considerable expertise in the field of inflammatory disease and experience with both experimental human and animal models. Crystallise plans for how future researchers may move between the organisations for mutual benefit.
Start Year 2018
 
Description Richard Day two-way secondment to Cook Myosite and to UCL 
Organisation Cook Myosite Inc
Country United States 
Sector Private 
PI Contribution The current application of the TIPS microcarrier technology is focussed on development of a treatment for incontinence, but the technology is amenable to other cell-based therapies involving myoblasts as well as other types of adherent cells, which may be of interest to Cook Myosite in the future. As part of the KE activity, UCL will share with Cook Myosite and discuss non-confidential data demonstrating attachment of other cell types to TIPS microcarriers. The outcome of the KE activity will contribute to the long-term commercial development plan for TIPS technology. TIPS microcarrier technology represents a platform from which a number of different treatments could be developed. These have different risk/reward profiles. Muscle repair is a major unmet clinical need. Independent analysis assessing commercial opportunities reported a product targeting muscle repair using TIPS microcarriers for cell based therapy is a potential breakout opportunity and first to market indication with a high risk/high reward profile.
Collaborator Contribution Our interaction with industry and investors has raised key questions relating to the comparison of TIPS microcarriers and existing bioprocessing performed in commercial settings. The KE activity will address this and provide UCL with an understanding of existing myoblast manufacturing processes performed by Cook Myosite. This will also assist with evaluating how the new technology will be assimilated with existing upstream and downstream bioprocessing capabilities currently at Cook Myosite. During the KE activity Cook Myosite will provide an in kind contribution of cells and reagents for evaluation and advise on interpretation of data. The cells will be evaluated at UCL and the data will be shared with Cook Myosite. Strategically, this will provide an opportunity for UCL to assess and validate the use of the TIPS microparticle platform as a microcarrier delivery system in combination with Cook Myosite products. Outcomes from the KE activity will contribute to the gap analysis for bioprocessing of myoblasts combined with TIPS microcarriers and a concurrent UCL-led review of the regulatory pathway required for development of a new clinical investigation product. The preparation of a regulatory strategy that identifies data requirements for non-clinical, quality and clinical activities is essential to guiding the development programme to be included in the proposed Horizon 2020 bid. The gap analysis and regulatory review for manufacturing future clinical grade products will provide an indication of full development costs and timings and contribute towards mapping partner engagement/funding requirements for the Horizon 2020 bid.
Impact The project will help build two-way knowledge exchange and collaboration with a key commercial partner in this space. This is essential for the planned H2020 bid and further development of the technology towards a clinical investigation product. - Secured H2020 award
Start Year 2018