Cambridge – Confidence in Concept 2019
Lead Research Organisation:
University of Cambridge
Department Name: UNLISTED
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 Confidence in Concept (CIC) scheme is a key part of MRC’s translational research strategy and provides annual awards to institutions to flexibly support a portfolio of early stage translational research projects. CIC is designed to accelerate the transition from discovery research to viable translational projects by supporting preliminary studies to establish proof-of-concept so that the approach will then become competitive for more substantial translational funding.
Organisations
- University of Cambridge (Lead Research Organisation)
- Marseille Biological Cancer Laboratory (Collaboration)
- Apollo Therapeutics (Collaboration)
- University of Wisconsin–La Crosse (Collaboration)
- Piramal Clinical Research (Collaboration)
- Cambridge Academy of Therapeutic Sciences (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
People |
ORCID iD |
| Patrick Maxwell (Principal Investigator) |
Publications
Bouchaoui H
(2023)
ACSL4 and the lipoxygenases 15/15B are pivotal for ferroptosis induced by iron and PUFA dyshomeostasis in dopaminergic neurons.
in Free radical biology & medicine
Mahoney-Sanchez L
(2022)
Alpha synuclein determines ferroptosis sensitivity in dopaminergic neurons via modulation of ether-phospholipid membrane composition
in Cell Reports
Potts M
(2023)
Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity.
in Cell reports
Ryan S
(2023)
Therapeutic inhibition of ferroptosis in neurodegenerative disease
in Trends in Pharmacological Sciences
Soucy J
(2023)
Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium
in Molecular Neurodegeneration
| Description | A Novel Therapy for Urinary Tract Infections |
| Amount | £123,978 (GBP) |
| Funding ID | TTI2021 1 |
| Organisation | Rosetrees Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 02/2025 |
| Description | CE PoC funds Pig Purchase and Maintenance |
| Amount | £10,000 (GBP) |
| Organisation | University of Cambridge |
| Department | Cambridge Enterprise |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | |
| Description | Cell surface biomarkers to predict outcome of COVID-19 upon hospital admission |
| Amount | £50,000 (GBP) |
| Organisation | Addenbrooke's Charitable Trust (ACT) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 11/2020 |
| End | 09/2022 |
| Description | Development of drugs to combat bacterial biofilms |
| Amount | £28,995 (GBP) |
| Funding ID | MC-PC-19032 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2023 |
| End | 03/2023 |
| Description | Ex Vivo Perfusion for Collagen Graft Assessment Prior to Porcine Studies |
| Amount | £4,272 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2024 |
| End | 05/2024 |
| Description | External Consultancy with Avania BV for animal trial planning |
| Amount | £14,675 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2023 |
| End | 12/2023 |
| Description | Fast50 This is a convertible loan from Cambridge Enterprises to funding continued development of a prototype membrane, as well as full development of a business plan, and work with experts in regulatory compliance and quality management systems. |
| Amount | £75,000 (GBP) |
| Organisation | University of Cambridge |
| Department | Cambridge Enterprise |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | |
| Description | Membranes and the reduction of clinical adhesions |
| Amount | £75,000 (GBP) |
| Organisation | University of Cambridge |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | |
| Description | NBIC ICURe |
| Amount | £6,320 (GBP) |
| Funding ID | ICURe 2022 BioTryp Theraputics |
| Organisation | National Biofilms Innovation Centre |
| Sector | Private |
| Start | 04/2022 |
| End | 05/2023 |
| Description | Preliminary whole cell lysate analysis experiments |
| Amount | £50,000 (GBP) |
| Organisation | Addenbrooke's Charitable Trust (ACT) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 11/2020 |
| End | 09/2022 |
| Description | Targeting cell death by ferroptosis in Parkinson's disease |
| Amount | £20,039 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Confidence in Concept Scheme |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Title | A quantitative serum metabolite ratio to predict fetal growth abnormalities |
| Description | Using data and samples from the POP study (Lancet 20151), we developed a metabolite based test (Nature Medicine 20205) which predicts extremes of fetal growth and enhances clinical prediction achieved by ultrasound (detailed below). We aim to develop a clinical grade, validated assay based on this research. We envisage a blood test which identifies pregnant women who are at increased risk of fetal growth abnormality. We anticipate that this test will replace tape-based measurement of the symphyseal-fundal height as the primary method of screening pregnant women for SGA and LGA at term. We envisage that the blood test would screen for fetal size at ~36 weeks of gestational age (wkGA). Women who screen positive with the ratio would be further evaluated by ultrasound. Where both the blood test and scan indicate a growth abnormality, the absolute risk of a severe growth abnormality is high. We anticipate that these women would undergo more intensive monitoring and earlier delivery. We believe that use of this test would prevent adverse outcomes through better detection of fetal growth abnormalities but reduce iatrogenic harm and costs by reducing the number of false positives associated with the existing methods of screening. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | The first milestone for the CiC project was to develop quantitative MS based assays of the four metabolites. We sent serum samples to LGC and they sourced standards for three out of the four metabolites used in the ratio. Our last meeting with the team was 04/08/21. They reported that they now had good quantitative assays for two of the metabolites (N1,N12-diacetylspermine and 1,5-AG). For the 1-(1-enyl-stearoyl)-2-oleoyl-GPC (P-18:0/18:1) metabolite, they have now resolved with a very high degree of certainty that there is a large spectroscopic peak related to this target. It is a strong signal and well within the detectable range in the pooled serum. However, it is a structural isomer of the metabolite identified in the original assay. They are planning to collect more data and then discuss the sample ID with Metabolon. There is less progress in developing the assay for 5alpha-androstan-3alpha,17alpha-diol disulfate, as it has not been possible to source a suitable standard. We have always been aware that this was a possibility and our patent identified estriol-3-sulphate as an alternative. Currently, LGC are working to source an estriol-3-sulphate standard. As the first milestone was to develop quantitative assays for four metabolites, we have made good progress but there is still further work to be done to achieve this. Next steps would follow successfully achieving milestone 2, hence we envisage this in the future. |
| Title | Detecting minimal residual disease in cancer to improve patient outcomes: accelerating implementation of novel ctDNA assays through dried blood spots. |
| Description | Establish a proof-of-concept for the utility of DBS as a cancer liquid biopsy, by assessing samples from patients with lung and H&N cancers •Assess SCNA in DBS, and compare to matched venous blood plasma DNA as the current 'Gold Standard' detection technique •Compare the absolute and fractional quantities of circulating tumour DNA (ctDNA) derived from DBS vs. blood plasma •Correlate findings with clinical data to determine thresholds for monitoring treatment response, MRD detection and prediction of relapse |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | Collected over >350 dried blood spots in >35 patients undergoing curative chemoradiotherapy for locally advanced cancers. Protocols for collection, patient satisfaction questionnaires, and plasma samples well established. Initial analysis for 50 dried blood spots completed. Initial work presented at several forums including the Cambridge RADNET symposium, and the trial methodology presented at the British Thoracic Society and ESMO. Complete analysis of remaining dried blood spots with additional leveraged funding, including analysis of dried blood spots from normal volunteers collected through other avenues for negative controls. This is needed to develop the methodology for truly sensitive ctDNA detection. Continue to make progress in implementing in additional clinical cohorts based on initial results here. |
| Title | Whole cell lysate and plasma membrane protein analysis of PBMCs from individuals with mild/severe/critical COVID |
| Description | Our initial findings have been extremely interesting, highlighting key differences in protein expression between different staff/patient groups with COVID. We have initially focused on analysis of whole cell lysates from PBMC collected from individuals testing SARS-CoV-2 positive through the CUH/University Pods (mild or asymptomatic disease) and from patients testing positive upon admission to CUH (severe / ITU). Specifically, we have identified substantial whole cell proteomic differences between staff with mild or asymptomatic disease, and patients admitted with COVID. Furthermore, there are phenotypic differences between patients who are admitted then discharged compared to those who progress to ITU. These may ultimately provide important biomarkers to predict disease progression. We have now extended this analysis to examine plasma membrane protein changes in a limited subset of individuals, which recapitulate and extend the findings from whole cell proteomics. We have identified six cell surface markers of severity, which we are in the process of validating by flow cytometry, both on the same and different cohorts. Preliminary whole cell lysate analysis experiments are complete, with data analysis underway. Additional funding has been secured from Addenbrooke's Charitable Trust. To be of greatest clinical utility, cell surface proteins need to be identified, whose expression level predicts the future severity of disease, since these will facilitate real-time flow cytometry-based patient assessment. Furthermore, it is vital to determine which changes in phenotype reflect disease severity, as opposed to disease stage. We have now conducted a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we have defined a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, the cell surface proteins CEACAMs1, 6 and 8, CD177, CD63 and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CD177+ and CD16+CEACAM1/6/8+ mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry and identify immune cell populations that could be targeted to ameliorate immunopathology. |
| Type Of Material | Cell line |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | Our study has now concluded, with the publication indicated below. We identified several novel, robust cell surface markers that relate to COVID-19 severity, which may be useful in prognostication and potentially even with other severe respiratory infections. |
| Description | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Organisation | Apollo Therapeutics |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. |
| Collaborator Contribution | Collaboration for the CiC project include: (i) Cresset Discovery Services, Litlington, UK: in silico hit expansion. (ii) Piramal Pharma Limited, India: Synthesis (iii) Optibrium Limited, Cambridge Innovation Park, UK: in silico ADME and toxicity. (iv) Ebba Biotech AB, Sweden: Assay development - PoC assays. (v) Dr William Schwan, University of Wisconsin-La Crosse, La Crosse, WI, USA: Clinical strain of E. coli - PoC assays. (vi) Dr Christine Farr, University of Cambridge, Department of Genetics: Cytotoxicity assays. (vii) Dr Katherine Stott, University of Cambridge, Department of Biochemistry: ITC assays. Discussion for the commercialisation of the CiC project include: (i) Amanda Wooding & Helen Young: Cambridge Enterprise. (ii) Trevor Perrior: Cambridge Enterprise Expert in Residence (iii) Cathy Boucher: Cambridge Academy of Therapeutic Sciences. (iv) Richard Butt: Apollo Therapeutics. (v) Gavin Whitlock: Sandexis. (vi) Nicola McCarthy: Milner Therapeutics Institute (vii) Sanjay Phogat: GSK |
| Impact | n/a |
| Start Year | 2021 |
| Description | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Organisation | Cambridge Academy of Therapeutic Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. |
| Collaborator Contribution | Collaboration for the CiC project include: (i) Cresset Discovery Services, Litlington, UK: in silico hit expansion. (ii) Piramal Pharma Limited, India: Synthesis (iii) Optibrium Limited, Cambridge Innovation Park, UK: in silico ADME and toxicity. (iv) Ebba Biotech AB, Sweden: Assay development - PoC assays. (v) Dr William Schwan, University of Wisconsin-La Crosse, La Crosse, WI, USA: Clinical strain of E. coli - PoC assays. (vi) Dr Christine Farr, University of Cambridge, Department of Genetics: Cytotoxicity assays. (vii) Dr Katherine Stott, University of Cambridge, Department of Biochemistry: ITC assays. Discussion for the commercialisation of the CiC project include: (i) Amanda Wooding & Helen Young: Cambridge Enterprise. (ii) Trevor Perrior: Cambridge Enterprise Expert in Residence (iii) Cathy Boucher: Cambridge Academy of Therapeutic Sciences. (iv) Richard Butt: Apollo Therapeutics. (v) Gavin Whitlock: Sandexis. (vi) Nicola McCarthy: Milner Therapeutics Institute (vii) Sanjay Phogat: GSK |
| Impact | n/a |
| Start Year | 2021 |
| Description | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Organisation | GlaxoSmithKline (GSK) |
| Department | GlaxoSmithKline Medicines Research Centre |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. |
| Collaborator Contribution | Collaboration for the CiC project include: (i) Cresset Discovery Services, Litlington, UK: in silico hit expansion. (ii) Piramal Pharma Limited, India: Synthesis (iii) Optibrium Limited, Cambridge Innovation Park, UK: in silico ADME and toxicity. (iv) Ebba Biotech AB, Sweden: Assay development - PoC assays. (v) Dr William Schwan, University of Wisconsin-La Crosse, La Crosse, WI, USA: Clinical strain of E. coli - PoC assays. (vi) Dr Christine Farr, University of Cambridge, Department of Genetics: Cytotoxicity assays. (vii) Dr Katherine Stott, University of Cambridge, Department of Biochemistry: ITC assays. Discussion for the commercialisation of the CiC project include: (i) Amanda Wooding & Helen Young: Cambridge Enterprise. (ii) Trevor Perrior: Cambridge Enterprise Expert in Residence (iii) Cathy Boucher: Cambridge Academy of Therapeutic Sciences. (iv) Richard Butt: Apollo Therapeutics. (v) Gavin Whitlock: Sandexis. (vi) Nicola McCarthy: Milner Therapeutics Institute (vii) Sanjay Phogat: GSK |
| Impact | n/a |
| Start Year | 2021 |
| Description | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Organisation | Piramal Clinical Research |
| Country | India |
| Sector | Public |
| PI Contribution | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. |
| Collaborator Contribution | Collaboration for the CiC project include: (i) Cresset Discovery Services, Litlington, UK: in silico hit expansion. (ii) Piramal Pharma Limited, India: Synthesis (iii) Optibrium Limited, Cambridge Innovation Park, UK: in silico ADME and toxicity. (iv) Ebba Biotech AB, Sweden: Assay development - PoC assays. (v) Dr William Schwan, University of Wisconsin-La Crosse, La Crosse, WI, USA: Clinical strain of E. coli - PoC assays. (vi) Dr Christine Farr, University of Cambridge, Department of Genetics: Cytotoxicity assays. (vii) Dr Katherine Stott, University of Cambridge, Department of Biochemistry: ITC assays. Discussion for the commercialisation of the CiC project include: (i) Amanda Wooding & Helen Young: Cambridge Enterprise. (ii) Trevor Perrior: Cambridge Enterprise Expert in Residence (iii) Cathy Boucher: Cambridge Academy of Therapeutic Sciences. (iv) Richard Butt: Apollo Therapeutics. (v) Gavin Whitlock: Sandexis. (vi) Nicola McCarthy: Milner Therapeutics Institute (vii) Sanjay Phogat: GSK |
| Impact | n/a |
| Start Year | 2021 |
| Description | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Organisation | University of Cambridge |
| Department | Cambridge Enterprise |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. |
| Collaborator Contribution | Collaboration for the CiC project include: (i) Cresset Discovery Services, Litlington, UK: in silico hit expansion. (ii) Piramal Pharma Limited, India: Synthesis (iii) Optibrium Limited, Cambridge Innovation Park, UK: in silico ADME and toxicity. (iv) Ebba Biotech AB, Sweden: Assay development - PoC assays. (v) Dr William Schwan, University of Wisconsin-La Crosse, La Crosse, WI, USA: Clinical strain of E. coli - PoC assays. (vi) Dr Christine Farr, University of Cambridge, Department of Genetics: Cytotoxicity assays. (vii) Dr Katherine Stott, University of Cambridge, Department of Biochemistry: ITC assays. Discussion for the commercialisation of the CiC project include: (i) Amanda Wooding & Helen Young: Cambridge Enterprise. (ii) Trevor Perrior: Cambridge Enterprise Expert in Residence (iii) Cathy Boucher: Cambridge Academy of Therapeutic Sciences. (iv) Richard Butt: Apollo Therapeutics. (v) Gavin Whitlock: Sandexis. (vi) Nicola McCarthy: Milner Therapeutics Institute (vii) Sanjay Phogat: GSK |
| Impact | n/a |
| Start Year | 2021 |
| Description | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Organisation | University of Cambridge |
| Department | Department of Biochemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. |
| Collaborator Contribution | Collaboration for the CiC project include: (i) Cresset Discovery Services, Litlington, UK: in silico hit expansion. (ii) Piramal Pharma Limited, India: Synthesis (iii) Optibrium Limited, Cambridge Innovation Park, UK: in silico ADME and toxicity. (iv) Ebba Biotech AB, Sweden: Assay development - PoC assays. (v) Dr William Schwan, University of Wisconsin-La Crosse, La Crosse, WI, USA: Clinical strain of E. coli - PoC assays. (vi) Dr Christine Farr, University of Cambridge, Department of Genetics: Cytotoxicity assays. (vii) Dr Katherine Stott, University of Cambridge, Department of Biochemistry: ITC assays. Discussion for the commercialisation of the CiC project include: (i) Amanda Wooding & Helen Young: Cambridge Enterprise. (ii) Trevor Perrior: Cambridge Enterprise Expert in Residence (iii) Cathy Boucher: Cambridge Academy of Therapeutic Sciences. (iv) Richard Butt: Apollo Therapeutics. (v) Gavin Whitlock: Sandexis. (vi) Nicola McCarthy: Milner Therapeutics Institute (vii) Sanjay Phogat: GSK |
| Impact | n/a |
| Start Year | 2021 |
| Description | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Organisation | University of Cambridge |
| Department | Department of Genetics |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. |
| Collaborator Contribution | Collaboration for the CiC project include: (i) Cresset Discovery Services, Litlington, UK: in silico hit expansion. (ii) Piramal Pharma Limited, India: Synthesis (iii) Optibrium Limited, Cambridge Innovation Park, UK: in silico ADME and toxicity. (iv) Ebba Biotech AB, Sweden: Assay development - PoC assays. (v) Dr William Schwan, University of Wisconsin-La Crosse, La Crosse, WI, USA: Clinical strain of E. coli - PoC assays. (vi) Dr Christine Farr, University of Cambridge, Department of Genetics: Cytotoxicity assays. (vii) Dr Katherine Stott, University of Cambridge, Department of Biochemistry: ITC assays. Discussion for the commercialisation of the CiC project include: (i) Amanda Wooding & Helen Young: Cambridge Enterprise. (ii) Trevor Perrior: Cambridge Enterprise Expert in Residence (iii) Cathy Boucher: Cambridge Academy of Therapeutic Sciences. (iv) Richard Butt: Apollo Therapeutics. (v) Gavin Whitlock: Sandexis. (vi) Nicola McCarthy: Milner Therapeutics Institute (vii) Sanjay Phogat: GSK |
| Impact | n/a |
| Start Year | 2021 |
| Description | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Organisation | University of Cambridge |
| Department | Milner Therapeutics Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. |
| Collaborator Contribution | Collaboration for the CiC project include: (i) Cresset Discovery Services, Litlington, UK: in silico hit expansion. (ii) Piramal Pharma Limited, India: Synthesis (iii) Optibrium Limited, Cambridge Innovation Park, UK: in silico ADME and toxicity. (iv) Ebba Biotech AB, Sweden: Assay development - PoC assays. (v) Dr William Schwan, University of Wisconsin-La Crosse, La Crosse, WI, USA: Clinical strain of E. coli - PoC assays. (vi) Dr Christine Farr, University of Cambridge, Department of Genetics: Cytotoxicity assays. (vii) Dr Katherine Stott, University of Cambridge, Department of Biochemistry: ITC assays. Discussion for the commercialisation of the CiC project include: (i) Amanda Wooding & Helen Young: Cambridge Enterprise. (ii) Trevor Perrior: Cambridge Enterprise Expert in Residence (iii) Cathy Boucher: Cambridge Academy of Therapeutic Sciences. (iv) Richard Butt: Apollo Therapeutics. (v) Gavin Whitlock: Sandexis. (vi) Nicola McCarthy: Milner Therapeutics Institute (vii) Sanjay Phogat: GSK |
| Impact | n/a |
| Start Year | 2021 |
| Description | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Organisation | University of Wisconsin–La Crosse |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. |
| Collaborator Contribution | Collaboration for the CiC project include: (i) Cresset Discovery Services, Litlington, UK: in silico hit expansion. (ii) Piramal Pharma Limited, India: Synthesis (iii) Optibrium Limited, Cambridge Innovation Park, UK: in silico ADME and toxicity. (iv) Ebba Biotech AB, Sweden: Assay development - PoC assays. (v) Dr William Schwan, University of Wisconsin-La Crosse, La Crosse, WI, USA: Clinical strain of E. coli - PoC assays. (vi) Dr Christine Farr, University of Cambridge, Department of Genetics: Cytotoxicity assays. (vii) Dr Katherine Stott, University of Cambridge, Department of Biochemistry: ITC assays. Discussion for the commercialisation of the CiC project include: (i) Amanda Wooding & Helen Young: Cambridge Enterprise. (ii) Trevor Perrior: Cambridge Enterprise Expert in Residence (iii) Cathy Boucher: Cambridge Academy of Therapeutic Sciences. (iv) Richard Butt: Apollo Therapeutics. (v) Gavin Whitlock: Sandexis. (vi) Nicola McCarthy: Milner Therapeutics Institute (vii) Sanjay Phogat: GSK |
| Impact | n/a |
| Start Year | 2021 |
| Description | Membranes and the reduction of clinical adhesions |
| Organisation | University of Cambridge |
| Department | Cambridge Enterprise |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are continuing to use our novel EPD manufacturing technology to produce our proof-of-concept product membranes. We are also working on integrating the technology with more conventional technologies such as freeze-drying to produce combination products which have the advantages of both techniques and can produce more complex architectures. |
| Collaborator Contribution | We have successfully raised £75,000 as a convertible loan from Cambridge Enterprise, and £10,000 and access to the Accelerate@Babraham accelerator program which includes lab space, teaching, and fundraise support. |
| Impact | We are working with Cambridge Enterprise and discussed best ways to engage with clinicians in the NHS, as well as routes to market, and distribution methods within the UK. From our expert partners we have received additional market information regarding both the anti-adhesion membranes and dural membranes, including regulatory pathway, market scopes, and competitor analysis. Clinician interviews are currently ongoing using standardised scripts we have developed in order to determine preferences, desires, and shortcomings of products currently available on the market. |
| Start Year | 2021 |
| Description | Objectives of efficacy assessment and retention of FITC-labelled hydrogel |
| Organisation | Marseille Biological Cancer Laboratory |
| Country | France |
| Sector | Charity/Non Profit |
| PI Contribution | The project comprises preclinical methodology which will inform safe (maximum tolerated) and efficacious doses of Gemcitabine upon intra-cavity delivery. Patient-derived xenografts do not recapitulate the infiltrative extent of glioblastoma observed clinically. Therefore, our approach leverages a rat syngeneic surgical resection model which has previously been used for the successful clinical translation and adoption of Gliadel wafer. We have concluded the objective of establishing a maximum tolerated dose for Gemcitabine-loaded hydrogel. A dose escalation of 1.0wt% to 5.0wt% (maximum hydrogel load) of Gemcitabine was assessed for acute toxicity upon post-surgical delivery to animals bearing orthotopic brain tumours. No acute toxicity was observed as determined by no loss of animal weight, no appetite loss, and no signs of neurological deficits. Therefore, we will progress the maximum tolerated dose (5.0wt%) for efficacy studies. |
| Collaborator Contribution | As a mitigation for the completion of our project objectives, we have identified a collaborator at University of Marseille with dedicated expertise using the same brain tumour surgical resection models. |
| Impact | We are in the process of finalising a collaboration agreement and transfer of remaining budget to University of Marseille to complete the objectives of efficacy assessment and retention of FITC-labelled hydrogel. The planned work is scheduled to initiate in May 2024, concluding in September 2024. |
| Start Year | 2024 |
| Title | Cell surface biomarkers to predict outcome of COVID-19 upon hospital admission |
| Description | Preliminary whole cell lysate analysis experiments are complete, with data analysis underway. Additional funding has been secured from Addenbrooke's Charitable Trust. I would anticipate an initial publication from this work by the end of 2021, writing and final experiments underway at present. To be of greatest clinical utility, cell surface proteins need to be identified, whose expression level predicts the future severity of disease, since these will facilitate real-time flow cytometry-based patient assessment. Furthermore, it is vital to determine which changes in phenotype reflect disease severity, as opposed to disease stage. |
| Type | Therapeutic Intervention - Cellular and gene therapies |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2020 |
| Development Status | Under active development/distribution |
| Impact | Translation to clinic for prospective validation; validation of marker expression over time during COVID. Development of robust cell surface markers that may predict severity of COVID. |
| Title | Development of drugs to combat bacterial biofilms and antibiotic persisters |
| Description | To optimise and expand our list of top hits, we have performed: (i) Affinity assays with purified E. coli tryptophanase enzyme using Isothermal Titration Calorimetry (ITC). This allowed direct demonstration of inhibitor-enzyme interaction and accurate measurement of potency (Kd). (ii) Cytotoxicity assays using mammalian cell culture (CyQuant LDH Cytotoxicity assays in THP-1 mammalian cell line). This allowed initial toxicity testing of top hits to determine their suitability for human use. (iii) Pharmacokinetics "ADME" (absorption, distribution, metabolism, and excretion) and toxicity predictions of promising candidates using in silico platforms (Quantitative structure-activity relationship (QSAR) & toxicity (Derek Nexus) models, StarDrop, Optibrium). This allowed initial predictions of the suitability of our top hits for drug development. (iv) Proof-of-concept (PoC) biofilm inhibition assays with fluorescent biofilm-indicating dye (EbbaBiolight 680, EbbaBiotech) using clinical strains of uropathogenic E. coli. This allowed confirming the ability of our top hits to inhibit biofilm formation in clinical strains of E. coli. (v) In silico hit expansion based on our top hits via a ligand-based virtual screening and de novo design platform (in collaboration with Cresset Discovery Services). This exercise produced an additional 30 designs that have the potential of improved activity. (vi) Synthesis of top 10 designs (in collaboration with Piramal) |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Refinement. Clinical |
| Year Development Stage Completed | 2021 |
| Development Status | Under active development/distribution |
| Impact | At the beginning of the MRC CiC project, we had a list of 5 top inhibitors (effective inhibitors that passed PoC testing against laboratory strains of E. coli). With the help of the MRC CiC grant, we have expanded our list to 9 top inhibitors. These 9 top candidates did not only pass PoC testing in laboratory strains but also in clinical strains of uropathogenic E. coli. Additionally, they passed the in silico pharmacokinetic and in vitro Cytotoxicity filters, and their affinities are in the range of 1 - 10 µM (antibiotics that are used to treat UTIs, such as ciprofloxacin, are within the same range of affinities), thereby confirming their suitability to be taken further for pre-clinical development. Note: we are still in the process of testing the synthesised compounds. Therefore, additional hits may be added later to our current list of 9 top candidates. The next stage of progress towards clinical use will begin with in vitro ADME testing of our top candidates to confirm the in silico predictions, thereby confirming their pharmacological suitability as potential drugs for human use. The compounds would subsequently be tested in the mouse (where UTI models for the study of biofilms are well-established) by third party companies (e.g. Charles River, Sequani). |
| Title | Enabling wider application of molecular imaging of pituitary adenomas through a fluorine-18 radiotracer |
| Description | The project commenced 01 Jan 2021. From Jan-mid Feb, initial preparatory work (ahead of a first test synthesis) was completed as planned. On 19th February the first test run for the new tracer 18F-FET was completed successfully in the Wolfson Brain Imaging Centre Radiopharmacy Unit (WBIC RPU). We obtained over 5.3 GBq of product, almost 3.6 in the patient vial, which represented a high yield. The synthesis was repeated to confirm the robustness of the methodology for reliable production of high yields of 18F-FET. In parallel, the product was sent for sterility testing and a process for QC validation was established. The third and final validation was completed by 15 Apr 2021. The sterility test results were also satisfactory. Accordingly, the radiotracer was approved for clinical production and use in the pilot study. As indicated, the protocol, participant information leaflets and consent forms have been prepared for submission via IRAS in preparation for submission for ethical review. This phase has been delayed due to several reasons: i) several clinical academics from our group were required to undertake additional clinical duties, including working on the frontline, during the second peak of the pandemic earlier in the year; ii) Dr Koulouri (co-applicant) has been on maternity leave since February; iii) Mr Kolias (co-applicant) was seconded to a full-time senior clinical fellowship post in London and has only returned to Cambridge from 01 Sept 2021. In addition, the PET/CT scanner in Cambridge is due to be replaced in the very near future. Initial estimates suggested this work would be completed during the summer of 2021, but this was subsequently revised to October 2021. We have however learnt in the last few days that this date has been revised again and has now been pushed back to early 2022. We have an NIHR Academic Clinical Fellow (Dr James MacFarlane) working on the project and he will be supported by Mr Kolias, who has returned as an Academic Consultant. We are therefore working to secure regulatory approvals as soon as possible to capitalise on the amended change to the PET/CT scanner replacement schedule. |
| Type | Diagnostic Tool - Imaging |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2021 |
| Development Status | Under active development/distribution |
| Impact | We have confirmed that 18F-FET can be manufactured to GMP standards using the GE FASTlab cassette-based synthesiser, thus establishing a robust and reliable method which can be rolled out to other radiochemistry facilities and PET/CT units. Comparison with 11C-Met in the pilot study will allow a decision to be made whether 18F-FET should proceed to a larger multi-centre study to assess its potential utility for imaging pituitary adenomas and whether it could replace 11C-Met as the clinical tracer of choice. At this stage, given the requirement for a specialist radiopharmaceutical unit to synthesise the radiotracer, and for specialist surgical services to act on the findings of the molecular imaging, we anticipate this research will have limited immediate relevance to LMICs. |
| Title | This is an interdisciplinary project that uses an innovative approach to develop a new speech coding strategy for cochlear implants. It combines technical development and software programming with behavioural evaluation studies and the use of specialised research interfaces for custom stimulation of the human auditory system. |
| Description | Our project is still ongoing, to complete the data collection for the real-time version of the TIPS strategy, which has been delayed by ethical approval. We will communicate these results to our industry stakeholders and take the conversation forward on how to test a take-home trial for the TIPS algorithm. In parallel, we will go back to the science and address some questions that are still unanswered, such as what mechanisms are crucial for TIPS processing and whether it would benefit from individualisation. |
| Type | Therapeutic Intervention - Medical Devices |
| Year Development Stage Completed | 2023 |
| Development Status | Under active development/distribution |
| Impact | We have obtained further evidence that the TIPS algorithm has the potential to substantially reduce power consumption of CI devices, while not harming speech perception. This has been confirmed in realistic listening situations in comparison to the baseline everyday strategy of 12 CI listeners. We also found that real-time conversion of the TIPS algorithm can provide comparable results and lays the foundation for its implementation in CI devices. |
| Title | Vivo animal safety test of membrane production method please |
| Description | Accelerate@Babraham: This is a biotech accelerator programme over 5 months, including lessons and teaching on fundamental aspects of running an early stage biotech company and transitioning from lab to product, as well as including lab space and access to facilities and networking. Fast50: This is a convertible loan from Cambridge Enterprises to funding continued development of a prototype membrane, as well as full development of a business plan, and work with experts in regulatory compliance and quality management systems. |
| Type | Therapeutic Intervention - Medical Devices |
| Year Development Stage Completed | 2023 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| UKCRN/ISCTN Identifier | OECD GLP, ENV/MC/CHEM (98)17 |
| Impact | Using data gathered by ourselves and our expert partners, including meetings with surgeons and regulatory experts, we have chosen to focus on developing products for the dural membrane and advanced woundcare markets initially. We have carried out extensive business and technical planning, including development of a 5+ year Gantt chart for all business activities, a company business plan, costings, and competitor analysis. We have received the results from our in vivo clinical trial which demonstrated that our novel manufacturing technology did not raise any additional safety concerns when compared to conventional fabrication methods. We have used expert panels of surgeons to explore potential product concepts and are moving forward with a chosen device concept, with work currently ongoing to produce a proof of concept device demonstrating all features of the implants. We are currently undergoing our seed round at the moment and have a lead investor onboard. We did not secure investment during 2023. Company CEO has identified new potential investment leads which are very early stage and speculative at this point. These will be followed up in the coming period. |
| Company Name | CamRegen |
| Description | CamRegen develops collagen-based medical devices. |
| Year Established | 2021 |
| Impact | Update 2023: Discussion: We have worked with Callisto to perform consulting work and initial interviews with clinicians. We have also worked with Cambridge Technology Development Limited on development of prototype manufacturing devices and design work. We have worked with a number of regulatory specialists including James Pink, Evera Regulatory Advisors, and Element. |
| Company Name | Cambridge Medical Innovation Ltd |
| Description | |
| Year Established | 2020 |
| Impact | CMI Ltd has been awarded an Innovate UK grant to pilot the technology in NHS Scotland. An NIHR i4i grant application was submitted in December 2020 to cover development and pilot of an integrated platform to enable DigiVis and other digital tests to work within NHS clinician and patient workflows. Cambridge Enterprise has enabled Free of Charge use of DigiVis during the Covid crisis to support remote consultations at CUH and catch up vision screening by CCS. |
| Description | An Article on the Gonville & Caius web site describing the commercialsation and research in the field of recurrent urinary tract infections. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | The purpose was to keep members, alumni and friends of the College informed about the research being carried out by College members and the benefits that we hope will follow from its commercialisation. Broader awareness of the problem of recurrent UTIs and our initiative to develop a new treatment |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.cai.cam.ac.uk/news/bid-resolve-recurring-utis |
| Description | CI volunteer appreciation day at the MRC CBU, Cambridge. UK |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Study participants or study members |
| Results and Impact | The primary audience were CI users, who take part in our research studies and their partners. Geographical reach was local and regional. This activitity was attended by about 40 volunteers. We presented our research studies and findings to CI recipients. There were discussions and feedback sessions. This event was well received and shared knowledge and findings with the target audience of our research. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Cambridge Graft Survey |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | We conducted a feedback survey (https://www.survio.com/survey/d/M1E9O9D4X3V5W6W9O) via KRUK's patient network on whether our approach of making bioengineered vessels for vascular access in haemodialysis would be acceptable. The answers illustrated that patients are having issues with their current grafts, what is important to them in a new one and whether they would be open to trying custom-made collagen-based grafts in the future if clinical trials are successful. 89.5% of respondents felt that the ability to produce custom-made grafts to satisfy patients' needs is a very important feature. 73.7% of respondents had no concern about the use of bovine collagen, however, the remaining 26.3% had minor concerns. The survey also revealed that some respondents had questions and concerns around the use of new technologies. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.survio.com/survey/d/M1E9O9D4X3V5W6W9O |
| Description | Clinician Meeting 2023 - Potential Product Concepts |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | We held meetings with approximately 16 clinicians from both the neurosurgical and woundcare fields to discuss their needs, as well as to look at potential product concepts. The feedback from these meetings was used to determine an appropriate product concept to take forward which showed significant potential benefits over currently used products. Meetings are ongoing with some of the surgeons contacted, as well as additional surgeons, to continue to obtain feedback and drive product requirements. |
| Year(s) Of Engagement Activity | 2023 |
| Description | End user/clinician interviews |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | We have undergone two phases of meetings with surgeons relating to their problems with current devices, requirements and desires for new products, numbers of procedures, hospital product supplies, and overall openness to new products. In the first phase of meetings, we met with 3 abdominal surgeons to discuss anti-adhesion membranes and 3 neurosurgeons to discuss dura substitute membranes. As a result of discussions with abdominal surgeons, it was determined that many surgeons felt that post-surgical adhesions were an under-recognised but potentially serious complication. However as they generally took more than 12 months to develop post-surgically, often without symptoms, they rarely saw the outcomes of surgeries they had previously performed making it a problem "down the road" for both surgeons and clinical commissioners and hence a low priority issue as interventions didn't affect the current fiscal year. They also raised issues relating to problems with potential clinical trial complexity, low product costs, and limited guidelines on adhesion prevention. Discussions with neurosurgeons showed that both spinal and cranial surgeries required dura substitute products in almost all surgeries, and that the current products were not satisfying all the clinician requirements. Surgeons lacked confidence that products would remain in position post-surgery and that this increased risk of CSF leakage or infection was forcing them to keep patients in hospital for monitoring. Surgeons working with higher pressure fluids such as at the base of skull or spine suffered from more significant problems with CSF leakage and were interested in products which could adhere to the dura to prevent leakage. All surgeons were interested in natural products with higher durability. Following these discussions, we decided to concentrate on development of dura substitutes rather than anti-adhesion membranes due to the size and ease of accessing the market. In the second phase, we have met with a further 4 neurosurgeons who have provided us with further confirmation of the initial issues that were highlighted, as well as additional data on product usage, physical product requirements including thickness, strength, suturablity, and fluid resistance. Using the product requirements and specifications from these interviews we are currently producing proof of concept devices for testing and to demonstrate to clinicians to get feedback on usability. Additionally, we are currently arranging to carry out a further 6 interviews with neurosurgeons from the UK, EU, and US. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Open Days at Engineering Department and Masterclass at Robinson College Cambridge |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | The aim is to introduce school students to Engineering including Bioengineering |
| Year(s) Of Engagement Activity | 2022 |