Bioengineering to reduce animal use and improve drug development

Transcription

1 Bioengineering to reduce animal use and improve drug development Anthony Holmes PhD Programme Manager Technology Development NC3Rs Institute of Bioengineering Launch Event Queen Mary, University of London 8 October 2015

2 The NC3Rs Independent, scientific organisation Established by Government in 2004 Use the 3Rs as a framework to support UK science, innovation and animal welfare Work with research funders, academia, industry and regulators broad remit Budget ~ 7 million per annum 20 posts based in London Activities divided between: Funding research and innovation in universities and other research organisations Science programmes led by the Centre s team of scientists

3 What do we do?

4 Opportunities from the NC3Rs Funding basic research CRACK IT Open Innovation Non-Animal Technologies (NATs) Project & pilot grants Response mode scheme for hypothesis driven research PhD Studentships To embed the 3Rs in the training of grad. scientists David Sainsbury Fellowships To support early career scientists in becoming independent researchers Challenges A competition to develop new 3Rs technologies which improve business processes or lead to new marketable products Solutions A technology partnering hub for showcasing ideas, technologies & products and finding new markets and collaborators Application of NATs for more predictive safety & efficacy testing Collaboration with Innovate UK & UK research councils Strategic investment to maximise UK impact UK roadmap for NATs coming later in 2015 NAT SIG for partnering, networking & funding group/non-animal-technologies

5 The challenges. Recognising opportunities Regulatory Funding Collaboration Technology readiness Validation

6 A pipeline for bioengineered products Basic Research Identifying market needs/crosscompany analyses Innovation & Early Stage Commercialisation Commercial Development & Expansion Change in practice and policy NC3Rs works across all phases to overcome the barriers to application of new bioengineered products

7 Applying regenerative medicine approaches to drug development Applying human cell and regenerative medicine technologies to efficacy and safety testing of new drugs April 2015 Jointly hosted by NC3Rs and UKRMP with support from the Stevenage Bioscience Catalyst Aim was to explore whether regenerative medicine, organ- and cellbased technologies could have predicted drug product failure prior to clinical (human) or preclinical (animal) trials. A short workshop report with recommendations based on workshop discussions is being drafted and designed

8 Applying regenerative medicine approaches to drug development Endpoint Opportunities for bioengineering Biologics development 3D liver technology to: Characterize sinusoidal dilation across species, Explore the mechanism of toxicity Develop biomarkers

9 Applying regenerative medicine approaches to drug development Endpoint Opportunities for bioengineering Biologics development 3D liver technology to: Characterize sinusoidal dilation across species, Explore the mechanism of toxicity Develop biomarkers Cardiovascular toxicity Intelligent tissues combining multiple cell types. Investigate structural changes on exposure to drugs that match those seen in vivo Gene targeted ips lines that report on cell stress, proliferation, energy and hypertrophy Inclusion of fluidics, imaging and detecting secreted biomarkers

10 Applying regenerative medicine approaches to drug development Endpoint Opportunities for bioengineering Biologics development 3D liver technology to: Characterize sinusoidal dilation across species, Explore the mechanism of toxicity Develop biomarkers Cardiovascular toxicity Intelligent tissues combining multiple cell types. Investigate structural changes on exposure to drugs that match those seen in vivo Gene targeted ips lines that report on cell stress, proliferation, energy and hypertrophy Inclusion of fluidics, imaging and detecting secreted biomarkers Nephrotoxicity How can tubular necrosis, degeneration, and dilation be modelled in cell or tissue-based assays? In vitro models are extremely valuable in the evaluation of drug toxicity and should be further explored for nephrotox

11 2D: Single cell High throughput Low tissue complexity Low cost High content imaging Progress through OI CRACK IT Challenge - Inpulse Cardiotoxicity is one of the most common causes of preclinical and clinical attrition Challenge aim: To generate a physiologically-relevant cardiac contractility platform with phenotypically mature cells that move Ca 2+ and metabolically generate energy 3Rs impact: Reduce need for contractility studies in dogs, efficacy studies in mice, and screen compounds for early go/no-go decisions 2D: Monolayer 2.5D: Muscular Thin Films 3D: Engineered Heart Tissue Low throughput High tissue complexity Higher cost Lower content imaging Endpoint measurements - Structure - Function - Ephys, Ca 2+, Contractility (±load) - Proliferation - Survival

12 Progress through OI CRACK IT Challenge - Nephrotube Nephrotoxicity accounts for 19% of all drug failures in phase III Challenge aim: To develop a multi-compartmental, microfluidic tissue assay that models the renal tubular injury observed in nephrotoxicity 3Rs impact: Reduce need for in vivo nephrotoxicity models and improve translation to the clinic Endpoint measurements - TEER - ROS levels - RNA/protein expression - Transport function - Mitochondrial toxicity - Apoptosis - Tox pathway activation

13 Non-Animal Technologies - An emerging area of strategic importance To accelerate the integration of NATs into drug & chemical development to improve safety & efficacy prediction Emerging area of strategic importance

14 Non-Animal Technologies - An emerging area of strategic importance To accelerate the integration of NATs into drug & chemical development to improve safety & efficacy prediction Emerging area of strategic importance Establishing a world leading NATs sector in the UK Increased investment NATs roadmap Workshops and events NATs Special Interest Group -

15 Driving change in practice - Rodent Big Brother CRACK IT Challenge to develop an automated non-surgical system, to measure activity and temperature in rats & mice Uptake of technology and change in company practice with roll-out across organisation Facilitated through NC3Rs technology partnering hub, CRACK IT Solutions: Wider uptake across industry and further changes in practice Application in other areas, including SCI working with QMUL researchers

16 Basic Research Identifying market needs/crosscompany analyses Innovation & Early Stage Commercialisation Commercial Development & Expansion Change in practice and policy Technology readiness Recognising opportunities Funding Validation Collaboration Regulatory

17 Further information Website: OR E-newsletter: @NAT_SIG