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Phenomics Discovery initiative
The Phenomics Discovery Intitiative (PDi) is a public private consortium that aims to enhance translation of phenotypic biology into novel therapeutics for patients. The consortium is made up of pharmaceutical companies, and the Universities of Dundee, Edinburgh and Oxford.
What does PDi do?
PDi selects, develops and validates pre-competitive phenotypic assays that are innovative, relevant to human disease and pertinent to the PDi pharma partners.
Assays are selected globally from the academic, clinical and SME communities, developed into robust assays, and run on NPSC’s industry-standard phenotypic screening platform, against a best-in-class non-proprietary chemical toolbox tailored to phenotypic screening. NPSC delivers high quality data packages, including chemical entities that perturb a phenotype, aid target/pathway identification, and can provide starting points for drug discovery campaigns.
Assay recruitment and selection
Assay proposals representing major areas of unmet therapeutic need are well represented with 22% of projects being relevant to oncology, 12% to CNS diseases, 9% to gastrointestinal disease, and 9% to immunology. Respiratory, cardiovascular, metabolic and rare diseases are also represented.
PDi's initial portfolio contains
- A complex human brochoepithelial cell (HBEC) assay, with an air-liquid interface mimicking the real situation in the lung, will be used to screen for novel anti-virals in common respiratory diseases.
- An assay that aims to identify novel ways of boosting cancer immunotherapies by reactivating “exhausted” T cells.
- An assay, which targets Endoplasmic Reticulum (ER) stress as a therapy for alpha-1 antitrypsin deficiency in liver cells.
- An assay aimed at manipulating cancer cell self-renewal in the brain cancer glioblastoma.
- An assay which aims to identify novel approaches that either bypass cellular senescence or selectively target senescent cells, which may reduce age-related tissue dysfunction and prolong healthy lifespan.
- Targeting signalling in cell proliferation as an approach in cancer treatment is being addressed with an assay that aims to influence the so-called “Hippo” pathway.
- A High Content (HC) screen in human white blood cells will attempt to identify compounds that inhibit NLRP3 inflammasome activation, in this case applied to finding treatments for Alzheimer’s disease. The phenotypic assay, based on a mouse bone marrow derived macrophages (BMDMs) cell line will be used as a model to find inhibitors of the NLRP3 inflammasome before further testing in human in vitro assays.
- Phagocytosis plays a key role in clearance of bacteria and apoptotic cells in infected or damaged tissues and its impairment has been implicated in chronic inflammatory diseases, autoimmune diseases and solid tumour oncology. NPSC will aim to find small molecules that stimulate mouse macrophage phagocytosis, whilst converting the model to utilise equivalent human cells.
- Targeting immune suppressive molecules expressed by tumour-associated macrophages is thought to be a good way to improve efficacy of immunotherapy against metastatic breast cancer. NPSC will be working on a co-culture cell model to find small molecules that inhibit macrophage-mediated Natural Killer (NK) cell suppression in order to enhance cell-based immunotherapies.
- A novel phenotypic screen aiming to discover small molecules to reduce the replication of enteroviruses that are increasingly linked to mild and severe respiratory diseases.
A more detailed description of the the PDi portfolio can be found in press releases here (round 1 selection) and here (round 2 selection).
Benefits to academic partners
Benefits to academic, clinician and SME participants.
Participants can apply to PDi with either assay concepts and ideas, developed assays in low throughput or ready-to-screen assays in 96/384 format.
Selected assays are screened free of charge - PDi covers all the costs of:
- Assay development from concept to high throughput format. Whatever the start-point, PDi staff will work closely with the participant to ensure the biology is maintained.
- Reagents including any requirements to generate cell lines and cell/tissue culture
- Access to a high quality industry-standard compound collections
- Access to world-class high content screening facilities and state of the art chemoinformatics and bioinformatics.
The generated industry-standard data is owned by the applicant.
This includes knowledge of the identity of validated hit compounds. Assay development and screening results data are also shared pre-competitively between all consortium members.Industry participants are free to use the validated assay in-house on proprietary compound sets in so-called “private” screens.
Benefits to industry
Benefits for industry partners
PDi develops and validates innovative phenotypic assays that are driven by industry needs.
- Each partner can directly nominate 8 assays over 5 years.
- As part of a consortium, industry partners benefit from cost and risk sharing between peers in a pre-competitive space.
- Screening data and protocols from validated assays are shared between all consortium members.
- Industry participants are free to use the validated assay in-house on proprietary compound sets in so-called “private” screens.
- A PDi contract is already in place and negotiated to meet pharma needs, for an annual membership fee.
- View full T&Cs
The focus of the PDi consortium will be the development of novel phenotypic assays amenable to high throughput screening, with the goal of identifying new pathways and mechanisms for drug discovery, by employing systems with higher potential for translation into the clinic. The phenotypic screens we will use are more relevant to patients and their disorders and as such the goals of the PDI are to advance drug discovery towards improved clinical outcomes through joint academic-industry collaboration".