Diana Spencer reports on ELRIG UK’s Drug Discovery in Scotland Forum, held in the grandiose surroundings of the Royal College of Physicians Edinburgh in September.

The Drug Discovery in Scotland Forum showcased how Scotland is shaping drug discovery using approaches including traditional small molecules, therapeutic proteins, CRISPR/ RNAi and cell therapies, as well as how these are being used in 2D and 3D models. The main talks were punctuated with short technology focused updates from the event’s industry sponsors.

SRC kinase inhibitors, organoids and functional genomics

The first speaker was Asier Unciti-Broceta, Personal Chair of Medicinal Chemistry – Innovative Therapeutics at the University of Edinburgh, on the topic ‘Discovery and preclinical development of eCF506/NXP900, the first total inhibitor of SRC kinase’. He explained how the history of SRC research has always been inherently linked with cancer research. He took delegates through the history of the discovery of the oncogene v-Src and proto-oncogene SRC, onto the development of SRC inhibitors like dasatinib and bosutinib, which are approved to treat chronic myeloid leukaemia.

Unciti-Broceta then moved on to the discovery of eCF506 from a novel family of compounds that selectively inhibit SRC family kinases in an inactive formulation, making them more effective than current inhibitors. The compound has now been licensed to Nuvectis Pharma who started Phase I trials in 2024 in various cancers.

The next speaker was Laura Rosenberg, a Director in the Discovery Sciences department in AstraZeneca, on ‘Understanding mechanisms of cancer drug sensitivity and resistance using functional genomic approaches.’ Rosenberg emphasised the importance of genomics in understanding the mechanisms behind drug resistance and how using scaled CRISPR screening platforms can increase the probability of success. She discussed the reasons behind project failures at AstraZeneca, which have been increasingly due to efficacy of the compound, and the importance of pre-clinical linkage between target and disease. The company is now employing the 5R framework (right target, right tissue, right safety, right patient, right commercial potential) and has 23% project success compared to an industry average of 14%.

Rosenberg went on to explain how CRISPR screening can enhance the drug discovery process and the advantages offered by pooled and arrayed CRISPR screening. She then focused on how this approach had been used in ER+ breast cancer to identify gene knock-outs driving resistance or sensitivity to current therapies, and the discovery that high expression of OXPHOS genes is associated with poorer outcomes.

Next up, Elad Katz, Founder of Navigate Precision Biology at the University of Dundee, presented ‘Oodles of organoids: scaling up disease models for drug discovery’. He began with a look at the challenges facing drug discovery, including the fact that 90% of drug research fails to reach approval, and asked whether organoids could be part of the solution to reduce the time, cost and waste in the process. He then introduced NaviPlate, designed at the University of Dundee, which offers various advantages such as requiring very few stem cells to seed. His team has so far focused on human kidney disease modelling, with more recent efforts to use NaviPlate to produce miniaturised heart, lung and even bone organoids.

Immuno-oncology assays, KMO inhibitors and miniaturised screening

After lunch, Adele Hannigan, Chief Business Officer of Antibody Analytics, spoke on ‘Modelling the tumour microenvironment: Immuno-oncology assays and inducible cell line platforms (IndEx-2) to characterise antibody-targeted therapeutics’. Hannigan looked at how the field of immuno-oncology has expanded in the last decade or so, with the development of new treatments like immune-targeted therapeutics, immune cell engagers and engineered cell therapies such as chimeric antigen receptor T cells (CAR-T). However, she points out that these therapies bring the risk of T cell exhaustion which results in educed proliferative responses and loss of effector function. Hannigan presented a case study of CLN-987, a highly potent CD-19 targeting T cell engager characterised using the IndEx-2 system, which is predicted to work in low expression levels of CD19 and could be a potential treatment for B-cell malignancies.

Following the talk, Dr Mariana Vaschetto, Head EMEA/APAC, Collaborative Drug Discovery, presented a Technology Spotlight on ‘Simplifying informatics: A single unified collaborative solution’. She comments: “We are grateful for the opportunity to present CDD Vault at the Drug Discovery Scottish Forum. At CDD, we aim to empower scientists with a secure, intuitive platform for managing and sharing their chemical and biological research data. ELRIG conferences provide an ideal platform to showcase new developments, including our AI-driven functionalities for uncovering new leads, our enhanced ELN framework, and analytics tools like Curves for complex experiment analysis.”

Scott Webster, Co-Founder and Chief Technology Officer of Kynos Therapeutics and Professor of Medicines Discovery at the University of Edinburgh, then gave his presentation ‘Discovery & development of KMO inhibitors for the treatment of inflammatory conditions’. Kynos Therapeutics is a spinout company from the University of Edinburgh developing inhibitors of kynurenine 3-monooxygenase (KMO). The presentation described the discovery and development of these small-molecule inhibitors of KMO, which are being developed as first in-class medicines to limit the damage to secondary organs during a systemic inflammatory response.

The drugs were optimised as part of a collaboration with GSK, and Kynos has now completed a Phase I trial with its lead molecule (KNS366), which has been shown to be safe and to engage the target. The research team has also found high KMO expression in the human endometrium and tested its KMO inhibitor KNS898 in a mouse model of endometriosis.

Then there was a Technology Spotlight Presentation from CryoLogyx’ Tom Congdon on ‘No more routine cell culture: Assay-ready cell banking for drug discovery and beyond’. He commented: “I was delighted to attend the ELRIG Drug Discovery in Scotland meeting. CryoLogyx sponsored the event and was able to present our latest work and showcase our assay-ready products. Being able to present our work at the Royal College of Physicians was a real treat and is by far the most impressive building we have set up our booth in! The organisers arranged a great programme of speakers all doing incredible work on organoids and 3D cell culture for drug screening and disease modelling, and the great work done in Scotland on developing new therapeutics.”

The final speaker of the day was Michele Zagnoni, a Reader at the University of Strathclyde and CEO and Co-Founder of ScreenIn3D, who spoke on ‘Screening complex in vitro models of disease at scale’. He explained how different in vitro complex models of human disease from clinical samples can be miniaturised and screened at a scale for combination therapies, using different approaches based on microfluidic and lab-on-a-chip technologies. He introduced delegates to UpScale3D translational models of human disease, which provide ‘human-like’ drug screening, decrease the time to results for all 3D screening-based assays, and provide unique miniaturisation capabilities for combination studies.

Diana SpencerAbout the author

Diana Spencer is Senior Digital Content Editor at DDW. She has nearly 20 years experience in both print and digital editorial roles for B2B publications dedicated to the life sciences sector, including medical and pharmaceutical industry journals/magazines.