Details: BioVaria Munich - Europe's leading showcasing Event for LIFE-SCIENCE Technologies

Q5*

First-in-Class Highly Selective IKKα Inhibitors Targeting the Non-Canonical NF-κB Pathway to Combat Aggressive Inflammation Driven Cancers and Diseases.

Dr Simon Mackay, University of Strathclyde

Cancer Research Horizons

Challenge

Chronic inflammation drives the pathogenesis of castration resistant prostate cancer (CRPC) and colorectal cancer (CRC), promoting immune suppression, metastasis and treatment resistance. By manipulating cytokine production, IKKα sustains a hostile treatment-resistant microenvironment to enable tumour proliferation.

Technology

Kaplan–Meier analyses in prostate and CRC patient cohorts show that elevated IKKα expression associates with poorer overall survival, supporting IKKα as a clinically relevant target with prognostic value as a patient selection biomarker.

The multidisciplinary team across the Universities of Strathclyde, Glasgow and Adelaide has developed the first and only series of small-molecule inhibitors that selectively perturb IKKα-driven noncanonical NF κB signalling with exquisite potency (< 200 nM) without impacting the IKKβ-mediated canonical pathway and its associated undesired effects at 30μM across multiple CRPC and CRC cell lines.

Ex vivo, in CRPC patient-derived explant models, our lead compounds totally outperform enzalutamide and have comparable effects in murine and patient-derived organoids that are representative of right-sided, inflammatory-driven mutational states of CRC. The lead series reduces tumour-promoting chemokine synthesis in the tumour microenvironment (TME), indicating dual action on cancer cells and inflammatory burden.

Commercial Opportunity

Strathclyde/CRH’s first-in-class portfolio of IKKα small molecule inhibitors has the potential to transform outcomes in inflammation-driven cancers, including CRPC and CRC, with strong expansion opportunities into CLL, pancreatic cancer, multiple myeloma, TNBC, hepatocellular carcinoma and inflammatory diseases.

The team comprises world-class scientists who are directing the assessment of lead compounds in ex vivo and in vivo gold-standard models of CRPC (David Waugh and Lisa Butler, Adelaide University) and CRC (Owen Sansom and Joanne Edwards, Glasgow University).

With a suite of compounds and a derisked translational path, CRH and the University of Strathclyde seek licensing, co-development, and venture building partners to accelerate this globally leading IKKα programme into clinical development and ultimately patient use.

Development Status

Backed by over ~£2.9m in translational funding investment (MRC-UKRI; CRUK/CRH), the team is advancing preclinical candidate selection by optimising SU1644 and undisclosed leads to move candidates closer toward IND-enabling and first-in-human studies. The most recently developed series via MRC-DPFS funding has significantly improved in vivo pharmacokinetic parameters to initiate extensive in vivo efficacy studies in Q2 2026.

Patent Situation

Multiple IKKα selective compound series provide broad chemical space coverage and freedom-to-operate. WO2023218201A1 and WO2024228035A1 have entered national/regional phases (EU, US, JP, CN, AU, CA KR), and cover IKKα inhibitor pharmaceutical compositions, and their therapeutic use in proliferative disorders (e.g., solid tumours and haematological malignancies) and other IKKα implicated conditions. A priority patent covers the most recent series with the requisite PK parameters for in vivo efficacy studies.

Q5*