Iolanda Micco, head of discovery chemistry at Axxam, delivered a presentation on targeting P2X7 from early discovery to a clinical stage candidate. Micco began by introducing Axxam as a science-driven drug discovery company based in Italy, with headquarters in Milan and additional labs in Naples, as well as business offices in the US, Denmark, and Switzerland. She highlighted Axxam's expertise in the early stages of drug discovery, from target identification to preclinical candidate selection.
Micco discussed the platforms and skills developed in-house, including in vitro biology, optogenetics, iPSC cells, organellar electrophysiology, and RNA biology. She emphasised the importance of the hit identification phase, where chemical matter is selected for further development. Axxam introduced virtual screening and validated hits in-house from both chemical and preliminary ADME perspectives.
The presentation then shifted focus to Breye Therapeutics, a Danish company developing therapies for vascular retinal diseases. Micco explained that current treatments for these diseases often require intravitreal injections, which have poor compliance. Breye aimed to develop oral treatments with high ocular exposure.
Micco elaborated on the significance of the P2X7 receptor, a ligand-gated cation channel activated by high ATP concentrations, found in the CNS, photoreceptors, and immunocompetent cells. She detailed the receptor's role in inflammation cascades and its potential as a target for Alzheimer's disease and retinal diseases.
The programme began at Axxam, where high throughput screening identified promising hits that progressed to lead optimisation. Micco described the iterative cycle used to evaluate potency, selectivity, and ADME profiles, leading to the identification of a robust lead compound. The lead compound demonstrated high potency, no ADME problems, and good PK in both mouse and rat models.
Micco concluded by highlighting the successful transition of the lead compound to Breye Therapeutics for further development. She emphasised the importance of teamwork, resilience, and having fun while working on scientific programmes.
