Preclinical data from Pieris' inhaled IL-4Ra antagonist, from ERS:
>>AZD1402/PRS-060, an inhaled Anticalin® IL-4Ra antagonist, potently inhibits IL-4 induced functional effects in human whole blood, which can be employed translationally in clinical studies.
Katerina Pardali, Fanyi Jiang, Mary Fitzgerald, Gabriele Matschiner, David Keeling
Introduction: AZD1402 is an Anticalin protein in clinical development that has the potential to offer an inhaled treatment for asthma patients suffering from T2-driven disease through selective blockade of IL-4Ra.
Aims and objective: To characterise the effect of AZD1402 on IL-4Ra signalling in human whole blood (WB) and establish a method to evaluate the functional impact of systemic exposure to AZD1402 following inhaled dosing.
Methods: WB from healthy subjects was stimulated with IL-4 in the presence or absence of AZD1402. Phosphorylation of signalling components and released soluble biomarkers were quantified using FACS and multiplex ELISA, respectively.
Results: Stimulation of human WB with IL-4 resulted in increased levels of phosphorylated STAT6 (pSTAT6) and in the release of eotaxin-3, TARC, and MDC. AZD1402, when added to WB samples (n=12), inhibited pSTAT6 in a concentration-dependent manner and with similar potency to the anti-IL-4Ra monoclonal antibody dupilumab (IC50 values 1.3 and 0.6 nM, respectively). Inhibition of the release of the soluble cytokines eotaxin-3, TARC, and MDC by AZD1402, at equivalent potencies to dupilumab, was observed (IC50 values of 1.9 nM, 1.2 nM, and 2.6 nM, respectively). The low level of variation observed render this method suitable to detect the presence of systemic (pharmacologically active) levels of AZD1402 following inhaled dosing.
Conclusions: AZD1402, potently inhibits IL-4Ra signalling in human WB with IC50 values comparable to those of dupilumab. pSTAT6 responses in WB are used in the NCT03384290 Phase I trial to assess systemic exposure.<<
The trial is by inhalation or IV. I assume the latter is not the preferred method of administration that they'd try to bring to market. Injection just competes with dupi, so I figure inhalation is the route they'll push. But not sure what patients would prefer. A few subQ injections is not that onerous.
Obviously not a near term threat to dupi.
Cheers, Tuck |
