Case studies

In one case, a sponsor delegated to Aepodia early clinical planning, including identifying and implementing biomarkers for a CNS compound. The primary objectives were to confirm target occupancy and proof of pharmacological activity. The secondary objectives were to construct PK/PD modeling for Phase 2 dose selection. Aepodia has integrated PET expertise and has carried out PET in FIM studies. We have also used ongoing PET data to launch Pharmacodynamic Studies in an umbrella approach in different study sites and countries.

For this program, the sponsor gained rapid access to key data, such as receptor occupancy, pharmacological activity, and the dose selection rationale for a Phase 2 program.

Aepodia has significant experience in the use of imaging technologies in drug development. Conducting those studies in Europe has significant advantages: not only access to imaging technologies at affordable costs, but also access to top of the line radiochemists and centers with direct access to patients, all with extremely competitive timelines. Furthermore, some government incentives encourage the use of these imaging biomarkers in neurodegenerative diseases, for example.

For this CNS compound with a narrow safety margin from animal data, no predictive safety and tolerability were indentified and, therefore, biomarkers reflecting brain activities (direct or indirect) were needed. Aepodia recommended that the Sponsor introduce CSF (cerebrospinal fluid) collections in the first multiple ascending-dose study (MAD) of this compound with a new mechanism of action (MOA). The results of the clinical study confirmed that the compound was crossing the blood brain barrier. However, no effect was detected on CSF biomarkers specific to this MOA. Consequently, compound development has been stopped (“Quick Kill”) before launching a costly Phase 2 program in target patient populations.

For this project, the Aepodia operational team managed the study set-up and conducted studies with very short timelines, saving at least three months of equivalent Phase 1a/b development.
In comparison to CSF studies performed in US, the set-up is shorter and the costs are far less expensive (about 50% less), as compared to European sites

With very aggressive timelines, Aepodia implemented a human sleep model in a study center with Phase 1 capabilities with access to patients. Aepodia has integrated this specific PSG study within an umbrella program of studies performed in various EU countries. Aepodia’s recommendation was a two-part study with an adaptive design in the second study part (for assessing the dose-effect relationship). We quickly generated robust pharmacodynamic data in the first study part, thereby confirming the expected mechanism of action for this known molecular target, and obtained exposure response data in the second part of the study. In addition, the PSG parameters generated in this human sleep model were used to validate secondary potential indications. Aepodia has a long history of experience in using and interpreting EEG, including sleep EEG, in drug development. We have experienced in FIM programs, including studies in Sleep Labs, but also for late-stage development, with ambulatory PSG & sleep assessments.