Drug Development
The challenge
Product development accounts for approximately two-thirds of all R&D costs and efficiency in this process is crucial for commercial success. Understanding the efficacy and safety of an inhaled product is complex and there are several important considerations specific to the route of delivery. The physical presentation of a substance to the airways has a significant impact on the lung response, particularly the immune response, which can raise concerns for safety.
Our solutions
ImmuONE provides expert assistance in understanding the inhaled biopharmaceutics of a formulation, from aerosolisation to deposition in the airways and interaction with the biological substrates of the airways.
Our in vitro solutions for product development include:
- Aerosolisation of a product onto the cell culture models, developing insights into how the formulation impacts cellular response
- Human cell culture models for a more relevant assessment of drug efficacy and toxicity in human systems, aligning with evolving regulatory expectations
- Characterising absorption, distribution and metabolism (cellular uptake, fate and accumulation) in lung cells
- Designing bespoke assays to capture the relevant biological interactions of the product
- Characterising the toxicological potential of the product with airway epithelial and immune cells
- Knowledge sharing and expert support in biomechanisms and cell responses, providing valuable insights and guidance to navigate the complexities of translational approaches.
- Accelerated timelines compared to initiating in-house R&D programs for inhalation studies, allowing for faster access to support from established industry experts.
Case study
ImmuONE was approached by a company that had developed a pioneering antibody-drug conjugate (ADC), a unique therapeutic designed for systemic administration to selectively target cancer cells and deliver potent chemotherapy agents. However, this novel approach presented a significant challenge. Potential lung toxicity, as observed in in vivo studies, raised histopathological concerns related to adverse alveolar macrophage morphology.
To address these concerns, the company collaborated with ImmuONE for a customised assessment. The primary objectives included evaluating off-target toxicity, cytokine release, and ADC uptake into macrophages and epithelial cells. The aim was to determine whether the macrophage response was adaptive or adverse. ImmuONE’s in vitro models provided more precise data for human macrophages, which is crucial for making informed decisions.
Our initial research suggests that the observed injury was likely a result of the cytotoxic effects of the payload. Furthermore, the potential for target-independent uptake, particularly in macrophages, may contribute to lung toxicity. ImmuONE is actively investigating this mechanism, delving into potential uptake pathways and evaluating various macrophage subtypes to enhance our understanding of ADC-induced lung toxicity. These efforts aim to bridge the gap between in vitro and in vivo studies, ultimately facilitating improved early-stage decision-making in drug development.
