Demonstrating Bronchodilator Activity of RCD405 in Human Lung Tissue 

Chronic obstructive pulmonary disease (COPD) remains one of the leading causes of mortality worldwide, with significant unmet need for therapies that address both airway constriction and the underlying inflammatory processes driving disease progression.

Arcede Pharma (formerly Respiratorius AB) is developing RCD405, a novel inhaled therapeutic candidate with dual bronchodilatory and anti-inflammatory properties. To support continued development and provide data requested during scientific discussions with regulatory authorities, Arcede sought to demonstrate the bronchodilatory efficacy of RCD405 in human-relevant experimental systems.

This case study highlights how REPROCELL's fresh human tissue platforms were used to evaluate the functional effects of RCD405 in ex vivo human airways.

As promising respiratory drug candidates progress towards clinical development, demonstrating efficacy in translationally relevant models becomes increasingly important.

While conventional in vitro assays and animal studies provide valuable information, they do not fully replicate the complexity of human airway physiology. Arcede required data showing that RCD405 could induce bronchodilation directly in human tissues and generate evidence supporting further development decisions.

The study objectives were to:

• Assess the bronchodilatory activity of RCD405 in human airway tissue
• Compare responses against established respiratory therapeutics
• Generate human-relevant efficacy data to support regulatory discussions and development planning

Human Airway Tissue Model

REPROCELL utilised fresh human lung tissue obtained from consented donors undergoing surgery.

Small airway segments were isolated from donor lung tissue and prepared for functional assessment using ex vivo tissue bath technology. This approach enabled direct measurement of airway smooth muscle contraction and relaxation within intact human tissue.

Experimental Design

Human airway rings were:

• Mounted in wire myograph systems to measure airway function
• Pre-constricted using a contractile stimulus
• Treated with increasing concentrations of RCD405
• Assessed for bronchodilatory responses across a concentration range

For comparison, clinically established bronchodilators were evaluated alongside the test compound.

Functional Readouts

Airway relaxation responses were quantified and compared against maximal relaxation controls, enabling assessment of both potency and efficacy within a physiologically relevant human tissue environment.

Concentration-Dependent Bronchodilation

RCD405 produced a clear concentration-dependent relaxation of human airway tissue, demonstrating functional bronchodilator activity directly in human lungs ex vivo.

Comparable Activity to Established Therapies

The bronchodilatory response generated by RCD405 was comparable to responses observed with established therapeutic agents used as positive controls within the study.

These findings demonstrated that RCD405 could effectively relax constricted human airways and provided evidence supporting its potential therapeutic application in respiratory disease.

Human-Relevant Translational Data

By generating efficacy data directly in human tissues, the study provided translational evidence that complemented existing preclinical research and supported continued progression of the programme.

Greater Confidence in Development Decisions

Human tissue-based testing enables researchers to evaluate candidate therapeutics in biologically relevant systems that closely reflect clinical physiology.

By demonstrating bronchodilator activity directly in human airways, this study provided important evidence to support key development decisions before advancing into more resource-intensive stages of drug development.

Relevance to COPD and Severe Asthma

Airway constriction is a hallmark feature of both COPD and severe asthma. Confirming activity in fresh human airway tissue helps establish translational relevance and provides greater confidence that observed pharmacological effects are meaningful within the target tissue.

Platform Advantages

REPROCELL's human respiratory tissue platforms enable:

• Direct functional assessment in fresh human airway tissue
• Quantitative measurement of bronchodilation and bronchoconstriction
• Evaluation of drug responses in physiologically relevant systems
• Generation of translational data to support preclinical programmes

This study demonstrated that RCD405 induces concentration-dependent bronchodilation in fresh human airway tissue, providing clear evidence of pharmacological activity in a clinically relevant ex vivo model.

By leveraging human lung tissue assays, REPROCELL enabled:

• Functional assessment of a novel respiratory therapeutic
• Comparison against established bronchodilator therapies
• Generation of translational data supporting programme advancement

These findings highlight the value of human tissue-based respiratory models for evaluating efficacy and informing drug development decisions in respiratory disease.