Aqualung Therapeutics Receives FDA Clearance for Phase 2a Progressive Pulmonary Fibrosis Trial
Key Insights
Aqualung Therapeutics (search) received FDA clearance for its Phase 2a PAISANO trial evaluating ALT-100 mAb (search) in patients with Progressive Pulmonary Fibrosis (search), marking the company's second approved IND application.
The humanized monoclonal antibody targets eNAMPT (search), a master regulator of immune response that contributes to excessive inflammation and organ fibrosis in life-threatening lung conditions.
FDA waived the requirement for prior idiopathic pulmonary fibrosis (search) studies based on compelling preclinical evidence and clinical safety data from previous trials.
Aqualung Therapeutics (search) announced that the Food and Drug Administration has cleared its Phase 2a study of ALT-100 mAb (search) as an anti-inflammatory and anti-fibrotic therapy in human subjects with Progressive Pulmonary Fibrosis (search). This represents the clinical-stage immunotherapeutics company's second FDA-approved Investigational New Drug application, following its 2022 clearance for acute respiratory distress syndrome (search).
PAISANO Trial Design and Regulatory Pathway
Upon securing its next funding round, Aqualung will initiate the multicenter PAISANO trial – Preventing the Advance of Lung Fibrosis via the ALT-100 Antibody – to investigate the safety, pharmacokinetics, pharmacodynamic, and efficacy of ALT-100 mAb (search). The FDA waived the requirement for a prior idiopathic pulmonary fibrosis (search) study due to compelling preclinical evidence and clinical safety evidence.
Progressive Pulmonary Fibrosis (search) is a life-threatening condition that affects patients with underlying lung diseases that are either idiopathic or associated with autoimmune disorders. The condition represents a significant area of unmet medical need, with limited therapeutic treatment options currently available for patients.
Novel Therapeutic Target and Mechanism
ALT-100mAb is a humanized murine monoclonal antibody designed by Aqualung Therapeutics (search) to neutralize the protein eNAMPT (search) (extracellular nicotinamide phosphoribosyl transferase). This protein was first identified as a novel therapeutic target by Aqualung Therapeutics CEO and Founder Joe GN Garcia MD. eNAMPT functions as a master regulator of the immune system and contributes to excessive inflammation and scarring (fibrosis) of critical organs. By neutralizing eNAMPT, the ALT-100 mAb (search) effectively halts this immune response.
Clinical Development Foundation
The FDA approval follows a successful Phase 1a study in 32 healthy adult volunteers and a Phase 2a study in 15 patients with moderate to severe ARDS, along with extensive small and large animal toxicology studies and more than 20 peer-reviewed publications validating the preclinical utility of ALT-100 mAb (search).
"Our dramatic disease-attenuating effects of the ALT-100 mAb (search) in preclinical models of lung fibrosis combined with the preliminary evidence of ALT-100 mAb's ability to dampen innate immunity activation and disease severity in the PUERTA ARDS trial gives us great confidence that this therapeutic drug will help address the unmet needs of patients with PPF," stated Garcia.
Company Platform and Future Directions
"The Aqualung team is delighted that the FDA cleared our PAISANO study design," said Stan Miele, President and Chief Business Officer of Aqualung Therapeutics (search). "With limited therapeutic treatment options for these patients, there is a significant clinical and medical need for novel therapies."
Aqualung Therapeutics (search) features an immunotherapeutics platform targeting eNAMPT (search) through its Next Gen platform, eNamptor™, which includes the ALT-100 mAb (search), a plasma-based biomarker panel to predict disease risk and severity, and a genotyping assay to identify genetic risk of disease development, severity and mortality. This IND enables Aqualung to continue conducting human clinical trials that address the unmet therapeutic needs of patients with serious inflammatory, fibrotic diseases and cancers.