December 22, 2025 | Juno Beach, Florida — Aqualung Therapeutics announced that the U.S. Food and Drug Administration (FDA) has cleared its Phase 2a clinical study evaluating ALT-100 mAb, an investigational anti-inflammatory and anti-fibrotic monoclonal antibody, in patients with Progressive Pulmonary Fibrosis (PPF). The clearance marks the company’s second FDA-cleared IND, following prior authorization to study ALT-100 in acute respiratory distress syndrome (ARDS), and enables initiation of the multicenter PAISANO trial upon completion of the company’s next funding round.
Science Significance
ALT-100 mAb is a humanized monoclonal antibody designed to neutralize extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a protein identified as a master regulator of innate immune activation and fibrosis. Excessive eNAMPT signaling has been linked to chronic inflammation, tissue scarring, and organ dysfunction, particularly in the lungs. By targeting this upstream driver, ALT-100 aims to interrupt pathological immune responses rather than merely addressing downstream symptoms. Preclinical models of lung fibrosis have demonstrated dramatic attenuation of disease progression, supporting the scientific rationale for advancing into human studies focused on fibrotic lung disease.
Regulatory Significance
The FDA’s decision to clear the Phase 2a PAISANO study reflects regulatory confidence in the totality of evidence supporting ALT-100 mAb, including Phase 1a safety data in healthy volunteers, prior Phase 2a experience in ARDS, and extensive small and large animal toxicology studies. Notably, the FDA waived the requirement for a prior idiopathic pulmonary fibrosis study, citing compelling preclinical and clinical safety data. This waiver underscores the strength of the mechanistic and translational evidence and highlights regulatory flexibility when addressing serious diseases with high unmet medical need under Good Clinical Practice (GCP) standards.
Business Significance
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From a business perspective, the FDA clearance represents a critical value-inflection milestone for Aqualung Therapeutics as it transitions toward a broader clinical-stage pipeline. The upcoming PAISANO trial is designed to assess safety, pharmacokinetics, pharmacodynamics, and early efficacy, positioning the company for subsequent mid- to late-stage development. Progress in PPF complements Aqualung’s existing ARDS program and strengthens its immunotherapeutics platform targeting eNAMPT, enhancing attractiveness to investors, strategic partners, and collaborators focused on fibrotic and inflammatory diseases.
Patients’ Significance
For patients, the clearance offers renewed hope in a therapeutic landscape with limited options. Progressive Pulmonary Fibrosis is a life-threatening condition affecting individuals with idiopathic or autoimmune-associated lung disease, often leading to irreversible lung scarring, declining respiratory function, and premature mortality. Current treatments primarily slow disease progression and do not adequately address underlying immune drivers. ALT-100 mAb’s advancement into Phase 2a trials introduces the possibility of a disease-modifying therapy aimed at halting or reducing fibrotic progression, potentially improving quality of life and long-term outcomes for patients with PPF.
Policy Significance
The FDA clearance aligns with broader regulatory and public health priorities to accelerate development of therapies for serious, progressive diseases lacking effective treatments. By enabling mid-stage clinical evaluation and waiving certain development prerequisites, regulators demonstrate a science-driven, risk–benefit approach that encourages innovation while maintaining rigorous oversight. The decision also reflects policy support for targeted immunotherapies and precision approaches that address root causes of chronic disease, reinforcing the role of adaptive regulatory pathways in advancing patient-centered innovation.
The FDA’s clearance of Aqualung Therapeutics’ Phase 2a PAISANO study marks a pivotal advancement in the clinical development of ALT-100 mAb for Progressive Pulmonary Fibrosis. By combining strong mechanistic science, robust preclinical validation, and disciplined regulatory engagement, the program exemplifies how cGxP-aligned development strategies can accelerate promising therapies toward patients with profound unmet needs. As Aqualung prepares to initiate multicenter clinical evaluation, the study represents an important step forward in the pursuit of innovative, disease-modifying treatments for fibrotic lung disease.
Source: Aqualung Therapeutics press release
