Calluna Pharma Launches Phase 2 AURORA Trial of CAL101 to Halt Lung Decline in IPF Patients

Calluna Pharma AS, a clinical-stage biotechnology company developing first-in-class antibodies for inflammatory and fibrotic diseases, has announced initial patients have been dosed in the Phase 2 AURORA trial of the first-in-class monoclonal antibody for idiopathic pulmonary fibrosis (IPF).

The monoclonal antibody, named CAL101, targets S100A4, a damage-associated molecular pattern (DAMP) protein linked to severe and potentially life-threatening fibrotic conditions.

Jonas Hallén, M.D.

“S100A4 is a central mediator of both inflammation and fibrosis and, importantly, the communications between immune and stromal cells (such as fibroblasts),” Jonas Hallén, M.D., chief medical officer of Calluna Pharma, told Managed Healthcare Executive. “It is released from stressed or injured cells, acting as an upstream signal that amplifies and sustains a broad spectrum of downstream pro-fibrotic and pro-inflammatory pathways.”

S100A4 has also been shown to activate lung fibroblasts — the key effector cells in fibrosis — and promote their proliferation, differentiation into myofibroblasts and abnormal buildup of scar tissue. It also contributes to the inflammatory response by recruiting immune cells and inducing the release of cytokines.

“This dual role makes it a more comprehensive target than therapies that focus on a single downstream pathway,” Hallén said.

CAL101's mechanism of action is fundamentally different from currently available IPF therapies, such as nintedanib, sold under the brand name Ofev, and pirfenidone, sold under the brand name Esbriet, according to Hallén. The current therapies have a broad spectrum of activity, he said, and that results in spillover effects on physiological tissue functions, leading to a relatively narrow therapeutic window.

“Because S100A4 predominantly functions as an upstream amplification mechanism, we have the opportunity to comprehensively dampen disease-causing pathways yet leave them intact for physiological responses,” he said. “This strategy has the potential to drive better efficacy coupled with a favorable safety and tolerability profile.”

The AURORA study is enrolling patients across multiple sites around the world. Toby Maher, M.D., the coordinating investigator and a professor of clinical medicine at the Keck School of Medicine at USC, noted that it helps to minimize the influence of any single region and contributes to making the trial results more generalizable to the broader, real-world IPF patient population.

“The Phase 1 study found that adverse events were balanced across participants in the placebo and active CAL101 groups,” he said. “Importantly, this not only included healthy volunteers but also a cohort of patients with a mild inflammatory disease, providing additional support for the favorable safety and tolerability profile. However, we are now treating a different patient population, and we will pay close attention to any potential emerging safety signals, particularly those related to the drug's mechanism of action and the infusion procedure.”

To gain a more complete understanding of CAL101’s effectiveness and its impact on patients’ lives, the study includes several secondary and exploratory endpoints essential for providing a holistic view of CAL101’s clinical benefit beyond just FVC. These endpoints, which will be important to future development and regulatory interactions, include quality of life and patient-reported outcomes to capture CAL101’s impact on symptoms such as cough, daily activities and overall well-being.

“Through our characterization of the biology of S100A4, we have identified some circulating biomarkers of particular interest,” Hallén said. “These biomarkers relate both to the mechanism of action of CAL101 and the IPF disease process.”

Calluna Pharma is partnered with Qureight, which will support AI-powered imaging to provide a measure of lung architecture changes beyond pulmonary function alone.

“While not a primary endpoint for a Phase 2 trial, we will capture important clinical outcomes such as large reductions in pulmonary function, hospitalizations and mortality,” Hallén said. “By targeting DAMPs, we are using a platform approach to build a pipeline across a wide range of fibrotic and inflammatory conditions. A positive outcome in the CAL101 AURORA study can potentially unlock a large number of opportunities in other organ-specific fibrotic diseases as well as fibro-inflammatory diseases such as systemic sclerosis.”