Novel targets aim to stop lung scarring—where current drugs only slow it—while improving tolerability and unlocking fibrosis in other organs next
Lung diseases are having a moment in drug development and life science investment, with idiopathic pulmonary fibrosis (IPF) gaining particular traction.
IPF is a chronic, progressive lung disease characterized by irreversible scarring (fibrosis) of lung tissue, making it stiff and difficult to breathe.
Several IPF‑focused or lung‑fibrosis‑focused biotechs have raised significant capital recently, such as Avalyn Pharma for its $100 million Series D. Big Pharma such as Bristol Myers Squibb has also joined the arena.
The interest in the lung space confirms what BioSpace reported earlier this year in discussions with investors on hot therapeutic areas. Several named IPF as a key focus area, citing new modalities, targets and pending patent cliffs driving innovation.
The global IPF market generated almost $3 billion in 2025 and is estimated to reach US nearly $7 billion by 2035.
Halting disease an unmet need
IPF therapies approved in the U.S. and in Europe are Boehringer Ingelheim’s Ofev (nintedanib) and Legacy Pharma’s Esbriet (pirfenidone). Boehringer’s Jascayd (nerandomilast), approved in the U.S. in October 2025, is not yet approved in Europe.
All approved therapies slow disease progression by about 50% annually but don’t arrest disease progress, said Jonas Hallén, co-founder and CMO of Calluna Pharma. Thus, patients get worse at a slower pace. As their lungs stiffen, everyday movement becomes difficult, in addition to a worsening cough.
Thus, halting disease progression is of utmost importance, agreed Hallén and Georg Vo Beiske, CEO of Tribune Therapeutics. Current approved therapies don’t address the underlying disease drivers.
Both companies are developing therapies with novel targets for IPF. Calluna’s CAL101 is targeting the protein S100A4, potentially switching off the downstream pathways involved in scar tissue formation characteristic of IPF. The company announced on April 22 completed Phase II AURORA study enrollment.
Tribune Therapeutics’ preclinical pipeline is focused on interrupting signaling by key CCN protein family members that play a key role in the profibrotic pathway.
Poor SOC tolerability profile
Besides a desirable improvement in efficacy, many patients discontinue treatment due to poor tolerability, Hallén and Beiske agreed. Gastrointestinal (GI) issues are the most problematic, Beiske said. And for patients that opt for multiple therapies in parallel, the combined GI effects discourage continued therapy.
“Whoever is able to bring forward the first therapy that will be able to stop fibrosis and have a tolerable profile will be a huge winner for patients,” Beiske said. Ultimately, Hallén and Beiske agreed targeted combination therapies with better efficacy and minimal side effects is the path forward for improved IPF treatment.
Excellent gateway indication
IPF can be seen as a gateway proof of concept for a broader range of fibrotic indications, Hallén and Beiske agreed. “If you’re able to turn off the fibroblast in the lungs, there is high probability will affect fibroblasts in other fibrotic diseases,” Hallén said.
End-stage kidney disease is associated with fibrosis and is of keen interest to explore further, Beiske said. Fibrotic liver disease is also considered, especially with the surrogate marker of liver stiffness potentially becoming an approvable endpoint.
Since S100A4 is an alarm signal that is present whenever there is injury and stress in the tissues, there are several potential indications for Calluna to pursue once CAL101 is successful in IPF, Hallén said. Systemic sclerosis, a multiorgan, fibrotic inflammatory disease where there’s also a very large unmet need, is of interest.
You can hear more on this week’s Denatured podcast episode.
