DWN12088 Fares Well in Study of Healthy Volunteers

DWN12088, an investigational therapy for idiopathic pulmonary fibrosis (IPF), showed promising anti-fibrotic properties and appeared to be safe and well-tolerated in a recently-completed Phase 1 clinical trial that enrolled healthy volunteers.

Daewoong Pharmaceutical, the therapy’s developer, now plans to start a Phase 2 trial later this year.

“We have established the basis for [Phase] 2 trials by confirming safety, tolerability and pharmacokinetic profile of DWN12088,” Sengho Jeon, CEO of Daewoong, said in a press release. “In addition to lung fibrosis, we will expand our research on fibrosis in other organs such as heart, liver, kidney and skin.”

The company presented the results in an abstract titled “Safety, Tolerability and Pharmacokinetics/Pharmacodynamic Assessment of an Oral, Selective Prolyl-tRNA Synthetase Inhibitor, DWN12088, for the Treatment of Idiopathic Pulmonary Fibrosis in Healthy Subjects,” at the American Thoracic Society 2021 International Conference, held virtually May 14–19.

Fibrosis, or tissue scarring, is characterized by excess production of a protein called collagen, of which the amino acid proline is a key component. DWN12088 is an investigational IPF therapy that limits the body’s ability to produce collagen by preventing an enzyme called glutamyl-prolyl-tRNA synthetase from adding proline to the protein’s sequence.

The study (DWN12088101), which took place in Australia, evaluated the safety, tolerability, and pharmacological properties of DWN12088 in 72 healthy adults.

Volunteers were separated into two groups. They received either single or multiple ascending doses (SAD and MAD, respectively) of DWN12088 or a placebo. In the SAD group, 40 individuals received either DWN12088 or a placebo at doses ranging from 100 to 600 mg. In the MAD group, 32 participants received DWN12088 or a placebo at doses ranging from 25 to 200 mg, twice daily, for two weeks.

The investigational therapy appeared to be safe and well-tolerated, with no serious adverse side effects reported in either dose regimen group. The most common treatment-related side effects were gastrointestinal disorders.

DWN12088 also showed potentially promising anti-fibrotic effects by being able to lower the levels of type 3 procollagen peptide, a byproduct of fully-formed collagen that often builds up in the bloodstream of people with IPF.

The candidate medication showed further anti-fibrosis potential in a separate abstract, also presented at the conference, titled “Synergistic Anti-Fibrotic Effect of a First-in-Class PRS Inhibitor, DWN12088, and Standard-of-Care Therapeutic Agents for IPF.”

This presentation highlighted data from a separate study that evaluated the anti-fibrotic effects of DWN12088 when given in combination with the approved anti-fibrotic medications Ofev (nintedanib) and Esbriet (pirfenidone).

Researchers in this study treated human lung cells with a combination of Ofev and DWN12088, or with each therapy alone. They also treated a mouse model of induced-pulmonary fibrosis with a combination of Esbriet and DWN12088, or with each compound alone.

While DWN12088 alone lowered the levels of fibrosis markers in cells and collagen production in mice, the combination treatments led to greater effects than either treatment alone. These observations suggested that DWN12088 has the potential to become a new IPF therapy, both as a standalone treatment and as a combination therapy.

DWN12088 has been designated an orphan drug for both IPF and systemic sclerosis in the U.S.