When KIN001 was given with Esbriet, an approved treatment, the reduction in fibrosis was even greater than that seen with KIN001 alone.
Based on these early data, the company plans to launch a one-year and placebo-controlled Phase 2 clinical trial of KIN001 in IPF patients, including those using Esbriet or Ofev (nintedanib), also an approved disease treatment.
“These preclinical data strongly support the potential of KIN001 to be an effective treatment for IPF and fibrotic disorders of the lung and other organs, both in single or combination therapy,” Thierry Fumeaux, Kinarus’ chief medical officer, said in a press release.
Anti-inflammatory, anti-fibrotic potential seen in IPF treatment, KIN001
IPF occurs when scar tissue forms in the lungs. Over time, scarring (fibrosis) makes it difficult for the lungs to work as well as they should, leading to disease symptoms that include shortness of breath, a persistent dry cough, and fatigue.
While the cause of IPF is unknown, some medications can help ease its symptoms and slow progression. However, some patients do not tolerate these treatments well, and others do not respond to them as expected.
“Many patients stop therapy with the currently available drugs, due to side effects and lack of efficacy,” Fumeaux said.
KIN001 combines two active substances: pamapimod and pioglitazone. Pamapimod works by blocking the activity of the p38 mitogen-activated protein kinase (MAPK), a protein that helps cells grow, move about, and carry out specific functions. It appears to have both anti-inflammatory and anti-fibrotic properties.
Pioglitazone is approved to help lower blood-sugar levels in people with type 2 diabetes. It works by making cells more sensitive to insulin, an hormone that plays a key role in regulating blood sugar uptake.
Scientists at Kinarus found that combining pamapimod and pioglitazone makes their effects stronger and longer lasting.
In the preclinical study, researchers demonstrated that KIN001 significantly reduced lung weight and fibrosis in a mouse model of lung injury. The investigational therapy also outperformed Esbriet in lessening lung fibrosis.
Combining KIN001 and Esbriet had a greater anti-fibrotic effect, suggesting that KIN001 may provide additional benefits when used alongside standard-of-care therapies.
RNA sequencing — a technique allowing scientists to know which genes are active (turned “on” or “off”) in a sample — also showed that KIN001 toned down a number of genes that are usually turned on whenever there is inflammation in lung fibrosis.
“Our data demonstrate that KIN001 possesses broad anti-inflammatory and anti-fibrotic properties which increase the probability that a patient may respond to KIN001,” Fumeaux said. “Together with our superior safety profile, demonstrated in clinical testing to date, this indicates that KIN001 may be more effective and better tolerated than available drugs.”
Planned Phase 2 trial to include patients on standard-of-care therapies
The Phase 2 trial plans to enroll up to 80 IPF patients, including those using Esbriet, Ofev, or other standard-of-care treatment. People currently not on any IPF treatment will also be considered for eligibility.
Those enrolled will be randomly assigned to either the experimental oral treatment or a placebo. The study’s primary goal is changes in forced vital capacity (FVC), a measure of lung function, from the study’s start to week 52 with KIN001’s use.
KIN001 is also being tested in KIN-FAST (NCT05659459), a Phase 2 safety and effectiveness study in up to 400 people with a positive SARS-CoV-2 test and COVID-19 who have not been admitted to a hospital. It is currently enrolling at sites in Germany and Switzerland.
Preclinical data “also support the potential of KIN001 to reduce severity and long-term organ damage in COVID-19,” Fumeaux said.
Kinarus previously announced a potential partnership with a group in China to support KIN001’s further development, including Phase 2 clinical testing.
