Therapeutic Approach

KIN001 is a novel combination of pamapimod, a highly selective inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and pioglitazone, a marketed drug for the treatment of type 2 diabetes. The p38 MAPKs are central regulators of the cellular response to inflammation, viral infection, and stress signals. The p38 MAPKs also play roles in diverse biological processes such as cell proliferation, chemotaxis, tissue fibrosis, and angiogenesis. Kinarus has discovered, through its own research, that combining pamapimod with pioglitazone improves the efficacy and durability of response, providing a unique and differentiated therapeutic in KIN001.

Kinarus is rapidly advancing its combination therapy to address the urgency of the COVID-19 pandemic. At the start of the pandemic, it appeared that the world was facing a serious respiratory disease. As time has passed, it has become apparent that the heart, liver, kidneys and the nervous system may be affected. These long-term consequences, such as scarring of the lungs and lasting damage to the heart muscle, contribute to the syndrome described as "long COVID." Even patients who shrugged off the initial infection can be left with long-term negative impacts on their quality of life.

Broadly active drugs that have anti-inflammatory, anti-fibrotic, and anti-viral activity are critical to target the multiple facets of the disease. The virus causing COVID-19, SARS-CoV-2, hijacks the p38 MAPK pathway for replication, so KIN001, by blocking this pathway, and also reducing other disease pathologies, is an attractive strategy. Kinarus has discovered that KIN001 has antiviral activity against SARS-CoV-2, including against its variants of concern. KIN001 also possesses anti-inflammatory and anti-fibrotic activity. These multiple mechanisms of KIN001 suggest its potential to address both acute and long-term consequences of COVID-19.

The KIN001 combination therapeutic offers additional opportunities. In ophthalmology, an oral drug may complement current anti-VEGF targeted therapies that require frequent clinical visits to receive direct injections into the eye. KIN001, as a tablet, may offer a way for patients to maintain vision while reducing the frequency of these unpleasant injections. In addition, real-world experience has found broad undertreatment leading to continued vision loss. KIN001 may address this need by providing a convenient oral treatment that can be taken at home. KIN001 may also provide a treatment option in countries and regions with poor or no access to anti-VEGF therapies or specialty clinics. KIN001 will be evaluated in a phase 2 clinical study in patients with wet age-related macular degeneration to test its potential to reduce the frequency of anti-VEGF injections by contributing to durability of response.

Idiopathic pulmonary fibrosis is a rare and terminal lung disease. Two drugs have been approved to treat IPF but have shown modest benefit and significant side effects. Kinarus has discovered that KIN001 reduces lung fibrosis in preclinical models both alone and on top of current therapy. KIN001 will be evaluated in a phase 2 clinical study in patients with IPF.