KAR101 (Ramatroban), an orally bioavailable small molecule is a dual, reversible and potent antagonist of two G protein coupled receptors (i) Prostaglandin D2 (PGD2) receptor subtype DP2 (D prostanoid receptor 2; previously known as CRTH2) and (ii) thromboxane A2 (TxA2) receptors. Ramatroban (Baynas®, Bayer, Japan; dose: 50 mg and 75 mg tablets oral BID), also available as a generic from Kotobuki Pharma, Japan, has been safely and effectively used for the treatment of allergic rhinitis in Japan for the past 20 years. Given the scientific mechanisms and great potential that Ramatroban holds, KARE Biosciences aims to repurpose this drug for a variety of indications including COVID-19, sickle cell disease, cardiovascular disease, Alzheimer's disease, cancer, weight loss and more.
COVID-19: As of August 2021, around 199 million people have been infection with COVID-19 and there has been over a 4 million deaths. Evidence around the pathogenesis of COVID-19 is becoming clear. We need safe and effective drugs that are orally bioavailable and therefore practical in ambulatory patients since the majority of COVID-19 patients are outpatients. Currently, the focus is on anti-thrombotic and antiviral therapies. Ramatroban, also known as Elpidazo, is a potent reversible dual receptor antagonist of the thromboxane A2 and the prostaglandin D2 receptors (TPr and DPr2, respectively) that may potentially serve as an anti-thrombotic and an immunomodulator in COVID-19.
Fibrosis, also known as fibrotic scarring, is a pathological wound healing that leads to considerable tissue remodeling and the formation of permanent scar tissue. There are many different types of fibrosis, including idiopathic pulmonary fibrosis, cirrhosis, cardiac fibrosis, renal fibrosis and more. The prevalence of idiopathic pulmonary fibrosis in the USA varies between 14 and 27.9 cases per 100,000 population using narrow case definitions, and 42.7 and 63 per 100,000 population using broad case definitions (Nalysnyk et al, 2012). Ramatroban is a potential treatment for fibrosis which affects the lives of millions of people.
Cardiovascular disease describes a range of conditions that affect your cardiovascular system, especially with aging. This includes coronary artery disease, atherosclerosis, arrhythmias, congenital heart disease, cerebrovascular disease, myocardial infarction, etc. The anti-platelet and anti-inflammatory effects of Ramatroban can potentially treat and prevent cardiovascular disease.
Millions of children and adults globally and about 100,00 people in the US suffer from sickle cell disease (SCD). Many often develop painful vaso-occlusive crisis that diminish the quality of life and lead to mortality. The current FDA approved drugs for SCD are hydroxyurea, L-glutamine, crizanlizumab and voxelotor. Despite the recent advances, SCD patients remain at a high risk of developing fatal vascular complications driven by platelet activation. Ramatroban as a dual receptor antagonist of the DPr2 and TPr receptors can target platelet activation and treat thrombotic vasculopathy, thus potentially improving survival of SCD patients. Ramatroban may target heme induced platelet activation by blocking CLEC2 signaling and reduce the thromboinflammatory state of SCD.
Alzheimer's Disease is the most common cause of dementia accounting for 60-80% of dementia cases. Alzheimer's disease is a progressive disease that reduces the longevity and quality of life for many by severely impairing cognitive ability and day to day functions. There is no definitive treatment for Alzheimer's disease, but emerging evidence is beginning to shed light upon the underlying causes of the pathogenesis of Alzheimer's. Ramatroban is a promising treatment for neurological diseases, including Alzheimer's and Parkinson's Disease, given the potential underlying mechanisms.