Target – Ryanodine receptor type 2 (RyR2)

RyR2 is the Ca   -release channel that regulates the strength and frequency of heart contractions. In the normal heart, Ca    release via RyR2 is a tightly regulated process with discrete release during heart muscle contraction, and cessation during heart muscle relaxation. Certain genetic mutation in RyR2 or other disease changes result in a dysfunctional RyR2. Under these conditions, the channel is no longer tightly regulated and becomes leaky leading to loss of normal heart rhythm or, in some cases, heart failure.

​

Disease – Catecholaminergic polymorphic ventricular tachycardia (CPVT), an orphan disease.
Elex Biotech is focusing its initial development efforts on oral treatments for CPVT, a disease with an estimated prevalence of 1:10,000, and typical onset in children 7-9 years of age, and causes about 15% of sudden cardiac deaths in apparently healthy young individuals. There are no FDA-approved treatments for CPVT. Current medications (mainly B-blockers) are used off-label in spite of having limited efficacy and significant side-effects that negatively impact quality of life and compliance. The overall mortality rate is 30%-50% by 20-30 years of age. The majority (~60%) of CPVT cases are known to be caused by mutations in RyR2. Approximately 30% - 50% of patients treated with B-blockers eventually require an implantable cardioverter-defibrillator (ICD) to prevent cardiac arrest. Only 5-10% of pediatric patients survive out-of-hospital cardiac arrests, often with severe neurological sequelae. ICDs are expensive to implant and maintain, do not prevent arrhythmias and can produce inappropriate shocks which actually induce arrhythmias (38% of shocks were inappropriate or unnecessary; 46% resulted in additional healthcare costs). Elex biotech's drugs are specifically designed to target the cause of the disease, rather than managing some symptoms while creating other problems.

​

Approach

Elex Biotech has synthesized a library of ~200 novel compounds and screened for compounds that normalize dysfunctional RyR2 channels but do not affect normal RyR2 channels. The company has demonstrated in vivo proof of concept by preventing ventricular tachycardia in a mouse model of CPVT that carries a RyR2 mutation without affecting normal heart rhythm.