# Development of Novel Compounds for Treatment of Heart Arrhythmias in CPVT

> **NIH NIH R44** · ELEX BIOTECH, LLC · 2021 · $971,323

## Abstract

PROJECT SUMMARY
The goal of this project is to complete the preclinical development of Elex Biotech's novel compounds that
target and treat the underlying molecular cause of catecholaminergic polymorphic ventricular tachycardia
(CPVT) CPVT. There are no FDA-approved treatments for CPVT, a rare genetic disorder affecting 1/10,000
individuals, with typical onset in children 7-9 years of age and no reported differences by gender. CPVT results
in potentially deadly arrhythmias and is responsible for 15% of sudden cardiac deaths in apparently healthy
young people. Only 5-10% of pediatric patients survive out-of-hospital cardiac arrests, often with severe
neurological sequelae. The overall mortality rate is 30-50% by age 20-30. Approximately 60% of CPVT cases
are known to be caused by mutations in type 2 ryanodine receptor (RyR2), the calcium release channel that
regulates the strength and frequency of heart muscle contraction. However, current medications (mainly -
blockers) do not target RyR2, and are used off-label in spite of limited efficacy and significant side-effects.
Approximately 30% - 50% of patients treated with -blockers eventually require an Implantable cardioverter-
defibrillator (ICD) to prevent cardiac arrest. ICDs are expensive to implant and maintain, do not prevent
arrhythmias and can produce inappropriate shocks which actually induce arrhythmias. In Europe, flecainide is
used along with -blockers, but it may cause or exacerbate existing heart rhythm problems and has a Block
Box Warning in the US. Delivering a safe, effective and targeted CPVT treatment is the goal of this program.
To complete preclinical development of this targeted novel therapeutic, the Company will apply its considerable
synthetic chemistry expertise with the guidance of experts in medicinal chemistry and preclinical toxicology to
optimize its 2 pre-lead candidates, select a lead and take it through IND-enabling studies. Elex Biotech's
Target Product Profile (TPP) was specifically designed to develop a safe and highly effective oral drug that can
be taken 1-2 times a day for the treatment of CPVT. With the use of the Company's well-established animal
models of CPVT and available standard preclinical toxicology and pharmacology assay systems, Elex Biotech
will evaluate multiple analogs of each pre-lead and select a best lead candidate based on our TPP along with
input from potential pharmaceutical partners. The Company will apply for Orphan Designation for its lead
candidate and design and implement a plan for IND-enabling studies based on a pre-IND FDA meeting. At the
end of the project, Elex Biotech will have a data package to support an IND filing. In order to accomplish these
goals, the following specific aims are proposed:
Specific Aim 1. To design and synthesize pre-lead compounds using results from in vitro and preclinical
studies. Specific Aim 2. Lead drug candidate selection. Specific Aim 3. Complete IND-enabling studies.

## Key facts

- **NIH application ID:** 10176557
- **Project number:** 5R44HL114206-06
- **Recipient organization:** ELEX BIOTECH, LLC
- **Principal Investigator:** Sandra Lee Shotwell
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $971,323
- **Award type:** 5
- **Project period:** 2012-08-21 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176557

## Citation

> US National Institutes of Health, RePORTER application 10176557, Development of Novel Compounds for Treatment of Heart Arrhythmias in CPVT (5R44HL114206-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176557. Licensed CC0.

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