RT-100 (AC6 gene transfer)

The company’s lead product candidate, RT-100 for the treatment of congestive heart failure (CHF), is a first-in-class, single-dose gene therapy candidate designed to safely improve heart function. Granted Fast Track designation by the U.S. Food and Drug Administration (FDA), RT-100 is in late-stage clinical development. A Phase 3 trial of RT-100 is expected to commence in Q1 2018.

More than a decade of intensive research shows that RT-100 has the potential to substantially benefit ailing hearts without the well-known drawbacks of many current heart failure therapies. Our scientific founder, Dr. H. Kirk Hammond, discovered that AC6 (adenylyl cyclase type 6) was down-regulated in the hearts of CHF sufferers. AC6 is a protein found in heart muscle cells that regulates heart function. Dr. Hammond and his colleagues developed a method of gene transfer designed to up-regulate AC6 content in the heart. This is the basis for RT-100.

How it works

RT-100 is an investigational gene therapy product that is infused during cardiac catheterization – a commonly performed outpatient procedure similar to an angiography – directly into the arteries that feed the heart. This method of gene transfer has been shown to safely and efficiently deliver AC6 directly to heart muscle cells. The gene encoding human AC6 is delivered via a modified adenovirus vector that is able to enter the cells but cannot reproduce itself (Ad5.hAC6). The AC6 is taken in by the heart and has been shown to persist in heart muscle cells. Unlike small molecule drug treatments, which work to decrease demands on the body, this gene therapy is aimed at improving overall heart function. Rather than slow progression or minimize symptoms of CHF, RT-100 has the potential to halt and reverse the CHF-induced remodeling of the heart, enabling it to pump more effectively.

Preclinical studies

In extensive preclinical studies of CHF, a one-time administration of AC6 gene transfer safely improved heart function, sustained the improvement and reversed the CHF-induced remodeling of the heart, protecting it from further CHF-related damage. These results supported a recently completed Phase 2 clinical trial in heart failure patients. The National Institutes of Health’s (NIH) National Heart, Lung, and Blood Institute awarded funding for the preclinical studies and subsequently the Phase 2 clinical trial.

Phase 2 clinical trial

The Phase 2 clinical trial of RT-100 – funded via a public-private partnership between the NIH’s National Heart, Lung, and Blood Institute and Renova Therapeutics – assessed the safety of five doses of Ad5.hAC6 versus placebo in patients with symptomatic heart failure. Results from the study – directed by Dr. Hammond and published in the Journal of the American Medical Association (JAMA) Cardiology – indicate that a one-time administration of AC6 gene transfer safely increases heart function beyond optimal heart failure therapy.

The randomized, double-blind, placebo-controlled trial included 56 patients who were studied for up to one year at seven medical centers throughout the United States. Forty-two participants received Ad5.hAC6; 14 received a placebo.

The trial demonstrated that two endpoints showed differences between the two highest doses of AC6 (combined) versus placebo:

  • AC6 gene transfer increased left ventricular peak –dP/dt (p=0.029). This is a direct measure of the heart’s ability to fill.
  • Left ventricular ejection fraction increased in AC6 subjects at 4 weeks (p=0.0037) and tended to be increased at 12 weeks (p=0.16).

Although this initial study was small, the data suggest potentially promising benefits in morbidity and mortality with RT-100, which were key safety measures in the Phase 2 trial: After one year of follow-up, one death of 42 (2.4%) in the AC6-treated group and one death of 14 (7.1%) in the placebo group had occurred (p=0.40). The annual heart failure hospital admission rate was 9.5% in the treatment group versus 28.6% in the placebo group (p=0.10).

Next up: FLOURISH – Phase 3 clinical trial

We have completed an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) for RT-100 AC6 gene transfer for the treatment of patients with heart failure and reduced ejection fraction. The FDA meeting – for which Renova Therapeutics submitted Phase 2 trial results along with a proposed Phase 3 clinical trial protocol – was the next step in our efforts to propel forward the development of this novel gene therapy for heart failure patients.

Renova Therapeutics will proceed with conducting a randomized, placebo-controlled, double-blind multi-center Phase 3 trial of a one-time intracoronary administration of RT-100 for patients with heart failure and reduced left ventricular ejection fraction. The primary endpoint will be the reduction of the event rate of all – first and repeat – heart failure hospitalizations occurring after RT-100 intracoronary injection from baseline to 12 months (the study period). Patient safety will continue to be monitored during a follow-up period following completion of the study.

This pivotal trial – known as FLOURISH (Heart Failure with Reduced Left Ventricular Ejection Fraction: One-time Gene Transfer Using RT-100 – Intracoronary Administration of Adenovirus 5 encoding Human AC6) – is expected to commence shortly across 60 medical centers in the United States. View more on (NCT03360448).


Renova Therapeutics is studying RT-100 for the treatment of congestive heart failure.

How it’s different

RT-100 is the result of decades of work on the science of gene therapy. Lessons learned as the industry evolved were critical in taking the technology to a new level and have been factored into the development of RT-100. We understand that several factors play a critical role in gene therapy – if any of these components are missing, a gene therapy will not be successful:

  • Gene: The right gene that is central to the disease-reversing process and
    effective when inserted in the cell(s)
  • Vector: The delivery method used to transport the gene to its target cell(s)
  • Cell target: The right cells to receive the gene
  • Transfection %: The level of uptake of the gene in the target cell(s) due to the right delivery method and route of administration

We believe RT-100 has all of the components to be a successful gene therapy product.

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