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. RT-100 is in late-stage clinical development, and a Phase 2b/3 trial of RT-100 is planned.

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.  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.

Preclinical Studies

In extensive preclinical studies of CHF, a one-time administration of a vector encoding AC6 safely improved heart function and reversed CHF-induced adverse remodeling of the heart. These results supported a recently completed Phase 2 clinical trial in patients with symptomatic heart failure.

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 with low ejection fraction (HGrEF). 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 a vector encoding AC6 safely increases heart function beyond optimal heart failure therapy.

The randomized, double-blind, placebo-controlled trial included 56 patients 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 measure of the heart’s ability to fill and is used to assess LV diastolic function, which is abnormal in HFrEF)
  • 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). Importantly, patients with non-ischemic HF showed robust and persistent increases in EF at both time points.

Although this initial study was small, the data suggest potentially promising reduction in HF hospitalization 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=0.095).

International Regulatory Status

Medicines and Healthcare products Regulatory Agency (MHRA, UK) Renova was awarded Innovation Passport (IP) by the Medicine & Healthcare products Regulatory Agency (UK). The UK’s Medicines & Healthcare products Regulatory Agency (MHRA) on August 10, 2022, awarded Renova Therapeutics the Innovation Passport (IP) for AC6 in the treatment Ambulatory patients with symptomatic low ejection fraction (40% or lower) heart failure (HFrEF) with elevated NT-Pro-BNP.

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