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 that has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA). A pivotal 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.
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
Renova has been awarded an Innovation Passport (IP) August 10, 2022, by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) through the Innovative Licensing and Access Pathway (ILAP) program (application ILAP/IP/22/56146/01). The IP was for “AC6 in the treatment of ambulatory patients with symptomatic low ejection fraction (40% or lower) heart failure (HFrEF) with elevated NT-Pro-BNP.”
The Company is also evaluating other pathways that will expand market opportunities to other regions with the potential to accelerate commercialization.