AC6

FLOURISH Phase 3 clinical trial in patients with heart failure and reduced ejection fraction (HFrEF) to begin in Q1 2018 SAN DIEGO, Dec. 14, 2017 /PRNewswire/ — Renova™ Therapeutics, a biotechnology company developing gene and peptide-based treatments for cardiovascular and metabolic diseases, announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the company’s lead product candidate, RT-100 AC6 gene transfer (Ad5.hAC6), for the treatment of heart failure with reduced ejection fraction (HFrEF). The FDA’s Fast Track program is designed to expedite the development and review of drugs and biologics with the potential to treat serious or life-threatening conditions and address an unmet medical need. A Fast Track designation enables more frequent communication with the FDA throughout a product candidate’s development and review process, ensuring questions are answered and issues are resolved quickly. The designation allows for Rolling Review of a New Drug Application (NDA) or Biologic License Application (BLA), meaning a company can submit individual sections of its application to the FDA as they are completed, rather than waiting until every section is completed to submit. The designation also provides eligibility for Priority Review, if relevant criteria are met – potentially resulting in quicker access to patients. “We’re pleased to work closely with the FDA to advance rapidly the development of RT-100 to treat heart failure patients,” said Dr. Jack W. Reich, CEO and Co-founder of Renova Therapeutics. “Despite some medical advancements, heart failure remains a progressive and fatal disease affecting millions of people worldwide. That’s why we look forward to initiating a Phase 3 trial with RT-100 early next year, with hopes of eventually submitting a BLA and ultimately bringing this life-changing therapeutic to patients as quickly as possible.” RT-100 AC6 gene transfer involves infusing an inactivated adenovirus vector encoding human adenylyl cyclase type 6 (Ad5.hAC6) into the arteries that feed the heart during cardiac catheterization, a commonly performed procedure. AC6 is a protein found in heart muscle cells that regulates heart function and appears to be down-regulated in heart failure patients. Results of a Phase 2 clinical trial indicate that, through a one-time administration, RT-100 safely increased heart function beyond optimal heart failure therapy. The treatment also lowered the heart failure hospitalization rate at 12 months, which will be the primary endpoint in the program’s upcoming Phase 3 trial. Renova Therapeutics will conduct a randomized, placebo-controlled, double-blind multicenter Phase 3 trial of intracoronary delivery of RT-100 to evaluate safety and efficacy. 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 in Q1 2018 in the United States (ClinicalTrials.gov Identifier: NCT03360448). About heart failure Heart failure is a chronic disease characterized by the inability of the heart to pump sufficient blood to meet the body’s demands. It is a progressive and fatal chronic condition, and symptoms worsen over time. Heart failure afflicts more than 28 million people globally and is the only cardiovascular disease that is increasing in prevalence.1 In the United States, it is the most common cause of emergency hospital admissions in patients 65 and older.

This randomized, placebo-controlled, double-blind multicenter 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 in Q1 2018 in the United States (ClinicalTrials.gov Identifier: NCT03360448). Richard McCloskey, MD, Executive Vice President of Clinical Development at Renova Therapeutics, will present details of the FLOURISH trial during a poster session on January 16, 2018. About RT-100 RT-100 AC6 gene transfer involves infusing an inactivated adenovirus vector encoding human adenylyl cyclase type 6 (Ad5.hAC6) into the arteries that feed the heart during cardiac catheterization, a commonly performed procedure. AC6 is a protein found in heart muscle cells that regulates heart function and appears to be down-regulated in heart failure patients. Results of a Phase 2 clinical trial indicate that, through a one-time administration, RT-100 safely increased heart function beyond optimal heart failure therapy. The treatment also lowered the heart failure hospitalization rate at 12 months, which will be the primary endpoint in the program’s upcoming Phase 3 trial. RT-100 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA). About heart failure Heart failure is a chronic disease characterized by the inability of the heart to pump sufficient blood to meet the body’s demands. It is a progressive and fatal chronic condition, and symptoms worsen over time. Heart failure afflicts more than 28 million people globally and is the only cardiovascular disease that is increasing in prevalence.1 In the United States, it is the most common cause of emergency hospital admissions in patients 65 and older. References: Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation. 2013;127:e6–e245.

San Diego, CA – Renova™ Therapeutics, a biotechnology company developing gene and peptide therapies for cardiovascular and metabolic diseases, today announced its co-founder’s online publication of an article in Human Gene Therapy. The article reviews four published clinical trials using gene transfer in patients with heart failure with reduced ejection fraction (HFrEF). The review finds that, while efficacy varied among the clinical trials, gene transfer was not associated with an increased rate of adverse events, supporting further investigations using this treatment method in the HFrEF patient population. The review, which will be published in the May 2017 print issue of Human Gene Therapy, was co-authored by Dr. H. Kirk Hammond and Dr. William Penny, both Professors of Medicine at the University of California – San Diego and cardiologists at the Veterans Affairs San Diego Healthcare System. Dr. Hammond is a co-founder of Renova Therapeutics and a consultant to the company. The authors reviewed safety and efficacy results of four trials utilizing three gene transfer strategies: intracoronary delivery of adeno-associated virus type 1 encoding sarcoplasmic reticulum Ca2+-ATPase (AAV1.SERCA2a; CUPID 1 and CUPID 2); endocardial injection of a plasmid encoding stromal cell-derived factor-1 (pSDF-; STOP-HF; and intracoronary delivery of adenovirus-5 encoding human adenylyl cyclase type 6 (Ad5.hAC6). Results of the AC6 clinical trial indicate that, through a one-time administration, AC6 gene transfer safely increased heart function beyond optimal heart failure therapy. This Phase 2 trial was funded by the National Institutes of Health (NIH), the Gene Therapy Resource Program and Renova Therapeutics, via an NIH public-private partnership. “With safety results indistinguishable from placebo, we can confidently advance our gene transfer clinical trials,” says Dr. Jack W. Reich, CEO and Co-founder of Renova Therapeutics. “The potential therapeutic value of gene transfer in heart failure patients is tremendous.” Renova Therapeutics will conduct a randomized, placebo-controlled, double-blind multicenter Phase 3 trial of intracoronary delivery of Ad5.hAC6 (known as RT-100) to evaluate safety and efficacy. The primary efficacy endpoint will be heart failure hospitalization rate 12 months after randomization. This pivotal trial is expected to commence this year at 60 medical centers in the United States. About heart failure Heart failure is a chronic disease characterized by the inability of the heart to pump sufficient blood to meet the body’s demands. It is a progressive and fatal chronic condition, and symptoms worsen over time. Heart failure afflicts more than 28 million people globally and is the only cardiovascular disease that is increasing in prevalence. In the United States, it is the most common cause for emergency hospital admissions in patients 65 and older. References: Dr. William F Penny and Dr. H. Kirk Hammond. Randomized Clinical Trials of Gene Transfer for Heart Failure with Reduced Ejection Fraction. Human Gene Therapy. March 2017, ahead of print. doi:10.1089/hum.2016.166. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation. 2013;127:e6–e245.