Renova Therapeutics, Inc.

istock, Alona Horkova In this deep dive, BioSpace explores the diverse therapeutic modalities now in development, as well as the opportunities and battles for market dominance in this emerging space. The cardiovascular drug development space is experiencing a renaissance. With the recent approval of BridgeBio’s Attruby in transthyretin amyloid cardiomyopathy (ATTR-CM), the $300 million January launch of heart disease–focused Kardigan and numerous novel gene therapies in development, a new era is dawning in the battle against the world’s leading cause of death. Countless companies, from big pharmas like Pfizer and Novartis to smaller biotechs including BridgeBio and Regenxbio, are looking for a piece of the pie, and the market for cardiovascular drugs is projected to grow from around $150 billion in 2024 to $207 billion by 2033. Projected Cardiovascular Market Growth DATA SOURCE: PRECEDENCE RESEARCH ATTR-CM: Alnylam Eyes Approval A decade ago, ATTR-CM, a disease of the heart muscle, was “basically . . . a death sentence,” BridgeBio CEO Neil Kumar told BioSpace in November. Since then, two novel treatments have been approved—Pfizer’s tafamidis, marketed as Vyndaqel and Vyndamax, in 2019, and BridgeBio’s Attruby in November 2024. These transthyretin stabilizers could be joined this year by Alnylam’s Amvuttra (vutrisiran), which the FDA has accepted for review in ATTR-CM with a target action date of March 23. An RNAi therapy, Amvuttra is already approved to treat polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis and would add a differentiated mechanism to the ATTR-CM treatment toolbox. Also contending in the ATTR-CM space are AstraZeneca and Ionis Pharmaceuticals, who are working together on Wainua (eplontersen), an antisense RNA silencing therapy. Like Amvuttra, Wainua is approved for hATTR amyloidosis. The candidate is currently being studied in the Phase III CARDIO-TTRansform study , which is expected to read out in 2026. The companies are competing for a share of the global transthyretin amyloidosis treatment market, which is projected to hit $9.35 billion by 2030. GLP-1s’ Next Gambit? GLP-1 agonists—biopharma’s hottest commodity—are making headway in cardiovascular disease, in addition to obesity, diabetes and other indications. In March 2024, the FDA approved a label expansion for Novo Nordisk’s Wegovy (semaglutide) to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and obesity or overweight. Not to be outdone, Eli Lilly’s tirzepatide, marketed as Mounjaro and Zepbound, in August showed significant therapeutic benefit in patients with heart failure with preserved ejection fraction. Several other companies including Amgen and Structure Therapeutics are also conducting trials studying the cardiovascular benefits of GLP-1s. Cardio Gene Therapies Cardiovascular disease is also a target of precision therapeutics, with companies including Renova Therapeutics, XyloCor and Tenaya Therapeutics developing gene therapies for congestive heart failure, chronic refractory angina and hypertrophic cardiomyopathy, respectively. This space has been buoyed by early clinical successes, including Rocket Pharmaceuticals reporting clinical benefit in a Phase I trial and Lexeo Therapeutics making progress in Friedreich’s ataxia cardiomyopathy. Editor’s note: This article was originally published as a special edition of ClinicaSpace, BioSpace’ s weekly newsletter covering clinical trial results and research news on Feb. 10. You can subscribe here .

Renova is exploring new therapeutic opportunities that have the potential to expand the use of Renova's gene therapy platform to include several pathologies associated with diabetes and heart failure. CARLSBAD, CA & SAN DIEGO, CA / ACCESSWIRE / June 12, 2024 / Renova Therapeutics, a biotechnology company developing gene therapy-based treatments for cardiovascular and metabolic diseases, announced today current and potential future clinical directions that can expand the use of its gene therapies to treat additional debilitating diseases. Renova is pushing ahead with its two most advanced therapies and is poised to launch a phase 2b/3 clinical trial for heart failure (HF) and a first-in-human trial for type 2 diabetes (T2DM) upon approval by regulatory agencies. In addition to its potential to treat type 2 diabetes as demonstrated in preclinical studies, Renova's Ucn2 gene therapy has potential therapeutic applications for type 1 diabetes, non-alcoholic fatty liver disease (NAFLD) (also known as metabolic dysfunction-associated steatotic liver disease (MASLD)), hypertension and heart failure. NAFLD Non-alcoholic fatty liver disease (NAFLD), for example, which is a common cause of liver failure in the U.S.,[1] was present in models of diabetes in the preclinical studies. Ucn2 gene transfer significantly reduced fatty infiltration six to eight weeks after a single intravenous delivery of the therapeutic product. Type 1 Diabetes Preclinical data demonstrated that a one-time intravenous injection of AAV8.Ucn2 has beneficial effects in a murine model of insulin deficiency analogous to type 1 diabetes. Beneficial effects included marked improvement in abnormal glucose flux, reduced retinopathy, and reduction in mortality from 94% to 18% (p<.0001). In addition, published preclinical studies have shown the usefulness of Ucn2 gene transfer in heart failure with reduced ejection fraction (EF) and heart failure with preserved EF. Renova received an NIH STTR Award to investigate the use of Ucn2 gene transfer for type 1 diabetes and associated left ventricular dysfunction. Hypertension Hypertension is a major risk factor for both heart failure, stroke and kidney failure leading to dialysis. In 2020, about half of U.S. adults - 122 million patients - had hypertension (high blood pressure).[2] Despite many anti-hypertensive drugs on the market, hypertension continues to contribute to the high incidence of these conditions. These data underscore the challenge of managing hypertension effectively, providing a rationale for gene therapy for this pervasive and difficult to treat disease. Preclinical studies are investigating the use of Ucn2 gene therapy for hypertension. Renova holds worldwide, exclusive licenses to key patents covering composition matters and delivery methods as well as clinical data. The Company intends to further develop its internal intellectual property (IP), acquire strategic IP, and utilize market exclusivity for its gene therapies granted by the regulatory agencies. "Despite the many therapies we now have for diabetes, we still see too many patients with inadequate blood sugar control and frequent complications of diabetes. Gene therapy is clearly one of the most promising new approaches to reducing the impact of diabetes," said Dr. David Horwitz (MD, PhD, MBA), member of Renova's Scientific Advisory Board. Dr. Horwitz previously served as Global Chief Medical Officer at the Johnson & Johnson Diabetes Institute and is a former member of the FDA advisory panel in clinical chemistry and toxicology. "Renova is privileged to have Dr. Horwitz as part of its Scientific Advisory Board. His expertise in health care and wealth of knowledge in metabolic diseases is a great asset to the Company in advancing its products and helping patients worldwide," said Renova CEO Dr. Vijay Mahant. About Renova Therapeutics Renova Therapeutics is developing definitive, one-time gene therapies to restore the health of people suffering from chronic diseases. The company is focusing on gene therapy treatments for heart failure and type 2 diabetes, two of the most common and devastating chronic diseases in the world. The company's lead product candidate, RT-100, is a treatment that delivers a therapeutic gene directly to the heart during a routine outpatient procedure and has the potential to increase heart function in millions of patients with heart failure. The Company's product pipeline also includes a groundbreaking gene therapy in preclinical stage for sufferers of type 2 diabetes. Renova Therapeutics was founded in 2009 and is led by an experienced management team in biopharmaceuticals and gene therapy. For additional information about the company, please visit . DISCLOSURE NOTICE: The information contained in this release is as of June 10, 2024. Renova Therapeutics assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. Media and Investor Contact: +1 858.461.1837 info@renovatherapeutics.com [1] Cotter TG, Rinella M. Nonalcoholic Fatty Liver Disease 2020: The State of the Disease. Gastroenterology. 2020 May;158(7):1851-1864. doi: 10.1053/j.gastro.2020.01.052. Epub 2020 Feb 13. PMID: 32061595. [2] Martin et. al. 2024 Heart disease and stroke statistics: a report of U.S. and global data from the American Heart Association. Circulation. Published online January 24, 2024. doi: 10.1161/CIR.0000000000001209. Contact Information Vijay Mahant CEO info@renovatherapeutics.com 619-992-3260 SOURCE: Renova Therapeutics, Inc. View the original press release on newswire.com.

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.