Positive Results from Studies of Retrotope’s RT011 in Animal Models of Retinal Degeneration to be Featured in Oral Presentations at 2nd Annual Dry AMD Therapeutic Development Summit
Data Demonstrate RT011 Offers Dose-Dependent Protection Against Retinal Lipid Peroxidation (LPO) and Cell Damage, as well as Preservation of Visual Function
Findings Provide Rationale for Advancement of RT011 into Clinical Development for the Treatment of Dry Age-Related Macular Degeneration (AMD)
LOS ALTOS, CA – October 19, 2021 – Retrotope, a clinical-stage biopharmaceutical company focused on the development of novel, first-in-class therapies for degenerative diseases, today announced that positive results from preclinical studies of RT011, the second compound to emerge from the company’s novel technology platform, are being reported in multiple oral presentations at the 2nd Annual Dry AMD Therapeutic Development Summit. Findings to be presented demonstrate that RT011, which is being developed as an oral therapy for the treatment of dry age-related macular degeneration (AMD), provided dose-dependent protection in animal models of oxidative damage implicated in dry AMD. Importantly, study results showed that animals treated with RT011 experienced preservation of retinal cells, photoreceptors, and visual function relative to control animals. The conference, which is being conducted in a virtual format, is being held October 19-21, 2021.
The study results provide rationale for Retrotope’s advancement of the RT011 program into clinical development for the treatment of dry AMD, an irreversible, degenerative retinal disease that afflicts millions of individuals in the United States alone and is the leading cause of blindness and visual impairment worldwide. The company expects to file an Investigational New Drug (IND) application for RT011 in the first half of 2022 and initiate first-in-human clinical studies in dry AMD soon thereafter.
The first presentation, entitled, “Examine Iron-induced Oxidative Stress & Inflammation in a New Mouse Model of GA,” is being delivered by Josh Dunaief, M.D., Ph.D., Adele Niessen Professor of Ophthalmology, FM Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania. As part of his presentation, Dr. Dunaief will provide an overview of findings for RT011 in a preclinical iron-induced oxidative stress and inflammation model of geographic atrophy. This model is designed to induce lipid peroxidation (LPO), autofluorescence, and acute photoreceptor death, leading to progressive retinal atrophy. Study results demonstrated that animals treated with RT011 experienced decreasing levels of retinal damage with increasing tissue concentrations of RT011. Importantly, the treated animals experienced substantially complete protection against retinal cell damage at a specific retinal RT011 threshold that could easily be attained with oral dosing.
The second presentation, entitled, “Breaking the Vicious Circle of AMD Progression with Oxidation-Resistant DHA,” is being delivered by Karsten Schmidt, Ph.D., senior vice president, ophthalmology at Retrotope. In his presentation, Dr. Schmidt will highlight the molecular link between oxidative damage of highly polyunsaturated (PUFA) retinal lipids, complement activation and AMD. He will report further data demonstrating the protective effects of RT011 against oxidative damage.
“There is a critical need for new therapeutics that have the potential to address the underlying disease processes that drive the onset and progression of dry AMD before it can advance to the stages at which it significantly impairs patients’ vision,” said Peter K. Kaiser, M.D., Chaney Family Endowed Chair for Ophthalmology Research and a professor of ophthalmology at the Cleveland Clinic Lerner College of Medicine, and keynote speaker at the Dry AMD Therapeutic Development Summit. “To this end, I am encouraged by these preclinical study findings for RT011 as they suggest an elegant novel mechanism of action against the retinal cell damage and death that lead to vision impairment for dry AMD patients. Especially exciting is the fact that this novel therapy is delivered orally, offering convenience of administration while removing the need for invasive injections that can serve as a barrier to treatment for some patients.”
“These promising preclinical data provide clear evidence of target engagement with RT011 as shown by the protective properties observed in animals treated with the compound relative to control. Equally important was the observed dose dependent nature of the protection,” said Dr. Schmidt. “In its entirety, this collection of data offers a compelling rationale to advance RT011 into clinical studies as an orally administered potential treatment for dry AMD.”
In addition to the data being reported at the conference, Retrotope has also completed a 26-week oral toxicity study of RT011 in rats that demonstrated the compound to be well tolerated with no adverse findings in any dose group, further supporting the company’s plan to file an IND application for the program.
RT011 is an isotopically stabilized, synthetic docosahexaenoic acid (DHA) discovered and developed with Retrotope’s novel platform technology. This platform is designed to combat the oxidative stress and cellular degeneration that arises from LPO. While all healthy human tissues undergo this physiological process of cell degeneration and repair, it is now well-established that a number of serious degenerative diseases are precipitated when the LPO process becomes out of balance.
In the case of AMD, an expanding body of scientific research has connected uncontrolled oxidative stress and the damage it causes to photoreceptors and the retinal pigment epithelium (RPE) to the progression of this disease. The pathological LPO that drives oxidative stress in the retina is fueled by DHA, the most dominant of all PUFAs found within photoreceptors and the neuroretina. By replacing natural DHA with the chemically stabilized RT011, Retrotope aims to down-regulate uncontrolled, disease-causing LPO, without impacting the critical role that DHA plays for visual function.
About Dry AMD
Age-related macular degeneration (AMD) is a degenerative eye disease that upon progression to advanced stages impacts a patient’s sharp, central vision, causing it to become blurry or obstructed. The disease results in difficulty in conducting daily tasks such as reading, driving or recognizing faces. AMD is fairly common, affecting millions of Americans, and is a leading cause of vision loss among individuals 50 or older.
AMD occurs in two forms: dry and wet. Dry AMD is the most common form of the disease, accounting for approximately 80 percent of all AMD cases. It begins with the formation of drusen (small yellow deposits) beneath the retina, which progressively expand in size and damage the retina over time (intermediate AMD). Upon further progression, cells waste away and die (geographic atrophy) which can cause central blindness. Dry AMD affects more than 7.5 million Americans and more than 20 million adults in the western world. Treatments for this condition are limited and there are no approved oral therapeutic options.
Retrotope is a clinical-stage biopharmaceutical company focused on the development of first-in-class therapies for degenerative diseases ranging from orphan neurodegenerative indications to large market degenerative conditions. The company leverages its proprietary drug discovery platform to create novel, disease-modifying drugs designed to combat the oxidative stress and cellular degeneration that arises from lipid peroxidation (LPO). It does so through the creation of isotopically stabilized synthetic versions of polyunsaturated fatty acids (PUFAs) that trigger the downregulation of the LPO process. The company’s lead development candidate, RT001, is a clinical-stage isotopically stabilized, synthetic linoleic acid (LA) that is in development for a range of orphan neurodegenerative diseases, including infantile neuroaxonal dystrophy (INAD), Friedreich’s ataxia (FA), amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and progressive supranuclear palsy (PSP). In addition, the company is advancing its second development candidate, RT011, an isotopically stabilized, synthetic docosahexaenoic acid (DHA), toward the clinic for the treatment of dry age-related macular degeneration (AMD).
For more information, please visit www.retrotope.com.
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Stephanie Diaz (Investors) Tim Brons (Media)