ROME Therapeutics Announces Preclinical Data Demonstrating Inhibition of Endogenous Reverse Transcriptase Activity Blocks Immune Response in Autoimmune Disease Models

CAMBRIDGE, Mass.–()–ROME Therapeutics, a biotechnology company harnessing the repeatome for drug development, today announced new preclinical data demonstrating the ability of endogenous reverse transcriptase (eRT) inhibition to block pathological immune responses in autoimmune disease models. The results highlight the role of eRT in modulating the immune response, supporting its potential as a therapeutic target for autoimmune disease. The data will be presented today at the American College of Rheumatology (ACR) Convergence 2021 Virtual Meeting. ROME has identified eRT as its first target and will continue to advance this program to identify eRT inhibitors for further development.

“ROME is the first and only company founded to explore the novel biological area of the repeatome, which has clear pathological implications in autoimmune and other diseases. These data demonstrate the role that repeat-encoded eRT plays in the body’s innate immune response,” said Dennis Zaller, Ph.D., chief scientific officer of ROME. “For our first therapeutic target, we will be pursuing eRT, which is both biologically relevant and pharmacologically targetable. We are actively advancing this program to identify novel eRT inhibitors for further development as we work to revolutionize the treatment of these challenging diseases.”

Approximately 60% of the human genome consists of repetitive sequences of nucleic acids, known as repeats. Certain repeats, such as LINE1 and HERV-K, encode functional eRTs. These eRTs convert RNA into DNA in the cytosol, triggering nucleic acid-sensors, such as cGAS, leading to a viral mimicry response characterized by production of Type I interferon. Because excess Type I interferon production can lead to autoimmune disease, eRT inhibitors, which block the reverse transcription of repeat RNA into DNA, have the potential to improve pathological outcomes.

The data show that a potent and selective eRT inhibitor, Compound A, demonstrated the following:

– Inhibition of LINE1 retrotransposition in a cellular assay

– Inhibition of Type I interferon response in a cellular model of Aicardi-Goutières Syndrome

– Attenuation of antigen-specific T cell responses in MOG-immunized mice

ACR Presentation Details

Abstract #1064080
Title: Inhibitors of Endogenous Reverse Transcriptases Suppress In Vitro Type I Interferon Responses and In Vivo Antigen-specific T Cell Responses

Date: Monday, November 8

Time: 2:15 – 2:30 p.m. ET

About ROME

ROME Therapeutics is developing novel therapies for cancer and autoimmune diseases by harnessing the power of the repeatome – vast stretches of uncharted genetic material that have long been dismissed as the “dark genome.” With several drug targets identified and multiple discovery programs underway, ROME is moving rapidly to leverage this new frontier in biology. To lead this exploration, ROME has assembled a team of world-class leaders across fields including oncology, immunology, virology, chemistry and machine learning. ROME is based in Cambridge, Mass. For more information, please visit www.rometx.com.

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