“BRD9 inhibition is a novel target for the treatment of HD identified by our proprietary high throughput organoid phenotypic screening platform,” said Fred Etoc, Chief Scientific Officer of Rumi. “We have previously demonstrated, in vitro, that BRD9 inhibition rescues several of the biochemical dysfunctions known to occur in HD and thus could be disease modifying. The new in vivo data reported in this presentation provide both behavioral and molecular validation of this target. We are currently working on developing a brain penetrant BRD9 inhibitor that can ultimately enter IND enabling studies. Finally, these experiments demonstrate the usefulness of RUMI’s platform to discover potential new targets in a therapeutic disease area such as HD where new hypotheses are needed.”

To demonstrate in vivo proof of concept, the researchers employed a long-lasting siRNA to block BRD9 in R6/2 mice, an animal model for HD, then evaluated the mice versus control animals on several behavioral and biochemical parameters. Compared to control R6/2 mice, treated mice showed a statistically significant reduction in mutant huntingtin (mHTT) protein aggregations in both the cerebral cortex and dorsal striatum. Aggregation of mHTT in neurons is a molecular hallmark of HD and a marker for disease progression. Additionally, two validated HD behavioral assays were evaluated: distance traveled and rearing behavior. Treated mice demonstrated a significantly increased total distance traveled at eight weeks post treatment compared to untreated mice. Rearing behavior also showed a statistically significant increase in total rearing at 10 and 12 weeks of age compared to control mice. Both measures are behavioral biomarkers for improved mobility, which is rapidly impaired in this mouse model. These data demonstrate the potential of a novel disease modifying therapeutic target to reverse pathologies in a HD animal model. 

Title: Deep learning analysis of micropattern-based organoid screens reveals BRD9 as a new potential target for Huntington’s disease
Authors: Shaun Peterson, Tomomi Haremaki, Yudelca Ogando, Carlota Pereda, Arjun Adhikari, Ali Brivanlou, Fred Etoc
Time/Date: 1-4 p.m. CEST, April 26

About Rumi Scientific
Rumi Scientific’s mission is to identify and develop novel therapeutics for rare and neurodegenerative diseases by employing its revolutionary synthetic human tissue platform to produce more predictive data leading to a safe and faster clinical trial process. The Company’s lead program is an orally available bromodomain-containing protein 9 (BRD9) inhibitor in lead optimization for the treatment of Huntington’s disease. Founded in 2016, Rumi licensed foundational technology from The Rockefeller University developed by co-founders Ali H. Brivanlou, Ph.D., and Eric D. Siggia, Ph.D. For more information on Rumi Scientific, please see www.rumiscientific.com or contact info@rumiscientific.com.

Rumi Scientific:
Allen Fienberg, Ph.D.
Chairman and Chief Executive Officer
allen@rumiscientific.com

Fred Etoc, Ph.D.
Chief Scientific Officer
fred@rumiscientific.com

Investors:
Burns McClellan
Lee Roth / Cameron Radinovic
lroth@burnsmc.com / cradinovic@burnsmc.com

Source: https://www.globenewswire.com/news-release/2023/04/26/2654886/0/en/Rumi-Scientific-Announces-Data-Demonstrating-Disease-Modifying-Effect-of-BRD9-Inhibition-in-a-Huntington-s-Disease-Animal-Model.html

“Our human organoid-based high throughput drug discovery platform has already identified multiple molecules and targets warranting further development,” said Ali H. Brivanlou, Ph.D., co-founder of Rumi Scientific, and the Robert and Harriet Heilbrunn Professor and head of the Laboratory of Synthetic Embryology at The Rockefeller University. “Having reached this point, it became clear that a CEO with expertise in advancing preclinical programs to clinical-stage candidates was needed to drive our continued progress. Allen’s extensive neuroscience research and drug development experience positions him ideally to lead the advancement of our lead program in Huntington’s disease (HD) and of our earlier-stage programs in autism spectrum disorder and Alport syndrome. On behalf of the Rumi Scientific team, I am pleased to welcome Allen to the Company and look forward to its ongoing evolution under his leadership.”

Dr. Fienberg joined Rumi after serving for more than 20 years as Vice President of Business Development at Intra-Cellular Therapies, Inc. (ITI), which he co-founded in 2002. While at ITI, he was responsible for all business development activities along with various preclinical science initiatives. As a co-founder Dr. Fienberg also participated in early-stage fundraising, investor relations, legal and various administrative functions. From 1999-2001, Dr. Fienberg was a staff scientist at the Genomics Institute of the Novartis Research Foundation and was appointed a Research Assistant Professor at The Rockefeller University from 2001-2002. Dr. Fienberg earned his A.B. degree in Genetics from the University of California, Berkeley, and his Ph.D. in Human Genetics from Yale University. He completed post-doctoral studies at The Rockefeller University under the direction of the late Dr. Paul Greengard from 1991-1999.

“What attracted me to Rumi was their highly innovative, phenotype-based drug discovery capabilities based on their unique high throughput organoid screening platform,” said Dr. Fienberg. “The platform evaluates drug-induced changes in phenotypes observed in neural organoids, rather than employing the traditional approach of identifying targets against which molecules are then tested. The platform has already identified molecules with the potential to impact several underlying pathological processes in HD. The platform is adaptable to almost any disease and thus has tremendous potential. I look forward to working with the talented team at Rumi to advance this and other potential therapeutic candidates.”

About Rumi Scientific
Rumi Scientific’s mission is to identify and develop novel therapeutics for rare and neurodegenerative diseases by employing its revolutionary synthetic human tissue platform to produce more predictive data leading to a safe and faster clinical trial process. The Company’s lead program is an orally available bromodomain-containing protein 9 (BRD9) inhibitor in lead optimization for the treatment of Huntington’s disease. Founded in 2016, Rumi licensed foundational technology from The Rockefeller University developed by co-founders Ali H. Brivanlou, Ph.D., and Eric D. Siggia, Ph.D. For more information on Rumi Scientific, please see www.rumiscientific.com or contact info@rumiscientific.com.

Rumi Scientific:
Allen Fienberg, Ph.D.
Chairman and Chief Executive Officer
allen@rumiscientific.com

Fred Etoc, Ph.D.
Chief Scientific Officer
fred@rumiscientific.com

Investors:
Burns McClellan
Lee Roth / Cameron Radinovic
lroth@burnsmc.com / cradinovic@burnsmc.com

Source: https://www.globenewswire.com/news-release/2023/03/30/2637568/0/en/Rumi-Scientific-Appoints-Allen-A-Fienberg-Ph-D-as-Chief-Executive-Officer-and-Chairman-of-the-Board-of-Directors.html