Data demonstrate the ability of an RSwitch system to regulate transgene expression in neurons in vivo

Additional data presented demonstrate the potential use of RSwitch to solve cardiotoxicity challenges in gene therapy applications for the treatment of Friedreich's ataxia

Data to be presented at the American Society of Gene and Cell Therapy (ASGCT) 2025 Annual Meeting

WOBURN, Mass., May 13, 2025 /PRNewswire/ -- Rgenta Therapeutics, a clinical-stage biotechnology company pioneering the development of a new class of oral small molecules targeting RNA and RNA regulation for oncology and neurological disorders, announced the presentation of preclinical data demonstrating the potential and versatility of its proprietary RSwitch technology to enable the fine-tuning of transgene levels in gene therapy applications with orally administered small molecules specifically built to meet the needs of each indication with a range of pharmacokinetic properties. The data will be presented at the American Society of Gene and Cell Therapy (ASGCT) 28^th Annual Meeting, which will be held from May 13 -17th, 2025, in New Orleans, LA.

"The data presented at this year's ASGCT meeting provide evidence to support the advantages of our RSwitch technology which is designed to deliver precise temporal control of therapeutic transgene expression over a wide dynamic range and is applicable to a variety of gene and cell therapy applications," said Travis Wager, Ph.D., co-founder and chief scientific officer. "While there are existing methods to control transgene expression in gene therapy, they typically rely on engineered transcription factors and repurposed pharmacology, are not specific to the switching system, and consequently do not provide particularly tight control of the transgene's expression. Rgenta has developed a platform for imparting gene therapy vectors with selective, dose-dependent regulation by orally bioavailable small molecules, RDrugs. Aided by massively parallel sequence library screening and deep learning-driven design, we have built RDrugs to meet the needs of each indication with a range of pharmacokinetic properties enabling direct control, via RSwitch, of specific pre-mRNA splicing events needed for the regulated production of the therapeutic payload."

In a poster titled RSwitch Enabled Gene Therapy to Fine Tune Frataxin Expression for the Treatment of Friedreich's Ataxia, Rgenta scientists presented data demonstrating the ability of RSwitches to enable dose-dependent control with up to 4000-fold induction of gene expression by a specific RDrug. RSwitches were able to control gene expression in both high and low strength promotors. Data were also presented from an RSwitch-regulated AAV gene therapy designed to express frataxin (FXN) for the potential treatment of Friedreich's Ataxia (FA). FA is a progressive neurodegenerative disease caused by a genetic deficiency of FXN, which is a small, nuclear-encoded mitochondrial protein believed to act as an iron chaperone or iron storage protein. While constitutive replacement of FXN by AAV vectors has shown promise in animal models, multiple studies have demonstrated the cardiotoxic effects of unregulated FXN overexpression making this gene therapy a good candidate for regulation of gene expression by a system such as RSwitch. The data demonstrate that an RSwitch-regulated FA expressing AAV-gene therapy achieves dose dependent expression of FXN in the heart with RDrug and human endogenous FXN levels in mice at low RDrug levels. A second test system demonstrated the ability of Rgenta's RSwitch and corresponding brain penetrant RDrug to regulate expression of a transgene in the brain.

"Our proprietary RSwitch technology provides an example of the power of Rgenta's RNA-targeted small molecule platform and represents a potentially game-changing tool for the development of regulatable gene and cell therapies that could improve the safety of these medicines," Simon Xi, Ph.D., cofounder and chief executive officer of Rgenta. "Rgenta's internal pipeline is focused on the application of our platform to inhibit disease driving therapeutic targets, such as MYB for the treatment of solid tumors, including adenoid cystic carcinoma and colorectal cancer, and hematological cancers such as acute myeloid leukemia, and PMS1 for the potential treatment of repeat expansion diseases such as Huntington's disease. We see the value of our RSwitch technology as a potential partnering opportunity with companies developing gene and cell therapies to improve the clinical success of these gene replacement therapies for difficult to treat diseases such as FA."

About RSwitch
RSwitch is a proprietary regulatable gene therapy system that enables oral, small molecule drug control of transgene levels in gene and cell therapy applications. RSwitch encodes a "dimmer" switch that makes the expression of transgene dependent on the administration of an oral small molecule drug (RDrug) that controls the system. Only when the drug is administered is the system activated. Furthermore, the level of gene expression is dependent on how much drug is administered. This precise gene control has the potential to enable fine control of the expression of a therapeutic protein. Rgenta has demonstrated the RSwitch system's feasibility in vitro and in vivo, achieving dose-dependent expression of reporter transgenes following small molecule administration. RSwitch technology offers versatile control across multiple gene and cell therapy applications, and the company is actively exploring strategic partnerships.

About Rgenta Therapeutics
Rgenta Therapeutics is a clinical stage biotechnology company developing a pipeline of oral RNA-targeting small molecule medicines with an initial focus on oncology and neurological disorders. Our proprietary platform mines the massive genomics data to identify targetable RNA processing events and design small-molecule glues to modulate the interactions among the spliceosome, regulatory proteins, and RNAs. Our lead programs and unique approach are unlocking the therapeutic potential of historically undruggable targets in human diseases. Learn more at: http://www.rgentatx.com.

Contacts
Investors: 
Sylvia Wheeler
Wheelhouse Life Science Advisors
Swheeler@wheelhouselsa.com

Elizabeth Wolffe, Ph.D.
Wheelhouse Life Science Advisors
Lwolffe@wheelhouselsa.com

Media
Aljanae Reynolds
Wheelhouse Life Science Advisors
Areynolds@wheelhouselsa.com

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SOURCE Rgenta Therapeutics