MENLO PARK, Calif. & DALLAS–(BUSINESS WIRE)–ReCode Therapeutics, a biopharmaceutical company powering the next wave of genetic medicines through superior delivery today presented new preclinical data from the company’s inhaled mRNA-based molecular therapy program for the treatment of primary ciliary dyskinesia (PCD) in three posters at the American Thoracic Society (ATS) 2022 International Conference, taking place May 13-18, 2022 in San Francisco. The company’s mRNA-based program in PCD uses ReCode’s first-in-class Selective Organ Targeting (SORT) lipid nanoparticle (LNP) delivery platform, which enables the targeting of organs and tissues beyond the liver via a variety of administration routes.
There are currently no approved treatments for primary ciliary dyskinesia (PCD), a rare genetic disease with inherited mutations that cause the loss of ciliary activity (and therefore the loss of normal mucus clearance) in the airways. Patients with PCD have a high burden of morbidity with chronic respiratory infections, bronchiectasis, and often develop respiratory failure.
ReCode is developing a disease-modifying mRNA-based approach for the treatment of PCD caused by mutations in DNAI1, an essential gene for ciliary movement. Using the company’s proprietary delivery platform, DNAI1 mRNA is formulated in ReCode’s SORT LNPs, nebulized, and delivered as an aerosol directly into the airway. The intent is for the mRNA delivery to lead to DNAI1 protein production in target cells and therefore enable rescue of ciliary function.
“These promising new data demonstrate that our SORT LNP-formulated DNAI1 mRNA can be precisely delivered directly to the intended cells within the lungs, without significant exposure to other tissues. Importantly, treatment was shown to be well-tolerated, allowing for repeat administration. Additional preclinical data show that our DNAI1 mRNA has low immune reactivity, rescues ciliary function, and results in long-lasting functional recovery,” said David Lockhart, Ph.D., Chief Scientific Officer and President, ReCode Therapeutics. “The totality of data presented at ATS today reflects the broad potential of our novel SORT LNP platform to deliver highly targeted mRNA-based therapies and supports the continued development of inhaled mRNA as a promising disease-modifying therapy for primary ciliary dyskinesia, a rare disease with no approved treatments.”
New data presented today at ATS included:
- Results from a non-human primate model show that ReCode’s SORT LNP-formulated mRNA is well-tolerated and can be nebulized and delivered directly to the lungs as an inhaled aerosol without significant exposure to other tissues. Robust delivery of DNAI1 mRNA to the lung and expression of human DNAI1 protein in relevant target cell types, including ciliated, club, and basal cells, was observed. Study results showed rapid clearance of LNP lipids which suggests the potential for well-tolerated repeat administration.
- In a proof-of-activity study using the human bronchial epithelial (hBE) cell-based PCD model, SORT LNP-formulated DNAI1 mRNA delivered as an aerosol successfully rescued ciliary function that was shown to persist for weeks after the last treatment.
- A preclinical design showed that the optimized DNAI1 mRNA reduced immune reactivity and was well-tolerated.
Full details from the data presented at ATS 2022 can be accessed via the Publications section on ReCode’s website.
ReCode will also present new preclinical data from its mRNA-based therapeutic program for cystic fibrosis on Wednesday, May 18th. These data demonstrate the ability of SORT LNPs to deliver optimized, functional CFTR mRNA as an aerosol directly to the intended cell targets. These preclinical data support further investigation and provide a potential therapeutic approach to address a significant patient population that is not eligible for current CFTR modulator therapy.
Poster Title: Functional Rescue of CFTR by Aerosolized Delivery of Optimized CFTR mRNA Using ReCode-LNPs in Primary Human Bronchial Epithelial Cells Derived from Patients with Cystic Fibrosis
Poster Number: 705
Session Title: D109 – Airway of Interest: Epithelial and Smooth Muscle Function in Health and Disease
Date and Time: Wednesday, May 18, 2022, 12:45 – 2:15 p.m. PT
Location: Room 2009/2011 (West Building, Level 2), Moscone Center
Presenter: Daniella Ishimaru, Principal Scientist, ReCode Therapeutics
About Primary Ciliary Dyskinesia
Primary ciliary dyskinesia (PCD) is a rare genetic disease characterized by deficient mucociliary clearance (MCC), chronic respiratory tract infections, bronchiectasis, and declining respiratory function. Mutations in more than 40 different genes result in dysfunctional cilia and loss of MCC. PCD is a life-limiting disease with a high burden of morbidity and no disease-modifying treatments available to patients. There are estimated to be more than 87,000 patients affected with PCD across North America and Europe, with more worldwide.
About the SORT LNP Platform
ReCode’s novel Selective Organ Targeting (SORT) lipid nanoparticle (LNP) technology is a modular genetic medicines delivery platform with broad potential applications across a range of organs and tissues, target cells, and therapeutic modalities. ReCode’s proprietary SORT LNP platform enables the flexibility to target specific organs and tissues while de-targeting the liver.
Beyond its highly selective targeting capability, ReCode’s SORT LNP platform is further distinguished by its versatility in both mode of administration and the diversity of genetic cargoes that can be delivered, which include mRNA and gene correction components. Together, these qualities form the foundation for opportunities to unlock the full potential of genetic medicines.
About ReCode Therapeutics
ReCode Therapeutics is a biopharmaceutical company powering the next wave of genetic medicines through superior delivery. ReCode’s Selective Organ Targeting (SORT) lipid nanoparticle (LNP) platform is a next-generation LNP delivery technology to target organs and tissues beyond the liver. The SORT LNP platform is the foundation for ReCode’s pipeline of disease-modifying mRNA and gene-correction based therapeutics for genetically defined diseases for which there are few or no current treatments. ReCode’s lead programs are focused on primary ciliary dyskinesia, and cystic fibrosis caused by Class I mutations. ReCode is leveraging its SORT LNP platform and nucleic acid technologies for mRNA-mediated replacement and gene correction in target cells, including stem cells. For more information, visit www.recodetx.com and follow us on Twitter @ReCodeTx and LinkedIn.