안녕하세요 보스턴 임박사입니다.
Lipid Nanoparticle (LNP)는 Alnylam Pharmaceuticals, Pfizer/BioNTech, Moderna에 의해 이미 상용화된 검증된 Delivery system인데요 현재까지는 Liver Delivery에만 되는 것으로 알려져 있습니다.
UT Southwestern Medical Center의 Daniel Siegwart 교수 연구팀은 2020년 Selective Organ Targeting (SORT) LNP를 Nature Nanotechnology에 발표했습니다.
그리고 이후에 Lung SORT를 이용한 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)에 대한 치료제 가능성을 발표했습니다.
이 연구결과를 바탕으로 ReCode Therapeutics가 설립되어 $80 Million Series A를 받았습니다. Orbimed Advisors가 Series A를 주도했습니다.
ReCode will use the proceeds to continue the preclinical development of its lead programs in primary ciliary dyskinesia (“PCD”) and cystic fibrosis (“CF”). The Company expects to file an Investigational New Drug Application (“IND”) for both programs in 2021. In addition, the Company will advance its proprietary non-viral lipid nanoparticle (“LNP”) delivery platform for organ-specific delivery of RNA therapies and gene editing components.
그리고 3년여의 노력 끝에 Primary Ciliary Dyskinesia (PCD) 치료제인 RCT1100의 임상시험을 시작했습니다.
ReCode Therapeutics, a private, clinical-stage genetic medicines company using superior delivery to power the next wave of mRNA and gene correction therapeutics, announced today that the first healthy volunteer participants have been dosed in a Phase 1 clinical trial of RCT1100, a first-in-class, mRNA-based genetic medicine for the treatment of people with primary ciliary dyskinesia (PCD) caused by pathogenic mutations in the DNAI1 gene.
There are currently no approved treatments for PCD, a rare genetic disease caused by inherited mutations leading to 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 and bronchiectasis, and often develop respiratory failure. RCT1100 is designed to be a disease-modifying mRNA-based therapeutic for PCD caused by pathogenic mutations in DNAI1, a gene that encodes a protein essential for ciliary movement. Formulated using ReCode’s proprietary SORT LNP delivery platform, RCT1100 is nebulized and delivered as an aerosol directly into the airway using an optimized eFlow®Nebulizer System (PARI). The intent is for the mRNA delivery to lead to DNAI1 protein production in target cells and thereby rescue ciliary function. Preclinical results supporting the mechanism of action of RCT1100 in vitro and in vivo were presented at the American Thoracic Society (ATS) 2022 International Conference.
Preclinical results는 아래에 발표한 Poster가 있습니다.
임상시험에 진입함과 함께 $260 Million 규모의 Series B를 할 수 있었습니다.
ReCode Raises $260M in Series B Financing to Advance Lead Programs – Biospace 9/20/2023
The California company will use its Series B raise to further advance its clinical development programs for primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). The money will also help ReCode boost its Selective Organ Targeting (SORT) lipid nanoparticle (LNP) pipeline with mRA and gene correction therapies for musculoskeletal, central nervous system, lung and liver indications.
ReCode’s SORT LNP platform allows for the targeted delivery of the encapsulated mRNA modalities and other corrective gene therapies, according to the company’s website. Unlike first-generation LNPs, which are taken in by the liver following administration, SORT LNP’s are specifically engineered with a biochemically unique fifth lipid that directs the nanoparticles to their specific target organs.
Currently, ReCode is harnessing its technology to target lung diseases such as PCD and CF. Its most mature candidate is an inhalable mRNA therapeutic that targets the DNAI1 gene, which in PCD is mutated and produces a faulty protein, leading to impaired ciliary movement.
In March 2023, the company announced that it had dosed its first batch of healthy volunteers in the Phase I study of the candidate. ReCode expects to file an Investigational New Drug application during the second half of this year.
Intellia, ReCode partner on genetic medicines for cystic fibrosis – Biopharmadive 2/15/2024
Intellia Therapeutics will work with a private biotechnology company to develop genetic medicines for cystic fibrosis, with an initial focus on people who have limited or no available treatment options.
Intellia noted how its platform includes “DNA writing” technology, a tool that has attracted considerable interest and investment in recent years. Tessera Therapeutics, for example, was created by Flagship Pioneering — the same biotech incubator that founded Moderna — and is built around “gene writing” technology that it claims can alter DNA in various ways, from changing single units of genetic material to adding in entire genes. Those qualities may make gene writing especially useful in diseases like cystic fibrosis where the genetic causes are well understood.
현재 Pipeline은 아래와 같이 Lung Delivery와 CNS Delivery Program이 있습니다.
CFTR mRNA치료제의 임상시험이 곧 시작될 것 같습니다. 기대가 됩니다.
BOSTON DR LIM 