Seven miRNA-focused companies pioneering new therapies in 2024

MicroRNAs (miRNAs) are small, non-coding RNA molecules, typically 21–23 nucleotides in length, that play a crucial role in regulating gene expression. They function by binding to complementary sequences on messenger RNA (mRNA) molecules, leading to mRNA degradation or inhibition of protein translation. Several companies are advancing candidates relying on miRNAs in 2024.

miRNAs have garnered significant attention due to their involvement in various diseases – alterations in miRNA expression profiles have been linked to cancer, cardiovascular diseases, and neurodegenerative disorders. This connection positions miRNAs as both potential biomarkers for disease diagnosis and as therapeutic targets.

The therapeutic potential of miRNAs lies in their ability to modulate gene expression pathways. By designing miRNA mimics or inhibitors, researchers aim to restore normal gene expression patterns disrupted in disease states. 

In this article, we take a look at seven up-and-coming companies in the field of miRNA.

aceRNA Technologies

• Lead technology: RNA Switch technology – preclinical
• Area of focus: Precision mRNA therapeutics with miRNA-responsive control
• Recent news: Secured $6.1 million (960 million JPY) in series B funding

aceRNA Technologies specializes in the development of mRNA-based therapeutics that leverage its proprietary RNA Switch technology. Founded in Japan, the company focuses on enhancing the precision and safety of gene therapies by incorporating cell-type-specific control mechanisms.

The company’s RNA Switch technology is designed to regulate therapeutic gene expression based on the activity of specific miRNAs within target cells. This approach enables the activation or suppression of therapeutic genes in response to intracellular miRNA levels, reducing off-target effects and improving treatment specificity. 

Incorporating miRNA-responsive elements allows aceRNA’s therapeutics to detect miRNA signatures unique to specific cell types or disease states. For instance, the RNA Switch can ensure that therapeutic genes are only activated in cancer cells or other target tissues, leaving healthy cells unaffected. 

In May 2024, aceRNA Technologies announced the successful completion of a series B funding round, raising $6.1 million (960 million JPY). 

While still in preclinical development, aceRNA Technologies’ innovative use of miRNA-responsive mRNA therapeutics positions it as a promising player in the RNA therapeutic landscape.

ARTHEx Biotech

• Lead candidate: ATX-01 – phase 1/2 started in 2024
• Area of focus: myotonic dystrophy type 1
• Recent news: $44 million series B and set to initiate phase 1/2 trial in February 2024

Founded as a spin-off from the University of Valencia, ARTHEx focuses on creating RNA treatments for genetic diseases, with a particular emphasis on myotonic dystrophy type 1 (DM1).

DM1 is a genetic disorder characterized by progressive muscle wasting, weakness, and myotonia (delayed muscle relaxation), caused by an abnormal expansion of CTG repeats in the DMPK gene, leading to toxic RNA accumulation and disrupted cellular functions.

The company’s lead investigational compound, ATX-01, is an antisense oligonucleotide designed to bind specifically to microRNAs that are abnormally overexpressed in the tissues of patients with DM1. By addressing the root cause of the disease – specifically, toxic DMPK RNA and insufficient MBNL protein – ATX-01 aims to restore normal cellular function. The therapy utilizes a fatty acid-conjugated oligonucleotide to enhance delivery to muscle tissue, allowing for very low active doses.

In May 2023, ARTHEx Biotech announced the closing of a $44 million (€42 million) series B financing round. This funding is intended to advance ATX-01 into clinical development for the treatment of DM1. ARTHEx also received clearance from the U.S. Food and Drug Administration (FDA) to initiate the phase 1/2a ArthemiR trial of ATX-01 for DM1. 

Biorchestra

• Lead candidate: BMD-001 – preclinical 
• Area of focus: Neurodegenerative diseases
• Recent news: Shared positive preclinical data for BMD-001

Biorchestra is a South Korean biotechnology company specializing in RNA-based therapeutics aimed at treating neurodegenerative diseases. Founded in 2016, the company focuses on developing solutions for conditions such as Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).

The company’s lead candidate, BMD-001, is designed to target microRNA-485-3p (miR-485-3p), which has been implicated in the pathogenesis of Alzheimer’s disease. Indeed, overexpression of miR-485-3p is associated with neuroinflammation and neurodegeneration. BMD-001 employs an antisense oligonucleotide approach to inhibit miR-485-3p, aiming to reduce amyloid-beta and tau protein accumulation, key features of Alzheimer’s disease.

To enhance delivery across the blood-brain barrier, Biorchestra has developed a proprietary brain drug delivery system (BDDS). This system uses a polymeric complex based on polyethylene glycol (PEG) to enhance the stability and delivery of the antisense oligonucleotide. This helps the therapeutic agent cross the blood-brain barrier and target neurological cells, it ensures precise delivery to the central nervous system.

BMD-001 is still in preclinical development and studies in non-human primate models have demonstrated that intravenous administration of BMD-001 leads to significant reductions in amyloid-beta and tau proteins, as well as decreased neuroinflammation. 

In April 2023, Biorchestra announced progress in the BMD-001 program, reporting broad biodistribution across the brain and effective target engagement. These results support the progression of BMD-001 toward formal clinical studies for Alzheimer’s disease, ALS, and Parkinson’s disease.

Cardior Pharmaceuticals

• Lead candidate: CDR132L – phase 2
• Area of focus: Heart disease
• Recent news: Cardior Pharmaceuticals to be acquired by Novo Nordisk

Cardior Pharmaceuticals is a German company specializing in the development of non-coding RNA-based therapeutics for cardiovascular diseases. 

The company’s lead candidate, CDR132L, is an antisense oligonucleotide designed to inhibit microRNA-132 (miR-132), a regulator in pathological cardiac remodeling processes. Elevated levels of miR-132 in cardiac tissue are associated with adverse remodeling and heart failure. By targeting miR-132, CDR132L aims to halt and reverse detrimental cardiac remodeling, thereby restoring normal heart function.

The miRNA targeting candidate cleared phase 1b clinical trial in 2020 and demonstrated a favorable safety profile and beneficial cardiac effects in heart failure patients.

CDR132L is currently in phase 2 for patients with reduced left ventricular ejection fraction after myocardial infarction. The primary endpoint focuses on changes in left ventricular end-systolic volume, a key indicator of cardiac function.

In March, Novo Nordisk announced it would acquire Cardior Pharmaceuticals for up to €1.03 billion ($1.08 billion). The acquisition aims to bolster Novo Nordisk’s cardiovascular disease pipeline, with CDR132L being a central component of the acquisition. 

Ceria Therapeutics

• Lead technology: CNP-miR146a – preclinical
• Area of focus: Inflammatory disorders
• Recent news: $2 million SBIR grant

Ceria Therapeutics develops treatments for inflammatory disorders using miRNA delivery platforms. The company’s proprietary technology focuses on conjugating miRNAs with cerium oxide nanoparticles (CNPs) to create stable therapeutics. This approach enhances the delivery and activity of miRNA molecules. 

The company’s first candidates rely on CNP-miR146a, a conjugate of cerium oxide nanoparticles, and microRNA-146a, a miRNA with potent anti-inflammatory properties. By targeting key pathways involved in inflammation and oxidative stress, CNP-miR146a acts as a “molecular brake,” offering a novel approach to managing inflammatory diseases. 

The company recently received a $2 million Small Business Innovation Research (SBIR) grant from the National Institutes of Health (NIH) to advance its non-healing diabetic foot ulcers (DFU) candidate CTX-001. In September 2023, the company had already received a $2.1 million SBIR grant for the development of CTX-002 for the treatment of progressive inflammatory lung disorders. In October 2023, the same program was awarded $3.8 million from the United States Department of Defense’s (DoD) U.S. army.

Resalis Therapeutics

• Lead candidate: RES-010 – preclinical
• Area of focus: Metabolic disorders, including obesity and fatty liver disease
• Recent news: Secured strategic equity investment from Sanofi to accelerate development of RES-010

Resalis Therapeutics develops RNA-based therapies for the treatment of metabolic disorders. Based in Italy, the company focuses on targeting miRNA pathways to address conditions such as obesity, fatty liver disease, and nonalcoholic steatohepatitis (NASH).

The company’s lead candidate, RES-010, is an antisense oligonucleotide designed to inhibit microRNA-22 (miR-22), a key regulator of lipid metabolism and energy homeostasis. Overexpression of miR-22 has been linked to metabolic dysfunctions, including increased lipid biosynthesis and reduced energy expenditure. By targeting miR-22, RES-010 aims to restore balance in these metabolic pathways, offering a novel therapeutic approach to metabolic disorders.

In October 2024, Resalis Therapeutics announced a strategic equity investment from Sanofi to accelerate the development of RES-010 through clinical trials. Resalis Therapeutics’ focus on miRNA-based therapies positions it as a promising player in the RNA therapeutics space. With its innovative approach and growing support from major industry partners, the company is poised to make significant contributions to the treatment of metabolic diseases.

Transcode Therapeutics 

• Lead candidate: TTX-MC138 – phase 1/2
• Area of focus: Cancer
• Recent news: FDA clearance to initiate phase 1/2 

TransCode Therapeutics is a clinical-stage oncology company based in Boston, Massachusetts, focused on developing RNA-based therapeutics to treat metastatic diseases. The company aims to address advanced solid tumors by targeting specific miRNAs implicated in cancer progression.

The biotech’s lead candidate, TTX-MC138, is designed to inhibit microRNA-10b (miR-10b), which is recognized as a regulator of metastasis in various solid tumors. Overexpression of miR-10b has been linked to increased tumor cell migration and invasion, leading to metastatic disease. 

Building on promising results suggesting that TTX-MC138 can effectively reach metastatic sites, TransCode received clearance from the FDA to initiate a phase 1/2 clinical trial. This trial is designed to evaluate the safety and preliminary efficacy of TTX-MC138 in patients with advanced solid tumors.

miRNA, a promising subsector that still faces challenges

According to Grand View Research, in 2023, the global miRNA market was valued at approximately $1.58 billion and is projected to expand at a compound annual growth rate (CAGR) of 12.87%, reaching around $3.64 billion by 2030.

This growth is driven by the increasing recognition of miRNAs as critical regulators in various diseases, including cancer.

Despite the promising outlook, the development of miRNA-based therapeutics faces several challenges. Efficiently delivering miRNA therapeutics to specific tissues or cells remains a significant hurdle. Ensuring that these molecules reach their intended targets without degradation or unintended effects is crucial for therapeutic efficacy.

miRNAs can also potentially interact with multiple mRNA targets, leading to unintended gene regulation. Minimizing these off-target effects is essential to prevent adverse outcomes. Ensuring the stability of miRNA therapeutics in the bloodstream and reducing potential immune responses are other critical challenges in the area.

Advancements in nanotechnology, chemical modifications of miRNAs, and targeted delivery systems are paving the way for more effective miRNA-based therapies.