How Aptadir’s DiR RNA Technology Could Reactivate Silenced Genes

Milan-based Aptadir Therapeutics has raised €40 million ($45 million) to advance experimental RNA medicines for genetic conditions and cancers that are difficult to treat. Its approach, called DNMT1-interacting RNAs (DiRs), is designed to prevent DNA methylation at targeted genes and potentially restore their activity. The therapies are still preclinical, so their potential has not yet been established in patients. 125

How Aptadir’s DiR approach is intended to work

DNA methylation can silence genes. Aptadir’s DiRs are designed to bind to and inhibit DNMT1, an enzyme involved in DNA methylation, at specific genetic locations. The company’s proposed distinction is that this action can be locus-specific, rather than inhibiting methylation across the genome. 13

In Fragile X syndrome, Aptadir’s goal is to reactivate the silenced FMR1 gene. The company lists Fragile X among its areas of research, and its lead candidate Ce-49 is described as targeting the silenced gene. 413 This is a proposed therapeutic strategy, not evidence that the approach has been proven to treat the condition.

Aptadir has also identified other genetic disorders and cancers as potential applications. The underlying idea is to restore the activity of genes silenced through abnormal methylation; the company’s projects include cancer and rare-disease areas. 113 Which indications will ultimately progress, and whether the approach works safely and effectively, remain open questions.

What the $45 million seed round will support

The €40 million ($45 million) financing is intended to advance Aptadir’s RNA-inhibitor medicines for difficult-to-treat genetic conditions. The company is also developing its platform for possible use in cancers that have been difficult to treat. 125

4BIO Capital led the round. Participants included Aptadir’s earlier investor EXTEND, CDP Venture Capital, Indaco Venture Partners, XGEN Venture, CE-Ventures, Angelini Ventures, Kerna Ventures, Italian Angels for Biotech and Club degli Investitori. 325

Coverage has described the financing as the largest seed round for an Italian biotech and among Europe’s largest. Those are reported rankings, rather than an independently verified comparison in the materials available here. 2

A preclinical program, not an established treatment

Aptadir remains at the preclinical stage, according to reporting on the financing. 1 The company’s approach is therefore a research program, not an available therapy. Its central promise is the possibility of addressing diseases in which a gene has been switched off; whether DiRs can deliver that result in people will require further development and clinical testing.

Founder and CEO Giovanni Amabile has described Aptadir’s focus as diseases caused by the silencing of a gene that would normally produce a protein. 2 That framing captures the company’s hypothesis, but the therapeutic potential still needs to be tested.