Milan-based startup emerges from national deep-tech hub with plan to advance preclinical development
AptaDir Therapeutics secured $1.6 million in pre-seed funding in September 2024 through EXTEND, a joint venture between CDP Venture Capital SGR and co-investors Angelini Ventures and Evotec SE. The Milan-based company plans to use the capital to refine Ce-49, its lead asset targeting myelodysplastic syndromes, and advance its preclinical development program.
The approach hinges on RNA aptamers—short, structured sequences that bind and neutralize DNMT1, an enzyme that maintains DNA methylation patterns across the genome. When those patterns go awry in cancer cells, tumor suppressor genes fall silent. AptaDir's platform attempts to reverse that process with what the company describes as greater selectivity than current epigenetic drugs.
A discovery rooted in natural biology
The technology traces back to a 2013 Nature paper by Annalisa Di Ruscio, a physician-scientist at Beth Israel Deaconess Medical Center and Harvard Medical School. Di Ruscio identified naturally occurring RNAs that interact with DNMT1, blocking methylation at specific genes. Those molecules offered a biological proof of concept: cells already use RNA to fine-tune which genes stay accessible.
AptaDir evolved synthetic aptamers from those natural sequences, engineering them for tighter binding. A 2023 study in Nature Communications described the selection of high-affinity candidates with binding constants of approximately 100 nanomolar. In leukemia xenograft models, Ce-49 induced demethylation comparable to azacitidine—a mainstay DNMT inhibitor—but produced a different pattern of gene expression, hinting at mechanisms the team is still unpacking.
Di Ruscio co-founded the company alongside Vittorio de Franciscis, an aptamer specialist at Italy's National Research Council; Daniel G. Tenen, founding director of the Cancer Science Institute of Singapore and a Harvard professor; and Marcin Kortylewski, who studies oligonucleotide immunotherapies at City of Hope. The group brings decades of combined work in noncoding RNA and cancer biology.
Chasing selectivity in blood cancers
Myelodysplastic syndromes, the initial target, represent a cluster of blood cancers that frequently resist or relapse after treatment with azacitidine and decitabine. Those nucleoside analogs incorporate into DNA broadly, carrying toxicity that constrains how much doctors can dose. AptaDir's bet is that neutralizing the methyltransferase enzyme directly—rather than trapping it on DNA—might spare healthy cells while still restoring silenced tumor suppressors.
The company is also exploring what it calls "captaDiRs," locus-specific aptamers that pair DNMT1-binding domains with gene-targeting motifs. A study published in NAR Molecular Medicine in 2026 by Di Ruscio's group demonstrated the concept in Fragile X syndrome, where hypermethylation silences the FMR1 gene. Whether that work translates to therapies remains speculative, but it suggests the platform could extend beyond oncology.
Italy's first EXTEND spinout
AptaDir holds the distinction of being the first biotech to emerge from EXTEND, the Italian National Technology Transfer Hub launched in October 2022. The initiative pooled more than €23 million—€15 million from CDP Venture Capital—to commercialize academic discoveries across the country. In a sector where state-backed capital often struggles to move at startup speed, EXTEND represents an experiment in whether institutional money can nurture early science without smothering it.
"Aptadir is the first biotech company born from EXTEND," Claudia Pingue of CDP Venture Capital said at the time of the funding. "Aptadir represents one of the best examples of where science innovation can create a new potential therapeutic for underserved conditions in adults and children, such as MDS and Fragile X Syndrome."
Giovanni Amabile, the company's executive chairman and CEO, noted that preliminary data suggest the aptamers are "highly selective, stable and non-toxic," with potential across multiple disease areas. That language is cautious, as it should be for a preclinical asset.
A crowded field, different modality
The company holds pending patents on DNMT1 aptamers with binding affinities below 100 nanomolar, with priority dating to October 2019 and filings in the U.S., Europe, and through the Patent Cooperation Treaty. Assignees include CNR and affiliated institutions, a common structure for academic spinouts in Italy.
AptaDir enters an epigenetic-medicine landscape thick with competition. Tune Therapeutics recently raised $175 million for epigenome-editing programs. Chroma Medicine pursues base-editing strategies to control methylation. Both companies operate at scales that dwarf AptaDir's current resources.
Still, the aptamer modality carries lower upfront capital requirements than genome-editing platforms, at least at early stages. Barcelona-based Aptadel Therapeutics, which is developing aptamer-drug conjugates for Ewing's sarcoma, raised €2.1 million in a seed round several years ago—a data point that suggests the format can advance on modest budgets, though perhaps at a slower pace than more generously funded competitors.
Whether AptaDir's selective approach to DNMT1 inhibition offers meaningful advantages over existing therapies will depend on clinical data the company has yet to generate. The path to clinical trials remains uncertain. For now, the startup has secured enough runway to find out whether its scientific premise translates beyond xenograft models.
