French biotechnology company Ciloa has secured €6.5 million ($7.6 million) in government funding through the France 2030 'Biotherapies and Biomanufacturing of Innovative Therapies' initiative to advance development of its groundbreaking drug candidate APN-sEV for treating obesity and type 2 diabetes. The funding, awarded through the 'DIADEME' project and organized by Bpifrance on behalf of the French government, will enable clinical development up to Phase IIa and implementation of large-scale manufacturing under Good Manufacturing Practices (GMP) conditions.
Breakthrough in Adiponectin Stabilization
Ciloa's APN-sEV represents a significant scientific achievement as the world's only recombinant, stable and functional form of adiponectin. Adiponectin, known as the 'Guardian Angel' of the metabolic system, possesses anti-inflammatory, antioxidative stress, antiapoptotic and insulin-sensitizing properties that demonstrate first-line therapeutic potential in several metabolic diseases, including type 2 diabetes, cardiovascular and skin diseases, retinopathies, and hormonal cancers.
"For over twenty years, people have tried and failed to produce a stable and functional form of adiponectin. We are the first to succeed, by combining adiponectin with small extracellular vesicles (sEV, or exosomes) to unlock its great therapeutic potential," said Robert Z Mamoun, CEO of Ciloa.
The company has developed a unique bioengineering technology for small extracellular vesicles with all types of proteins, with the technology's robustness demonstrated by a portfolio of over 130 proteins targeted on or within the sEV. Through its proprietary sEV bioengineering technology and reliable procedures, Ciloa has produced several batches of APN-sEV that have remained stable at 4°C for several months.
Promising Preclinical Results
Preclinical trials have demonstrated remarkable effectiveness of APN-sEV against obesity, type 2 diabetes and associated liver impairment. The therapy significantly reduces excess weight, clears fat storage in tested organs, substantially increases insulin sensitivity and contributes to glucose regulation. Notably, APN-sEV uniquely preserves all muscle mass, even when used in combination with current anti-diabetic products on the market.
"We have shown that the properties of APN-sEV stem from its action on specific metabolic pathways other than those targeted by current anti-diabetic products," said Bernadette Trentin, CSO at Ciloa. "APN-sEV is therefore highly effective in complementing these medications, paving the way for a safer, more comprehensive and sustainable treatment of many metabolic diseases."
Clinical Development Timeline and Manufacturing
With the secured funding, Ciloa will develop a first-in-class and first-in-human drug composed of adiponectin introduced via small extracellular vesicles. The company plans to implement production of APN-sEV and conduct the regulatory preclinical trials required to ensure safety. Phase I clinical trials are scheduled to launch in 2027, with Phase IIa planned for 2028.
The biomedicine will be produced using Ciloa's specialized production line developed for bioengineered small extracellular vesicles, including creation of stable lines, upstream processing, downstream processing, and quality controls specific to engineered small extracellular vesicles and added proteins. To safely produce injectable APN-sEV for human use, the production line will be transferred under GMP conditions.
Addressing Global Health Challenge
The therapy targets a substantial global health burden, with type 2 diabetes and obesity affecting approximately two billion patients worldwide. Ciloa's approach offers potential advantages through its distinct mechanism of action compared to existing treatments, potentially providing complementary therapeutic benefits.
Ciloa, which spun out of the French National Centre for Scientific Research (CNRS) and the University of Montpellier, is a pioneer in in vivo bioengineering of small extracellular vesicles for therapeutic and preventative purposes. The company's patented proprietary technology is supported by its EVENGI platform, which has produced more than one hundred sEVs containing different proteins of medical interest across applications in metabolic diseases, vaccines against emerging viral threats, and oncology.
