Vincenzo Natali laughs ruefully at the notion that he is 'big in France'. As with seemingly every other notable English-Canadian film-maker, his work is more successful critically and commercially in France than in his own country.

It is a proud tradition, which certainly places him in good company (David Cronenberg, Atom Egoyan, Guy Maddin). His 1997 low-budget feature debut Cube drew more than 800,000 admissions in France, as opposed to a gross of $500,000 in North America in 1998. His succeeding films, 2002's Cypher and 2003's Nothing, drew more interest in Europe than at home. He was also the only Canadian to direct a sequence in the 2006 portmanteau feature Paris Je T'Aime.

His new film, Splice, is being co-produced by France's Gaumont. But there is every indication this one may also put Natali on the radar in North America.

On the set in Toronto, Loic Trocme, head of sales and acquisitions for the Paris-based distributor, says the director's sensibility was key to Gaumont's participation. Having backed English-language productions such as Luc Besson's The Fifth Element in the 1990s, Gaumont is pushing into international film-making with the likes of Michel Gondry's The Science Of Sleep. 'We want to back 10-12 projects a year, including two or three English-language projects,' he says. 'We don't want to make American movies. In terms of risk and storytelling, Splice is quite different from the usual creature movie.'

Natali is proud of his Euro-vibe. 'My tastes straddle European and US cinema. I like both but there is something about the Canadian sensibility that seems like a bridge between the two. That's very much my taste. I like stuff that's left of centre, but I'm also a great lover of big Hollywood movies.' Splice, he says, is such a bridge. 'It will appeal to the mainstream but it's something a studio would never make.'

Set in present-day Toronto, Splice tells the story of two cutting-edge geneticists (Adrien Brody and Sarah Polley) linked by marriage and scientific zeal. Experimenting with genetic material they hatch a plan and, to their astonishment, an egg. The result is a creature they christen Dren, a lifeform even they could not have dreamt up.

Natali conceived of Splice more than 10 years ago as the follow-up to his smash debut. It was 1998, and a newspaper image of a freakish man-made mutant mouse prompted Natali to ponder the future of genetic engineering. A decade later, the science fiction he imagined is now fact. The film's producer, Steve Hoban of Toronto-based Copper Heart Entertainment, says: 'A month before we started shooting, the UK government gave its approval to human-animal hybridisation.'

The film has its own diverse and tangled DNA. As early as 2000, the project had been optioned by Robert Lantos' then-recently launched Serendipity Point Films. But nothing happened and other projects intervened for both parties. 'Robert Lantos chose to do Men With Brooms instead,' says Hoban.

Over the years Natali would tinker with the script and, when pressed for ideas at film festivals and industry meetings, he would mention his 'baby'. In 2003, he met Guillermo del Toro at the Fantasporto Film Festival in Portugal, and del Toro's partner at LA-based production company Angry Bulls started calling. So he sent them the script.

At the Gerardmer Film Festival, another fantasy-themed event, he reconnected with Yves Chevalier, a producer with BAC Films he met during the Cube hoopla, whom he also told about Splice.

For four years Natali was holed up in LA developing material. 'It was horrible,' he says. 'It's the worst feeling in the world. But I've learned the most important quality for a film-maker is patience.'

Then, right out of the blue, Chevalier rang. Now a producer's representative, he had been contracted by Gaumont to lead the above-mentioned international production charge. He wanted to know if Natali had a project; when Chevalier found he had a crack at the - albeit belated - follow-up to Natali's French hit, he convinced Gaumont to jump. Meanwhile, del Toro's team wanted Splice to be Angry Bulls' inaugural production.

Then pal Hoban, who produced Nothing, had a look at the Serendipity contract and realised Natali could shop Splice without having to buy back the option immediately. That was 18 months ago.

Says Natali: 'You wait and you wait and you wait and then all of a sudden you almost don't have time to do it.'

Everything came together quickly, including a whopping $26m budget. Polley was a lock from day one. Brody signed on after CAA passed him the script. Del Toro will 'present' the picture and executive produce, alongside Gaumont chief Franck Chorot. Seville Pictures signed on to distribute in Canada.

As for the creature, Dren, she was a god-send: French actress Delphine Chaneac auditioned for her role by performing a kata - a series of martial-arts moves. 'She's a major discovery,' says Natali.

Asked to explain Chaneac's allure but constrained by the risk of spoiling her character's secret, Natali searched the ceiling for clues. 'She's a creature. A beautiful creature. There's something alien about her. It's more than just physical prowess. She has an indescribable quality. She's a step up on the evolutionary ladder.'