Ask most people to name a Belgian biotech with a llama-based antibody technology, and the chances are that the first name mentioned will be Ablynx. Now another company, Argen-X, is vying for a piece of the action with a plan to list on Euronext Brussels.
There is, of course, a connection: the group’s three founders are ex-Ablynx executives. But there the similarity ends, Tim Van Hauwermeiren, Argen-X’s chief executive, tells EP Vantage. With four large partners already in place, the six-year-old company will now hope to move quickly to beat Ablynx and MorphoSys at their own game.
The business models might be similar, but the technology is Argen-X’s. It stems from a discovery – predating the formation of Ablynx – that the llama’s immune system has two distinct “compartments”: mini antibodies, or nanobodies, on which Ablynx focuses, and full, conventional ones comprising two light and two heavy chains.
Argen-X is exploiting the conventional antibody repertoire, and thus is not competing with Ablynx, but rather with antibody companies relying on transgenic mouse technologies. “The power of the llama is that [its antibodies’] variable regions are extremely close to the human’s,” says Mr Van Hauwermeiren.
“You get a much more powerful immune response than with inbred [transgenic] animals. And using just two or four llamas you can beat what you can do by immunising tens of thousands of mice.” Manufacturing is via a contractor, with high expression levels and good stability achieved.
Already this technology, dubbed Simple Antibody, has attracted Lilly, Shire and more recently Bayer and Boehringer Ingelheim. Argen-X also boasts three enhancing technologies that modify antibodies’ Fc portions, which were previously assumed to be inert.
As would be expected, this technology base has led to an in-house R&D pipeline and a dual business model similar to the one employed by MorphoSys, though Mr Van Hauwermeiren insists that, in contrast to the German firm, “we’re firing on both cylinders from day one”.
Be that as it may, the focus of the planned IPO is likely to be on the pipeline, which enjoys two phase I oncology projects: ARGX-110, an anti-CD70 MAb, and ARGX-111, which targets c-met.
There are several industry projects blocking CD70, a tumour-expressed antigen, while Celldex’s varlilumab targets CD27, the corresponding T-cell receptor for which CD70 is the ligand. This is still a poorly understood pathway, and paradoxically CD27 activation produces a T-cell-stimulatory response.
Blocking c-met, meanwhile, has taken a serious blow with the failure of the most advanced project – Roche’s MetMab – in phase III (Roche lung cancer failure throws c-met inhibition into doubt, March 3, 2014). But Mr Van Hauwermeiren says Argen-X takes a “radically different view of c-met biology. ARGX-111 is fundamentally different from MetMab.”
While Roche targeted EGFR-resistant tumours to strengthen its Tarceva franchise, Argen-X is more interested in the finding that c-met is involved in metastasis. “We’ve designed a molecule that completely blocks c-met and goes after circulating tumour cells.”
He adds: “Previously we had to say we weren’t afraid of Genentech being ahead of us. Now we have to explain that we’re not afraid of Genentech’s failure.” Ultimately, though, the MetMab flop could be hard to explain away until more clinical data emerge for ARGX-111.
This issue will gain importance as Argen-X moves towards seeking partners for its pipeline assets, and while the amount of cash being sought in the float has not been disclosed it is clear that Argen-X needs funds to get to a point at which projects can be licensed out.
Heart of the strategy
“Partnering is at the heart of our strategy, but the question is how and when. It would not be right for our shareholders to do a global deal now,” Mr Van Hauwermeiren says.
ARGX-110 could be taken into phase II in house in the orphan indication of Waldenström’s macroglobulinemia, which could serve as the basis for a broader deal in haematological cancers. ARGX-111 needs to be partnered at the end of phase Ib.
But, given the optimism, why Euronext? Mr Van Hauwermeiren concedes that Euronext is a “perhaps not the best” market for biotech – that prize belongs to Nasdaq – but he points to companies like Thrombogenics, for which it worked well, and stresses that Europe-listed groups like Ablynx and Galapagos boast a 20-40% US shareholder representation on their registers.
“Is [Euronext] the final stage? I don’t know; it could be that we continue in the direction of Nasdaq.”
For now Argen-X must concentrate on getting its float away while the iron is hot and before the summer lull sets in. It is anyone’s guess what the markets will be like come September.
|ARGX-110||Phase Ib, 54 pts, advanced malignancies||NCT01813539|
|ARGX-111||Phase Ib, 35 pts, advanced cancer||NCT02055066|