Built from the remains of crop developer DevGen’s decision to scrap its pharmaceutical arm, private Belgian company Amakem is now preparing to advance its first candidate into the clinic in glaucoma.
Chief executive Jack Elands tells EP Vantage that an €18m ($25m) series A funding round announced today will be sufficient to support the research into the rho kinase (Rock) inhibitor dubbed AMA0076 through late 2013 or early 2014, when it hopes to have phase IIb proof-of-concept data, the typical deal-making threshold for drug discovery biotechs.
Red eye blues
Rho kinase inhibitors have been tried in glaucoma and have largely failed because they have caused a condition called hyperaemia that can manifest itself in red eyes - for example, Santen Pharmaceutical had to scrap its phase II candidate DE-104 last year. However, Mr Elands says Amakem believes its approach better targets cells in the trabecular meshwork, the main tissue that aids in relieving intraocular pressure (IOP) by draining fluid.
It is able to do so because AMA0076 is degraded by enzymes found outside the eye but not inside it, a result of the group’s localised drug action platform. The metabolites are an inactive compound with no off-target effects, which Amakem hopes will avoid the excess ocular blood flow that can cause red eyes.
“We can therefore dose at higher doses and possibly more frequently,” Mr Elands says. “If we can dose at higher doses, we can get a much more robust IOP lowering than has been possible with the other Rock inhibitors.”
Glaucoma treatment is dominated by prostaglandin F2 analogues like Pfizer’s Xalatan, Allergan’s Lumitan and Novartis’ Travatan, acquired with its buyout of Alcon last year (Novartis ups offer to grab Alcon growth, December 15, 2010). Xalatan, known generically as latanoprost, is still forecast to be the biggest seller in glaucoma in 2016 with $541m in sales, even though it lost patent protection in March 2011. Last year, it achieved sales of $1.75bn. Lumitan and Travatan will also lose patent protection in 2014.
Thus, AMA0076, an eye drop, will need to prove its value in an increasingly genericised field.
“The dose that other Rock inhibitors have been limited to is a dose where you see a marginal benefit when compared to latanoprost. The industry is looking for, and the ophthalmologists are looking for something that is substantially better than latanoprost. We think we can get there,” he says.
In addition to avoiding the off-target effects, Mr Elands says the company hopes it will be more effective than prostaglandins, which rely on reducing IOP by allowing fluid to drain through the uveoscleral pathway. However, that pathway grows less effective with age and consequently is prone to drug resistance, and indeed is a particularly troublesome one as glaucoma tends to be a disease of the elderly.
Disappointment begets opportunity
Amakem was formed last year with €1.5m in seed financing from LRM, Life Science Research Partners and VINNOF, the Flemish innovation fund. DevGen became an early investor through an in-kind technology contribution, which allowed three of its former scientists to continue the development of technology shelved when DevGen was unable to find a buyer for its pharma division and shuttered it in 2008.
The €18m round continues the involvement of the three original investors, but was led by Forbion Capital Partners with new contributions from Credit Agricole Private Equity and Vesalius BioCapital.
Based in the life-sciences incubator at the University of Hasselt, Amakem is now completing pre-clinical work on AMA0076 and expects to begin clinical trials late in the second quarter of 2012. Should the Rock inhibitor achieve proof of concept, as a minimum the group will consider the exit strategy of a trade sale but Mr Elands hopes the results are strong enough, and that other candidates are far enough advanced, that licensing to a larger partner will be the preferred strategy.
To that end, the company is working with a second Rock inhibitor candidate, AMA247, in inflammatory diseases, with chronic obstructive pulmonary disease a target indication. Late last year, the company received a €1.3m Belgian government grant to pursue that indication.
Mr Elands notes that it will be harder for a small private company to advance in that indication. In glaucoma there is a single, clearly defined endpoint that responds relatively quickly, intraocular pressure, so clinical trials can be short and relatively small. However, measuring improvements in COPD patients using AMA247 will take longer and require larger trials. Thus, ‘247 is a more likely candidate for an early partnership. An update on the product's development is expected by the end of the year, Mr Elands says.
Meanwhile, early development work on kinase inhbitors in other ophthalmological indications is underway, with a compound that will be ready for an investigational new drug application on a similar timeframe to ’76. But Mr Elands will not commit to a specific indication, as the group wants to strengthen its data before it begins discussing it openly with regulators and potential partners.
“We have very interesting data for three indications. We’re working our way around from a marketing opportunity and cost opportunity standpoint to determine what the most sensible indication would be for us to go after,” he says.
In many of the ophthalmological indications, such as wet age-related macular degeneration (AMD) and diabetic macular oedema (DME), he notes that existing and candidate therapies have only targeted single biological targets – such as excess growth of blood vessels in AMD – and have not addressed other components of disease (Therapeutic Focus - Looking beyond VEGF in diabetic eye disease, August 31, 2011).
“We are looking at those other components to be able to extend the reach of medication,” he says. “I think we’ve only started scratching the surface.”
But for now the clear focus is on its most promising compound, the glaucoma treatment ’76. Showing success for a novel drug in the disabling eye condition would validate Amakem’s technology and build its value, a development that will both please its investors and stoke interest from big pharma partners.