This article has been updated to correct details regarding SYL1001's development timeline.
Spanish RNAi drug developer Sylentis is gearing up to begin a phase II trial of its investigational glaucoma treatment SYL040012, which could start as soon as by the end of the year, Gene Silencing News has learned.
At the same time, the company plans to begin a second phase I trial of an RNAi-based treatment for dry eye-associated pain, called SYL1001, later this year, according to a Sylentis spokeswoman.
SYL040012, Sylentis' lead drug candidate, comprises an siRNA against adrenergic receptor beta-2 that is delivered topically to the eye. In animal testing, the drug has proven able to both reduce intraocular pressure and prevent glaucoma.
In 2009, the company advanced SYL040012 into a phase Ia trial of healthy volunteers, and found the agent to be both safe and well tolerated. A follow-up phase Ib study examined the drug in volunteers with slightly elevated ocular hypertension, but who were not receiving therapy for that condition.
With the completion of those trials, Sylentis is now poised to start a dose-finding phase II trial of SYL040012 in patients with glaucoma, as well as those with bona fide ocular hypertension, according to Natalia Wright, the company's head of intellectual property.
The trial is expected to enroll 80 patients at 12 different centers throughout Europe, she said. Sylentis is awaiting clearance from German authorities to begin the study, and expects to have cleared all regulatory hurdles in time to begin enrollment before the end of 2012, she added.
Meanwhile, work is underway to start phase Ib testing of SYL1001, a topically delivered siRNA drug targeting transient receptor potential cation channel subfamily V member 1, or TRPV1, which plays a role in pain sensitivity and is the target of investigational small molecule-based pain drugs under development by other firms.
Wright said that the planned study, which follows a phase I trial in healthy volunteers, is expected to enroll a small number of dry eye patients beginning in the fourth quarter, and will be conducted in Spain.
Looking Beyond the Eye
When Sylentis was spun out of Spanish biotech firm Zeltia in 2006, it was firmly focused on ocular and digestive diseases (GSN 3/29/2007).
Although glaucoma had always been its lead indication, the company at the time touted its work in Crohn's disease, as well as earlier-stage efforts in neurodegenerative disorders and post-traumatic neural injury.
While this works continues, Wright said this week that these programs have been de-emphasized recently as Sylentis focuses on its two clinical-stage candidates.
In 2010, Roberto Weinmann, the COO of Zeltia subsidiary Pharmamar and who at the time handled Sylentis' business-development activities, told Gene Silencing News that the company was working on both Crohn's disease and ulcerative colitis, and that these efforts would take advantage of a proprietary oral-delivery technology (GSN 4/1/2010).
On the central nervous system front, the company was focused on cerebral ischemia and dementia, which would both take advantage of a development-stage intranasal delivery approach, he added.
At that time, Weinmann declined to provide specific details about these programs given their nascence. This week, Wright indicated that Sylentis had pulled back on its work with them.
“We're a small company so we have to use our resources wisely,” she said. “We've been focusing more on [ophthalmology] lately, and we still have those [other] programs in the R&D pipeline, but we're not concentrating on them as much at the moment.”
As a small company, Sylentis is also interested in finding bigger partners to help it carry its drugs forward, and Weinmann indicated in 2010 that doing so was something the firm was interested in. While conducting phase I and II studies were within its abilities, he noted, "a phase III requires a large number of patients and I don't know that we could afford it at this point."
Still, phase III trials remain a long-term objective, and Wright said that the need for partnerships is not a pressing one.
“We receive financing from the Zeltia Group, and that allows us to do a bit more than the average company of our size,” she noted. “It is still something we are considering, but nothing is finalized.”
Wright added that, in the end, waiting until positive phase II data had been obtained “might be a better moment” to strike a deal as it would allow Sylentis to obtain better terms than if it were partnering an earlier-stage drug candidate.