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Spanish Start-Up Sylentis Hopes Eye, GI Programs Will Fly in RNAi Rx Space

Less than a year after it was spun out of Spanish biotech firm Zeltia, Sylentis is hoping to become a major player in the RNAi drugs field with programs in ophthalmology and digestive disease.

The company, which currently has five full-time employees focused on research and development, is also in the process of establishing a scientific advisory board  to help shepherd its lead drug compound — a treatment for glaucoma — through primate testing and into the clinic.

The firm also said it hopes to find a partner with clinical experience, and has been negotiating with an undisclosed US ophthalmology company.
According to Sylentis Vice President Catherine Moukheibir, the company was formally established as a wholly owned subsidiary of Zeltia early last year, but its core RNAi technology had been under development by another Zeltia unit, Genomica, since 2005.
“This is typically how we do things at Zeltia: We start spending a little bit of money on a low-key basis within one of the labs, and if something looks promising we will create a separate [unit], fund it, and recruit for it,” she told RNAi News last week.
After early research at Genomica proved promising, Zeltia created Sylentis to continue RNAi R&D in ophthalmology, with specific programs in glaucoma and dry eye, and gastrointestinal disorders, namely Crohn’s disease and ulcerative colitis.
The company also has an ongoing program investigating the potential of RNAi to treat neurodegenerative disorders and post-traumatic neural injury.
As its most developed program, however, glaucoma is the focus of much of Sylentis’ attention. Already, preclinical work has shown that a topically delivered siRNA drug can reduce intraocular pressure in rabbits, Moukheibir said.
With that work completed, “we are now working with [non-human] primates,” which should be completed by the end of the year, she said. She added that Sylentis hopes eventually to submit the primate data for publication in a peer-reviewed journal.
Although the primate work will take months to finish, Sylentis is already considering its options for moving into human testing, Moukheibir said.
“I think we would prefer to work with a partner because … you are talking about a significant capital investment and you are talking about a knowledge [of clinical development] that we, today, do not have,” she said. “We are talking already to one [undisclosed US] company in ophthalmology that could be interested in partnering with us, [but a deal depends] on what the terms are.”
Meanwhile, Sylentis’ Crohn’s disease program — its second most advanced — continues to move through mouse studies as the company explores various “non-invasive” delivery approaches for siRNA drug candidates, including a suppository-based system being developed in-house.
Sylentis is collaborating with researchers from Universidad Complutense de Madrid on both the glaucoma and Crohn’s disease projects.
Moukheibir declined to provide specific details on the delivery approaches being used in the two pipeline programs. She also declined to comment on the siRNAs being developed other than to say that Sylentis is exploring the use of modifications.
Additional details would be made available in journal publications, she said.
Some details, however, have already been made public in patent application filings.
For glaucoma, Sylentis has filed two international patent applications including PCT/GB2005050134, entitled “Treatment of Eye Disorders Characterized by an Elevated Intraocular Pressure by siRNAs.”

“This is typically how we do things at Zeltia — we start spending a little but of money on a low-key basis within one of the labs, and if something looks promising we will create a separate [unit], fund it, and recruit for it.”

Filed on Aug. 23, 2005, the application claims “sequences and protocols for treatment of eye conditions by use of RNA interference,” according to its abstract. “Target genes are selected from those responsible for aqueous flow or aqueous outflow, while particularly preferred conditions to be treated include glaucoma and uveitis.”
Sylentis also has a patent application pending with the US Patent and Trademark Office, No. 20060234970, covering the use of short interfering nucleic acids, such as siRNAs, to decrease expression of genes linked with intraocular fluid drainage.
The company also has filed a number of other patent applications with the WIPO, including PCT/GB2006050051, which covers the use of siNAs to treat intestinal disorders; and PCT/GB2005/050139, which covers the use of siNAs to inhibit a gene receptor associated with neuronal degradation.
Despite this patent application portfolio, Sylentis does not expect that it will have the freedom to operate in the RNAi space without licensing some third-party IP.
Moukheibir noted that her company is aware of IP estates controlled by the RNAi drug field’s two biggest players: Alnylam Pharmaceuticals and Sirna Therapeutics, which is now a subsidiary of Merck.
“We know about the InterfeRx program that Alnylam has, for example,” she said, referring to Alnylam’s IP out-licensing program established in 2003 (see RNAi News, 12/19/2003). “They know us, we know them, [and we] talk to them.
We’re conscious that there are important players in this field that we will have to deal with, and it’s fine,” she added. “We are on a collegial relationship with” those companies.
That said, Sylentis has not signed any licensing deals just yet, and when it may do so is unclear, Moukheibir said.
“I don’t think there is a decision on that yet,” she said.

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