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Sylentis Eyes Second Part of Phase I/II Trial for Glaucoma Rx, Searches for Partners

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By Doug Macron

Having just wrapped up the first part of a phase I/II trial of its siRNA-based glaucoma therapy, Sylentis is on the lookout for a partnership deal that could help accelerate the drug candidate's development, a company official told RNAi News last week.

The drug, called SYL040012, is an siRNA targeted against adrenergic receptor beta-2 and delivered topically to the eye. According to Sylentis, it has demonstrated the ability to both reduce intraocular pressure and prevent glaucoma in animal models.

Although the company had originally expected to move the drug into human testing only in collaboration with a partner (see RNAi News, 3/29/2007), it later decided to go ahead on its own into the clinic with the support of its parent company, the Spanish pharmaceutical firm Zeltia (see RNAi News, 2/19/2009).

The first portion of that study, which was conducted in Spain and enrolled 30 healthy volunteers, began in September and was completed "a few weeks ago," Roberto Weinmann, the COO of Zeltia subsidiary Pharmamar, who handles business-development activities for Sylentis, told RNAi News last week.

"Safety was excellent and tolerability was excellent," he noted, adding that "we [also] have good indications of efficacy in healthy volunteers with high intra-ocular blood pressure."

Although phase I studies are not typically powered to evaluate efficacy, Weinmann said that phase I trials in glaucoma have "a very high predictive value for the success in phase III." He cited a 2008 paper in Eye describing a literature review that indicated that "early phase trials [in glaucoma] usually approximated the results of later regulatory studies and post-commercialization trials."

Currently, Sylentis is collecting the phase I data and preparing to report them to Spanish regulators, Weinmann said. Assuming a positive outcome of that review, the company expects to begin the second part of the study, which will evaluate glaucoma patients, by this summer, he said.

Thus far, the company is only planning to conduct the clinical trials in Spain, not only for financial reasons, but because "there is reciprocity in the European Union," where a drug that is approved in one country benefits from a streamlined regulatory process in other member nations, he noted.

Still, Sylentis would like to find a partner or partners for the program, both for Europe and the US, to help accelerate the glaucoma drug's development and provide the resources necessary for eventual phase III trials.

"If we had a partner, that would mean that we would have more funds and could continue with a trial in a much faster … fashion," while exploring the possibility of commercialization beyond Europe, he said. At the same time, "a phase III requires a large number of patients and I don't know that we could afford it at this point."

Weinmann said that Sylentis expects that it could carry the drug to the end of phase II development on its own before needing the help of a bigger ally. Nonetheless, the company is actively searching for a partner.

"There are contacts being made," he said.

Pipeline

Although Sylentis' glaucoma effort — its sole clinical-stage program — is its top focus, the company is also advancing a number of other drug candidates through the clinic, including a topical siRNA-based treatment for dry eye.

Weinmann said that the company is preparing an investigational new drug application for that agent, and expects to begin human testing in January. He declined to comment on the drug's target, but said that "we have very nice preclinical evidence of its efficacy."

Also in the pipeline are programs in Crohn's disease and ulcerative colitis, which are expected to use a proprietary oral delivery approach that he said is still in the early stages of development. He declined to provide details on the delivery technology, citing the competitiveness of the space.

Rounding out Sylentis' in-house drug programs are central nervous system-focused projects in cerebral ischemia and dementia, both of which are still in the research phase of development.

Weinmann noted that the company is developing an intranasal delivery technology for these because "the path to the brain from the nose is much shorter than others."

According to Sylentis, this approach also avoids issues of siRNA degradation associated with systemic delivery and the difficulty of passing the blood-brain barrier.

Weinmann also declined to comment on this technology because of its early-stage status.

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