SYL-1801

The plant, which has a surface area of 400m2, will serve both Sylentis' manufacturing needs and those of other pharmaceutical companies. Sylentis, a wholly owned subsidiary of PharmaMar (MSE:PHM), today inaugurated the first plant in Spain and the third in Europe for the manufacture of oligonucleotides approved under GMP (Good Manufacture Practice) standards at the Madrid Technology Park in Tres Cantos. Oligonucleotides are short chains of DNA or RNA that are manufactured by chemical synthesis and are the active ingredient of a new class of drugs. This plant is already functioning to meet the needs of both tivanisiran and SYL1801. These products, owned by Sylentis, are based on RNA interference technology. Tivanisiran is currently being evaluated in two Phase III studies for the treatment of dry eye disease and SYL1801, for the treatment of age-related macular degeneration. This plant, a pioneer in Spain, plans to provide services to other pharmaceutical companies that require the manufacturing and analysis of oligonucleotides. Currently, the demand for drugs based on RNA technologies is increasing and in Spain this need has not been met internally, depending instead on other countries. "This first plant in Spain is a milestone, not only for Sylentis, but also for the pharmaceutical industry in our country, as it will have the capacity to produce this type of next-generation pharmaceuticals, with the aim of making them available to patients to cover their therapeutic needs that have not been met so far," said Ana Isabel Jiménez, Director of Executive Operations and R&D at Sylentis. The inauguration was attended by Cristobal Belda Iniesta, General Manager of the Instituto de Salud Carlos III; Ana Isabel Cremades Rodríguez, General Manager of Research and Innovation and Technology of the Community of Madrid; Jesús Moreno García, Mayor of Tres Cantos; Ion Arocena, General Manager of ASEBIO, accompanied by José María Fernández, President of PharmaMar; Luis Mora, Managing Director of the PharmaMar’s Oncology and Virology Business Units and Ana Isabel Jiménez, Director of Executive Operations and R&D at Sylentis.

This trial involved 36 healthy volunteers who were administered eye drops for the treatment and/or prevention of retinal diseases, such as macular degeneration. This study provides evidence that SYL1801 is safe and well tolerated; therefore, the Phase I has met the primary safety endpoint. SYL1801 has been developed by Sylentis and is based on RNA interference (RNAi) technology. Sylentis, a PharmaMar Group Company (MSE:PHM), today announced the completion of the first Phase I study with its investigational compound SYL1801 for the treatment and/or prevention of choroidal neovascularization, a common cause of retinal diseases such as Age-Related Macular Degeneration (AMD) or diabetic retinopathy. The trial was conducted in 36 healthy volunteers with two treatment intervals: Single Ascending Dose (SAD) with one day of treatment, and Multiple Ascending Dose (MAD) with seven consecutive days of treatment. Four different ascending dose levels of SYL1801 administered once daily were evaluated, while the highest doses were administered both once daily and twice daily. All administered doses of SYL1801 in ophthalmic solution form were safe and well tolerated for the duration of the clinical trial. SYL1801 represents a breakthrough in the development of innovative drugs through gene silencing technology based on RNA interference (RNAi): its administration in the form of eye drops blocks the synthesis of the NRARP receptor (Notch-Regulated Antichiral Repeat Domain Proteins), which is involved in choroidal neovascularization (AMD pathology) and could change the paradigm of treatment of this disease. Ana Isabel Jiménez, COO and Research & Development Director at Sylentis, commented “the culmination of this phase I study is another step towards achieving a more effective treatment that is less disruptive and less painful for patients, since the drugs traditionally used for this type of ailment are antibodies. That is, large molecules that cannot reach from the ocular surface to the retina and are, therefore, administered by intravitreal injections.” The application of SYL1801 in the form of eye drops could be a new therapeutic option for the treatment of retinal diseases involving neovascularization processes. Age-Related Macular Degeneration (AMD) It is estimated that the number of individuals with AMD will reach 288 million in 2040. AMD is the leading cause of irreversible visual impairment in the elderly population of developed countries, accounting for 8% of all cases of blindness worldwide. The overall prevalence of AMD among 45-85 year olds is 8.7%1,2. Currently, neovascular AMD is treated with regular intravitreal injections of anti-VEGF agents, a very uncomfortable procedure for patients and a large financial and time investment for healthcare systems. 1 Deng, Y., et al., Therapeutic potentials of gene silencing by RNA interference: principles, challenges, and new strategies. Gene, 2014. 538(2): p. 217-27. 2 Jonas, J.B., C.M.G. Cheung, and S. Panda-Jonas, Updates on the Epidemiology of Age-Related Macular Degeneration. Asia Pac J Ophthalmol (Phila), 2017. 6(6): p. 493-497.