- 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.
Madrid, March 14th, 2022.- 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%[i],[ii].
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.
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Headquartered in Madrid, PharmaMar is a biopharmaceutical company, focused on oncology and committed to research and development which takes its inspiration from the sea to discover molecules with antitumor activity. It is a company that seeks innovative products to provide healthcare professionals with new tools to treat cancer. Its commitment to patients and to research has made it one of the world leaders in the discovery of antitumor drugs of marine origin.
PharmaMar has a pipeline of drug candidates and a robust R&D oncology program. It develops and commercializes Yondelis® in Europe and has other clinical-stage programs under development for several types of solid cancers: Zepzelca® and ecubectedin. With subsidiaries in Germany, Italy, France, Switzerland, Belgium, Austria and the United States. PharmaMar wholly owns other companies: GENOMICA, a molecular diagnostics company; Sylentis, dedicated to researching therapeutic applications of gene silencing (RNAi). To learn more about PharmaMar, please visit us at pharmamar.com.
Sylentis is a pharmaceutical company that develops innovative therapies based on gene silencing technologies or RNAi. This technology enables the design of molecules capable of selectively inhibiting the synthesis of disease-causing proteins. Sylentis has developed numerous therapies based on this novel technology and currently has a strong program in ophthalmology with one candidate in Phase III clinical trials: tivanisiran, for the treatment of dry eye. Sylentis is also researching and developing other new products for the treatment of various eye diseases such as ocular allergies and retinal diseases. For more information, visit www.sylentis.com.
SYL1801 is an RNAi-based drug administered as eye drops that selectively inhibits NRARP receptor production. NRARP, by regulating the Notch and Wnt signaling pathways in endothelial cells, plays an important role in the control of choroidal neovascularization. SYL1801 is a synthetic small double-stranded RNA (siRNA) oligonucleotide that acts through a highly selective mechanism of action. Non-clinical studies conducted by Sylentis with SYL1801 have demonstrated high capacity to inhibit this target specifically. The reduction of its expression in the retina, observed in animal models, correlates with vessel regression and decreased retinal vascular growth following topical administration.
SYL1801 is a product under development to treat age-related macular degeneration, with potential for development for other pathologies involving choroidal neovascularization.
About RNA interference (RNAi)
RNA interference is a technology that seeks to reduce abnormal protein production by silencing messenger RNA. RNAi represents a breakthrough as a new mechanism of action to address numerous pathologies. Some pathologies, such as age-related macular degeneration, are caused by an alteration of certain proteins. This technology can act by reducing or controlling in a very specific way the production of the proteins involved in each pathology. Compounds based on RNAi technology tend to have a longer effect than traditional drugs and few side effects, due to their high specificity.
[i] Deng, Y., et al., Therapeutic potentials of gene silencing by RNA interference: principles, challenges, and new strategies. Gene, 2014. 538(2): p. 217-27.
[ii] 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.