information: Presentation of results at a congress
Announcement: presentation of results at the ARVO 2017 Annual Meeting
Company: Pharmaleads (France)
mechanism: enzyme inhibitor/dual enkephalinase inhibitor. PL265 is a Dual Enkephalinase Inhibitor (DENKI). Enkephalins are endogenous pentapeptides with morphine-like activity. They are degraded by two enzymes, the enkephalinases NEP and APN, from the zinc-metallopeptidase family. Drugs called DENKIs are able to improve pain management by increasing the local concentrations of enkephalins, inhibiting the two enzymes responsible for their degradation.
Disease: ocular pain
area: Ophtalmological diseases
- On May 12, 2017, Pharmaleads announced positive efficacy and safety results of PL265, a novel Dual ENKephalinase Inhibitor (DENKI), in a preclinical study for ocular pain. This study was conducted in collaboration with The Vision Institute in Paris, France, and assessed the anti-nociceptive effect of PL265 in experimental models of ocular pain / dry-eye syndrome. This preclinical study evaluated both mechanical and chemical cornea sensitivities of experimental models in response to corneal injury and inflammatory pain after being treated twice a day with a drop of either PL265 (at a 10 mM concentration) or of phosphate-buffered saline (PBS) in the right eye for five days.
- These results were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2017 Annual Meeting in Baltimore on May 11, 2017, showed that topical instillation of PL265 significantly increased the corneal mechanical threshold on day 5 compared to PBS-treated in corneal injury models (49.00 ± 4.58 mg vs 29.60 ± 4.43). In inflammatory pain models, topical PL265 showed potent anti-nociceptive effects and models treated with PL265 exhibited an increased mechanical threshold at day 5 (61.00 ± 14.70 mg vs 24.00 ± 4.00 mg).
- In addition, the palpebral closure time induced by topical capsaicin (100 ?M) was significantly decreased after PL265 treatment, in both corneal (97 vs 201 seconds) and inflammatory pain (70 vs 170 seconds) models. In non-operated models (without corneal injury), topical instillation of PL265 for 5 days did not alter the ocular surface or corneal mechanical sensitivity compared to PBS-treated models.
The results of this study provide the first evidence that PL265 is highly effective in decreasing ocular pain after various experimental corneal lesions and also brings to light novel anti-inflammatory properties of the drug. It also proves that the drug has no anaesthetic properties in the absence of corneal injury.
Pharmaleads is looking for a partner to support the development of PL265 in the ophthalmology field. The company is also developing an oral formulation of PL265 for the treatment of neuropathic pain. PL265 has completed Phase I single ascending dose (SAD) clinical trials and demonstrated good safety and tolerability. Pharmaleads anticipates to start a Phase I/IIa clinical trial with PL265 in ocular pain in 2018.
- • On May 5, 2017, Pharmaleads announced that a poster presentation on its Dual ENKephalinase Inhibitor (DENKI) PL265 has been accepted for presentation at the upcoming Association for Research in Vision and Ophthalmology (ARVO) 2017 Annual Meeting which is being held from May 7th - 11th, 2017 in Baltimore, US. The poster session is entitled « Dual enkephalinase inhibitor (DENKI) PL265: a novel topical treatment for ocular pain? ». It wil be presented on May 11, 2017. The data being presented assesses the anti-nociceptive effect of PL265 in experimental models of corneal pain.