History of Berlirem

• In 2014, Berlirem GmbH was founded. The company followed the aim to improve and optimize the treatment of Parkinson´s Disease (PD) with L-DOPA (LD). The marketed therapies did not meet the aim to reach a constant dopaminergic stimulation (CDS) in patients. The approach of Neuroderm to administer L-DOPA as a subcutaneous solution (2013) was judged as unsuitable because of narrow restrictions of drug solubility, local tolerance and patient´s acceptance. Berlirem decided to invest into research of patentable, highly water-soluble LD-esters.
• The primary explorations centered around a Glycerol-LD ester and Penta-Erithrol-LD ester, alongside other polyalcohol LD-esters. A collaboration with Innovent (Jena) was established.
• From 2018 to 2020?, Berlirem entered a license agreement with Britannia, aiming to develop highly soluble LD esters for subcutaneous infusion to ensure CDS in PD patients. Meanwhile (and as expected by the Berlirem team), Neuroderm had to modify its developmental system: two sc-infusion sites and the reduction of carbidopa (CD) for tolerance improvement were needed. The LD/CD mass ratio was 8:1. Another player in this area was ABBVIE, who
published first results with ABBV-951 in 2019. With a mixture of phosphate esters of L-DOPA and carbidopa the company claimed that higher LD levels were achieved by subcutaneous infusion of the phosphate esters due to an apparently better skin tolerability.
• After separation from Britannia, Berlirem developed a system of small voluntary clinical-PK studies for rapid selection of the development candidate and for other decisions in terms of decarboxylase (AADC) and COMT inhibitors. During this program we selected Penta-LD as development candidate (over Gly-LD), determined the relative potencies of Benserazide and Carbidopa, quantified the LD-bioavailability add-on of Opicapone (OC) and calculated the half-life increases after AADC-inhibition.
• On basis of the accumulated know-how, Berlirem established an optimized treatment schedule for CDS suited for all grades of PD. The system consists of sc-infusion of LD using the known Arginine formulation. The daily LD doses were much lower than in the products of Neuroderm or ABBV-951 and thereby circumvents skin tolerance problems. The dose lowering effect is achieved by an optimized AADD-inhibition (dose and dose distribution).
• The new treatment scheme was patented (IP)
• The new, and patented treatment scheme opens the chance to combine Foslevodopa (FLD) with the optimized AADC-inhibition method for a new product, because FLD is not protected by a patent. Only the combination of FLD and Foscarbidopa (FCD) is patent protected. But FCD is not needed ac sc-infusion drug when the optimized AADC-inhibition would be applied.
• In 2023, the patent for BER-203 was granted, entering the PCT phase. Berlirem initiated a search for (strategic) partnerships to further advance its innovative endeavors.