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 LD as a subcutaneous solution (2013) was judged as unsuitable because of narrow restrictions in terms of drug solubility and local tolerance.
• Berlirem decided to invest into research of patentable, highly water-soluble LD-esters.
• The primary explorations centered around a Glycerol-LD ester (Gly-LD) and Penta-Erithrol-LD ester (Penta-LD), alongside other polyalcohol LD-esters. A collaboration with Innovent (Jena) was established.
• In 2018, Berlirem entered into a license agreement with Britannia, aiming to develop highly soluble LD esters for subcutaneous infusion to ensure CDS in PD patients. Meanwhile – as expected – Neuroderm had to modify its developmental system: two sc-infusion sites and a dose reduction of carbidopa (CD) were needed for tolerance improvement. The LD/CD mass ratio was increased to 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 LD and CD the company claimed that higher LD levels were achieved by subcutaneous infusion of the phosphate esters. The higher skin tolerability of the water-soluble esters enabled higher LD-equivalent doses.
• After separation from Britannia in 2020, Berlirem developed a system of small voluntary clinical-PK studies” to speed up development processes including the selection of a candidate. In addition, the single and combined effects of amino acid decarboxylase (AADC) and catechol-O-methyl-transferase (COMT) inhibitors on the metabolic clearance of LD were studied. During this program we selected Penta-LD as development candidate (over Gly-LD), determined the relative potencies of Benserazide and Carbidopa, quantified the add-on of Opicapone (OC) to the LD bioavailability 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 circumvented skin tolerance problems. The dose lowering effect is achieved by an optimized AADC-inhibition (dose and dose distribution).
• The new treatment scheme was patented (IP)
• The new, and patented treatment scheme opens the chance to also combine Foslevodopa (FLD) with the optimized AADC-inhibition method for a new product, because FLD is a free compound. Just the combination of FLD and Foscarbidopa (FCD) is patent protected. However, FCD is not needed as a sc-infusion drug when the optimized AADC-inhibition is applied.
• In 2023, the patent for BRM-203 was granted, entering the PCT phase. Berlirem initiated a search for (strategic) partnerships to further advance its innovative endeavors.