Date: 2016-03-10
Type of information: Milestone
Compound: inhibitors of protein-arginine deiminases (PADs)
Company: Evotec (Germany) Padlock Therapeutics (USA - MA)
Therapeutic area: Autoimmune diseases
Type agreement: collaboration
Action mechanism: Protein-arginine deiminases (PADs) catalyze the hydrolysis of peptidyl-arginine to form peptidyl-citrulline on histones, fibrinogen, and other biologically relevant proteins. They post-translationally modify proteins by converting arginine residues to the related amino acid citrulline. This process is called deimination or citrullination. Citrullination removes a positive charge from the protein surface, with the potential to affect protein structure and function. In some patients, citrullinated proteins are recognized as foreign by the immune system. In these patients, PAD activity is thought to produce the autoantigens that drive the development of autoimmune disease. The PAD family consists of five enzymes with varying tissue distributions. Proposed PAD functions include epigenetic control of gene expression, neutrophil extracellular trap (NET) formation and skin keratinization. Overexpression and/or increased PAD activity is observed in several diseases, including rheumatoid arthritis, Alzheimer's disease, multiple sclerosis, lupus, Parkinson's disease, and cancer.
Disease:
Details: * On January 7, 2015, Evotec and Padlock Therapeutics announced that they have successfully completed an initial goal in a programme focused on developing inhibitors of protein-arginine deiminases (PADs) and have further extended the collaboration that was first signed in January 2014. Padlock is a company that is developing medicines targeting protein-arginine deiminases (PADs), enzymes with an important role in the generation of autoantigens, inflammation and immune complex formation in autoimmune diseases. The collaboration initially began in January 2014 and now extends through March 2017. As part of the collaboration, Evotec provides a full range of research activities and expertise to Padlock including in vitro biology, high-throughput screening, structural biology, medicinal and computational chemistry and DMPK. Over the next period, Evotec and Padlock will progress multiple programmes through hit-to-lead and lead optimisation with the goal of delivering multiple development candidates.
Financial terms: Under the terms of the initial agreement, Evotec was awarded a success payment and equity grant in addition to research payments. In the next phase of this agreement, Evotec is eligible for over $ 13 m in research payments and milestones.
Latest news: * On March 10, 2016, Evotec announced the achievement of a key pre-clinical milestone in the ongoing alliance with Padlock Therapeutics. The programme focuses on developing inhibitors of protein-arginine deiminases (“PADs”), first-in-class compounds for autoimmune diseases such as rheumatoid arthritis and lupus. The milestone triggers a significant milestone payment to Evotec. The collaboration, now in its third year, could potentially extend through March 2017. Evotec and Padlock plan to progress multiple programmes through hit-to-lead and lead optimisation with the goal of achieving multiple development candidates. Under the terms of the initial agreement, Evotec was awarded the opportunity to earn success payments and an equity grant in addition to research payments totaling over $ 13 m.
