Many of the change agents I have seen in 2019 are derived from changes in regulatory law, commercial downscaling, and impact from patent expiry strategies. The largest external regulatory change came from the issuance of the long-awaited EMEA Annex I, clarifying which technologies are required and acceptable, when and why.
The change in operational focus, from clinical scale-up to commercial scale-down, is enabling use of smaller, modular, flexible fillers with self-contained isolators. In parallel with the approval of biosimilars and biobetters, there is strong industry focus on individualized micro-batches, for CAR-T solutions and gene therapy products. The use of process automation and robotics have increased in all fill-finish unit operations. Widespread implementation of ready-to-use/ready-to-sterilize components and single-use (SUT) in upstream and downstream (SUS) through final fill designs have changed how facilities are planned, reducing plant size and changing warehouse space to accommodate densely packaged plastics goods.
Filling modalities have also been changing; bags that can be mated to lock-luer fittings with pre-sterilized needles and blow-fill-seal/form-fill-seal are re-emerging as processes that offer potential unit cost reduction. Traditional vial and syringe container designs are also changing as suppliers improve standardize offerings while having options including clear plastics.
The most exciting technological or scientific advancement that has influenced our business strategy in 2019 is our novel epigenetic regulator program. Unlike gene therapies, which target and modify DNA directly by inserting specific genes into patient’s cells, epigenetic regulators control or modify gene expression through processes that do not alter the sequence of DNA directly. Our lead asset DUR-928 is a small endogenous molecule that plays an important role in regulating cellular functions such as lipid homeostasis, inflammation and cell survival, crucial pathways involved in many acute and chronic diseases. DUR-928 has shown positive results in a phase IIa trial for the treatment of alcoholic hepatitis, a devastating acute condition with high mortality rates and limited therapeutic options. We are also advancing programs in other indications that could benefit from DUR-928, such as non-alcoholic steatohepatitis (NASH) or psoriasis. We believe that epigenetic regulation is a powerful and untapped treatment approach for many challenging diseases.