Genetic Engineering & Biotechnology News

JUL 2017

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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Page 27 of 45

26 | JULY 2017 | | Genetic Engineering & Biotechnology News take a different approach to half-life ex- tension. These companies have developed peptide prodrugs that differ chemically but share the characteristic of undergoing cleav- age under physiologic conditions at a steady, predictable rate. Acendis' TransCon delivery platform has been applied to parathyroid hormone, human growth hormone, C-type natriuretic peptide, and ranibizumab (for treating macular edema). Several TransCon peptides for treating diabetes are in preclini- cal studies conducted by Sanofi. Similarly, Prolynx has developed self- cleavable linkers that undergo beta-elimina- tion to release native peptides either to gen- eral circulation or to macromolecular carri- ers such as polyethylene glycol or hydrogels. The carriers retain the drug within the sub- cutaneous injection space, where the drug is released under controlled kinetics. "When you inject subcutaneously, the temperature and buffering capacities are con- stant, so you can design a chemistry system with known rate of cleavage," Dr. Rhodes notes. "That timeframe can be very specific." To prolong the circulating half-lives of proteins, peptides, and small-molecule drugs, Amunix deploys a technology that emulates PEGylation. Amunix' XTEN platform uses a soluble, chemically defined protein polymer and a recombinant fusion approach to cre- ate peptide-XTEN fusion molecules directly through conventional protein expression and without subsequent chemical modification. Dr. Rhodes dispels the notion that mod- ern peptide manufacturing occurs via solid- phase synthesis. He notes that Novo's GLP- 1-like peptides and insulins are made re- combinantly. PEGylation and modifications for albumin binding are added at the end. "Yields from solid-phase peptide synthesis are in the 20–30% range after purification," he notes. "Some solution-phase processes, such as AjiPhase from Ajinomoto, can get to larger molecules very quickly, and [with] high yield and purity." Delivering the Goods Drug delivery has been a fertile area for peptides as well as small-molecule drugs. Many involve devices. For example, Intarcia Therapeutic's Medici Drug Delivery System™ is a subdermal system compris- ing a matchstick-sized osmotic minipump, a formulation that stabilizes peptide drugs for at least one year, and a pump place- ment and removal tool. Once the pump is in place, extracellular fluid diffuses into the pump at one end through a semipermeable membrane. Then the fluid enters the osmotic engine, which expands to drive a piston at a controlled rate, forcing the drug out steadily and consistently through the other end of the device. The Medici pump holds enough drug to treat the patient for up to one year. Paul Feldman, Ph.D., who heads discovery and translational medicine at Intarcia, notes that the Medici pump is a versatile delivery platform: "It's suitable for many drug types, including peptides, antibody fragments, and even small molecules." The limitations are drug potency and, to a lesser extent, solubil- ity. Because the Medici pump is small, it can Economic & Robust Solution The NEW OXYPro Optical Oxygen Sensor Scan QR code for more information: Practical Solutions for Today's Bioprocess Challenges N I N T H A N N U A L A U G U S T 2 1 - 2 5 , 2 0 1 7 | B O S T O N , M A T H E W E S T I N C O P L E Y P L A C E Register Early and SAVE $400 off your Event Registration Peptide-Based Therapuetics Continued from page 24 Bioprocessing Drug Delivery Experts is a drug product development firm that specializes in the integration of complex formulations, delivery systems, and device technologies. With respect to peptide therapeutics, the firm works to combine sustained release (via formulation approaches) and sustained exposure (via conjugate approaches). As this image indicates, many conjugate approaches are available to developers interested in extending the half-lives of peptide drugs. The Medici Drug Delivery System is a matchstick- sized osmotic minipump that is placed just under the dermal layer of the skin to deliver a continuous and consistent flow of medication. This system, which was developed by Intarcia Therapeutics, allows for proteins, peptides, antibody fragments, and other highly potent small molecules to be stabilized at or above human body temperatures for three years or longer.

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