How Aro Biotherapeutics Is Advancing Genetic Drugs Supply

questions and answers

Aro Biotherapeutics’ genetic medicine platform uses Centyrin, an artificially produced human protein, to more precisely target and treat diseased muscle and immune cells.

Sue Dillon (left) and Karyn O’Neil. Photos courtesy of Aro Biotherapeutics

NextUp is a weekly NextHealth PHL feature that highlights the local leaders, organizations, and research that shape the Philadelphia area’s life sciences ecosystem. E-mail [email protected] with parking spaces for NextUp.

WHO: In 2018, Susan Dillon and Karyn O’Neil – two former Janssen Pharmaceuticals executives – believed they had technology that could transform and advance genetic drugs. This technology, which O’Neil developed while working for the Johnson & Johnson subsidiary, targeted RNA-based gene drugs at the “right place” in the body: the diseased gene itself. In the same year, the two secured an exclusive worldwide license for the novel gene targeting platform from Janssen and co-founded their own company Aro Biotherapeutics.

What: Aro Biotherapeutics, based in University City, is a biotechnology company focused on “creating a new class of therapies that modulate gene expression so we can modify potentially defective genes that cause disease,” said O’Neil. Rather than using monoclonal antibodies (which are not as direct or precise in their targeting) as treatment, Aro uses an RNA-based approach to target disease-causing genes and target muscle cells and immune cells.

They do this with their proprietary human protein, Centyrine, which is super small, ultra stable, and highly soluble. Dillon says that centyrine is not only stable inside and outside the cell, but is also selective and efficient, and binds to receptors on cells in need of treatment.

When: In the first three years of operation, Aro has optimized its technology to pave the way for early drug candidates. They compiled data to show that Centyrine can successfully target various RNA-based therapies in animal models. In preclinical tests, Aro showed that centyrine can reduce a relevant target gene in skeletal muscle that is important in rare genetic muscle diseases. In addition, they found that the effect on the target gene is permanent, with an observable reduction four weeks after a single dose.

In January 2020, Aro partnered with Ionis Pharmaceuticals to develop a pipeline of selective drug targets based on centyrine. Just five months ago, Aro closed its Series A funding and raised $ 88 million in seed funding. Dillon says this will allow Aro to get its first molecules into the clinic later this year and eventually demonstrate a proof of concept in human studies – one for genetic muscle disorders and the other for immune disorders.

What it means: The two biggest challenges with genetic drugs, according to Dillon, are that some are not particularly stable in the blood and accumulate in vital organs, namely the liver and kidneys. “If you have a disease where you want to take genetic medicine to another tissue, it can be difficult because most of them don’t get to where they’re supposed to be on their own,” says Dillon. “That is only possible if the drug is injected directly into the diseased tissue.” Aro’s targeting mechanism helps to transport genetic drugs into certain cells, especially those that are not liver-based.

Why it matters now: Centyrine is classified as an oligonucleotide – a short strand of RNA that can be engineered to recognize defective genes and alter the genetic message encoded by those defective genes. According to O’Neil, the challenge with oligonucleotides in the past has been getting them to the actual location of the disease. Therefore, Centyrin from Aro works to recognize certain cells and to bind them chemically to oligonucleotides. In this way, Aro directs the oligonucleotide to the correct cellular address (like a GPS does a car) to overcome the oligonucleotide delivery problem.

Additionally, Dillon says their technology platform is versatile when it comes to disease type. “I see our technology as a whole new approach to treating a range of diseases that require precise and targeted therapy,” says Dillon. “I believe that once we have really optimized our technology, we can use it on multiple gene targets that will potentially help treat a wide variety of diseases.”