Advancing Development and Manufacturing of Microbiome-Derived Therapeutics (BIO 2024)

At BIO 2024 in San Diego, Calif., which was held on June 3–6, Pharmaceutical Technology® Group’s Chris Spivey spoke with Aaron Cowley, PhD, chief technical officer and co-founder, Captozyme, and chief scientific officer, ReciBioPharm, the biologics unit of Recipharm following a spate of acquisitions (1–3).

The age of the microbiome, according to urban legend, was ushered into existence when Francis Collins, head of National Institutes of Health (NIH) (on a “nano-sabbatical” to the Broad institute), was discussing with Eric Lander the probable slowdown in funding the sequencing of “simply more organisms” for the sake of keeping infrastructure and technology refinements going. In that discussion, Collins suggested that the hitherto unheralded organism surrounding and living within the already sequenced organisms should provide significantly valuable biological data about both the disease states, as well as the underpinnings of good health, within said organisms.

Fast forward to today, and the field of microbiome research has dramatically matured, alongside the processes, analytical development, and manufacturing of living biological products (LBPs) that have, in many ways, become an end result of this line of inquiry. The potential of this therapeutic class concomitantly gives rise to the need for specialized support to develop and manufacture microbiome-derived therapeutics and has led to a rise in companies providing LBP-related solutions. As stability of product and reproducibility of manufacturing processes have become more standardized, the regulatory support environment and guidance has, of necessity, been playing catchup. This is in large part due to LBPs’ unique mechanisms of action and the absence of well-established precedents—and, also, a deeper understanding of the interaction between well-characterized administered microbial strains and host microbiome.

As a chemist by training Aaron Cowley, PhD, chief scientific officer, ReciBioPharm, became interested in the relationship between enzymes and microbes and the products of those interactions. In the interview, Cowley stated that “As a bio-factory the redox potentiometry of microbes is an important element to microbes andtheir function”. He continues to explain how gut microbes “regulate your body”.

“The microbiome keeps you in homeostasis. If you have too much extra sugar, the microbiome will shift upwards to be able to degrade that sugar. And if you have too much of other food types, it will shift downwards. Most CDMOs [contract manufacturing and development organizations] work with E. coli [Escherichia coli] and yeast that love air and need oxygen. There [are] very few [microbe species] [for whom] oxygen is actually a four letter word. So, being able to do tech transfer and train people has blossomed into its own field. There are a few hundred microbiome companies now, and it’s a challenging field because there are trillions of organisms in the gut, and their functions all vary. So, being able to pull out a few organisms to show cause-and-effect in disease is like trying to find life in the universe. It’s quite daunting,” Cowley explained.

Despite this, and while automating and optimizing manufacturing remains a priority, Cowley is enthusiastic about the rapid evolution of advanced therapy medicinal products in general and how, in some ways, the combined and overlapping lessons are helping provide new and more powerful insights. These individual-patient-by-individual-patient data streams, when seen from a pattern-recognition prism, can be combined to reflect back on or give the ability to both understand and deliver a more personalized approach to medicine.

References

1. Arranta Bio. Arranta Bio Announces the Acquisition of Captozyme, Creating a Center of Excellence for Microbiome Development and Clinical Supply. Press Release. Nov. 13, 2019.
2. Recipharm. Recipharm Acquires Arranta Bio, a CDMO Leader in Advanced Therapy Medicinal Products (ATMPs), to Expand Its Biologics Offering in the US. Press Release. Feb. 18, 2022.
3. Recipharm. ReciBioPharm: Biologics. recipharm.com/recibiopharm (accessed Oct. 3, 2024).