By Jonathan D. Grinstein, PhD
Helge Zieler, PhD, believes in the promise of biologic and genetic medicines. But for any new medicine based on nucleic acids or proteins, it’s all for nothing if the biomolecule cannot be made after conceptualization and all the way through clinical trials and commercialization.
“As new drug modalities or vaccine formulations are discovered, their manufacturing is an issue that needs to be addressed right from the beginning,” said Zieler. “If it’s not, a company may spend [millions of dollars] developing that, and then they run into a manufacturing problem and can’t move it forward.”
The development of state-of-the-art discovery and production systems for protein and nucleic acid medicines is exactly where Zieler is calibrating his newly formed company, Primrose Bio, where he will serve as CEO.
According to Zieler, “Primrose Bio can come in and help drug companies address the manufacturing concerns and challenges of new drug active ingredients in the early stages of the development of these modern and complex protein and nucleic acid medicines.”
Primrose Bio is the result of a merger between two companies, Primordial Genetics and Pelican Technology Holdings, which specialize in developing biological manufacturing systems for nucleic acids and proteins, respectively.
“The pairing is unique and exciting to us because we think we can attack a broad panel of products in the pharma industry, and we can also enable the discovery of novel pharmaceuticals,” said Zieler.
As part of the transaction, Ligand Pharmaceuticals has contributed $15 million in funding, which Zieler said will be used to continue and, in some cases, expand existing programs from the merging companies and to provide the resources to create novel production manufacturing options for complex pharmaceuticals.
Order of the Pfenex
Zieler created Primordial Genetics as a synthetic biology company focusing on developing technology for improving microbes and enzymes and leveraging that capability to work on improved mRNA manufacturing solutions to facilitate the development of drugs like the COVID-19 vaccines, which are riddled with challenges. The manufacturing of mRNAs is very template-specific, with parameters that facilitate the translation of an mRNA because of bespoke elements in each template and each drug formulation.
“It’s not one size fits all,” said Zieler. “You have to develop dedicated manufacturing systems that are centered around RNA polymerases for each mRNA. What we bring to the pharma industry is a panel of polymerases that can handle different templates, lengths, challenging sequences, and cap analogs that need to be incorporated and the ability to produce these active mRNAs at a good yield and high quality so that the manufacturing costs are manageable.”
Zieler seized the chance to collaborate with Pelican, formerly known as Pfenex, which Ligand acquired in 2020 because they had developed a platform for producing therapeutic proteins that was second to none in the biotechnology world. With the combination of protein and nucleic acid manufacturing systems, Primrose Bio has a promising future for genetic medicines and mRNA vaccines.
“[Ligand] thought that paired with [Primordial Genetics], this could make a good combination that would receive traction in the markets and traction among investors,” said Zieler. “Since March of this year, we have been in intensifying merger discussions to bring these two entities together and launch a new standalone privately owned company, Primrose Bio, that works on the manufacturing systems and develops manufacturing systems both on the nucleic acid side where Primordial was and on the protein side where Pelican was. This is one of the best combinations of technologies currently in the biotechnology world around us.”
The new perennial
This merger to form Primrose Bio isn’t just bringing two companies under one roof that will remain siloed; rather, the intent is to cross-pollinate as much as possible. The Pelican Expression Technology platform—utilized by leading pharmaceutical companies including Merck, Jazz Pharmaceuticals, Alvogen, the Serum Institute of India, Arcellx, and others—will help Primrose make the enzymes for nucleic acid production. While these enzymes have been developed in Primordial Genetics, producing them is not Primordial Genetics’ specialty. Primordial Genetics will be able to use Pelican’s protein expression technology to enhance and efficiently produce their current products, such as their RNA polymerase. The RNA polymerases—enzymes used to synthesize the mRNA in novel vaccines and therapeutics are key for producing nucleic acids that do not trigger immune responses and that ribosomes can translate very effectively.
According to Zieler, the synthetic biology knowledge coming from the Primordial Genetics side will improve and upgrade Pseudomonas fluorescens, the production organism that is the foundation of the Pelican Expression Technology platform. Also, Primordial Genetics will develop its nascent technology around the enzymatic synthesis of oligonucleotides of all sizes.
“The pharma industry already employs these [oligonucleotides] in drugs as active ingredients, for example, RNAi-based drugs,” said Zieler. “The pharma industry is trying to move away from chemical manufacturing because it’s dirty and restricts their ability to build manufacturing plants.”
Zieler said that it is the pharmaceutical industry’s dream for RNAi or other types of genetic medicines to be manufactured enzymatically. If Primrose can solve this problem, this could break the bottleneck in nucleic acid production and the challenge of keeping these processes from harming the environment.
Zieler is excited about the wonderful synergy of very complimentary technology that is both commercially and scientifically exciting. With the merger complete, the potential for new manufacturing technologies that enable 21st-century vaccines and therapeutics really starts once the combined teams get their hands dirty in their new digs in San Diego and start collaborating, innovating, and combining the deep experience and track record of both sides into a new vision of biotechnology products.
