A biotechnology company has re-invented how biologic drugs are invented by using the patented technology to use the food algae spirulina to deliver therapeutic proteins.
The technology has unlimited potential for developing biologic drugs for highly prevalent diseases such as C. difficile infection, norovirus, and traveller’s diarrhoea.
To learn more, Digital Journal spoke with Lumen Bioscience Co-Founder and CEO, Brian Finrow.
Digital Journal: What types of bacteria is spirulina composed of?
Brian Finrow: When people buy spirulina in the grocery store or smoothie bar they think of it as an algae, but in fact is technically classified as a cyanobacterium. Its taxonomic name is Arthrospira platensis.
DJ: How did the research lead to spirulina being a source of therapeutic proteins?
Finrow: Researchers have known since the 1980s that spirulina would be a great biomanufacturing host—including for the kinds of applications we’re pursuing now. But despite heavy investments by many research groups, it resisted all prior attempts at genetic engineering.
Lumen scientists were the first to crack that long-standing barrier. Once that was done, we started looking around for useful applications. To our surprise, we discovered that there is actually a very robust literature on orally delivered therapeutic proteins, although most people are unaware of it.
If you compare our current development pipeline against that prior research there are many overlaps. For example, prior researchers have already demonstrated that oral protein therapeutics can improve outcomes in C. difficile infection, inflammatory bowel disease, infant diarrheal disease, and kidney stone disease. These studies go back to the 1980s.
We prioritized C. difficile infection because it is a horrific disease that afflicts millions each year and costs our health care system dearly.
DJ: How straightforward are spirulina organisms to grow and harvest? What were the challenges?
Finrow: This is a major advantage of the platform. Every aspect of growth and harvest is remarkably simple compared to the three main conventional biomanufacturing systems (E. coli, Chinese hamster ovary cells, and yeast). All those conventional system require sterility, complex growth media, and expensive downstream purification.
By contrast, spirulina grows in salt water with LED lights (no sugar feedstock) and it does not require sterility or (for oral delivery) downstream purification. In fact, grocery-store spirulina is actually grown outdoors in gigantic ponds frequented by spiders, insects and migratory birds. This gives a sense of how easy it is to grow and harvest spirulina.
Of course, our products are therapeutics intended for treating very serious diseases so we carry out our production in doors, under fully controlled conditions. But it is still 1000% easier than conventional biomanufacturing.
DJ: How does the Lumen platform operate?
Finrow: It is very simple. We have indoor production tanks that we fill with city water mixed with about a dozen mineral salts. To this we simply add a small amount of engineered spirulina cells from our cell banks (inoculum) and turn on the LED lights.
The cells grow and divide until they reach a certain density. Then we harvest the entire mixture and dry it in a spray-drier. This same machine is used to make powdered milk, so its simplicity and scalability match that of the upstream growth system.
In short, all aspects of the production system are incredibly simple and scalable. This allows us to focus all of our time and effort on finding the very best therapeutic proteins for diseases we’re working to treat.
DJ: What types of biologic drugs are being developed?
Finrow: Our most advanced clinical program (LMN-201) targets C. difficile infection. This is a bacterial infection of the gastrointestinal tract that costs the U.S. healthcare system between $5 and $8 billion per year in direct expenses, with 12-week mortality rates in certain populations approaching 10%. It is a horrific disease.
LMN-201 is comprised of four therapeutic proteins. Three of these are antibody-like proteins that bind and neutralize the bacterial toxin that mediates pathogenesis in humans (called TcdB). The fourth is an enzyme that directly degrades the C. difficile cell while leaving the healthy commensal bacteria alone. It is a potent one-two punch.
The choice of therapeutic protein for each program is unique, however, because every disease is unique. Other classes of therapeutic proteins in our pipeline include peptides, cytokines, and other classes of enzymes.
DJ: What are the main challenges during manufacturing?
Finrow: The production system is so simple, there are few challenges to daily operation.
The main challenge we face right now is simply the fact that we are running so many clinical trials, with so many different therapeutics, that it creates a lot of complexity for the manufacturing team in keeping everything straight. We’re building out a second GMP suite right now to alleviate this.
In the longer term, we are working on another important goal right now. For products like LMN-201 that are primarily intended for developed world applications, the cost only needs to be between around 100x cheaper than conventional biomanufacturing systems. Cost-wise, we are already where we need to be for those applications.
But for certain developing-world applications, we want the costs to be even lower: 100x to 1,000x cheaper than conventional biomanufacturing systems. For example, with Gates Foundation support we are developing an oral antibody cocktail to prevent the infant diarrheal diseases that still kill hundreds of thousands of kids every year in the developing world. The Foundation’s cost target is audacious: just $10 for a 90-day supply. We are not quite there yet—it will take significant economies of scale—but I’m proud to say that we are on track.
DJ: For your medication against Clostridioides difficile, how straightforward was it to obtain regulatory approval?
Finrow: For this program we have obtained regulatory clearance to run clinical trials in both Australia and the United States. It was straightforward in both cases.
DJ: What is next on the horizon?
Finrow: Our main focus right now is getting our first product onto the market and building out the commercial infrastructure to launch—first in the U.S. and then worldwide.
