If Lumen Bioscience achieves its goals, patients will be able to take its drugs the same way some people supplement breakfast: a spoonful heaped onto a bowl of cereal or mixed into juice. The startup harnesses spirulina, protein-rich cyanobacteria touted by many health enthusiasts as a “superfood.”
Lumen CEO Brian Finrow acknowledges spirulina’s health benefits, but that’s not why his company embraces it. Seattle-based Lumen turns spirulina into tiny factories that churn out therapeutic antibodies. Finrow says the Lumen technology overcomes many of the challenges of working with cyanobacteria. Research has yielded a crop of gastrointestinal disorder drug candidates, the most advanced of which is on track to Phase II testing. Now Lumen has $16 million in financing to develop its biologic drugs that don’t need to be injected but instead are taken like food.
“Think of it as an edible drug,” Finrow says.
Image: iStock/Olivier Le Moal
Antibodies are designed to bind to an antigen on the surface of a target cell. That specificity spares healthy cells from side effects, which makes antibodies attractive as drugs, says Finrow, a former senior vice president at Seattle-based Adaptive Biotechnologies. But antibodies are large molecules—too big and complex to be made by chemical synthesis. Manufacturing them in a lab is time consuming and expensive, which limits the applications of these medicines.
Lumen builds on the work of co-founder Jim Roberts, a longtime scientist at the Fred Hutchinson Cancer Research Center. Earlier in his career, he was credited as a co-inventor of technology that coaxes mammalian cells into making monoclonal antibodies, research conducted at Columbia University. At Lumen, Roberts takes a similar approach to spirulina.
Engineering a food product to produce a biologic drug is not a new idea. Earlier efforts failed, mostly because it’s hard to produce enough of the biologic. If a patient must eat the equivalent of an acre of a crop a day to receive therapeutic benefit, it’s just not feasible as a drug, Finrow says. Spirulina has been grown at scale in the US since the 1970s, which means that it has a long track record and plenty of safety data, Finrow says. Furthermore, sprirulina is packed with protein so a little sprinkle goes a long way. The biggest challenge is figuring out a way to make those protein stores therapeutic.
Antibodies are proteins. Lumen gets spirulina to produce them by engineering the cyanobacteria’s genome. But the company doesn’t use CRISPR or some other gene-editing technique, which Finrow says would only make antibody production more complex and more expensive. The Lumen technology takes a gene that codes for a desired protein and inserts it into one or more designated locations in the spirulina genome. As spirulina grow and divide, they make the antibodies and pack them inside their cell membranes. Engineering also controls how much of a desired protein is produced in each cell.
Spirulina only need water and light to grow. The spirulina that’s sold by grocers and health food stores is grown in outdoor ponds, then dried. Lumen produces its spirulina much the same way, though it does so in a controlled 20,000 square-foot-indoor facility in Seattle’s Fremont neighborhood. The end product is a greenish powder of dead, desiccated cells.
“Once you solve the manufacturing problem, you can go after diseases,” Finrow says.
Traveler’s diarrhea is Lumen’s lead disease target. The company aims to prevent the condition from developing in the first place. The Lumen drug, a capsule filled with the green powder, is intended to be taken by a traveler once a day, Finrow says. In the gut, the cell membrane breaks down, releasing its antibody payload. Those antibodies stand ready to bind to and neutralize toxic bacteria they encounter. The antibodies and pathogens are then swept from the gastrointestinal tract with bodily waste. In Phase I testing, the drug candidate was shown to be safe and well tolerated by patients. It’s now being readied for a Phase II test expected to start in early 2021.
The FDA initially didn’t even require a Phase I test, partly because of spirulina’s long safety record as a food product, Finrow says. The door was also open to pursue spirulina as a medical food, an FDA designation for products intended for dietary management of a disease. Finrow says Lumen opted to conduct clinical trials and develop its products as drugs because the company wanted to generate data about its candidates. He adds that winning FDA approval of Lumen’s products as drugs should give patients more confidence in their therapeutic benefits.
Lumen’s pipeline includes candidates for norovirus and Clostridioides difficile infection, both of which the company aims to neutralize in the gut. Though norovirus might best be known for outbreaks that have occurred on cruise ships, Finrow says this virus is also a problem in nursing homes. There are no FDA-approved norovirus therapies or vaccines.
A number of companies are developing therapies for C. diff, notably Cambridge, MA-based Seres Therapeutics, which recently reported positive Phase III data for its capsules of live spores intended to treat the infection by restoring the gut microbiome to a healthy balance. Finrow acknowledges Seres’s progress but adds that Lumen could offer a scalable alternative to the expensive process of manufacturing live biological therapeutics.
Skin diseases and respiratory conditions are next on Lumen’s list of potential applications. Finrow says they’re an extension of the company’s current research. Like the gut, the lungs and the skin are regarded by the immune system as external because all three interface with aspects of the outside world. The company hasn’t publicly disclosed which skin and lung conditions it aims to treat, but Finrow says the ones investors ask about most include wound healing and influenza.
The Lumen technology has potential applications beyond human health. The ability to make massive amounts of biologic molecules could apply to the production of microbes used in manufacturing plant-based meat alternatives, Finrow says. The technology could also be used in animal health products. Lumen isn’t pursuing those opportunities on its own, but Finrow says the company is open to talking with partners interested in exploring such applications.
Biofuel is one application the company won’t pursue. While the Lumen technology can be used to make alternative fuels, Finrow says it’s probably not economically viable. Sapphire Energy and Joule Unlimited stand as examples of startups that raised hundreds of millions of dollars to develop their synthetic biology approaches to biofuel production, only to find that plummeting oil prices made their products uncompetitive.
Lumen collaborators to date include the Bill & Melinda Gates Foundation, which has also contributed funding. The company has also worked with government agencies such as the National Institutes of Health and the National Institute of Allergy and Infectious Diseases, as well as academic institutions including the University of Washington, the University of Virginia, and Tufts University.
The cash infusion announced this week, a Series B round of funding, was co-led by new investor WestRiver Management and earlier investor Bioeconomy Capital. They were joined by other earlier investors Avista Development, Columbia Pacific, Lumen’s founders, and Seattle-area angel investors. The company says the new cash brings the total investment in the company to $68 million total. Finrow says the funding will support Phase 2 tests of the traveler’s diarrhea drug candidate, as well as plans to advance the C. diff and norovovirus candidates to clinical testing next year.