Lumen Bioscience – Using Well-Known Food Algae Spirulina to Deliver Therapeutic Proteins

The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter—a major cause of infant mortality in the developing world—prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms.

Lumen Bioscience is one such company that develops oral antibody therapeutics using spirulina. The astonishingly high cost of traditional drug development meant that using orally delivered biologics to address therapeutic targets in the GI tract and other topical sites wasn’t commercially viable. Researchers around the world have long suspected that spirulina would be a valuable tool for making biologic drugs if only it could be engineered, but these efforts failed for decades. That’s no longer true. Lumen’s patented biologic drug platform shortens the development process, reduces costs and risks, and accelerates time-to-market, making us the first company to make orally delivered antibody drugs commercially viable. Lumen was the first to achieve this breakthrough, and this in turn makes orally delivered biologics commercially viable for the first time.

Moving Fast to Save Millions of Lives

Lumen believes biologic drugs offer the fastest, safest and most effective way to treat many prevalent diseases that traditional biopharma tools have failed to solve. These cures are especially well suited to addressing the unintended consequences of antibiotics and to the developing world, where a lack of infrastructure makes traditional drugs unavailable to millions of vulnerable children and adults.

Treatment for Clostridioides difficile Colitis:  Traditionally considered a hospital-acquired infection, C. difficile is increasingly arising in the broader community. For this reason, the shelf-stable, orally delivered format of Lumen’s product is an important addition to the tool kit for treating and preventing this disease. Long-term consequences can include chronic diarrhea, severe intestinal inflammation, surgical resection, and death. Insidiously, the very thing that is used to treat this infection—broad spectrum antibiotics—is also the thing that causes the disease. C. difficile therefore appears at the top of the CDC’s antimicrobial threats list year after year, and in 2009 was estimated to single-handedly drive 2.3% of all US hospital costs.

Treating Covid (SARS-CoV-2): Covid-19 is widely known as a respiratory disease, but its GI symptoms are well documented. The now-famous ACE2 receptor is abundantly expressed on the cells lining the GI tract, and over half of Covid-19 sufferers show symptoms of GI distress, and up to a quarter show only GI symptoms. GI infection by the virus can have serious long-term effects, and high enteric viral loads are thought to contribute to fatalities from acute respiratory distress syndrome (ARDS) and wet-lung disease. Lumen’s Covid-19 product is designed to block GI infection and rapidly flush the virus from the GI tract, thereby reducing disease symptoms and potentially reducing transmission rates.

Treating Crohn's disease and ulcerative colitis: Inflammatory bowel disease (IBD) is a systemic autoimmune disease, but it has an obvious nexus with the gastrointestinal tract. The two main sub-varieties—Crohn’s disease and ulcerative colitis—have many available treatments on the market today, but it remains a major unmet medical need: current treatments are costly, require inconvenient injection delivery, and come with severe side effects. There are no approved therapies at all for mild-to-moderate Crohn’s. A safe, affordable, orally delivered drug to root out IBD at its source is a straightforward application of Lumen's technology, and would constitute a major advance for the field.

Treating Cardiometabolic Disease: Cardiometabolic disease (CMD)—a cluster of related conditions that includes obesity, diabetes, and cardiovascular disease—afflicts hundreds of millions of people worldwide, and the associated health and economic burdens continue to grow. An estimated 17.9 million people died from CMD in 2019, representing nearly a third of all global deaths. Of these deaths, 85% were due to heart attack and stroke. Today, over three quarters of deaths from cardiovascular diseases take place in low- and middle-income countries. Lumen is collaborating with Novo Nordisk, a global leader in CMD, to develop metabolically active molecules produced and delivered using spirulina.

Producing Daily, High-Dose Biologic Drug

In the traditional world of drug development it is commonplace for companies to spend many years and huge sums of money developing extraordinarily expensive drugs intended to help relatively small groups of patients. Lumen focuses on the rapid development of biologic drugs that will help hundreds of millions of people at costs far lower than previously thought possible.

The company designs and manufactures therapeutics against disease targets that have been inaccessible to the biopharmaceutical industry because of the astonishingly high cost of traditional methods. Now, for the first time, Lumen can make antibodies and other biologics at a cost that allows for daily, high-dose, oral and topical delivery. The company’s current programs target markets that are enormous, the treatment modes of action are well researched, and the unmet medical need is obvious.

How it works

The Organism: Being extraordinarily high in soluble protein, spirulina cells are able to express far higher amounts of therapeutic proteins than any other food crop (>60%).

Engineering: A gene encoding the therapeutic molecule (for example, an antibody) is introduced into the spirulina chromosome. When that strain of spirulina is grown, the cell manufactures the therapeutic protein and stores it away inside the cell.

Production: The production system requires only water, salt, CO2 and light, so it is cheap and rapidly scalable. Harvesting is done by spray-drying the biomass into a powder comprised of spirulina cells, each one filled with a therapeutic protein "payload." The entire process is done at its integrated Seattle lab and cGMP plant, which accelerates pre-clinical and clinical development.

Delivery: This powder can be packed into dose-specific capsules, which don't require refrigeration and are shelf-stable at room temperature. While the cells do not survive the drying process, the cell membrane protects the therapeutic proteins during transit through the stomach when orally delivered, and releases them in the small intestine where they can bind to and neutralize their disease targets.

The Visionary Leader Upfront

Brian Finrow is a Co-Founder and the Chief Executive Officer of Lumen Bioscience. He brings the skills and experience of a lawyer to a position that, in the biotech world, is more typically occupied by a scientist. This is essential to an enterprise like Lumen, which is rethinking drug development from the ground up to emphasize speed, efficiency and ease of delivery, and whose approach is so innovative that traditional ways of thinking about IP and regulatory pathways oftentimes do not apply.

Prior to co-founding Lumen, Brian oversaw complex negotiations with various major biopharma companies and managed IP strategy for Adaptive Biotechnologies, where he was Senior Vice President and General Counsel. As senior attorney at the law firm Cooley LLC, his practice focused on equity financing and M&A transactions, and negotiating complex biotech licensing and collaboration deals. With over 15 years of legal and commercial experience at these market-leading, innovative firms, he is well positioned to develop creative, win-win deal structures with other organizations.

“Our patented technology enables us to manufacture orally delivered biologic drugs at a cost that’s two to three orders of magnitude lower than traditional biotech manufacturing systems.”