Clostridioides difficile, commonly known as C. diff, is a significant health threat in the U.S. Recent estimates suggest that C. diff, a common bacteria, can cause infection in roughly 500,000 patients annually in the U.S., with around 30,000 of these cases resulting in death. “Actually, it’s more like 5 million when you think about it in terms of people at risk,” estimated Brian Finrow, founder and CEO of Lumen Bioscience, a biotech specializing in developing novel biologics. C. diff infection (CDI) is especially prevalent and dangerous in the immunocompromised elderly patients who are hospitalized or have been in nursing homes for long periods. “It’s a huge cost driver,” Finrow. Annual U.S. costs tied to CDI have eclipsed $6 billion per year. The infection is especially prevalent and dangerous in the elderly. Complicating matters further, recurrent CDI infections are common, affecting anywhere from 20% to 35% of patients with an initial infection.
A spirulina-based biologics approach to address a significant health threat
Lumen Bioscience (Seattle) is pursuing a novel approach to prevent recurrent CDI by developing an oral biologic drug, LMN-201. In developing the drug, Lumen is using a platform based on spirulina, a blue-green algae. Spirulina as a production host provides cost-effective manufacturing of this complex therapeutic, overcoming a common barrier to developing oral biologics.
“The core technologies are fundamentally based on cell engineering technology,” Finrow said. But it would be reductive to say that Lumen Bioscience is solely a spirulina company. It wouldn’t be fair to say that companies like Amgen or Genentech are solely Chinese hamster ovary (CHO) cell companies, even though many of their products are developed with the help of these cells. Similarly, “it’s not entirely accurate to think of us as just the spirulina company,” Finrow said.
Still, spirulina is a clear driver enabling Lumen’s oral biologics platform. As a photosynthetic cyanobacterium, spirulina supports cultivation at massive scale in saltwater using just sunlight and carbon dioxide. Lumen has engineered spirulina to act as a highly productive biomanufacturing host, with the capacity to generate biologic drugs at yields 10–100x greater than conventional cell cultures. The spirulina cells encapsulate the biologic drug payload and protect it as it travels through the stomach before releasing the therapeutic proteins in the intestines. This oral delivery system provides targeted disease treatment while overcoming the high cost barriers that typically hinder large-scale production of complex biologics. Though spirulina sits at the core, Lumen aims to tap this underlying platform technology to address multiple therapeutic areas spanning infection, inflammation, vaccines, and metabolic disease.
Late-stage testing for LMN-201 to start in 2023
The biologic combines antibody and enzyme proteins designed to neutralize both C. difficile bacteria and toxins directly in the gastrointestinal tract. In October, Lumen won $16.2 million in Department of Defense funding to advance LMN-201 through late-stage trials starting in late 2023. The Phase 2/3 REPREVE trial will enroll roughly 375 patients across the U.S. to test LMN-201’s ability to both improve treatment outcomes and prevent recurrence in recently diagnosed CDI patients.
LMN-201 combines multiple therapeutic proteins that work together to neutralize both C. difficile bacteria and the toxins it produces directly in the gastrointestinal tract. This novel approach aims to break the cycle of CDI recurrence caused by antibiotic use, which can disrupt commensal bacteria. “The biologics we make target C. diff specifically, and don’t really interfere with anything else in the body,” Finrow said. LMN-201 won FDA Fast Track designation earlier in 2023.
Lumen Bio intends for the drug to be compatible with the standard-of-care antibiotics used to treat the infection while offering a more convenient and less expensive option than therapies like fecal microbiota transplants (FMT) or the monoclonal antibody bezlotoxumab.
Diverse pipeline tapping spirulina’s flexibility
While LMN-201 is Lumen’s most advanced program, the company also has Phase 2 programs for campylobacter (LMN-101) and COVID-19 (LMN-301) using its protein biologics platform. Preclinical programs focus on recombinant vaccines for malaria and antibiotic-resistant infections, an oral drug for inflammatory bowel disease, and a collaboration with Novo Nordisk on cardiometabolic disease therapeutics produced in spirulina.
Again, the flexibility of spirulina is a driver of the diversity of its pipeline. “For the GI, you consume the spirulina, which is the microbe itself and also a food,” Finrow said. For nasal delivery, the company uses extra processing to create a nasal spray. “The idea is to coat the upper respiratory tract with antibodies. The approach offers particular promise for high-risk individuals such as those who are immunocompromised taking an airplane flight. Making an neutralizing antibody cocktail for an infection like COVID-19 would be “too much for conventional technologies, considering the sterile fermenters and the typical GMP factory setup,” Finrow said. “We’re aiming to make [our COVID-19 product] safe and tolerable enough to be sold without a prescription, and cheap enough to hang on a rack at the bookstore in the airport. That’s the plan.”
Support from Novo Nordisk and the Gates Foundation
In 2021, Lumen Bioscience entered into a collaboration with Danish pharma giant Novo Nordisk to develop therapeutic proteins produced in spirulina to treat cardiometabolic conditions like obesity, diabetes, and cardiovascular disease. The partnership aims to harness Lumen’s platform for large-scale, low-cost oral biologics manufacturing using spirulina with Novo Nordisk’s expertise in metabolic disorders.
The company has also received funding from the Gates Foundation to address diarrheal diseases via a neutralizing antibody cocktail. This support includes a significant grant for developing LMN-101, an anti-campylobacter therapeutic, which is part of a broader initiative to combat diarrheal infections with a neutralizing antibody cocktail. These infections remain a major health challenge, especially in developing countries.
A new area of focus for the company is kidney stone disease, which are primarily crystals of calcium oxalate. Lumen Bioscience is working on a product based on an enzyme that degrades oxalate in the GI tract to prevent its absorption and the formation of kidney stones that can follow.
Focus on prevention
The common theme running through the company’s programs is prevention, Finrow said. “We want to prevent COVID. Treating it is also important, but it’s much better for the patient to not get the disease in the first place,” Finrow said. Similarly, with LMN-201 the goal is to prevent C. diff recurrence. “Although it’s nice if we can also treat the disease, the real value for society is in preventing it in the first place,” he added.
The support from the Gates Foundation to combat diarrheal diseases in the developing world could also enable Finrow to market the same product to a different demographic — travelers from the developed world going to regions where such diseases are common. Finrow applied this concept to traveler’s diarrhea, noting that “if there’s a 50-50 chance of [a tourist] spending half their vacation in the bathroom” on a trip to the developing world, people would likely buy an inexpensive product “not to treat traveler’s diarrhea, but to prevent it.” Finrow summarized: “That’s a common theme across all of our programs, and it’s directly a function of the affordability of our manufacturing system.”
Filed Under: Biologics, Gastroenterology, Immunology, Infectious Disease