Special Report: Reinventing Biologic Drugs – Part 3

Part 3: Thinking differently

An interview with Brian Finrow, CEO Lumen Bioscience: by Mark Edwards

Novel thinking benefits from diversity in people, training, and experience. Brian Finrow and co-founder Jim Roberts recruited a highly diverse team for Lumen Bioscience, with deep expertise in synthetic biology, protein design, immunology, photobioreactor engineering, and cell physiology.

“A typical company assembles a group of individuals with a relatively narrow set of skills within a discipline and focuses on a singular challenge,” says Mr. Finrow. “Lumen’s diverse scientists and engineers’ individual skills and experiences — and the interplay among them — are the catalyst for discovery and exploiting the potential of this new biomedical platform.”

Lumen has created a unique portfolio of commercially viable biologic therapies, while establishing a foundation upon which an entirely new generation of scientific discoveries and therapies will be brought to market. Each team member brings the vision and skills needed to achieve the Lumen mission, which is:

Reinvent how biologic drugs are invented

Biologic drugs like Enbrel®, Humira®, and Keytruda® have revolutionized how diseases like cancer and arthritis are treated in the developed world. Unfortunately, modern drug inventions are slow and costly. A recent JAMA study concluded that a single drug development may take a decade and cost $1 billion or more. The result: very high-cost drugs which are available to only a few people.

Modern biologics were developed to address therapeutic targets such as bacteria and viruses in the gastrointestinal tract and other topical sites. Some biologic drugs have been developed at a cost of more than $10 million. Modern biologic drugs are not commercially viable at scale, due to a variety of factors.

• Cost of production, often $200 per gram, which makes the biologic too costly for all but wealthy individuals. A single treatment protocol may require 5 to 10 grams of the biologic.
• Cumbersome administration medically supervised with intravenous application or injection.
• Administration in a hospital by a trained medical professional, which makes them unavailable to most patients, even in the U.S.
• Costly shelf stability requiring constant refrigeration which severely limits distribution.
• Multiple applications, which requires more hospitalization and multiplies costs.

The Lumen Bioscience strategy of reinventing the way metabolic drugs are made and delivered includes:

• Reduce drug development time by 10x. Lumen has exceeded this goal substantially.
• Reduce biologic production cost per dose by 10x. The Lumen team has already achieved 100x lower cost. Production cost of $1,000 for other modern biologics treats only two people. Lumen can treat nearly 300 patients for the same cost. Lumen Bioscience can treat 145x more people with $1,000 in production.
• Eliminate the need for IV or injection. Lumen’s solution uses oral self-administration.
• Create natural shelf-stability without refrigeration. Lumen’s dried spirulina culture creates a shelf-stable biologic medicine. The spirulina biomass powder can be packed into dose-specific capsules which 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. The therapeutics are released in the small intestine where they can bind to and neutralize their disease targets.
• Eliminate the need for medical professionals for multiple doses with oral application.

Lumen has become the first company to make orally delivered antibody drugs commercially viable for large numbers of patients who had no viable solution prior to Lumen’s biologics.

Novel goals

Mr. Finrow explains that Lumen created a novel biologic drug platform strategy that shortens the development process, reduces costs, and risks, and accelerates time-to-market. The Lumen team set goals for:

• High efficacy: beat the 33%-66% relative risk reduction previously reported for other CDI preventatives
• Oral delivery: to eliminate adoption barriers and health services and facilities costs associated with other preventatives — no IV needles, no enema, no bowel prep
• Safety: Relative to injected antibodies, orally delivered antibodies offer important safety advantages by preventing systemic exposure. Relative to alternative therapies such as fecal microbiota transfer, there is no risk of donor pathogen transfer with monoclonal protein therapeutics.
• Scalable manufacturing: The market for a safe and effective C-Diff preventative is massive nationally and globally. Manufacturing injection-grade antibodies is not scalable and too costly to meet patient needs.
• Shelf stability: As Covid-19 showed, refrigerated supply chains limit availability.

The Lumen team knew they needed an organism that grew quickly and expresses high levels of protein. They wisely selected spirulina, which grows 100 times faster than beef protein and delivers 2.5 times the protein of beef per kilo. As an added benefit, spirulina protein is absorbed by the body four times faster than beef.

Novel production platform

Production of therapeutics in spirulina begins with genes encoding the antibody or other therapeutic proteins that are engineered into the spirulina organism under control of a constitutive promoter. Once dried, the powder is prepared for delivery to patients as an ingested pill. Spirulina’s natural ability to accumulate soluble proteins allows the active therapeutic protein to be accumulated at levels up to 10% of the powder dry weight. The production process is described in the Lumen Bioscience graphic.

Spirulina are grown under normal photoautotrophic conditions in bioreactors and accumulate the therapeutic protein in the cytoplasm. Cultivation requires only minerals, light, water, mixing, and air.

The VHHs frameworks are antigen-binding regions or single domain antibodies, called nanobodies. Spirulina biomass is harvested, rinsed, formulated, and spray dried. Spirulina harvest from the culture occurs semi-continuously, which maximizes future yields. Dried biomass is formulated into tablets or capsules.

Spirulina cells offer many interesting biotechnological and bio-medical properties due to their small size, high solubility, and stability. The nanobodies demonstrate high affinity and specificity for specific antigens.

Lumen Biosciences set off on a quest to serve millions of patients with high need but no means. To accomplish this, the Lumen team had to rethink both algae industry business models and biomedical models. Their novel solution: design and build a low-cost, high efficacy antibody-like protein development and manufacturing platform to treat and prevent gut diseases. In Brian Finrow’s words: “Reinvent how biologic drugs are invented.”