Orally delivered antibody drugs made commercially viable for the first time

Science

Recombinant biologic drugs like insulin and antibody therapeutics have revolutionized health care since their initial development in the 80s and 90s. They allow researchers to make drugs for diseases that cannot be treated with traditional small-molecule pharmaceuticals because they are safer and more precisely targeted. However, high manufacturing costs have limited their application to rich-world diseases such as cancer, and autoimmune disorders. These challenges are compounded by the fact that the cost factor is rarely considered in the early stages of drug development. As a cultural matter, most venture investors, academic researchers and large biopharma companies do not weigh the cost of new drugs until long after they’ve been developed and launched, at which point it is too late. The conventional wisdom is that biologic drugs are only suitable for rich-world disease where health care systems can afford to pay 10s or 100s of thousands of dollars per treatment. This is deeply unfortunate because there are many diseases of the G.I. tract that, as a technical matter, can be easily treated with biologic drugs. Adoption is blocked by the overwhelming cost barriers of traditional antibody manufacturing systems. For example, diarrheal diseases are a major cause of infant mortality and morbidity in the developing world, inflict large economic costs on civilian travelers, and are the most common health threat faced by deployed military personnel. Treatment relies exclusively on antibiotics, because vaccine development for these pathogens has failed for decades. Even then, antibiotics are not approved for prevention and widespread usage is driving the emergence of antimicrobial resistance. Sometimes they can even make the disease worse. Lumen’s technology provides a solution to these problems: an antibiotic-free, ultra-low-cost, cold-chain independent, orally delivered, food-grade immuno-prophylactic for the prevention of diseases of the gastrointestinal tract, including the ones described above. Lumen's technology creates biologic drugs for oral delivery at a cost similar to small-molecule drugs — a breakthrough that allows Lumen to develop new drugs to address enormous unmet needs in healthcare that have remained unsolved in both developed and developing countries. Lumen’s manufacturing costs are low enough even for large-scale distribution into developing countries to prevent and treat infant diarrheal diseases, diseases that still cause high levels of infant mortality and morbidity. With support from the Bill & Melinda Gates Foundation and Lumen’s uniquely far-sighted venture capital investors, Lumen is poised to revolutionize how these diseases are treated. Following a very positive response from the US Food and Drug Administration in mid-2019, Lumen’s first drug will enter clinical trials in late spring, 2020.

Project Overview:

Lumen makes its biologic drugs by engineering a microbe called spirulina (Arthrospira platensis) to express the active drug molecule (most commonly an antibody) within its cell membrane. These cells are grown indoors, and the entire biomass is then dried to a powder. This powder is comprised of spirulina cells, each one ﬁlled with a therapeutic antibody "payload." This powder is then packed into dose-speciﬁc capsules, which don't require refrigeration and are shelf-stable indefinitely at room temperature.

The spirulina cells do not survive the drying process, but research shows that, when consumed, the cell membrane protects the therapeutic antibodies during transit through the acidic environment of the stomach, but conveniently releases them in the small intestine where they can bind to and neutralize the disease target.

This approach — making biologic drugs for delivery within a food substance — has been demonstrated in principle many times before but Lumen's technology makes this approach commercially viable for the ﬁrst time. It was long suspected that spirulina would be a valuable tool for making biologic drugs if it could be genetically engineered. But despite decades of efforts by many well-funded groups around the world, all attempts failed. Lumen was the ﬁrst to achieve this breakthrough, and as a result was recently granted a broad patent on this technology (U.S. patent #10,336,982).

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Platform Technology:

With this bioengineering technology in hand, the process of making a new drug is straightforward: (1) a gene encoding the therapeutic molecule (typically an antibody) is introduced into the spirulina chromosome, (2) when that strain spirulina is grown, the gene expresses the therapeutic protein inside the cell's cytoplasm, (3) the production system requires only water, mineral salts, and light so it is cheap and rapidly scalable, (4) harvesting the spirulina is done by simply spray-drying the biomass.

Lumen can manufacture orally delivered biologic drugs for 2-3 orders of magnitude lower cost than traditional biotech manufacturing systems. This is possible because:

1. being extraordinarily high in protein (>70%), spirulina cells are naturally able to express far higher amounts of therapeutic proteins than any other food crop or microbe

2. being an extremophile (pH>10), aseptic conditions are not required, and cap-ex utilization is nearly 100%

3. given spirulina's decades-long history of safe consumption, costly puriﬁcation is not required — the entire biomass can be eaten whole

Importantly, Lumen has already de-risked the manufacturing elements of this project, having established a large-scale (>4,000-liter) biomanufacturing plant in late 2018. This large-scale pilot plant has been operating, under GMP conditions, for almost two years, and received third-party audit certification in early 2019.

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Funding Development:

All of our programs address diseases that traditional biopharma technologies have failed to solve for decades. In addition, all of them are closely associated with the increasing challenges of antibiotic resistance, and most are major causes of infant mortality and morbidity globally. Consequently, we have obtained research grants from a wide range of government agencies (e.g. NIH, USDA, Dept of Energy, US Dept of Defense) and from NGOs (e.g. Gates Foundation, Wellcome Trust).

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Impact:

Many chronic diseases — in both the developed and developing world — are technically solvable with modern biologic drugs, but until now the high cost of manufacturing biologics has blocked commercialization. Lumen's technology allows for the development, manufacturing, and delivery of orally delivered biologic drugs for a cost as low as small molecule drugs. This makes it feasible to treat and prevent these diseases for the first time. Following approval, Lumen has committed to the Gates Foundation that it will make its products available, at minimal markup, for distribution to infants in the developing world.

Even for retail customers from wealthier, developed-world countries, Lumen’s drastically lower cost structure enables a retail price of as little as $50 for a 2-week supply, affordable by all travelers. The enormous size of this market — there are 50-100 million travelers each year from the developed world to regions where traveler’s diarrhea is endemic — is so large that the regulatory approval costs are commercially viable, even at such a low final sales price. The impact in lives saved and economic loss avoided will be vast.

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Orally delivered antibody drugs made commercially viable for the first time

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