In an interview with PharmaShots, Brian Finrow, Co-Founder and CEO of Lumen Bioscience shared his views on the critical need for a scalable and cheaper method to engineer antibodies as a potential treatment for Covid-19. He also shed light on why it is time for the industry to reevaluate plant-based biologics manufacturing as a possible way to bring drugs and how genetically engineering spirulina can help scale, speed up and reduce the cost of biologic drug development and manufacturing

Shots:

• Plant-based production of Abs eliminates the cost and complexity, paving the way for large-scale manufacturing
• Lumen, with funding in part from the Bill & Melinda Gates Foundation, is using its spirulina platform to target diseases, including Covid-19, C. difficile infection, and traveler's diarrhea. Lumen's spirulina-based system can make Ab therapeutics for 1/1,000th the cost of traditional manufacturing methods
• Lumen has developed an antibody cocktail to prevent or reduce the severity of Covid-19 and reduce viral shedding. The Army Medical Research and Development Command (AMRDC) and the Gates Foundation seed-funded the initial development

Tuba: Can we have a glimpse of Lumen's patented technology?

Brian:  Our foundational patent filings (here) have a very detailed explanation of the original version of the technology, although it has come a long way since that 2014 filing. We're getting better at sharing our work with the broader world, starting with a couple of public presentations earlier this year and an improved website not to mention conversations like this one! In early 2021 we aim to publish at least 3 significant peer-reviewed papers that will draw back the curtain a lot more.

Source: Lumen Bioscience

Tuba: a. Explain how Lumen's plant-based manufacturing works

Brian:  A virtue of our system is its extreme simplicity in our view an underrated virtue in our industry, and the thing that makes our products so much more rapidly scalable and inexpensive than traditional technologies.

Lumen's large-scale cGMP manufacturing facility has been operating since 2018 and is illustrated in the flow diagram at right. Production runs are initiated by filling the open-topped photobioreactors with city water mixed with just a few mineral salts photosynthetic cells need very little to flourish. The photobioreactors are illuminated by high-intensity LED lights, which provide the energy for cell growth. CO2 is sparged to maintain pH within operating parameters, and air is sparged to prevent settling.

Optimizing the geometry of the bioreactor frame was a matter of considerable complexity, so that was a significant effort a couple of years ago. But now that we have that optimized design, they are extremely simple to build and operate, in particular, because we use disposable plastic bags to simplify cleaning between production campaigns. Importantly, because spirulina is so robust and the products are intended for oral consumption, sterility is not required for safety. This fact alone makes their operation dramatically cheaper than traditional batch fermentation systems.

Partial harvests are carried out periodically for transfer to downstream processing, and the remaining culture is re-diluted with fresh media. True continuous production like this makes exponential growth possible, enabling Lumen to rapidly scale up drug supply in response to emergencies like Covid-19.

Downstream processing for most products consists of simple de-watering and spray-drying of whole biomass. For Lumen's initial passive vaccines for enteric targets, the drug product was whole, spray-dried spirulina biomass containing the therapeutic biologic agent.

Tuba: b.  and how the company is deploying this to treat the GI element of COVID-19

Brian:  Lumen has developed an antibody cocktail to prevent or reduce the severity of Covid-19 and reduce viral shedding. The Army Medical Research and Development Command (AMRDC) and the Gates Foundation seed-funded the initial development.

This antibody cocktail is being finalized now for planned spring Phase 2/3 clinical trials, and it's in vitro performance equals or beats all of the viral neutralization metrics previously published by other groups. The antibody proteins have been further optimized for rapid, low-cost manufacturability and a high degree of stability both on the shelf and in the G.I. tract this fully rounded optimization for real-world impact sets it apart from others that have been published.

Tuba: What inspired you to focus specifically on GI symptoms of COVID-19?

Brian:  Although Covid-19 is most notorious for its pulmonary symptoms, the now-famous ACE2 receptor is also expressed at very high levels in epithelial cells of the G.I. tract. So it is not surprising that the GI manifestations of the disease can be quite severe, contributing to ARDS, liver failure, and, in some patients, requiring intestinal resection (here are links to just a couple of papers on that).

There is also an emerging consensus that fecal-oral transmission is likely an important factor in the so-called 'superspreader' events. One recent paper demonstrated that SARS-CoV-2 can continue replicating for at least 3 months in the GI tracts of some patients, which may be contributing to the 'long Covid' phenomenon that some patients suffer through. Intuitively, this is easy to understand: norovirus is another well-known virus that infects the human G.I. tract, and like Covid-19 it is notorious for causing outbreaks in nursing homes, cruise ships, and military vessels.

Most importantly, absolutely no other groups are working on this key aspect of the disease. So, given the obvious utility of our technology platform, we feel an obligation to do whatever we can.

Tuba: How genetically engineering spirulina can help scale, speed up and reduce the cost of biologic drug development and manufacturing?

Brian:  Developing, testing, and manufacturing traditional injection biologics is horrifically expensive and time-consuming, in part due to the inherent risks of injecting non-natural proteins into the bloodstream.

By contrast, Lumen has intentionally built its entire product development environment to be simple and intrinsically safe. This starts with the fact that spirulina itself has a 50-year safety record in the US (hundreds of years in traditional societies). In addition, mucosally delivered biologic drugs are inherently safer than their injected counterparts because they generally don't reach systemic circulation, which dramatically lowers the risk of off-target effects or toxicity. And just compare our manufacturing system (simple salt water in an open photobioreactor) to the space-age technologies, bunny-suit sterility, and exotic media components used to manufacture traditional CHO antibody drugs.

This relentless war against complexity accelerates timelines and dramatically lowers the cost of developing and making new branded pharmaceuticals it's something we're very passionate about.

Tuba: How Lumen's technology aid in meeting the current demand for vaccines in the pandemic?

Brian:  The accomplishments of companies like BioNTech/Pfizer and Regeneron this year are incredible. And I mean that literally: if we had described those completed timelines achievement to an industry pundit 18 months ago, they would not believe it.

And yet, the pandemic is still with us, and will likely drag on through 2021. The lingering challenges that impede broader, faster adoption of those products highlight some advantages of Lumen's technology. For example, Regeneron's product a traditional injection monoclonal antibody drug is extremely difficult to manufacture in the quantities demanded. It must be administered by IV, which makes distribution cumbersome, and must be shipped in refrigerated conditions, which is easy for the US and Europe but a huge challenge in Africa and India. The BioNTech/Pfizer vaccine is available in greater quantities, but the -80°C storage/distribution challenge is particularly acute, especially outside the US and Europe. Among other lessons, the Covid-19 pandemic has taught us that we cannot afford to be indifferent to epidemics in other countries, so this isn't just about being charitable.

By contrast, Lumen's products are shelf-stable and far easier and cheaper to manufacture in enormous quantities. We believe that the mucosal delivery modality (rather than injection) and simplicity will also expedite clinical development without compromising safety. The simpler, safer development path should also enable even faster response times in the next pandemic for less than the billions of dollars devoted to traditional technologies through Operation Warp Speed.

Our technology is not the solution to all the world's problems; no single technology platform can be. But it seems clear that the Lumen platform's advantages development speed, manufacturing scalability, shelf stability, and affordability make it a useful and complementary new tool for this and future pandemics.

Tuba: Can we have a discussion on Lumen's pipeline products?

Brian:  Lumen currently has 4 publicly disclosed programs: Covid-19, C. difficile infection, norovirus infection, and traveler's diarrhea. They're all extremely widespread infectious diseases of the G.I. tract.

Infectious diseases (IDs) are not the darling of investors far from it but despite that conventional wisdom, we believe that these are enormous commercial opportunities. In the past, investors in ID companies were limited to one of two traditional technologies: antibiotics and vaccines. For reasons that have been exhaustively researched by many groups including the WHO, PATH, and the Wellcome Trust, new product development in both of these areas is afflicted by severe market failure.

Our products bear much more of a resemblance to the infectious disease business model that Gilead has successfully pursued for years: selling treatments and preventatives for widespread infectious diseases that lack alternatives and for which repeat dosing is required. There is enormous pent-up demand for a solution to these pervasive diseases, but there hasn't been a scalable technology solution until now traditional drug development technologies have failed over and over again. Lumen's technology just happens to be exactly the right tool for the job.

Tuba: What are the future targeted indications for which Lumen is planning to develop affordable biologic drugs?

Brian:  It would be premature to share more at this time (and in some cases we're constrained by confidentiality agreements), but when you consider that our platform allows for the delivery of arbitrarily large amounts of biologic drug, often in cocktail formulation to topical targets (G.I. mucosa, upper airway mucosa, skin, etc.), it's apparent that there's an enormous amount of unmet medical need out there for which our technology could help address.

Some examples might include autoimmune diseases of the GI tract (e.g., Crohn's disease, ulcerative colitis, celiac, etc.), metabolic diseases (e.g., diabetes and other imbalances), diseases involving enzyme deficiencies (e.g., hyperketonuria, hepatic encephalopathy, etc.), and infectious diseases that infect via the upper airways (e.g., pandemic influenza).

Tuba: Put some light on the grant that Lumen received from the US Army Medical Research and Development Command?

Brian:  See Q2b and Q3 above.

The Army’s stated goals are to (1) initiate Phase 2 clinical trials by spring 2021, and (2) be in position for mass-scale cGMP manufacturing of the resulting product by summer 2021 (assuming FDA approval; in our view 'mass-scale' means 1-3 billion doses/year capacity). The project is on schedule and on budget.

 Tuba: Would like to share anything specific about your company with our subscribers/readers?

Brian:  We're hiring as fast as we can, and Seattle is a beautiful city that's a wonderful place to live! Here's a photo of some of the R&D team on the deck just outside our lab the Fremont neighborhood on Lake Union is a wonderful place to work.

Tuba: Are you planning for collaboration or looking for funding opportunities in near future?

Brian:  We are not currently fundraising, and we continue to enjoy strong support from our VC investors.

We are, however, quite interested in building more relationships with other companies in the industry particularly those with deep domain expertise in the disease areas I highlighted in Q7 above, and companies that have institutional capabilities complementary to our own (particularly late-stage clinical development and international distribution).

Image Source: KV Berlin

About Author:

Brian Finrow is the Co-Founder and Chief Executive Office of Lumen Bioscience. Additionally, Brian Finrow has had 3 past jobs including SVP & General Counsel at Adaptive Biotechnologies.

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