Fancy French Cheese Made with Microbes

Fancy French Cheese Made with Microbes

Welcome to Codon. Each week, I highlight biotech startups and report on scientific advances. Sometimes I publish essays, too. Subscribe for free:

Go online and order some mesophilic and thermophilic bacteria, lipase enzymes, and brine solution. Wait a few days for the packages. When they arrive, take them to your kitchen and follow this YouTuber’s instructions to mix them all together. Wait a few days and voila! You have made Grana Padano (REDACTED) cheese.

Actually, wait. Don’t do that! And if you do, definitely don’t share it online.

Italy, France, and many other countries in Europe take their cheese very seriously. So seriously, in fact, that they’ve been known to send cease-and-desist letters to anyone who labels cheese with their protected terms without permission. Grana Padano cheese must originate from the Emilia-Romagna region of northern Italy. It must be made with specific ingredients, in a specific way. This and dozens of other cheeses from Europe have “protected geographical status.” France alone has nearly 60 protected cheeses.

With so much cheese snobbery in Europe, breaking into the space with a dairy-free option — let alone competing with high-end French cheeses — seems a daunting prospect. But that’s exactly what Paris-based startup, Nutropy, is planning to do. The company today announced a $2M raise to scale up their technology and, eventually, roll out high-end, dairy-free cheese products. The pre-seed round was led by Beast, Big Idea Ventures, and Trellis Road. I spoke with co-founders Nathalie Rolland and Dr. Maya Bendifallah as they coasted on a train over the Swiss alps.

Nutropy uses recombinant DNA, yeast, and fermentation to produce real milk ingredients, identical to those produced from cows, but without lactose or cholesterol.

The company is also using yeast to produce dairy fatty acids and casein, proteins found in milk that other dairy-free companies cannot, or are not, producing. After extracting the milk ingredients from a bioreactor, Nutropy makes reconstituted milk and uses it to make high-end cheeses with “a French touch.” The casein, in particular, “gives animal-free cheese products the texture and creaminess” found in animal cheeses, according to a company press release.

“Today, nobody is making complex cheese out of non-lactose sugars and powdered casein fats,” says Bendifallah. Most incumbent dairy-free cheese companies are focused on mozzarella, which is relatively simple to make.

But this, in itself, is a problem: There are a lot of incumbents in the animal-free dairy space. New Culture raised $25 million last year to make — you guessed it! — animal-free mozzarella. Perfect Day is already selling animal-free dairy products, including a whey protein powder, that is made from proteins produced in yeast. That product is lactose-free and purportedly emits 84 percent less greenhouse gases than traditional dairy production. Imagindairy is also making animal-free milk from yeast cells; they want to create a milk substitute that looks, smells and tastes like the real thing.

Nutropy’s niche is in the high-end cheese market. Their first product — speculatively — will be a “sort of Camembert,” although they won’t be able to call it that thanks to strict naming rules issued by France’s Institute of Origin and Quality.

“We are particularly interested in working with aged cheeses and French cheeses,” says Rolland, who met Bendifallah through their shared interest in reducing climate change impacts from animal agriculture. Rolland was previously director of Agriculture Cellulaire France, a French association that pushes for cellular agriculture and cultured meat products.

In Europe, animal-based milk products are heavily subsidized. In the early stages of Nutropy’s business development, then, their products “are going to be slightly more expensive than the animal-based products,” says Bendifallah.

Rolling out fermentation-based cheeses to a European audience won’t be easy, either. A Pew poll from 2020 found that just 16% of French respondents think scientific research on gene editing — any research at all — is appropriate. That was the lowest value for any country surveyed. “In the end,” says Rolland, those most likely to adopt dairy-free cheeses are “people who care about animal welfare and environmental benefits.”

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VX nerve agent is bad. The British developed it at Porton Down in the early 1950s. Cuba used it during the Angolan Civil War. There’s also evidence that Iraq used it against the Kurds in 1988. Now, a new paper in Science Advances reports an enzyme engineered to detect and emit a signal when in contact with VX. The real question: If I carry this biosensor around, and it ‘beeps,’ is it already too late for me?

For a Cell paper out this week, the Fischbach lab made a synthetic microbiome with 119 species of bacteria. When they gave the bacterial mixture to mice without a microbiome, the colony established itself in the gut; the mice developed a healthy immune system. This is an incredible advance in synthetic microbial communities — something I worked on for many years — and is potentially a starting point for rebooting the microbiome for patients with C. difficile infections or other gut-related conditions.

California-based Grail developed a test, called Galleri, that looks for cancer DNA in the blood. It could one day be used to detect certain cancers months before other screening tools — and it can predict where a cancer is located within the body. Now, results are out from the company’s Pathfinder study; 6,600 adults aged 50 and over were offered the Galleri test. The test flagged potential cancer in 92 people; further tests confirmed cancer in 36 people. The test’s specificity (true negative rate) was 99.1 percent. But only about 38 percent of people who tested positive actually had cancer.

A malaria vaccine developed at the University of Oxford maintains its high efficacy (about 77% in a phase 2b trial of 450 children) a full year after initial injections. The goal is to roll the vaccine out, pending approval, by 2023.

Three epigenome-editing biotechnology companies have spun out since 2021. Tune Therapeutics and Chroma Medicine raised $165 million between them last year. Earlier this year, Stanford spinout Epic Bio raised a $55 million series A round. They all have the same goal: “…complete control of gene expression — to turn things on or off, for as much as we want, for as long as we want, in the cell types that we want,” says Duke professor and Tune co-founder, Charles Gersbach.

A Swiss startup, called Cultivated Biosciences, is trying to create molecules that mimic “high-fat cream using a GMO-free yeast fermentation process.” The goal is to make dairy-free products that taste like real dairy products. This startup intrigues me because they’re using fermentation to mimic mouth feels; the textures and microstructures that mimic dairy. I’m pretty sure they use fatty Yarrowia lipolytica yeast for their fermentation, but I’m not certain. They’ve raised $1.5 million in pre-seed funding.

The coolest company news this week: Innervace just raised $40 million in a series A round. They are “developing the first implantable biofabricated neural pathway” to restore dysfunctional neural circuits in the brain.

DNA-based data storage could soon go mainstream. Boston-based Catalog — a company using synthetic DNA to store digital data — just partnered with Seagate to use the latter’s electronic chip technologies.

Good Therapeutics (which is, let’s be honest, a horrendous name) was developing a protein-based therapeutic for cancers. They never ran a clinical trial, but they did raise $30 million in total funding over the last six years. And now Roche has bought them for $250 million. Let this be a lesson: A bad company name won’t stop you from getting rich.

The European Union blocked Illumina’s efforts to acquire Grail, the incredible cancer diagnostics company behind Galleri (which I wrote about above), for $8 billion.

Arsenal Biosciences closed a $220 million series B, one of the largest raises of the year, to build out their CAR-T therapies for solid tumors.

Onego Biosciences is making egg whites inside of bioreactors. The Finnish government’s business fund just gave them a $4.5 million grant to scale their efforts.

Colorado-based Think Bioscience raised $17M to develop “small-molecule therapeutics that target difficult-to-drug proteins” using synthetic biology and engineered enzymes.

Bond Pet Foods, also based in Colorado, is using fermentation to make meat proteins for animals to eat. They’ve raised $17.5 million in Series A funding.

Synthace, a cloud-based R&D software company, appointed a new chairman to their board: Donald Deieso.

Benchling, the cloud-based software for biotechnology, released a full pipeline to design, model, and experiment with modified RNA. The goal is to take a bite out of the growing RNA therapeutics space.

Speaking of RNA…Orbital Therapeutics just launched with funding from ARCH Venture Partners, a16z, and other investors. They’ll develop RNA therapeutics. Their chairman is John Maraganore, too, who was the founding CEO at Alnylam and helped develop RNAi-based therapeutics for amyloidosis and other conditions.

The fermentation company, Lesaffre, has acquired Recombia Biosciences, a multiplexed genome editing company, for an undisclosed amount.

DucentisBio Therapeutics, a preclinical biotech company developing therapies for inflammation and autoimmune diseases, was bought out by Arcutis Biotherapeutics at a $400 million valuation (with $16M in cash upfront).

Biomaterials company, Modern Meadow, has a new CEO: Catherine Roggero-Lovisi is replacing Anna Bakst.

COUR Pharmaceuticals is developing immune-modifying nanoparticles to treat autoimmune disorders. They’ve just closed $30 million in financing from Alpha Wave Ventures.

STORM Therapeutics builds enzymes that modify RNAs to treat cancers. They’ve just appointed a new CEO: Jerry McMahon, who was previously CEO at Harpoon Therapeutics and Kolltan Pharmaceuticals.

DNA synthesis company, Ansa Bio, appointed a new chief business officer.

Cell therapy company, Orca Bio, is building a 100,000 square-foot facility in Sacramento, California. They’ll use the new space to develop and commercialize Orca-T, a therapy for blood cancers that’s currently in Phase III trials.

iLiAD Biotechnologies is building and testing a vaccine for pertussis, which kills 200,000 people each year. They plan to do a phase II Human Challenge study and will infect people with Bordetella pertussis to test their vaccine’s efficacy. They’ve just raised $42.8 million in a series D round.

Israeli startup, BioBetter, is using engineered tobacco plants to produce cheaper growth factors, a crucial ingredient for cultivated meat. They’ve just raised $10 million in a series A.

And finally, who cares, but Verily (which has a drug discovery platform) just raised a billion dollars from parent company Alphabet and some other investors. Blah blah blah, money printers go brrrr.

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Until next time,

— Niko // @NikoMcCarty // [email protected]

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