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Startup using yeast to make drug components raises $73M

Startup using yeast to make drug components raises $73M

This is an excerpt from Medically Necessary, a health care supply chain newsletterSubscribe here.

The idea: A California company producing active pharmaceutical ingredients with engineered yeast raised $73 million to bring its first product to market.

The company, Antheia, will focus on making complex chemicals normally extracted from plants.

The funding was led by Viking Global Investors and included Sherpalo Ventures and Hillspire. The new funding comes amid a push from policymakers to manufacture more drugs and APIs, largely sourced from abroad, in the U.S. 

Led by Stanford bioengineer Christina Smolke, Antheia hopes its production process will make the supply chain for drug components more resilient. 

“What we want to do is be able to use nature … as the inspiration, but not as the raw supply to make these medicines,” Smolke told FreightWaves.

The process: Smolke and her team insert genes, sometimes dozens of them, into yeast to turn them into factories for complex pharmaceutical ingredients.

“It would look very similar to a fermentation,” Smolke said. “You have a big vat where you grow the yeast. You give them sugar. Over a period of days, they are converting that sugar to your API.” 

Her team identifies enzymes in nature that produce a desired product and then they figure out how to incorporate them into yeast.

The new genes all work in concert. Some genes produce chemical precursors and others transport chemicals around the cell.

Last year, Smolke reported in Nature that her lab had engineered yeast to produce hyoscyamine and scopolamine, complex alkaloids used to treat neuromuscular disorders.

In that paper, the yeast only produced low concentrations of the APIs. Antheia says those compounds are in early stages of development.

Now the company claims that it is producing other APIs at “commercially relevant” levels, but it hasn’t reported those results in a peer-reviewed journal. The company hasn’t yet revealed which API it intends to bring to market first.

Antheia says it has successfully completed trial runs for several hundred liters of fermenting yeast. The next step is to scale up the process to vats capable of fermenting hundreds of thousands of liters. 

Dongming Xie, a researcher at University of Massachusetts Lowell who uses biomanufacturing to produce products like pigments and fatty acids, said jumping up to commercial production levels will be a big challenge.

“It’s not easy. You can make a good strain, but it doesn’t mean you can make it a commercially feasible fermentation process,” he told FreightWaves.

Producing at a commercial scale isn’t as simple as using a bigger vat, Xie said. Higher volumes can change the chemistry, so it’s important for biologists and engineers to work together throughout that process. 

“It’s good to have strain development and process development that have some overlap,” he said.

Still, he’s optimistic that with enough time Smolke’s team can overcome those challenges.

The problem: Many of the active ingredients for critical medicines, such as aspirin or the cancer drug Taxol, come from plants. In some cases, the supply chain for APIs starts with a farmer growing a crop, which is then processed to extract the desired ingredient. 

“Leveraging many of these organisms as a manufacturing platform is not ideal,” Smolke said. “If you have to grow a plant and extract that active ingredient from a plant or a tree, that’s a really inefficient process.”

Smolke says that type of long, geographically concentrated supply chain is vulnerable to disruptions like climate change, natural disaster or political unrest. She hopes a lab-based process will eliminate some of those risks. 

“The current processes are very susceptible to these types of events … not only because they’re occurring out in open fields but also because plants grow slowly,” she said.

Peng Xu, a researcher at Israel Institute of Technology who is working on similar biomanufacturing projects to produce medicinal products, believes biomanufacturing can make the supply chain for APIs more resilient.

“The good thing about this is it could stabilize the supply chain,” he told FreightWaves. “This kind of technology doesn’t really rely on farmers.”

The timing: The COVID-19 pandemic increased demand for certain drugs and also disrupted global supply chains, making it difficult to source some medicines last year. 

Nearly 75% of the facilities producing APIs and nearly half of facilities making finished drugs for the U.S. market are located overseas.

Now many lawmakers are looking for ways to increase the production of drugs and APIs in the U.S. Sen. Gary Peters, D-Mich., has introduced a bill to offer loans and support to companies manufacturing drugs and medical devices in the U.S. Last month, Sen. Jacky Rosen, D-Nev., introduced legislation to support nonprofit drug manufacturers in the U.S.

Smolke argues that biomanufacturing may be a good way to make that happen. She says the process is less labor intensive than synthetic chemistry. She claims it also has a smaller environmental impact, making it easier to comply with U.S. regulations. 

“It’s impractical, essentially impossible, to think about moving the conventional manufacturing approaches to the U.S. for production,” she said. “We don’t have the right climate to grow these crops. … And it would be hugely more costly.”

Backstory: Drugmakers have been using living cells to produce medicines for decades, especially drugs such as penicillin, that were discovered in microorganisms.

Other companies have also engineered yeast to produce drug components. In 2014, the drugmaker Sanofi started selling antimalarial drugs produced with genetically engineered yeast.

By 2015, Sanofi stopped making the product because it wasn’t economically competitive with traditional manufacturing methods, according to a news report in Nature

Smolke argues Antheia’s work is a big step forward because the company will produce molecules that are very complex. 

Smolke’s team modified 26 yeast genes to produce hyoscyamine and scopolamine. She said previous yeast stains only incorporated a handful of new genes.

It’s much harder to produce complex molecules with synthetic chemistry. Smolke argues that should make biomanufacturing economically competitive for those products. Xu agreed with that assessment.

“The harder and longer the pathway, the more complex the molecule, it will be more promising for synthetic biology,” he said. 

What’s next? In addition to scaling up production for its first products, Antheia will use some of the new funds to expand the types of products the company can produce.

Smolke said the technology is adaptable and the company could modify yeast to make a variety of products.

“Fermentation of active ingredients for pharmaceuticals is not, in itself, a novel manufacturing concept,” she said. “What is new, is … the breadth of complex molecules, the breadth of chemistries, that we can reconstruct within the yeast.”


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6 July 2021, 23:30