Calico Purring Right Along With Life Extension Research

Earlier this month, Alphabet (GOOG) took the air out of its Loon subsidiary, a former moonshot project for deploying internet around the world using high-flying balloons. Apparently, the economics just didn’t work out. No word on how much Google’s parent company spent on Loon, but SoftBank had sunk $125 million into the business in 2019. This seems like the latest sign that the tech giant is tightening its belt a bit in an increasingly risky regulatory environment. That made us wonder what’s happening with another venture that isn’t contributing anything to its bottom line. Let’s dive into Calico, a subsidiary focused on life extension research and development.

What is Calico?

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Calico is pretty much the opposite of Verily Life Sciences, the Alphabet unit working to digitize healthcare in every possible way. Verily is one of the few companies that does generate some revenue among the $461 million that its sideline subsidiaries earned through the first nine months of 2020. Some of the joint ventures connected to Verily are developing apps or new medical devices, with a certain amount of publicity and transparency. Calico operates more like a nonprofit research center that’s secretly working on some biotech version of the Manhattan Project, so most of what we read is pretty superficial and saccharine. 

Examples of Calico R&D

At face value, Calico is pure anti-aging R&D, starting at the very beginning of the problem with “what is aging?” For example, one of its public-facing projects involves studying how yeast ages, apparently without in situ experiments involving a teenager’s room. The premise (in very broad strokes) is that if we can understand how yeast age at the cellular level, we could all one day look like Brad Pitt forever. But the biggest news to emerge is that Calico scientists created a bit of new technology to help analyze the yeast cells, enabling “genome-wide characterization of the aging process,” which certainly sounds significant and was published in a peer-reviewed journal.  

New microscope developed by Calico Labs.
The big brains at Calico also found the spare time to develop a new microscope that’s better than anything on the market today. Credit: Calico

The Miniature-chemostat Aging Device (MAD) purifies 50 million old cells in a single test tube to speed up the search for genetic biomarkers of aging. An additional platform that sounds similar to the technology used in lab-on-a-chip solutions developed by companies like Berkeley Lights (BLI) allows scientists to observe the “entire aging process in single cells – hundreds of thousands each week – allowing them to screen for lifespan-extending modifications that can increase the yeast lifespan” beyond that of your ordinary lab yeast. The company integrated computer vision and machine learning to recognize cell division from time-lapse images or to measure the age of a cell directly from static images. 

The First Clinical Trial

While a new cell-counting gizmo using AI sounds great, that’s certainly not something out of reach for any large research university. Calico is a company that has at least $2.5 billion in funding thanks to its most high-profile partnership with AbbVie (ABBV), a pharmaceutical company with a market cap of nearly $200 billion as of late January 2021.

Chart shows Google investments in other business units.
Calico is so off the radar that we’ve resorted to five-year-old charts that show you where Google places its Other Bets. Nest has since moved to another revenue category. Credit: Visual Capitalist

The companies first joined forces in September 2014. Three years later, Calico and AbbVie had already burned through $1 billion, but that didn’t stop the duo from extending their research collaboration and kicking in another $500 million each, according to the San Francisco Business Times. So you would think there’s some high-pressure expectation to produce an anti-aging Brad Pitt pill or something significant. What has all that money produced? According to the company, the partnership has resulted in “two dozen early-stage programs addressing disease states across oncology and neuroscience and … new insights into the biology of aging.”

The 2018 deal makes Calico responsible for research and early development until 2022 and for advanced collaboration projects through Phase 2a clinical trials through 2027. In fact, there’s actually a whisper of something finally gaining traction. Endpoints News was the first to report that a team from Calico and AbbVie is conducting a phase 1 safety study to test a drug called ABBV-CLS-579 for treating solid tumors. The article also noted how one of the company’s principal investigators just published a paper in Nature on how Calico is using AI to predict genome folding from DNA sequence alone.

Mining Genomic Data at Scale

Calico is mining for answers to longevity in human DNA by creating its own hardware and software to automate and accelerate that search. One of its other high-profile ventures, in fact, involved mining the genetic database of Ancestry.com for three years. The Holy Grail was to find genetic commonalities among those who live longer, but research delivered some unexpected results. Another study based on the Ancestry data in another prestigious journal, Genetics, found that while longevity runs in families, DNA isn’t as strong an influence on how long an individual lives, so just because Grandpa Joe lived to 103 doesn’t mean you’re going to outlive a lifetime of junk food.

Other ongoing collaborations include the Broad Institute of MIT and Harvard, the Buck Institute for Research on Aging, and C4 Therapeutics (CCCC), a small-cap biotech company focused on treating diseases of aging, including cancer, by degrading proteins known to drive disease.

Conclusion

Pretty much every story on Calico refers to the fact that the former Genentech CEO Art Levinson, who has a PhD in biochemistry, is in charge of the Alphabet subsidiary. Acquired by Roche for nearly $47 billion about a dozen years ago, Genentech was considered the world’s oldest and most successful biotechnology company. It’s also worth noting that he serves on the boards of Apple and the Broad Institute, as well as formerly served on the boards of small-cap biotechs, including Amyris Biotechnologies, a synthetic biology stock. He is also an advisor on a bunch of scientific boards. So the assumption is that this guy knows what he’s doing – in terms of his scientific expertise needed to lead one of the most well-funded, private, anti-aging R&D labs in the world.

As we told you more than five years ago, Calico will likely forever be an innovation lab similar to Alphabet’s DeepMind AI lab in London. The only thing close to a pure-play in the longevity theme is perhaps C4 Therapeutics, which has developed a novel platform for harnessing the body’s natural mechanisms for regulating protein levels to fight diseases of aging. But the Boston area biopharmaceutical company is on pace to double its losses in 2020 from 2019, and it gets all of its revenue from collaboration agreements like the one with Calico. We’ll just have to wait for a Brad Pitt pill and make our money on the market the old-fashioned way – over time.

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