| WEEKLY ROUNDUP Hello, Reader. For all that artificial intelligence has accomplished over the last few years, one thing it has not yet achieved is the creation of a new blockbuster drug from start to finish… Essentially, going from drawing board to pharmacy. But AI has made major contributions to the drug development process. A recently approved therapy from one of the world’s largest pharmaceutical companies benefited from such a contribution. Back in the early 1990s, biopharma firms Eli Lilly and Co. (LLY) and a partner discovered a new drug they called xanomeline. Early tests found this drug was helpful in slowing cognitive decline related to Alzheimer’s. It also reduced the delusions and hallucinations that come with the disease. There was, however, a major problem. The side effects associated with xanomeline were so severe that more than 50% of Phase 2 study participants dropped out. Xanomeline was eventually shelved. But that wasn’t the end of the story… Longtime readers know that AI healthcare is a trend that I’ve been following closely this year. So, in today’s Smart Money, let’s take a look at the rest of this story – and at whether this company should be in your portfolio… Almost a decade later, the Boston-based biotech company PureTech Health PLC (PRTC) became interested. They realized that xanomeline’s efficacy came from its ability to bind to certain receptors inside the brain, while its side effects were caused by activating receptors outside he brain. That’s a complex issue, but suffice to say, it meant that the problems with xanomeline were solvable. So, PureTech bought the rights to the drug from Lilly. The PureTech team went on to identify at least 65 binders and 114 suppressors that could be combined to offset xanomeline’s side effects. However, they knew that testing all 7,410 of those combinations would have been impossible in real life. To produce a solution, PureTech’s team turned to predictive algorithms, a form of AI. The details of their process remain a trade secret. But we do know that PureTech’s AI eventually stumbled onto a perfect combination. Even better, it was a molecule named trospium chloride, a generic drug for bladder control that the U.S. Food and Drug Administration (FDA) had already approved in 2004. Trospium chloride, PureTech’s researchers discovered, could counteract xanomeline’s severe side in patients’ bodies, while leaving xanomeline to perform its work in their brains. While we still don’t know if this newly created drug can be used to treat Alzheimer’s, PureTech was able to demonstrate its ability to reduce delusions and hallucinations. And that proved useful in treating a separate disease: schizophrenia. These results were presented in a landmark Phase 2 trial in 2019. At this point, you might be wondering why we’re still talking about PureTech. With a market cap around $500 million, PRTC is clearly not, as I hinted at above, “one of the world’s largest pharmaceutical companies.” Well, PureTech had spun out the division behind this discovery as Karuna Therapeutics. And late last year, Bristol-Myers Squibb Co. (BMY) – market cap: $115.2 billion – acquired Karuna for a stunning $14 billion. In turn, Bristol-Myers finalized approvals with the FDA, which it received last month for schizophrenia. It’s hard to overstate how important this drug, now known as Cobenfy, will become. Cobenfy is considered the first medication for schizophrenia with a new form of effectiveness in more than 30 years. Analysts at Cantor Fitzgerald forecast Cobenfy to generate more than $1 billion in annual revenue by 2026. In addition, Bristol-Myers plans to retest Cobenfy for its original purpose of treating Alzheimer’s, as well as bipolar disorder. Stifel analyst Paul Matteis believes that could help the drug achieve peak annual sales of $10 billion, which would suggest total lifetime sales north of $100 billion. If that ends up being the case, Bristol-Myers’ initial $14 billion outlay would look like a rounding error. All this was made possible by AI-powered drug development. And we foresee even greater innovations to come over the next decade as this technology improves. In Fry’s Investment Report, I frequently recommend AI healthcare superstars like Bristol-Myers, which I added to the portfolio in February of this year. Since my initial recommendation, the stock is up over 10%. And I continue to keep an eye out for the next generation of AI healthcare winners. To learn more about all of the AI healthcare stocks I recommend, join me at Fry’s Investment Report today. Now, let’s look at what we covered here at Smart Money this past week… | 
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