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​NEW Premium Notes​

​The One-Skill-a-Year Plan for a More Interesting Life | Ravi Gupta on The Art of Manliness with Brett McKay​

• We all have that list inside our head of things that we've always wanted to do but have never got around to doing for one reason or another. Whether it be learning a new language or attempting to shred some waves on a surfboard, these things often seem so insurmountable that we just continue to let them collect dust in our minds as wishful thoughts. After a bout of burnout that left him receiving concerned looks from other guests at a wedding he attended, Ravi Gupta revitalized his life around the process he wrote about in his book, The Invisible List: One Passion a Year, Every Year. We know what you're thinking, and the answer is no, this is not your ordinary bucket list. The Invisible List is about reframing how you think about aging, making your dreams feel more attainable, and ultimately living a more fulfilled life as a legitimate renaissance man​

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​Keytruda (Part Two): How Merck’s Pembrolizumab Became the Best-Selling Cancer Drug of All Time | Approved with Alex Kesin and Matthew Pech​

• Part two of this Podcast Notes Premium Series explains how scrappy corporate guerrilla warfare tactics kept the PD-1 project alive, why a healthy dose of FOMO forced Merck to finally commit to the clinical development of pembrolizumab, and why new leadership thought going all-in was the only way to save the sinking ship that was Merck

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​Peter Thiel: The AI Crisis, Europe’s Decline & the Battle for America | MDMEETS – Essential Talks with Mathias Döpfner​

• What happens when the West stops believing the future can be better? In this episode, Peter Thiel joins the conversation for a big-picture chat about AI, why Europe is falling behind, and whether the West can get back to building. They also get into politics, China and the future of longevity

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Top Premium Takeaways Of The Week

​The One-Skill-a-Year Plan for a More Interesting Life | Ravi Gupta on The Art of Manliness with Brett McKay​

​The Invisible List: One Passion a Year, Every Year by Ravi Gupta

• Your invisible list is all the stuff you’ve wanted to do but have never got around to doing

“If you don’t start to pull things off the list and nurture them, you can grow into a very cranky, regret-filled person”

• Example: Ravi had always wanted to learn salsa dancing, and he felt left out when everyone else at the wedding knew how
• Example: You see a movie that follows a similar storyline to an idea you had but never took action on

It's not the same as a bucket list!

• Bucket lists are for doing XXXX things
  • Examples: Going to Paris or seeing the Northern Lights
  • Bucket lists require relatively low XXXX​
• Invisible lists are for taking a XXXX to learn a skill or pursue a hobby you’ve always wanted to
  • “It’s really about tackling things that are hard and that require a XXXX to become at least intermediate at”
  • You can take the skill or hobby into future years, or XXXX as the “theme” of that year

The 5 rules for following your invisible list

• Rule #1. You must have a strict XXXX of one new thing per year
  • You have to honor the time and commitment it takes to XXXX at the thing from your invisible list
  • You will procrastinate doing the hard parts of your invisible list thing when you have something else to XXXX​
• Rule #2. You can continue pursuing things from XXXX​
  • Only as long as it doesn’t crowd out the exploration of your XXXX​
  • You also don’t have to continue doing the XXXX at all
• Rule #3. You must do the new thing for a XXXX​
  • You have to see the new thing through no matter what, even if you XXXX​
  • It’s like a parent telling their child that they have to finish what they XXXX​
• Rule #4. You should spend some time learning how to XXXX​
  • If you want to learn Spanish, you should read a book on how to learn XXXX​
  • Do it for no more than XXXX to start, then do it intermittently while actually doing the new thing
• Rule #5. You must be comfortable being less than XXXX​
  • It takes a lifetime to go XXXX, so don’t expect it in one year
  • The goal is to learn a domain XXXX so that you can enjoy it

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​Keytruda (Part Two): How Merck’s Pembrolizumab Became the Best-Selling Cancer Drug of All Time | Approved with Alex Kesin and Matthew Pech​

The PD-1 project survived through corporate guerrilla tactics

• Merck’s oncology department wasn’t backing the program, so the team found ways to keep it alive
• They pitched it as an HIV project to get “bureaucratic air cover”
• They brought in outside clinicians and quietly built a clinical plan
• They even downplayed the project so it could be used to test a new manufacturing technique
• Despite their efforts, the drug was eventually placed on Merck’s out-licensing list

A former colleague tried to take the project back

• Andrea van Elsas, the original champion of the program, had left Merck and started BioNovion with other former Organon colleagues
• The startup tried to XXXX the PD-1 program
• Michel Streuli, still at Merck, had to XXXX the project against his former colleague
• Streuli felt Merck had the resources and expertise to develop XXXX​

Bristol Myers Squibb’s results gave Merck a serious case of XXXX​

• In 2010, BMS presented striking XXXX from its PD-1 antibody, nivolumab
• Response rates of XXXX in melanoma and kidney cancer were remarkable for the time
• Merck realized it had to decide whether to pursue its XXXX​
• In 2011, it moved the drug into clinical trials with a 30-patient Phase 1 study focused on XXXX​
• Starting later meant Merck would eventually need to prove its treatment was better than a competitor’s, not just better than XXXX​

New XXXX changed the company’s direction

• By 2013, Merck was struggling after Singulair sales XXXX and its leading pipeline drugs hit major obstacles
• New CEO Ken Frazier brought in immunologist XXXX, who recruited clinical-development expert Roy Baynes
• After reviewing early study results, Perlmutter decided Merck should prioritize the XXXX​
• More than half of the company’s drug-development budget was XXXX​
• Merck went on to launch more than XXXX clinical trials across dozens of cancer types

The big bet required shielding the team from XXXX​

• Analysts questioned Merck’s decision to concentrate so much of its budget on XXXX​
• CEO Ken Frazier protected Perlmutter and Baynes so they could keep XXXX​
• The shift away from consensus thinking gave the project the XXXX it had previously lacked

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​Peter Thiel: The AI Crisis, Europe’s Decline & the Battle for America | MDMEETS – Essential Talks with Mathias Döpfner​

AI could renew belief in progress, but it won’t solve everything

• When people stop believing their children will have a better future, politics can become a fight over who gets what remains
• AI may create new growth, but it could also bring serious risks and instability

A XXXX